L-Methylfolate is a remarkable nutrient yet it can create significant side effects.

Those who have MTHFR mutations (especially the C677T MTHFR mutation) learn that methylfolate is critical to take – and that folic acid is critical to avoid. The issue is methylfolate can cause more harm than good if not started at the right time or tapered up slowly in amount.

UPDATE: June 25, 2019: I’ve gone through this article and thoroughly updated it. Surprisingly, it has held the test of time so not much has been added.

UPDATE December 7, 2014: Please read this article on how to prevent methylfolate side effects in addition to this one. I’ve since learned how to reduce the incidence of side effects even more.

There appear to be three types of responses to methylfolate:

FIRST: A person who can jump on methylfolate and feel absolutely wonderful. The only down side they experience is why didn’t they know about methylfolate before?!

SECOND: A person starts methylfolate has an amazingly incredible week where they are happy, interacting and alert. Then the second week comes and they switch to wanting to hide in a room by themselves or literally throw dishes across the room out of anger. Or they may become bed ridden from muscle aches, intense headaches or joint pain.

THIRD: A person takes a small amount of methylfolate and feels all the methylfolate side effects right out the gate.

Surprisingly, years later, this still holds true.

Methylfolate Side Effects:

[unordered_list style=”tick”]

  • irritability
  • insomnia
  • sore muscles
  • achy joints
  • acne
  • rash
  • severe anxiety
  • palpitations
  • nausea
  • headaches
  • migraines
  • nerves burning, stinging
  • runny nose


If you experience any of the above methylfolate side effects, I highly recommend you discuss it with your physician and get your dose of methylfolate reduced significantly or stopped for a week or two before reintroducing it.

Some people just don’t do well with methylfolate at all – and it may be you – so don’t force it.

Gain a deeper understanding about L-Methylfolate:

Why does methylfolate create such an amazing week and then create such severe side effects so soon after?

It has to do with methylation, pre-existing inflammation, overall nutrient status and other genetic mutations which exist yet you’ve no idea they do.

This gets complicated quickly so I am going to keep it simple.

There are two three four 7 things you can do to quickly quench most of the methylfolate side effects:

  1. Exercise mentally or physically (new)- be using your brain or your muscles, you’ll burn through methyl donors. When I’m on stage presenting, researching or learning something for the first time, I notice I have to take more methylfolate. While the opposite is true as well: When I’m on vacation or just doing something that’s easy, I do not burn through much methylfolate. Exercise increases the utilization of methyl donors so get after it. Go for a run or lift some weights or play some sports – just don’t bulldoze anyone 😉 If your child is going nuts on methylfolate, get him or her outside and kicking a ball around or chasing butterflies. Seriously. Run ’em.
  2. Consider 50 to 100 mg of niacin as nicotinic acid. Why? Niacin is broken down by SAMe. This means that excessive SAM is quenched by taking niacin. Niacin also helps transform folates – especially unreduced folates. There are many other things niacin does as well – beyond my understanding. I continue to look for them and will update this as I learn more.
    • NOTE: You may experience flushing for 20 to 30 minutes. This is not harmful. It simply makes you feel ‘warm’ everywhere.
  3. Consider liposomal curcumin to help quench inflammation. If one takes methylfolate before inflammation is controlled, the methylfolate will worsen it.  One may consider taking 2 capsules of Optimal Turmeric three times a day during times of inflammation.
  4. Consider Hydroxocobalamin as it is an excellent sponge for reducing nitric oxide levels. Methylfolate increases nitric oxide levels – which is why it is so effective in reducing headaches, pain, cardiovascular disease risk, thrombosis, preeclampsia, periodontal disease, etc – but at the same time, excessive nitric oxide levels are harmful as they end up producing serious radical damage via peroxynitrite. Hydroxocobalamin quenches nitric oxide quite effectively. Hydroxocobalamin also works to reduce hydrogen sulfide levels (great for those with high sulfate-reducing bacteria or sulfur-smelling stools/diarrhea).
  5. Limit intake of leafy greens until side effects go away. This is because leafy green also contain methylfolate and nitrates.
  6. Electrolytes – as methylfolate increases, so does cell division and when that happens, electrolyte deficiency can occur. Taking Optimal Electrolyte helps knock out some of these side effects. There is also some niacin in the electrolyte blend. The added potassium and magnesium in active amounts are very supportive of reducing side effects. Given that folates may increase neuroexcitation in the brain, magnesium and potassium are key to help calm this down.
  7. Glutathione – as cells divide with more methylfolate, glutathione levels get further depleted. Restoring levels can help significantly. Do it SLOWLY though – a few drops. Consider Optimal Liposomal Glutathione.

“If I cannot tolerate methylfolate or methylcobalamin, what forms of each could I tolerate?”

I get this question a ton.

If this is the case, perhaps you need to just stop taking any form of folate and B12 for a while. You’ll need to evaluate with your healthcare professional.

The other option is to take other active forms of folate and vitamin B12 which are not methylated.

Since you are not tolerating methylfolate or methylcobalamin, then perhaps you’d do well without the methylated forms.

This is possible.

Folinic acid is an active form of folate that is not methylated.

Hydroxocobalamin is a recognized natural form of vitamin B12 that is not methylated.

You can get them separately or in a combination Hydroxocobalamin and Folinic acid lozenge.

The lozenge allows you to cut it into smaller pieces, easier to use as you don’t have to swallow a pill and more importantly, it allows you to dissolve the nutrients slowly which has the benefit of getting into your system better.

Another benefit? It allows you to remove the lozenge from your mouth if you’re not getting desirable effects – ie side effects. If you swallow a pill – that’s it. You cannot take it out. A lozenge you can.

As with any nutritional supplement, you need to talk with your healthcare professional. Some are more educated in nutritional biochemistry than others.

Long Term Solution for your MTHFR Mutation

Now that you realize that methylfolate may be actually causing you side effects, I’d really like to see you get on a full program vs just supplementing.

Reading my book, Dirty Genes, will help you immensely.

You’ll learn about MTHFR and how to use methylfolate in depth, yes, but you’ll learn WAY more than that.

Empower yourself and take action the right way.

Dirty Genes is the guide you’ve been looking for.

It continues to be a bestseller month after month for good reason.

Dirty Genes book by Dr. Ben Lynch

You’ll see why once you pick it up and start reading 😉

Don’t like reading books? Want to get more in depth and see how it all ties together?
Get access to the Dirty Genes Course where I discuss how food, lifestyle, environment, mindset and genetics are influencing how you’re feeling – and how to deal with it all.

The Dirty Genes Course is where I bring in a lot of published research, translate it and make it actionable for you. It’s an extension of the book, Dirty Genes. There is a lot of science, biochemistry and actual examples of how to use this stuff in your daily life.

Is it going to be over your head in terms of difficulty?

Absolutely not.

You’ll learn a ton and you’ll be amazed how easy it is to implement what you learn.


  • Alina says:

    Dr Ben,

    Happy New Year!

    I’m CBS A360A homozygote and C677T heterozygote. For the last 3 years I’m fighting lyme disease and co infections and had been taking lots of antibiotics and supplements. I’m allergic to almost everything now and feel toxic every time I ‘m taking any medication, vitamins, supplements, etc. I have lots neurological problems and my worse are dizziness, fatigue, leg weakness and numbness. I’ve been taking NAC for chlamydia pneumoniae and helps a bit but makes me tired as well. I understand that with CBS A360A I have sulfate allergy and I have to deal with this mutation first before trying the protocol for C677T. I’ve tried B12 spray before and had very bad reactions to it. Could you please advise what could I do to get better.

    Thank you

  • Adam says:

    Hi, sorry i havent had time to read the entire thread. I’m just wondering if you actually have scientific evidence to back up this method of lowering methylfolate side effects. I mean, it looks nice theoretically and all, but it’d be even better if there were actual studies about a) methylfolate side effects on both the physiological and psychological level; and b) using the methods mentioned above to help those particular side effects , and showing some kind of proof that it did or didnt work. thanks.

    • Dr Lynch says:

      Hi Adam –

      When you have the ability to understand biochemistry and physiology, there is no need for research to back up these recommendations.

      I have plenty of science to back up my recommendation – not to mention plenty of clinical evidence.

      Niacin has been the go to for methylfolate side effects now for some time and continues to be very effective. Hydroxocobalamin is another one that is proving useful.

      This style of medicine and nutrigenomics is too new to have studies on everything we want, unfortunately. In time, there will be but it will take time.

      When you take a screaming angry child or adult who has taken many mgs of methylfolate and you see them improve dramatically within the space of 30 minutes to one hour from using niacin – you quickly become a believer.

      • Adam says:

        Okay, reason I asked is because I seem to have a very adverse reaction to methlyfolate. It reminds me of how mentally ill I was in my teen years, and this has greatly spurred the idea in my head that perhaps im an “overmethylator” , or was at some point. Or for some reason very sensitive to methyl supplements. Now, if a person got adverse reactions from Methylcobalmin rather than Methylfolate, could they also quench the side effects with niacin?

        Also, I’ve been taking a supplement with Calcium Folinate. Does this differ much from regular folic acid? I was guessing it was the best go-between from folic acid to 5mtfh.

        What about hydroxycobalmin? Would this be the superior go-between from Cyanocobalmin to Methylcobalmin, or is it practically the same as one of those?

        DO you have any suggestions for overmethylators (just some words or maybe some links if you already have the info somewhere here)? or is considering oneself an over or under methylator too simplistic and does genetic factors make the issue more compicated?

        Also, is it possible that people could be sensitive to methylation due to other factors, such as mercury floating around in the body and becoming methylated? That’s a crapshoot I’m sure but it was this wierd idea i had in the back of my head which probably holds no credence.

        Thanks a lot for the replies and hope to hear from you soon. I might try the methylfolate soon and quench it with Niacin but im quite worried.

        • Tonya says:

          Adam, did the doctor ever get back to you?

        • KeriB says:

          I think I may have the same issue. My doctor just prescribed this and boy can I feel it! And that’s not in a good way.
          I feel over stimulated like never before. I don’t know about studies but wondered if others felt like this. I appreciate your reply

        • Michele says:

          Go to Mensah Medical and you will be clinically TESTED via blood and urine which will show exactly ifnyou under methylated, overmethylate or have normal methylation, as well as low zinc, copper issues and/ or pyroluria. Both doctors are MD’s and their amazing work is based off William Walsh, PhD – he wrote book “Nutrient Power”. I find it’ insulting to have your excellent questions blown off by Dr Lynch as well as giving a “flip” rude reply. Shame on you! Furthermore, using niacin, a methyl steal IF you undermethylate is a bad idea. In fact, Dr Lynch I totally disagree with your approach and find it quite dangerous.
          And I speak from experience with a son who severely undermethylates and has as done AMAZINGLY well under the care of Mensah Medical for the past several years. You would be wise to learn from both doctors – Judith Bowman and Albert Mensah as well as read the research of William Walsh.

          • Dr Lynch says:

            Hi Michele –

            By reducing symptoms into two buckets – undermethylator and overmethylator – one may have incomplete care.

            While this works at times, over the course of time, it doesn’t because it is focusing on one area only vs whole body.

            I do not support the work of anyone who recommends using folic acid.

        • Dr Lynch says:

          Hi Adam –

          There are many factors which may increase one’s susceptibility to methylfolate.

          – high oxidative stress
          – low electrolytes
          – high glutamate in the brain
          – low downstream cofactors
          – blocked or dirty other genes downstream

          There is no published research because:
          1) it’s so recent and no one is really looking at it.

          2) many believe that methylfolate side effects don’t exist because it’s such an important nutrient. I attended a massive medical conference with over 1500 docs and main speaker said people don’t get side effects from methylfolate

          3) it costs a lot of money to do the research and funding hasn’t been sought out

          4) there is no incentive to do the research

          • Jan says:

            I would like to add that what is considered “normal” levels of anything is something which can vary from individual to individual.
            This can mean that what level of a nutrient one person requires may be quite different from another.
            We are all unique and complex.
            This is an area for future medical study and research.
            So to focus on any one nutrient is, in my opinion faulty reasoning.
            You need to go by how you feel to a large extent until medicine catches up.

          • Bob says:

            Just before recently testing positive as a heterozygote, I took three capsules over three days of Thorne B-Complex #12 with 600mcg of B12 (300 as methylcobalamin), 668mcg of Folate (200 as methyltetrahydrofolate, 200 as L-5-methyltetrahydrofolate, and the rest as L-5-methyltetrahydrofolic acid), and 80mg of Niacin. I also took 3 capsules in three other days of Thorne B-Complex #6 with 100mcg of B12 as methylcobalamin and 80mg of Niacin. I’ve had some bad GI and sleep problems that doctors have left me high and dry with that lead me to try to figure out how to self medicate myself. I am STUPID for trying things like I did on my own, but coincidentally I just realized what my genetic test results meant as being a MTHFR Heterozygote, and just read (AFTER my exposure to this methyl stuff) about adverse reactions to it. I have been suffering chronic fatigue and mental anguish since I took this Methyl B-Complex stuff with Methylfolate a couple of weeks ago, and wonder if there is an antidote for the damage I’ve done??? Will this wear off and allow my system to get back to where it was, or am I stuck in this hell until I do something to counter it? I’m afraid to try anything at this point, but I need some relief badly. My appetite is gone and I have no more weight to lose. What little motility I had has vanished completely, and all my strength is being used to keep my sanity. I’m going to see the Psychiatrist who gave me the genetic test as a result of my medication intolerance, but I’m not getting to him for a couple of weeks and I only hope he knows how to deal with all this. Somebody please tell me that this will pass, my system will balance back out, and I will be back to the way I was within reasonable time??? Thank you for any positive feedback!!!

          • Michele says:

            With all due respect, some people definitely DO get side effects from methylfolates. Specifically those who are undermethylated because methylfolates increase gene expression of sert transport proteins resulting in reduced serotonin neurotransmission. Folates, methylfates and Dominic acidARE excellent methylation agents BUT for the person who has low methyl activity with low serotonin activity are INTOLERANT to any kind of folate including methyl folate. I am a undermethylator and also
            Fall into this low serotonin as well as dopamine and norepinephrine activity. After two days on a methylfolate supplement I had a racing heart, extreme anxiety and felt depressed. I felt horrible. Likewise I feel the same on Niacine and I avoid it bc B3 reduces dopamine and acts as a dopamine reuptake promoter – hence lowering dopamine levels.
            This is good for someone who overmethylates but a very bad idea for
            The opposite group.
            William Walsh has a date vase of over 30,000 chemical assays in this
            Very subject. MTHFR genetic and related tests cannot predict the NET effect of
            SNPS (mutations) that enhance or express methylation. – Lab tests that DO show the net effect of methylation and therefore making treatment extremely accurate are two tests – the SAM/SAH ratio test and a whole
            Blood histamine test. An accurate diagnosis of methylation is essential to effective treatment.
            I will add this – 10 years ago my son had 6 mental health dx and had bad reactions to a number of psychiatric medications as well as certain supplements. I remember Niacin and methyl folates completely destabilized him, as bad as any psych medication.
            We found Mensah Medical and he was tested/ evaluated. He has a severe
            Methylation disorder and undermethylates as his main inborn issue. Along with adding specific methyl donors and augmenting supplements, they lowered his
            Copper, increased his low zinc and treated candida. His response was amazing – all of his symptoms stopped – he was no longer a psych patient bc his brain chemistry was healed. He has remained on his nutrient program; my sister and I – also severe undermethylators are being treated – all successfully and completely.
            Perhaps there are many who treat patients with the MTHFR testing and have success. There were also many MD’s who believed my son needed psych meds and said the Walsh Method would/ could never work. Well it HAS worked amazingly for thousands of people who were desperate and like is, had tried everything. I just hope and pray someone who falls into the undermethylated, low serotonin activity, doesn’t seriously regress if given N3 or methylfolates and decide to hurt themselves. Induced depression by the wrong supplements can be as dangerous as taking the wrong medication.

          • Marcia says:

            Julie said “With all due respect, some people definitely DO get side effects from methylfolates.”

            DUH. That’s the entire point of this specific webpage, but I guess you didn’t read the title of it.

            As for Dr. Walsh and his cohorts, while I’m glad you did well, Dr. Lynch is correct — it’s too simplified to put one in the bucket of being an overmethylator or undermethylator.

            Walsh states that there are five or six different ‘types’, which is also ridiculous, and says if (for example) one has ‘low folate depression’, then you will know you fit this category because you also have ‘high anxiety, panic, are non-competitive in sports, you have food or chemical sensitivities, a high musical or artistic ability, are an underachiever and have low libido’.

            What if you’re artistic, bad at sports, but have a strong libido and no chemical sensitivities? Does that mean there’s ANOTHER category? Of course is, and probably a thousand more.

            You stated that methylfolate results in ‘reduced serotonin neurotransmission’. That’s nonsense, with absolutely no published research to back it up. Methylfolate is a cofactor in the PRODUCTION of serotonin, that’s why it’s used (as well as folinic acid) to augment antidepressants.

            If Walsh or Pfeiffer had any serious credentials, they would’ve published at LEAST a few studies backing up their hypotheses. You can’t say they didn’t because they didn’t have the money. Walsh has made a fortune off of the desperate who fall for his simplistic views.

          • Marcia says:

            Bob — I hope you’ve found some relief since you posted your horror story. I can relate, I wish I couldn’t.

            One thing to mention — when one takes a b-complex, it’s very difficult to know what exactly caused the problem. It may have (and probably was the methylfolate), but it could’ve been the b-6 as well. There’s a thread online with hundreds if not thousands of people who had adverse reactions to b-6, even in tiny doses.

            As for myself, I’m going to stop all methylating supplements for at least a month. I seem to do better with adenosylcobalamin and folinic acid.

    • Amy Habing says:

      Omg. Get a life. You want studies, then find them yourself.

      • Mar Sav says:

        How completely insulting and incredibly unprofessional! Adam was making an entirely reasonable request for studies to back up your claims. It was a very smart and intelligent request. Your answer, on the other hand, leads me to seriously question your education and expertise. Why would you ever treat a person so poorly by making fun of them when they are simply trying to make an informed, educated decision about their health?! Shame on you-unprofessional!

      • Gayle Seaver says:

        I thought Adam presented good questions in a reasonable way. Your first answer was nice and professional. This one is just disrespectful. Makes me doubt your knowledge. Why get defensive? Just one more reason people have trouble with doctors.

      • Barbara Flowers says:

        Well that is just mean. I am searching for answers myself and there are many ideas and Dr.s on the internet that say just the opposite things…confusing and some of us can not afford hiring a a physician to help. So try to be kinder to those of us who are suffering and trying to find answers please.

      • Mean. We are hurting and searching for answers.

  • Shauna says:

    Dr. Ben, if hydroxocobalamin is effective in quenching nitric oxide, I wonder whether it might cause problems for those with the NOS D298E SNP who may have impaired ability to generate nitric oxide?

    This is important to me because several months ago I started 2.5mg methylcobalamin and 800mcg methylfolate and did really well: more energy, less pain, less brain fog. Then after reading some Yasko material a few months later, I added hydroxocobalamin, and now I’m not doing as well. There are a number of other factors that may account for the decline, but the addition of hydroxocobalamin would seem to be a possibility, given that I am heterozygous NOS. I may discontinue hydroxocobalamin for a while and see what happens. But would be curious to know Dr. Ben’s or anyone else’s thoughts on this.

    Also, what effect, if any, does adenosylcobalamin (dibencozide) have on nitric oxide levels?

    • Dr Lynch says:

      Hi Shauna –

      Yes – exactly right. If one takes hydroxocobalamin and has lower levels of nitric oxide, then I would imagine a worsening of symptoms to occur. It may or may not be related to the NOS snp as I am not sure how much that NOS snp affects nitric oxide production. Remember that methylfolate helps recycle biopterin into BH4 which is needed to support NOS and thus nitric oxide levels.

      What rs ID you have for that NOS snp? I’ll look in research to see how significant it is and how it changes the function of NOS. If you have some research or papers on it – please post here.

      • Shauna says:

        Thank you, that will be wonderful to know whether there’s anything relevant in the research. (I haven’t found anything, being limited to abstracts that turn up in Google searches.) The RS ID on the NOS SNP is RS6323.

        • Lawrence says:

          I may be wrong, but my records on rs6323 indicate that it is not related to nitric oxide… my records show that rs6323 is:
          Gene MAO A, Variation R297R, RS number rs6323, Alleles +G/-T (though Yasko says the alleles are +T/-G), Name monoamine oxidase A.

          The only NOS snp that my 23andme records include is the following:
          Gene NOS3, Variation D298E (G894T), RS number rs1799983, Alleles +T/-G, Name nitric oxide synthase.

        • Tonya says:

          Curious Shawna, did the doctor ever get back to you with his findings?

          • Marcia says:

            Tonya, Shawna posted her reply FIVE YEAR AGO. I highly doubt she’s checking this site for replies.

    • Kathleen says:


      I’m not a doctor, just a C677T, otherwise, regular person whom has done a lot of reading on the subject of MTHFR mutations. I read something authored by Dr. Yasko that if a person’s lithium levels are low and they add hydroxocobalamin, the person might experience problems. She advised that it is best to get a hair analysis test done to check lithium levels first. If low, then get the lithium levels up before adding hydroxo B12. Lithium drives hydroxo B12 to the cells.

      • Shauna says:

        Kathleen, thanks. I have read that, also, and my lithium levels on UEE were off-the-charts high, which “dumping” pattern is, according to what Dr. Amy is seeing clinically, not unusual for those with MTR/MTRR mutations, which I have. (As if things were not complex enough, already.) Dr. Amy wrote a note for me to run HMT to check lithium that way. The only trouble with trying to follow the Yasko protocol is the financial burden. Supposedly lithium has to be within a certain range, neither too high nor too low, so we can’t just go supplementing without testing, which is bit frustrating. Thank you for the reminder. I do still need to balance lithium.

  • Jessie says:

    Greetings! My 10 yr. old is compound heterozygous with normal B12 levels. It seems he can’t even handle 500mcg of L-5-MTHF without raging. His doc originally put him on 15mg of Deplin, then reduced it to 7.5mg, with both doses causing insomnia, anger, and borderline mania. We took 3 days off and then the doc started him today on 500 mcg, and he went right back into a rage (niacin to the rescue!). Any suggestions? We’ve been dealing with his mood disorder for 3 years, until we just recently got the MTHFR diagnosis. I had such hopes that we were finally on the right track, but today has been pure hell again. Any advice for what to do if even methyl can’t be tolerated at all? He’s been gluten/casein free for 7 months, eats a whole foods diet, and is in a very healthy home in general. Other than his unpredictable anxiety, rage, and ADHD, we are an otherwise stable household. All help and advice will be greatly, greatly appreciated.

  • Genevieve says:

    Hi Dr,

    I’m very interested by your website but english is not my first language so it’s hard to well understand all the details.

    I received the new that i’m homo C677T. My homocysteine, b9 and b12 levels are normal. I had 2 miscarriages this year following. Naturally, 3 years ago, I had 1 pregnancy that ended up because of trisomy 18.

    I take a lot of vitamines including 5 mg of B9 daily since 2 years. During ivf, I also take 1 baby aspirin daily.

    Do you think that’s enough if my homocysteine and vitamines level are ok. Or you suggest to take the active form of folate? Baby aspirin is enough to avoid miscarriage or should I take heparin or things like that?

    It’s hard to lost baby… The ivf process is not that easy… And this new is an other difficulty…

    Thank you so much for your advice and have a happy healthy new year!

  • Maryanne says:

    Hi Dr Lynch,

    I hope you can offer guidance!

    I started OMV yesterday as I am waiting for my 23andMe results and thought this would be a safe place to start. I took one with breakfast and one with lunch. I was quite energised/jittery until the late afternoon but slept well. Today I have severe brain fog and am back to baseline motivation (aka none). I am confused whether this is a methylfolate side effect or if it sounds more like a sulphur issue set off by amino acids in the OMV. Is this possible with only 2 capsules yesterday? I’m so disappointed as I’ve been brain fog free for a few months although still fatigued. I hope it is transient.
    I have ‘chronic fatigue syndrome’ and have had severe episodes of brainfog before. The worst following surgery and also while treating candida. I suspect I may have the A mutation although I have (slim) PCOS and that often correlates with some of the C conditions.

  • Dave Christensen says:


    I used myself as a guinea pig and gave myself massive doses of methylfolate plus methylation boosters to learn the limits. I took them before bedtime. After a week I finally got too much. I experienced the feeling of my head being in a microwave, and he electricity racing in my brain. It was uncomfortable but no other problems. Taking niacin calmed it right away.

    I believe that there are sensitive people who can get too much methylfolate with just a little. However I think that most people will only have good feelings. While your advice to start slow is wise, I caution you not to make the average person paranoid.

    I have sent several people to your site and their reaction was to be afraid that they were going to hurt themselves by having half a mini tab, and they looked for symptoms with anxiety and expectation.

    Knowing the power of suggestion, the placebo effect, I suggest that you first make it known that this is one of natures most wonderful vitamins that we need every day. People who get lots of it naturally in the Mediterranean diet with lots of fresh green are the healthiest, happiest most disease free people in the world.

    People living on rural farms around the equator have about 1/10 of the diseases we have in America. Multiple sclerosis is unknown in rural India. Access to fresh greens every day of the year is credited for some of this. I’ve never heard of a population of people who suffered any problems from eating lots of greens or legumes.

    On the other hand American’s health declines as we have less fresh greens in our diet.

    This is only a food. You would not get paranoid over eating a second serving of spinach. Most people are only going to feel better for taking this. Life with serotonin is a thousand times better!

    I am homozygous C677TT .

    Expect to enjoy this vitamin! ☺

    • Michael_M_Dowdy says:

      Hello Dave Christensen. I’m not a healthcare professional. Your comment is so true in most circumstances. But even natural and normally healthy things can have deadly potential. More specifically, spinach can be deadly to someone who is being treated with Coumadin/Warfarin for serious clotting issues. I have Factor V Leiden and MTHFR C677T++. I choose to treat my clotting issues with Aspirin because I am absolutely not going to give up healthy foods with vitamin K. I hope and expect to see Warfarin removed as an accepted protocol medication. Nobody will ever convince me that Warfarin, basically rat poison, is safe for humans. Respectfully, Michael Dowdy

      • Jenny says:

        I’ve been on warafin for 27 years with no ill effects. Id take warafin over Xeralto any day. I’d much rather test regularly and know what my clotting factors are than leave it to chance. Plus they are now finding problems counteracting Xeralto in cases of bleeding due to overdose or injury etc

        Long term aspirin use has loads of problems including issues with histamine intolerance.

        Re eating a healthy diet, my original heamatologist told me to avoid iron and vit k rich foods and i ended up sick. All the heamatologists I’ve seen since have told me to eat a healthy diet, still be aware of vit k rich foods and be sensible about the quantities you eat, and your warafin dose can be adjusted when needed.

        • Susan says:

          Hi Jenny, I am Factor V and MTHF and had 2 blood clots years ago. I am an RN. I am in total agreement with you about Coumadin!! I self test weekly and will stay on warfarin as there are no rescue drugs available for these new drugs. I had a hospitalization and needed to get a normal INR/bleeding time and there were several options-fresh frozen plasma and vitamin K are two. On the other new medications there is NO way to stop the bleeding quickly. Pradaxa has a rescue drug but not all hospitals can be guaranteed to have it. So, despite the fun commercials on TV, you and I are the safest!

        • JJ says:

          Eliquis may work for you… my bro had a lower GI bleed on Pradaxa, but has not had any issues with Eliqus. Just an FYI.

  • Amy Brekke says:

    Dr. I need a 2nd opinion. I went to a specializd antiaging natural doctor out in florida that I really respect and I wanted to go off of Zoloft and get on to something natural. After my extensive visit and through a series of strange techniques like pulling down on the arm of his nurse while he touch different parts of my body to see what supplements I would need, he put me on a regime that he felt would work best. I am now on and I hope you are familiar with the brands:
    Cerenity 3 capsules 2 times a day
    Gaia Adrenal Health (which I haven’t started yet because it was on backorder with his office) 1 capsule 2 times a day
    5-MTHF 5mg 1 time a day
    Corticare B 1 capsule 1 time a day
    Omega 2 times a day
    Vitamin D 2000 iu 2 times a day
    L-theanine 200mg 3 capsules at bedtime
    Neuromag Magnesium L-Threonate 3 capsules at bedtime
    Gaba Calm disolve one at bedtime for sleep

    Now aside from the Adrenal Health, I began taking all of this as prescribed Nov 15th. I weaned off the Zoloft and I was feeling pretty good. Accept I noticed that after a couple weeks I started to feel a little more edgy and easily irritated/angered. Then 1 month exactly after starting to take these I began to get severe stomach cramping and diarrhea like every other morning or every 2 mornings. I thought at first maybe I was sick, but it kept persisting. I then thought maybe it is to do with some of the supplements. My doctor is very hard to communicate with because he is in Florida and he’s actually pretty popular and very busy, so while I did put in a request, his suggestion was to continue on the supplements and document what I eat and when I take my supplements and keep a diary of symptoms. I have tried to do this, but am sporatic with it. Anyway, I tried stopping the corticare b and that almost seemed to make things worse. (for my stomach) and then for 3 days now I went back on that and stopped the 5-MTHF and voila, no more cramps and diarrhea and actually I have a little constipation to be honest. But, since stopping that I do feel some anxiety and I feel reved up and have a hard time falling asleep. I don’t know what is going on with me. I hate it and I just don’t know enough about this to know what I should do. I thought maybe I could get a second opinion. Maybe it’s just too much 5-MTHF?? What do you think? Oh and plus the last 3 days I have also had a strange metallic taste in my mouth. Maybe unrelated. But, I just wish I knew.
    Thanks for your help. I greatly appreciate it.
    Amy (mom of 5 and need some help)

    • Kathleen says:

      Hi Amy,

      I’m on this forum because I have C677T mutation. I wanted to comment on muscle testing. I find muscle testing extremely helpful and only use muscle testing to find what supps I need, as well as quantity. Magnesium has caused me gastro distress. Maybe its the magnesium that is causing your bowel distress??? Juicing more than once a day can also causes diarrhea. I had agitation and headaches too. It was from the methylfolate in my multi vitamin. Specifically, initially methylfolate didn’t bother me until taking it daily for about 3-4 weeks. We reach a point where we don’t need it daily (see Dr. Lynch’s podcast). I now take it every 4 days. Listen to your body and take it when you get the ‘feeling’ that you need it. Your body will tell you – just listen. It takes practice and trust in your intuition, together with a little trial and error when it comes to listening and taking action, or not (most likely you do this already). Hormone balancing is helpful, too. But take only bio-identical hormones. Dr. Lee’s Progesterall works very well and is natural. The estrogen you need to get from a doctor (I use an OB/GYN) and it’s compounded.


      • Renee says:

        Hello I hear this a lot about people saying magnesium gives them stomach distress there different types of magnesium 95% of the magnesium out there does go straight out your bowels the one magnesium that you need to get is called magnesium GLYniate doctors best Has a great magnesium GLY that is 100% absorbable And the beauty of it it gets into your cells which is where it’s needed instead of out through the toilet when it’s not wanted. We learned this from a natural path my daughter take 600 mg before bed I take 800 mg before bed it does not give us any diarrhea whatsoever in fact it has helped her migraines and my fibromyalgia immensely

        • Dianna Pele says:

          Hopefully you figured it out by now but this one of magnesium also hurt many people especially those overproduce oxalates I need to be on a low oxalate diet. I just find it so arrogant help people just go around and spout stuff off. What works for some people does not work for everyone. There are many different types of magnesium and each person needs to research the various forms and figure out which one works for them. Do you even know that that form of magnesium is sedating, while magnesium malate actually gives energy??

  • Iatrogenia says:

    Dr. Ben —

    I am heterozygous for the 677T and 1298C MTHFR variants.

    My nervous system has been sensitized by antidepressant withdrawal syndrome since 2004 and I cannot take any B vitamins, they are too activating. This includes methylfolate and methylcobalamin. They will prevent me from sleeping, and I get little enough sleep as it is.

    I try to eat green leafy vegetables every day, but you’ve stated this will be inadequate to compensate for compromised MTHFR variants.

    How would you deal with this? Are there any precursors that would assist methylation, such as n-acetylcysteine, for example?

    • Dr Lynch says:

      Hello –

      If you eat uncooked leafy greens daily, that may be enough support – especially if you reduce your environmental exposures, eat well and sleep well.

      I am currently making a B vitamin complex that is without folate and B12 – it should be available in the coming weeks at

      You may take creatine and some phosphatidylcholine complex to support methylation – also Glycine helps. Taking these during the day is important – not in the evening.

      If you have difficulty sleeping, consider taking 1/2 tablet of Niacin along with 1 capsule of GABA prior to sleeping.

    • Amy Brekke says:

      I take 1-2 GABA Calm disolvable tablets at night to help me fall asleep, I have also used them during the day to calm down anxiety and it works like a charm. Just thought I would put that out there. (Ps Orange taste better than mint)

    • Brian says:

      I just read your comment about being sensitized from antidepressants. Are you saying that you are hypersensitive to anything that might stimulate your nervous system? I only ask because antidepressants and other psychotropic medications cause my symptoms to worsen (e.g. anxiety/depression). When I take them, I feel like my nervous system is being overstimulated and I can no longer tolerate most of this stuff, even at micro doses . I am set to start L-Methylfolate this week, but I am actually scared because of it’s potential side effects (anxiety, insomnia, irritability). I’m just wondering if I am now predisposed to the same thing. Would you mind if I asked you specifically what you experience when you take Methylfolate and B vitamins?

  • Fiona says:

    Two years ago, my doctor started me on high doses of methylfolate (1mg) and methylB12 (1mg). My fatigue and depression were resolved within the week. Then, over time, I started to have severe anxiety and palpitations. I lowered my dose dramatically and felt better at that low dose. Then I ran out of the kind of pill that could be divided. So, I switched to a multi-vitamin from Thorne (Basic Nutrients V) that includes methylated forms of both of those vitamins. More anxiety, insomnia, palpitations. So I stopped taking it. Then, about a month later, I thought I should give it a try, so I took one. Within half an hour the anxiety and palpitations were back and I hardly slept that night. That was two nights ago. The anxiety is slowly fading. I don’t have the other things on hand to see if they will alleviate the symptoms. I don’t know what kind of mutation I have, if any.

    • Michael_M_Dowdy says:

      Hello Fiona. I’m not a healthcare professional. We live in a time that our privacy is quickly disappearing. I prefer to know what’s wrong with me so I can hopefully make some positive differences for myself and others. Carefully think about the decision to be tested and weigh the consequences either way. It’s reasonable to believe that all of us probably have or will have some methylation problems since they’re currently studying only two of over fifty possible locations, specifically the 677 and the 1298. The mapping of the human genome was a huge undertaking. If you decide to be tested it can point you in the right direction to improve your health. Think seriously before you make a decision. You’re at the right website to learn about methylation problems. It can be overwhelming to learn of our genetic mutations. Dr. Ben Lynch and Seeking Health have provided tons of information. You can watch his videos here and on youtube that may influence you one way or the other. Wishing You All The Best. Michael Dowdy

  • Ten years ago I took a high dose of supplements (trying deal with depression). EM POWER PLUS they were called. When I was done with the supplements after one year, my sex drive was about 20%. It was always normal until I started taking the supplements. I thought it would come back but it never did.

    I took a small dose of Deplin two days ago and my sex drive has been zero ever since. Stunning.

    The supplement had huge amounts of folic acid. What happened to my sex drive initially? Why the amazing drop with tiny dose of Deplin?

  • Rose CLaudia says:

    Dear Dr Ben, I just found out that I tested positive for the Mthfr gene mutation, c677t, homozygous. My first question is does this mean that both of my parents had this mutation? My daughter tested positive also she is exactly the same as I. Does this mean it is likely that all of my children have it? How about my siblings? I am working with a functional med Dr, she has just prescribed supplements for me , but never mentioned the side effects that you speak of. I have not yet started the supplements I just received this news. Frankly I am confused about all of it. Any suggestions as to where to go from here? Thank you, Rose Claudia

  • Angeli L says:

    Could someone please clarify when to take the niacin amd turmeric? I have been tested compound heterozygote C677T and A1298C. I began taking 250 mcg in the late morning- only to experience severe fatigue and drowsiness 4-5 hours later for the rest of the day. So, I stopped again until I have an answer to the following question:
    Am I supposed to take the niacin and turmeric TOGETHER with the methylfolate, or am I supposed to wait 4-5 hours until the symptoms occur, and take it then?
    Thank you!

    • Dr Lynch says:

      Angeli –

      Please work with your doctor on this.

      One should take niacin only as needed and as directed – as with any supplement.

      Niacin will increase drowsiness as it increases serotonin.

      To combat that, consider using Tyrosine or the methylfolate.

      Typically, niacin is recommended only when needed and also sometimes before bed as it helps with sleep.

      • Angeli L says:

        Dr. Ben,

        Thank you for the prompt reply! I thought Niacin combats the sideeffects of methylation? I am getting drowsy and extremely fatigued from the methylfolate. I thought Niacin will help that? I don’t have insurance, and therefore don’t work with a doctor. I’d appreciate if you could clarify. Thank you!

      • JJ says:

        Old comment… but it is my understanding that niacin is great for OVERmethylators, because it REDUCES their high levels of serotonin…

        Could you clarify?

        • Dr Lynch says:

          Hi JJ –

          The whole overmethylator and undermethylator concept is too narrow. Niacin actually can feedback inhibit the IDO1 gene which would actually conserve tryptophan and thus steer it towards serotonin. So it may indirectly increase serotonin.

  • Wendi says:

    Hi Dr. Ben,
    My daughter was placed on 15mg of Deplin by her psychiatrist 3 months ago after failing numerous antidepressants for endogenous depression and suicidal thoughts. Within 2 weeks her response was amazing. She went from nearly being hospitalized back to a typical 13 year old girl. Her psychiatrist had given me a copy of the drug study from his journal. It mentioned the MTHFR mutation and the more I read about it the more I was convinced she had to have the mutation. Long story short, I was turfed from genetics to hematology and both refused to do the test. I went to a local lab with a prescription from her primary and she came back as homozygous for the C677T mutation. I was tested too and came back compound heterozygous C677T/A1298C. That was a few weeks ago. Eight days ago my daughter came home from school with a migraine. (She has suffered from them since she was 11). Later that evening she had unbelievable aches in her joints and muscles. When I looked up the side effects of Deplin I knew this had to be it and I didn’t give it to her that day and gave her niacin SR and it calmed down the muscle pain but not the migraine. It has been 8 days and she still has a migraine and still has leg pain. I took her to the pediatrician on Monday and he told us to call the neurologist. She prescribed a medrol dosepack Tuesday and saw her in clinic today. The medrol was not helping so she took her off it after one day. I told her I thought my daughter was over-methylating since her B12 is only 370. She told me to not put too much stock into this mutation and was quite annoyed I was the one who initiated genetic testing and that this opens up a pandora’s box. She said her B12 is considered normal and that this could not be the cause. She barely glanced at the list of methylfolate side effects I gave her and told me my daughter is probably having this reaction because I took her OFF of Deplin. I again emphasized that I took her off of Deplin AFTER the migraine and the muscle/joint aches began so this could not be attributed to Deplin withdrawal. She has now been off Deplin a full week as of today and still has muscle aches and a migraine. The neurologist scheduled her for an MRI, MRA and an orbital scan on Friday. I still think all this is due to too much deplin and a lack of sufficient blood levels of B12 amongst other vitamins as I did not know about supplementing with B12 until it was too late. Luckily I had been giving her riboflavin and magnesium for a couple of years for the migraines. In the last few days I have added in methylcobalamin and will also add pyridoxine. She is seeing genetics on Monday and I am hoping someone will listen to me. I feel very let down as this is a large university hospital and I expected more. Not to mention the fact that I work there as an inpatient pharmacist. It seems as if hematology is the only department that puts any stock in this mutation, and anything else that MTHFR is linked to is treated as hearsay. I had to be extremely pushy to get her this appointment on Monday and I am hoping they can help guide us through this. If not, could you direct me towards a practitioner that will take this seriously? We live in Rochester NY but am willing to travel.

    • Rebekah says:

      Hi Wendi, I’m not a dr, I’m a mom w/a sick 13 yr old as well. Ask the hematologist to have her homocysteine levels checked, that will be evidence that a regular doctor should be able to wrap his/her brain around as to how the MTFHR mutation is being played out in her body. I am sorry she has been going through all this. My daughter has also had episodes of depression that seem to be physiologically based. I recently tried giving her one St. John’s wort pill each morning, that did seem to help. Whatever you try, it’s best to start small and work your way up. The body gets used to one way of working, and it can have a bad reaction to an otherwise good thing if there is too much all at once. You have to look at whatever else she is being given to make sure there are no bad interactions. Look it up on Pubmed to get an idea, there have been studies with children. Don’t get a super cheap brand. I would wait until after the MRI and all that. What ever you can think of to cheer her up, try it. Also, I would recommend you always research any treatment/med that is suggested by your kids docs first. They don’t care as much as you do, and you and your daughter are the ones who will have to deal w/the results. Isn’t it telling how some docs get annoyed and suspicious when you seem to not be clueless about a subject? That is telling….they are not docs you want to deal with. They prefer you to be naive so they can feel superior. If you are in pharmacy, you are smart enough to understand these things, whatever they have learned. Good luck, R

    • Michael_M_Dowdy says:

      Hello Wendi. I’m not a healthcare professional. This is new stuff for most doctors. I was started on 7.5mg Metanx to start after finding I was homozygous for the C677T mutation and I took it for over a month. I don’t get headaches normally but I sure had them then. Eventually I’ve found the right dose for me and it was much less than 7.5mg. This website was the most helpful to me. I take psyc meds too and even though I saw improvement I still continue with my other meds. Methylation problems are treatable but new things have a way of showing up when you change the metabolism cycles. I was in my 30’s before issues linked to my MTHFR mutation showed themselves. I think you did the right thing stopping the Deplin for your daughter when you did. Before anyone knew about the MTHFR gene they made it through life. I’m taking 2400 micrograms a day of 5 L MTHF now and doing okay. The stigma of mental health issues is a serious problem. The ones smart enough to realize they need help are actually ahead of the game in my book. The ones that don’t know they have problems are really the worse off of all. I hope Dr. Ben can point you to a good doctor experienced in nutrigenomics. For now be patient and study to get an understanding of these slightly complicated nutrition problems. Good nutrition and good sleep are extremely important. Foods with the methyl donor trimethylglycine are important. If you and your daughter don’t get the TMG in your diet you may wish to take it as a supplement. It’s inexpensive and readily available. It’s derived from beets. Undenatured whey protein provides an abundance of amino acids which is also extremely important to those with full-blown MTHFR. Immunocal is in the PDR and is sometimes covered by insurance policies. I wish you the best. Michael M. Dowdy

      • Iatrogenia says:

        Note: There is nothing special about Immunocal as an undenatured whey protein. There are far less expensive undenatured whey protein products on the market.

        The company that makes Immunocal paid for some studies to make it eligible for Medicare reimbursement. This is not so much a tribute to quality or effectiveness but plain out-and-out soaking the government for an exorbitantly priced supplement.

        (I’ve corresponded with the company to get their amino acid profile, which they refuse to release — a very suspicious policy for a “medical food.”)

        • Michael_M_Dowdy says:

          Hello latrogenia. I’m not a healthcare professional. Respectfully I have to differ with you about Immunocal. If you don’t know what the ingredients are how can you say there’s nothing special about it? Higher prices for patented items is what encourages further research. It wasn’t by accident that it’s listed in the Physicians Desk Reference. If I could afford it I would use it. The fact that it’s undenatured whey protein which is a huge difference in it’s bioavailability compared to others marketed that are denatured. In processing by using different things like the adding of lecithin to make it easier to mix, the adding of flavoring, heat, and other things destroy much of the effectiveness of other brand whey protiens. To make sure that Immunocal is more effective very strict measures are taken to assure it’s effectiveness and quality, therefore it’s patent. It would be my first choice if my insurance would cover it. MTHFR mutations reduce the efficiency of the body to break down and metabolize amino acids so my belief is add more amino acids and help the digestive system to be able to produce the necessary methyl donors to improve the methylation cycle. Maybe I’m wrong! Immunocal, Deplin, and Metanx are all medical foods but they’re recognized name brand products that undergo strict quality control so they can be prescribed by doctors. Thalidomide used to be prescribed proving things can go horribly wrong. After reversing the twist of a carbon molecule, L versus D, it looks the same in a mirror but the twist can totally change the molecule’s function. As far as soaking the government goes, the government and FDA set forth what they feel is good enough to prescribe. You clearly seem to understand the need for whey protein to be undenatured. I’m using an undenatured and organic whey protein because it’s what I can afford. Study the information provided by the National Institute Of Health website (nih) and see what leucine, a branched chain amino acid found in whey protein, does to the pancreas. Study how a gene can be turned on or off, how environment can cause a mutation, or what the founder effect is and resulting mutations, and the shortening of the strands of DNA with age. Study the Arih2 gene. It’s shocking to learn what information is available if you just look for it. With over twenty thousand genes in a human cell plenty of things can go wrong! The public trust is important but it’s easily shaken. Respectfully, Michael_M_Dowdy

          • Iatrogenia says:

            The amino acid profile of a whey protein isolate is essential to evaluating its suitability.

            I suggest you try corresponding with the Immunocal folks and see if you find their responses credible.

            As a rule of thumb, I would not take any supplement, and I mean any supplement at all, where the purveyor will not disclose ingredients. Supplement manufacturers take advantage of desperate people just as much as pharmaceutical manufacturers do, and will make claims for their products to make sales.

    • Michael_M_Dowdy says:

      Hi Wendi. Based on my own experience Rebekah is absolutely right. How are you and you daughter doing? Hormones are soon coming into play because birth control hormones can cause clotting problems once birth control pills are taken. Ask her hematologist. It may be a good idea for both of you to be tested for other clotting issues like Factor V Leiden since you’re both homozygous MTHFR C677T. Keep studying. Michael_M_Dowdy

      • Mary says:

        Hi Michael – you speak a language that resonates and I’m totally overwhelmed by this as a mother with a child on Deplin. Would you be willing to email with me off the forum?

    • Naomi says:

      HI Wendi,
      I am heterozygous for C677T but have a bunch of other mutations that really impact B12 absorption, conversion to active form and transport to/use by the cells. I would strongly recommend you read the book “Could It Be B12?”. Bear in mind that while it is not a bible it is written by 2 very experienced medical professionals, a nurse and a doctor, and gives excellent advice on the tests needed to establish B12 deficiency (which are NOT done as standard by virtually any medical practitioner) and what the practical level are for B12 deficiency. It certainly sounds like you’re on the right track, though. For the meantime, why not try sublingual methycobalamin tablets and see if they have any effect? And I found that getting my genetic testing done was hugely helpful too. I did it with 23andme. You get a shed load of raw data which is pretty much impossible to assimilate on your own (unless you’re a researcher in genetics) but there are a few really good sites that can run the data and give you a breakdown. Hope this helps.

      • Pamela says:

        If your blood work shows very high levels of B-12 BUT you are heterozygous for C677T – does that mean I AM absorbing B12 but just too much of it? or does it mean it’s not getting absorbed at all and so it’s “floating” around my blood not being truly absorbed. Anyone know?

        • Renee says:

          TO me it means your taking the wrong B12 and your body does NOT know what to do with it since it cant convert it to Methyl which is the entire issue with MTHFR DO NOT take Cyanocobalaminn B12 mthfr have hard or no way to turn it into methylcobalamin B12.. so take methylcobalamin (methyl B12) so your labs show a high b 12 since it just sits in your body.. thats from the research I have done. Join the group MTHFR on facebook lots to learn

          • Pamela says:

            Actually, the form of B12 I’ve been taking for 15 years, since I was first diagnosed with Chronic Fatigue (didn’t find out about C677 till a year ago), is Methylcobalamin PF in injectable form. I get it from a compounding pharmacy that doesn’t add any preservatives to it. What now?

        • Lynn_M says:

          The serum B-12 test shows total B-12, which is the active form of transcobalamin B-12 plus the inactive form of haptocorrin. That is the drawback of the serum B-12 test, that you don’t know how much of the inactive form you have vs. the active.

          That’s one reason the urinary MMA test is preferred as a more accurate indicator of B-12 status. However, the MMA test is actually a measure of adenosylcobalamin, which is active in the mitochondria. Adenosylcobalamin and transcobalamin interconvert, but not also perfectly, so the MMA is not a perfect indicator of transcobalamin B-12.

          • Pamela says:

            Thanks. The test said:
            Vitamin B12 – 1737 HIGH
            Folate (Folic Acid), Serum – >19.9 (no indication of low or high) the optimum should be >3.0 …
            Should I stop any B12 supplementation including the Methylcobalamin shots?

          • Pamela says:

            I should have written the median for B12 – the normal range is between 211 and 946.

          • Lynn_M says:

            I wouldn’t make any decisions based on a serum B-12 test. You could get a urinary MMA test, either as a stand-alone test or part of an Organic Acids Test. Though I wouldn’t be concerned about your level of serum B-12, and I certainly wouldn’t be concerned if that was reflecting a high inactive haptocorrin B-12 level.

            Injectable methylcobalamin is easily degraded by ambient light to hydroxycobalamin. Even though it’s in an amber bottle, unless the bottle and syringe have been protected by wrapped aluminum foil and kept out of the light otherwise, Freddd at Phoenix rising has reported that it degrades to hydroxyB12 in about a week. I like the adenosyl/methylB12 sold at, which comes in a lightproof pump and is applied as a red topical oil that rubs in the skin in less than a minute. It is as efficacious as taking subcutaneous injections of B12.

            If you want to continue with injectable, subcutaneous is supposed to yield better results than IM. More consistent B12 levels are achieved.

            You may need adenosylcobalamin as well as methylcobalamin. I felt a big difference once I added adenosylcobalamin to methylcobalamin. At that time I was taking both sublingually, but I noticed even more benefit once I started the transdermoil product.

        • Renee says:

          Actually I’m still suspicious of this so-called pharmacy that you’re getting your B12 from I would go a whole Nother route to make sure you getting proper they could definitely be slipping you the cheap stuff but overseas especially! I’ve been researching chronic health issues for many years because I haven’t myself I have seen some pretty shocking things over the years as far as pharmacies go.

          • Kathleen says:


            I’d like to try the transdermoil product from the site you mentioned. How does one know which is needed? I’m hetero C677T. Mutated homo are: 2 COMT, 1 CBS, MTR hetero, 3 MTRR hetero. All these are on the NutraHacker with notations about B12. Some are in need of one type of B12 while others indicate another type and are conflicting in some. I won’t be testing. I’ve been using Dr. Lynch’s sublingual Hydroxo B12 (1/2 tab) and B12 with MTHF (MB12). Haven’t had any problems that I can place on B12 or Methylfolate.

        • Shauna says:

          Amy Yasko has found that lithium is critical for getting methylcobalamin into the cells. I had an abnormally high serum B12 level, and then learned through a Hair Metals Test that my lithium level was in the gutter, so evidently my body was unable to use all the B12 that was available in the blood, from my supplementation of sublingual methylcobalamin. You might get your lithium levels checked via either blood or hair test. I am now taking lithium orotate, and although I haven’t yet rechecked my B12 status, it has made a huge improvement in my mood. Anyway, lithium may be something you could look into.

  • Kathleen says:

    Having the C677T mutation, I began consuming lots of dark leafy greens for the folate. NOW, I have a kidney stone!!! My initial concern consuming Kale was my thyroid. Had no idea Kidney stones were a threat to watch out for. How can I consume foods high in folate, dark leafy greens, in order to rely less on supplementation, and not get kidney stones? I have no idea what is to come with this kidney stone – I’m told lots of pain. I thought I had a muscle spasm in my side towards my back just below my rib cage – it was my kidney. Any suggestions on dissolving it? Today I drank olive oil and lemon juice, followed by a glass of water; 30 minutes later and every 30 minutes – lemon juice, water and ACV. Burdock tincture, dandelion tea, Aloe Vera Detox. My kidney is still having pain. No fever.

    • Heather says:

      I am told by my dr that eating only one type of green consistently can cause oxylate issues so there is a need to change the greens that you consume – kale, spinach, corriander, boc choy, mint, lettuce etc.

  • Laurel says:


    I just learned of the MTHFR mutation as a possible explanation for fibromyalgia symptoms, and I’m waiting for the 23andMe results. I have a question about histamine.

    I once took a tablet of niacin (not time released) and had an extreme reaction. Flushing at first, and then severe gut clenching (with vomiting, stooling, and uterine cramping and bleeding.) I actually had the same reaction to morphine during childbirth.

    To have such an extreme reaction to a tablet of niacin, could this be a sign of low histamine? (My thinking is that if histamine receptors are up-regulated due to an apparent deficiency, then stimulating histamine release would cause an extreme reaction.)

    I usually feel terrible when I wake up after 8-10 hours of sleep, but taking histidine makes me wake up perky like a morning person. (It also makes me itch all night, so I don’t really like that part.)

    Anyway, I’m wondering if I should try niacin… starting *very* slow with a time-released version?


  • Marcie Marwood says:

    I have every side effect listed. I have two other complicating factors that could cause similar side effects, but I am suspicious of the Methyl B. I have sent my Doctor a message to inquire. I currently take 1ml per day. I am anxious for relief, especially from the monumental migraine.

  • Rebekah says:

    Hello Dr. Lynch, I have a 12 yr old daughter who has had a lot of symptoms of a mast cell disorder; she did not have a raised tryptase, so the dr we went to sent us on our way. She was a healthy baby. Around age 8 she started having odd symptoms. I took her to many drs and they all wanted to find something common, which they did not. She has been traumatized by all the medical nonsense, so I have been trying to take care of her myself. I put her on a low histamine diet, adding omegas, probiotics, and (occasionally) tumeric for a while. She has improved a lot, but still has symptoms, especially heat, exercise intolerance and fatigue. I did have her dna run with 23andme-and she is heterozygous C677T A1298C …plus I ran her info through and she is homozygous (++) for BHMT-02, 04, and 08. She also has the COMT 158M (AG) and BDR Taq (GG). I have read that with COMT (she is +/-), people may have trouble with methyl donors. Do you think supplementing with L5MTHF and Methylcobalamin would be wise? I haven’t been able to find a dr in my area that will spend any time thinking about her case. We are clear across the country from you in Florida.

  • Chris says:

    Hi Dr Lynch,

    I have been doing methylation injections”fairly” regularly. The other day I did one and experienced extreme fatigue within 10 minutes. I took a small amount of niacin which helped me clear my head. What is going on here? Is it a liver issue? Do I need a liver detox?

    Thank you so much! You are doing good work here.

  • Candi says:

    I started your B12/methyl folate sublingual about two weeks ago. I have since started getting more brain fog than normal but the worst is the heart palpitations. I get them after I sit down.

    • Dr Lynch says:

      Hi Candi –

      You need to discuss dosage with your doctor – and also whether or not it is right for you to take a supplement.

      For now, you should stop using the supplement and consider using the Niacin.

  • Brittany says:

    I am a 25 year old female, diagnosed with depression and ADHD mid teens, was on antidepressants and ritalin until 21 years old. Got off everything, depression never came back, but symptoms of ADHD and extreme fatigue and brain fog did. Put on Adderall, hated it, switched to Vyvance, love it.

    I feel like the Vyvance is just covering up symptoms of the real problem, so am always looking for the ROOT of the problem, in order to treat it.

    got tested, came up homozygous for C677TT. Psychiatrist had never even heard of this before.

    Tried Deplin (while still on Vyvance), that first day felt horrible brain fog and dizzyness. After a week of getting no better, stopped that, and tried just 1 mg of the same thing. Still no better. Took a few weeks off, felt better, started back on at 200 MCG, still felt brain fog, did that until it seemed to get better, thinking I could work my way up, past some kind of “healing crisis”.

    I take supplaments to support homocysteine levels (which are normal) as well as liver function, and I’m up to 1mg of deplin

    The only thing that seems to help (besides vyvanse) is methyl-b12. I sometimes take 50 mg a DAY which can get expensive, and I’m not sure if I can overdose on it.

    should I just stop taking the deplin? am I taking too much methyl-b12? it’s the only thing that lifts the brain fog.

  • Katherine says:

    I am Compound Heterozygous MTHFR and I also have a protein s deficiency. I have know about both of these for 12 years now. While pregnant I took folgard (sp?) and Lovenox. After the baby, I just took a baby aspirin a day and the hematologist told me I didn’t need to worry about the MTHFR outside of pregnancy. FF to last week when I met with my primary doctor (MD and Naturopath) to discuss some other issues and he was curious why I was not taking anything for it. He suggested I take two Methyl-Guard Plus capsules a day. So I started last Wednesday. One in the morning and one in the evening. Late Friday night, I started feeling nauseous and restless. I then vomited twice. All day Saturday, I was very week, tired, dizzy and had a 102 temp. All the things I got when I did a candida cleanse last year to stop the migraines. I had no idea this would come from this supplement. Saturday night I had horrible night sweats and that was the last of the toxin release. Now I have a sinus infection that started on Monday. I did take some activated charcoal on Saturday to absorb some of the toxins. I am treating the sinus infection with raw garlic and raw local honey and a sinus rinse.

  • Susanne says:

    Does methylfolate supplementation affect DNA methylation? Specifically, recent research suggests that some DNA methylation can inhibit tumor supression genes, in ovarian cancer for example. Does the oral supllement increase the methlyation process on DNA?

  • Tammy Tomek says:

    Talked to my primary care Dr. Today, told her of my (+/+) MTHFR didn’t want anything to do with me, told me to talk to my psychiatrist!!! I feel absolutely terrible! Been trying to supplement myself…making big mistakes..lots of side you know of any MD’s in Michigan that will be willing to help me??? I live by Flint no…willing to travel, had to miss work, I don’t know how I have held it together this long. New to all of this and have no family or friends that help me. Iam 52 yrs old..many many different issues and getting worse with age..hard to figure out all alone…I think I took supplements wrong..and probably not the correct dosages. I just learned from your site today that you should not take some at the same time, etc.. just diagnosed 1 month ago from 23&me, c677t ..iam lost, confused,and very sick right now. Thinking of stopping supplements, clear my body and starting over…and still on a lot of persribed medications….need a Dr. To work with me!!!!! Any suggestions?????

  • Colleen says:

    Hi DR Ben,I am heterozygous 677, my daughter 16 years homozygous 677 .i have hypothyroid , CFS ,both b12 deficient . My 3 children all ADHD youngest also ASD .My younger 2 children and husband most likely have one or two copies of the mutation.we are taking optimal multivitamins and kids Op multivitamin from seeking health.Im taking the ones with iron.we started off with 1 daily for one week ,2 daily now 3 daily.i have read with one or two copies we shouldn’t need anymore Methylfolate than what is found in a multivitamin.if we feel ok on say 3 capsules should we stay at that for now even though it’s lower than recommended husband is on 4 capsules a day .my daughter and I have methylcolobamin injections 2 monthly. I have read we need to also include adenosylcobalamin to make it all work well but I can’t see it listed on the optimal multivitamin. If it was we may not absorb it anyway so I’m confused a little.Thanks again Dr Ben giving us potential to improve our health and life .

  • Hi Dr Ben. Thank you so very much for your site. I was diagnoses 10 days ago with c667t homozygous and was put on methyl folate 1000mcg. I also have migraines, Hashimotos and Ehlers-Danlos Syndrome Hypermobility type and Interatitial Cyctitis. In the last week, everything is acting up! I have had daily migraines, forgetting words and things and increasing aching. But what is really bad is intense bilateral calf throbbing! I’ve suffered with this nightly off and on but it is BAD the last week. I can’t even sleep. I called my dr who diagnosed me and she said I should stop the methyl and see if it’s just a virus. And that I sounded dehydrated. So I’m home, drinking fluids and miserable. Do I stop taking the methyl or continue and get some niacin. Thank you.

  • Susan says:

    Dr. Ben, I meet your #3 response to methylfolate: A person takes a small amount of methylfolate and feels all the methylfolate side effects right out the gate.

    History: I have been searching for over 11 years now for answers to my chronic fatigue, fibromyalgia like symptoms. I also have history of complex migraines including hemiplegia, aphasia and classic with aura. I have white spots in my brain that neurologists say are from my migraines. I have had 2 abnormal EEG’s showing temporal lobe seizure activity (I get focal seizures, olfactory hallucinations). I was diagnosed with hypothyroid in 2004 and take 175mcg currently. I have also been on low dose prozac (20mg) for about 12 years (couldn’t get through the day without crying without it). The prozac seemed to help the migraines and my frequency went from about 12/year to about 3/year and they are now mostly ocular migraines only. I was recently put on Oxcarbazepine and Clonazapam for the focal seizures. Using muscle taken during a biopsy in 2012, I recently had that tested for CoQ10 and it came back abnormal/low. I had been taking 200mg/day of Ubiquinol (Hydrosoluable QH) and I upped that to 400mg/day about 6 weeks ago. My neurologist put me on B100 plus extra 300mg B2 which I have been on for about 18 months now. Basically, a “mito cocktail.” My biopsy histochemical and enzymology were basically normal (all levels were low normal) and my carnitine was on the low end of normal. I started levo-carnitine (333mg/3x/day) last fall. I also had organic and amino acids done in 2012 and they were all in the normal range. My Vitamin D has been low or low normal for years as well (20’s to low 30’s). I take 5000iu/day and it’s still not enough.

    My B100 has 400mcg of Folic Acid, B12 (cyanocobalamin) 100mcg and 100mg Niacin (among the other B vitamins). It is the Kirkland brand from Costco.

    1 year ago on Valentines Day, I had an Atrial Septal Defect closed with an Amplazter Septal Accluder. This was found just before my 46th birthday. I wonder now if my mother has folate issues?

    I recently did the 23andMe testing and then read more about the Methylation Cycle defects. I only have one mutation on MTHFR A1298C, (C677T was CC/normal), but, it turns out I have many of the other mutations. The problem is, some of my mutations seem to contradict each other in how to manage them. I am having trouble determining how to interpret these together. I asked to have my homocysteine and methylmalonic acid tested last week. The first came back normal at 7.7, the other has not come back yet. I will add that my CRP-hs has been elevated for at least 8 years (since we started testing it). It is currently 7.8, it has never been below 4. My heart looks great as I had an angiogram at the time my ASD was closed so this is not cardiac. So, I have chronic inflammation and even after losing 20lbs this past year, my CRP went up. I am trying to eat better and have started moderate exercise.

    My B12 plasma came back normal (600’s) and my PCP said to try B-12 and folic acid if I wanted but insisted there was no value in testing homocysteine (which I later convinced him to order). He deferred me to “my specialists” which I can’t find anyone in my insurance network in Colorado. My Neurologist nurse told me to see “my geneticist” when I mentioned the MTHFR findings.. I said “what geneticist,” again, I can find no one for adults in my state (they are all at Children’s).

    So, I am basically on my own. Since the mutations contradicted each other, I decided to try Methyl-B12 (5000mcg under tongue) and Methyl Folate (500mcg in capsule) yesterday morning. Big mistake!!

    I had the following problems:
    extreme sore muscles (like the flu, all over but worse in my shoulders and back)
    extreme achy joints
    mild anxiety
    severe fatigue (fell asleep at my desk at work in the morning, then took a 45 minute nap in my car at lunch, fell asleep for another hour at 8pm)

    Last night after reading your post, I ran to the pharmacy and bought time release Niacin. The only time release one I could find was a capsule and can’t be split so I ended up taking the 250mg capsule. Most of the symptoms improved fairly quickly.

    Here are my mutations that were ++ or +-:
    COMT V158M rs4680 AA +/+
    COMT H62H rs4633 TT +/+
    COMT P199P rs769224 AG +/-
    VDR Taq rs731236 AA +/+
    MAO A R297R rs6323 GT +/-
    MTHFR A1298C rs1801131 GT +/-
    MTRR A66G rs1801394 AG +/-
    MTRR A664A rs1802059 AA +/+
    BHMT-08 rs651852 CT +/-
    AHCY-01 rs819147 CT +/-
    AHCY-19 rs819171 CT +/-
    CBS C699T rs234706 AA +/+
    SOD2 A16V rs4880 AG +/-
    SOD2 rs2758331 AC +/-
    NOS2 rs2248814 A AG +/-
    NOS2 rs2274894 T GT +/-
    NOS3 rs1800779 G AG +/-
    NOS3 rs1800783 A AT +/-

    Here are my medications:
    MEDICATION 8am 4pm 12am
    Oxcarbazepine 450mg N/A 450mg
    Baclofen 10mg
    Fluoxetine 20mg
    Levothyroxine 175mcg
    Levocarnitine 330mg 330mg 330mg
    Aspirin 81mg
    Clonazepam N/A N/A 0.5mg
    Ubiquinol 200mg 100mg 100mg
    B Complex 100mg
    B2 (Riboflavin) 300mg 100mg N/A
    Vitamin E 400 iu
    Vitamin D3 5000 iu
    Vitamin C 1000mg
    Omega-3 Fish Oil 1000mg 1000mg
    Calcium 500mg 500mg N/A
    Magnesium 250mg 250mg N/A
    Zinc 15mg 15mg N/A

    I just also read your reply about not taking Vitamin C within 45 minutes of methy-B12 so that might have been an issue as well.

    What I am taking has helped to an extent. It hasn’t hurt (until the methyfolate and methyl-B12 yesterday). Should I take anymore folate or B12, should I try the hydroxy forms? What about Phosphatidyclcholine (to help BH4)? It looks like CoQ10 and Carnitine were good choices for the CBS mutations, should I add Molybdenum and GABA?

    I just want to feel better and I am not there yet.

    Thanks for the info on the Niacin, it was a life saver last night. If it was the methyl-folate that caused this, does that mean the methylcobalamin is ok or should I switch to hydroxy form? Should I avoid all methyl forms of stuff and assume I am over methylated already? Are my mutations the cause for my chronic inflammation (ESR is normal by the way)? Nothing I have tried to help lower my CRP has helped (including curcumin) and weight loss. My PCP wanted to put me on statins (my cholesterol recently went over 200, up 35 in a year) but my Cardiologist said no need since my vascular system is great and because of my myopathy/myalgia like problems. My PCP pushes statins and said “well I guess if you aren’t going to use them, there is no reason to keep testing CRP.” Well, to me, this is the only measure of my inflammation and a way to see if what I am doing is helping. With my variety of mutations, how to I manage these as a whole?


    Susan Davis

    • Susan Davis says:

      Following up to my own post. I think my first step is to take care of my inflammation. I can’t seem to normalize my CRP (never below 4 and last test was over 7). I have tried taking Curcumin pills for several months, this was before my last test. One of the methylation reports said my mutations indicate I should not take curcumin. I have lost 20lbs in the past year and my numbers still went up. I am also starting some exercise which has been hard due to how bad i usually feel. I am at a loss for how to attack this head on??

      Can I ask also, do my defects play a role in my cholesterol and CRP numbers or are they simply a sign of blockages in the pathway and oxidative stress?

      • Michael_Dowdy says:

        Hello Susan. Have you considered trying virgin coconut oil to reduce inflammation? If you research it you may wish to try it. Medical opinions have changed a little bit regarding coconut oil’s benefits as well as benefits received from red palm oil. It is an easy diet change with possible benefits. I don’t think I’ve ever had testing for CRP or MMA. There is a lot of information available from the nih and ncbi on coconut oil. They also have useful information on the benefits of trimethylglycine as another methyl donor in the diet. I’m only a patient and not a healthcare professional. I hope this is helpful for you.

  • HJ says:

    My daughter (11) has been special since birth. She has *always* had constant pain that is not relieved by OTC meds. She is on serotonin and elavil now, one to act as a pain reliever for her autonomous nervous system (stomach pain without traditional medical cause after numerous medical procedures) and the other to help her mood issues. She has constant random nerve misfires also. I tested her on 23andme and here are her results: hetro MTHFR C667T AND A1298C; homo COMT V158M, COMT H62H, VDR Taq, and MTRR A66G; and hetro MAO-A R297R, BHMT-02, BHMT-08, AHCY-01, AHCY-19, AND CBS C699T. I am not sure if we have any doctors who are MTHFR-literate in our area, and I would like to start her on a protocol. After reading the above, I am concerned about CBS issues before starting metafolin. Can you please advise me?

  • Michael (NW) says:

    Hi, does anyone know where to get these additional methyl defects tested?

    GSTM1 – major detoxifier
    HNMT – processes histamine (primary is DAO)
    GAD – glutamate to gaba
    QDPR – recycles BH4


    • Dr Lynch says:

      Hi Michael –

      What do you mean? You can test all those with 23andMe I believe.

      • Susan Davis says:

        The new v4 chip at 23andMe dropped about 300000 snps including some of the methylation cycle ones. Without the Rs numbers, I can’t check the ones he listed, but it is likely they were dropped. I had several N/A’s when I ran my recent results through several of the online reporting tools.

        • Michael_Dowdy says:

          Hello Susan Davis. Your information stating that 23andMe now use a V4 chip which reduces the snp’s listed/provided by about 300,000 is disturbing to say the least. Do you have an idea of approximately the date the change occurred? I first downloaded my raw data on 09/09/2013 so I hope that my first download included the 300,000 snp’s that you say aren’t listed now. Thanks in advance. Michael Dowdy

      • Michael (NW) says:

        Hi, I did the $99 23andMe test, and it had NOTHING to do with methylation from what I saw. Seemed to be a waste of time and money for me as I was looking for more detailed methylation information. It was more about ancestor stuff and what diseases I might look forward to when I get older, etc… Nothing about methylation like MTFR etc…..

        I did an actual methylation test via Dr. Yasko’s web site, but it didn’t include those other items that I had listed above…..I can’t find anyone who tests for those.


        • Renee says:

          Contact Jessie Armine or Shawn Bean on Facebook for your free first consult to tell you what you need to do.

        • Kathleen says:

          Hi Michael,
          I recently got my 23andMe results. I got the same impression, initially, as you – until I did the next step. You need an interpretation of the 23andMe raw data. To begin that process, I went to and clicked on ‘Sterling App’ which is on the top bar to the left next to Radio Show. Once you hover your cursor on Sterling App a drop-down menu will be displayed. Select Order/View Reports and follow the instructions. The cost is $20 and the app will access your 23andMe raw data and present to you an interpretation with hyper-links to Pubmed research so that you can read the research on the mutations listed in your report. You will see the MTHFR mutations, as well as lots of others. This process is very easy. Once you have the report you can save it to your hard drive. Hope this helps.


          • Susan Davis says:

            I used as well as geneticgenie, promethease, livewello, nutrahacker etc. to upload my raw data and get Methylation gene related results. Some include more snps than others in their report and as I mentioned before, the V4 chip at 23andMe is missing a few that used to be provided. But, I was pleased with all these for different reasons.

        • ML says:

 Is Dr. Armines website he works w Shawn as well… Is helping me with mine really knows his stuff.

        • Michael (NW) says:


          Thank you for all the great responses. I will look into these…

          I have another question, not sure if this is the right forum section to ask, but thought I would try…. I’m CBS ++ and BHMT +-. Since I have an issue in the sulfation process, does this mean I’m not making Glutathione properly? I had another test show that I had a high need for Glutathione…


          • Dr Lynch says:

            Michael –

            There are many reasons why one doesnt make glutathione.

            Most CBS snps are down regulations – and if that is the case – yes – your ability to make glutathione is lessened a bit.

            CBS 699 variant actually increases the ability to produce glutathione – but also hydrogen sulfide – and reduces homocysteine levels too much possibly.

            BHMT snps – many are not clinically relevant. I am still determining which BHMT snp is actually relevant as most do not seem to do much according to research.

            A high need for glutathione has many reasons:
            – low B6
            – low serine
            – high oxidative stress
            – viral infections
            – low cysteine
            – low glycine
            – mitochondrial dysfunction
            – cell membrane oxidation
            – heavy metals
            – bacterial infections
            – etc

          • Michael (NW) says:

            Thank you Dr. Lynch for taking time to respond. I’m actually CBS C699T ++. Previous tests showed I had a high/normal homocysteine levels and high/normal histamine levels. The NutrEval test by Genova Labs, showed I had a high need for B12 and Glutathione. I can’t methylate B12 as I previously had B shots and now my B12 is 1500+. I’m MTRR A66G ++ so that might be why…. So, not sure what is going on. I’m having a SpectraCell test done which apparently looks inside the cells to see what I’m deficient in, sounds more accurate than a standard blood test. It will be interesting to see if I still have a need for Glutatione, etc….

        • Charity says:

          Same- felt like 23andme test was a complete waste of money and it was all about ancestor stuff that was also very incomplete.

  • AW says:

    I am compound heterozygous. I’m 46 years old and have had type one diabetes for 33 years. I started taking Methyl Guard 9 days ago, one tablet per day as per my doctor’s instructions. Felt fabulous and amazed at the difference it made to my energy and concentration. In fact, I felt quite hyped up at times. Then yesterday my doctor started me on 2 Methyl Guard tablets per day. By last night I had a bad headache and felt quite irritable. This morning I still have the headache and also feel very queasy. I rang my doctor who told me to take no Methyl Guard tomorrow and then go back to one tablet a day for another week, and then slowly titrate up. It’s hard managing the headache and queasiness with type one diabetes given I can’t really stop eating… I will persevere!

  • Stephen LaCorte says:

    I would like to note that I am homozygous on MTHFR – A1298C, MTRR – A66G,
    MAO A – R297R, and VDR – TAQ

    I can not tolerate any amounts of methlyfolate nor hydroxocobalamin. If I take either of these together or alone, I get severe insomnia (even when taken early in the morning). 3am the following night feels like it should be 3pm after taking these. The effects where off with discontinuance.

    Also, I would like to point out Dr. Julia Newton’s research at the University of Newcastle that demonstrates a correlation between cerebral vascular control and skeletal muscle pH in CFS/ME.

    The discussion of this research surmises that the periphery may be affecting the CNS. This may be due to a pH gradient problem between the blood and the muscles. The research refers to another study showing increased lipid peroxidation indicating a poor membrane integrity speculating this as a potential pathway for pH gradient issues between the muscles and blood.

    More recently, Dr. Newton gave a preview of her current research (soon to be published) at the Action for ME Conference in the UK. This video clip of her presentation suggests more and more the possibility that the periphery is responsible for problems in the CNS for patients with CFS/ME. I asked for Dr. Newton’s opinion on whether this may be the case in an e-mail and she responded, “possibly.”

    This research may help pave the way for more emphasis on problems with the redox potential of the cells in the muscles of patients – e.g. methylation, glutathione depletion, etc.

  • Jodie McGuire says:

    Hi Dr. Ben,
    My Dr. put me on a daily injection of methylfolate/B12 right out of the gate. She warned me of over methylation by saying, “If you get flu type symptoms, take some niacin”. She never warned me about the anxiety and insomnia. In no time at all, I was LOSING MY MIND with the most severe anxiety, nervousness, racing thoughts & insomnia I have ever experienced. I did not put two and two together until about 10 days into my injections when I googled if they could be causing my symptoms. I was LIVID! I now use your Seeking Health brand and I just break it in half and take it every other day. Been doing so for two weeks and thus far I haven’t had any bad reactions.

  • Sharon Elston says:

    I tested positive for one heterozygote MTHFR mutation C677T, after having been on a prescribed 1 mg 5MTHF for about a month beginning Aug 2013. There were no noticeable side effects, although I’ve suffered from joint and muscular aches for about 10 years. I am a 63 yr old female. My (substitute) naturopath prescribed it because she thought it might be the answer to my perpetually low B12 levels. Since she told me that my test results were “normal” , I had given it no further thought.
    Since then, my regular naturopath has reviewed my test results and sent me to this site for more information. Under his care, I am currently preparing to take a Spectracell test to determine my nutrient levels in order to better understand my supplement needs. In the meantime, I have stopped using the 5MTHF as well as most of my other supplements. Any thoughts on this?

  • Jaime says:

    Dr. Ben, I really hope you can answer my question. Is it possible to get a reaction from foods that are high in folate? Every time I eat a cup of cooked spinach I feel the same kind of anxiety/agitation like when I take methylfolate. I am heterozygous1298c. It has happened several times (at first I thought it was a coincidence). Is there a connection? Will taking niacin with my spinach help? Thank you so much for your outstanding research and wonderful website.

    • Dr Lynch says:

      Jaime –

      Yes it is – absolutely.

      Do ‘pulse’ your eating of folate rich foods. I notice too that I may feel a bit over the top with green leafy veggies.

      Eat more proteins and reduce the veggies to balance out a bit.

      The niacin can help.

      It may also be high nitrates in the spinach. Consider also hydroxocobalamin and/or glutathione to help reduce the nitrates from oxidizing and reducing the amount of nitric oxide.

      • Jaime says:

        Thanks so much for your confirmation and advice! This is all so complex and yet I know I need to figure it out. I greatly appreciate your generosity to take the time to answer questions and share this important information.

        • Lynn_M says:

          Spinach is also very high in oxalate, which can cause reactions.

        • Michael_Dowdy says:

          Hello Jaime. Lynn_M is quite correct. You need to be careful and balanced because kidney stones can form. Excessive protiens can be harmful. I’m fortunate and have never had a problem with kidney stones because I’m horrible about not drinking enough water. Drink good pure water like distilled water to protect your kidneys and flush harmful build-ups. Be careful to not over-treat problems and always check to see if you may be taking toxic levels of anything you take on a regular basis. One size does not fit all and we’re all different. Toxic levels may be necessary to correct some problems but should be reconsidered when using long term. Michael M. Dowdy

    • Stephen LaCorte says:

      I am homozygous 1298C and on MAO A. I can tell you first hand that when I juiced red dandelion greens, I had severe insomnia, felt very hot, and mild muscle twitching on the nights following. Unfortunately it took me three nights of this suffering to discover the connection. I am also curious if niacin might be helpful for this kind of reaction.

      I cannot tolerate any amounts of methylfolate or hydroxocobalamin – any amounts (even when taken early in the morning) will cause insomnia and some anxiety. If I take a large dose, I won’t be able to fall asleep until at least 3am. I get very wired by tired from lack of sleep. The benefit I do get is more energy and less feeling of air hunger. But the bad definitely outweighs the good for me.

      • Kathleen says:

        I’m experimenting with magnesium to help with sleep, because when I began correcting for C677T sleep disturbances also began. Magnesium is doing the trick in helping me to sleep through the night. I also take GABA 100mg, 5HTP 50mg, and Ornithine by Now. Once I added the magnesium I began to sleep thru the night but I still take all the other stuff listed before bedtime. I’m looking more into magnesium deficiencies and looking at RnA drops (magnesium that supposed to be delivered to cells). But just from Natual Vitality magnesium in small amounts I’ve had improvements in wellbeing and sleep. But magnesium can cause a huge disturbance to the bowels – I learned the hard way. That’s why I’m looking into RnA Drops. Hope this helps.

        • Renee says:

          Using magnesium glycinate As your magnesium supplement cutback any stomach discomfort 99.9%! Find your best dose by adding one capsule every day until you have a soft stool That will be your cell Saturated dose! That’s what my natural path had me do and it’s worked beautifully for years. Best of luck

  • terri says:

    Hi all, I notice on here answers are few and far between but I thought I’d try anyway as I’ve read through everything and can’t find anyone with my issue. I’m heterozygous 677 and 1298 with normal homocysteine levels (6). I have anxiety, ocd that comes and goes and panic disorder daily for the last 7 years. High stress brings this on but it seemed to last longer this time than back when I was younger. (I’m 32). I am single and have no children. Last summer I had food poisoning or something that spurred lpr and reflux symptoms with throat spasms that were worsened by anxiety and 7 month later I’m still healing. I’m lactose intolerant and off gluten and grains right now. I upped my greens but stopped almost all supplements because of stomach reflux issues. I have taken 5htp, NAC, and a host of other supplements for anxiety for years and we haven’t been able to balance neurotransmitters for years now as per urine tests. Since my homocysteine is normal, how would I go about treating my neurotransmitter problem? I don’t want drugs, I want to treat it from the root. I want to helpy body make and balance its own neurotransmitters. Keep in mind I’m on a 10 food diet right now while weaning off Nexium and healing my lpr and swollen throat. Any advice is helpful and appreciated. I’ve searched the web bit no luck.

    • Kathleen says:

      Hi Terri,

      I’m on here because of C677T hetero. My friend 1298 and 677 but doesn’t have the issues you describe. Perhaps other mutations causing the anxiety, etc. I have anxiety issues but not debilitating. Both parents have anxiety disorders. I first noticed anxiety by awakening in the middle of the night with a sense of rushing adrenaline for no apparent reason. I figured it was anxiety. I taught myself EFT (see using the video library that I purchased. The anxiety went away and never bothered me again that same way, in the middle of the night. I’ve always had social anxiety issues (hate the word disorder), and I neutralized that problem by about 90% using EFT, which is a meridian tapping technique. It works! I believe that I can also correct mutations by using tapping and cannot see why it wouldn’t work. Should you decide to learn about EFT and the technique of using it, you will see how you can change how your DNA expresses. I recently began taking Lithium Orotate 20mg/day and I feel better, not that I was feeling bad but I noticed an improvement in my mood and energy level – more buoyant and outgoing. My 23andMe uncovered some unpleasant things that I need to be watchful for and avoid stress, and litium was suggested on the NutraHacker report I purchased. I highly recommend NutraHacker to analyze your 23andMe raw data, in addition to uploading the raw data to I also found inositol to be calming. The NutraHacker is going to tell you what you need to take. From the NutraHacker I learned that Tyrosine would be helpful, and that was on my intuitive radar. Hope this helps.

      • Terri says:

        Thank you Kathleen. I was on Lithium orotate 5 mg. for years and yes, it does work on mood. I recently stopped all supplements for anxiety because I want my body to produce its own neurotransmitters. My DO/MD has a high autism population of patients and says he is well versed in MTHFR. He tells me there is no CBS or SUOX test but would look into CBS. He doesn’t think highly of Amy Yasko and the tests are too expensive. In addition, is down while the FDA investigates and they have a disclaimer that they only do heritage nationality testing and not health testing right now. My doctor also didn’t seem to think highly of it either. He gave me B12 liquid, methylfolate 1000 mcg as well as what is in my multi vitamin, and DMG liquid to take. I haven’t started any of it. He is blood testing my heavy metal detox ability, B12, folate and doing a food sensitivity test next week. He says there are no tests for methylfolate levels. So, aside from Amy Yasko and 23 and me which is not up and running, does anyone know of a CBS, SUOX and COMT test that is affordable? I’m supposed to go back on the NAC that I’ve been on for another reason for like 5 years, as soon as possible but I don’t want to until I have CBS tested. Also, what is the link between low neurotransmitters and MTHFR? Is it COMT?

        • Rebekah says:

          As far as I know, the 23andme test will still give you the genes, you would just have to look them up one by one in the area where your personal info is on the page. You would go to the spot, and type in, say COMT, and you would get all the ones that 23andme has of yours. Last I heard, it cost $99., which is pretty cheap for all the genetic info you have access to. If you really want all that info, mine as well pay less for it–just do a little digging to find out if you will be able to access the info, and the price…You would have to find out if the alleles you have are considered problematic, so you would run the data through the Prometheus program or the few others that are available. IDK if the feds have gone after these companies yet, though.

        • MIchael (NW) says:

          Hi Terri, why doesn’t your doctor not like Dr. Amy Yasko? I did take the Methylation test that is available on one of her web sites. It was expensive. But, the problem I have with it, I have multiple defects and they recommend too many supplements. I know that would not be good for me to be taking all those things and would be expensive. I need to find a doctor who knows more about this stuff and put together a plan to get the methylation cycle working better. I’ve done my own research and have put together my own plan for now as I don’t have any local doctors around here that really know anything about this stuff. There is one cardiologist who has a web page that goes into great detail about how to support the different defects, but not sure how he got his info, but he seems to know what he’s doing so I’m pulling ideas from his info to help with my methylation defects.

          Anyway, I have tried Lithium Orotate 5mg and even 10mg now and then, and it does produce a calming effect. My ND said I could try it, but try it consistantly for awhile to see how it works. He treats people at doses up to 15mg-20mg I think. I’ve read reviews where people said it helped with anxiety and depression and they are not bi-polar. Sounds like it can be a helpful mineral. So, I will try it consistantly for a while to see how it goes.

          You said you stopped all your supplements due to anxiety. Did you figure out what migth have been causing your anxiety? I guess it depends on what all you were taking. I know that certain supplements will cause me to feel stimulated. And I suppose if you take something that your body didn’t need, ou might push your methylation cycle the wrong way.. Kind of a trial and error some times, and finding the right balance. I just wish I knew of a doctor in my area who knew more about this methylation stuff, it’s just such a new technology.

          I’m pretty disappointed with the 23andme test. Didn’t provide any methyation data that I could see. But the test I took from, which I think is one of Dr. Yasko’s site was helpful. Just didn’t like the suggestions they made to fix things as I thought it was a pretty canned recommendation. And didn’t seem to be very customized for me, and didn’t really provide a good plan. Just here are all the supplements to take for these defects, etc. And there were lots. So, I just take my test results and show other doctors hoping for some insights (haven’t really gotten any but have found doctors interested in looking at it), and do my own research and seem to be doing okay so far.



        • Dr Lynch says:

          Terri – 23andMe is up and running – read this genetic testing article and follow the instructions how to run the data through and get a report.

  • Pamela says:

    I was diagnosed with a single C677T mutation a year ago, the doc that tested me for it told me to take 1 cap of Methyl Protect (which has 2000 mcgs of Folate and 1000 mcg of B12). He said all I needed to do is take two a day for the rest of my life and that was it. Well, by October of last year I was waking up with severe inflamation of my joints in my left hand (pain/stiffness), that would go away after a few hours. Then in December I started having mild anxiety (attacks) and in January low level depression, plus weird feelings in my brain (emotions), also, had blood work in Dec that showed super high levels of Vit B12 and Glutamate/Glycine, so I decided to do some research of my own and that’s when I found your website and learned that it’s not that simple. So I stopped taking the Methyl Protect completely and started taking 100 mg of Niacin every day, plus Thianine, and this week gave up gluten and most dairy. I have an appt with Dr. Nancy Mullan today who is an expert on Methylation Genetics to help me balance my chemistry.

  • Kathleen says:

    Dr. Lynch, or anyone who might know:

    How does one increase Bh4?

    Thank you!

  • Adrien says:


    Could seborrheic dermatitis and periodontal disease an indication of methylfolate deficiency? Thanks

  • Terri says:

    I am heterozygous for both 677 and 1298. I have been on Vitaprime, a multivitamin which has 400 mcg of B12 and 800 mcg of methylfolate, for several years. My anxiety, OCD thoughts, and panic attacks have not improved. I was also on 5htp and several other supplements for this but stopped them last month. I’m interested in my body producing more neurotransmitters on its own. How do I go about this? My doctor just put me on 1000 mcg B12 methylcobalamin liquid twice a day and 1000 mcg methylfolate in addition to what is in my vitamin but I have only taken B12 once a day and haven’t started the additional methylfolate because I’m worried about side effects. He also wants me to take DMG. Can you give me your thoughts on all this and what am I missing as far as helping my body produce neurotransmitters. Also, I have cricopharyngeal spasms and LPR symptoms of reflux, swollen throat, digestive issues. Being on a 10 food low acid low histamine diet is really helping. Lots of kale and greens and some proteins and apples mostly.

  • Terri says:

    I also want to say that I took the B12 liquid (methylcobalmin)1000mcg for a few days and felt weird in my head, like not myself. So I cut it down to 500mcg today and feel ok. Also, my multivitamin has 50mcg of B12 methylcobalmin and adenosylcobalamin and 60 mg of Niacin and Folate is 400 mcg. I mistakenly thought it was more. None of this has helped my anxiety over the years. My doctor doesn’t seem to want to test for COMT and MAO but they are responsible for breaking down neurotransmitters, right? Is there something I can get tested to see how well I’m making neurotransmitters? What is stopping my body from this?

  • Caroline says:

    I am very confused by the terminology being used on this website. My understanding is that the normal gene is 677CC. A heterozygus mutation is 677CT. A homozygus mutation is 677TT. So you can’t be homozygus 677CT you would be 677TT. Also when I got my 23andme results back it did not have results for two genes, just one, and it was 677CT. I also have a heterozygus 1298CA (normal is 1298AA and homozygus is 1298CC). I understand that we have two copies of every chromosome except males who have the xy, but I’m not seeing on 23 and me results where it tells me results from each gene. It just says that i have the 677CT and 1298CA mutation, but doesn’t tell me if it is on one gene or both. Can someone help with this?
    Incidently my homecysteine was 16.8!! I started on a supplement with B6, B12, TMG and regular folic acid (5mg) and it went down to 7 something. I am now taking the active form of folate along with many other supplements. I took 3 mg yesterday, headache today (and i never get headaches), so I reduced to 1mg and will try adding niacin and curcumin. Thanks for all the info on this site. I wish more people knew about this.

    • Susan says:

      Caroline, here is how I understand it. If you use the terminology C677T, that means that at point 677 on MTHFR Gene, you have a C to T translation. So, if someone says they are homozygous C677T, it means that both alleles have the C->T mutation. On 23andMe, when browsing, that would show up at TT because they show you the findings for each allele (not what it was expected to be or the commone allele type). So, when browsing, you would see CC, CT or TT to indicate your 2 copies. If you see TT, you are homozygous for the C677T mutation, if you see CT, you are heterozygous for the C677T mutation and of course CC means you are normal for the C677T mutation (meaning you don’t have it). I haven’t really seen the notation 677CT, but in that case, you I think you would be notating what each of your alleles show. I believe however that 677 C>T is the same as the C677T notation meaning C becomes T at 677. Note also that 677 is not a GENE, but a location (or snp) on the gene MTHFR (that codes for a protein).

      A gene will have many bases, every 3 bases is a codon that defines an amino acid. If you look at this chart: You will see that some amino acids have several combinations of codons that will define them (example, Valine= GTT, GTC, GTA, GTG, you can see that the 3rd position ca be T, C A or G and it will still code for Valine). So, for example, base 677 is the middle base of the codon (677/3 = 255.66). So, if you know what the 3 bases at 676,677,678 should be, you can see what it codes for. Then, if C becomes a T in the middle, you can see what in now codes for by looking in the chart. For some mutations, the change does not affect what it codes for, I think those are called “missense mutations.” basically, those types are not problems. But, if the mutation changes what it codes for, then it becomes more a possible issue.

      I agree, the notation can drive you batty. It is really confusing. I hope what I explained makes sense. I wish that 23andMe would atleast tell us what the “Expected Allele” is when we are browsing. Also, I think that A=T and C=G when you are researching.

  • Adrienne says:

    I have a quick question regarding taking Methyl Guard – I have started off slowly, one tablet per day and increase by one tablet every week. I am now up to 3 per day, and am taking 2 in the morning and 1 in the evening. I have the worst insomnia, and was awake until 3am last night. Should I be taking all 3 of the tablets (and subsequently 4, 5 and 6) each day in the morning? Or should I be taking the tablets in two doses a day, say 2 in the morning and 1 or 2 in the evening? Will taking them all in the morning assist with alleviating the insomnia? Many thanks 🙂

  • Adrienne says:

    I have a quick question regarding taking Methyl Guard – I have started off slowly, one tablet per day and have increased by one tablet every week. I am now up to 3 tablets per day, and am taking 2 in the morning and 1 in the evening.

    For the past 2 nights I have had the worst insomnia, and was awake until 3am last night. Should I be taking all 3 of the tablets (and subsequently 4, 5 and 6) in the mornings? Or should I be taking the tablets in two doses a day, say 2-3 in the morning and 2-3 in the evening? Will taking them all in the morning assist with alleviating the insomnia?

    Many thanks to anyone who can assist with this – I am compound heterozygous and new to all this 🙂

  • Ashlee says:

    Hi Dr. Ben-

    I am 8 weeks pregnant and have been on optimal prenatal for a year(800 mcg folate). I’ve been doing really well-sleeping 8-10 hrs per night. My ob convinced me to up my folate by 400 mcg. I couldn’t sleep a wink! Was this dangerous? Do you recommend just dropping back down? Since I am still in the first trimester, I am worried about doing permanent damage.

    Thanks so much,

    • Dr Lynch says:

      Hi Ashlee – sleep is important 😉

      I’d inform your doc that you are not sleeping.

      Reducing back down is likely the best option but again – that is up to your doc.

      Increasing magnesium may also be supportive.

    • Kathleen says:

      Hi Ashlee,
      What if you backed down to 800mcg, then slowly increased your folate to what your doc wants you to take. My sleep was also disturbed, for some reason, and magnesium has completely helped in getting and keeping me asleep through the night. I use Calm magnesium by Natural Vitality, but go slowly at first. I did the recommended 1tsp dose and it caused bad diarrhea. After being at the dosage of 1/4 tsp for about a month, I recently increased it from 1/4 tsp to 1/2 tsp before bed, because I’m reading a lot about magnesium insufficiency in many people being common. Seems magnesium is the foundation of the function of our enzyme activity and when we get methylation working better by taking folate the demands for magnesium increase, putting more pressure on our body’s for magnesium that it doesn’t have enough of, so our sleep suffers.

      By the way, I’m not a doctor or a member of the medical community. Just sharing what has worked for me.

  • Jan says:

    Dr. Ben,

    My daughter had her first methylated b12 injection (only .5 ml) and had a severe reaction (chest pains etc.) She is homozygous. Since the injections are too much for a start, what do you suggest in terms of a sublingual option? And should she take the niacin now even though the shot was a week ago? She still feels horrible.

  • Kreiss says:

    Hi Dr. Lynch, I suffer from severe depression. I was tested for gene mutations and got this, but don’t know exactly what mutation it is:
    MTHFR T/T – The explanation says I have reduced conversion of folic acid to methylfolate.
    COMT val/val. – The explanation says I have higher COMT activity.

    My doctor prescribed for me 15 mg of deplin, along with an antidepressant, and I got very anxious. I told the doctor, and he insisted it was not due to the deplin. I stop taking the deplin, but since then I feel anxious. I also, have the COMT mutation. How do you treat patients who have both mutations, and is there anything I can to do stop the anxiety. What tests do you recommend I should do. Thank you very much for your help.

    • Lynn_M says:

      You are homozygous (double mutation) for MTHFR C677T. The COMT is normal, ie., unmutated. The COMT they are referring to is COMT V158M. Met/Met is the mutated version.

      Your doctor is ignorant. Anxiety is a well-known phenomenon resulting from the high levels of methylfolate found in Deplin. Niacin will be helpful in relieving the anxiety. Dr. Lynch has discussed the use of niacin to counteract the effects of methylfolate many times on this website.

      You need to start at much, much lower doses of Deplin or methylfolate and slowly build up. Maybe half a gram to start with, although some people are sensitive to even that much. You also should be taking methylcobalamin, aka methylB12, and probably other nutrients as well.

    • Michael_Dowdy says:

      Hello Kreiss. Lynn_M is certainly correct about how powerful methylfolate is. It may well be the most powerful substance I’ve ever used. Not knowing your doctor though I don’t think I’d call him ignorant, but I would say he’s uneducated in treating with Deplin. Four hundred micrograms may cause powerful and unwanted side effects. Fifteen milligrams might be enough to treat you for a whole month. You’re at what is probably the best site to learn about MTHFR mutations and how to treat them. Study the blogs about the effect methylfolate has on patients. I’ve been treated by a very knowledgeable psychiatrist for nearly twenty years now and even though I feel better after taking methylfolate his recommendation to stay on the medications he has prescribed for me as well is obviously the right treatment for me. If your doctor doesn’t realize that he needs to listen to you and learn more about these new findings then maybe he is ignorant. A lot of patients have a pretty good idea of what’s wrong with them and their doctors should listen to what their patients say

  • Joe says:


    You sound very antagonistic and potentially mentally ill. Why must you fight the good doc on this matter so? ODD?


    • Alan says:

      What in the world?

      Pop psychology is not of much use in a place like this, but if you can’t resist, at least quote the exact words of the person you are attacking.

      I can find nothing posted by anyone using the name David that remotely deserves this kind of nonsense.

  • madge says:

    hi dr ben —

    i recently tested positive for 2 copies of the A1298C mutation (homozygous).
    (C677T was neg/normal)

    my MD prescribed 500 micrograms methylfolate daily and in a week start methylcobalamin 500 micrograms daily.

    i began with a pill form of methylfolate 400mcg by jarrow. i didn’t feel so great but had maybe a touch more energy. then i found the seeking health supp. line and first started with one optimal chewable multi and felt actually worse. today i just did a half of an active B12 with L-5-MTHF only and feel almost non-functional (nausea, fatigue, short of breath, achy). is the sublingual / losenge or chewable version more potent to the system or any thoughts? i know my gut isn’t great. i’d love to be able to take your formulas bc they are made precisely for MTHFR. if you suggest niacin is there a brand or form of it that is recommended? and do we have to continually take niacin with these supplements?


  • Naomi says:

    Started with 400mcg metafolin to 500mcg methycobalamin to 50mg niacin back at the beginning of September. Dropped the niacin (wasn’t getting any side effects) and added 100mg B6 by end of October. Gradually titrated up from beginning September 2013 to now (March 2014) to 8000mcg metafolin to 10,000mcg methylcobalamin to 200mg P-5-P and feeling wonderful! I got my genetic profile done with 23andme in December and results came back in January. They indicate multiple mutations affecting B12 absorption, conversion and transport into/out of cells, as well as a high tolerance for methyl donors. Been TTC our second child unsuccessfully for almost 2 years at age 42 with endometriosis, cysts, fibroids and adrenal fatigue; since Sept 2013 (and taking metafolin/MB12) my cycles have regulated, lengthened and resolved luteal phase defect. Since increasing the doses of metafolin/MB12, basal body temperatures are now in healthy range (very low before) and stable, as are all other fertility signs. General health has improved, along with energy, endurance and clarity of mind. Thanks for all your work on this topic, Dr. Lynch. It has been incredibly helpful.

  • Sue says:

    My husband is Compound Heterozygous.

    His naturopathic doctor started him on one tablet of Homocysteine Factors by Pure Encapsulations. He was instructed to take in it the morning on an empty stomach. Within a 7-10 days she increased it to 2 tablets at one time, in the morning, on an empty stomach. He also started taking the probiotic that she recommended – Florajen 3.

    After several days of taking the increased dosage, he broke out in a HORRIBLE rash/hives all over his body. He was very sick. He stopped taking both of the supplements and contacted the doctor who did not believe the problem could/would be from the new supplements.

    GRADUALLY, with a lot of Benadryl, the reaction subsided and 3-4 weeks is pretty much gone. My husband has been on a long list of prescription medications for his heart, COPD, and arthritis pain for a long time. More recently he has been experiencing gout.

    My husband did start going for acupuncture treatments – one treatment so far. It did make him feel better. The acupuncturist said his liver is not happy and gave him a supplement which does not seem to bother him.

    My husband is now very reluctant to try the MTHFR supplement again.

    Could the problem be that he was detoxing too quickly? Any recommendations?

    Thanks for your help.

    • Selina says:

      Hi Sue.

      I am homozygous for c667 and had started taking the active b-12 with methyl folate. After about a week and a half I started breaking out in hives. It was super random. One day it was half my scalp, on another day it was my neck. My thumb swelled up and turned bright red (like I had smacked it with a hammer) and my upper lip even swelled up one day. My doctor told me it was detox. I started taking liver support supplements and continued with the b12 and eventually those symptoms went away. I don’t know if this info helps your husband, but that is what worked for me.

      • Dr Lynch says:

        Selina and Sue – and others experiencing hives/runny nose after starting methylfolate/B12:

        There is increased SAM production in the body when giving b12 and methylfolate – which is a bonus; however, the histamine may not be fully broken down if one is low in vitamin B1 or vitamin B5.

        For this reason, it is a good idea to start with a trace mineral complex (with food) and a b complex without folate and B12 to support all pathways prior to pushing SAM production.

        Talk with your doctor about this.

        • Terri says:

          Is there a certain form of B1 and B5? Is there a test to determine our levels? My histamine level is normal but I have extreme congestion (no allergies according to the allergist). We think the congestion is from reflux/LPR reflux but can it be related to MTHFR? How can we tell if histamine is broken down?

        • Sue says:

          Received the Trace Mineral Complex and B Complex Without Folate and B12 yesterday and my husband started taking them this morning, after breakfast.

          1. Is one capsule of each enough? He’s a large person. Does that matter?
          2. Does he wait until he’s feeling good or at least better to start the Active B12 with L-5-MTHF Lozenges?
          3. Should he avoid leafy green vegetables until he starts the Active B12?

          It seems like everything we’ve done lately has only made him worse and he keeps getting sicker and sicker. The rash/hives on his arms is horrible and he feels achy all over.. He spends all day and all night in his recliner and just walking from his chair to the bathroom consumes all his energy.

          So far we’ve avoided going to his regular doctor who would mostly likely prescribe prednisone and antibiotics as he has done 3 or 4 times a year for the past five or six years. And with his naturopathic doctor not believing the rash could be from the supplements we got from her, we really don’t have a doctor to consult. I am ever so thankful for this website.

  • Courtney says:

    My doctor prescribed me at 7.5 mg Deplin, but told me that I can also opt to take over the counter methyfolate. I notice that over the counter methyfolate is only sold in micrograms. I’m confused. How much over the counter methyfolate should I take to get an equivalent dose to 7.5mg of Deplin? Thanks.

  • Amber says:

    Hello MTHFR Community –

    I am new to the world of genetic mutations and would appreciate your help in understanding my 23andme results (run through application). I had severe side effects when I started with 1000mg of methylfolate/1000 mg of methylcolbamin (for MTHFR C667T Homo ++) which led me to do further testing. Here is a list of my Homogenous snp results from 23andme:

    – MAO A R297R (rs6323) ++
    – COMT (rs6269) ++
    – MTHFR C677T (rs1801133) ++
    – GAD 1 (rs12185692 and rs3828275) ++
    – NOS 2 (rs2274894 and rs2248814) ++
    – FUT 2 (rs492602 and rs601662 and rs12185692) ++
    – ACE Del 16 (rs4343) ++
    – MTHFS (rs4846049) ++
    – MTHFD1L (rs17349743) ++
    – 4927 Region (rs6822844) ++
    – SOCS -1-82OH>T (rs33977706) ++
    – IRF5 (rs4728142) ++
    – CYP4V2 (rs13146272) ++

    I am a 37 year old female who started to develop problems with reoccurring miscarriages 6 years ago. After the birth of my daughter 5 years ago I was diagnosed with PTSD (which led to insomnia/anxiety). The methylfolate/coblalamin seem to worsen my symptoms. I did an overall GI test….and ended up treating my yeast overgrowth with a Yeast Busters Kit, Nystatin and Probitoics. I did try taking Niacin & Curcumin with methylfolate/coblalamin and they seem to offer temporary relief….but not long-term.

    I am now a stay-at-home mother of two kids (5 and 2) but the effects of the Post Traumatic Stress/Anxiety/Insomnia are hard… the point where I recently started taking 100 mg of Zoloft (antidepressant)….which does not seem to be helping like they said it would….which has led me to start taking Trazadone (sleeping pill) which helps me sleep (sometimes) and sometimes I even need Ativan. I feel like all of these prescriptions have only made things worse. For the most part (over the past 5 years) I have treated my PTSD with natural supplements (5HTP, Fish Oil, B Vitamins, Magnesium, Vitamin D, Probiotics, DHEA, Melatonin, Valerian, Vitamin E, Multi, Q10, l-glutamine, G-aminobutyric acid, suntheanine, phosphatidylserine, protein shakes, among many others and a healthy diet). It all seemed to help but did not get rid of the PTSD. I regret my decision to try the prescription way but I am committed now. Also important to note I am also doing CBT Therapy…..

    Any advice….tips….or recommendations for doctors would be appreciated. I am living in Ottawa, Canada and MTHFR is not something that is well known or understood. I have been working with a naturopath but once we get into genetics it is leaving their area of expertise.

    Thanks again for your comments.

    • Kathleen says:

      Hi Amber,

      Need to make this short. I’m C677T Heter with some of the same mutations as you. Prior to learning about MTHFR and doing the 23andMe, I had been doing EFT ( for various physical pain and emotional stuff such as depression and anxiety with great success. I would highly recommend you download the free EFT manual and teach yourself. I purchased the video library and haven’t looked back. I feel that seeing the numerous ways in which EFT works for different people and their issues has been a tremendous help, as technique is important. Sometimes using it in a very basic way is enough, sometimes it helps to know technique in more depth. Renowned scientists and physicians are very into EFT, such as Bruce Lipton, Phd., Dr. Hyman, Dr. Mercola, Dr. Shealy, Dr. Pat Carrington, and the list goes on. I just started using it for moods (swinging from euphoric to seemingly normal and it has worked very well). I’m testing it on addressing specific SNPs by addressing the location of the mutations. Hopefully my energy body will will correct the genetic defects. There are also the nutritional supplement balances that you need to strike a balance that works for you and I’m sure others will comment on that soon.

      • CatLady says:

        Hi Kathleen:

        I am seeing a PhD-level psychologist/therapist for my anxiety, depression, and PTSD. She has just started teaching me about EFT/tapping. I agree that it does provide some relief, even though I am only in the early stages of learning about it.

        This morning when my pulse was racing in the 120s-130s, my heart was pounding, and it felt like my heart was going to explode (due to my L-methylfolate reaction), doing several rounds of the most basic EFT/tapping helped to relieve the heart pounding sensation but did not reduce my pulse (at least not immediately). Another good site for EFT/tapping resources (some free, some to buy) is here:

        Something else that I find helpful, too, when the L-methylfolate side effects are worst (or when any bad neurological medication reaction happens) is to drink some chamomile tea. It definitely has a temporary calming effect.

  • Irv says:

    Hi Dr. Ben:

    I was just diagnosed as C677T Homozygous. I started on Methyl Protect by Xymogen and I’m having a few hours of calm followed severe anxiety (more than usual). I’m also experiencing muscle aches and migraines in the morning upon waking.

    I know you mentioned healing the gut first so I’m starting slow but drinking a gluten-free protein shake made of chia, rice, pea protein. I did try Niacin (50 mg) yesterday and it seemed to help for the anxiety. Am I a victim of methyl trapping because I’m not taking the methylcobalamin first, sublingually? Thanks.

    • Terri says:

      I doubt it. I have been taking the methylcobalmin with the Methylfolate and when I increased the dosage of methylcobalmin last week, I had 3 or 4 days of flu like symptoms. I know it’s not the flu because they would come and go. I’d feel wonderful, then bam, wake up with achy muscles and hurt all over. I felt out of it and very crabby/moody. Then, all of a sudden, I’d feel better, only to have it return again. I just went back to my original B12 dose and increased it by a smaller amount. Today I was ok again after a couple days back on a smaller increment.

  • Laura says:

    I just wanted to recommend a book by Dr. William Walsh called Nutrient Power. It has changed my life. He doesn’t talk so much about MTHFR defects, be he talks in great length about the methylation process, which I think we are all having issues with. Methylation issues cause a ton of problems from anxiety, depression, adhd and autism. Dr. Walsh addresses these issues separately and gives nutrient based recommendations. I am homozygous for A298 and had difficulty tolerating any dose of methyl folate. This is what turns me on to the book. He says that undermethylaters don’t tolerate folate but respond well to SSRIs and same-e. He explains why in the book but I wouldn’t relay it well. I started taking Same-e in October and it has had amazing results. I have always had the anxiety, but never believed I had depression until I started taking sam-e. It is that noticeable of a difference. This is a fustrating issue for us all and such a puzzle to figure out, but this book gave me a lot of answers. So maybe it will help some of you.

    • simon says:

      Hi Laura,

      I am aware of Dr. Walsh’s work and it turns the current MTHFR paradigm on its head. Themost reason Methyfolate makes many or most undermethylators worse is because folates tend to strip methyl groups from chromatin and are deacetylase inhibitors that favors acetyl over methyl, thereby increasing and serotonin reuptake and making less serotonin available at the synapse So, it will help Methlyation but end up making the patient feel worse.

      Therefore Walsh suggests attacking the Methylation issue a different angle especially if depression is a issue. I was wondering if Dr. Ben could comment on this issue?


  • CatLady says:

    Since this forum section seems more active, I’m going to try posting here. My original posts with all of the details and links to depression/L-methylfolate research articles are here:

    1) I had no 5-MTHF side effects while taking 15mg daily for nearly 3 months (to augment antidepressants, do not know for sure if I have a mutation or not, but it is likely) . Then I tried switching brands (over-the-counter to prescription form), but same dosage and both a calcium salt version. Took 1 dose of the prescription Deplin version and started having ALL of the mentioned side effects (except for acne/rash), PLUS terrible uncontrollable crying spells, shakiness, dizziness, chest pain/tightness, panic attacks, fatigue, pulse rate in the 120s-130s, diarrhea, etc. And what is worse is that these symptoms have continued for 4 days, so far, even though I stopped the Deplin (only took 1 dose) and went right back to my original 15mg version from MethylPro. My worst symptoms occur between 3am and about 11am. I take the 5-MTHF capsule at lunch around 12:30pm.

    2) I was already taking curcumin, so I did not get any change from it. Taking about 62.5mg niacin (nicotinic acid version, time-release; 500mg pill is too difficult to break into 10 pieces, so I cut it into 8 pieces) does help *temporarily* to relieve symptoms if I take several doses during the day. I also get no flushing reaction at all from the niacin, which makes me wonder if I have become waaaaay over-methylated. I have not tried hydroxocobalamin yet as I cannot find any near me and will need to order it if this does not resolve. I do take cyanocobalamin about 2-3 times per week, though. Taking additional Xanax (alprazolam) throughout the day seems to relieve the symptoms the fastest, but again it is only temporary. I wake up lots of times during the night now and the full reaction begins to ramp up again around 3-5am every single day.

    3) I have no idea what is going to happen. I was doing well for 3 months, and the L-methylfolate *seemed* to be helping some for my depression, but now I feel horrific and cannot function most of the day. I am wondering if I was severely under-methylated initially but after 3 months on a high dose now I have gone to the other extreme and become over-methylated. I am starting (as of yesterday, 3/20/14) to decrease my dose… dropped it down by half to 7.5mg for yesterday and (later) today. Afraid to drop too much too fast and end up with a discontinuation reaction if it is affecting my neurotransmitters so strongly. Tomorrow (3/22/14) I plan to drop the dose in half again (to roughly 3.75mg), if nothing gets worse today. I guess I will continue lowering the dosage until I can get off the L-methylfolate entirely for a short time and level out, hopefully stopping these reactions. Then I will probably try restarting it at a tiny dose compared to what I had been taking.

    4) No. My psychiatrist (a D.O.) is allowing me try complementary meds as an adjunct to my other anxiety/depression meds since I am only a partial responder after 2.5 years of recent medication problems. I am a Registered Dietitian, a published researcher, and have my MPH, but I am currently on disability and cannot work due to my symptoms. I only have partial functionality and it varies a lot from day to day.

    5) No. I started myself out on the full 15mg of (6S)-5-methyltetrahydrofolate calcium salt (Extrafolate-S brand) without any problems for the first 3 months. Did not have problems until I tried to switch brands (from over-the-counter brand to prescription brand, both a calcium salt version, both at 15mg). Now I have switched back to my over-the-counter version BUT the debilitating symptoms have not stopped… they actually got worse over the first few days and now have leveled off at the same intensity daily.

    It is now Friday, and I remain terribly sick after switching on Monday (just ONE DOSE) from MethylPro’s 15mg L-methylfolate (source = Gnosis’s Extrafolate-S, pure [6S]-5-methyltetrahydrofolate calcium salt) to Deplin 15mg (which is also [6S]-5-methyltetrahydrofolate calcium salt). I had been on the MethylPro L-methylfolate for 3 months (since 12/23/13) without any side effects.

    I have been reading as many of the posts as I can in all of the forums here for the past several days. It has been very helpful. I recognize a lot of my symptoms in what you all have posted, which helps me feel a little better knowing that others have been through this before. And adding the niacin seems to have helped, which is new to me. However, I need to know how you finally got the symptoms TO STOP.

    Did you completely discontinue the L-methylfolate (for how long) and restart it at a tiny, tiny dose (in the micrograms [mcg] range instead of milligrams [mg])?

    If you were taking a large amount (1mg or more) for at least several weeks, did you just stop taking it “cold turkey”? If so, did you have any side effects from stopping it “cold turkey”?

    I have left messages with my psychiatrist, who is familiar with Deplin, but I have not yet heard back from him. I am pretty sure his response is going to be the same as it has been in the past when I have had bad reactions to switching meds or trying new meds — to wean completely off of the medication slowly and take extra Xanax until the symptoms subside; basically to ride it out until it stabilizes. His response is perfectly valid — I know he cannot miraculously make these things stop — but trying to “ride out” these symptoms is HORRIBLE… even with the benefit of the niacin and Xanax. I feel like I want to crawl out of my skin. And I just got a call back from his office… can’t get in to see him again until April 7th. He does have an emergency after-hours line, but I hate to call that and disturb him when I know he really cannot do anything for me besides to reassure me and tell me to wean off the medication.

    Any comments/suggestions are welcome. I am so disturbed by what has happened. And I can’t stand being a blubbering cry-baby with uncontrollable fear and physical symptoms every single morning. I’d stop taking the L-methylfolate at all today if I wasn’t so afraid of a discontinuation/rebound reaction. I just don’t know what to do or who to turn to.

    • CatLady says:

      This morning (Saturday, 3/22/2014) is the first morning since I took the 1 dose of Deplin 5 days ago (3/17/2014) that I woke up WITHOUT the crying spells. I still had a lot of pounding heartbeat, super elevated pulse (120s-130s), shakiness, anxiety, etc., but the crying wasn’t there… nor was the cold/chills, shivering, dizziness, etc. It wasn’t “good” but it was definitely “less bad.” I’ve spent most of today resting on the couch.

      I wonder if it had anything to do with me only taking half (7.5mg) of my L-methylfolate (Extrafolate-S from MethylPro) on Thursday and Friday. Well, today (Saturday), I decreased the dose by half again… down to 1/4th (3.75mg) of my original 15mg L-methylfolate dose. We will see what happens tomorrow morning. I have my fingers crossed that I won’t feel any worse and perhaps might feel a little better. If all goes well, I am going to keep lowering the dose by half every 2 days until I can come off the L-methylfolate completely and allow my body to reset itself before I consider re-starting it again at a much, much lower dose and possibly with methylcobalamin.

      Again, any comments are appreciated. This has been a rough experiment. I have been knocked flat on my back this entire week… barely functional, mostly being in bed all day.

      • Michael_Dowdy says:

        Hello CatLady.Try less methylfolate but add some TMG anhydrous. Betaine HCL is discussed as helpful with high homocysteine levels. Virgin Coconut Oil may help with inflammation and gut problems. Red Palm Oil is supposed to have huge benefits as well although I’ve never used it. Research particularly the NIH, NCBI, and Wikipedia for a better understanding. This site is very helpful also. I’m not a healthcare professional, only a patient that’s trying to learn. Best wishes, Michael M. Dowdy

        • Michael (NW) says:

          I take Betaine HCL for digestion issues. I’ve read that it might have similar methyation action as TMG, (I think they are both derrived from Beets), but I’ve also heard Betaine wouldn’t work as a methyl donor. Has anyone read where Betaine would work as a methyl donor? If so, since I take one (650mg) with each meal for digestion, I wonder if I could over methlyate taking Betaine HCL?

          Also, I’ve been on St. John’s Wort for at least 7 months now. Taking Perika brand from Nature’s Way at 1200mg. I think it’s helping, but still have depression. My anxiety and panic is way low now. I was diagnosed via a spectracell test as being low in magnesium, zinc, B12 and Manganese. Funny thing is, I’ve been getting magnesium methyl-b12 shots but I guess it’s not enough.

          So, I started supplementing Mangesium Chloride liquid. I could feel it work in my brain immediately, and gave me a more calm feeling, yet it makes me sleepy. It’s not helping me sleep better yet, but it definatley seems a bit sedating. Not sure if that is a good thing or not.

          The other question I have for people is that I have the MTRR defect, but not MTHFR. Methyl-Folate is supposed to lend a methly donor to B12 to help methylate B12, but I have an issue with my B12 and I have WAY too much of it in my blood. I think the high limit is 800, and I have 1500-1700. This was probably due to the B shots I was getting which contained cyanocobalamin. So, I take Methly-b12 now. Also my levels of folate are more than adequate. I was wondering though, if Methyl-Folate is supposed to lend a methyl donor but can’t in my case, does that have a negative effect on my methlyation status and how folate works to create neurotransmitters, etc…?

          I also have adrena fatigue, and am taking small doses of DHEA which has helped with preventing major mood/energy dips around lunch and 3-5pm. I also take one dose of Isocort (plant cortisol) which also helps. And some Tyrosine. But, I’m having a terrible time with insomnia still. It was getting better but after adding one Isocort it’s now worse, yet, Isocort is helping me. Not sure what to do there.

          I am getting better, but I need sleep, but my brain just feels over stimulated, not anxiety, not panic, not nervousness, just stimluated by adrenaline it seems, or caffeine which I take non of. Very frustrating.

          To CatLady, have you had your magnesium levels checked? Might help with some of your symptoms. There are some great bits of inf on the Internet about magnesium deficiency and how it effects so many processes in the body. You could try a low dose of magnesium, whatever form you feel is best for you, and see if it helps calm your nerves, anxiety, etc…….


      • Michael_Dowdy says:

        Hello CatLady. I forgot to mention the 5-L-MTHF crosses the blood brain barrier. It seems reasonable to believe there may be serious effects on brain chemicals. SSRI’s probably are very interfered with. Tricyclic antidepressants might be a better choice when combined with methylfolate. I’m not a healthcare professional. Maybe Dr. Ben will weigh in. Thanks for sharing. Michael M. Dowdy

  • simon says:

    Seems like my keyboard is undermethylated too., rewriting the above without the typos

    Hi Laura,

    I am aware of Dr. Walsh’s work and it turns the current MTHFR paradigm on its head. The reason Methyfolate makes many or most undermethylators worse is because folates tend to strip methyl groups from chromatin and are deacetylase inhibitors that favors acetyl over methyl, thereby increasing serotonin reuptake and making less serotonin available at the synapse So, Methylfolate will help Methlyation but end up making the patient feel worse.

    Therefore Walsh suggests attacking the Methylation issue a different angle especially if depression is a issue. I was wondering if Dr. Ben could comment on this issue?


    • Terri says:

      Since I started the increased dosage of B12 and methylfolate (I feel more effects from B12 methylcobalmin), I’ve been moody, my cycle is off completely, and lately, more angry and aggressive. I’m wondering if, based on what you said, a different form of the B12 and folate will help panic attacks and anxiety I’ve suffered with for years. I feel less anxious and less panic on what I’m taking now, but still suffering with LPR reflux and throat spasms. I wonder if this impacts the gut at all since 80% of neurotransmitters are housed in the gut. You might be on to something. Perhaps reflux can be cured by helping the methyl cycle as well!

    • Laura says:

      Simon, Thanks for the comment. You explained it well! I would like to hear Dr. Ben’s thoughts as well!

    • Roger says:

      WIlliam Walsh’s info is decades out of date. He still recommends FOLIC ACID for his patients, something that Dr. Lynch and many others now know is the worst possible thing to do.

      • Simon says:

        His research is most certainly decades out of date. He took the initial work of Carl Pfeiffer and expanded on it, seeing thousands of patients patients with emotional/mental help conditions performing over 25,000 test essays. He gives folates be it folic acid or methyfolate for those who are OVERMETHYLATED based on whole blood histamine testing and trains physicians and psychiatrists world wide. Pick up “nutrient Power lest you continue to make baseless comments.

      • Simon says:

        His research is most not certainly decades out of date. He took the initial work of Carl Pfeiffer and expanded on it, seeing thousands of patients patients with emotional/mental help conditions performing over 25,000 test essays. He gives folates be it folic acid or methyfolate for those who are OVERMETHYLATED based on whole blood histamine testing and trains physicians and psychiatrists world wide. Pick up “nutrient Power lest you continue to make baseless comments.

  • Jana Rocha says:

    Hi Dr.Lynch,

    I am heterozigous for C677T, Homocisteine 11,7 but two month ago was 19,2. I reduce it with NAC.

    My doubt is :

    What do you think about NAC to reduce homocysteine
    What about FOLINIC ACID
    What about food containing folate like lettuce, spinach, beetroot etc. instead to take the suplemment L-5-MTHF.

    Many thanks in advance for your reply


  • Courtney says:


    I am new to this community and frankly, quite overwhelmed. My doctor initially prescribed me 7.5 mg Deplin because I am intending to try to get pregnant in the next few months. After starting Deplin, I started to do more research and was surprised to find the abundance of information that suggests the benefits of methylfolate for a number of issues, including depression and anxiety. This last issue is of particular interest to me, as I have been weaning myself off of several medications that I have been taking for depression and anxiety, in anticipation of trying to get pregnant.

    I have been feeling hazy since taking the Deplin, but have also felt fairly calm and stable in my mood. How can I ascertain if the 7.5 mg Deplin is a good dosage for me, or if I should be altering my dosage? My doctor also knows that I am on a B-complex that has methylfolate, as well as a prenatal vitamin with methylfolate. Without any guidance, how can I determine if I am overdoing it on the methylfolate and how can I work towards getting the dosage that will help with my depression, anxiety, as well as the right dosage for pregnancy? I see many members of this online community mention different supplements from methylfolate that they are also taking. Where do you find the information for which of these supplements you should take?

  • Merrick says:

    I do not have a known MTHFR issue however react very badly to any intake of folinic acid or methylfolate. I am trying to figure out why this could be.

    I am MAOA++ and have Hashimotos, adrenal insufficiency, Lyme and mold toxicity.

    My symptoms when using the supp (even at low doses) are EXTREME irritability, anger & rage, increased anxiety, nausea, joint pains, headaches, fatigue and many others. The worst being the moods. When I stop the supp it goes away within a day or two.
    My folate & B12 levels have been tested and are good but I am deficient in all other B’s so I will continue to supp those. (Thanks for making the B Minus!!)

    Just not understanding why I have the issue with the folate. Is it just toxins? overmethylating? Any insight?

    • Michael_Dowdy says:

      Hello Merrick. Since Merrick is a unisex name I need to ask your sex as it relates to the MAO A ++ finding. I’m wondering if the extreme rage you’re experiencing is resulting from Brunner/Brunner’s Syndrome if you’re male. I can find only a little information on MAO A mutations. Even though you don’t have the predominately studied methylation mutations (677 and 1298) other mutations may be possible. Since methylfolate crosses the blood brain barrier should it be considered a psychiatric substance even though it’s classified as a medical food? That’s one of the most serious questions I have for Doctor Ben. Thank you for sharing. Would you please weigh in Dr. Ben?

      • Merrick says:

        Hi and thanks for replying. I am female. I do have COMT +/- a few MTR/MTRR as well as BHMT issues. Not sure of any of those play a part in this as well. I know the COMT might.
        I stopped all forms of folate and B12 for now. I feel SO much better. I used some niacin and it was a huge relief. I was happier than I had been in months…over a year really. (I have been very sick for a long time now)
        Recent testing showed me to be deficient in all of the B’s BUT folate & B12, so maybe it’s possible I don’t need them as much right now. I will keep the folate out and try B12 first when I re-introduce them. It’s good to know the niacin helps so much. I have been using the B-Minus with no issues so far.

        I was nervous to try the curcumin again due to it being an MAO inhibitor. I don’t want to mess up anything there. I wonder if Dr. Ben knows anything about that??

        Most of my inflammation markers are low, however I know that may not always mean I don’t have some, especially with the illnesses that I have. To have that bad of a reaction to methylfolate and folinic acid there has to be some reason. I think it has been happening for a LONG time now, but I have NO clue it was that. I mean I was debilitated for months. Then unable to tolerate them, started again and slowly but surely, debilitated again. This was a B complex, not folate by itself ever.

    • Michael_Dowdy says:

      Hello Merrick. I forgot to mention that I’m not a healthcare professional or expert, I’m only a patient using methylfolate. Thanks again for sharing. Michael Dowdy

  • Julie says:

    Hi Dr. Ben,
    Taking the methylfolate and B12 for 1.5 months caused problems with immunity for me. My doctors don’t seem to understand why/how to fix it. I would obviously discuss any ideas with them, but what could one do to repair when this has happened?
    I stopped the methylfolate and have been taking extra niacin and riboflavin, as well as everything else I can think of to ramp up immunity.
    I obviously was not someone who should have been taking the active B12 protocol- I now realize my immune system was in too vulnerable a state, and I’m trying so hard to regain homeostasis.
    Perhaps I need to be taking the niacin for the amount of time that I was taking the methylfolate.
    Any thoughts would be so greatly appreciated.

    • CatLady says:


      What kinds of “immunity problems”? What has happened?

      • Julie says:

        Hi, yes, I didn’t really want to say because I didn’t want to make my question about the actual symptom- I have an increase in demodex mites, which is an immune dysfunction thing, and possibly a fungal related thing as well. I have lyme so that makes me more succeptible I guess to immune dysfunction.
        I’ve been doing everything conceivable to relieve the problem, but I feel something stuck from taking the methylfolate.
        I have a history of strong, lasting reactions. Not sure about my genetic mutations yet; I did order the test yesterday : )

    • Julie says:

      I am taking Niacinamide, not flushing Niacin by the way.

      • Michael_Dowdy says:

        Hello Julia. Niacin and niacinamide are quite different. Niacinamide is apparently very good for the skin. It seems to have helped my skin in healing time. A good diet and restful sleep are very important in every aspect. Stress is a killer.

        • Julie says:

          Thanks Michael! So is it true that it has to be the flushing type to bring down methylation? I was reading Dr. Klinghardt’s writing about Niacin/Niacinamide and it sounded like he was saying they could be used interchangeably, but perhaps for this purpose they can’t.

          • Michael_Dowdy says:

            Hello Julie. I really don’t know. I’m extremely interested in hearing that question answered by Dr. Ben. Wait for his answer and we’ll both learn. Use these search words on google; niacin methyl trapping nih

          • Dr Lynch says:

            Hi Julie –

            I prefer nicotinic acid but both may be used. They both need SAMe to be broken down. There may be other routes of niacin breakdown but at the moment – the one I know mainly uses SAMe. This is partly why high dose niacin can cause liver damage – because it can deplete SAMe – especially in those with inadequate methylation support.

  • Alicia says:

    1. severe headache, insomnia, mood swings, extreme irritability, skin rashes especially around eyes, mouth and ears, and muscle/joint pain
    2. Niacin did help the headache, not sure about other symptoms as I also stopped the methyl folate.
    3. Not there yet – now only up to 0.5mg every other day
    4. Yes, Deplin 7.5
    5. No, it did not go well…

    Hi Dr. Lynch,

    I would like to thank you for creating this website and providing help to so many of us. Your website and 23andme raw data interpretation report has helped me down this rabbit hole of symptoms and causes. After getting my 23andme report last year, had nothing unexpected or any high risks aside from restless leg syndrome and clotting issues (family history). Yet my list of symptoms continued to grow and worsen so I assumed a lot of it was just in my head (of course some still could be…). I’ve had extensive blood/urine/stool tests done with everything but B12 within normal. I am a 30 yr old female that eats well, exercises and is plagued with skin and gut problems with severe sulfite sensitivity.

    I’ve known for about 5 years that I have low B12 levels (low 300s even with Nascobal) and recently was lead to your site by a chiropractor. With my report from your site, I went to a new doctor that is aware of these conditions. I was prescribed 7.5mg Deplin and was assured I would need that high of a dose. (Admitting that at the time I didn’t watch the video do my research as I got in the next day.) As you can guess it was not good = insomnia, irritability, mood swings and skull cracking headaches after about 5 days of supplementing. I picked up some Niacin and that somewhat helped… then I found your comments where you mention trying taking smaller amounts of niacin more frequently and decrease folate even further. I purchased your 1mg methyl folate lozenges and cut them in half. Currently I am down to every other day at 0.5mg with 100-150mg niacin and 0.5mg+ methyl B12 daily – all in the early morning (will be changing it up to hydroxy/adeno B12 in the next day when it arrives). I am starting to sleep better with fewer headaches. I also went back to being gluten-free for the last month since seeing my HLA was homozygous mutated and have a better understanding of the zonulin pathway. I also have been living a vegan lifestyle for the last couple years and make most of my own food, soaps, lotions, etc.

    Also, a colleague (Nephrologist) mentioned that I might have some sort of mastocytosis- I have over 20 of 58 symptoms. I found that with CBS mutations, BH4 can be reduced leading to mast cell degranulation. He said that I should try cromolyn. Quercetin may be better? One of your products has it but at low doses. What are your thoughts?

    Can you and others here help me on what I should be doing next (will be following up with my doctor soon)?

    From watching your video and reading more, it looks like I should also be taking molybdenum, magnesium, potassium, Ashwagandha, vitamin C, curcumin, higher amounts of probiotics.

    It appears, like many others here, I have a complicated mess of genes:

    Gene SNP Risk Result
    MTHFR C677T rs1801133 A AG +/-
    BHMT R239Q rs3733890 A AG +/- convert homocysteine to methionine
    CBS A13637G rs2851391 T TT +/+ increased homocysteine concentrations
    CBS C19150T rs4920037 A AG +/- “ (increase sulfates in urine)
    CBS C699T rs234706 A AG +/- “
    GIF (TCN3) rs558660 A AG +/- Decrease in GIF to uptake B12
    TCN1 rs526934 G AG +/- B12 binding protein-low B12 levels in cells
    TCN2 C766G rs1801198 G GG +/+ “
    COMT rs6269 G GG +/+ decreased degradation of catecholamines
    COMT 61 rs769224 A GG -/- Greatest susceptibility to mood swings
    COMT H62H rs4633 T CC -/- -/- lowest dopamine
    COMT V158M rs4680 A GG -/-
    MAO A R297R rs6323 T TT +/+ same as COMT (G is higher activity)
    MTHFD1 C105T rs1076991 C CC +/+
    MTHFD1 G1958A rs2236225 A AA +/+ “
    MTHFD1L rs17349743 C CT +/- “
    MTHFD1L rs6922269 A AG +/- “
    MTRR A66G rs1801394 G AG +/- decreased folate reduction to methionine
    MTRR-11 A664A rs1802059 A AG +/- “
    MTRR rs1532268 T CT +/- “
    MTRR rs162049 G AG +/- “
    MTRR rs3776467 G AG +/- “
    ACE Del16 rs4343 G AG +/- increased angiotensin activity
    AGT M235T/C4072T rs699 G GG +/+ functional change in angiotensin
    HLA rs2858331 G GG +/+ Gluten
    FOXE1 rs1867277 A AA +/+ Thyroid cancer
    FOXE1 rs7043516 C AC +/- “

    In addition to this list, I have numerous clotting factor mutations along with other methylation mutations (7 NOS het) and GAD (5 homozygous).

    Thanks for your help,

  • Karin says:

    Hi Dr.Ben,

    I have mutations on both MTHFR-genes, and also mutations on BHMT-genes and COMT-genes.
    I started with 400mcg methyl-folate,400mcg methyl-B12 orally, 100mg niacinamid (and also 5-P-5) alltogether maybe 5x/week, and maybe 1x/week hydroxy-B12 s.c. That was fine in the first 2-3 weeks. Then I added 1000mg PhosphatidySerine/Cholin and sometimes 1000mcg sublingual methyl-B12. There I got strong side-effects: especially Inflammation in the brain-area, also some joints starting aching a little, kind of fibromyalgia, pain in the liver-area that worried me most, tiredness in the brain, and yes I could throw dishes half day long! Therefore it’s hard keeping up working.
    I made breaks of a week repeatedly, but as soon as I start again only for 1-2 days all the symptoms are back! I think what troubles me most is methyl-B12.

    Best regards,

  • Karin says:

    …and I forgot: 500mg curcumin&peperin I am taking as well. Inflammation is still there a lot 🙁

    • Michael_Dowdy says:

      Hello Karin. I see you think your headaches are caused by brain inflammation caused by taking methylfolate? Have you tried reducing the amount of methylfolate you’re using? After I reduced the amount of methylfolate I was taking my headaches stopped. I tried increasing the amount I was taking some and I experienced headaches again. Thanks for sharing! Michael Dowdy

  • Michael_Dowdy says:

    Hello Dr. Ben Lynch. It seems common that headaches are experienced with methylfolate use. Headaches are extremely uncommon for me but I experienced headaches when I first started taking methylfolate. Why do patients taking methylfolate experience headaches? Also, can patients form a dependency or addiction and suffer with resulting withdrawal symptoms when reducing or cessation of methylfolate?

  • Michael_Dowdy says:

    Hello Dr. Ben. Methylfolate / 5 L MTHF had a profound effect on me in both physiological and psychological ways. The dosage which I first tried was 7.5mg Metanx if I recall correctly. I now use a much smaller dose. I know it’s classified as a medical food, a vitamin, but it has such strong effects I’m surprised it’s not classified as a drug. Are there any statistics kept on 5 L MTHF with regard to suicides by those who have taken it? Should it be classified as a drug? Thanks in advance. Michael Dowdy

  • Corina says:

    Dr. Ben,

    I am homozygous for MTHFR A1298C and MTHFR C677T polymorphism. So far all I have been given is Deplin 15 mg so far and for the 2 weeks that I have been taking it I have felt no side effects. I was just wondering how long it takes for you to feel results and just what exactly I should expect. I have read a lot and it is a bit hard to discern my own situation.

    Thank you,

  • Scott U. says:

    Thanks for the great resources provided here. Per the questions above, I am a 58 yo male suffering from about 30 years of depression. Nothing much helped, then my therapist recommended a genetic test which showed a double-whammy on the C677T. She prescribed 15 mg of Deplin and I took it with hope for the first time in a long time. Unlike the cases in the article above there was no immediate effect but she said it would take a while to kick in (just as SSRIs do). After about a month I began really feeling a difference, with better moods and a much clearer head and memory. But shortly thereafter I began to get irritable, then angry, and finally downright viscous. Having read the above I took some Niacin and stopped the Deplin. I am now on the rollercoaster down but fear going back to where I was before.

    Not sure where to go from here. Per your protocol I guess I start over with small doses and work up. I really think I may have found an answer to a large part of my depression and don’t want to let it go.

    I live in Connecticut; does anyone know of MTHFR knowledgable medical help in this area? I’d love a full workup and professional oversight but just about all the references on this site are for West Coast doctors.

    Regardless, thanks for the help and hope,


  • Jill says:

    I have been newly diagnosed with A1298c homozygous. Thru my GP, I started with one dose 5000 mcg B12/1000 mcg folate sublingual prior to breakfast and felt slightly better thru the day with my neuro symptoms. At bedtime i experienced heart palpitations, felt hot and had insomnia the entire night. The next day, mid AM, I had bilateral calf pain and felt crappy. My GP said just take everyother day and that I don’t need anyother genetic testing(only tested for A1298c and C677t). I see a NP tomorrow who specializes in epigenetics. Keeping fingers crossed.

  • Tam says:

    If you have inflammatory bowel disease you risk making yourself very ill with methylfolate!!

    I am homoz c677. I made the mistake of taking methylfolate together with methylcobalmin and P5P. I felt awful and it put me into a colitis (UC) flare. This was starting with a small dose and only once a week. I discussed this on a forum for people with UC and several of us experienced the same.

    This study found pro-inflammatory effects in the body with the mutation with folate with some participants

    People with UC are at increased risk of bowel cancer and it is known that folate is implicated in this. It may be that having a mutation in the folate transporter SLC19A1 increases risk – I am hetero on two snps here.

    Also, from my own research I find that vitamin B2 is vital to integrity of mucous membranes and preventing anaemia. 1/3 of people with UC have anaemia. If you up your methylfolate, although in theory it should not need B2 as a co-factor at this point in the cycle, it may well still be leeching B2 away from the other vital activities it performs in the body.

    There is also a mystery around UC in that it is a disease of non-smokers, very often flaring for the first time in the first year after smoking cessation. There are studies that show that smoking suppresses folate, B12 and B6. It may well be that the genetics of many with UC is that that suppressing these allows another vitamin (s) or some other substance freedom from being a co-factor where they are performing in a way that is, as yet, not understood .

    IBD is one of the fastest growing diseases in developed countries, and heartbreakingly appearing more and more often in young children, probably due to environmental factors, such as having killed off good bacteria through pesticides and antibiotics, therefore bodies are put under extra strain and if the balance of nutrients is wrong for the bowel, disease will worsen.

    • Michae_Dowdy says:

      Hello Tam. Excellent response! It’s really all about food additives, environmental DNA damage, and experimenting with synthetic supplements versus natural, isn’t it? Did folic acid cause the the 677TT mutation or was it that combined with thimerosal that caused autism in children? Was 5-D-MTHF tested on humans before 5-L-MTHF was decided upon as being safer? What about the mao a mutations and what caused them? Is it just human imperfection or was it environmental damages? Where do we go from here? Do you think genetic repair or vaccines using human DNA is the answer? I have a lot of questions but no real answers. What about the question of ethics? Tell me! How do you think brain mapping will go – better than the human genome project? Which comes first – treat the inflammation or treat the cause? I suggest coconut oil and trimethylglycine and possibly whey protein as a short term help. I’m not a healthcare professional or a molecular scientist. Look what happened with L vs. D with thalidomide. Michael M. Dowdy

      • Tam says:

        Wish I had some answers. Whey Protein is intriguing. High in lactoferrin which is detected in the stools of IBD people and goes up according to severity of disease. Opinion split as to whether more would help or whether the iron in the colon would cause more oxidative stress

    • Michael_Dowdy says:

      Hello Pam. I tried using daily extra virgin coconut oil to replace butter with some success with gut inflammation.

  • Mitch Fillion says:

    Hey Dr. Ben,

    I found out I have the C677T mutation. High homocysteine levels even though I’ve been eating raw vegan for over a year now. I also have decreasing low red blood cells, every blood test every 4 months shows a lower RBC number. My creatinine is low, my HDL cholesterol is very very low, low in zinc the last time I tested though I’ve been supplementing. I’ve been on 1000mcg of b12 per day for awhile and uMMA levels tested fine. Whenever I try to take 5-MTHF (tried the thorne research brand which is 1mg) I have a severely bad reaction where I get a crazy bad skin rash and I am up all throughout the night feeling like an evil demon (dark thoughts, anxiety, etc) and on the days that I’ve tried the methylfolate I’ve made sure to take an extra 1000mcg of methylcobalamin so I’m taking 2000mcg that day. I’ve tried this three times now and it’s been a nightmare each time I’m so afraid of taking methylfolate now. I end up slamming doors and screaming at my girlfriend the next morning whenever I take it, it just turns me into a crazy evil person, its strange…

    • Lynn_M says:


      You could take Metametrix’s UMFA test, which measures both unmetabolized folic acid and also 5-MTHF, to find out if you really need to take 5-MTHF. You can order the test through Dr. Ben’s site here:

      I suspect your raw vegan diet is responsible for your low RBC and low cholesterol.

      Your high homocysteine may be resulting from an inability to metabolize methionine well, due to another methylation genetic SNP.

      Your behavioral symptoms and skin rash sound like those associated with folate excess. Have you tried taking niacin when you’re reacting like this?

      Dr. Ben has responded to others experiencing rashes from methylfolate. Search on this: “ rash” to find his responses.

    • Tam says:

      Suggest that you have your B2 levels checked. Your vegan diet is lacking B2 to start with and MTHFR needs B2 as a co-factor. Anaemia, skin and mucous membrane problems are proven symptoms of B2 deficiency and behavioural suspected

  • Michael_Dowdy says:

    Hello Dr. Ben Lynch. Folic acid and folate are both available as supplements so is the food additive folic acid going to be replaced with methylfolate since folic acid is a problem to those with MTHFR mutations?

    • Lynn_M says:

      Michael Dowdy,

      Certainly not. As a matter of fact, if you read this, the FDA has proposed new guidelines for supplements. Among their proposals is to eliminate the word folate from supplement labels and require the labeling to call it folic acid. So the suspicion is that they want to make methylfolate ultimately available only via a prescription.

      The comment period on these new proposal ends June 2, 2014.


      • Michael_Dowdy says:

        Hello Lynn. That is shocking information. Everybody should read that. I was also just reading at states that “At least 40 mutations in the MTHFR gene have been identified in people with homocystinuria.” With that in mind it would really be a terrible shame if methylfolate was only available as a prescription. It seems that likely that everybody could benefit from supplemental methylfolate, in the right dose of course.

      • Michael_Dowdy says:

        Hello Lynn. Have you heard any new information as far as guidelines for 5-L MTHF? Respectfully. Michael Dowdy

    • Dr Lynch says:

      Hi Michael –

      Dream on 🙂

      I wish.

      I doubt it though – as folic acid is much more stable than methylfolate.

  • mariam says:

    I was diagnosed with homozygous c677t in October 2013 my naturopathic doctor has me on b-complex with 10 mg 5-mthf I take one daily and milk thistle vital brain powder and multi-element vitamin c when I first started taking the b-complex I did notice palpitations and I had headaches and some nights I was restless it didn’t last to long I did notice a lot of my inflammation was leaving my body and I starting to feel better I have RA and have been battling candida infection (gut) for about 3 yrs since she discovered I have this gene problem I haven’t had any candida infection and I no longer have any Asthma symptoms I would like to know if my type of gene can cause infertility in women?

  • Michael_Dowdy says:

    Thank you Lynn. I appreciate you and hope you’re doing well.

  • Teresa says:

    I am a double A1298C and was poisoned by levaquin three years and four months ago. It effects all my tendons and other connective tissue. Stiff and sore and sometimes I lose use of a particularly inflammed area or tendon. Like I am limping around right now due to an inflammed plantar fascia and I lost use of my right thumb for one straight month; I could hear the tendon snap when I tried to bend it. It also affects other systems like the nervous system and memory. I haven’t recovered yet. I believe that as MTHFRers we are at more risk to damage as we cannot detox properly. I would recommend NONE of us take these drugs from the fluoroquinolone family. And I don’t say that lightly. They are potent, potential deadly antibiotics. A few have even died and some are bed ridden. Sometimes tendons rupture (break) even after just a few pills; often the ruptures are the achillis tendon right above the foot heel.

    • Lynn_M says:

      I read an article somewhere that identified a gene that makes people susceptible to damage from fluoroquinolones such as Levaquin and Cipro. It was not the MTHFR gene. I don’t think 23andMe tested for this other gene, so I don’t remember what it was.

      Teresa, you may have a SNP in this other gene as well. I think it’s easy to blame MTHFR for too many things.

      • Teresa says:

        Actually I have many mutants along the methylation path (11). If you find out which one, please let me know as it may be important in finding a healing. Well from what I have gathered A1298C MTHFR mutant causes problems with detoxing so that would likely be at least part of the problem for me. Maybe not the entire problem though.

  • Kathleen says:

    Dr. Lynch,

    Where can reliable information be found about Pyroluria? There are a few labs and the reference ranges vary widely. One says 12.75 is HIGH, while another says over 20 is positive. Is 12.75 reason for concern?


    • Joy says:

      Hi laurel. My son and I both take niacin as advised by our doctor as we both have mthfr homo gene mutation. We both experienced this flush the first time which we were told means that our body really needed it and was eliminating toxins. For us, we found it best to take it either with food or just after as it seems to minimise the flush. It could be that your first dose was too high.

      The dr advised to start with 100mcg Oce a day to start and increase after a week to twice a day then 3 times a day after another week until we were on 500 mcg per day. Stay on that for approx 4 weeks or until the bottle of niacin is finished. Then start on 250 mcg pills 2x a day and see how you feel. We did this and now take 1500 mcg 2x a day with very few instances of the flushing.
      It is best to take a smaller dose multiple times a day rather than a single larger dose once a day. We both still flush occasionally but nothing like the gut wrenching first flush we experienced. I get mild asthma and find I flush more in asthma season so I increase my dose leading up to this time and have only flushed twice in the last year and only mildly.

    • Joy says:

      Hi Kathleen. My son was tested with a result of 73 so quite high. My doctor explained that everyone on the planet produces pyrolles but release them and excrete them quickly in urine. Some people with pyrolle disorder keep them in their system for much longer than normal so the higher the score the more they are not releasing them. Pyrolluria is also known as kryptopyroluria and pyrolle disorder.
      Pyrolles contribute to the fight or flight response and in most people subside within minutes of being out of the stressful situation. A score of 12.5 is quite normal so good news for you but it does depend on the units of measurement they are using. Your test scores should have a score rating on the report that advises you if this score is normal, low, medium or high so het a copy of the report from the doctor. Higher scores mean that the affected person is in a constant state of fight or flight. My sons heart rate was often over 120 at rest. The pyrolle explains that. He also has a homozygous mthfr gene mutation so we have a double whammy when it comes to anxiety.

  • Catharine says:

    This medication may not be right for you if you have diabetes, kidney or liver disease,
    and an under-active thyroid. Researchers have prolonged studied the effects of fish oil on a
    variety of populations and several diverse circumstances even so, they had
    not attempted to decide how it impacts an infant’s immune process until eventually not long ago.
    A recent study by researchers at UCLA’s Jonsson Comprehensive Cancer Center suggests
    the Huntsman Cancer Institute is right to focus heavily on diet when it comes to cancer.

  • Marc says:

    I dont know if I have the gene or not, but I started on 15 mg, per advice of my ND, of Deplin. For depression, which has almost always been present in some form from moderate to severe for most of my life. This was compounded by a TBI over a decade ago. I’ve been on it for about 15 days now. Seem to be having some side effects. Almost manic episodes, usually followed by depression the next day, mood swings, not sleeping as long or deep, anxiety. I am wondering if I should reduce the dose? I’m thinking of half-ing the 15 mg dose and taking 7.5. I just took some niacin a few minutes ago, so I don’t know the effect of that yet. He also recommended that I get some Methyl B-12 to add to the mix. what do you think?

    • Michael_Dowdy says:

      Hello Marc. Do a search for A566 L_Methylfolate and study the documents you find online. They will give you an idea of the upper limit of methylfolate recommended as a food additive in Australia and New Zealand and the medical claims that can or cannot be made on the subject of neural tube defects. There is also plenty of information available online which discusses methylfolate’s effect on neurotransmitters. Research this Dr. Ben site for some of the best information and recommendations available on what you’re looking for. Study a lot. Michael M. Dowdy

  • Pam Dalton says:

    I just discovered my MTHFR and other defects in November-MAO++,VDR Bsm+-,VDRTaq+-,All MTRR+-,BHMT2/BHMT4+-,SHMT1+- I have late stage chronic Lyme disease as well as Hashimotos thyroiditis, pernicious anemia, adrenal exhaustion, and multiple chemical sensitivity. I am having a hard time getting a handle on how to manage all these challenges, the stress is wearing me down, and now I have developed atrial fib. Amazingly, my homocysteine level is in the normal range, but I have been taking TMG for several years. Can the MTHFR plus added defects and resulting neurotransmitter deficiencies cause atrial fib? Can you suggest a place for me to start? It seems like what I need to do for one problem exacerbates one or more other problems! No one doctor knows about all these areas, let alone MTHFR. Plus most infectious disease doctors tell me it is “politically incorrect” to treat my Lyme. All this is not to mention the huge COST involved! I’m overwhelmed!!

    • Kathleen says:

      Hi Pam,

      I’m on this forum due to MTHFR of my own, C677T. In reading your post, I’d like to suggest this Facebook started by Carol Savage, M.D. who also has mthfr and lyme disease. She’s very knowledgeable and helpful, as well as the people on that Facebook page: “MTHFR Gene Mutation” is the Facebook page to search for.

      Best wishes,

  • Shawn Bean says:

    I have the pleasure of working with several well respected LLMD through out the United States which can do an incredible job of using antibiotics to kill or beat the pathogen back into remission AKA its cyst form. What is highly over looked is the ground work, but looking at the basics. Lymies who are already stressed are coming to a more stressed environment when they are being bombarded by antibiotics. Some times these people are being bounced all over having bad reactions. Many LLMD will send their patient in advance to get detailed crowd work done before entering into antibiotics. The analogy I use for my clients to make them understand is a simple one “Would you drop a Bomb if you did not know where the bomb shelter? Would you roll of of bed one day and try to run a marathon with out proper training?” This is essential what LLMD who are not taking an integrative approach are basically doing. When you combine the integrative approach of alternative and allopathic medicine you will get the best of both world. If the foundational work is done properly then the majority of the genetic expression will be addressed in the process with out any specific protocols. People with lyme are having a better quality of life and been helping to keep the lyme in remission for longer then normal due to the fact their bodies are finely tuned machines. Practitioners or doctors who are following cookie cutter protocols are totally clueless of the complexity of the methylation cycle and worse of all are looking to make a fast buck not having the best intentions for their patient/client. Do not get caught chasing the rabbit down the rabbit hole as many are doing. The end results are not just costing money, but may also worsening one’s health. People need to understand they are messing with the master genetic switch board of your body. if you throw the wrong switch it could accelerate cancer in the body. This has happen to a few people who were self medicating which luckily was able to be reversed.

    • Teresa says:

      Shawn, It sounds like Lymies need to know the potential for more disability, when taking certain antibiotics. The group of powerful antibiotics fluoroquinolones can cause people that cannot detox well a lot damage to tendons and other tissues. Sometimes taking years to recovering, a few no recoverly at all. Anyone taking these antibiotics needs to have lots of information to figure out if taking these drugs are worth the risk it to them.

  • Carolyn says:

    Hello Dr. Ben,
    My pharmacist told me to take some methylfolate with methylcobalamin, as he said that my blood tests show that I have some sort of problem with methylation, and he thinks it’s probably MTHFR.
    I started taking the supplement two weeks ago in very small doses (approximately 20mcg-100mcg/day, and sometimes skipping days). I have been on a roller coaster of scary symptoms since. When I felt that I had taken too much of the supplement and got headaches, dizziness, brain fog, depression, and feeling very “off”, I took a B-complex vitamin that contains niacin but not methylfolate (I don’t have any pure niacin supplements to take) to counteract the methylfolate. However, I would always become extremely fatigued and depressed after doing this. So, I would take more methylfolate, hoping that it would make me feel better again.
    Interestingly, sometimes it DID make me feel better. At other times, though, I would simply rebound back to the original symptoms of overmethylation– and they would be even more severe than they were the first time. I went on a spiral of taking B-complex, then MTHF, then B-complex, then MTHF, etc., until I finally felt acceptable enough to stop taking all of them.
    I have decided to never take a B-complex vitamin or methylfolate ever again. However, I’m still feeling some of the effects (dissociation, brain fog, depression) of taking too much methylfolate, even though I haven’t taken either of the supplements in two days.
    By the way, I’ve recently ordered an MTHFR test from Seeking Health, just to make sure that I actually do have an MTHFR mutation.

    Will these effects go away? Do some people just get stuck with them? Will my methylfolate level go back to what it used to be on its own?


  • Teresa says:

    It is likely that you have other mutants along the methylation pathway. I couldn’t take any 5-MTHFR because of my COMT mutant. It took me two years for my heart to stop racing and palpating; I was also experiencing heat radiating from inside my chest and bad anxiety. This was after only taking it for four days . I ended up in the ER enveloped in an indescribable hell. A beta blocker saved me from jumping off a cliff. I cannot take b’s anymore and I cannot tolerant a converted B complex. But I can tolerate converted B-12 well which is good because I am low. Think about getting all the mutants on the methylation pathway checked.

    • Michael (NW) says:


      Does anyone know where to get these additional methylation pathway defects checked?

      GSTM1 – major detoxifier
      HNMT – processes histamine (primary is DAO)
      GAD – glutamate to gaba
      QDPR – recycles BH4

      Dr. Yasko’s MEthylation test does not cover these.

      • Terri says:

        23 and me does HNMT and GAD I think…?

      • Lynn_M says:

        My v.3 23andMe test checks for 7 GSTM1 SNPs, 49 HNMT SNPs, 15 GAD1 SNPs, and 19 QDPR SNPs.

        • Michael (NW) says:


          I’ve had the 23 and Me test done. And there were absolutely no Methylation results that I could see at all. Not sure why everyone keeps pointing to that test. I found it 100% useless in that regards. It was kinda interesting to see that I might be susceptible to some health concerns as I get older due to heritage etc…, but that doesn’t help me with Methylation results like the ones I got from Dr. Yasko’s Methylatoin test. Unless I’m missing something here?

          • Lynn_M says:


            You most definitely are missing something. 23andMe is not user friendly like Dr. Yasko’s Methylation Pathways test. However, Yasko’s test gives you the result of something like 30-40 SNPs, whereas 23andMe gives you the results of almost a million SNPs. 23andMe is a much more powerful test, but you have to be informed to access the results and make them meaningful. 23andMe does not report anything about methylation genes on their health overview reports except possibly health risks related to ++ C677T. To know the results of your methylation genes, you have to go digging into the Browse Raw Data section.

            Once you log in, you will see your name on the upper right and a down arrow next to it. Click on the down arrow, and a pop-up menu appears. Click on Browse Raw Data and that takes you to a screen where you can search on either a gene name or the rs number of a snp. Be sure to include the rs and then the number. For example, you could search either on MTHFR in the gene box, which will yield your results for 59 different MTHFR SNPs, or you could enter for example rs1801133, which is the C677T SNP. To know if you have the mutated SNP or not, you can check out the population diversity for your alleles at dbSNP. On the far left column of your SNP results page, there is a + symbol. Click on that, and a pop-up menu appears. One of those choices is dbSNP Lookup.

            If you want to make it easy on yourself, you could use either Livewello or Someone advised you about the mthfrsupport report previously. If you go to that link, there is an option to click on to see a sample report. They give the results of something like 200 SNPs, and they tell you which is the mutated version and if you’re +/+, +/-, or -/-.

          • Michael (NW) says:

            Hi Lynn_M,

            Thank you for the info. I just logged into 23andMe and followed your instructions. I was able to look up the other mutations GSTM1, HNMT, and QDPR but I didn’t see GAD, unless there’s another name for it. This is the one that coverts Glutamate to Gaba. Do you know what that one might be called?

            Anyway, when I look up a Gene, There’s like 30 to 50 items listed. What are all these individual readings? Not every easy to figure out. 🙂

            I might look into one of those sites that can discern this stuff, but rather not have to pay even more money to do so. We’ll see.

            Anyway, thanks again for the info!


          • Michael (NW) says:

            I tried the conversion app on Livewello. I’m disappointed as it did not include HNMT and QDPR which were listed on 23andMe. So, this was a waste of money, as it did not provide the info I thought it would. It does include a lot of other things, but not what I purchased it for. Oh well.


          • Michael (NW) says:

            Hi, wow, I have many more mutations, but not sure which ones are really accurate and whether or not they are critical and need attention.

            For example, I’m ++ for MAOA R297R and MAOB. This doesnt’ sound good, but it doesn’t tell me whether or not ++ means these enzymes are working over-time or not functional at all. I have depression, anxiety, etc…And I’m taking things to improve all that. So, would it seem these enzymes are breaking down these neurotransmitters too quickly? I am taking St. John’s Wort, and it kinda helped but after adding some 5-htp, things got better. But….

            Lots to ponder. Thank you.

          • Michael_Dowdy says:

            Hello Michael (NW). If you wish give me a call at 321-443-6597.

            Hello Michael (NW). Give me a call and I have some information on one of your other ++ mutations that I’ve done some real research on and I need a little more information to see if we are the same. This is probably the incorrect forum to discuss these. I’m happy to share my findings with you. Michael Dowdy 321-443-6597 EST whenever you wish.

          • Michael (NW) says:

            Hi Michael_Dowdy,

            If it’s methylation related, then I would assume it’s okay to discuss here, otherwise I can get in touch with you later. I’m at work, so it will have to be after hours some time…… When is a good time to get in contact with you?

            See my response to Dr. Lynch. I’ve included all the methylation defects I received from my 23andMe report.

            Thank you,

            Michael (NW)

          • Michael says:

            Any time of evening before 2AM EST.

      • Dr Lynch says:

        Hi Michael –

        23andMe does

        • Michael (NW) says:


          I got my 23andme data converted via livewello. Does livewello convert the data the same as “”? Not all SNP’s are included so I ask….

          Anyway, some of the same defects were reported both on my Dr. Yasko test results and 23andMe. Although there are MANY more defects listed on 23andMe. Makes me a little concerned….

          I have a couple of questions:

          It appears that some of these SNP’s seem to be something that would develop during the growth of a baby in the mother’s womb, something they would be born with or develop at a young age. Being an adult, I would assume some of these SNP’s wouldn’t relate to me if they haven’t already took place, like kidney development issues? For example, “AGT M235T/C4072T”?

          Also, I thought the MTFR gene defect had to do with not being able to convert folate to 5-MTHFR the usable form. Mabye that is true, but the info on my LiveWello test results for MTRR A66G says, “The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate….” I thought MTRR was not being able to make Methly-B12??? My impression from what I’ve read was that those with MTRR need methyl-b12. Or, do I need 5-MTHFR? Or, Both? I don’t have a defect at all in MTHFR, so it would seem that don’t need any 5-MTHF. So, I’m confused about the differences between MTHFR and MTRR….and what I need to help. I did have elevated high/normal histamine and homocystein.

          After reviewing all the results from my 23andMe gene defects, it seems to be a bit overwelming. Lots if issues. But, I’m gathering not all these would apply as an adult, although some do apply like the methylation issue based on my current health issues and test results. I’m assuming some defects might appear later in life. How do you know which ones you need to worry about and fix?

          If I have the CBS and SUOX defects, yet my ammonia and sulfur levels are normal, would that mean I carry the defective gene yet don’t actually have this defect condition myself?

          Anyway, here are my methylation results for both tests (Dr. Yasko and 23andMe). Of course there are many other SNP defects in the 23andMe tests, I’m only including methylation issues since this is a methylation support web site. 🙂

          Dr. Yakso:

          MTRR/A66G ++
          MTRR/11 +-
          BHMT/1 +-
          CBS/C699T ++
          VDR/Taq1 ++
          VDR/Fok1 +-
          NOS/D298E ++


          AGT M235T/C4072T ++
          C18orf56 (TYMS) ++
          CBS A13637G ++
          CBS C19150T ++
          CBS C699T ++
          DHFR ++
          FUT2 ++
          MAOA R297R ++
          MAOB ++
          MIR4761 (COMT) ++
          MTHFD1L ++
          MTRR A66G ++

          DAO +-
          FOLR2 +-
          FOLR3 +-
          GAD1 +-
          GIF +-
          HNMT +- (Histamine)
          MTHFD1 G1958A +-
          MTHFD1L +-
          MTHFR (LOC100506310) +-
          MTHFS +-
          MTRR-11 A664A +-
          NOS2 +-
          PEMT +-
          SLC19A1 +-
          SOD3 +-
          TCN1 +-
          TCN2 C766G +-
          QDPR +-

          Thank you.


          • Lynn_M says:

            Michael (NW),
            Regarding the GAD gene. If you notice in my April 18 2:49 am reply to you, I listed the GAD1 gene. That was your clue. You need to look up GAD1, not GAD. The gene search at 23andMe requires the exact gene name.

            Each gene has a number of SNPs associated with it. When you do a gene search at 23andMe, what is listed are all of the various SNPs associated with that gene. E.g., 23andMe lists 59 SNPs categorized as being MTHFR. They list 32 MTRR SNPs. Now if you click on the + sign on the left side of each SNP listed, a drop down menu appears of Google Scholar links for that gene and for that SNP, as well as the links for Entrez Gene and dbSNP. You can look at the population diversity listed near the bottom of each dbSNP SNP listing and find out in what percentage of the populations tested your genotype occurs. If your genotype occurs in a small proportion of the population, then it may be a dysfunctional mutation. Livewello uses the ancestral gene, that of chimps, in saying whether a particular SNP is mutated or not, so it is not totally reliable in indicating what is “normal” in human populations. The MTHFRSupport Variant Report can also mislead in representing what is “normal”.

            If you click on the Google Scholar links for the gene or the SNP, you’ll get an indication of how much research has been done on them. With MTHFR, as with many others, you won’t be able to get any information about a great many of the SNPs.

            23andMe doesn’t indicate whether anything is a defect or not in their Browse Raw Data . They only report your genotype for the SNPs they’ve tested. Their Health Reports gave some information, but they sometimes only looked at a few SNPs for each condition, so the reports could be misleading. The various interpretation services (e.g. Yasko, Livewello, MTHFRSupport) only look at a limited number of genes and SNPs. There are far more SNPs involved in methlyation than what any of them report on.

            So it’s very early days for the genetic testing consumer to figure out what their genotype means. If you look at the research articles yourself, you’ll find there is uncertainty about the significance of various genotypes. Because you have a certain genotype doesn’t mean those genes are expressed. Even if a SNP is expressed, a genotype does not mean a trait will be expressed as a phenotype. If you have a heterozygous or homozygous condition, it may mean you will see biochemical differences on lab tests, such as an OAT, but it doesn’t mean you would otherwise be able to tell.

            There is no one-to-one correspondence between having a certain version of a SNP and a physical expression, except for a few isolated cases like cystic fibrosis where one defective gene can cause a disease. With MTHFR, for example, you don’t know how all 59 SNPs are playing out together. Plus you have to look at epigenetic influences, which are huge, which would include lifestyle, nutrition, and spirituality. That’s why Dr. Ben keeps saying you have to treat the patient, not the SNP.

            In my case, my Spectracell micronutrient test showed low B12, plus I have had high MCVs. That, plus my brother having A1298C +/-, lead to me getting tested for MTHFR. I found I have a number of MTHFR and other mutations which explain why I have low B12, and now I know that B12 supplementation is important for me.

            I think a good strategy is to look at your physical conditions first and then see if you have any SNPs that would mean you have a vulnerability for that condition. Comprehensive functional lab testing like the Cardiac/Ion or OAT tests or a Methylation Profile from HDRI can identify biochemical abnormalities before they manifest as an illness. If a SNP isn’t impacting your functionality, then I don’t think you need to worry about it.

          • Michael (NW) says:

            Hi Lynn, thank you for the response.

            I noticed I had to look up GAD1 not GAD 🙂

            Anyway, now I have a bit of a delima. After comparing the Dr. Yasko Test with 23andME, Dr. Yasko’s methylation test showed I was MAOA – -, but 23andMe shows I’m MAOA and MOAB ++. This has a huge implication. But, knowing my symptoms, and what has helped, it would seem that I’m very low in Serotonin, as St. John’s Wort and 5-HTP is helping me. So, it would seem that I’m more MAOA – -. Although I guess I could still be ++ and have other reasons for depleted Serotonin levels. I’m also CBS ++ and BHMT +- so I could have low BH4 levels, well I’m also QDPR +- which would assume low BH4 I think…..

            But according to the heartfixer methlyation page, if I’m MAOA++, then I should avoid high tryptophan foods, (that would mean 5-htp would be bad), and only use low doses of SJW to avoid mood swings. Yet, SJW and 5-htp are greaetly helping. Hmmm.

            I’m also trying to determine the meaning of MTRR. I’m ++. I thougth this means I don’t make enough Methly-B12 or can’t recyle it or something? This would be why I have a HIGH level of unmethlyated B12 in my bood. So one would assume. But, reading the info about MTRR on 23andME, MTRR is from a lack of being able to convert 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. This makes it sound like I need 5-MTHF? But I thought MTHFR ++ would mean you needed 5-MTHF, yet I’m MTHFR – -. Although according to 23andMe I’m MTHFR (LOC100506310) +- which has to do with making an enzyme called methylenetetrahydrofolate reductase, and MTHFS +- which gene is an enzyme that catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate. Sounds like this recycles 5-MTHF back to 5,10…..Not sure what that implies.

            So, I’m trying to figure out, do I need methylB12, which I believe is indicated and seems to help me, and I have had tests that show I have a high need for B12, (Spectracell, NutrEval)….. But, do I also need 5-MTHF? My folate levels are usually elevated. So, do I have an issue converting it ? I’m not the standard MTHFR ++, I’m –. Is it high because it’s not being used enough to convert B12 to methylB12?

            Sorry, so many questions, and not enough doctors to understand how to help you.

            So, any guidence is appreciated.

            Thank you,


          • Kathleen says:


            There has been some conversation on MTHFR FB pages regarding reporting on variance reports from various variance report services that they are showing conflicting results, such as you are stating, i.e., MAO-A -/- on one, MAO-A +/+ on another, etc. This IS disturbing. Watch this National Geographic film on the Warrior Gene, MAO-A Maybe it will help you determine which you have. A scientist in the film made a very interesting connection between MAO and serotonin.

          • Lynn_M says:

            Michael (NW),

            This is in reply to your question about MAO A and MAO B. To reply to your question, one would need to know the rs number of the MAO A and B SNPs you’re referring to and what your genotype version is – the A, C, G, or T combination. MAO A has 48 different SNPs associated with it on 23andMe, MAO B has 96. With that knowledge, one could look up the rs number on dbSNP and look up the population diversity for your particular SNP version. One could also do something like a Google Scholar search on the rs number and see what has been reported about that particular SNP and your genotype version.

            I suggest you also do that for your MTRR SNPs as well as any other SNPs you have questions about. Yes, it’s hard work, making sense of journal article or something like Promethease or OMIM. It’s the only way I know to figure out the implications of having a particular SNP. And again, it’s only in rare cases that a particular SNP is deterministic of physical characteristics. I would advise treating for your physical condition, not for any particular SNP version. It would be nice to have a health professional to turn to to interpret everything for you, or maybe look at some of Dr. Ben’s videos, but short of that, the do-it-yourself way is to do the research yourself.

            23andMe does not assign +/+, +/-, or -/- to any of the SNPs. 23andMe makes no interpretation of their results, except in their Health Reports section, which they aren’t currently offering because of FDA restrictions. The + and – are something that an interpretation service such as Livewello or MTHFRSupport has provided, not 23andMe. dbSNP lists the ancestral allele for each SNP, and that is what Livewello uses as the -/- SNP. I don’t know how MTHFRSupport determines what SNP is -/-.

  • Duart says:

    I have been on Metafolate Folate 400 , one three times a week for about a month now and have no side effects at all. Am I just lucky or does it take a while for the side effects to show up? I’m also on a B12 mouth spray 3 times a week.

  • Tara says:

    I’m 27 years old and have been trying to start a family for 2 years. I have PCOS and was recently diagnosed with MTHFR heterozygous A1298C and C667T. I have suffered through 5 early miscarriages (all between 4-5 weeks), the 5th I’m actually going through now. I dont have a history of blood clots, but both set of my grandparents and an uncle suffered multiple heart attacks and strokes. My maternal grandmother always had multiple m/c’s and one child with cerebral palsy. I have a feeling she had MTHFR as well. Anyway, my doctor is of the mind that thrombophilias DO NOT cause issues with pregnancy but to be safe, put me on folgard and baby aspirin. But I still m/c’d again. I asked about methylfolate and she blows me off saying it’s not the recommended treatment and it’s supposedly worked for all her other patients. She also doesnt want to bother with Levenox starting after my IUIs. It’s extremely frustrating and I’m looking for encouragement. Am I right to demand to be switched to methylfolate and to give levenox a try? I’m also having genetic testing done to rule that out.

    • Alicia says:

      Tara, if you do m/c this pregnancy (which I’m sorry this has been such an ongoing issue with you and I hope that you don’t) and you decide to try again, I would find a new OB before you start trying and discuss your issues with them and how you want to handle them – preferably a high risk OB. I wouldn’t keep going to the same dr who is not listening to you. Best wishes.

  • Todd says:

    Hey Dr Ben, I was curious on your input of methylation and chronic lyme disease. I started methylation treatment at the same time as treating my infection under my doctors care, he suggested I do this to be able to de tox better and for an all around more comfortable time getting better.. Not that there is anything much comfortable about lyme lol!

    Anyways I was using 10,000mcg of methyl folate, 10,000mcg of methyl b12, 10,000mcg of adenob12, and 1000mg of carnatine daily, alongside a low dose b complex with active b vitamins.

    Also P5P at 10mg a day, and molybdenum for sulfur.

    I noticed some side effects but during the whole time it was impossible to tell if it was from killing bacteria, or from methylation reactions..

    I do know that there is some degree of ammonia issues, and obvious toxins from the lyme so I wonder what is my best approach to treat this? Should I continue methylation support or treat these underlying issues first? Keep in mind it may take a while to do so, or maybe lower my methylation supp doses?

    I do try and keep good levels of methyl b12 supplementation though as it helps my nerves, and protects against oxidative damage from the infection, I figured I could just lower the rest of the vitamins if necessary..

    I am definitely having over stimulation symptoms from the methylation supplements at times too and want to balance this out.

    Anyway I am just really lost and would love your input on addressing methylation in the treatment of lyme disease and my best approach to do this?

    I am heterozygous for C667t but no other known mutations.

    Thanks so much!


  • Robbie says:


    Mutation A1298C, and C677T.

    I am getting sores in my mouth, like cancer sores. Could that be from the Methlyfolate?

    Yes my doc initially started me at 15 mg. that was combined with B12 M, and other Bs. That did not work. Then I switched to 1 mg but no B12.

    Now I am 1 mg, with 1000 B12 may still be too much for me. Thanks for your info.

    • Todd says:

      Could be vitamin b2 deficiency. if you over do the methyl folate without using a b complex to keep other b vitamin levels adequate this can be an issue. Flooding the body with too much folate blocks the cells of thiamine. You should try at least 50mg if you are using high doses of methyl b12, alongside the methyl b12..

      Canker sores are a common symptom of thiamine deficiency.

      • jill e. says:

        How do you find a B complex WITHOUT Folic acid? It’s not around that I can find. I even find folic acid in my coconut milk 🙁
        I’m currently doing 2000 mcg 5-MTHFR and 5 mg Methylcobolamin. Reading my label for 5MTHFT, it has mag, stearate.. and that is a NO, NO and silica.

        However at this moment, I’m detoxing of every supplement! I’m doing the Niacin, Exercise, Sauna detox.. so far love it, but just started. Trying for 1 month.
        Figured I’d clear EVERYTHING out of my system, yes I’ve stopped taking all supps.. and I’ve several.
        I’ve lost some of the headaches I was having.. maybe I’ll just stick to B12 and complex.. ugh. Finding a knowledgeable Dr. will help.

        • Dr Lynch says:

          Hi Jill –

          My company, Seeking Health, offers two B Complexes –
          1) B Minus – all B vitamins except B12 and folate
          2) B Complex Plus – all B vitamins – no folic acid – only methylfolate

          We don’t use folic acid in anything of ours. Only two products contain magnesium stearate – a time-release and a chewable. No way around it for those.
          Silica is fine – no issues with that.

  • Alicia says:

    I have been on “Neuro Methylation Cream” for 11 days and it has 5-MTHF in it and I have done nothing but feel good. Haven’t had a second week crash. I had symptoms of irritability and psychoses and pain before. I also have Lyme Disease and am detoxing better so feel better from that too. I am compound heterozygous. The cream does not say how much 5-MTHF it has in per pump.

    • Todd says:

      I can relate to your symptoms so much alicia, I had bouts of severe agitation, rage, and hallucinations among the other brain, heart, and nerve issues. So many other things, lyme really does have like a MILLION symptoms haha! Thanks for letting me know it helped so much! THe only trouble I am finding is the inflammation caused by the methyl folate, combined with the herxing and treatment It makes a double whammy of multiple inflammation processes… 🙁

      I am confused though because I thought methyl folate is a powerful ANTI inflammatory lol! I think it must be detox, raising inflammation in the system while it takes care of toxins to get rid of, I can’t imagine any other reason for it. I do need it though because of my mutation so I am just gonna have to ride out the inflammation, though my nerves hurt so bad!!

      Definitely de toxing much better just super exhausted and feeling hit hard with de tox from the methylation supplements, as long as it is helping though I am all for it! 🙂

  • Michael_Dowdy says:

    Hello Dr. Ben. Application A566 goes into much detail regarding the maximum recommended tolerable daily dose of folate or L-5-MTHF, calcium that can be used in Australia and NZ as a food additive. It is far much less that the amounts found in Deplin and Metanx. If a marketed vitamin lists folate on its ingredient list can folic acid be allowed as the actual ingredient they’re using? Folate and folic acid are completely different, aren’t they?

    • Lynn_M says:

      Folate is the generic term for Vitamin B9. It can be used for folic acid, 5-MTHF, and L-5-MTHF. It a label doesn’t identify the folate as activated or 5-MTHF or metafolin, I would suspect it to be folic acid. Even if it is 5-MTHF, the form you want is L-5-MTHF.

      • Michael_Dowdy says:

        Hello Lynn. There were a couple of reasons I asked. My understanding is that folate is the natural form found in foods but folic acid is synthetic. The synthetic has to go through changes once ingested but this is hindered by MTHFR mutations. Did you get a chance to read any of the Application A566 documents? They are a little lengthy. Respectfully Michael Dowdy

        • Lynn_M says:


          Your understanding of the word folate is incorrect. From Application A566, p. 2, “Folate is a B-group vitamin and the general name for a group of structurally-related compounds, both naturally-occurring and synthetic.”

          Folate is an umbrella term. Folic acid is a folate, L-5-MTHF is a folate. The shorthand people use to refer to naturally occurring tetrahydrofolate derivatives is to use the word folate, but it’s a sloppy use of the term folate. If you want to refer to just the natural forms of folate, to be precise, you need to be more specific than saying folate.

          In regards to what is permitted on a label, since folic acid is a folate, manufacturers can use the word folate to identify folic acid in their product.

          • Michael_Dowdy says:

            Hello Lynn_M. Could the problems that people are experiencing be partially because of methylfolate being taken at the same time synthetic folic acid is still being fed to use in folic acid fortified foods?

          • Lynn_M says:


            Folic acid, whether from “enriched” food or supplements, will bind to the cellular receptors for folate and competitively inhibit natural forms of folate from binding to those cellular receptors. Folic acid gets metabolized quicker than methylfolate and so will get to the cellular receptors faster.

        • Greg says:

          Hi Michael,
          The main form of folate found in nearly all foods is 5MTHF. It is normally polyglutaminated, which helps it to stay within the cells. In your intestine you take most of the glutamate residues off the 5MTHF and basically absorb non-glutaminated 5-MTHF. Now the problem is that the receptor for folate uptake will take up both folic acid and 5MTHF, and is proposed to have a higher activity towards folic acid. This means that if you take 5MTHF with folic acid fortified foods, it is possible that the folic acid will be taken up preferentially.
          As for processing within the cell, both folic acid and 5MTHF have to be processed to become active. For 5MTHF it needs reduced methylcobalamin in methionine synthase (MTR), so if you are not taking or do not have sufficient MeCbl the 5MTHF will be almost useless. You could try taking it before meals, although it is very poorly soluble, so you may need plenty of water.
          Lynn_M is pretty much spot on with the definition, although most people do not really understand this point.

          • Michael_Dowdy says:

            Hello Greg. I take 5MTHF. I’ve read that folic acid is processed in the intestines and becomes FormylMTH and that 5MTHF gets processed later in the liver. It’s difficult to avoid folic acid but the 5MTHF needs to be taken in advance of any folic acid so it can reach the receptors first. Now I take the 5MTHF well in advance before getting any folic acid into my system so it reaches the receptors first. But another problem exists because to manufacture 5MTHF two types of isomers are used to make it racemic. Only half of the 5MTHF is or gets converted into 5-L MTHF once it’s processed in the liver. What happens to the other half of the isomers used to make 5MTHF racemic? Is any of it processed into 5-D MTHF? What are the properties of 5-D MTHF? Is there a possibility of chiral toxicity since different isomers are present? Call me if you wish at 321-443-6597. Respectfully, Michael M. Dowdy

          • Greg says:

            Hi Michael, Happy NY.
            Good questions.
            Theoretically it would depend upon the ability of the folate receptor, or the reduced folate carrier to recognize the D or L isomers, which I don’t remember.If they recognize both, then the D will compete with the L and so you will get lower uptake of the active.The intestinal transporters seem to have quite a high uptake capacity, so this may not be a problem there. The follow-up enzymes are normally stereospecific, so won’t react with the D-form so it should be excreted. The previous study that I quoted on intestinal uptake did not appear to suggest the formyl conversion, so if you have the reference please cite it and I will look over it. As I said before I wouldn’t get too hung up on whether you have folic acid (folate being the ionized form) or 5MTHF. The studies cited didn’t find a difference. There will be a difference in the gut solubility of 5MTHF as the methyl group will reduce the solubility as you have removed H-Bonding and put in an extra hydrophobic methyl group. Presumably this is a problem hence the development of the various 5MTHF chelates that are sold. Without actually testing the pH titratibility, my guess would be that the solubility of 5MTHF would only be one tenth that of the ionized folic acid, which presumably would be sodium folate in the intestine. So i may be that you are losing more of the dose down the toilet with the 5MTHF. Of course this would not worry the manufacturers one little bit.Of course any dose of folic acid or 5MTHF that is above the uptake capacity in the intestine will also end up at the local water processing system feeding the bugs there.

  • Renee says:

    folate is active form, folic is in active form it needs to turn into the active form, some MTHFR’s cant do that depending on what mutations have expressed..

    • Lynn_M says:

      The word folate, by definition, includes all forms of vitamin B9. Folate refers to both active natural forms and folic acid.

      • Michael_Dowdy says:

        I guess I should have asked about the difference between L-methylfolate and D-methylfolate? I thought L was natural and D was synthetic. I thought it referred to the refraction of light when passed through a molecule of each. Isn’t the twist of natural vs. synthetic opposite directions of refraction? The bigger question is what tests were done on humans to determine effects and side effects of each?

      • Michael_Dowdy says:

        Hello Lynn_M and Dr Ben. When I was looking through “Application 566” I saw that the terms folate and folic acid could be used interchangeably which I found very disturbing. Did I misread or misunderstand that? Folate (umbrella term as you say Lynn) does not necessarily mean “natural” or “active” which is precisely what I was referring to. But what’s the most interesting thing I found in the “Application A566” documents was that there was a determined upper tolerable limit of methylfolate (5-L-MTHF) of 1mg. I don’t think it should be allowable to use folate as an umbrella term to include natural and synthetic because it’s too confusing. Renee’s idea that folate meant natural or active was the same as what I thought before reading through “Application A566.” I’m going to read through them again but I’m pretty sure my memory is serving me correctly on the terminology and quantities. If 1mg is the upper tolerable level or limit of 5-L-MTHF why do you believe people (and children) are being prescribed up to 15mg?

    • Michael_Dowdy says:

      Hello Renee. It’s unfortunate that it’s not that easy when it comes to what manufacturers can use the words “folate” and “folic acid” to encompass. Lynn_M is EXACTLY correct unfortunately. What you’re saying is also correct also but the manufacturers can mislead with the use of “folate” or “folic acid” in their list of ingredients. Take a little time to read through the “Application A566” documents and you’ll see why I raised that question. To me it’s absolutely frustrating to learn that “folate” can include synthetic products. L-5-MTHF is the natural form (folate) but it can be called “folic acid” on the ingredients. I don’t think it should be allowed to use the terms alternately to encompass either which they wish. Also in those same documents it’s acknowledged what the upper amount of methylfolate is tolerable to people. Take some time and read the documents and I’m pretty sure you’ll share my frustration. Best Regards, Michael M. Dowdy

  • Diane says:

    My 18 year old son has a defect at C677T, heterogymous. He was diagnosed as bi-polar. His doctor gave him samples of Deplin, 15 mg and told him to take them for 1 month. My son took the capsule daily for a 4-5 days and then told me he didn’t want to take it, that he just didn’t feel good about it.I didn’t like the dye and fillers, either, I read a little bit on-line about starting with a lower dose, so I ordered a 5 mg dose of methylfolate, thinking that was low enough. My son took it for 2-3 days and then the next day he took it, in the evening, he had a reaction I’m assuming was due to the folate. He was just going to bed and he came out of his room telling me to call 911. I did not, but asked him what was going on. He complained of a racing heart, great anxiety and said he felt like he was going to die. I did not have niacin on hand to give him. He had taken an L-theanine capsule and a phosphatidyl serine capsule before going to bed(the folate early evening), so I thought he was having some sort of reaction to those or possibly the combination of those with the folate. My son seems to react strongly to all kinds of meds and supplements, especially to caffeine so i just wasn’t sure what was going on. It was in the morning that I recalled all I’ve read about overmethylation reactions. ALSO, i assume my son inherited the gene mutation from me, as I have CFS/Fibro, IBS, allergies and chemical sensitivities and depression. I began taking 5 mg of methylfolate and on day 3 began hurting much worse than usual, like I hurt when exposed to chemicals in clothing stores. Then, I read that folate detoxes the body and to begin slowly or symptoms can be intense. I have backed off and now have niacin on hand. I am taking a multi with folate and a B Complex with folate, so I’m not sure how much extra to take or if I even should take extra since Dr. Lynch says he thinks a multivitamin with folate and methylcobalamin is probably enough for the C667T heterogymous person. My worse suffering, though, is my chemical sensitivities and so I know my detoxification system isn’t working properly.

    • Michael_Dowdy says:

      Hello Diane. I have 2 copies of the 677CT mutation. My initial reaction upon taking 7.5mg was to run to the ER. I didn’t go though realizing it was the Metanx. My system can only tolerate 1200 micrograms a day. If I had taken 15mg Deplin I’m sure I would have ended up in the ER. You will find the best information on this website. I agree with the idea to start very low and work upward. I used to take a B-complex made by Nature’s Measure trademark that is stated to have 400 micrograms of “folate.” I called the manufacturer of the B-complex and they told me it was “folic acid” as the ingredient. “Folate” can be a tricky term. Heterozygous for the mutation is common but everybody is different in their needs and responses to methylfolate. I personally can’t imagine why anyone would need a dose of 15mg based on my own experience. It’s very easy to find conflicting information on the web but Dr. Ben’s information is the very best and most trustworthy I’ve found. I’ve studied a lot and so should you. Wait for Dr. Ben’s response. Very Best Wishes, Michael M. Dowdy

  • Dan says:

    Hi Dr Lynch,

    I have not felt well for a little over 15 years now. My main issues are brain fog, vision is unbalanced, fatigue and anxiety. I had an episode about three months that led to a visit to the ER – I had difficulty breathing, feeling like my throat was closing and nasal passage was inflamed. This led to a serious panic attack with after shocks for about a week.

    I went to every MD type doctor you can think of and have been relieved to find out I’m not allergic to anything, heart is healthy, GI tract is in tact… I was sent home with Xanax, acid reflux med, nasal decongestant, corticosteroid, and a few others. I never took any of them.

    I had a consultation with my sister who is an ND in Arizona, she suggested I get blood work done for several things that my MD never heard of but was ok with including them. One marker that came up extremely high was homocysteine. My level was 22. After reading the seriousness of it I almost had another panic attack. My sister the ND suggested I get the 23andme test done and start low on methyl folate, TMG, methyl b-12, p-5-p, riboflavin phosphate. I also take magnesium, zinc, calcium, potassium, and 5-HTP before bedtime.

    I’m still waiting for my 23andme results but have noticed worsening symptoms since methyl folate, TMG, and b-12. I take 1mg of each and it completely knocks me out. I’ve tried to increase each by a 1mg hoping my body just needed to adjust – not the case, made me even worse. I’m worried if I take niacin I will be stopping whatever the supplements are try to kick start.

    I was wondering what your thoughts are on my homocysteine levels and my reaction to the supplements. Will the Niacin slow down any progress that may be occurring?

    Any thoughts you may have would be greatly appreciated.



    • Terri says:

      I have similar symptoms but low homocysteine-panic attacks are the worst! I wasn’t able to take any methylfolate or methylcobalmin except what was in my multivitamin. I am detoxing sulfur first. If you use the heartfixer page or Amy Yasko’s free ebook, it will give you more information. I would get some sulfate test strips from Amazon and start on a low thiol diet. It is supposed to open up the pathways that other Snps might be causing issues with. Also, some people have better luck with hydroxocobalmin instead of methyls. Methyls can create stress reactions on those who have high sulfates or those with CBS or COMT issues.

      • Dan says:

        Thanks, Terri. I will mention this to my ND. I skimmed through the heart fixer page and it sounds like high sulfate and high homocysteine are not common.

        At this point I plan to stay at 1mg of methyl b-12 and methyl folate until I get my result back. Or increase at a lot slower pace.

    • jill e. says:

      I would stop the 5 HTP, your probably taking to help you sleep.
      TMG.. ? for depression? take just your folate/b12, zinc and Magnesium.
      I’ve worked in the medical/Holistic field for several yrs. and we tend to over supplement ourselves when we’ve multiple issues.
      I’m currently taking 50-100 mg Niacin to flush out all this stuff, along with exercise and 30-60 mins of sauna/steam/epsom salt baths…to detox. Pick 1 or 2 that you’re able to do. I belong to a gym, so steam and sauna are my choices then a bath a week.

      Then I will start my supplements again. I feel really good not being on the methylfolate and methylcobolamin for now.
      High Homocysteine is not good! mine actually went down to 5 after taking 5 MTHFR.
      diet is helpful with this too. Make sure your eating Good, organic grass fed only meats!!!
      The Niacin, exercise, sauna detox has been the best and easiest detox I’ve found for my lifestyle. Can find this on Dr. Mercola’s site.

  • Mabelle says:

    I’m homozygous MTFHR, C677T. I had a PE and suffer from depression, bipolar and anxiety. I take a lot of antidepressants, Wellbutrin 200mg twice a day, Abilify 10 mg and Trazadone 100 mg. I’m in warfarin for life. I started taking a month ago Jarrows methyl folate, and a week after methyl colabamine( Vit B12). I have been having cramps in my legs and the pain last for a week. I am also having muscle pain. My potassium and rest of electrolytes are normal. Could it be overmethylation? I’ve also heard that it can be magnesium but I haven’t been tested for it. Please let me know, what do you think. Also what brand of Vitamins with the methyl folate and methyl Vit 12 do you suggest. I stopped my regular vitamins and the Super B complex prior to taking the methyl.



    • Michael_Dowdy says:

      Hello Mabelle. Do you have any other clotting issues? Betaine or Trimethylglycine are discussed on the NIH site as treatment for elevated homocysteine and homocysteinuria which can cause vascular problems. Methylfolate treats the root cause of these problems. A potassium supplement at night might help with leg cramps. Diet alone probably is not providing enough magnesium and a supplement of both electrolytes is probably the right direction to go. Statins can cause leg and muscle pain so talk to your doctor about this, it can be very serious. Synthetic folic acid is bad for someone with your mutations. Jarrow B-right has 400 micrograms of methylfolate in it, it’s what I take every morning. Don’t take more than one B-right. It will keep you awake at night. That may or may not be enough methylfolate for you since you have 2 copies. It’s a very good starting place though. Avoid folic acid the very best you can and any supplement which contains folic acid in it’s synthetic form. I hope warfarin sodium is done away with soon as the recommended protocol treatment for PE prevention. It’s pretty much rat poison and kills rats by causing them to bleed out in their digestive tract. It kills people with brain hemorrhaging and requires constant monitoring. Read the British reports on Warfarin as well as the AAOS (American Association of Orthopedic Surgeons) recent reports on Warfarin and alternatives to prevent DVT, VTE, and PE and then talk WITH your doctor. Be careful, very careful, to prevent any injury to yourself which could cause you to bleed out. If you switch to aspirin the effects of aspirin are irreversable which is not the case with Warfarin. That’s the only positive I can see with Warfarin, a medicine I hope is very quickly done away with. I will absolutely not use warfarin sodium for myself. There are much better choices of medications to prevent DVT, VTE, and PE if your insurance will cover them. I use aspirin daily and virgin coconut oil twice daily for my Factor V and MTHFR 677CT++ clotting problems. I also find Trazadone to be an extremely frightening medication. These are just my feelings and positions and I’m not a healthcare professional. Study here! Always consult your doctor! Respectfully, Michael Dowdy

  • Catharine says:

    I have c677t mutation. My doctor rec I take Methyl-Guard ByThorne. It has several ingredients but for the purpose of this posting 1.2mg of Methylcobalamin. After only taking one I was practically bed ridden. I had brain fog, achy joints, migraines, and was really irritable, I mean really angry and my depression deepened. This lasted for 3-4 days. There was never a plan B for me. I did the cycle for the past 10 months. At the urging of my doctor I finally invested in genetic testing and this added information helped him to finally come up with another option for me. It also led me to this website where I found out I was not alone. I never knew of the use of niacin or curcumin. To complicate matters I have Lyme disease, Hashimotos, a brain tumor and several more illnesses to add to my buffet menu of symptoms. It is my hope to resolve my detox pathways issues and to then move onto my other health issues. I am now taking 1/4 tablet of your sublinquil B12 and will follow your motto of starting low.

  • Ken says:

    Took my first methylfolate tablet tonight. I haven’t been tested for anything but I can tell you that I have suspected I have had amemia all my life. Iron has helped a bit, B12 a bit but less so, folic acid, not at all. I can take 5 mg of it and it doesn’t do a damn thing. When I read about the poor absorption problems that some people can have I felt this was worth a shot, and went out and got some.

    Well here’s my side effect, this is the first time I’ve ever felt completely healthy in my life, after just a couple hours of one 1 mg tablet. I have taken pretty much every supplement known to man and it’s all about trying to feel good, I have done a pretty good job of that but still there was something missing, a great deal missing to be honest.

    I got what was missing and then some from this one little tablet. I realize that it takes time to heal from this but I am already there. It might be possible I guess to improve from here but I cannot imagine it, we will see though.

    This is very exciting. My chronic fatigue is gone. My mental fog is gone. All the negatives are gone. My blood sugar is better already, I have diabetes and have struggled with that a bit more than I would like to. Maybe this will even help that as well, that would be a bonus for sure.

    I did take this with 10 mg of NADH but I take that already and it wasn’t that although the two together may be synergistic.

    Thank you Dr. Ben for turning me on to this and I look forward to continuing to take this and seeing what the results may be.

  • carlametho says:

    my doc told me to take 1000-5000mcg per day of metho folate
    and b12 methocobalamin 3-4 times a week.
    it really seems like some this missing
    if i take more than 3000 i get a rash on my side under my arm and it takes days to go away

    Is there a better combination I could take?

  • Luca says:

    Hi doctor Lynch,
    I’m from Italy and i’m a man with homozygous mthfr c677t.
    My medic give me (endomox) with normal acid folic nac and b12 not methyl,and i felt horrible…then he give me (prefolic) 15 mg of methylfolate same thing… I start to read information from your website fortunately, and i start to figure out what to do… and that i’m not alone to have side effects…
    I have one question (i read all your article for my mutation ).
    I never had fisical problems until 28 years,but i had “mental problems” like panic attack…my medic give me for 3 years xanax and frontal,probably intoxicating my body… Then when i was 27 years old i start to have the first symptoms like loss of libido and hair loss and I felt that my heart beat more slowly… So in my totally stupidity and ignorance i start to take creatine in high doses for 2 month…and i felt better…but when i stopped all the symptoms came back in more strongly… after that ,from 28 to 31 i never felt ok… now I’m trying with 4mg of methylfolate (the lowest dose for the Italian market) but i don’t feel better… now i’m waiting for methyl b12 sublingual 1mg…to take it togheter..
    I’m desperate cause any doctor in Italy can help me…and someone has worsened the situation.. i’m starting to be vegan,and i eliminate glutin and any form of milk cause i discovered i’m allergic for both.

    I apologize if I have dwelt, and for my english

    • Luca says:

      Sorry i i forgot to say that i’m taking levofolene that is not methyl folate but levofolinic calcium pentahydrate… it is ok ?

  • Ann says:

    Hi Dr. Ben,

    I am compound heterozygous for C677T and A1298C. I started taking Deplin–I had 7.5 mg. tablets and for the first day took half of a tablet, and then the next day took the whole tablet, and then the following day took two tablets. The day I took one tablet I was very depressed and cried a lot (I have trouble with depression but this was worse than usual). The day I took 2 tablets I was very anxious and agitated. I know from your website that anxiety can be a side effect, but can depression also be a side effect? Thanks.

  • Mel D says:

    The symptoms or side effects referred to above sound very much like an endocrine autoimmune reaction to grass grains. Are there grass grain-derived ingredients in most forms of active mthf?

  • Terri says:

    I watched Kathleen’s youtube video post on MAO A and warrior gene.
    How does one find whether they have 2R, 3R, 4R or 5R? (repeats)?
    There are so many snps on the MAO genes that I’m confused. I know that G/C means warrior and A/T means normal, right?
    Also, is T lower activity and G is higher activity dopamine?
    Also, is MAO A or COMT or both responsible for warrior/worrier genes?

  • Emily Riley says:

    I need help! I recently found out I am heterozygous A1298. I have had 3 miscarrages and 1 healthy pregnancy. I am trying to get pregnant again. My ob doctor recommended I be on 2000 mcg of methyl folate. I started taking 1000 mcg of methyl folate and have felt fine for about a month. I upped it to 2000 mcg about a week ago and now my muscles are so achy! I can barely move my neck the muscles hurt so bad and my back muscles are very achy as well. I have had a few times I feel like I have had brain fog and I also a few times I felt very irritable. I am taking 500 mcg of methy B12. What is the correct dosage I should be taking of my supplements? Are there others I should be taking as well. I so badly want to have a healthy pregnancy and not lose another baby! In your article you state that these side effects happen if you have inflammation. How do I know what my inflammation is and how do I get rid of it? Also i should mention I am planning to take Clomid during my next cycle…is there any worry of my body reacting negatively because of my MTHFR mutation?

  • Michael_Dowdy says:

    Hello Dr. Ben. Can environmental reasons cause MTHFR mutations and if so, how can they be distinguished from genetically passed on mutations? Is folic acid fortification going to continue under the FDA even though it’s now know to be toxic when exceeding known safe levels? Is the presence of the folic acid food additive that’s forced upon us in our food part of the problems and side-effects that result when trying to use methylfolate?

  • Flo Levia says:

    Ive been taking 5 mg. of compounded 5MTHFR for over 2 months. By the end of the first month, my brain fog has all but disappeared and my energy is better than it’s been in years. About a week later, my left knee totally fell apart — baker’s cyst, severe pain in joint after 10 min, of walking. Unresponsive to physio/acupuncture/biopuncture/massage/CST. Naproxen helps a little, but my mobility is being threatened and my other knee is starting to worsen as well. My N.D. asked me to go on Wobenzyme Relief (a new product) and Ultimate Glucosamine( not the sulfate — I don’t tolerate sulfur products).
    AM I taking too much 5MTHFR??? Is this a side effect from it or just coincidence?? Is adding those other 2 products all that’s needed?
    I would be grateful for any feedback!

  • Lori in Columbia, MD says:

    MTHFR a1298c homozygous mutation was diagnosed just this past fall, and I began methylfolate supplementation on my own. For a couple of weeks, I felt absolutely fantastic: happy, clear-headed, energetic, whereas I usually feel quite the opposite. Chronic fatigue, fibromyalgia, chemical and food sensitivities, and crushing depression have been my constant companions for 30+ years no matter what I have done to help myself or what medical or alternative treatment I have undergone. So I was thrilled to have such a powerful response to the methylfolate. Unfortunately, I was taking way too much, and became extremely irritable, impulsive, hypomanic, and generally crazy. The worst part, however, was the extreme muscle cramping and insomnia that occurs with methylfolate supplementation. I had to completely stop and recover slowly, painfully from the life-damaging effects of insomnia and muscle tears and knots.

    Finally I saw a doctor in April, someone who is the regional methylation expert. He said the tight muscles were due to my overall methylation status being poor, so I began taking SAMe, l-methionine, TMG, and methylcobalamin in a daily schedule and began feeling fantastic again. I thought, Finally, I am solving this problem! However, the feeling good rapidly and severely crashed into terrible insomnia and cramping again, with temper tantrums and other debilitating psychological symptoms. I am exhausted. I have tried small amounts of methylfolate with niacin to temper it, but no go! I just don’t know what to do. The doctor I went to see doesn’t seem to really know how to help me, only how to sell me hundreds of dollars worth of supplements from his in-office shop. He also swears by a combo of folic acid and hydroxycobalamin, and he has had his own formula made of this combo. Yet this evening, on the thyroid summit call, I heard Dr. Ben say that we must avoid folic acid. It’s all so confusing. And I am now completely exhausted and brain-foggy, so it’s impossible to do anymore research.

    Where do I go from here? There truly is no one to help me here, despite being in the neighborhood of Johns Hopkins and the NIH.

  • Michael_Dowdy says:

    Hello Dr. Ben Lynch.An idea came to my mind today. Other than simple overdosing of 5-L-MTHF maybe the troublesome side effects exist because of combining 5-L-MTHF with synthetic Folic Acid. Is it possible that synthetic Folic Acid is the real root of the problems and side effects and possibly has to be totally eliminated before methylfolate can work properly? Is it possible that the two cannot be safely combined?

  • Lori in Columbia, MD says:

    I left out while recounting my story that the second time around that I had to stop taking methylating supplements, I had been taking a new B-complex by Country Life with active forms of all the B vitamins. The form of folate in that supplement turned out to be 800 mcg of methylfolate. I had thought I wasn’t taking methylfolate, so I was chagrined to realize I was merely repeating the mistake of several months before.

    I also get severe muscle cramping when I am exposed to a variety of common but toxic chemicals in new commodities, especially new carpeting, paint, and refinished furniture. There has been talk in doctors’ offices about autonomic nervous system injury due to my body’s inability to produce glutathione and detoxify the offending chemicals. I sometimes wonder if this injury is permanent. I also wonder if I have brain damage from toxic exposures without the capacity to produce glutathione; that would explain the nightmarish ideations I am sometimes possessed by.

    • Michael_Dowdy says:

      Hello Lori, MD. I also wonder what has caused all of my neuropathy. Flouroquinolones, organophosphates, DDT, or pfthalates possibly? I’m sure it’s due to more than just diabetes. Your body is producing glutathione or you would be dead, maybe it’s just not producing enough. Take the precursors for glutathione. Stress is my worst enemy. It sounds like it might be your’s also. It might be a good idea to treat for that first. I’ve been treating with methylfolate with some changes in my neuropathy but it’s a long way from cured. I’m not a healthcare professional, just a patient. I hope you improve.

  • Momwithmthfr says:

    I was diagnosed with MTHFR C677 and A1298 in 2005 during my second pregnancy. At that time, and during my other pregnancies I was put on a strong Folate/b12/b6 supplement and during pregnancy #4 I took blood thinner shots daily. I recently suffered a miscarriage with baby#5 and due to my health, plan on having no more children. It seems that my doctors in the this area no nothing about mthfr and what I need to do or take (besides during pregnancy.) I have always suffered from ibs and after baby #4 was born had bouts of depression and panic attacks. I was put on Paxil and it helped a lot, but the problems have crept back up since my miscarriage in the fall. Right now I take 20mg Paxil daily, Prenatal vitamin, fiber and st johns wort. I have always had a very low energy level and want to figure out what I need to feel better or someone who can help me figure that out?? Also, should I have my children tested? Ages 9,7,5 and 2??

    • Matina says:

      Hi! I a not a doctor and have struggled myself wit the whole mutation issue. I also have both C677 and A1298 genes, and have struggled with finding a treatment that would steadily treat my anxiety and depression. Several years ago I too was put on Paxil for panic attacks. I felt great for the first time in my life, but struggled with the weight gain, loss of libido, and tinkering with withdrawing from it. Recently I spent three or more weeks in a terrible withdrawal just from lowering my clonazapam dose so I can just take one medication that will help me as I am presently on three different ones. The reason i felt compelled to respond to your post was that I noticed that you said you take Paxil and also St. John’s wart. I have to tell you that this in itself is very dangerous. You should research this combination. Another thing I have noticed about me from all of my treatments is my sensitivity to anything that is used to treat my depression or anxiety that is not from the medical field while taking my prescription medicines. They seem to react or interact. For some reason I get over stimulation in my brain from even the purest form of natural treatments with make my depression and anxiety worse and then adds in irritability. When one struggles with these issues of depression though we can’t just stop the medicines, but for some of us combining them makes the problems far worse. So I have had to stop and re-evaluate which is working and helping me the most and improving the quality of my life more. As opposed to the constant trial and error and set backs and never feeling any better even though some do. We re all different in our chemistry. Plus not all doctors really know what they are talking about nor do all they take time to start slow. As said I just spent the past three weeks in a terrible withdrawal all because my natural path who new I was taking the clonazopam didn’t take the time to ask or discuss how much, how often, did I skip or miss doses frequently, etc. before starting my on this supplement. The result was massive over stimulation of my brain while in an unrealized withdrawal. Today I actual am beginning to feel better thanks to stopping all of the supplements and giving my brain a break. You see when we take anti depressants something different is going on in our brain then the normal person without these medicines. Anyway I just hope you look into the St. Joh’s Wart combination.

    • Matina says:

      PS Paxil does tend to make one sluggish. I took mine at night for a good night’s sleep. Yes, I would also have my children tested to at least get a window in the future to understand better some possible symptoms they may display or have.

  • Heather says:

    My son is homozygous for 1298c. Upon reading this article he has had some symptoms like sore muscles and joints and have said that heart has felt funny…now I’m concerned. I can just stop this for now and how to I reintroduce the metabolite? I’ve read the Optimal Vitamin chewables?


  • Sabrina says:

    Hello Dr. Ben,

    I was wondering what some of the reasons for having Response #2 to Methylfolate are? Is it because Nitric Oxide builds up in your system? Should people with Response #2 continue to take methylfolate, and take other supplements to lessen the side effects? Since the supplement helps these people at first, it makes me wonder what kind of regimen people with response #2 need. Maybe they only needed a little more methylation, and too much off-sets the balance?

    I do not know what MTFR genes I have, but I have been trying supplement after supplement to try and cure my anxiety/depression. I’ve spent probably over $1000 and it’s been over a year that this has been a severe problem. I was on a B complex with folic acid for a long while and I felt amazing, but then all of a sudden I had a depressive episode (while I was ONLY on the B supplement and glycine) and needed to stop the pills entirely. I decided to go through the list of all the B’s in the supplement and find out what was doing me good, and what may have caused the depressive episode (I am beginning to think too much folic acid built up). 400 mcg methylfolate has been a godsend so far, it’s worked better than most any other supplement I’ve tried, but I’ve only been on it 3 days and I’m worried it will just be a temporary help, and I won’t really finally be ok, just fools gold. That seems to be the story of my life lately.

    I am going to get some methylcobalamin just in case anything does happen, and I have Niacin on hand as well. I am hoping that even if I do encounter side effects down the road, the combination of these supplements will allow me to continue the benefits I’m getting from methylfolate so far? I noticed the first dose made me feel a little overstimulated, but also very interactive and happy, which is good for me, rather than feeling like my emotions are blunted. Niacin is too much of a downer/relaxant for me, but it does help relieve stress. I noticed Niacin seemed to kind of cancel out methylfolate’s effects for me, but I’m sure it will be useful if too much builds up in my system. Niacinamide seems to have a completely different effect on me than Niacin.

    Thanks for the article!

    • Madge says:

      Hi Sabrina,
      If you are taking methylfolate (or in fact other folate analogues) you need to also take methylcobalamin (B12) or you don’t process the 5-MTHF effectively. What is more you need to take the MeCbl at a similar time to the 5MTHF.
      The best thing to balance it all up is the mix of Ado/MeCbl that is supplied topically in an oil by I would be careful with niacin it can cause flushing, niacinamide is much better.

  • Brian says:


    I recently found out that I have genetic mutations on one copy of the A1298C and C677T (compound heterozygous). My homocysteine level was out of range as well, B12 was normal and B6 was very high. I had these tests done at the request of a naturopathic doctor. I began seeing this doctor because I have very bad depression, anxiety and insomnia. Unfortunately, I cannot tolerate psychotropic medications of any class, because they elevate my symptoms to where they become out of control. I can’t simply handle it. Recently my new psychiatrist thought I was bipolar, but after trying two mood stabilizers, I had to get off after only a couple days because of the above mentioned problems. So, I started seeing the naturopathic doctor to try and solve the medication mystery. The doctor mentioned starting me off at 500mg of L-Methylfolate. Being that I am ultra sensitive to medications and my anxiety, depression and irritability levels are already high (cannot even tolerate 1 cup of tea) I’m not sure what dosage is right for me or if I should even be taking this stuff at all. The other thing is that I don’t know if my inflammation is under control or not, and I know that using L-Methylfolate can make it worse. I take a small dose if Trazadone (25mg) for sleeping and I know that irritates my stomach. I could really use some guidance as far as dosage and whether or not this supplement will do more harm than good. Thank you so much.

    • Terri says:

      500 mg or mcg? Milligrams is far too high. I would begin very slowly with methylfolate. Did you have your other snps done on 23 and me? Before beginning any methyls you might want to consider reading Yasko’s free ebook and look into detoxing. I’d also be aware of my other snps. Certain people with COMT and VDR taq issues tolerate less methyls than those with other allele combinations. Detoxing should be your first line of order before introducing methyls as well.

      • Brian says:

        Hi Terry,

        In the email correspondence with my naturopathic doctor, she mentioned starting off at 500 mg of L 5MTH, not mcg and working up to 1 gram. I don’t know if there is any difference between L 5MTH and L-Methylfolate.

        In regard to detoxing, she did suggest a special diet, where I cut out several food, however, I could not afford to buy supplementary foods that would allow me to keep my weight (I have lost significant weight) up because I am out of work and have no income due to my current condition.As far as as my medications are concerned, I am on 1mg of clonazepam in the evening and cannot go off it being that’s the only relief I get from my symptoms. I am also on 25mg Tazadone (50mg being the minimal dose prescibed) for a few weeks now to help with sleep. It took me two weeks just to be able to tolerate that small amount, that’s how sensitive I am to medications. Unfortunately, Trazadone is the only thing that will allow me to sleep. Part of this “illness” is that I literally cannot fall asleep. I’ve used other natural sleep aids in the past but my body has gotten used to them. I am in a bind.If I stop the Trazadone I won’t sleep and my overall psychiatric condition worsens.

        Forgive me, but I am not familiar with the abbreviations you mentioned in your reply: snps, COMT and VDR.

        After reading through this website I fear that L-Methylfolate might push me over the edge being that my levels of anxiety and depression are so high as it is.

        Thank You

        • Lynn_M says:


          You need to get clarification of the units from your doctor. The doses and units you report your doctor told you to take are at least a thousand times too high. 1000 mcg = 1 mg, 1000 mg = 1 gram. Often people that aren’t sensitive to medications and supplements start off with around 800 mcg, which is the lowest tablet size of Metafolin, which is L-5-MTHF. L-5-MTHF or the newer and supposedly more stable formulation 6S-5-methyltetrahydrofolic acid are the forms of L-methylfolate that you want to take. You want to avoid any products labeled L-methylfolate, because these contain racemic forms and are inferior. However, L-methylfolate is also a term people often use generically in comments such as on this forum.

          Some people do have problems starting even with 500 mcg. Your history does sound suspect for potential issues. These people find they can start with just a crumb of a tablet and eventually slowly build up their dose. Low folate levels can cause high homocysteine levels, so it sounds important that you do start trying L-5-MTHF, even if you have to start with miniscule doses like 1 mcg. L-5-MTHF provides methyl groups to the body. It would be good to have niacin on hand, because it uses up methyls as it metabolizes and thus counteracts L-5-MTHF. You can take niacin if you start to have unpleasant symptoms from L-5-MTHF.

          Your A1298C and C677T are SNPs (single nucleotide polymorphisms) of the MTHFR gene. COMT and VDR are genes and some people have variant SNPs in them as well. These two genes affect metabolism of methyl groups. If you tested with 23andMe, they would give you the results of nearly a million SNPs. There are many other genes that impact how well you metabolize medications. A knowledgable interpretation of a 23andMe test could help explain why you have issues with pharma drugs.

          I agree with Terri that detoxing and a clean diet and lifestyle are important first steps though.

          • Brian says:

            Hi Lynn_M &Terri,

            First, let me thank you both for taking the time to respond to my post.

            Lynn, the doctor had mentioned 500mg not mcg. I also researched 23andMe testing and it appears that they are currently having issues with FDA and “no longer offer…health-related genetics reports to new customers.” At this point they can only offer ancestry information and “uninterpreted raw genetic data.” Would this kind of testing be sufficient enough for explaining my difficulties with pharmaceutical drugs? If not, is there an alternative? I will admit that I am absolutely frightened because I have been stuck in this psychiatric state for well over a year and it’s chronic and immensely painful, not to mention what the long-term effects of enduring this is doing to my brain (impairment of memory recall, logic, etc,).

            In regard to detoxing, I would LOVE to do it. Unfortunately, the 1mg of clonazepam is the glue that is holding me together and the 25mg of Trazadone is literally the only way I can attain sleep. If I titrate off my state will worsen. This what I meant in my last post when I mentioned I was in a bind.

            Any evidenced-based advice is welcomed and appreciated.

            Thank you

          • Lynn_M says:


            Your doctor was absolutely using the wrong units when she said 500 mg. You need to bring that to her attention, because that kind of mistake can harm people, and you sound like you would be particularly vulnerable to harm.

            You and many other people have misinterpreted the changes the FDA has imposed on 23andMe. The health reports they previously offered were of little value, at least for me, unless a person had one of the limited number of genetic conditions they identified or the genetics that predisposed them to react to any of the maybe 20 or 30 drugs they reported on. None of those health reports dealt with methylation issues. The valuable part is the uninterpreted raw genetic data, and 23andMe still provides that. Once you get your 23andMe test results, there are other services that will help you interpret the data. That is a whole ‘nother post. It could potentially explain your difficulties with pharma drugs if you have defects in any of the family of detox genes, such as the CYP class of genes. If you have a bad liver, well maybe your genes wouldn’t explain that. For $99, and some effort on your part in educating yourself about your genome, there might be a lot to learn about yourself. Of course genetics isn’t destiny, but I think it’s a useful tool, if you’re willing to do some research. Dr. Amy Yasko’s free online book that Terri referred to is useful reading.

            I wasn’t saying you needed to drop your pharma drugs. But try to live and eat as healthfully as you can. Did something change that put you in your psychiatric state over a year ago? Did you lose a job then, or was perchance a SmartMeter installed in your home?

          • Brian says:

            Hi Lynn_M,

            I will definitely see about finding the money to purchase the 23andMe kit.As you mentioned avenues for interpretation are for another discussion, which i am definitely interested in. Are you in the medical field?

            To answer your questions, I will give you a summary:

            Age 17 I was put on Zoloft for some depression and d/c after 1.5 years because I was feeling fine.

            Age 24 I had major onset of MDD and Panic Disorder. Went back on Zoloft and felt like I was losing my mind. I had to fight for control of my sanity, or so it felt. The psychiatrist then tried me a minimal dose of Paxil, which I responded similarly to. This was the beginning of my inability to tolerate psychotropic medications (possibly because I was bipolar then, although I don’t experience mania or hypomania. Perhaps a different reason all together). Finally, I was put on Lexapro, which helped me significantly, although I still experienced some anxiety and MDEs, it gave me my life back. You might be asking yourself, “if he was bipolar, then, how was he able to be on antidepressant without a mood stabilizer for so long?” The answer is that Bipolar depression doesn’t always present in a stereotypical fashion. Some times Bipolar people go under the radar for several reasons.

            During my time on Lexapro, my psychiatrist tried to add medications and even cross-taper other meds, however there was no real change in my condition. I was stable and living my daily life but still experiencing the abovementioned MDEs and anxiety.

            Around 33 year old I began to experience an odd problem. Whenever I would engage in exercise, I would have an onset of these weakness/fatigue episodes. They were strong and would put me in bed. I went to every kind of doctor but nothing significant was found. I eventually decided to come off of my medication because it was suggested to me that it might be serotonergic syndrome, which made sense because the issue completely resolved when I titrated off my medication. I remained on a minimal dose of clonazepam (.125mg with melatonin) to help with sleep.I will admit that my depression and anxiety did worsen to an extent, but I was still functioning normally.

            It wasn’t until late March 2013 when I was prescribed Prednisone for inflammation in my back and neck that I began to experience a significant deepening of depression (frequent and long crying spells), panic symptoms and insomnia that I had not experienced for years. So, for the second time in my life I was experiencing a terrible onset of these symptoms. Since that time, I have tried medications from all classes, medications that I once tolerated and micro doses of other psychotropic medications (including mood stabilizers), all of which exacerbate my symptoms to an intolerable point. I am not having typical reactions to these medications. For example, mood stabilizers do not work on the same systems as antidepressants. However, when I take them, there is a “sharp” and very intense sadness localized in my chest and I experience this kind of stimulated anxiety. This experience is different from that of an SSRI, SNRI, etc.I am not negating the effects of psychosocial stressors, but what I experience consistently when taking these medications is a biochemical reaction. My body is not adapting or processing them correctly.

          • Lynn_M says:


            I am not in the medical field. I am a widow with no one to answer to except my dog, which allows me the time to follow my passion and read about medicine, genetics, nutrition, and biology. I have enough of a science background that I can comprehend most of what I am reading, and of course with A1298C+/+ and other SNPs impacting folate and B12, I am looking for knowledge that will help me personally.

            You do seem to be a complicated case, the kind most doctors throw their hands up at. 23andMe seems like a good stepping stone to getting started in seeing what kind of genetic anomalies you might have. Functional testing would probably also be helpful, but they all cost a lot more money.

            You might benefit from reading the forums at, particularly and

            Phoenix Rising is targeted for people with CFS, but even if you don’t have CFS, most folks there have methylation problems, so it gets discussed. There’s a wealth of information there. Unfortunately it’s not an organized body of knowledge.

            For a reference as to folate dosing and the correct units, look at the treatment recommendations in the Merck Manual for folate: They refer to dosing in ug. The italicized u is the abbreviation for mcg.

          • Lynn_M says:

            I shouldn’t have referred to an italicized u. The Merck Manual uses the Greek lowercase “µ” (Mu). µg is the abbreviation for mcg. See

          • Lynn_M says:


            In a comment I made that is still awaiting moderation, I referred to the folate section of the Merck Manual at The treatment section refers to dosing in µg, which is the abbreviation for mcg.

            I think your doctor has confused µg as meaning mg rather than mcg, and thus the error in the units she used in her dosing recommendation.


            The United States-based Institute for Safe Medication Practices (ISMP) and the FDA recommend that the symbol µg should not be used when communicating medical information due to the risk that the prefix µ (micro-) might be misread as the prefix m (milli-), resulting in a thousandfold overdose. The non-SI symbol mcg is recommended instead.[1] [2]

          • Brian says:

            Hi Lynn_M,

            Thank you for you reply and the links. I’m sorry about the delay in getting back to you. I’m not sure why, but it seems that I cannot reply to the last reply you left, or several of them for that matter. This website only gives me the option to pick a few postings of yours to reply to.

            Yes, you’re correct. My situation is atypical and no one has been able to help me with figuring out my issues with tolerating psychotropic medications. I would guess that maybe 2% of the U.S. populations has this issue. Even researching on the net, I cannot seem to find anyone who cannot tolerate almost all classes of psychotropic medications.I have consulted with various psychiatrists who have no clue as to why this is happening. This has been a frightening 15 months and I have yet to see anything promising. The longer these issues continue, the worse I get. My brain continues to wire itself in response to these symptoms, causing them to become more severe and my memory, concentration and logic continue to erode. Seemingly there is no way out.

            As I think I mentioned in my last post, I am definitely scared to begin L-Methylfolate because my anxiety and depression are already at such high levels. I already have insomnia and my depression is what you would call an “agitated depression,” so the side-effects of L-5-MTHF do not look appealing. I met with my ND last Friday and she started me on some supplements to reduce inflammation (Meriva-500-3mg/day and OmegAvail-2 capsules/day), before starting the L-5-MTHF (1mg). I also met with a family psychiatric nurse practitioner, who has some understanding of methylation and psychiatric issues. She started me on 500mg of B12 liquid (although my B12 levels were not low) and she wants me doing B12 injections (1000mg) for 1 week, all for the purpose of absorption and nerve function. However, I’m not sure if this will somehow interfere with taking the L-Methylfolate.

            I’m supposed to start the L-5-MTHF 2-4 weeks after taking Meriva-500 AND OmegAvail Hi-Po. However, I have no idea if this is enough time to reduce inflammation or if I even have any inflammation at all. Also, as I’ve continuously read on this website, a small dose of Niacin can be helpful in extinguishing the side-effects of the L-5-MTHF. This of course raises more questions. If Niacin produces a flush or has the potential to cause more anxiety, I don’t want to go anywhere near it. There is no-flush Niacin and Niacinamide out there as well. I was going to go with the no-flush formula, but do you need the flush of regular Niacin to reduce symptoms? Niacinamide seems like a safer bet than Niacin as well. So, which is the “safest” in regard to anxiety and what would be the correct dose?

            I looked into 23andMe and it just seems like people can go around in circles with genetic testing. This is also difficult if you don”t have the money. Due to my condition, I am out of work and my father is helping me with the expense of ruling out the medical. I will definitely consider 23andMe but I just don’t know if it will just raise more questions that can’t be answered or responded to with treatment

            Lynn_M and anyone else who might have any insight as to why I cannot tolerate psychotropic medications, please feel free to respond to this post.

            Thank you kindly.

        • Teresa says:

          Brian, this is in response to why you cannot tolerate psychotrophic drugs. Just two things I wanted to mention. While taking some drugs you cannot eat certain foods like grapefruit with Celexa. Also the way some drugs reaction with one another can be a problem; and your doctors may not be aware of their negative interactions. Just a though.

          • Greg says:

            HI Brain, many of the drugs that you talk of bind to the dopamine receptor, and their activity is neutralized by methylation using COMT or similar. You say you haven’t had the 23andme assessment, this may tell you that you are currently deficient in methylation capacity or that you have genetic variants of the COMT gene. You would need to use 5MTHF, plus methylB12 and probably AdoCbl, plus riboflavin. If you don’t have the combination you will not do so well. I believe that Lynn may have additional suggestions.

  • Stacey says:

    My mutation is MTFR c677t

    What methylfolate side effect have you experienced?
    severe leg pain
    severe headache that do not respond to pain reliever
    decreased appetite
    Did the niacin, hydroxocobalamin and curcumin help you resolve your methylfolate side effects?
    I have not tried it yet.
    Did you suffer through the initial methylfolate side effects only to come out feeling great in the end? Or worse?
    Definitely worse.
    Did your doctor start you on a 1 mg or more initial dose of methylfolate and that set you off?
    My dose is 1000 mcg …. after the inital side effects I waitied a week and the side effects appeared milder but 3 or 4 days later I had a very bad episode where I became very light headed, tembling; I felt like I had to fight to stay conscious. I was nauseated with a terrible headache that has lasted 3 days now and I had diahrea for 24 hours.

  • Claudia says:

    I am hetero c677t and my doctor prescribed Neevo DHA which contains Metfolin and active l-methyl folate. I took this for a year with no adverse side effects, but also no success in maintaining pregnancy.
    Now that we have given up trying to have a baby, my prescription for Neevo ran out and I started taking active l-methyl folate and methyl b12 and have had horrible side effects of aching back, insomnia and sore throat.
    Why the reaction now after taking Neevo for a whole year with no problem?

  • Michelle says:

    I just started taking 5MTHF 1mg and feel very foggy and tired. Is this normal and if so, will it go away? Unfortunately, I have anxiety, but cannot take any medication without having bad reactions (I’ve tried 6 different ones so far). My naturopath put me on 5-MTHF and said to take for five days to see if there is a reaction, before adding more supplements. I already don’t feel well. Any suggestions?

  • Michelle says:

    I just started taking 5MTHF 1mg and feel very foggy and tired. Is this normal and if so, will it go away? Unfortunately, I have anxiety, but cannot take any medication without having bad reactions (I’ve tried 6 different ones so far). My naturopath put me on 5-MTHF and said to take for five days to see if there is a reaction, before adding more supplements. I already don’t feel well. Any suggestions?

  • Mary Lin says:

    Hi Dr. Lynch,

    I’ve been on anti-inflammatory supplements for years, including circumin every day and several others in rotation, including boswellia. I have been trying for six months to figure out the correct dose and form of methylfolate with no success. I am homozygous for 677T and have digestive ailments (colitis, digestive distress) and mood issues (depression, anxiety, irritability) on and off throughout life. I THOUGHT the inflammation was under control before starting the MTHFR. I tried several brands of pills, and every imaginable dose on the low side up to 2400 micrograms a day. I then stopped completely and have started doing a juice of high-folate greens every day. My doctor (functional medicine) just put me on the mehtylfolate cream from Numedica. By the third or fourth day I woke up with headache, nausea, horrible neck pains (they had been starting up a little bit in days previous) and now I just feel unbelievably awful. Are there some people who just cannot supplement with methylfolate? Could I be getting all I need from the green juice (of leafy green lettuces, spinach, kale and/or chard, celery, sometimes a bit of carrot) ?

    • Madge says:

      Hi Mary,
      Technically you can get all the 5MTHF that you want from food. The main form of folate in food is 5MTHF, with the exception of spinach, but here 80% is 5MTHF. Your headaches could be lack of riboflavin (B2), which is an essential co-factor in MTHFR and several other enzymes involved in methylation and in the inactivation of dopamine and adrenalin. Are you hypothyroidic, as this leads to a deficiency in FAD and FMN, which are made from riboflavin. Also in order for 5MTHF to be effective you need to take high dose methylcobalamin (a form of vitamin B12), otherwise you can’t utlize the 5MTHF properly.

      • Mary Lin says:

        The cream has a high does of methylcobalamin, and I’m definitely not hypothyroidic, and did the Spectracell test and was not low in riboflavin. What form of MTHF is in spinach – and are you suggesting the green juice with spinach is all I need?

        • Madge says:

          As you are MTHFR, you need foods with predominantly 5MTHF. Studies show that 5-formyltetrahydrofolate which is a significant constituent of the total folate in lettuce, spinach, carrot, and peppers. I can’t tell you whether these forms of folate are taken up as readily as 5MTHF, but it is known that folate (folic acid) in supplements will interfere with uptake of 5MTHF.
          So to get the folate from food you can eat liver, most types of beans and peas, and broccoli, beets and lentils. Not sure how any of these would fare in a shake.
          I don’t know how good the Numedica cream is. I use the b12oils, mixed Ado/Me Cbl which has been great for me.

  • Barbara says:

    I have 250mg time release niacin. Should I break the tablet to take smaller dose? Feeling pretty detox ish.

  • Caroline says:

    I was taking large doses of folic acid (5mg) a day to get homocysteine down. I then found out that I had methylation defects (6778 – hetero amoung others). I started on the 5MF and got horrible headaches that took a very long time to go away completely (greater than 2 months). I thnk it was becasue of all the folic acid i had built up. so how do i get my levels of folic acid down? or is it just time? i’m not taking any supplements now, but i’m sure my homocysteine is creeping back up. i don’t want to start back on anything for fear of those debilitating headaches returning. How to clear out this toxic folic acid????

    • Greg says:

      I have not been able to find out why large doses of folic acid and it would appear to also be 5MTHF cause head-aches (it is not actually listed as a side effect), but if you have MTHFR mutations or other methylation issues, you will no doubt be deficient in methylB12 (and generally AdoCbl) as well. You need to take MeCbl at the same time as 5MTHF to get an effect.

  • Momwithmthfr says:

    Dr. Ben, I’ve suffered with MTHFR side effects for years and was diagnosed in 2005 during my 2nd pregnancy. In 2012, about 6 months after giving birth to baby #4, I started having panic attacks and was hit with depression. I was put on Paxil and it helped, but I have had several episodes in the last two years. None of my doctors are familiar with MTHFR (except during pregnancy), so everything I know, I have learned from you and my online research. I just realized this week that I could order Methyl Folate on my own and today I was excited to get my bottle Seeking Health’s Active 12 with L 5-MTHF, but I am nervous about the side effects 🙁 I started tonight with a half dose and am praying for good results. Do you have any advice for me?? I’m hoping this will help me with the effects of MTHFR, but mostly with the anxiety and depression that I have had.

  • Ann Lewis says:

    Just curious if heterzigous C677T causes symptoms. I have read a lot about cardiac symptoms and blood clots but mine are not that. I have read on other sites that the heterzigous don’t usually need treatment. Appreciate any help you have on this. I don’t want to take meds/supplements unnecessarily. Thanks in advance.

  • Laura says:


    I was diagnosed with homozygous C677T and currently do not have any physicians following me for MTHFR. I have chronic recurrent pericarditis with many flares following open heart surgery in 8/12; was taking folate, then started L-5-MTHF 1000 on my own. I’m also taking 2 capsules of Complex C3 Curcumin 500 mg. per day. After reading this I’m stopping the methylfolate immediately. I also have a question, have you ever come across a patient with homozygous C677T having chronic recurrent pericarditis? I’m thinking the reason for the recurrence and it not “burning itself out” is because of the genetic mutation. My internist feels as though he might be missing something and I believe the MTHFR mutation is the missing link here. Please respond and thank you for all you do.

  • Mirjam says:

    Hi there, i have C677T heterzygous. Took 400 mcg L-mehtylfolate and felt great.
    Then I made the stupid mistake of taking 1200 mcg because another specialist (internist) told me so. Felt ok for 3 weeks on that and then the side effects slowly kicked in. Now i feel mentally off, disabled even at times. My brains are missing something and my friends tell me I talk weird. I forget what I am about to do in the middle of a task. Staring and feeling high on methylfolate.. It is horrible. Does anyone recognize this? I can hardly find anything on these neurological symptoms and am a bit worried. I eat very very healthy, juicing 1Lt daily filled with greens as well. Iron is too high, homocysteine is normal. I take B6, Zinc, magnesium and mehtylcobalamin. Just ordered niacin. Hope that will help. I need to be out of this limbo feeling. Who recognizes this? Thanks Dr. Lynch for all your info, gonna blow my docter away with all these facts in our next meeting. Regards from the Netherlands, mirjam

  • Renee Reyer says:

    Dr. Ben,
    I have neurological Lyme late stage. Awful depression, anxiety and tremors. Hard to walk. Two doctors just tested me for MTHFR. One positive 1298 and one positive 677. I think that is the worst combo? Both of those doctors however thought they should do nothing about it so I found a doc on your site who also seems to down play MTHFR and wants to treat my adrenals and dopamine, I feel like I am allergic to B vitamins. I feel like this is a big issue especially with the Lyme and don’t know who can help me and if my body will allow me to detox from the Lyme do to the MTHFR and low gluthithione? One of the doctors just said go on your site. I ordered some Methyilated vitamins and reacted poorly. Sorry about spelling. Hard to type. I live in mI. Will see Lyme doc in NY end of July. Feeling sort of hopeless.

    • Catharine says:

      Dear Renee, I spent some time reading posts today and saw yours. I too have neurological Lyme. Have been ill for over 25 years. I am positive for 677 and have all kinds of issues trying to get my detox pathways to clear. Many protocols lead me to Herx. I am applying for SSD I am hoping that once I win my case (my lawyers assure me I will) I can afford the care I need. I am from CT am now living in AZ I think it will be quite a challenge for us to detox from the tick borne illnesses without dealing with our MTHFR issues. I am not a physician but from my experience I think it wise to address the MTHFR issues as best as you can. I am having challenges finding a dosage that doesn’t cause me to Herx. I am working with a chiropractor here who is educated in 23 and me testing results. It seems to me that if your detox pathways are not working and you attempt to detox from Lyme etc you are going to end up with one toxic soup in your body. I understand your feelings of hopelessness. I wish you all the best on your journey I know it is not an easy one. It is a good thing you KNOW your genetic mutations. Hopefully that information in the right hands will lead you to better health. Take care. Catharine

  • Genevieve says:

    Can the detox from starting methylfolate (400mcg/day, by itself at present) cause liver pain?

  • Ginette Novello says:

    Whenever I take niacin or B6, I feel like I’m coming down with a bladder infection! Could I have Pyroluria?

  • K says:

    1. What methylfolate side effects have you experienced?
    Rapid demineralization of teeth and staining (and later terrible aching of teeth)
    Strong diuretic effect when taking MB12 and/or TMG/DMG
    Continually fighting a viral outbreak beginning a day or two after starting
    Emotionally – Easily triggered (though this was not initially)
    Energy slumps between doses
    2. Did the niacin, hydroxocobalamin and curcumin help you resolve your methylfolate side effects?
    I’m just trying out niacin, 50 mg
    3. Did you suffer through the initial methylfolate side effects only to come out feeling great in the end? Or worse?
    Other than the strong diuretic effect when taken together with MB12 and/or TMG/DMG, I felt GREAT at the start! The negative effects came a bit later.
    4. Did your doctor start you on a 1 mg or more initial dose of methylfolate and that set you off?
    I started on 400mcg 2/3 times daily, and when I saw it did wonders, I quickly started taking 800 mcg twice daily, sometimes three times daily until I quit taking any in the evening b/c of it negatively affecting sleep.
    5. Did your doctor taper you up gradually and slowly on methylfolate? How’d that work for you?
    See above.
    After I noticed the teeth problem I took it down to 400 mcg, twice daily and started on MK-7 and minerals. The extreme aching of my teeth went away, and I just felt a tugging sensation in my teeth about an hour or so after taking the methylfolate. I haven’t changed the dose, but I do not feel the pulling any more. My teeth or still stained, and still appear translucent in a vertical spotty pattern. (It took the dose down about 10 days ago.)

  • Suzanne says:

    I have both MTHFR mutations. My clinician placed me on Thorne Methylguard plus one a day and I took this for 4 weeks, not noting any major changes, next visit she asked if I was having or remembering my dreams and as I said no she increased the dosage to 2 each day. I took this for another four weeks and started realising that my fuzzy, hang over head and lack of motivation was probably coming from the tablets, I recently dropped back to one again but intend to only have a few a week or maybe even stop it for a bit. I am looking forward to this settling down. I have a lot of imflammatory SNPs as well as increased phase one detox an decreased phase two detox.

  • Karen Nichols says:

    My son has mutations on both C677T and A1298C. He also has a severe seizure disorder. Recently, I began increasing his methy-folate from 500 Mcg/day to about 4 mg/day ( did this over several weeks). I increased the methyl-folate, knowing there are others with CFD who have seen great seizure reductions with higher doses of methyl-folate ( between .5-2mg/kg/day). Since getting to about 4 mg/day of methyl-folate ( along with 1000 mg of methyl-B12), our son is doing much better cognitively during the day, with better communication, focus and sharpness and fewer seizures. However, at night after we give his anti-epileptic drugs ( Keppra and Vimpat, only given at night), he has many short seizures through the night, a big increase from our norm. My question is: could the folate be causing the nocturnal seizures or interacting with the medicines somehow to increase seizures? Any feedback would be greatly appreciated.

    • Greg says:

      Hi Karen, There is quite a bit of literature suggesting that epilepsy can be the result of folate, and/or vitamin B12 deficiency. Your son with his C677T and A1298C mutations would no doubt have been deficient in intracellular folate and methyl B12 and after a while adenosylB12. Now for some reason when people, and it looks like your son is one of them, start on 5MTHF they can get short seizure-like reactions. You should firstly get his B12, MMA and Hcy checked, plus his intracellular folate. Then as part of the treatment you should introduce methylfolate and methyl B12 (and generally adenosylB12). If you do it right you may be able to actually give up the anti-eplieptic drugs.For the B12, you won’t ever get enough in orally, so you would need to get injections or use the transdermal oils from b12oils. With the seizures, they generally go away as you continue treatment, although they can be a bit of a fright at first.

  • Wendy says:

    I have the compound of both strings. I found out mid June 2014. (7 weeks ago) my doctor put me on 5mgs of methyl folate. I felt like superwoman the first week, but mid second week I started to feel crazy. It took me 2 weeks after that to finally do my own research and stop taking the methyl folate. I’m still having very negative effects. I thought I was insane and almost checked myself into a mental instatution. With the support of my husband and mother I’ve been able to have hope

  • Christine Phillips says:

    Hi Dr. Lynch,
    I was started on Methylfolate, BH4, Selenium, 5htp at the same time. By day 10, I was so fatigued, had joint and muscle pain, developed Adhesive Capsulitisti to left shoulder, and not sleeping well that I had to stop. I have my 23 and me raw data analysis showing Hetero C677 and A1298, with multiple other SNP’s. I’m nervous to start again with methyls. Any suggestions?


  • Bernadette says:

    After 9 miscarriages , I tested positive for MTHFR c677t mutation. Also tested positive for lupus antibody.(blood clotting issue)Linden V? I delivered a healthy rainbow last October with the help of lovenox and baby aspirin and progesterone. I just miscarried 2 weeks ago again.My question is do I need to be taking a different kind of prenatal?dr’s told me I have a mthfr mutation, but didn’t tell me what I should be doing about it. before conception and also if I hopefully get pregnant again. Any over the counter supplements I can start on my own?

    • Madge says:

      If you have MTHFR mutations, it is fairly typical to have miscarriages. I would check your husband, it is quite likely that he has them too. Then when you have the pregnancy you may have some homozygous fetus that would then miscarriage. You need to supplement with high vitamin D, 5MTHF (folate analogue), make sure your riboflavin levels are high (a requirement for MTHFR) and I bet your vitamin B12 is low, so you need to probably start with injections and ultrahigh oral supplements or b12oils ado/meCbl. For your vitamin B12, make sure it is well above 400 pg/ml – don’t listen to the docs, unless you have one that knows methylation mutations backwards. Let us know how you go and good luck. Not sure if anyone in the group has had amnio to test for the fetus – anyone?

      • Greg says:

        Madge is right, but I would go further. You need to keep supplementing through the pregnancy and then through breast feeding. I would then suggest that you have the baby (lets be hopeful) genetically tested so that you know what his/her profile is. This will better equip you for later on. You then should keep up folate and B12, probably for the rest of the child’s life – but this depends upon the genetics. You need to keep the vitamin D high to make sure that you give the child’s nerves the best chance. There is a huge correlation between vitamin D deficiency and autism, particularly when combined with methylation “issues”. If you want to chat “off-line” you can email me at Good luck. Sorry if it sounds a bit blunt, but it is best to know before hand.

  • Andrea says:

    I recently found out that I am heterozygous C677T and started Methylfolate about 1 week ago. I had read most of the protocol and my naturopath recommended that I start out with 1600mcg twice a day. I knew that was probably going to be too much, and that I should taper up, but I tried it anyway. I got a headache almost immediately. So, the next morning I started with 800mcg (1 tablet) twice daily. I didn’t feel anything really for a few days, but then I started noticing increase in anxiety as well as OCD symptoms, emotional lability, etc.

    I’ve been going through a lot, but noticed that over the last week since starting that I have NOT been processing well. I decreased the methylfolate to 1/2 tab in the am and pm. The anxiety seems to have decreased but the OCD symptoms are still hanging around.

    I have been mostly gluten free for 2 years, we avoid it as best we can. I don’t drink or eat dairy products. I take a good probiotic, EFA’s, P5P (I also have pyroluria), zinc, and I’m taking magneleuvres (it’s a magnesium supplement).

    I’m wondering what else I need to do? I originally found out about the MTHFR mutation due to recurrent miscarriage with the last one having a very large subchorionic hemorrhage that ended the pregnancy.

    • Madge says:

      You definitely will need to supplement with high dose methylB12, as you will almost certainly be deficient, and in addition you can’t process 5MTHF without methylB12. Do you have other mutations apart from MTHFR, nearly everyone dose.

      • Andrea says:

        I have been taking MethylB12 for over a year due to the pyrolruia, so I feel balanced with the dosage that I’m taking regarding that. I haven’t been tested for any other mutations. Should I? Where do go for further testing? I’m currently being followed by my naturopath, and I think she would be happy to do more testing if I feel it’s needed.

        I started the methylfolate at 400mcg twice daily because I wasn’t tolerating the larger dosages. I started out with a massive headache, so I cut back, then a few days later had some pretty big anxiety which isn’t normal for me, then I just felt really foggy. I took some niacin and am feeling better. But I think I’m gonna take a break for a bit and see what needs to be done next.

  • Cassandra says:

    I am homozygous C677 for the last 2 years I have been struggling with low adrenals, hormone issues, panic and anxiety. I finally found an integrative doctor who is helping me. I am taking vit C, vit D, svhizandra, taurine, inositol, B complex 100 with folic acid, pantothenic acid, milk thistle,probiotics, omega 3. I have been eating a paleo diet for 8 months and all of my inflammatory markers are low. Homocysteine is 6.9 and CRP is 0.26.
    My doctor told me to start vessel care which has 800mcg methyl folate and 1000mcg B12.
    I started this 2 days ago and have been feeling very tired and yesterday felt “off”
    Is this from the vessel care? What do I do? How long does the methylfolate stay in my body?

    Do I keep taking it and maybe the symptoms lessen? Is it my body decompressing because I am on vacation and away from home stress?
    I’m freaking out a bit. It’s my youngest child’s bday today, she is 15, and I want to be able to enjoy our vacation?

    Thank you

  • Corina says:

    A few months ago I found out I had a double copy of a1298c. My Dr put me on 15mg of deplin. I also take 15mg of generic pill for anxiety, 150 extended release welbutrin, 20mg of zenzedi for my fairly recent diagnosis of adult ADD. A large dose of vitamin D because I was very low. My mutation explains alot of things. My doctor told me it would take up to a year for me to see much difference. I have a horrible memory and have trouble sleeping. My joints ache alot and my upper back and neck muscles hurt and tighten up with any amount of physical exercise. I used to exercise alot and it would hurt and I’d deal with it but now I don’t exercise at all due to it being worse. Even though I am on anxiety and depression meds I still have anxiety and still feel the depression. It is all a little better but the anxiety isnt. The ADD med don’t seem to help much at all. I would love to eventually get off of all these meds.
    HELP PLEASE! As you all are I’m sure this is all so frustrating yet scary at the same time. I have so many questions and my doc don’t seem to be very knowledgeable about this mutation other than to check for it and give me deplin. He basically told me the side effects were in people’s head because the 15 mg has never made me feel anything. I would just like someone to help answer my questions! !
    Thank you,

    • Lori in Columbia, MD says:

      Hi Corina,

      Your situation sounds so much like mine that I’m replying for what it’s worth.

      First, a doctor who says all of any phenomenon is “in people’s heads” needs to be replaced – fast! Sounds like the kind of doctor who learned at some conference that chronically ill patients need to be tested for the MTHFR mutations, and if present, treated with Deplin, end of story.

      Second, Deplin and all forms of methylfolate give me monster cramps and muscle spasms, even in every little muscle of my body. Life becomes impossible. If your pain is due to muscle cramps, consider dropping the Deplin. Also, get a good program of all-over stretches for daily practice (yoga is good), and find a good neuro-muscular massage therapist.

      Third, I have chronic Lyme disease, undiagnosed and untreated by decades of doctors. Your situation could very well be Lyme, and most doctors don’t “believe” in chronic Lyme disease. Find a “Lyme-literate” doctor who can treat the whole picture and not just each individual symptom. And who can treat you like the worthwhile human being you are!

      Do not underestimate the prevalence of undiagnosed, untreated Lyme disease. Even cases of known tick bites treated with the proper antibiotic can develop into serious health conditions, since the organism(s) can evade antibiotics by use of biofilm encystment. There are also common co-infections. This is why a truly Lyme-literate doctor is necessary. The simple Lyme test your mainstream doctor may perform will often be dead wrong for complicated reasons.

      When you finally get some hard-core scientific proof of a reason why things are askew, such as the MTHFR mutation, it’s easy to think this is at the base of all your health problems, since here is a rare affirmation of dysfunction and there have been few of them for many of us. While methylation issues must be cleared up with the help of a knowledgeable doctor, don’t rule out Lyme. It’s a HUGE issue for lots of people who hadn’t suspected it.

      Best wishes,

    • Madge says:

      Hi Corina, You can’t process Deplin without methyl B12, and generally if you are in the situation that you need 5-MTHF you will be very low on methylB12 and eventually adenosylB12. Now depending upon your genetics you may not be able to process cyano, or hydroxcobalamin and so you will need high dose methyl/adenosylcobalamin. As far as I know the best source of this is from b12oils. The next thing is that in order for your MTHFR and several other enzymes to work you will need FAD from vitamin B2 (riboflavin). Have you had your thyroid checked, because if you are hypothyroidic you can’t convert riboflavin to FAD, so you will need to take thyroid meds. I wouldn’t jump down the Lyme disease connection just yet until you have tried the above. Anyway, you will need to do the above, plus more if you have Lyme anyway.

      • Greg says:

        Hi Corina, technically if you eat enough leafy green vegetables you don’t actually need 5MTHF, which is why the MTHFR alleles do not affect a lot of people, but you also need it in combination with lots of vitamin B12, so if you get low in B12 or folate you can start you spiral down-wards. Do you have other genetics that may affect your condition? In addition, when you get the head-ache are you eating carbs or not? For some reason lots of people who use 5MTHF get head-aches, but no-one seems to know why. The most likely reason is from an acetone head-ache, which can come from protein break-down. Vitamin B1 deficiency seems to cause it as well. I certainly would welcome someone’s explanation on the head-ache.

  • Jennifer D says:

    I’ve been taking 15mg of l-methylfolate for about 4 months. It solved many of my issues but did feel a little over stimulated. By my ups and downs stopped and my mood leveled out. However, I found I can’t add other b vitamins and tolerate very well. Coincidentally on a lab test with a different provider, it showed too much folate. I’ve been experiencing anxiety, dry mouth and a sense of burning skin all over. Can thirst and burning be side effect as well of too much folate? Will this resolve if I stop it or only with niacin? I am heterozygous C677T with homocysteine around 11. My husband and older daughter are heterozygous A1298C and my youngest compound heterozygous C677T/A1298C. I’m feeling anxious and scared right now about extra thirst and especially the burning skin sensation. Please help me know if this is normal and can be resolved and how. Thank you.

    • Madge says:

      Hi Jennifer, in order for you to process methylfolate, you need methylB12, so I would think that if you have not been supplementing with high dose B12 you are now B12 deficient, possibly only in methyl B12, but after a while you become deficient in both methyl and adenosyl B12. Your symptoms fit with some of the symptoms of B12 deficiency. You can see the chemistry at . When you had your folate test, was it intracellular folate or serum folate, it makes a huge difference?
      My suggestion would be to get the Ado/MeCbl mix from b12oils . Apply the oils at the same time as you take the 5MTHF. Do you know what other methylation associated mutations you have, as these also make a difference to what you also need to take? The people at b12oils will give you help with this if you want. Good luck.

  • Bob Robertson says:

    I am homozygous for A1298C. My doctor suggested Thorne Methyl-Guard Plus. I immediately developed extreme headaches. I then tried methylcobalamin alone and got headaches. I do have a mouthful of amalgams. Could this be the problem?

  • Crissy says:

    My 9yo daughter has compound herterozyous and her functional md recommended MTHF-5 5mg daily.along with some other targeted aminos. She has a lot of gut issues allergies and so on. I am scared to death to give it to her but know she needs something as she is really having a lot of problems. Any help is much apprecitated!

    • Madge says:

      Hi Crissy, your daughter will definitely need methyl B12 as well as the 5MTHF, and she may need other supplements as well, but it depends upon her genetics as to what she is likely to need. She will also probably need adenosylB12, as she will sacrifice this to make methylB12. You can get the mixed oils from . You simply rug them on the skin. They are wonderful.

  • Raquel Ont says:

    According to blood work i received, it shows a “single mutation (AI298C) identified) any other results (C677T) were negative. Have been feeling very ill. Could you please shed some light on this? Thank you!

  • Raquel Ont says:

    According to blood work i received, it shows a “single mutation (AI298C) identified) any other results (C677T) were negative. Have been feeling very ill. Extreme lethargy, sweats, achy. Have been under immense stress that last 2yrs. Could you please shed some light on this? Thank you! Nothing for autoimmune all other tests were negative.

  • Shannon says:

    Oh my….. where do I start. I have had Fibromyalgia for several years, I don’t take anything for it per say. I have a long story but I won’t go in to it I just stumbled across this website while looking at side effects for Methyl Folate. OMG I had NO idea what this even was. My so called doctor put me on L-5-MTHF and Potassium/Magnesium Citrate over a year ago. He didn’t tell me anything about it just to follow the directions on the bottle. I take it everyday, it is 1,000 mcg, I don’t take any B vitamins, never heard about taking Niacin…. I have had a lot of side effects, mental fog, dizziness, mood swings, depression, etc… it was so bad a couple weeks ago. I have low blood pressure and am peri menopausal. I went to this doctor that is a MD calling himself a “Functional Doctor” as I wanted to see someone that knew something about Fibromyalgia. A couple of months ago he prescribed me Estradiol and progesterone and I was having serious issues with depression, anxiety, mood swings and was an emotional wreck. before the hormones and worse after taking them. I went in for a follow up appointment a couple of weeks ago and he told me to go off the estrogen that might help the depression, anxiety, etc and if it didn’t take a anti depressant that he gave me samples for. My blood pressure is low, too s he wanted me to start on some steroid to bring it up. I Do NOT like taking drugs, never have and I have been a wits end… I did NOT take the anti depressant, read up on it and the side effects were awful and I didn’t take the steroid either. I always check out side effects of anything that I put in my body, but for some reason I have NEVER checked out the side effects for the Methy Folate until yesterday after being on it for over a year!!!! I believe this is the cause of most of the issues that I have been having. I have never been tested for the MTHFR, my cousin believes that I probably have this gene as she has both and her mom and my dad were brother and sister. I don’t know what to do, she suggested going off the Methyl Folate and starting on Jarrow Methyl B-12 1/4 of the pill and building up… I am so sick of doctors and drugs and feeling like crap….. I don’t know what to do. I know that I am not going back to that pill pusher doctor that doesn’t even test before giving me stuff. Help me if you can!!

  • Greg says:

    Hi Shannon, it is an interesting problem, Fibromyalgia. No-one really knows why it occurs. It is also interesting in that the world distribution doesn’t really help you to find a possible cause. Thus, it does not partition with vitamin D deficiency, which is a common cause of many neuronal and mitochondrial problems. There also doesn’t “seem” to be an association to MTHFR mutations, according to the literature. No does it appear to associated with folate or B12 deficiency, however, it is possible that these studies are not particularly well done. It does share significant symptoms to B12 deficiency, particularly as co-morbidities, some of which you have stated you have.side effects, mental fog, dizziness, mood swings, depression, etc. IF your genetics is telling you that you may have MTHFR issues, then you will need to take high dose B12, plus 5MTHF, as the 5MTHF won’t work without methylB12. There are some papers on treating FM with high dose B12.

  • Christina says:

    Dear Dr. Lynch,

    I was diagnosed with MTHFR, and have been advised by my doctor to increase my supplementation of B12 and Folate, in addition to a baby aspirin (81 mg) each day. Most days, I remember to take the B12 and Folate; however, I don’t always take the aspirin because I also have Ulcerative Colitis, and I fear that the aspirin would irritate my colon.

    I’ve also ordered a kit from 23andME, in hopes of finding out a little more about MTHFR that orthodox medicine may not reveal. I’m worried that my body is not absorbing the B complex supplement (with added folate) I’ve just began taking by Pure Encapsulations. I don’t always remember to take the supplement, and I’m uncertain if that is a bad thing or not. I would rather get my nutrition/supplements from food, but it can be so expensive.

    Would you be able to give me some insight on whether or not the ingredients listed below are safe for everyday?

    Any additional feedback you could share would be greatly appreciated.

    Thank you, doctor!

    The supplement facts are as follows:
    Thiamin (as thiamin HCI) 100 mg
    Riboflavin (vitamin B2) 5 mg
    Niacin (as niacinamide) 100 mg
    Vitamin B6 (as pyridoxine HCI) 10 mg
    Folate (as Metafolin, L-5-MTHF) 400 mcg
    Vitamin B12 (as methylcobalamin) 400 mcg
    Biotin 400 mg
    Panothenic Acid (as calcium pantothenate) 100 mg
    Riboflavin 5′ phosphate (activated B2) 10 mg
    Pyridoxal 5′ phosphate (activated B6) 10 mg
    Inositol Hexaniacinate (no-flush niacin) 10 mg
    Ascorbyl Palmitate (fat-soluble vitamin C) 16 mg

    • Dr Lynch says:

      Not a bad formula and should be overall safe for the typical person. The amounts are not very high for most of the nutrients while others are quite good. May need more support than that for other nutrients but everyone is different.

  • Juhl says:

    Hi Dr Ben, I am grateful to discover this sight today!! A nurse that I met in travels informed me that I should research the methylation concept. Since last month I have watched several of your videos and read a bit about all this new news for me regarding MTHFR. I do not have an MD here that seems to understand this. I have become frustrated with the attitude that it is just because of my “age”. (I turned 50 this year). However, the more I read and learn I know it is not just age related concerns because have been dealing with issues since i was a baby (near death from respiratory disorders) and many issues with allergies through out my life. I even had a sever allergic reaction to a sulfur antibiotic within the last 6 months with only 1 dose.
    I have tried SO MANY ATTEMPTS to find solutions. I am considered to be in pretty good APPEARING shape for my age. Not over weight… I eat pretty healthy, juice, was vegetarian until I was told that i should add meat again this year ETC…
    I ordered DNA testing and I’m heterozygous MTHFR C77T & MTHFR A1298C , Homozygous CBS A360A , heterozygous MAO A R297R among other heterozygous factors.
    I started taking Methyl Folate, TMG crystals, and Superior B12 this month Aug 2, 2014.
    At this time I stopped taking all vitamins and supplements I had taken prior attempting to support my body. Since a week after starting my baby fingers have been aching!!! My joints seem to be sore to the touch on my hand. Prior to this I did not seem to have issues with joints expect for knee pain when working out at times…. I just read that taking the niacin may help. Any feedback and support are greatly appreciated.
    Going through all my savings trying to feel better…. Juhl

  • Allsmiles says:

    Hi there! I am trying to find someone’s successful protocol who has compound heterozygous for 1298 and 6777. I’ve done so much reading and I’m relatively healthy learned about this gene mutation through a random test my doctor requested due to prior migraines about 4 years ago. I have an appointment with a hematologist next week but want to make sure I have an idea!

  • Kay says:

    Dr Lynch, Mom just went on 1000mcg methyl B12 and 800 mcg methylfoltate this week per dr order. Yesterday and today woke up with nausea and yesterday seemed to have fast heart. looks like side effects from above post. I am writing to see if we should stop Methyl B12/Folate or reduce to 200mcg each and start slow? Very long story as I am sure many of us have them. But would like for her NOT to have side effects due to short term memory loss. Please if you see this post reply to post or better yet to email
    Thank you!

    • Dr Lynch says:

      She’s making too much epinephrine and possibly too much nitric oxide. You should stop it and give some niacin to counteract the effects. The NADH + CoQ10 lozenge may be quite helpful for her memory loss. Have her place 1 lozenge under her tongue and allow to dissolve. Your mother may also be deficient in magnesium given those symptoms. Consider magnesium glycinate.

      • Kay says:

        We did stop B12/folate Friday (4 days) . Should have mentioned she was on 3 days of 250mg Glutathione also. She had stomach cramps/diarrhea on Thurs/Friday. Found this to be symptom of Glutathione also. She was also on Lactalose 30ml daily for past month due to constipation/high ammonia levels detected when admitted to memory unit 1 month ago. Her MgRBC is 5.9 so it is not low. Homosycteine is 9-10 last two readings, CRP is .5 (“normal”). I will get niacin locally and order NADH/CoQ10. Yes on MgG. Can MTHFR gene mutation be a “cause” of dementia (symptoms)? This is what we are dealing with.

        • Dr Lynch says:

          High ammonia levels can cause dementia – the brain cannot function in high ammonia amounts. Need to get on sodium/magnesium butyrate – from BodyBio or Pharmax. Also consider Acetyl-L-Carnitine to help lower ammonia as well as the NADH/CoQ10. Need to evaluate gut bugs and restore them. Consider the Doctors Data CDSA x O/P x 3

          • Kay says:

            Through BodyBio they have cal-mag butyrate or sodium butyrate – which one? Also, would CDSA 2.0/P through Genova Diagnostics ( be okay? Doctors Data has theirs, but because none of these will probably be paid by insurance, I believe the first test will be better cost option. BTW, probably because of MTHFR her lead levels are at 18 (should be <2) After starting B12/folate we were to do a 6 wk detox on DMSA (3 days/11 days off) but after having reaction to glutathione and not being at home to see her 24/7 I can't do that to her just yet. Do you detox first or get methylation going first? thank you for your time.

  • Pam says:

    I was confirmed homozygous 1298cc (double mutation). 667 testing was normal.

    14 months ago, my doctor started me on:

    l-methylfolate 15mg tablet, 1x daily
    methylcobalamin 5000 IU compounded injection, 1x weekly
    ATP/Glutathione injection 1cc, 1x weekly
    high quality B complex (note: this included Niacin)

    I had severe anxiety…and I read on your forum about Niacin being a “mop up” for excess folate., so I got off the B complex, and started taking individual B vitamins so I could control each of them as time goes, if needed again, without disrupting anything else I took. I also did some research and found there is optimized the B1 and B6, so switched those out a little bit later on after I took out the Niacin.

    1) taking out the Niacin for me was a HUGE improvement…daily anxiety was virtually gone within 48 hrs, and now I might have one episode a month (I’m still trying to figure that out).
    2) taking the optimized B1 and B6 seemed to take the edge off…a bit hard to describe, but I have a better “calm” feeling than before the switch. The separate B vitamins are very close to the complex amounts.

    My current protocol that seems to fit me – keep in mind I have almost 30 years of damage (my symptoms go back to very traumatic years of 1984-1985). I have confirmed nerve damage (thoracic, cervical neck and optic nerves).

    – all once a day, unless noted:
    Benfotiamine B-1 (thiamine) 150 mg
    Vitamin B-2 (riboflavin) 100 mg
    Biotin 5,000 mg
    Choline 250 mg
    Pantothentic Acid B-5 100 mg
    Vitamin B-6 (co-enzymated) 100 mg
    Inositol 250 mg
    L-Methylfolate B-9 15 mg – required Rx
    Methylcobalamin B-12 5000 iU – compounded, intramuscular (weekly only)

    I also take:
    Adenosine Triphosphatase – ATP 1 cc compounded, intramuscular w/Glutathione (weekly)
    Magnesium 500 mg
    Manganese, Chelated 10 mg
    Potassium (blend 5 types) 200 mg
    Vitamin D-3 5000 iU – I do best on softgel
    Zinc (monomethionine complex) 30 mg

    I have, over time, temporarily removed each one, and saw a difference – adding it back proved positive, so over time we have settled on this. My ATP & GLU levels are slowly improving (they were bad to start…at 1/3 of what they should be!).

    I am sure to take all the B vitamins together, and take the remaining oral vitamins together at a different time a few hours later. D3 is at bedtime.

  • Bob Robertson says:

    When tests my LLMD ordered showed I am homozygous for A1298c, I was told to take methylated B12, so I began Thorne Methyl-Guard Plus .
    Within days I had a “tight band” headache, so I stopped taking it.
    Our pharmacist suggested that I try taking just methylated B12, and then add the methyl folate and the B6 if I tolerated the B12.
    Once again on the second day the headache returned.
    Several times I’ve tried again, but I just don’t seem to tolerate B12.
    Can anyone explain this or suggest something?

    • Pam says:

      Hi Ben – what doses and brand/maker of the vitamins and methyls are you taking? The b9 maker is usually on the Rx bottle if you get it from a pharmacy.
      I take l-methylfolate – manf: Virtus (15mg /1x daily) and 1 intramuscular b-12 injection 5000IU, compounded by a local certified pharmacy (once a week).
      There maybe too much too soon, or imbalance between the dosage amounts.
      There is also the possibility your electrical pathways are awakening and the side efects are temporary.
      It took me 2 years to tweak my protocols. I also went through a brief time my system was very unhappy – processes restarting but not enough to keep them going just yet.
      Hang in there.

  • Lisa Pollice says:

    Hi! My name is Lisa and I’m recently found out that I have the heterozygous C677T mutation.

    Apparently this has been causing me issues for a very long time – we just never did know why. My list of symptoms is like the poster child for this. I’ve also had cancer seven years ago.

    Something that IS odd – which turned out to be the reason I ended up getting tested for MTHFR is that I have been experiencing severe angioedema and urticaria which does not respond well to antihistamines – nor have we really been able to find a root cause.

    I cleaned up my diet (no grains, no dairy, no sugar and therefore very little fruit except apples and lemons and I’m only eating chicken breast and salmon for protein, and lots of fresh vegetables) – only to find that my MTHFR symptoms and the angioedema GOT WORSE.

    I’ve been intubated three times from this. And now I’ve been on daily prednisone for six weeks trying to keep the hives and swelling at bay… which I now fear is only a dog chasing it’s tail.

    My question is this: Can you please help me understand the link between MTHFR and how it causes histamines and inflammation – and could MTHFR be the cause of my IgE level being over 1,000???

    My immunologist is convinced that I’m allergic to something and I’ve just been so careful and clean – and this has been happening for over ten years and if there is a common thread of an allergen – it is beyond me. He has started me on Xolair shots – in the hopes of bringing down my IgE levels.

    But I’ve long maintained it’s not allergy related – and now it does seem that there is a connection between this mutation and inflammation and histamine – I just cannot seem to grasp what it is.

    Most of my inflammation symptoms start in my gut… sometimes my esophagus gets so swollen I can barely swallow liquids. When this happens – it is like a cascade – and all the other symptoms which I now know are MTHFR symptoms come on full force.

    Can you help me understand the connection between inflammation / histamines and MTHFR well enough so that I can explain it to my immunologist??

    I don’t want to seem dramatic – but I am literally fighting for my life here… one of these times I’m not gonna make it to the ER in time.

    Thank you so much for your site and all the information. You’re a Godsend.


    • cassandra says:

      I am a RN and I am homozygous for the C677.
      It really does sound like you have a true food allergy. It could be the apples, salmon and/or chicken. My son gets a itchy throat when he eats certain apples. there are hundreds of strains of apples. We now peel them and rinse them and he can eat them.
      you need to get the Cyrex assay for food allergies completed. You may be surprised at what you are allergic to.


    • cassandra says:

      Also forgot to mention that the Cyrex Assay can test for chemicals as well. It may be that you have an allergy to a chemical that they possibly spray on the fruit and veggies.

      I hope this info helps you out. I suggest the Cyrex because regular blood testing is for immediate response, the Cyrex tests for long term and delayed reactions.


      • Lisa Pollice says:


        Is this something I can have my immunologist order? (The Cyrex) Thank you so much for your input… and we do actually eat apples every day… many varieties. I always joke that my kids are apple snobs.

        Warm regards,

        • cassandra says:

          Yes your immunologist can order this. It must actually be ordered by an MD. The good thing is that they save your serum for approx 90 days if you need to add on tests.

          look for yourself. and the customer support team was great!

          Keep us updated. This may be your life saver!


          • Lisa Pollice says:


            Thank you so much for the link. I can give it to my doctor and see if she’ll be willing to set herself up an account with cyrexlabs. I read they don’t take insurance and my insurance won’t reimburse for outside labs… so I’m assuming this is gonna be a pretty penny. Sigh. 🙁

            Warm regards,

          • cassandra says:


            🙁 yes it is costly however, add up all of the copays from recent MD visits and ER visits…….

            I have a credit card just for the medical and claim it on taxes at the end of the year. do you have any flex spending?

            It can cost up to $600 to get the full food and chemical panel.

            but you can start with one panel and then add as you can.

            I hear you, I am a single mom with 3 children and I am the sole provider.

            Sending you the positive energy!


    • R says:

      Hi Lisa, The severity of your symptoms would point to more than just the snp you have relating to folate. Look up Mast Cell Activation Syndrome and alternatively Carcinoid. Go through the symptom list and decide which one might match yours best. Not many doctors are familiar w/MCAD. You should ask your dr to test your tryptase level, once when you are not reacting, once when you are (within 4 hours I believe). That will give the dr an idea of if you have too many mast cells, or they are just over reacting,…or otherwise. When you look up carcinoid, there is a urine test you should ask your dr to order for you. MCAD is diagnosed by excluding other conditions (such as carcinoid). Make sure to insist you get an epipen set from your dr if you are having reactions such as throat swelling, it may save your life. (look up anaphylaxis if you haven’t been told about it yet) Best of luck and remember YOU must always advocate for yourself if you note that your dr is not really into helping you!!

    • Beca says:

      Hi Lisa, I’m sorry to hear you’ve had so much trouble! Do you have an epipen for when you have an a bad episode? I was thinking, you may want to investigate whether you could have developed a mast cell dysfunction. There is a condition called mast cell activation disorder that causes similar symptoms. Also, something called mastocytosis, this means having too many mast cells.

  • Shelley says:

    My husband purchased the test for the mutated gene and found he has the MTHFR 677C;T TT mutation. We purchased the Optimal Multivitamin Plus and the HomocysteX Plus. He has had severe side effects including headaches, irritability and depression. He took them for about 2 weeks the first time He stopped taking the supplements for a week and then stated back at a low dosage. 2 a day vitamin and 1 homocystex. He has taken them for 1 week this time around and the symptoms have all come back. He is also very red in the face. How long should he stop and how much should he start back taking and how often? Thank you for your help.

  • Mary Lin says:

    The allergy issue with MTHFR mutations is actually a histamine problem which is now being studied in relation to autism and Aspergers. People with autism and Aspergers have a very high rate, as high as 98 percent, incidence of MTHFR mutations. This relationship is something we’ve been talking about quite a bit in our online group, Aspergers Health and Fitness Network.

    • Lisa Pollice says:

      Mary Lin,

      Thank you so much for your reply. I will navigate over to the Aspergers Health and Fitness Network and check it out. My friend who lives in Orlando and is the head of a Down Syndrome foundation – just mentioned to me on Facebook that they deal with MTHFR mutation in these kids too.

      This is all knew to me and just overwhelming and scary. Thanks again for the helpful link.

      Warm regards,

      • Lisa Pollice says:

        Mary Lin,

        Sorry to bother… I just pasted ‘Aspergers Health and Fitness Network” into my google search and the site to which you are referring is not super clear. Can you send me a link?? Sorry again…

      • Mary Lin says:

        It’s a Facebook group —

        I do believe Dr. Amy Yasko goes into this extensively, the histamine connection and MTHFR. Check out her website under her name. I will post more links to the histamine/MTHFR info as I run across them.

        Kind regards,


        • Lisa Pollice says:

          Thank you Mary Lin! I’ll “Like” the group now and also check out Amy Yasko’s site. Thanks for the information!

          Warm regards,

          • Greg says:

            Hi Lisa,
            The connection to MTHFR and histamine is quite simple. You break-down histamine via two methods. One uses histamine methyl transferase, which requires SAM, so if you are low on methyl B12 and are not taking 5MTHF you will have trouble with histamine breakdown. The other way you break-down histamine is with Diamino-oxidase, which requires FAD. If you are hypothyroidic you may be very low on FAD. Do you have your full 23andme profile as this will tell you how stressed you will be as far your FAD requirement. Many of the methylation associated mutations (including MTHFR) require extra FAD. I am happy to look at your 23andme profile if you want. Do you only have histamine intolerance or have you proceeded all the way to CFS?

          • Lisa Pollice says:

            Hi Greg!

            Thank you for taking the time to reply. I’m so grateful that there are so many people willing to take some time out and help someone else. What a blessing.

            You make the whole thing sound very simple. I will need to take what you’ve given me and read and research to fully understand it. This is day 4 and I’m already kinda getting good at identifying all these acronyms… 5MTHF is 5, methyltetrahydrafolate??? I think?

            I didn’t learn of this through 23&me. My naturopath tested me for this as a one off because she suspected. Although I now see the benefit of 23&me and will do it as soon as I can.

            Prior to this, for the last 15 years – I have felt as a general rule fairly miserable. It’s somehow cyclical but I could never figure out how. Aches and pains and exhausted all the time. But times of being OK. I was always athletic and in really great shape – and during a time of great stress – one day it just all changed. My whole body. I went to numerous doctors. Everyone did bloodwork, said I was fine and sent me on my way.

            But then, my allergies and asthma kept getting worse and worse – completely uncontrolled and I would get these huge hives and massive swelling. These episodes would happen two to three times a year. Three times I’ve had to be intubated because of loss of airway… but I’ve had to go the hospital almost every time this pops up.

            When you go to the ER they are just concerned with stabilizing your airway and giving you mass amounts of steroids and antihistamines and epinephrine. Then they admit you – and then the parade of hospital doctors come around and they don’t know what to do – and they all say the same things, “Hmmm you must really be allergic to something. Have you tried allergy injections?” And after a few days of pumping you full of steroids – they cut you loose and tell you to follow up with your allergist.

            So – this is how it has been SO LONG and I can tell you that until you wrote it – I’ve never heard of “histamine intolerance” and I had to ask someone what CFS was…. LOL. Of course, I’ve heard of Chronic Fatigue – but have never been diagnosed.

            But I will tell you that when I read about histamine intolerance – that’s me exactly. The strangest things will make me flush and get mild hives. Drinking kombucha makes me feel ever so slightly drunk and very flushed… and forget it if I have a glass of wine… usually brings on an asthma attack.

            So I have bent your ear long enough. I appreciate your help and input. Right now, I am sitting here covered in hives, with 80mg of prednisone on board today, trying to figure out how in the world to get off this Merry-Go-Round.

            I don’t know how – but I feel as though me taking the prednisone is only making it worse… adding more toxins in. But right now it’s the only thing keeping me out of the hospital.

            I think tomorrow I’m going to start severely limiting what I eat. ( I have already been on a very restricted diet – but another lady pointed out that it really still sounds like food allergy). We’ll give that a go.

            Also, I’m going to go see if I can find a supplement with diamino-oxidase in it and see if that does anything.

            Thank you again for your reply and for taking the time. It’s much appreciated.

            Warm regards,


  • Greg says:

    Hi Lisa,
    Get your 23andme done, then if you want I will go through it and I can give you a way forward. I would also get an OAT done, but it is very expensive.
    Other things to check are whether you are hypothyroidic and also to get your homocysteine and methylmalonic acid (MMA) levels done. These are all predictive and help you going forward. When you have it all, or even just the 23andme, contact me and I’ll go through it with you.
    In the meantime, make sure that you have plenty of B group vitamins, they certainly help and B3 is a definite for your alcohol, as both alcohol dehydrogenase and acetaldehyde dehydrogenase need it to work effectively.
    Also you can’t supplement with DAO effectively, but you can help your own work better with extra vitamin B2.

    • Dr Lynch says:

      Greg –

      What do you mean you cannot supplement with DAO effectively?

      I am sorry but who the hell are you?

      You preying on people trying to get them as clients via MTHFR.Net is not appreciated.

      I’m done reading your comments here. They are just wrong.

      I am all for engaging in debates – but not when it is wasting my time and providing so much confusion to people who are already confused.

  • Rachel says:

    Hi Dr. Ben!
    I am writing because i am at a loss (like most when we turn here) I am so excited about all this info you are sharing,(so THANK YOU!!!) because I am being told that “the mutation you have doesn’t affect methylation” and as far as i am concerned, it sure does! I have A1298C, and my 9 year old daughter does too (but i’ll get to that) I had pregnancy multiple pregnancy loss, chronic fatigue, anxiety, lots of joint pain and some depression, at a young age and I had no idea it all added up- i went to a specialist in TX for chronic fatigue, and she explained that most do not have it, and after testing, – she was like “whoa! you sure do have it!” using the markers that she tested for- we then began weekly injections of glutathione, and at first i thought it was crap, and after about the 5th injection, wham! i started to feel so much better! and then guess what? I was able to sustain a pregnancy (which was why i stopped the injections, i didn’t realize the connection, and was terrified i’d lose another baby!) – I only found out about my MTHFR from my travel file that i had to bring with me for the last 2 months of my high risk pregnancies (but i noticed it on there with my 2nd child, not my first, and no one ever told me!!!) anyhow, two years ago, we had a big move, and at that time, we were treating our (then seven year old) with high EPA for ADHD, which really worked, once we moved, it didn’t work anymore, she had her first ever panic-attack, OCD like symptoms and high anxiety and and her behavior went nuts! – she begged me for medication to “make me better, mommy” it broke my heart, so i went to the dr, and we tried many meds and lots of fails, but we are now on focalin, and Zoloft and it’s OK, (but i’m totally against it) but i keep telling them that i think this is bigger than ADHD, she has the energy of ADHD, and if she is bored, the attention span of ADHD, but an almost photographic memory and retains info unlike anyone i have ever met- sooooo, fast-forward to now—> i took her to an integrated pediatrician, she had no idea that i had MTHFR, and i see that it was one of the tests she was running on her- it came back positive for the same as I, and also, she had low Catecholamines: low normal levels of Dopamine, Norepinephrine, and Epinephrine,low vitamin D and and low magnesium- now we were recommended to start her on glutathione assist from Kirkman labs 1x a day- I started looking at MTHFR a few years ago and came across the “HolyMTHFR” blog, and i felt like she was writing about my daughter! when searching for answers though, everything says that our mutation is insignificant, and is not really associated with all of these things, but I am positive they are, as I am living them with myself and my daughter!!!!! what is the deal? is there anything else you can recommend or suggestions, and who to speak to in GA about this? we have insurance, but not much extra for out-of pocket, because we are recovering from a lay-off, but she is 9, and i am terrified that i will not get her the correct help in time- thanks in advance for reading this! please let me know your thoughts!

    • Greg says:

      Hi Rachel,
      It is good that you have found this site and that you are on your way to discover what you may need to help you. I wouldn’t get too excited about MTHFR genetics, especially any +.- snps that you have. These people are perfectly healthy. The majority of the population has +/- alleles in any particular location. There are, however, lots of other associated snps that you should be aware of, which, when viewed in context are arguably more important. Really the most important alleles are those where you have +/+ status. FYI even A1298C is not disproportionally expressed in CFS individuals. If you have a complete 23andme txt file I am happy to look at it and suggest things that you might want to try.

      • Michael_Dowdy says:

        Hello Greg. MTHFR mutations can be deadly, especially on women using birth control. One copy can kill in some situations so be careful with advice. It is very important to seek a doctors advice. I’m not a healthcare professional and I only share my personal experience but everyone with mutations should seek a doctor’s help. Thanks far sharing. Respectfully, Michael M. Dowdy

        • Greg says:

          Hi Micheal, if you look at the frequency of MTHFR mutations at most of the alleles, the frequency of -/-, +/- and +/+, is actually very similar. They fit in to pretty much a standard Mendelian ratio of 1:2:1. That is 25% of the population has the homozygous dominant, 50% has the heterozygous condition and 25% has the homozygous recessive mutation. Now it wasn’t always the case. Thus for MTHFR C677T, the frequency of the TT allele is very low, and as you suggest the homozygous recessive allele can kill, particularly if there is no folate supplementation. However, the enzyme activity of the heterozygous condition is still relatively high at 65%. It is not quite that simple though. If you have sufficient folate as 5MTHF in your diet, and if you have hormal riboflavin levels you are OK. Thus in the population the heterozygous condition thrives, else we wouldn’t be having the discussion. So, given that the heterozygous condition exists at around 50-60% of the population, and they appear not to have problems, then one cannot make a case for heterozygosity as being a problem in itself. Thus, in most people with CFS and other conditions, it is not solely the one mutation, but it is a combination of diet and the other mutations. In the womb it is clearly different, and here, when 2 people with MTHFR c667T +/- try to have children, then there is the possibility of the TT condition and yes now there is a problem, either the child is aborted, or if folate supplementation occurs the child is born and then this can give rise to various developmental problems and ASD, IF the child is not supplemented properly with folate and vitamin B12. This, however, was not the original comment. People who have made it successfully through child-hood with no problems and who are heterozygous (60&) of the population can potentially get problems if they are stressed or for some reason change their diet to say vegetarianism or to being vegan. In this case their vitamin B12 levels drop with time, they can then no longer process 5MTHF to generate methionine and then SAM, and they have problems with supplemental folic acid, due to their “slightly” reduced MTHFR activity.This then can get much worse if they have low levels of riboflavin in their diet (as FAD is an essential co-factor for MTHFR) or if they have hypothyroidism. As far as the birth control pill, the reason that this is a problem is not necessarily the MTHFR allele status (remembering that 50-60% are heterozygous) but the fact that many birth control pills also lead to B12 deficiency. If you then consider that often many of the people are not consuming enough dietary folate or have nutrient deficient diets, it is not necessarily the MTHFR condition that causes the problem, otherwise 50-60% of the world would have it, and they don’t. This can be seen with many people who get problems later in life. They were fine for decades, so their genetics was not the problem, it is something that they change, such as the birth control pill, etc. A corollary to this is the fact that some of the MTHFR mutations/alleles have a very low incidence of +/+ in developing countries or countries that don’t supplement with folate (as low as 3%). The MTHFR +/- incidence is even higher than in say the USA, or Europe. Thus it is diet plus genetics that is the problem, but you could say that for nearly every enzyme reaction in the body. If you don’t provide enough co-factor the enzyme works poorly, regardless of the genetics. There are exceptions to this of course. MAO and COMT being two of the big ones. If everyone who was heterozygous for MTHFR, CBS, MTRR, or MTR alleles went to the doctor, then more than 50% of individuals would be at the doctor. I think it is more important to consider the combination of alleles in MAO, COMT, VDR, BHMT, NOS, MTHFR, MTRR, etc and then look at the symptoms and the diet, and then to approach the supplementation logically given what we know about the enzymes and what determines their activities. If you break-down the symptoms, the genetics and things such as AOT results, it is actually quite predictive and fascinating.

          • Michael_Dowdy says:

            Hello Greg. Dr. Ben Lynch clearly states that the expression of the gene is more important than the snp when it comes to treating it. If other clotting issues are present and you throw birth control pills into the mix, death can become a major concern because of the risk of embolisms for women. I’ve seen it. MTHFR + Factor V Leiden + birth control pills can = death by blood clots. I’m talking about the risk to potential mothers when using birth control pills. I have two copies of the 677CTmutation. I would probably never have known it except a family member very nearly lost her life after using birth control pills. Have you found the answer for the reason for headaches after using methyfolate? After the brain mapping studies are done maybe the answer will become clear. After greatly reducing my dosage of L5MTHF I no longer experience headaches. As far as discussing gene mutations with doctors someone is fortunate to find any doctor willing to take the time that is necessary to discuss it. It becomes very complicated and time consuming because everybody is different and a lot of doctors would rather avoid it than address it. 7.5 and 15 mg are extremely high doses ofv methylfolate and way exceed what has been determined to be the maximum daily tolerable amount of L5MTHF calcium salt for adults as stated in “Application A566.” Everyone should read these documents. They’re a little lengthly but well worth reading. Respectfully, Michael M. Dowdy

        • Greg says:

          Hi Michael,
          I don’t seem to be able to reply directly to your last comment, so hopefully you can find this. If you look at the biological activity of the MTHFR protein, the mutations are not actually as bad as everyone makes out. This is very frustrating as it shows a lack of understanding of enzyme kinetics and enzyme function. Basically in the 677CTmutation, the functional activity of the enzyme is about 30% of the wild type 677CC. Now this sounds bad but, in 50% of the population who are heterozygous for the mutation, they have two types of enzymes. The wild type and the 677TT variant. The result is that the enzyme activity is the average of both proteins, so it is around 60%. Now 50% of the population have this amount of activity. You with the C77TT variant therefore have an enzyme whose actiivity is only half of the average in the population. Now if you look at the frequency of TT genotype is is pretty much what you would expect from a standard Mendelian segregation, which shows that it is not negatively selected against, and is not conditionally lethal.
          Now that is the theory behind the enzyme, so what is all the fuss about. Basically the enzyme kinetics depends upon you having maximal levels of the enzyme substrate 5,10,methylenetetrahydrofolate, but also maximal levels of FAD (derived from riboflavin) and also NADP (derived from vitamin B3). Now if your levels of riboflavin are low, this is particularly bad if you have the TT variant as the enzyme has “trouble” holding onto the FAD. Now the enzyme activity is much lower, and this is when the problem arises. So it is not necessarily the enzyme mutation in itself, it is having low levels of the co-factor. Any statement that is made about the problems with having the “TT” variant has to be taken with this in mind. This can clearly be seen in hypothyroidism, where there is a problem in making FAD. The result is that the MTHFR enzyme has very low activity. The result is that folate can’t cycle through the methylation cycle and so large quantities of methyl B12 are used up as there is little or reduced 5MTHF. A similar problem will be seen if riboflavin levels are low. You would need to have data on functional riboflavin before you could make conclusive statements about the relevance of MTHFR status. This can be obtained using the EGRA data. Further to this is the high occurrence of functional riboflavin deficiency, which has been noted in many studies in the UK, Europe and the USA. One can only speculate but this may be due to the scare about high cholesterol, which has resulted in people having less milk and lower egg consumption, both of which are excellent sources of riboflavin.

      • Rachel says:

        Hi Greg (and Michael)

        Thanks so much for responding! I agree about other things being a factor, as our diets and stress levels are high- from everything I am reading, the A1298C mutation, has not been studied as much as the c677t mutation, and the compounds- i completely understand that the others are more significant, but reading about one child’s struggle, was crazy, as it was like she was talking about my daughter, and this was BEFORE she was even administered a blood test- I was completely sure, just from reading that blog, that my daughter was MTHFR+, and i was right- here are some more facts about myself that i did not add, when i was on birth control, i would almost pass out- not sure why, but i had to go off, as my health was not stable while i took it. (It was weird!) also, we did not know that we had MTHFR in our family, and I really have no Idea if my sister even had it, but she passed away at 37 years old from a heart attack, and an autopsy was performed, and there was no cause to be found- but it was a heart attack- she didn’t even have caffeine in her system, all she had was tums, because she thought she had heartburn- is it related? i have no clue, but, in my opinion, there is still a lot of research to be done for the A1298C, because I do not consider my system running at 60% to be “slightly lower” than normal. – 40% is HUGE! if I received 40% less in my paycheck, that would cause a bit of a bind for myself and my family, so in my opinion, (as research shows) 50% of the population have my mutation, now many of them do not know they have it, or if they do, they have run into the same road blocks I have run into with Doctors, there is not much awareness- we also have MANY people with depression, anxiety ADHD and so on, all things that are symptomatic of this mutation, and people are medicating with synthetic drugs, which is treating the symptom, not the problem- I bet if you researched that 50%, i can guarantee that the majority of them have ailments that coincide with symptoms of lower methylation- most doctors do not know about MTHFR, I have been told it is only important during pregnancy, I also was told that “there are other pathways” (yes, there sure are but there are many ways to get from NY to California toom but some routes take longer and are less gas efficient, and that what is occurring in us A1298C’s) – I am so frustrated to read that A1298C isn’t considered a big deal, because when i got my daughters Organic acid panels back, the “catecholamines” were low, which is exactly what i expected, and that was before we even had her blood drawn for the MTHFR test- and from what i see, that is exactly what would be low, for someone affected by MTHFR- I was given very high doses of FOLIC ACID each day with both my pregnancies by my high risk perinatal specialist, who knew i had MTHFR! so in my opinion, this is proof that there needs to be more education – my girls were both born with dents where there tail bones are, and my youngest daughters dent was so deep when she was born, the dr was visibly concerned and started stretching her skin apart, to make sure it was closed, after about 10 minutes, he said that there was a bottom to it and there is no reason for concern- is that weird? i think it is, especially because we do not have any neural tube defects in either of our families- thankfully, those dents are gone, but I do feel now, looking back, that they had something to do with taking folic acid, and not folate- I know i am going off on a tangent here , but I am so frustrated that this mutation is minimized, and is having such a large affect on our lives- thanks so much for responding, and Sorry this was all over the place, but i am just trying to get the answers i need to help my girl!
        have a fantastic night! 🙂

        • Dr Lynch says:

          Rachel –

          Many people minimize the MTHFR mutation – and they are flat out wrong.

          All it takes is reading countless studies and talking with people having the MTHFR defect – and working with them as patients.

          I do not know who Greg is or what degree or background he has – but I do know that his reducing the significance of the MTHFR defect is wrong.

          Yes – you can say of course Dr Lynch says that because he has a whole website dedicated to it.

          Well – yeah! Because MTHFR is IMPORTANT.

          I would not spend so much time and effort on something that is just a fad or blown out of proportion.

          I will debate this all day and all night – and in fact, I do – often.

          You wanting to use as your own forum to discredit it is fine – but you’re wasting your time.

          You can do it on other forums and bash my work and the significance of MTHFR – which is fine.

          The more people who try to discredit MTHFR and my work make me only fight harder to make it more known as a serious issue.

          Now – there is a huge reality check that needs to occur as some people blame all their issues on the MTHFR polymorphism – which is WRONG. It’s not that easy – given that there are nearly 20,000 or so genes in the human body.

          The point is MTHFR is a central gene for supporting recycling of homocysteine back into methionine and into SAMe.

          Your point of BHMT making SAMe is fine – for the liver and kidneys.

          But what about the brain? And all the other tissues/organs/cells which need methylation to function?

          The liver does most of the methylation reactions – but other tissues need support, too.

          It’s a balancing act – and if MTHFR was so redundant, then why do we even have the gene in the first place?

          Why is MTHFR so prevalent in recurrent miscarriage, infertility, neural tube defects, depression, etc? If BHMT was the big dog on the block, and people just chowed on protein all day, then all these conditions would not be an issue.

          But they are – and MTHFR is one of the most studied genes associated with the conditions above – and that’s only a tiny partial list.

    • Madge says:

      hi There,
      If you send a request to they can look at your 23andme data, plus your symptoms and suggest what you may need to help. They are currently doing this as a free service. I have heard some pretty good reports. Anyway it is probably worth a try.

  • xaevir says:

    Is there a way to reverse the effects of taking niacin? It can make me sure groggy on even really small amounts.
    In the post you say this:
    “Niacin is broken down by SAMe. This means that excessive SAM is quenched by taking niacin. Niacin also helps break down glutamate and therefore increase GABA.”

    So is there a way to increase glutamate or decrease GABA?

    Thank you!

    • Dr Lynch says:

      Bobby –

      Yes. Consider:
      L-Tyrosine to boost dopamine and norepinephrine – 250 mg to 500 mg to start – away from food.
      Adrenal Cortex – to support adrenals
      Panthothenic acid – to support energy production

      Niacin increases serotonin which also increases melatonin – so that may be what’s going on.

      You may have higher tryptophan levels than tyrosine.

  • Nick says:


    I was diagnosed with the double gene mutation a couple weeks back after complaining about general depression-like feelings (anxiety, irritability, general malaise) and was prescribed 1,000 mcg of L-5-MTHF from Seeking Health.

    I took the pill every morning for three days and thought I was starting to feel better, but this past Saturday (Day 4 on the meds) I had a terrible day. I was extremely irritable and really just wanted to be left alone for most of the day soon after I took my pill.

    Is this response something normal? And if so, what would be a good next step?

    I appreciate everything you’ve done Dr. Lynch and your website has been a great resource for me in the past couple weeks.



    • Dr Lynch says:

      Nick – that is very very common.

      I always tell doctors to prescribe methylation nutrients – and supplements in general – on an as needed basis.

      Listen to this:

      Stop the methylfolate.
      Take the Niacin – 50 mg every 30 minutes until anger is gone.
      Magnesium Plus – a combination of magnesium glycinate and P5P (active B6)
      Optimal Adrenal – a combination of herbs which really calm and stabilize people’s energy and mood – in a subtle way.

      Adapt and learn how to take your supplements. Need to ‘tune in’ to how you are feeling before taking the pill.

      If you are feeling great – take nothing.

      These nutrients are STRONG – and must be respected. Doctors are learning about this – and I am still as well. It is a brand new field we’re in now –

  • Donna says:

    New to MTHFR and confused! My 11 year old was diagnosed MTHFR C3677T, one mutation. Doctor diagnosed L-Methylfolate Calcium manufacturer Virtus. After researching the ingredients I believe it contains 800mcgs. Days 3-5 which is today, he is an irritable mess! Is 800mcgs the correct amount, is this too much? Over meth? UGH

    • Dr Lynch says:

      Yep. Seen this way too many times. I’d stop the methylfolate and give Niacin 50 mg lozenge. 800 mcg will make my compound heterozygous 9 yr old an irritable mess – so yours – very likely.

      • DM says:

        Dr Lynch – are you advising Donna to stop the methylfolate completely with her son? Or just stop for a while (and then re-introduce it)? My daughter gets irritable with too much, and I’m currently tapering her up, very slowly, after a several months without any. If someone has the MTHFR mutation, then they *need* the methylfolate, right? Or do only some people need it? Thanks in advance for your advice.

        • Dr Lynch says:

          DM – I am not advising Donna – I am recommending that she consider stopping the methylfolate for a period of time – not entirely. People with MTHFR can obtain methylfolate from leafy greens – but many times people need to supplement as well. However, the amount needed depends on the situation and on the person. If you notice you or your child doing well with the methylfolate, note how they were prior to getting it. If they stay on it consistently, they may start to slide and get irritable, sore muscles, etc. It is an ‘as needed’ nutrient – as most are.

          Listen to this podcast.

  • Michael_Dowdy says:

    Hello Greg. All I’m saying is that you shouldn’t minimize the effects of MTHFR mutations, especially when combined with other blood clotting issues. I’ve nearly lost two family members because of clotting issues. I’ve seen it first hand. Dr. Ben has provided some of the most helpful information in dealing with these issues. This is critical when determining whether or not to use certain birth control medications. MTHFR mutations may be common but they affect different people differently and should not be minimized because of their deadly possibilities. Respectfully, Michael Murray Dowdy

    • Greg says:

      Hi Michael, I appreciate the history and concern about the mutations. I guess what I am saying is that in my experience it is not really the MTHFR status that is the problem, it is more likely to be other alleles in other proteins, such as MAO, COMT, MTRR, MTR, etc. High homocysteine in itself can lead to the problems that you elude to, and there are several papers trying to make a connection to this. The elevated homocysteine causes arterial damage, which in turn leads to a higher propensity to clotting. As you no doubt know, though, it is the continual production of homocysteine, without the subsequent conversion back to either methionine or alternatively transfer into the glutathione synthesis pathway via CBS. This problem is exacerbated by MTRR mutations, low folate, low methyl B12 and high levels of methionine in the diet (although this is not so common). So the problem is the elevation in homocysteine, not necessarily the MTHFR status. Homocysteine can be easily lowered either by additional B12 or folate. What often happens though is that the vitamin B12 deficiency is missed. FYI if you check out PubMed and look for either homocysteine PLUS folate deficiency or Homocysteine PLUS vitamin B12 deficiency, you will come up with scores of papers on this. Remember, once again that these studies are done in a typical MTHFR population, where roughly 50% are CC, 25% CT and 25% are TT. One of the best studies looking at this concluded the following “For MTHFR, as with homocysteine testing, no official guidelines exist as to who should be tested. In the absence of elevated homocysteine levels, MTHFR mutations appear to have no clinical relevance in regard to thrombosis and atherosclerosis. Therefore, one could argue that there is no indication to perform MTHFR genetic testing. ”
      This then suggests that it is the elevated homocysteine that is the problem, not the MTHFR status. Remember once again that 50% of the population is heterozygous, it is not just one or two individuals, it is the majority of the population. One problem that is often encountered with such studies is that they don’t present intracellular folate and vitamin B12 status, which would make the interpretations much easier. It is a worthwhile chat though, and I thank you for that. Greg ..

      • Greg says:

        Sorry the typical population should read CC 25% CT 50% and TT 25%, not CC 50% as stated above.

        • Michael_Dowdy says:

          Hello Greg. There’s a lot more possibilities of MTHFR mutation locations other than just 677 and 1298. I wouldn’t be surprised if just about everyone has some sort of mutation in the MTHFR gene. The NIH recognizes the use of Betaine HCL, another methyl donor, to reduce homocysteine levels. I question the effectiveness of Betaine HCL compared to “natural” TMG (trimethylglycine). Nutrigenomics is so individualized it’s difficult to find someone really willing to assist someone trying to use holistic medicine. Each individual needs to educate themselves through intensive personal study. Dr. Ben’s site is extremely helpful in this. Doctors can be overwhelmed when a patient hands them the information on which the patient has done with their own research. It’s very understandable that a doctor wishes to avoid this kind of time consuming treatment. What medical coding would you place it under anyway to make sure the provider gets paid for this kind of extensive visit? It’s problematic to say the least. If a person is having a problem digesting proteins it’s a very real problem. The most fortunate thing is that there are sites that people can educate themselves like this site. I think a situation exists though when a person is partially using folic acid from fortified foods and then adds methylfolate to the equation. This is what I question particularly in the case when someone is only heterzygous with a MTHFR mutation. Apparently a total of 1 mg of combined synthetic folic acid and methylfolate is all a person can safely tolerate. I base some of my thought on what I read in “Application A566.” Am I incorrect in my thinking or interpretation? I’d like to know Dr. Ben’s input on what happens when folic acid is combined with methylfolate and exceeds the maximum tolerable level, particularly considering the variable effective usage of folic acid in heterozygous and homozygous individuals. Dr. Ben Lynch or Lynn_M, what happens when both folic acid and methylfolate are combined in excessive levels taking into consideration the MTHFR variables? Is there a toxic level of combined folic acid and methylfolate? Thanks in advance. Michael

          • Dr Lynch says:

            Michael –

            Great answers – this one and many others. Thank you for contributing.

            When one takes folic acid, it competes with folate binding proteins and also binding to folate receptors.

            It’s not really a point of toxicity but more an issue of function.

            Imagine a bus, full of people, is driving and it needs to park at the stadium in the unloading zone. When it arrives, it finds that there is a minibus sitting there. It cannot park. The space is suitable for both a minibus or a full sized bus – but the issue is the bus load of people cannot park and get out.

            Imagine the bus as the folate binding protein, people as methylfolate and the parking spot as the folate receptor. Folic acid is the minibus.
            Now the people cannot get out and do what they need – just like the methylfolate cannot get off the binding protein and dock with the receptor.

            So – bottom line:
            TOSS FOLIC ACID.

            Avoid eating it as often as you can. It’s not always easy but do your best.

          • Greg says:

            Hi Michael, of course you are right about the multiple possible mutations, the problem is of course that they have alter function of amino acids to make a difference. The two recognized ones that have been shown to have modified function are 677 and 1298. That having been said in the heterozygous condition, you still have one copy of the enzyme that is working at maximal rate, so even if you really stuff up the other copy the maximum reduction that you get in activity will be 50%. Compare this to the heterozygous single mutation enzyme where the activity is around 60%, so not really much of a difference. Much more important and generally over-looked is the fact that you need to be replete in riboflavin and you need to make FAD, otherwise the enzyme activity will be really low regardless of the genetics. In my experience this very common. The next thing is that whilst MTHFR is the switch from the folate cycle to the methylation cycle, you can get to the folate cycle either by folic acid supplementation or folinic acid, or 5MTHF. You can only get to the folate cycle via 5MTHF if you have sufficient B12, otherwise addition of 5MTHF is useless. You do, however, need some form of folate for the folate cycle. On the other hand if you need to make SAM, you can get their via BHMT using betaine (trimethylglycine), a reversible conversion from choline. Data suggests that 40-50% of a “normal” person’s SAM comes from betaine. The more you go into the genetics and the possible implications of mutations in MTHFR, the less likely it is that the major health issues in those with CFS, and autism actually stem from these mutations. Technically, MTHFR doesn’t actually make anything biological. The folate molecule is basically a scaffold to get do chemical modification on, but the folate doesn’t act as a co-factor in any reactions in the same way that AdoCbl and MeCbl or BH4 does. As for folic acid and 5MTHF “fighting” for uptake, I am now skeptical that this is the problem that it has been put up for. As I said above, you can get into the folate cycle using either molecule. If you add 5MTHF to provide methyl groups, you only get one methylgroup per 5MTHF, unless it enters the folate cycle. At that stage it can be methylated over and over again and so provide 100 x N (where N is some variable) methyl groups. If you add folic acid the number is almost identical. You still need to go through MTHFR to process the methyl groups gained in the folate cycle, no matter what the starting folate analogue was. Further to get effective methylation via folate you still need MeCbl, plus riboflavin (as FAD) plus NAD. Whilst it is true that 5MTHF can unload its first methyl group before entering the folate cycle, it still needs to cycle to get any other methyl groups, and hence amplify the effect. There is no magic in this, just logic. Futhermore, in order to keep folate, or an analogue thereof it has to be polyglutaminated and 5MTHF is a very poor substrate for this. in addition, the real “starting” analogue of folate for the folate cycle is actually THF, which you can get to via folic acid, without B12.

          • Dr Lynch says:

            Greg –

            MTHFR does need B2 as FAD – absolutely correct – and it is often overlooked.

            I wholly disagree with you about using folic acid. It should not be used. Instead use a combination of folinic acid, methylfolate and methylcobalamin. The methylcobalamin and methylfolate will help produce THF which then can feed the rest of the folate pathway. So can choline moving through to sarcosine – and so can glycine.

            TMG is great – but it is mainly in the liver and kidneys – not the brain or other places.

            Research supports the issues between folic acid and transport binding proteins -and receptor issues. Folic acid actually downregulates folate binding proteins. A horrible situation- – especially in breast feeding children.

            People should have adequate B12 on board with 5-MTHF – and saying that 5-MTHF needs to have B12 in order to work – yes – that’s right. It does not make it ‘bad’ or make it right to use folic acid as a substitute. One MUST have adequate MTHF and B12 on board in order to support methylation in ALL tissues of the body – not just the liver and kidneys via BHMT.

            Also – clinically MTHF works. The difference one feels from using MTHF compared to folic acid is amazing – and life-changing for many many people.

            There are so many papers out there showing a reduced percentage of methylated folates in those with MTHFR compared to wild type. I don’t know why you are protecting folic acid. It just doesn’t make sense at all.

            Folic acid sucks and needs to go. Plain and simple.

      • Dr Lynch says:

        Greg –

        MTHFR is not only about homocysteine recycling.

        It’s about methylated folate.

        MTHFR produces methylated folate – that’s what it does.

        Homocysteine has three routes – elimination route via CBS and two recycling routes via MTR/MTHFR/MTRR and BHMT.

        Also one can have a ‘normal’ homocysteine yet have an elevated SAH. SAH is the marker of choice – not homocysteine.

        Methylfolate does more than just recycle homocysteine – it also increases nitric oxide levels.

  • Jess says:

    Hi Dr Ben
    I know this is off topic, but I read that if someone has gum disease then squeezing a capsule of CoQ10 onto the gums daily can help. Have you heard of this and do you think it would be beneficial?

  • Nancy says:

    I was diagnosed with the heterozygous A1298C mutation and Hashimotos thyroiditis 6 weeks ago. My doctor has me taking a product called Methyl Defense. One capsule contains 25mg Riboflavin, 10mg Vitamin B-6, 20mcg folate, 100mcg B-12, and 500mg Betaine Anhydrous.
    She wanted me to take 1 tablet daily for a week then up the dosage to 2 a day for a month. When I upped the dosage to 2 tablets, after a week I had severe headaches, a runny nose, itchy arms and felt like I had the flu. I went back to one for two more weeks then tried to go back to two but after a week the symptoms reappeared so I told the doctor that I am going to just stick with one a day.
    Yesterday I began taking a new multivitamin because the one I had been taking contained gluten. These vitamins contain 100mg of 5-methyltetrahydrofolic acid and 100mcg as calcium folate, along with 250mcg of B-12.
    Last night I noticed that my forearms were itching again and I woke up at 3:00am with a really painful muscle cramp in what I would presume to be my diaphragm. It ached really bad from my sternum through to my back.
    I was also put on 25 mcg Tirosint for my thyroid. Since taking this protocol I have developed a severely inflamed abdomen – not just my stomach but my intestines too. After calling the makers of Tirosint, I was told this symptom has been reported in some users when the dosage is too high. I have dropped my dosage to 13 mcg. Today was the first time of taking the lower dosage.
    All this to ask, do you think it is possible that my burning gut issues could be related to the Methyl Defense also? I am more tired and have more brain fog than I did before I started this regimen. I work out 3 days a week and the lactic acid builds up immediately when I lift weights. I also experienced this years ago when I did the Atkins diet, which is similar to how I am eating now. I have cut out all gluten, soy, corn and grains and have eaten very few starchy vegetables.
    I don’t think I have high inflammation markers. The tests that I had showed fibrinogen, hs-CRP and Lp-PLA in the optimal ranges but my Myeloperoxidase was 323 (pmol/L) which is only just above the optimal level of 320. That being said, I really don’t know how to interpret them properly, with medical understanding.
    Also, I was wondering if there are any particular instructions as to how and when to take the Methyl Defense. With food, or on an empty stomach? With other vitamins and supplements or on it’s own? I would so appreciate any help you can give. I am sick and tired of being sick and tired.
    Thank you! Nancy

  • Nancy says:

    Sorry! I made a mistake on the folate number. It is supposed to say 2000mcg.

  • irma says:

    I experienced symptoms of burning sensation in arms, back of head & face which now is flushed & turning red after taking supplement? Here is what I just took: methyl-Cobalamin 5 mg, optimized Folate(L-Methylfolate) 1000 mcg, complete B Complex, Ultra Chromium Picolinate 500 mcg & 1/2 tsp of vitaminC powder. I have both MTHFR mutations. This is 2nd time this wk I’ve had this reaction. Could it be the Folate? Is this too high a dose? All prescribed by doctor. Not taking thyroid meds at this time. Also took Bupropion XL 300 (generic for Wellbutrim). The B-complex has 100mg of Naicin.
    I will stop taking for 2 weeks. When I start up again how much should I take? And is it ok to take it with all the other supplements.

  • irma says:

    I forgot to mention that I have hashimoto but am not on thyroid meds.

  • Joe Riedley says:

    Hello Dr. Lynch, thank you for being the number 1 source of MTHFR and Methylation… I am not a Dr. but a patient. Here is my story:

    2 years ago I injured my leg, and shortly thereafter got a blood clot in my leg. I was put on blood thinners and my GP sent me to a cancer/hematologist who said I had a gene mutation After 3 months, the clot disappeared and I was removed from thinners and was prescribed 5mg of Folic Acid since I had high homocysteine levels. I didn’t know what all this meant but I started taking it. I decided to only take 2mg because I had read about issues with high doses of Folic Acid. At the time I didn’t know anything about gene mutations.

    My sister and myself had (almost crippling) anxiety for most of our lives. I noticed a year ago that my anxiety had almost completly diminished. A couple of months ago, my wife read something about folic acid helping with anxiety. I called my hematologist and asked her exactly what mutation I had. It was Compound Heterozygous A1298C & C677T. I immediately started doing extensive research on this topic and ran across your web site as the leading source of information on MTHFR.

    My sister was tested and it was found that she also has A1298C/C677T. Her Dr. tried to get my sister on L-MethylFolate, but insurance would not pay for it, instead they said it would need to be Folic Acid. I don’t understand how an insurance company can override a Dr’s recommendation on prescriptions, but that is another topic.

    My delima is this. first of all, in an audio stream, you said Methylation is complicated and you need to work with a Dr. But I have found that almost all doctors know very little on this topic. In fact I made an appointment with my Hematologist and she didn’t really know anything about L-MethylFolate and she told me I read the internet to much. I have found that if you go in to a GP and say you have anxiety, depression, then they want to prescribe a mind altering synthetic prescription.

    I purchased 400mcg L-MethylFolate from a health food store and started taking 1 tablet instead of the Folic Acid. After a week or so, I had many aches and pains in my body. I know you say this is to be expected, so I bought a multivitamin with 50mg of Niacin to take with the L-MethylFolate. I took this combo for a week and this did not help. I am taking the lowest dose possible of L-MethylFolate. My sister on the other hand has been taking Folic Acid (because of insurance) and her anxiety has greatly improved and she feels better.

    I have another friend who has Homozygous 1298 and she started on L-Methylfolate and she feels bad.

    It is hard for me to explain to my sister and friend that L-MethylFolate is better since it appears that Folic Acid Yields better results.

    Am I right in the understanding that your body has to sort of detox when doing Methylation? So after that happens, then you will not have any more symptoms? Or if you do have symptoms, does this indicate that you have other issues and you need to do something else?

    Also is there differences in quality of the L-MethylFolate? Any recommendations? Any ingredients to watch out for? Is taking the Niacin in a multivitamin OK, or do you need the sublingual form?

    A few months ago, I had never heard of MTHFR so I am trying to make sense of all this.

    Thanks in advance…..

    BTW, I eat very healthy, only drink water and rarely take in sugar and have done so for several years…

  • JJ N says:

    Hi all,

    I saw a new dr. about a month ago for a few different symptoms. She had a blood panel done included a MTHFR test in addition. We found that I have the Homozygous A1298C mutation. She told me that there wasn’t much research done on it but that I still might benefit from Methlyation. She put me on Methyl Protect, which has 2000 mcg of Methylfolate per capsule. She instructed me to take two in the AM and one in the PM. I am writing because at this very moment I have a string of what I hope and perceive to be side effects. I generally feel very slowed down and it has been hard to communicate with others and process thoughts. It feels as though my intelligence has been lowered or that there is a thick brain fog over me. I also am very tired, irritable and have some anxiety. If I am not talking or trying to concentrate, then I do feel decent. I started taking four capsules a day for the first two days and then dropped down to one every other day. I’m thinking now that I may want to stop entirely and allow my body to reset. I read this article and have ordered the recommended dosage to begin the steps it takes to properly supplement. These side effects have me extremely frustrated and I’d love to get some better answers from the forums. I feel like my Dr. just blindly prescribes without either A. paying more attention to what makes me unique and B. having up to date informatin. I have a few questions:

    1. Has anyone else experienced the slowed down feeling? Is this a sign of taking too much or a sign of not taking it often enough?

    2. Should I push through this and try to keep on the same dosage?
    3. I ordered this: and Niacin. Anything else I should take?
    4. Any additional information anyone can provide is extremely helpful.

  • Alison A says:

    Hello, this may have been asked before, but 755 messages is a lot to read through. I’m wondering what the generic or supplement(s) that is the equivalent to Deplin? ( if such a thing exists). $122 a month is too much for me to spend. Also, i think it may be contributing to weight gain.
    Thank you,
    Alison A.

  • Kendra says:

    My mom has the MTHFR mutation, so I have been wondering if I may have inherited it too. For the last few months, I was trying to get pregnant and I assumed I should take a methylfolate supplement just in case I can’t benefit from the folic acid in most prenatal vitamins. I started taking 400 mcg every day. This did trigger anxiety that I have been struggling with for a while now. (It’s not the first time though, I have had anxiety and panic attacks at various times in the past, before I ever took methylfolate). Well now I am preganant, and it’s still really early in the pregnancy. My mom discovered this article and told me about these side effects, which I had no idea existed. Now I’m not sure what to do. Am I harming myself with the methylfolate, or is it something I need to do for the baby, in case I do have an MTHFR mutation? This is my second pregnancy. My son did not have any neural tube defects or issues, and I took folic acid during that pregnancy. But I have been nursing all this time and I worry about depleted nutritional stores. Thanks so much for your help!

  • Jane says:

    The only side effect I experienced was sleep disturbance. First couple of nights after starting or increasing dose, I would fall asleep but wake around 2am with thoughts running.
    I already take methylcoalbumin and a Pfeiffer Formula. (Plenty B6 and zinc).
    This side effect passed over a couple of days. Ironically, even with disturbed sleep, I woke feeling like I had actually slept (i.e. rested) for the first time in years – perhaps decades. I started with 1 Thorne Research Methylguard for a fortnight, added another for a fortnight and then a third. Some months later the 2am wakeup call seems to have returned so I’m going to drop back to two tabs every other day.
    I feel great. I have more energy and the dysthymic mood I have suffered since my teen appears to have lifted. I’m sold.

  • bobby says:

    Found on ur website the perfect description of something that has plagued me but I thought I was alone:
    “excessive methylfolate may utilize BH4, thereby causing an increase in peroxynitrite and nitric oxide. These case pain, headaches, soreness, and neurologic tingling. By using up all of the BH4, it is not able to process peroxynitrite.”

    Is this a possible genetic snp defect? How can I get my doctor to prescribe it? I’m taking doses small as 50mcg and its still a plague in my life.
    Thank you so very much.

    • bobby says:

      After seeing the 10,000 cost of kuvan which makes it a pipe dream. Is there a way to increase bh4 naturally by supporting the precursors?

    • Madge says:

      It looks like the information that you are getting is not quite right. BH4 is formed after a series of reactions that require the folate cycle to be working properly (5MTHF + MeB12 will help, plus a functioning thyroid and riboflavin) BH4 is used in four essential reactions, Phenylalanine hydroxylase (which converts phenylalanine to tyrosine), tryptophan hydroxylase (which converts L-tryptophan to L-hydroxytryptophan, or serotonin), tyrosine hydroxylase (converts tyrosine to L-DOPA and precursor in the synthesis of dopamine, nor-adrenalin and adrenalin) and nitric oxide synthetase. What may be happening is that if you have high levels of methylfolate and you don’t have high enough riboflavin (B2) you turn on the synthesis of Dopamine, nor-adrenalin and adrenalin, but you can’t inactivate them as you don’t have a functioning MAO, which needs riboflavin (FAD).

      • bobby says:

        Thank you. Your information solved the issue perfectly. I was only taking the methylfolate and not the other b vitamins bc I was scared to take a multivitamin or b complex and I believe I depleted all of my b2 which limited ability to make bh4. A couple of b complexes later and all is solved

  • Jan says:

    I have chronic Lyme and many mutations in meth cycles. I am on 1 Pro NADH, 1 BH4, 1 MTHFR/MTR/MTRR & BHMT Assist. I am also on numerous supplements like COQ10, ALA, protelictic enzyme, Vit C time release, Vit D, K2, Astaxathin, and omega 3. And of course, 3 different kinds of antibiotics. My anxiety and insomnia has increased, but started to improve again after reducing down to 1 MTHFR and starting 1 Gaba.

    My primary problem now is my heart rate is faster. My resting pulse is in upper 70s and 80s. I have heart palpatations too. Any idea what would contribute to rapid pulse?
    I’ve tried a 500mg niacin (all I have right now) and don’t notice any difference.


  • bobby says:

    I tried taking p5p alone on an empty stomach and it has caused tremendous drowsiness in a bad way. Any ideas as to this cause? I read b6 supports the production of gaba so maybe thats the problem. I also have a similar problem taking niacin alone and I dont know if they would be connected. Thanks of any guidance on clearing this up.

  • Todd says:

    Is it necessary to supplement the other b vitamins with methyl b12/ Methyl folate? I only wanted to supplement the two, and a small dose of b2 for blocked absorption from folate. I never heard any studies showing b12/folate supplements cause deficiencies of other b vitamins so want to check and see.

  • Chrissy says:

    Hi Dr. Ben

    I’ve kind of just started this whole MTHFR, methylation pathways things so it all still really intimidates me especially considering I can’t really take in information anymore or read blocks of text at all. I started going to a naturopath about two months about Candida (yeast infection) which I’ve have since I was 13, chronic fatigue, jelly like muscles, psoriasis, blurred vision, body + brain disconnection, brain fog, cold feet, peripheral neuropathy, ringing in ears, leaky gut, digestion problems, feeling cold, depression, anxiety, depersonalization, derealization, headaches, add/adhd like symptoms, emotional disorders etc. It’s kind of just been following symptoms to get find what’s really wrong. My journey has been Candida + Leaky Gut > Thyroid +Adrenals > Heavy Metals/Chelation > MTHFR/methylation + Pyrrole disorder. It’s been a miserable experience. I often feel really flat, depressed, hopeless. I can barely think at all, my brain is a giant mushy, painful ball. I experience low blood pressure, hypoglycemic reactions if I stand too long so getting money from work to pay for all this has been hard. I found out I have high reverse T3 so taking slow-release rt3 helped a bit with the hypothyroid-like symptoms. I reckon a lot of it’s got to do with being inundated with heavy metals from being a bad methylator (mthfr + other snps possibly) having passed the blood brain barrier whilst also reeking havoc on my body. I smoked from the age of 17-20 (I’m 20 now) so I think that really added to the body burden. I get my results back about MTFHR and pyrolle disorder in two days but I’m pretty damn sure it’s this. I sent off a 23andme test about 4 days ago so I’ll get those results back in two-three weeks. I’m not necessarily looking for advice I was just kind of looking to vent but if you’ve got any for me that would be fantastic.

    Thanks so much.

  • My three children have tongue and/or lip ties, I have suffered from severe post-partum and pregnancy depression, and my oldest has ASD-style symptoms – so when I found myself unexpectedly pregnant with our (unplanned!!) fourth, I decided to dive into B9 supplementation. I’d already been taking methylB12 for awhile.

    For two months, I took SAM-E and B9/B12, and felt increasingly great…until I suddenly got an unrelenting two-week headache, culminating in several days of high anxiety and panic attacks.

    Over the past six weeks, since that headache, I’ve continued to experiment and also stopped taking SAM-E. Strangely, despite those first two months when I had excellent results with B9/B12, I now cannot take _any_ B9/B12 now without it triggering a severe headache. For the past six weeks I’ve tried: reducing my dose incrementally, taking it only every three days, then every week – and two days ago, taking a tiny dose after ten days of not taking any at all.

    But even with that tiny dose (100mcg), I felt intense anxiety and then an intense headache, and I imagine there must be more at play here than I can hypothesize about!

    I’m hoping this means that my body has enough folate from the foods I’m eating to sustain my pregnancy…and someday, I’d love to understand what’s going on, and be able to help others heal from the hell that mood disorders can be.

  • Ric says:

    My doctor is giving me a shot of: methyl tetrahydrafolate, methyl b12 and b complex I haven’t read a word about this shot on this site under these words. Can you supply a better understanding for me?

  • colleen says:

    Dear Dr. Lynch
    I was recently diagnosed with homozygous C. I was put on deplin 15 mg and have debilitating bloating and stomach upset. Should I taper it down to 1/4 pill and see if I feel better?
    Thank you for your time,

    • Dr Lynch says:

      Colleen – talk with your doctor about this – but it does seem you are having a bad response to it. You likely will feel better getting off of it and tapering up slowly. I believe the higher doses of methylfolate are rarely needed and do more harm than good personally. Some people need them – but few.

  • Genevieve says:

    This website has been so very helpful – thank you!

    I just found out I am heterozygous A. I started taking methylfolate and methyl B12 based on recommendations on this website back in July after finding out my mom has an MTHFR defect (right around the time we conceived after over a year of infertility – still wonder if that helped at all). My question is whether I need to be concerned about blood clotting issues during pregnancy with heterozygous A, or if the methylfolate is the main concern. I’m 18 weeks pregnant now, and so far no problems other than absolutely debilitating morning sickness (does that have any relation to MTHFR defects – maybe because of toxicity? I’d be interested if there’s any research on that – I’m sure hoping that taking methylfolate and detoxing a bit will help me have a smoother pregnancy next time around!)

    Thanks again for all the helpful info here!


    • Madge says:

      Over 50% of the population are heterozygous, so technically you are normal. Basic genetics learnt in high school will tell you this. You can also check this at SNPedia. If you are pregnant you need to supplement with folate, vitamin B12 and riboflavin, plus all the rest, iron, etc. I would really only have any concerns if you are homozygous recessive, which is actually not selected against as a marker. You do need to have higher levels of folate, B12 and riboflavin (vitamin B2) during pregnancy. I don’t know why doctors don’t test for it, but there you are.

  • Eve says:

    Is it possible that taking methyl folate could cause histamine intolerance? I am compound heterozygous. I was on GAPS to see if I could heal an egg intolerance. My Dr tested me for MTHFR polymorphisms because of 2 late pregnancy losses. I actually think they are unrelated to MTHFR because of the circumstances. Anyway – even ramping up slowly only to 1 mg, I was maxing out and getting severely irritable. Can not tolerate any form of B12: methyl/adeno/hydroxyl. . . I feel SO much better without methyl folate and was fine before taking it too. BUT ever since I started taking it, one by one, more and more foods casue a reaction in me: severe mood swings and sometime gas. I realized now the connection between the huge list now is they are all histamine foods.

    HELP please if you have any idea. I cannot tolerate many foods besides meat, vegetables, fruit – I am breastfeeding an 8 month old and have a 3 year old – so I cannot chance the mood swings with trying foods. Taking your liposomal C has been amazingly beneficial, another reason I think it’s histamine. Does any of this sounds familiar to you – so you can have a possible solution? I cannot even take probiotics. I used to be able to take Bifido (bc histamine degrading??) but cannot even take that anymore. Thank you for what you do. I look forward to more Drs being educated and open to this!

    • izzy says:

      Eve, I had a similar reaction and it took me months until I found out that magnesium supplementation helps with intolerances and histamines. The only form of magnesium I could tolerate was magnesium oxide orally, which I took for 4-6 weeks to bowel tolerance. Watch out for calcium imbalances though. Now I can eat normally again, except for coconut products.

    • Madge says:

      If you are having problems with methyl folate (the natural food substance form of folate) it will not cause histamine intolerance in itself. Over 50% of the population is heterozygous for most the methylation associated mutations so technically you are normal. If you want to check about this just go and look up the frequency in SNPedia. What is more likely is that apart from being vitamin B12 deficient, which you can become during prenancy you are also riboflavin deficient. This is an every increasing problem as people stop eating or reduce their dairy intake and also their intake of eggs (you can blame the cholesterol nuts for that one). The break-down of histamine or neutralization of histamine requires two enzymes that are dependent upon FAD (derived from riboflavin) MAO and DAO as well as histamine methyl transferase, which requires SAMe. In brief your problem has very little to do with MTHFR, but much to do with riboflavin deficiency. Most women also become riboflavin reduced/deficient during pregnancy. Over 80% of 16-18 year old girls in the UK are riboflavin deficient. You will also become FAD/FMN deficient if you have hypothyroid or don’t consume enough iodine.

      • Eve says:

        Interesting. I could definitely be deficient in other B vitamins. But when I looked on SNPedia, compound heterozygous is 20%:

        677CT/1298CA 19.8% – 2 heterozygous mutations (compound heterozygous) gs192

        but the histamine tolerance definitely came to a head and got very bad in correlation to taking l-methylfolate – which is synthetic. Folate in foods is fine for me.

        • Madge says:

          Yes compound heterozygous would be different. Theoretically if the allele has been around long enough it should end up as the single heterozygous condition would be 50%, with compound heterozygous (2 SNPs) would be 25%. Single homozygous would be 25% with compound homozygous around 6%.It is actually very hard to model this, as it depends upon when the mutation arises, is it distributed equally among different ethnicities etc, etc. The real issue is whether the heterozygosity is in the same copy of the gene or not. Current testing won’t tell you this and it appears to have been generally disregarded by “web chatter”. Thus, even if one copy of the gene has 100 recessive/inactive alleles in it, then the “normal” copy of the allele will still give you 50% of maximal activity, which will not be distinguishable from the “normal” distribution of activity, which would be around 63%. Now if you were to say that the 2 mutation alleles were on different copies of the gene, then the activity would be about 30%, as long as the allele effect was significant. It is very hard to tell this from ones genetics. What is more important is the concentration of riboflavin as FAD, as this has a huge effect on enzyme activity, and if the level is low enough the enzyme won’t work at all. Thus FAD is actually a much more component than the allele. Riboflavin deficiency is actually very common, and makes much more difference in the C667T allele, plus in MAO, MTRR, NOS, TYMS and DAO mutations. With the change in diets away from eggs and dairy – no thanks to the cholesterol lobby and the saturated fat lobby, no wonder there is an increase in many conditions such as obesity and diabetes. .

          • T says:

            Very interested to read this Madge as through research I had realised that vit B2 deficiency must surely be playing a part in my health difficulties. Other things that are draining it from our diet are keeping diary products in clear packaging I learnt as riboflavin is destroyed by light and the trend to exclude yeast from the diet as riboflavin occurs in yeast extract

          • Madge says:

            Hi T, yes riboflavin deficiency in itself can lead to B12 deficiency, as too can hypothyroidism, in which vitamin B2 is not converted to FAD and FMN. In a recent study in the UK over 80% of girls 16-18 years old were riboflavin deficient. Another very important enzyme that uses FAD is glutathione reductase, which is responsible for making sure that you have sufficient free, reduced glutathione (GSH). Rather than spend bucket of money on NAC, on glutathione, and other similar supplements the majority of people on this site would be better just making sure that they have correct thyroid function and that they are getting sufficient riboflavin in their diet. When you see the number of people on this site who are not consuming milk, cheese or eggs it is astounding. No wonder they have so many issues, most of which have nothing to do with their MTHFR status. If only they would eat a healthy diet!!!

  • JBlair says:

    Dr. Lynch, can taking Deplin 15 cause an Interstitial Cystitis flare? Thanks!

  • Michele Miller says:

    My 5yo daughter is heterozygous C677T and has moderate autism, largely nonverbal. She weighs about 60lbs and has been on methyl B12 shots every other day for several weeks now (was on it for over a year, then stopped, now started up again). Last week we started her on 400mcg of methyl folate (the label says quatrefolic (6s)-5-methyltetrahydrofolic acide glucosamine salt) and have seen increased irritability and some GI issues (loose stools). Is the dosage too high for her? Or should we be adding something else in conjunction with the methyl folate? Thanks so much for any advice!!

  • Alec says:

    Hi Dr. Lynch,

    I just found out a couple of weeks ago through a blood test from Health Diagnostic Laboratory Inc. that I have the MTHFR C677T. It says I am homozygous for the MTHFR C677 (T/T) polymorphism and have the normal or wild-type genotype for MTHFR A129BC (A/A). (whatever that means ?) Even though I would prefer not to have this condition, I was sort of excited to find out that I am not crazy! I am 55 years old, still play beach volleyball and take really good care of myself. With that being said, life has been very challenging to get through each day with the Brain Fog, and irritability that I have been feeling for at last 25 plus years. Maybe this would explain why as a child I had a learning disability and a very hard time focusing and paying attention (ADD). A couple of years ago a doctor put me on a low dosage of Adderall…I am only on 7.5 mg and it does help me stay on task. But the Brain fog and irritability come and go and are just brutal to deal with…especially trying to survive running a small business instead of thriving. I have also dealt with fatigue that is hard to figure out. It seems like if I try and sleep in, I feel worse. Then when I have not gotten enough sleep, sometimes the irritability hasn’t been as bad..that heavy head feeling…yuck!
    So my doctor who admits he is not an expert on this condition had me try 1 mg of the 5-mthf. Although at the beginning of the day my symptoms worsened, by the end of the day I did start feel much better. To make a long story short, as you mentioned above, I did have some great days, where I was clear with a good attitude and could take on my day easily and happily. Then the next day, the opposite. So after 1mg for the first few days, I cut back to a half that…but that was still too much. I then went down to about 200 mcg. and I felt bad about an hour and a half later, but then it was a little better by the end of the day. Last week the 200 mcg seem to be pretty good…but then yesterday, not good.It is frustrating, because I know my body needs this stuff, but I need the right dosage to use. I did try just two drops of Vitamin B12 methylcobalamin right after I took the 1/5 capsule of the 5-mthfr…an hour and a half later, the irritability came on 🙁 So not sure what to do at this point. Should I go off of it for a week and then start again with some niacin and the B12, 200 mcg of 5 – MTHFR? I did get some positive results but then bad…frustrating. Please help. Thanks! Alec

  • leina says:

    Dr Lynch

    I have the following mutations:.c677T and A1298C. I have tried varying types and doses of methylfolate. After a few days I feel better, (less brain fog, more relaxed, more energy, etc), then I start to feel HORRIBLE (brain fog, irritability, difficulty sleeping, nausea, muscle aches, etc). IT feels worse than before taking the methylfolate. Both of the functional medicine Dr’s I have seen, tell me I need to be able to handle and take a methylfolate. Even after I have reintroduced methylfolate again, the same horrible side effects/symptoms occur. Additionally, I have a terrible time tolerating any supplement or medication. What would you recommend?

    Also, where is the best place to find a list of foods to avoid (and dietary information) when dealing with methylation issues? I find there are conflicting lists out there.

  • Michelle says:

    My 15 year old daughter has been fighting Lyme Disease and Bartonella for 4 years and not getting much better, despite antibiotics. Her new doctor tested her for MTHFR and found she had the C677T Homozygous mutation. He wants to try to fix this problem before we try to treat with anymore antibiotics. He started her at a low dose methylfolate 800 mcg that is in a supplement called MultiThera 1. It’s actually a lot less than that even, because it is 800 mcg if you take 6 tablets! She is only taking one. After 2 days of taking it she had extreme pain all over – in her back, head, shoulders, etc. She also felt confused, angry and depressed. We then stopped it for 2 days and she started to feel better so we gave her 2 days of 1/2 a pill. The same thing happened. The pain came back, but slightly less, the confused feelings, bad migraine, and lots of inflammation. Her face looks extra swollen and puffy and she feels sick.

    Is this ever going to work? Should we try to get through this with Niacin? I’m not sure how that works. I ordered your Seeking Health Niacin Lozenges and Optimal Turmeric, but not sure how much to give her. Is there any dangerous side effects to Niacin? She does have a lot of inflammation from her Lyme and also a high histamine count.

    Thank you so much for any help or advice you have!

  • Kristen says:

    I am homozygous a1298c, and received the test results just over a month ago. of my children who have been tested, one daughter is homozygous for a1298c. (her provider immediately dismissed the result as unimportant. I strongly urged her to go to another provider.), and two sons are heterozygous for a1298c.

    One minor son is on mthf – and we started out very slow to buildup, and reduce to find an optimum dose. with his provider, I learned about mthf, learned about bioavailable vitamin forms, etc.

    For almost two years, I have been on a bio available b-complex, and multi. when I first started them, it was like a lightswitch had been flipped on. between them I get 600mcg of mthfr, 75mcg of p5p, as well as 600mcg of methylcobalimin. I also take 1mg of methylcobalimin. proomega fish oil. after the 200mg of 5-htp – I finally felt like “myself”. I recently started curcumin as well as some dietary changes due to inflammation and high liver numbers. I .also walk and do yoga regularly.

    A month ago, my dr immediately put me on 15mgs mthf rx. (l-methylfolate forte) I can be really slow to connect the following was because of the mthf, because with my sons, we moved slowly and had few side-effects. Also, I had a 2nd degree MCL injury that is still sensitive and will occasionally cause stiffness just from normal use.

    Initially, I felt hyper. I dreamed *a lot*. I didn’t sleep long enough. Then I had trouble staying asleep. I had to push myself to do things. I just started feeling “not well”. I hardly walked, and hardly did yoga. My legs were hurting as though they’d been injured. My chiropractor noticed my thigh muscles were cramping. Then my calves started cramping – as though a Charlie horse (but not quite). Massaging them was painful, and unhelpful. Other muscles became tired, sore, and even painful. Next, I just got tired. I had been taking 500mg of magnesium citrate, and thought maybe my levels were too high, so I stopped the magnesium. The pain in my calves increased sharply. My legs didn’t want to straighten, stretching them was difficult. I started up the magnesium citrate again, and added 99mgs of potassium citrate. I also paid more attention to my water intake, as it had slipped. The pain is much less, though still there but no longer debilitating, and range of motion is improved. (knee is still stiff from the injury.)

    Now I am having dizzy spells and headaches, sometimes with nausea, sometimes not. The headaches are an annoying level that make me feel “blah”, but not debilitating. I am more tired, and just want to sleep. But then, I’ll have bouts of energy and feel very productive, before things crash again.

    I reported these into my provider – and have been told to stop the mthf and see her in two weeks. I have concerns about going off as suddenly as I started. I am more inclined to wean off by dropping to 10mgs and then 5mgs for several days each. I just happen to have a shipment of thorne mthf coming today. (and I’m jaded enough to wonder if the thorne would be better molecular quality than the pharmacy’s l-methylfolate forte . . . )

  • Donna says:

    Dr. Ben,

    I was diagnosed five months ago with Celiac Disease and then last month Heterozygous C677T. I have been on Ortho Biotics for the last three months along with many vitamins along with turmeric, milk thistle and Red Clover Tea. I am 51 and was born with one kidney. The last three years I have been struggling with pain and muscles spasms with no relieve after back surgery and multiple interventions many of which I didn’t tolerate well.

    My Endocrinologist put me on L-Methyl-B6-B12 (includes 3mg folate/35mg/2mg) which I tried cutting into eight sections, but not able to because it crumbles. I have resorted to four sections and I don’t seem to be tolerating as my pain and muscles spasms are increasing to the point of having to take Niacin (500mg) prescribed. After having an Emergency Room reaction to Alpha Lipoid Acid, I have been using Biotin to help with muscle cramping and stopped taking all B Vitamins and Multi’s prior to finding out about the MTHFR Diagnosis. The doctors don’t know what to do with me and I need someone knowledgable in this field. Can you please advise what I should take? I just purchased a membership to

    • Donna says:

      Hi Madge,

      Thanks for responding to me. I am taking 4000IU of Vitamin D. I have my supplements below. My Endo has been great. I see my Gastro in another month and another Neurologist in two. I also have several non-specific white matter scars that they are watching. I am convinced it is from stress and possibly MTHFR as I just found out my cousin had a major stroke 12 years ago and they tied it to MTHFR as well. I wish he had told family about it. 🙁

      Tumeric 2 capsules
      Ortho Biotic (probiotic)
      Ester C 1000mg
      Vitamin E 400IU
      Magnesium Glycinate Chelated Buffered 200mg (X3)
      Evening Primrose 1000mg (X3)
      Vitamin D 4000IU
      Biotin 5000mcg (X2)
      Organic Non GMO Milled Flaxseed 2 Tablespoon

      I have been on a gluten free diet for four months and probiotics for three. How long does it take before i can absorb properly? I can feel the B Vitamins working, but my muscle cramping and pain are still an issue especially in the afternoon if I push myself. I want to get some of the supplements on, but I can’t afford to waste money. Help???

      Thank you….

      • Donna says:

        Where do I get that oil? How much do I apply and how many time a day?

        • Madge says:

          Hi Donna, you get the oils from .Talk to them about your condition and they will advise on the frequency. They have got a lot of people “over the line”, so its worth the effort.

          • Donna says:

            Hi Madge,

            I did talk with them. They said I should get tested for more possible genetic problems. I am going to talk with my doctor before I make any changes to my meds or supplements. Are you affiliated with that company? I never heard of this form of supplementation and it seems expensive for something I can’t research.

            What is your position with Dr. Ben Lynch? You seem to be commenting a lot on the blogs. I am just curious?

            Thanks for letting me know about that company and again I will talk to my doctor about that form of supplementation.


          • Kelly says:

            Skip the b12oils. B12 is degraded by light, so you’re correct to ask your doctor.

            I highly doubt Madge works for Dr. Lynch, more likely she works for the b12oil company, but that’s a guess, and of course might not be true.

            One thing I know for sure is that Dr. Lynch would tell you to avoid ALL FOLIC ACID in any sort of supplement as it will block the folinic and methylfolate forms of folate.

            Folic acid is synthetic — it is helping to cause the problems in those of us with MTHFR and other mutations. If your doctor doesn’t understand this, then he should watch some of Dr. Lynch’s videos on youtube.

          • Donna says:

            Hi Kelly,

            Thanks for your observation. Dr. Lynch should take a look at her comments and possibly have a conversation with Madge about her advice.

            I trust Dr. Lynch and am following his basic protocol, but working with my doctor as well. I just want to turn my clock back three years as I was fairly normal before a few changes that don’t need to be elaborated on, but the more I read the more I feel that I threw my body in to this state and it will take time to normalize things. I am finally on the right path! Thanks to Jennifer’s Way bringing light to this area which made me ask my primary doctor to test me for the MTHFR.

            Miracles do happen, just not in our timing…

          • Madge says:

            Donna and Kelly,
            I would appreciate it if you didn’t make assumptions on my behalf or where I work. I don’t work for either Dr Lynch or B12 Oils, however I am very interesting in finding out the truth of the chatter that appears on this site, and I respectfully suggest that you do the same.
            A couple of observations though. Whilst it is true that dilute (very dilute) solutions of methyl B12, and in fact most B12s can be degraded by light, concentrated solutions are very resistant to light, as they tend to protect themselves from light damage. B12oils appear to also know this as the bottles that I have got from them are light protected.
            Second there is a grave misconception about the use of folic acid or 5MTHF as far as folate cycling goes. Folate (folic acid) obviously works as a supplement otherwise it would not have reduced the incidence of Spina Bifida in the USA by 30%. Next, you have a series of enzymes that quickly convert folic acid to THF, for effective folate cycling. In contrast to 5MTHF, you can get folic acid into the folate cycle without the aid of methyl B12, however, on first pass through the cycle you don’t contribute to methylation. In contrast 5MTHF requires methylB12 to enter the folate cycle and in doing so contributes the methyl group to the production of SAM. After the first round ofteh folate cycle (a cycle that may repeat itself hundreds of times for each folate analogue) there is ostensibly no difference between supplementing with folate or 5MTHF. Third, the major MTHFR allele expressed in the community it MTHFR C665T heterozygous allele, so if you have this allele you are technically a “normal” representative of the community. Whilst there are around 18% who have MTHFR 665TT, their enzyme activity is only slightly less than +/- individuals. If you have ANY 665 alleles (TT, CT or CC) you need to have active riboflavin as FAD for the enzyme to work. It is the riboflavin level that determines activity much more than your genetic status. This has been spoken on before on this forum, but it appears to have been disregarded..

          • Kelly says:

            Hi Madge,

            Please note that I was guessing, and I also said ‘it might not be true’.

            Anyway, interesting that they go to the trouble of putting the b12-oil in a darkened jar so it won’t be destroyed by light, but then how does it keep from being degraded once one puts it on their arms or wherever?

            Yes, folic acid helped reduce spina bifida by 30%. Makes one wonder if they had used folinic acid, might that number have doubled or tripled?

          • Madge says:

            Hi Kelly,
            I too was concerned about the light sensitivity, and many people who inject with methyl keep their syringes wrapped in foil. When I contacted them, they said that they were very aware of the light sensitivity issue and hence this restricted the way they could deliver the product. Apparently in the concentrated solution, they have kept is exposed to light for over a month with no sign of formation of hydroxycobalamin. So it seems to work. When you rub it on the skin, it is only in light for about 15 seconds, and it rapidly goes in the skin. I wouldn’t put it on in bright sun-light though.

            Don’t think folinic would have made any difference, apparently B12 deficiency is just as big a contributor to poor neuronal development as folate deficiency. You can understand why when you see how important it is for the two to interact during methyl -swapping via MTR. Most women’s levels of B12 drop significantly during gestation, then even more so when they breast-feed.

          • Donna says:

            Hi Kelly,

            We have a very complex condition and many doctors do not have training, but this should start changing if we can bring this website to their attention which I have already given to my PCP. My Endocrinologist has some knowledge, but I need to point out the niacin dosage that he prescribed me. I am seeing a Cardiologist today because I have a very strong family history with heart disorders and a cousin who had a major stroke 12 years ago and it was tied into MTHFR (which I only just found out).

            I agree about the folic acid and neural tube defects. We have a lot of room for improvement with synthetic and GMO products along with our chemical ridden environment that is poisoning us. We need to all step up and do a small part to help fix the big picture.

            Let’s all be positive for each other while we begin to heal and bring this condition to the conversation with everyone we know.

          • Donna says:

            Hi Madge,

            I feel like you are talking with a lot of words and I don’t know enough to be able to comprehend. Dr. Ben Lynch has gone to great lengths to speak in layman’s terms for those of us who don’t hold medical degrees.

            Why don’t you explain who and what you are all about (doctor, nurse, patient) so we can understand your purpose on this site other than trying to undermine the positive support we get from others with our conditions? You shouldn’t feel offended if your intentions are positive.

            I would still like Dr. Ben Lynch give us a comment regarding your concerns of this site. I really don’t see how or why you have so much to say to so many bloggers. We are all trying to heal and don’t need confusion added to an already complex subject.

          • Madge says:

            Dealing with vitamin B12 deficiency is a very hard thing to do, and trying to get one’s head around the concepts of MTHFR, etc, etc, are also very hard, very complex, and very confusing. Because of this there are lots of posts that I see where people have either misunderstood the concepts, have got the concepts wrong or where people have almost been hysterical about their genetics and the implications, where they don’t need to be. I have read so many publications now on many of the concepts and believe I have a much better understanding than most people on the site. In my own little way I am trying to help sort out this area and summarize some of this literature, so hopefully it will help people sort the wheat (of which little appears) from the chaff (much of it). B12 deficiency can be devastating to many people and potentially 20% of the population is deficient.
            I always find it curious though, that even the best intentions can be harshly dealt with. It kind of makes you wonder where humanity is going.
            Many people who post on this site have paid hundreds if not thousands of dollars to have their data analysed and yet have not got better. Many of these same people are on thousands of dollars of needless supplements, that if they really knew what they did they probably wouldn’t use.
            If I can help even one person to overcome this minefield of mis-information then I feel that I have made a contribution. It does seem worthwhile, don’t you think?

          • Donna says:

            Hi Madge,

            I agree this is very confusing. Can you tell me why you are so interested and what your educational background is? One must have some type of connection to be interested in this subject.

            I want to be open minded and learn as much as I can. Where did you first start researching so I could possibly start there as well. Since I need to dig myself out of this hole of deficiency, I too want to learn and educate myself as much as possible.

            Thank you for being candid!

          • Madge says:

            Hi Donna, I have a degree in Biochemistry and find enzymes and enzymes kinetics curiously interesting.Also have done quite a bit of cloning and mol Biol. My mum went nuts (B12 deficiency) and I don’t want to go that way. My sister is almost certainly going to get diabetes and go the same way.
            In this world if you don’t learn about your disease you are at the mercy of others. It shouldn’t be this way, but it is. Just trying to help.
            You can find most of the science on a standard PubMed search, the biochemistry is in any standard text-book. The gene/allele frequencies seem to be being updated on SNPedia. I gather that it may be linked to the data being generated at 23andme, but I don’t know, so don’t quote me on it. SNPedia gives you a country and ethnicity break-down on gene frequencies. When you read any publication on MTHFR effects, you have to be very careful of the country of origin, as many countries don’t supplement with folate. Most of the supposed effects of MTHFR and other alleles go away if there is supplementation. Not sure about the riboflavin though, as most don’t look at it. It is very important for MTHFR, MTRR, MAO, DAO, GR and NOS, though. Studies with B12 supplementation generally use cyanocobalamin, so they should be viewed with a high degree of skepticism, particularly if they do the genetics or riboflavin status, which almost all don’t. If you find anything interesting please share it with the group. Hopefully you won’t get the same reception I had. I’m Shattered…

          • Robert says:


            I’m not sure what you mean when you say you’re shattered. No one has attacked you, no one has insulted you. It seems to me that people are just disagreeing with you. Don’t you think that’s fair, or do you not believe in freedom of speech?

            There are a lot of internet ‘experts’. I think it’s reasonable and important that people ask about your credentials, and even then, they should question those, as you, and I, and everyone here are just anonymous ‘voices’ on the web.

          • Lynn_M says:

            Robert and Donna,

            I do feel that Donna’s comments to Madge were an ad hominem attack. I thought her tone was ugly. And then she had the audacity to say “we should all be positive for each other”.

            Why should Donna insist on knowing what Madge’s credentials were, if she was a doctor or nurse, and what Madge’s purpose on this site was? Madge never represented herself as a doctor, and I think we ought to assume no one is a doctor, unless they’ve identified themselves as such.

            Anyone reading enough comments on this site ought to know how badly the medical community misunderstands and mistreats MTHFR related issues. I would take the advice of a well-informed patient any day over someone that might just have some credentials after their name. Patients have a self-interest in digging into this material – it’s our life that is on the line. Credentials usually mean someone was trained one or more decades ago, before this new age of epigenetics. It doesn’t take a MD, DO, ND, DC, or PhD to be able to read medical journals and understand this stuff.

            What would have been fair would be if Donna had raised questions about the specific information that Madge was giving, instead of invoking the name of Dr. Lynch to police Madge’s comments. No one gave an argument about the science of what Madge was saying. The science should be the subject of discussion. It is fair game to disagree with someone’s interpretation of the science, and its consequences, but I say leave it at that.

            I got roiled up by the Donna-Madge dialogue because I used to comment very heavily on this forum and I can identify with Madge. After my test showed MTHFR A12998C +/+ 3-4 years ago, I devoured this site. I was a zoology major in college, have an interest in nutrition and medicine, and can understand journal articles. If I thought I could make a contribution, I responded to comments. That took a lot of time. I fell down some stairs in November 2012 and was away from home and computer for a couple months while my fx right arm and lacerated left thumb healed. After that I realized I had been spending too much time responding to comments and only rarely comment now. I was fortunate in that I was never hectored the way Madge was. I would change some of my responses now, given that I’ve learned more. But then Dr. Lynch has made changes in his approach too. We all need to learn together, with good will.

          • Caroline says:

            I for one appreciate Madge’s comments and agree with Lynn M’s assessment of the situation. Carry on Madge, don’t listen to these jerks. You are trying to help people, they are whining about their problems hoping to get some free advice from Dr. Lynch and questioning the motives of those who offer information. If the only person they want advice from is Dr. Lynch then they should make an appointment with him. You’re a rockstar Madge, thanks for all the information you have shared with us.

          • Dr Lynch says:

            I am going to chime in here.

            I believe it is useful to have other people offer their ideas and thoughts about health here as long as it is constructive, supportive and cited with either personal experience or research.

            No one has all the answers.

            If we collaborate and share our thoughts/opinions, they support everything we are trying to do – and that is obtain and maintain health.

            Keep in mind that some people may not be performing at their best while commenting- due to feeling bad or stress or whathaveyou. Do try to see past that.

            In the event someone is constantly being negative or promoting something out of a conflict of interest, then they will be banned/blocked from commenting.

            I am fine with people discussing what they take, what doctors they see, what works for them and doesnt work for them.

            We must keep in mind what works for one person may be poison for another. Freddd is a perfect example. His case is unique and he needs to understand that. He has rescued himself which is amazing but he also needs to realize that it is his biochemistry – not everyone else’s.

            Health is tough to maintain – hard enough without having to deal with negativity.

            Thank you all for keeping it constructive here.

          • Robert says:

            Thank you Dr. Lynch for ‘chiming in’. I appreciate it, especially this:

            “Keep in mind that some people may not be performing at their best while commenting- due to feeling bad or stress or whathaveyou. Do try to see past that.”

            I’m definitely not performing at my best, and can say outright that that’s perhaps why I can be a little too blunt at times. Or maybe way too blunt. I’ll try to remember that in the future.

            Three or four years ago, I was going downhill, but could still walk. Then I got my methylation results back, and my doctor at the time proceeded to prescribe multiple methylation supplements (including one with folic acid in it!). I had a bad reaction, so I backed off them. I was broke, (on medicaid), so I turned to the CFS community, and found Rich, Freddd, Yasko, Heartfixer, etc., and was overwhelmed by the complexity.

            Rich was very kind and analyzed my test results, explaining that I was using my own muscle for fuel, and not using fats or carbs very well either. I could never get a clear explanation as to what was causing this block in the krebs cycle, except for possible heavy metals, which I’ve tried to address, but not successfully.

            Freddd seemed to be the most vocal, the most active ‘poster’ and had the most dramatic recovery, so I guess out of desperation I turned to him for advice. I know that I have to take the ultimate responsibility, but as noted above in my reply to Lynn, my reactions became severe. Maybe he didn’t understand them from his perspective and personal history, but still said I needed to push through these reactions.

            The reactions I had left me so shell shocked that it scared me off of trying any sort of methylation supplements for almost a year, and then, along with some very conflicting and in my opinion, odd recommendations from the Yasko/Heartfixer sites (where they say to avoid sulfate), left me in a state of total confusion and panic.

            Now three years later I’ve so much muscle in my legs that I can hardly walk (I use my mother’s old wheelchair just to get my mail), and left me housebound in a low-income apartment that’s right across the hallway from a laundry room that shoots out chemicals from air “freshners” and laundry softeners. I’ve been experiencing increasing allergies to those (I think) and possibly to the carpeting that covers half my apartment.

            But worst of all, this overall reaction to methylation has also convinced my family that methylation is dangerous and so they won’t help out so that I can move forward. They can’t explain why I’ve lost muscle, can’t take a shower, etc., but won’t help out. Friends who used to help are also not responding.

            I’m too fried, I’m too stressed now to beg for any more donations, so I guess my fate is sealed. Or at least it feels like it. Anyway, maybe it will serve as a warning to others to question everything, and ask for references when possible.

            But thank you for all your work, and I guess if I have this opportunity to ask you, I would hope that if you have some time, you might considering doing a page or a video on both the CBS mutation (and sulfur/sulfate) controversy, and also might comment on the study with CFS patients where they used folinic acid and found that 80% improved.

          • Robert says:

            Hi Lynn,

            An ad hominem attack is defined as responding to arguments by attacking a person’s character. I don’t see where Donna has done this.

            You said: “What would have been fair would be if Donna had raised questions about the specific information that Madge was giving…”

            If you’ll read the previous posts, that’s exactly what she did. Donna was quite polite, and only asked questions about Madge’s affiliations and education, after noticing that Madge keeps recommending “b12oils” as the place to get B12 — from a website that has been in registered for less than a year. Makes one wonder how long they’ve been in business and how much experience they have, compared with Dr. Lynch and others.

            Also, in her November 11th post above Madge suggested that folic acid is okay to use, but it’s use is misunderstood. That goes against all advice given for those with MTHFR and other mutations.

            I used to be like you and Madge — telling people what they should take and how often, as I was doing so much better than most patients with CFS — that is until my health took a nosedive. I guess that’s why I chimed in to ask Madge some questions. I don’t think in general that we have any business telling people what they should take or do, unless we’ve recovered substantially and stayed well. Even then, it’s a risky proposition, as we don’t know the whole picture of the person asking the questions.

            You have been polite and knowledgeable with your answers in general, but I’ve noticed errors when referring people to the infamous “Freddd” for advice, and also suggesting that Rich Van K only started recommending methylcobalamin in 2012. He’s been recommending it since at least 2009. He told me that my main issue was a lack of methylfolate in September of 2010.

            But again, I’ve done the same thing, so I’m not ‘attacking’ you — I’m suggesting that it is in fact, sometimes risky for patients to give out advice to other patients.

          • Lynn_M says:


            It appears to me that Madge’s motivation for posting here was questioned and it was impugned that Dr. Lynch needed to censor her. We have a difference of opinion about whether that constituted a character attack. Let’s leave it at that.

            Regarding my point about raising questions about the specific information Madge was giving out. You or Donna could have asked Madge the questions you raise in your reply to me about b12oils. You or Donna could have asked for a more expanded explanation of her position that folic acid is okay to use. Just because something goes against the advice usually given to MTHFR patients doesn’t mean there may not be some added complexity or viewpoint that should be discussed. Maybe someone with a background in biochemistry has information we should consider or ask about.

            Rich Van K.’s protocol for people with CFS/ME started out with the recommendation to use hydroxycobalamin, based on Dr. Yasko’s work and on the advantage of hydroxyB12 allowing some metabolic control over the amount of conversion to methylB12, as he saw it. Freddd strongly disagree, and I think discussions with Freddd tempered Rich Van K.’s recommendations so that he included methylB12 as well, depending on the patient. However, recommendations that Rich Van K. made to particular individuals may have differed from the general recommendations in his protocol. As for the question of dates you mention, at this point it’s been a few years and I don’t remember, but I find it curious that you think that minutia is relevant to this discussion now.

            Also, I’m not sure if you think my errors that you refer to were that I recommended that people read Phoenix Rising and read about Freddd’s advice, or if stated incorrect facts. I think many of the discussions at PR get into more complexity and sophistication than at this website and that it is a worthwhile resource. I also think Freddd’s recovery is remarkable and should be an inspiration to many. Since you say the infamous Freddd, it appears your opinion of him is lesser than mine. So be it.

            I don’t think it’s risky for patients to give out advice to other patients. I think it may be risky for patients to adhere to advice given out by other patients. It can also be risky for patients to adhere to advice given out by their doctors. Many people seemed to be appreciative of my comments. Even Dr. Lynch left me some nice comments. We will disagree about the merits of advice giving as well.

          • Robert says:

            Hi Lynn,

            Perhaps I was too harsh, so I apologize if I came off that way. And maybe I was nit-picking when it came to pointing out a couple errors, as we all make them, and so that was probably not called for. I have indeed noticed that Dr. Lynch has found your comments helpful. 🙂

            I think going forward, it would be helpful, say if one is referring to Freddd, or recommending his approach, to also point out that everyone is different, and that many have had bad reactions to his protocol.

            Yes, I did describe him as ‘infamous’, and maybe that was harsh as well, but I did so because although he has indeed softened his approach in the last year — for years, if someone had a bad reaction to his high-dose methylolate recommendations, he would basically tell them to push right through — that the reactions were an indication that they needed the methylfolate, or mb-12. For me, and many others, that was dangerous advice. The agitation, anxiety and irritability nearly drove me to suicide, and I know many others who also had severe reactions as well.

            I understand that because it worked for him so dramatically, that he would want to get this information out there to everyone else. I’m sure he’s a very nice man, and has the best of intentions. But again, up until about a year ago, he was insistent that his way was ‘the’ way, even to the point of subtly dissing the work of Rich Van Konynenburg after Rich passed away — a man who was trying to help him understand his unique situation, suggesting he may have a polymorphism in the MTHFS gene (which might explain Freddd’s intolerance to food folate, which started only 2 or so years ago.

            He still tells people that their reactions to methylfolate could be due to what he calls a ‘paradoxical folate deficiency’, which again, I believe is dangerous advice. He also says it could be due to a lack of potassium, which makes more sense to me, but again, until recently, rarely has he said one should start with lower doses.

            Freddd also suggests that angular chelitis is solely a symptom of folate deficiency, when in fact it can be a symptom of insufficient riboflavin and other b-vitamins.

            Anyway, I just think that when advice is given, that one needs to make sure they point out that everyone is different — different genetics, different exposures, toxins — and so what works for one person may not be safe or beneficial for someone else.

          • Lynn_M says:


            I think Dr. Lynch wrote just the right response and I don’t want to change that tone. I accept your apology, although I think of our dialogue as basically just expressing our differences of opinion.

            The more I’ve learned the last few years, the more humble I feel about thinking anybody in particular, including most especially myself, knows the best answers. I’ve been listening to the presentations of 3 summits over the last 2 weeks: the Digestion Sessions, the Anxiety Summit, and the Autoimmune Summit. A number of times I heard the experts say something that that I had heard other experts previously contradict. That wasn’t such a surprise. What was the surprise and the bonus for me was to hear brand new material and new lines of thinking. For example, Dr. Datis Kharrazian talked about the gut-brain axis, and he said many ailments that most people consider to be strictly gut issues actually can be attributed to bad brain function as the initiating factor. He gave some simple exercises to help retrain the brain. He also has a youtube video titled after his latest book, “Why Isn’t My Brain Working”. Mike Mutzel, author of The Belly Fat Effect, had some fascinating insights into the impacts of gut biome. I intend to get both of those books. Dr. Lynch has recommended Dr. Bruce Lipton’s work, The Biology of Belief, which I had read when it first came out. I think these types of approaches offer the best hope for health.

            When commenters here share their long litany of medical ailments, such as Heather above, and can’t find any solutions, I’m thinking that maybe a possible solution for them would be to explore these out-of-the-box types of approaches.

            As for the type of disclaimers you propose, such as pointing out that everyone is different, etc., or others stating that they are not a medical professional, I disagree with you yet again. I find reading those generic kinds of statements to be tiresome. If a person is aware of a particular danger or reaction, that would be a different story.

            As forum participants, I think we need to be responsible for what we do with any advice we see here. Anyone looking for health answers on a forum such as this needs to understand these limitations are inherent. And also understand that the field of methylation treatment is new, and that therapeutic recommendations are still evolving.

            I don’t believe I told anyone to blindly follow Freddd’s protocol. I repeated Freddd’s thoughts and directed them to look at Phoenix Rising, where there has been a lot of discussion on the merits of his protocol, good and bad. I prefer to direct people to resources, and then they have to do their own investigative work. Freddd was an out-of-the-box thinker. I will not say he was right about everything, but I think he stimulated new approaches. I wish he would do a 23andme test though.

            I’m sorry you had such ill effects from following his advice. I wonder how much of PR you had read first, though, and if you had seen the reports of people who initially couldn’t tolerate the high doses but had to gradually build up their dosing.

            Except for joint reactions to gluten, which took me 65 years to recognize, I’ve never had a negative reaction to anything, so I don’t have the same sensitivity as you do to the potential for negative reactions. My precautionary principal is to read all I can first about something. If you would counter that it is unrealistic to expect other people to do the same, I wouldn’t disagree with you on that point.

          • Donna says:

            Dear Lyn and Madge,

            I thought Madge responded back to me and we were fine. I did not mean to insult or hurt anyone’s feelings. I was just curious why she was directing business to the that website and what her experience has been either through education or experience. The website for B12Oils itself to me just didn’t feel right. I am entitled to my opinion.

            I am very comfortable with Seeking Health and that is where I choose to keep my business. All of this going back and forth about what I said is a little of board and we need to concentrate on healing.

            Sorry to anyone that I offended.


          • Lynn_M says:


            When I read the last two words of Madge’s response to you, which were “I’m shattered”, I didn’t think she was fine.

            I don’t know Madge. I know her name from seeing her posts on Chris Kresser’s B12 site. We do have one commonality – we both use the B12oils transdermal product – so I have a particular interest in her posts.

            I was one of the very first customers of the b12oils when it became commercially available in May 2013. Prior to commercial release, the developer had made reference to the product he was developing on Chris Kresser’s blog. I put some clues together, figured out who the developer was, and wrote to him. I was dissatisfied with using sublingual mB12. I have thin enamel, and I was concerned about the acid formulation of sublingual B12 etching my teeth. Also, my Spectracell micronutrient test showed I was deficient in B12 despite using the sublinguals. My MCV was in the mid 90s and my 24 hr. complete hormone test showed I was not making any methylated estrogen end products.

            About a month after I started daily use of the B12oils, I felt like my mood had brightened considerably and I was active again. I had an OAT test then, and the MMA part showed I was midpoint on their scale. I’ve used B12oils for 1 1/2 years and a few weeks ago I had more testing done. I get the results in 2 weeks.

            Although sublingual B12 is absorbed much better than oral, it still is pretty poorly absorbed. IM injections have a much higher absorption rate, but the B12 levels in the body peak and then decline rapidly. Many consider subcutaneous injections to be the best method, with the B12 released more slowly from the fat depots in the body. But I think we’d all prefer to avoid repetitive injections if we could.

            I’ve maintained communication with the developer and he’s explained the many trials it took to develop a transdermal product. B12 is a water-based product, but water-based products don’t pass through the skin because the skin is a lipid environment. He was able to develop nano-sized B12 water-based particles that are embedded in an oil base, which enable the B12 to pass through the skin, enter fat depots, and then get released into the blood stream as needed.

            I think Madge’s motivation to direct people to the B12oils website is that she found a product that worked for her and she wanted to help other people by letting them know about it. I feel the same way, although I was waiting to see how my test results turned out first. The developer said anecdotal reports have been very positive and there is a clinical trial currently being run on the B12oil. I hope at some point in time we might see a report comparing the efficacy of injectable, sublingual, and transdermal methods of B12 application.

            The developer is a biochemist with a very small company, and his lack of emphasis on marketing is reflected by the fairly plain website. I suggest going to, clicking on B12 Info in the header, and then clicking on the link for at the bottom of the page. That page has a lot of information about B12 deficiency written by the B12oils developer.

            I too believe Seeking Health has excellent products. But I think the new-kid-on-the-block B12 product might be kicking sublingual B12 down the road. We’ll see how the tests and trial turn out.

          • Dr Lynch says:

            Lynn –

            I invite you to try the Optimal Liposomal B12 with L-5-MTHF. The methylcobalamin and methylfolate are in liposomes which should absorb through the skin quite well.

            If you don’t feel any effect from it, simply call the office and ask for a refund. Do let me know your experience with it.

            We have a variety of liposomal products:
            – B12
            – methylfolate
            – glutathione
            – vitamin C
            – curcumin with resveratrol

            If people are not doing well with lozenges of B12, I believe that their glutathione levels are too low – at least one of the reasons.

            Thank you

          • Cyd says:

            Hi Dr. Lynch,

            That Liposomal B12 that you just mentioned to Lynn, do you think it could help me?

            My B12 levels are off the chart high in the blood at times and extremely low at others. My grandmother had pernicious anemia and I was diagnosed with it years ago, when I had huge RBCs. However, my latest doctor doesn’t agree since my blood levels were fine, so we discontinued the shots a long time ago.

            Recently, I went elsewhere and had the Spectracell test done (inside the cells) and the result was a functional B12 deficiency (<14) and a borderline folate reading (probably because I supplement with folate). None of the pharmacies will fill the prescription for the B12 shots (because there's a new stricter, very expensive certification they would have to get in order to make it), so I'm looking for anything that will help. I don't want the neurological damage I was starting to see in the past.

            In case it's pertinent, I'm compound heterozygous, with a bunch of other compromise genes on your chart.

            Thanks for your help,

  • Karen says:

    First of all, thank you so much for this website!! I’ve learned so much about why I’ve felt toxic, with a foggy brain for so many years!!

    I’ve recently been diagnosed with both C677T & A1298C. My doctor had me tested because I’m at a great weight and BMI, and I exercise regularly, yet my LDL and APO B are rising. We started began slowly with Methylated Folate and worked our way up in dosage, taking 10 mg for quite some time. He raised me to 15 mg because the brain fog and “toxic” feeling was better but not gone at 10mg. At 15 mg I am feeling great, EXCEPT for the extremely vivid dreams that keep me from getting a good nights sleep. One thing that no one could ever explain was that I could have one alcoholic drink and have a hangover the next day. Now I understand that my body was so toxic with Folic Acid that it couldn’t handle breaking down the alcohol (the same is true with taking pain pills)

    I am clear headed and my memory is so much better since beginning the protocol that my doctor has prescribed. If it weren’t for the vivid dreams I would be an extremely happy girl. Do you think that if I took a quarter of a tablet of Nicin before bed that it would help?

    I have to give a huge thank you to my doctor! What he didn’t know is that my daughter has had 6 pregnancies, 5 of which ended in miscarriage. We are excited and hopeful that her beginning to take Methylated Folate with allow her to have another child!

    In addition, my sister has an auto-immune disease called Interstistal Cystitis. She has the worst case her doctor has ever seen and is in constant pain to the point that she is on disability in her mid 40’s. We anxiously await to see if being on Methylfolate with help aleviate her symptoms! She’s only been taking it for a week.

    Any and all suggestions that would help me and my family are very much appreciated!


  • Deanna says:

    Thank you for your work!

    I am homozygous and heterozygous for a number of the methylation factors. I also struggle with hypothyroid, adrenal issues, and gut issues. I’ve been at work on all of this for over 2 years and nothing really seems to be improving. I am quiet irritable often, have odd blood sugar swings (despite eating a very clean diet quite low in carbs) and struggle with a lot of brain fog. Do you think that the methylb12, methyl folate, and sam-e I take could be contributing to any of this? Do you have any suggestions?

    • Dr Lynch says:

      Deanna –

      I would stop what you are taking now and discuss with your doctor about it.

      I would then consider:
      – Optimal Adrenal – 3 capsules with breakfast and 3 more around lunch ONLY IF you are stressed and anxious then. If not, just do in morning.
      – Adrenal Cortex – 1 capsule with breakfast and 1 more around lunch ONLY if you are tired.
      – Optimal Electrolyte – 1 scoop in a large glass of water and another one part way through the day.
      – Saccharomyces Boulardii – 2 capsules at night after dinner
      – Optimal Prenatal Protein Powder – 1/2 to 1 scoop in a smoothie in the AM to get your day started.

      – NADH + CoQ10 – 1/2 lozenge IMMEDIATELY upon waking – while you are in bed. Place under your tongue and allow it to dissolve. You should feel ready to get out of bed within about 5 minutes of doing this. It’s pretty amazing. Don’t overdo it. Don’t use it as a crutch. Use it when really tired and experiencing brain fog. It can clear both up right away. Also do not take more. It is a powerful combination of nutrients. If you feel nothing with 1/2 lozenge, then use the full lozenge. I never exceed 1 at a time.

      If eating low carb, be sure you are replacing it with either some protein and healthy forms of fat. Avocado, coconut oil, nuts/seeds, healthy grass fed meats, organic eggs, goat milk

      These nutrients should work quite well for you.

      Make sure you are eating more frequently – and the adrenal support will help balance your blood sugars – and so will the protein powder.

      All may be found at – which is my company. All the above supplements are designed and formulated by me and produced in a FDA approved manufacturing facility.

      • Deanna says:

        Thank you so much for taking the time to reply, Dr Ben! It is greatly appreciated.

        I’m curious about why you would suggest stopping the methylation supplements I’m on (methylb12, methylfolate and sam-e).

        Also, I found out today that I am officially in the 24% of the population sensitive to mold and have blood markers to show I likely have biotoxin illness. In that case, would any of your recommendations change or would you add anything? I will likely soon be starting cholestremine to help get the mold toxins out. It seems the methylation supps would be important during that time. Do you think the protein powder you suggested has what I need to replace those?
        Thank you!

        • Kelly says:

          Hi Deanna,

          I’m not sure if you follow Damien Blenkinsopp’s blog, but he’s recovering from mold toxicity, and reading one of his comments from 3 months ago indicates that he believes the dealing with methylation (epigenetics) is the ultimate answer to lasting recovery.

          Here is a quote from his comment on his blog:

          ” I believe ‘biotoxin illness’ is “epigenetic”, and that is where my most recent approach has been focused – which seems to be working out (I won’t talk about it until I’m sure though). So in my world, biotoxin illness is an epigenetic shift that just needs to be corrected back to the norm. A recent CFS epigenetic study showed large shifts in the epigenetic expression of genes for for the immune system compared to controls.

          That means that in order to eliminate sensitivity to mold/ mycotoxins, and eliminate any need for avoidance, you need to flip your epigenetics back. I’m not the first to think this, and have spoken with others who have completely recovered who believe this is what happened.”

          Here’s a link to the post:

  • Kay says:

    I was diagnosed with MTHFR A1298c HomozygousA two copies. What does this mean and what supplements should I be taking and how much.

  • Diana says:

    I have multiple family members with the MTFHR mutation. I have not yet been tested. I have had two miscarriages and feel terrible all the time. My sister insists i get tested and thinks this is the reason for my problems. I take a prenatal multi vitamin with 800mcg of Folic Acid, will it benefit me or hurt me to take Methylfolate along with this multivitamin until i can get to the doc and get tested? I have no idea about this mutation but do want to get it under control if I have it.

    • Madge says:

      Hi Donna, talk to the people at . They will look at your snps adn let you know the best way.

    • Kelly says:

      Shoot — I made a mistake — meant to reply to Diana, but replied to Donna instead.

      Diana — Dr. Lynch would definitely advise you to stop any sort of supplement or food that has synthetic ‘folic acid’ in it, as it will block methylfolate and/or folinic acid — the natural forms of folate.

      Watch Dr. Lynch’s videos on youtube — he’ll explain it there. Especially his “Introduction to MTHFR” video.

      No folic acid — it’s helping cause all these problems — because it’s synthetic and cannot be broken down by those of us with MTHFR mutations.

  • Leslie says:

    I am one if those people who has never had a negative side effect from Deplin. In fact, Deplin seemed to cure all of the symptoms I’ve had throughout my life. I recently read on this site about the consequences of taking too much Deplin and now I’m concerned about my health. My doctor doesn’t seem to be concerned. I have not supplemented with anything else such as B12, etc. Should I consider supplementing or tapering off Deplin? By the way, I am homozygyous MTHFE C677T.

    • Lynn_M says:


      From what I’ve read of other people’s comments, if Deplin was causing any negative effects, it would be obvious to you. The clinical trials that were run on Deplin supported the doses that are being used now. If you’re feeling well, I don’t see any reason to taper off Deplin. But I do think you should think about supplementing with B12, because taking just methylfolate without B12 can lead to methyl trapping.

      I think many people leaving comments on this site focus too much on their MTHFR mutations as being the all-cause explanation for their ills, ignoring their other methylation polymorphisms, their non-methylation SNPs, their diet, their supplements, their ability to absorb nutrition, and their emotional and spiritual health. We are such complex beings, and all those other factors will impact a person’s reaction to methylfolate probably as much as their MTHFR status.

  • gretchen says:

    Can too much methyl folate cause joint pain and stiffness? Have had joint pain and stiffness in my thumb for about 2 months, around the time I began to take methyl folate. I take 250 mg. of time release niacin twice a day and about 750 mcg of 5mthf / day.

    • Dr Lynch says:

      Gretchen –

      If you stop taking the MTHF and the joint pain goes away after some time – say 2 weeks – or with Niacin should be faster – then it could be related to the joint pain and stiffness.

      Methylfolate increases nitric oxide which can turn into peroxynitrite.

      Key to reducing those free radicals/reactive oxygen species is to ensure your SOD and glutathione levels are adequate – and arginine levels balanced – not high and not low.

      Also potassium/electrolytes are very important.

      I need to update this as a big supporter to reduce side effects from methylfolate.


      With your doctor’s permission, consider:
      Optimal Electrolyte – 1 to 2 scoops daily
      – stop methylfolate
      – maintain niacin
      Optimal Liposomal Glutathione – start LOW – say 1/4 tsp away from food – about 20 min before dinner or so.
      – apply castor oil to your thumb on the skin/topically daily/nightly
      – do contrast hydrotherapy on your thumb – alternating hot/cold. Google how to do it or watch youtube videos. It’s easy.

      One thing I just noticed – is typically if joint pain/stiffness with methylfolate is systemic – ie. whole body – not a local area.

      It may – in this case – be coincidence – but it also may not be.

      We all respond differently.

  • Kathleen says:

    In reading the latest thread on B12/Folate supplementation and the seeming cloud suspicion over this subject in this thread… I can attest that I took the plunge and ordered the B12oils after reading others positive comments on Dr. Carol Savage’s MTHFR FB about B12oils. I like the product and would definitely re-order. I have fatigue and I am very sensitive to time zone changes. I attended a class on EST, which is 3 hours time change for me. Normally I would be barely awake in such a situation, and in the afternoon of the class I was hitting a low point in my energy. Not believing that the oils would really do much, I applied them anyways. It made a significant difference and I was able to stay alert during that period of time that I would have had a very hard time staying awake, even nodding off. If you WANT to take a nap, don’t apply these oils beforehand. I did this recently and was kind of bummed that I couldn’t take a catnap. The customer service at B12 oils is excellent. I purchased the methyl/andeno (sp?) B12 combo and the B Group canister. That said, I also got figured out what dosage to take of Dr. Lynch’s Active B12 with L-5-MTHF – I take 1/2 in the morning and 1/2 late day. However, since I have the oils, I only take 1/2 the B12 with L-5-MTHF if I missed applying the oils in the late afternoon. Also, important – if you use the B12 Methyl oils, you must supplement with L5-MTHF. With the oils I take 1/2 of Dr. Lynch’s L-5-MTHF (without the B12). All above L-5-MTHF with and without B12 is use the lozenges. This dosage (above) has been perfect for me. I just hope that it’s enough. How do we know if we need to increase dosage or if what we are doing is enough? I am C677T hetero with all kinds of COMT, CBS, etc. mutations.

    I’ve heard a lot about the Organic Acid Test and hope to get that done in the future. This shows where your nutrient levels are and, therefore, used as a guide when choosing supplements if you are a DIY’er, like I am.

  • Anna B says:

    Hi there – thanks so much for your website – it’s been very helpful in improving my understanding of supplementation to deal with mthfr. I can’t answer your questions because I have just begun supplementation at low levels which will allow me to titrate up. But I have had problems with depression for about 30 years and of late had problems with fatigue, so I think I have found some pieces of the puzzle of these illnesses in looking at MTHFR – I believe that my most recent problems with fatigue has been caused by taking lamictal (which I have been taking for close to five years) – I learned that this can interfere with folate. So I suspect that I have a MTHFR mutation that has lead to problems with depression and fatigue. I haven’t been tested yet, but I hope to have the test soon. Anyway – my question to you is related to folic acid. I suspect that I am unable to convert folic acid and that it may be problematic for me to contain foods or supplements containing it (too bad I learned this so late in life – I’m 49 – but better late than never!). So it sounds like if you can’t convert folic acid the levels increase in your blood causing potential problems (I’ve found some articles on the web that propose a link to cancer – not sure documented this is?). Sorry for the long build up, but my actual question is – how long does the folic acid hang around in your blood – or how does the body get rid of this excess folic acid (in the blood?) – how long does it take. Just curious, haven’t found anything on the web on this. Again, really appreciate your website. I have a feeling that I will be prescribed Deplin at some point, so it is good to know about potential side effects from it … given that my psy-docs haven’t been very helpful in terms of providing information on potential side effects of drugs (e.g. lamictal), I am trying to learn as much as possible on my own.

  • Barb says:

    Dr. Lynch,

    Both my chilldren have been diagnosed with Heterozygous 677 / Heterozygous 1298. My oldest son (5 years old) was directed to take Deplin 7.5. which he has been on for a year. After the first 30 days of being on Deplin, we saw a huge improvement in the reduction of his aggression / physical behavior. My youngest son (3.5 years) was recently prescribed MTHF 5.0. from a different doctor. I asked why he would be prescribed a lower dosage than his brother when they both have the same mutations? She spoke with another doctor in the practice, who specializes in MTHFR/Predicitve Genomics and he suggested my 3.5 year should be on MTHF 5 twice a day. Both my boys are still struggling – neurotransmitters are still off. I am considering moving them both to MTHF 5, 2x daily to see if it helps, since the one doctor suggested it to our holistic pediatrician – do you see any issue with that dosage given my sons age? Mutations?

    • Madge says:

      Hi Barb,
      Don’t worry about your children being heterozygous for 677 and 1298, technically it is the normal condition (ie the most common genetics). Also don’t worry about spending the extra money on 5MTHF, folic acid (folate is fine) you are just wasting your money getting the more expensive material. If you are having problems with the children it is quite likely that they are either riboflavin deficient, and or B12 deficient. The change that you saw in behaviour would also have happened with folate. You do need to make sure that they have enough vitamin B12 though. Do you have any other genetics that you could share?

      • Lynn_M says:


        Given that the accepted wisdom in the MTHFR community that folic acid is not fine, and that Dr. Lynch, the host of this site, gets vitriolic when someone suggests that folic acid is fine for MTHFRers, I think you owe it to Dr. Lynch and the participants here to elaborate in great detail the excruciating biochemical details as to why you think folic acid and MTHF are functionally equivalent in our bodies. You must have good reasons for maintaining that stance, given that it has previously evoked fireworks here. You’ve given a short version of your thinking in a prior post, but I think more details are needed if you want us to see any merit in your tenet that folic acid is okay.

        • Robert says:

          I’m in complete agreement with you Lynn. Madge is giving “advice” with nothing to back it up, advice that is dangerous and goes against everything Dr. Lynch has been trying to explain over the last few years.

          In fact, he just did an interview the other day with Sean Croxton, where he makes this point several times, especially in the last 1/3rd of the interview:


          • Madge says:

            Hi Lynn, I didn’t understand this for ages, and I too believed this hype, until I had a chat to Greg. He said that the issue here that appears to be mis-understood is that everyone assumes that in the natural cycling of folate, that the methyl group in the folate cycle comes from 5MTHF. In fact if people only looked at the cycle, which has been provided on so many web-sites one will see that in the folate cycle (see the article Nijhout H F et al. J. Biol. Chem. 2004;279:55008-55016), which one could argue starts at THF (as it does in that article), the methyl group is actually added in by SHMT, so the methyl group comes from the end of serine, and goes to convert THF to 5,10-CH2-THF. Normally this functional group is modified in the folate cycle by thymidilate synthase, and by MTCH. Now if SAM is low, the methylene group is converted to a methyl group by MTHFR to form 5MTHF, and then the folate returns to the folate cycle as THF. In the process the methyl group is lost from the folate cycle and goes onto provide the methyl group on SAMe. Now in the perfect world this cycling can happen infinitely as long as all the enzymes and co-factors are present. Theoretically you would only need one molecule of folate, but you would need lots and lots of serine. That is no problem as serine is a non-essential amino acid and so you make it in your body. Given that so many sites actually provide the methylation chemistry diagrams it appears a bit incongruous that no-one actually appears to “read” the cycles. People should also realize that the introduction of the methyl group by SHMT is not at all dependent upon MTHFR status, but rather the SHMT genetics. I am not sure why it took me so long to realize this as the biochemistry is actually pretty simple. Further to this, it therefore doesn’t matter where the initial folate comes from that makes THF, what is more is that in the absence of methyl B12, folate will work to prime the folate cycle, whereas 5MTHF will not.

          • Greg says:

            Bravo Madge, a very good explanation, hopefully most people will understand. There is quite a nice picture of the chemistry at You can see the methyl group clearly outlined in red. Technically it is not a methyl group CH3, until it appears on 5MTHF, but at least you can see where it came from. You are also right about the cycllng of folate and it shows you just how smart the body is to be able to gain the group from the so common amino acid serine, which is a non-essential amino acid. In the best of all possible worlds you could make kilograms of methyl groups from one single folate molecule using the cycle. In contrast you would need multi-kilos of 5MTHF to provide the methyl group for SAMe if you didn’t use the folate cycle to “get” the group..

          • Marcia says:

            Madge and Greg: I guess you’re assuming that no one has SHMT mutations…

          • Greg says:

            Hi Marcia, No I am not assuming that no-one has mutations in either gene. The SNPedia data suggests that depending upon where you come from the incidence of +/- is around 10-50% of the population, with the frequency of the +/+ being 0-25% depending upon population. In preliminary data the incidence of +/+ is slightly higher in CFS and ASD, suggesting that it may have some effect, although it is certainly not a pre-condition for the condition. A greater effect though would be in persons who are vitamin B6 and B2 deficient, as the enzyme needs P5P. You could day though that it is a fairly critical enzyme in the whole folate cycle and therefore will have an ultimate effect on production of methyl groups from SAMe. Remember even in +/+ individuals the enzyme can still work, given enough folate, but the activity drops off dramatically if you don’t supply vitamin B6, and hence also B2.

        • Michael_Dowdy says:

          Hello Lynn. Something that seems to be missing in information is exactly what isomer is created when snythetic folic acid is converted. Dr. Ben discusses the difference in isomers on this site. This is unquestionably important when it comes to bioavailibity. But what happens when the body sees different isomers of MTHF at the same time? Apparently excessive amounts of folate add to the risk for certain cancers. If you’ve read “Application A566” documents on food standards it’s acknowledged that 1 mg is the is the maximum daily adult tolerable amount of folate. I don’t know what authority determines the maximum daily tolerable amount and whether or not it applies to those with MTHFR mutations. I assume that includes both folic acid and 5-L MTHF calcium salt combined. I’m not positive on it being the combined amount but that would make sense to me. Madge is obviously highly informed and I hope she’s open for discussion without being “shattered” when questioned about her opinions and beliefs. I believe that natural sources are likely to be far superior to synthetic and I doubt that anyone would argue that point. Thank you so much for all of the studying you do. I especially appreciate you for mentioning the fact that “folate” is an umbrella term which includes “folic acid” also, something which will likely cause significant problems in the future. Respectfully, Michael M. Dowdy

          • Cyd says:

            Hi Michael,

            You’re so right on this issue with folate being interchangeable with folic acid (in the minds of most medical professionals.) Even when you get a doctor who gets it, they send you to a pharmacy that doesn’t understand the difference. I’ve had this happen at two compounding pharmacies. The prescription was specifically for methylfolate and both places were about to use folic acid. I was lucky to hear them refer to it as such, and question them.

            In the first case, they said my insurance wouldn’t cover the sublingual in the MF form, and so they sent me capsules. It was a combo pill with methylcobalamin, I was essentially taking the folate alone, since the B12 doesn’t do well in the stomach. I couldn’t understand why the pill was crashing me, but it makes sense, since the folate was probably getting through without the B12!

            After visiting my doctor again, they switched pharmacies. During the ordering of the prescription, the clerk referred to having to order some things to make it, and mentioned folic acid. When I talked with the pharmacist, they said they’d have to clear it with my insurance before giving me the methyl version.

            I’m still waiting…

            We really have to be our own advocates on this stuff.

      • Lawrence says:

        From everything I have read, including the US government’s website on the genetic data from population studies, being heterozygous for C677T and A1289T is certainly NOT “technically… the normal condition… the most common genetics” (quoted from the above post of “Madge” on November 23, 2014).

        Granted, I last studied this in minute detail 2 years ago, after I personally was diagnosed with being compound heterozygous myself, and maybe something has happened in our understanding of C677T and A1289T in the last 2 years, but I expect it hasn’t.

        The last I read, being compound heterozygous for these two snps is the second-worst outcome possible, of the logical combinations (the worst outcome being: being homozygous for C677T).

    • Kristen says:

      when you say your children are hetero for 1298, and hetero for 677 – are you saying they are compound, in that they each have one of both? or one has 677 and one has 1298?

      from everything I have read – and I have a great-nephew who is compound 677/1298 – that is the worst combination. worse than being homozygous for the others.

      keep in mind – each child is physiologically different. what works for one, may or may not work for the other.

    • Eve says:

      I actually find this very interesting. I am also compound hetero. Would this mean supplementing with B6 and B2 additionally, or the same as in b complex?

      • Greg says:

        Yes, supplement with both. You need to check your thyroid function as well. If your are hypothyroidic you can’t convert B2 to FAD/FMN. You also won’t then be able to make active B6. If you are hypothyroidic you have a 50% chance of being B12 deficient as well. Whilst your genetics has some effect, the major affect is nutritional deficiency. You possibly will get enough from a standard multivitamin (check), but you won’t be able to cure your B12 deficiency if you have it.

        • Eve says:

          Not sure if I am hypothyroidic. Don’t think so though. So you are saying if you are hypothyroidic and B12 deficient, then you can only maintain your current low B12 with vitamins but never increase it?

          • Greg says:

            Not quite Eve.
            It is relatively easy to supplement with most B group vitamins, regardless of whether you are deficient or not.
            What you have to be able to do though is to convert the vitamins such as vitamin B2, to its active form FMN and FAD. You need a correctly functioning thyroid to do this. So if you are low in energy you need to test thyroid function. If your thyroid function then supplementing will quickly get your levels up. Vitamin B12 deficiency is different though, as you have lost a massive amount of your stores. The problem you then have is to raise the levels back up and to restock your liver. Given that the transport system for B12 can only handle about 6 ug/day, you can see it will take a long time to restock 2-5 mg in the liver. When you then consider that you may be losing 4-6 ug per day, it is almost impossible to get your levels up via oral supplements, or sub-linguals. The most obvious example of this is in people with pernicious anemia. When their stocks are depleted, even the injection of 1-2 mg each and every month does not restore their levels in the liver. This is despite all of the material getting into the circulation following injection.

          • Eve says:

            Ah, I see. Thank you for taking the time to explain that! So work on your thyroid before trying to right a B12 deficiency otherwise your treading water. Thanks!

  • Roseann says:

    I am homozygous for C677 and have SNPS on each and every methylation-related gene, some of them homozygous. I have a rare autoimmune progressive demyelinating disease After I started 400mcg of L-5-MTHF and 400 mcg of methylcobalamin with 100 mg of Niacinamide (as well as other B vitamins in a complex), all my anxiety disappeared and I felt wonderful for a week to 10 days. Then I noticed increasingly painful neurological symptoms. I am eating only the following: 9 cups of non-starchy vegetables daily, wild Alaskan fish, grass-fed/ grass-finished bison and lamb, organic/free-range chicken, pure form of EV olive oil, avocado oil, and (sometimes) a tsp of coconut oil, as well as organic berries. I simply do not know where to turn and what to do at this point. Do I discontinue the methyl forms? Or decrease their usage? If my Neurologist sees that symptoms are returning she will state that the expensive IV medicine is not working for me (but it has been a miracle worker in halting the progression of the disease!) and then I am doomed to steroids (which I cannot take) and more pain and disability. Please help.

    • Dr Lynch says:

      Roseann –

      We see this in a number of patients who experience complex symptoms.

      Improvement and then flaring of symptoms.

      I am working hard on pin pointing all the possible causes why this occurs.

      At the moment, here is what I suggest WITH YOUR DOCTORS PERMISSION:
      – For now, stop the B12 and MTHF.

      – Remain on the Niacin but I would switch to Nicotinic acid – 50 mg as needed.

      Optimal Electrolyte: when supporting methylation, it allows cells to divide and work harder. When this happens, they use up more K and Mg and nutrients needed for mitochondria.

      Optimal Liposomal Glutathione: when providing B12 and low in glutathione, the B12 can get oxidized and actually end up shutting down the methylation cycle due to oxidative stress. Start low – 1/4 tsp.

      – There may be an interaction with your meds. You and your doctor need to evaluate that.

      – Test your RBC Fatty Acid levels – can use Doctors Data or whatever your lab recommends.

      Acetyl-L-Carnitine – 500 mg three times a day away from food

      SOD – you may have elevated levels of peroxynitrite due to higher levels of nitric oxide and superoxide – for various reasons. Taking SOD daily and possibly twice daily will lower these. Definitely have to take the Optimal Liposomal Gltutathione as well as SOD breaks down to hydrogen peroxide which glutathione eliminates.

      • Roseann says:

        I am ++ for C677 and have every single one of the other snps making MTHFR more severe, some of them homozygous. When I reported a week to 10 days of feeling terrific on a pure B-complex containing Metafolin and methylcobalamin, followed by increasing neurological symptoms (burning/stabbing pain, etc) you kindly suggested I stop both methyl forms. Thank you for this advice: just two days after stopping the methyl forms of Folate and B12, the neurological symptoms are almost gone… amazing! I ordered the items you recommended (SOD, Electolytes, Liposomal Glutathione, etc) and now very curious to see the positive effects. Question: Niacinamide (just250, 2x/day) has lessened my awful anxiety over the entire progressive demyelinating disease vs health insurance ceasing coverage for the IVig treatments which stop its progression. Do I definitely have to discontinue the Niacinamide?
        Thank you so much for all you do for all of us! Hope your Thanksgiving is a warm and happy one!

  • Kim O. says:

    I’m wondering if I’m experiencing ill effects of 5-MTHF (Quatrefolic) supplementation. I’m not sure exactly how much is in my supplement. I’ve been taking it for about 6ish weeks. Last week I got an upper respiratory/sinus virus. When I stood from the toilet (eyes closed), I got a horrendous vertigo and fell into the wall. Then yesterday I was awoken from sleep (supine) with a horrendous vertigo episode. And last night I was awoken twice with horrendous vertigo episodes. I got out of bed for one and was listing to the right as I walked. And when I woke up I felt mildly dizzy/lightheaded still. I can’t believe I’d still be experiencing this from the virus last week as I got a steroid injection. I’m compound hetero. Could these vertigo episodes be due to methylfolate?!

    • Dr Lynch says:

      Hi Kim –

      There are many reasons for vertigo.

      Please do follow up with your doctor on it – and it sounds like you are.

      Methylfolate may be increasing symptoms of vertigo if your nitric oxide levels are high and your electrolytes low.

      The recommendations in this article are very important:

      I would definitely consider:
      – Optimal Electrolyte
      – Adrenal Cortex

      However – a virus could also cause these things – especially if there is pressure in your auditory nerves caused from inflammation.

  • Kathleen says:

    Kim O.

    Sorry to hear about your vertigo. A chiropractor, whom also had vertigo, came up with a maneuver that works – go here to watch her video:


  • Cyd says:

    I have one each of the C677T and A1298C.

    Also have homogenous SNPs for MTRR (folate, B12), PEMT (folate), MTHFD1 (choline), GPX1 (glutathione), GSTP1 (glutathione), MAO-Bs, MTRR (B12), SOD2s, BHMT-08, CBS A13637G…

    and heterogenous on a bunch of other MTHFRs and MTHFS, as well as COMTs, ACAT1 (folate), CBS, MTR, MTRR, VDR…

    and a ton of others, both hetero and homo. I just listed those that seemed relevant.

    My functional medicine doctor put me on a combination of 3mg methylcobalamin and 1 mg methyfolate. I was supposed to get the sublingual, but the compounding pharmacy changed it to a capsule. It gives me many of the listed side effects in this post (irritability, sore muscles, anxiety, palpitations, sometimes headaches or trouble falling asleep.)
    I got your time-released Niacin but forgot there were special instructions. So I just read the bottle and took a whole one (probably way too much) with food. I had no flushing at all, but an hour or so later, I started to feel awful. Shaky, weak, achy, headachy. I will take a lower dose next time but right now I need to know how to quench the niacin.

    The Nutrahacker report advised against curcumin (which surprised me) due to SNPs on the CYP1A2 and MAO-A genes, but encouraged it for other SNPs. I find that a lot. Some things say to take methylfolate and methylcobalamin, and others say not to. What’s a body to do?

  • Kate Houston says:

    I have mutation heterozygous C677T Started 5-MTHF 1 mg. Constipation started and got worse. After 2 weeks LLMD raised to 5 mg which made things even more worse. So, now in the last 24 hours have stopped all together. Never had constipation like this before. I will stop for 1 week and start back with 1/2 capsule to see if things change.

    thanks so much for this info.

  • Katy Eagle says:

    I have 1 heterozygous mutation for MTHFR C677T. My naturopath put me on HomocysteineXPlus. I even tried the regular one without the “plus” because the side effects were so bad: lethargy, brain fog, irritability, low mood and the worst one is my desire to drink alcohol again, which I have stopped doing for a few months. Whenever I try HomocysteineX (or ANY large dose of B-12 especially) I have the urge to drink. My naturopath said I probably have low blood sugar and to eat small meals. This is B.S.. I was fine before I tried this. So I will instead follow your protocol on this website for the
    “one copy of C677T mutation” by using your Optimal Multivitamin. I will start out with two pills a day and see how that works. Otherwise, it’s not worth it.
    Thank you,

  • PF Anderson says:

    This isn’t exactly a side-effect, but more of a drug interaction. MTHFR issues run heavily in my family, but I’ll spare you the details for the whole family and focus on my son, who is heterozygous for the A1298c allele. We rarely give him methylfolate, but have found it helpful when he is particularly malnourished and fatigued.

    Last weekend, there was an error in his prescription for Ativan for conscious sedation, which resulted in an overdose. We were dealing with this at home, following instructions given by the doctor, who was out of town for the holiday. He was just not coming out of it, and after pushing fluids didn’t work (other than to wake him long enough to go to the bathroom), I decided to try giving him some methylfolate. The idea was that it might help him wake up, have a little more energy, and maybe help clear the drug from his system.

    After taking the methylfolate, his symptoms got much worse, and we ended up taking him into the Emergency Room, which probably should have happened sooner. Now, Ativan is supposed to peak in your body 2 hours after ingestion, and the symptom spike after methylfolate was at 10 hours. We were also in the ER for a while because the only known antagonist for an Ativan overdose is a drug that causes seizures (which also run in my family). So, we did not give him the antagonist, and just waited it out, monitoring vitals.

    I was puzzled why he would have a more severe second spike that long after ingestion, so when we got home from the hospital I did more digging. There is nothing I could find in the literature (either Pubmed or pharma reference sources) about an interaction between Ativan/Lorazepam and methylfolate, so you would think it would be fine. I looked at drug interactions, OTC interactions, food interactions, and vitamin interactions. That was when I finally had a clue that his reaction might be linked to the methylfolate. While cobalamin (B12) is not listed as an antagonist for Ativan, it is listed as something that interacts. What it does is lessen the impact of Ativan. As MTHFR folk, we know that cobalamin also lessens the impact of methylfolate. So, the question now, which evidently hasn’t been tested, is if methylfolate and Ativan might interact?

    • Greg says:

      Hi there, I presume from your statement about your son’s MTHFR status that you have had his genetics tested. Do you know what his MAO status is? Don’t worry about his heterozygous for the A1298c allele. The majority of the population has this, so that is not the problem. Can you also tell use whether he is eating milk, dairy and eggs, or whether you have been advised against it.

      • Michael_Dowdy says:

        Hello Greg. Once again, I would caution you about minimizing on MTHFR mutations. I know for an absolute fact that Dr. Ben Lynch is correct about the expression of the gene being of upmost importance. Methylation is a critical and pivotal area in cancer studies. As far as someone’s MAO status there’s finally online information out which shows that the GT allel is the one for major concern and it’s association to “Brunner Syndrome” in males. This is evolving and changing science / medicine and what is believed correct today might change by tomorrow so be careful in advice. After brain mapping studies are complete I’m pretty sure the reasons for the headaches associated with methylfolate use may be understood more clearly. Most of us are here to learn from each other’s personal experience and are keenly focused on Dr. Lynch’s expertise. Respectfully, Michael M. Dowdy

        • Roy says:

          Hi Michael, I have been following this argument for some time, and sitting on the side-lines it would appear that you are somewhat at odds with what Madge and Greg have said. I don’t think that at any stage either of them said that methylation was not important, in fact I don’t think you will get any argument to the contrary. Of course it is vitally important for production of carnitine, creatine, MBP, inactivation of neurotransmitter, etc, plus over 100 reactions. What is a puzzle though is that I have seen many times that people who are using 5MTHF and who have a reaction to it are told not to take the 5MTHF. Surely this is a huge contradiction. If it is so essential surely one shouldn’t stop it. I think that we all agree that methylation is also essential for turning on and off genes. As for the statement on mutations, technically both Greg and Madge were right. For many of the alleles the heterozygous condition is the average condition, or even has higher prevalence. Thus, as they have both stressed, people should not worry about having these genetics. More they should worry about being vitamin deficient. Given the huge number of different fad diets around, which take no notice of proper nutrition, no wonder people are having problems. The argument could be made though that this is not due to their genetics, but rather their nutrient deficiencies. Thus lack of certain vitamins means that many of their enzymes won’t work. I think that this may have been the point that both of them were trying to make. Thus it is more diet than genetics that is the problem.

          • Dr Lynch says:

            Roy –

            The genetics help identify if someone is predisposed to a nutrient deficiency – or a blocked from the ability to use it. Those who respond poorly to methylfolate and have MTHFR have other issues in play. Methylfolate is a powerful nutrient. If someone responds poorly to methylfolate, it doesn’t remove the fact that they could be or are deficient in it. It simply means they are not ready for it.

          • Michael_Dowdy says:

            It’s easy to get sidetracked from the purpose of discussing the side effects of methylfolate. Dr. Ben’s opinion and advice is why I watch this site. I do not believe Madge’s defense of folic acid is correct. I hope to learn why headaches are associated with the use of 5-L MTHF. The high doses of Metanx and Deplin puzzle me. I’m hoping to learn from this site why problems are coming along with the use of methylated B 9. I am a patient with high risk for embolisms. I’m open to discussion but not to argument.

          • Dr Lynch says:

            Michael –

            Methylfolate increases nitric oxide. Nitric oxide is a vasodilator. Increased blood flow can increase headaches.

            Nitric oxide – when combined with superoxide (due to SOD snps or low cofactors for SOD) – produce peroxynitrite which is wholly damaging and can cause all sorts of issues such as headaches.

            I discuss it more in detail here – in Preventing Methylfolate Side Effects – I just updated the article actually.

            There are other reasons as well – I don’t know all of them but I continue to suss them out.

            I think glutamate is another reason why people get headaches from methylfolate – which is part of the reason why niacin helps. If that is true, then B6 and magnesium should help as well.

          • Michael_Dowdy says:

            Hello Roy. I have two copies of the MTHFR 677CT mutation. So are you telling me that diet alone can likely take care of my ineffective digestion of protiens? I don’t like or eat dark leafy greens or beets, in fact I would likely vomit if I tried to eat them. I’ve been diagnosed with CFS. I had mononucleosis in 1985 which is believed to be a possible cause of my CFS. Do you believe it’s possible that I may be malnourished and fat at the same time because of my problem digesting proteins? Are you saying that my problems can be fixed by diet and that genetics are not the major reasons for my poor health and severe atherosclerosis throughout my circulatory system. Do you think my neuropathy is able to be reversed with diet? My oldest brother died at 54 yoa and he loved and ate lots of dark leafy greens and appeared to be in much better health than me. I think he probably had the same full blown MTHFR since my mother also has two copies of 677CT and my disceased father had to have had at least one copy for me to have 2 copies. The odds for my six siblings don’t look that great when it comes to their possibility of MTHFR mutations. As an infant and toddler I was seriously underweight for reasons not understood until now. Learning my genetic problems gave me a pretty solid understanding of some of my problems. So what do you think? More diet than genetics? Can I be fat and malnourished at the same time? How do I fix myself? Is it lack of vitamins why my body doesn’t make methylenetetrahydrofolate reductase enzymes? Respectfully, Michael M. Dowdy

          • Michael_Dowdy says:

            Hello Roy. Until a couple of hours ago I thought folic acid was converted into methylfolate. These two abstracts informed me differently. Madge and Greg would do well to read them and think about them. Michael M. Dowdy

          • Michael_Dowdy says:

            Hello Roy. To my knowledge there’s no such thing as 5MTHF. Isn’t it a chiral molecule? What’s the chirality of FormylTHF and the unidentified 5MTHF? Michael M. Dowdy

        • Marcia says:

          Roy, with all due respect, I’m not sure you’re aware of what you’re proposing…

          If someone is exposed to high levels of environmental chemicals like fungicides and pesticides, or plastics, or the chemicals in air ‘fresheners’, especially on a chronic basis — all which affect our genetic expression — how is eating more vegetables going to help clear out the buildup of these toxins?

          • Roy says:

            Hi Dowdy, yes to all your questions, but I think perhaps people have offered you help before and at least Madge and Greg have offered suggestions that you have turned down.
            Yes of course it is possible to be over-weight and malnourished. Being fat is actually very diagnostic of your problems. I don’t think I have seen it discussed here though. Being overweight means that you are not calorie malnourished, but you are likely to be vitamin malnourished, and you even have identified one of the vitamins that you are not getting in your diet, viz folate (I don’t really care which folate analogue, but clearly your diet would leave you folate deficient. Considering your genetics, this would also lead to you being B12 deficient, but you would know this, as too would most people who visit the site. In short, yes it is possible to cure your CFS. FYI in some countries MTHFR 677 TT occurs at a frequency of 25%, which is what one would expect from non-selective, or non-conditionally lethal mutation, so it is certainly not a death sentence. Furthermore, presumably you were healthy before you got CFS, which again says that your genetics were not a problem before you got sick.
            It is one thing to seek information on this site, I would be very careful though what you believe. I think that they may be what Madge and Greg were trying to tell you. Good luck in your quest. Believe me you can get better.

          • Roy says:

            Hi Michael, thank you for making me aware of this rather odd study in compromised humans with TIPPS. If you read the first study a bit more carefully, you will see that actually in the study the folate was converted to 5MTHF, which is slightly different to what you are inferring. Further if you read through the paper you will find the following quote :”previous study… that showed that single 453-nmol doses of 13C5-folic acid (close to the 500-nmol dose in the current study) were extensively absorbed (∼90%) by the gut mucosa (28). Also, daily supplementation with either folic acid or 5-MTHF has been equally effective in raising red blood cell folate concentrations to the same extent .
            You also appear to have totally ignored the diagram that they have in the study that suggests that whilst folate can leave the intestinal epithelial cell via the MRP3 transporter that there is evidence that 5-formyl-THF cannot, and must be converted to 5MTHF before it can leave the cell (something that actually might not happen in MTHFR +/+ individuals).
            The authors also totally disregard a very major problem with the study in that the number of the cells in the intestine cover a massive area. About the size of a football field, and that these cells are highly metabolically active and they themselves would be consuming massive amounts of folic acid in the normal folate cycling. Another thing that they also fail to mention is that there is no evidence of basal to apical transport of folate or 5MTHF and that actually they should have been sampling the thoracic duct for folate analogues rather than the hepatic portal vein, so most likely they missed the majority of transport out of the intestine. So in short rather a rubbish study, although it did mention the “bone of contention” that “daily supplementation with either folic acid or 5-MTHF has been equally effective in raising red blood cell folate concentrations to the same extent” Hence from a biological point of view there was absolutely no difference. Now I think that that is what several people have been trying to tell you, albiet unsuccessfully. So you keep taking your high price supplements which you seem to be able to afford, but in the absence of any data to the contrary, I would suggest that folate itself would be just fine.

      • Kristen says:

        I feel it is a serious disservice to unequivocally state heterozygous individuals have no problems.

        I have two sons who are heterozygous 1298C – and symptomatic. that’s *why* they were originally tested. both are responding well to supplementation. my youngest – who is the most symptomatic – is responding exceptionally well to mthf supplementation. many of his issues are disappearing. he’s a different child. I have been able to stop many of his other supplements/rx.

        My husband is also heterozygous – and has noticed improvement in several areas – including sleep. an area he has struggled with for many years.

        and that’s just my immediate family who have actually been tested. (not counting those who are homozygous 1298.)

        • Dr Lynch says:

          Kristen –

          People with or without a MTHFR defect can feel significant improvement from methylfolate.

          The presence – or absence – of a MTHFR SNP doesn’t mean much as someone can be deficient in methylfolate either way.

          • Kristen says:

            then why not just test for folate levels and supplement according to that? why bother with genetic testing for the mutation? from discussions with multiple NDs, my understanding is those with even a single copy of the mutation can have reduced ability to use folate – and blood levels can be deceiving. my understanding for those with the mutation: Just because folate is there – doesn’t mean the body can use it very well. (eg: side-effects.). is this wrong? if so, please explain why. (I realize some can be fine, depending upon other factors.)

            to my limited understanding, being homozygous certainly could explain health problems I had as a child – why some improved and others worsened. why I responded the way I did to a specific diet in the past. (and a bad reaction to anesthesia! which greatly confused a subsequent anesthesiologist) also, possibly, why specific joint and vascular conditions showed up repeatedly in extended family members over three generations, despite their separate homes and variety in diet.

            thank you

          • Dr Lynch says:

            You need genetic testing for many reasons – and I get into them here in this video course. I also discuss folate metabolism, utilization, nitrous, etc. This course provides 13 hrs of training – and will answer a ton of questions for you.

          • Roy says:

            I agree. If you are deficient in folate, you need supplementation. Now your genetics can make you not utilize dietary or supplemental folate as well or as efficiently as another person, but it is still a folate deficiency. I might also point out that whilst methyl folate, which is given a huge rap here is important for production of SAM it is not the only source of methyl groups, nor is it the only folate analogue that the body needs. Next you can’t use 5MTHF if you are deficient in B12, and there in lies one of the big problems with 5MTHF use, that the folate group cannot enter the folate cycle without sufficient B12. This is very different for folic acid, the normal supplement. Here it can enter the folate cycle without B12. Given that only a minor role for folate is to produce 5MTHF then B12 deficient persons given 5MTHF cannot have a functioning folate cycle. This also means that you can’t get the addition of the methyl groups from DMG and carnosine to enter the folate cycle, thus you are effectively wasting two thirds of the methyl groups on betaine. In addition, you can actually replace the methyl group from 5MTHF just by supplementing with methionine and extra methyl B12, and you can provide the folate scaffold for the folate cycle using folic acid. Looking at all the comparative studies between follic acid and 5MTHF they were basically inconclusive as to which was better. There is however a huge difference in the cost of supplementing with folic acid in comparison to 5MTHF, a fact that is no doubt not lost on the manufacturers.Thus you can buy a multivitamin with all of your needs for basically the same cost of just buying 5MTHF.

          • Donna says:

            Dr. Ben and Company-

            I started my journey being diagnosed with Celiac and becoming gluten free and use of OrthoBiotics which was recommended by my Endocrinologist. I immediately started to see positive changes and for the first time was able to cut down on some of my prescription meds. I then read about the MTHFR and asked to get tested and tested positive for Heterozygous C677T. My doctor started me on Mentanx (generic version) which he wanted me to start with about 500mcg and work up to 1000mcg slowly and using Niacin as needed. Again I immediately had some positive results, but had to go slow and listened to my body. I worked up to 750mcg because of the composition of the pill and splitting it wasn’t very easy. I felt like I was getting some backlash from the pill and asked the company if it had gluten in it, and they said it didn’t. I wasn’t getting beyond the side effects due to the composition of the and started HomocysteX Plus and within two days some of the side effects from the other pill left from the and hope to continue to see positive results. I also would like to mention that I have been able to completely stop one of my meds I was taking for pain since my back surgery over two years ago. I am so proud to be where I am today after finally finding some help from a doctor who is willing to not put bandaids on my complaints and helping me find solutions through nutrition, gut healing and vitamin deficiencies.

            My one questions is now my TSH has just taken a turn south. I have always had an enlarged thyroid since as long as I can remember and always came back with normal readings. Now since under this Endocrinologist and he obviously doing more thorough testing is concerned that I am Hyperthyroid. He is giving me three more weeks to retest TSH, Total T3, Free T4 and TSI. The last thing I want is to go on a pharmaceutical medication and looking for opinions on how to help my Thyroid Panels. My last TSH was .32 on 11/27/14. On 3/3/14 TSH was 1.02, 7/21/14 was my baseline prior to starting gluten free diet and ATPO was 4, T3T 180; TSH .38; FT4 1.2. I am wondering how the methylation could be affecting my thyroid and how I should prepare for any adjustments with my supplements. I really don’t want to take medication that is going to poison my body and start another cycle of negative affects on my body.

            Opinions are appreciated…

        • Roy says:

          Hi Kristen, I think that there is a slight misunderstanding here and in several other discussions on MTHFR etc. Thus, it really doesn’t matter what your genetics is, or whether you have this or that allele, if you are deficient in a vitamin, of course you will feel better if you get the vitamin. The effect is not because of the allele, the effect is because the person is deficient in the vitamin. Thus, in your family it would appear that your diet is deficient in total folate, of whatever type. Thus, perhaps your green leafy veggies are a little less green than desirable, or perhaps you don’t have enough of them. Taking supplements is exactly that, you are supplementing your dietary deficiency by adding extra vitamins. The whole of the pharmaceutical vitamin supplement trade is banking on this. By anaology, vegans who don’t eat red meat will be deficient in iron, vitamin B12 and most likely riboflavin (vitamin B2). Now they have to supplement with vitamin B12, B2, and iron because they have a dietary insufficiency. This basic principle applies regardless of their genetics. With your family, it is not their genetics that makes them respond to supplemental 5MTHF, it is their dietary lack that means that they need it. You would have the same effect if you gave them heaps of green leafy vegetables. As far as the mutation goes, even Dr Lynch has said “My current stance on the heterozygous MTHFR A1298C mutation is that it is very common and does not seem to pose too much concern unless there are other methylation or cytochrome mutations present”.The other thing that is relevant is that most people have no problems with the vast majority of minor alleles if they are eating well. This is obvious as the solution to their problems is generally to supplement, further adding to the argument. There is a very old saying “you are what you eat”. Thus if you don’t eat your vitamins, you will be vitamin deficient.

          • Dr Lynch says:

            Roy –

            It does matter what your genetics are! What are you saying??

            It is not only if you are deficient in a vitamin – but how you are able to UTILIZE it!

            How is that nutrient going to interact with other genes?

            If one has MTHFR, GAD, COMT, MAO, PEMT, SOD, GSTM1, SULT, NOS, DAO snps – or any combination thereof – they may be deficient in various nutrients or compounds yes – but if you simply prescribe nutrients to treat the gene, there is going to be backfire. If you do not test the genetics and work with this patient, you are going to banging your head against the wall because of so many unique biochemical issues.

            Yes – dietary intake and lifestyle and environment have huge impacts on MTHFR and other genes – but to say genetics are not important is absolute insanity.

            Using genetics to identify how a patient is likely going to respond or be predisposed to various symptoms/diseases is very powerful.

            You telling me that all the studies done on genetics and conditions are worthless?


          • Dr Lynch says:

            Roy –

            What is your background? What is your clinical experience here?

          • Marcia says:

            Roy, one of the main problems we’re facing is due to the ‘fortification’ of many foods with synthetic FOLIC ACID.

            So I guess when you said “the pharmaceutical vitamin supplement trade is banking on this”, you were right when it comes to that aspect.

          • Roy says:

            In reply to Dr Lynch’s comment below: Yes we are all different genetically and now thanks to modern science and the amassing profits of 23andme we all now know that. The surprising thing is that if you take a persons genetics and try to work out whether they will be healthy or not, you can’t. Furthermore, before anyone knew their genetics, they were still getting better. How were they getting better, by better diet and nutrition. The heterozygous conditions that you see in the genetic analyses have been around for 100000s of years, they are not new and haven’t arisen since the generation of genetic testing. Hence people can be fine and healthy on what one suspects might be called bad genetics. Similarly many people who develop CFS/FM were perfectly fine on their “bad genetics” and probably would have died with their bad genetics if a major crisis had not occurred. Curiously too, many of these get better when their nutritional status is improved, despite these “bad genetics”. IF the “bad genetics” was so bad it would have been selected out long ago on the “survival of the fittest” paradigm. In short, good nutrition will overcome bad genetics. Get your nutrition wrong and you will be “malnourished” and suffer the consequences.

        • Greg says:

          Roy, I have been aware of this paper for some time, and from memory I have included it a review of uptake systems that I did a couple of years ago. At the time it looked rather suspicious, and I was not really convinced that the author has drawn the right conclusions from the data.
          Thus, “5-Formyltetrahydrofolate (5-HCO-H4folate) is one of the main naturally occurring forms of folic acid in foods, but its determination is complicated because of its high susceptibility to interconversion and oxidative degradation.” In addition, 5-Formyltetrahydrofolate (5-HCO-H4folate) is known to inhibit most of the folate dependent enzymes at physiological concentrations.”
          It thus makes it highly likely that firstly it is degraded in the intestine under their administration conditions, and due to its inhibitory activity it is highly unlikely that it is enzymatically converted to 5MTHF.

          In addition the time course of appearance of the 5MTHF in the formyl group also looks very odd. Even glucose, which is possibly one of the most rapidly taken up water soluble molecules takes 30-45 minutes to peak during uptake, which is what you see for the folic acid, yet the 5MTHF, which has had to be taken up, and converted from formyl to THF and then exported from the cell, has already peaked in the portal vein in less than 20 minutes. Truly unbelievable and certainly not physiological.

          What is more of a worry is that even the authors state
          “When single physiologic 634-nmol (280-μg) doses of stable-isotope–labeled folic acid have been given to subjects without a TIPSS, who were neither exposed to mandatory fortification nor self-supplementation, no unmetabolized labeled folic acid was seen in the systemic circulation, only labeled 5-MTHF”. So one wonders if their observations have to do with the TIPPS procedure.

          Still as you say, the bottom line was that “daily supplementation with either folic acid or 5-MTHF has been equally effective in raising red blood cell folate concentrations to the same extent (29)” Given that the most important place to have folate is inside the cell, this is probably more relevant.
          I agree with you about the metabolism of the cells of the GIT. This is a real problem with biodistribution studies using B12, folate, biotin, or riboflavin, that so much of the material is used by the cells of the GIT and doesn’t even see the circulation. Of course if the material is not metabolically active, as is the case for formyl-THF this wouldn’t be a problem, but then again who wants to study metabolically inactive and even inhibitory analogues of folate.

          • Michael_Dowdy says:

            Hello Greg. I don’t particularly care for these documents either. They leave what I believe to be a significantly important detail out, that the molecule created is a chiral molecule and yet all they say is 5MTHF. Folic acid, at least in rats, is processed into FormylTHF in the intestines them later into 5MTHF. What is the chirilaty of FormylTHF? What is the chirality of the final 5MTHF which started as folic acid? If it’s different from 5-L MTHF there likely lies the problems with side effects when taking 5-L MTHF. I’ve read of 5-D MTHF and 5-N MTHF as well. You’re obviously better read than I am but I don’t think my uneducated question about the chirality of the 5MTHF is insignificant. Do you have the answers? I wish I did! Is there a possibility of different chiral molecules presented at the same time causing a toxic effect? That might explain some of the serious negative side effects when taking 5-L MTHF, especially if folic acid has been utilitized first leaving the natural form of 5-L MTHF unused. Respectfully, Michael M. Dowdy

          • Michael_Dowdy says:

            Hello Greg. Can 5-D MTHF be created by MTHF reductase enzyme? If it’s presented does it cross the blood brain barrier? When we supplement with 5MTHF does 5-D MTHF flow through our blood? What happens when we present the wrong isomer in our system? Respectfully, Michael M. Dowdy 321-443-6597

  • Tesa says:

    I recently found out I am heterozygous MTHFR (6t one)
    And double MAO mutation. My nutritionist hasn’t started my protocol yet to prepare for pregnancy(ultimate goal). However, she has me on advaclear and im supposed to start ultraclear. I can’t seem to get through the advaclear I’ll take it every other day for a week and feel great. The following week is miserable severe headaches, raging mood swings, and fatigue. So I’ll stop the advaclear for a week, detox like crazy, and then start back up again. I haven’t even made it to ultraclear yet. This has been going on for 6 weeks! Any advice?

  • Tina says:

    My 19 yr old is heterozygous 1298C, homocysteine level in normal range, B12 high (1000), Western blot band 41 present (only that) and Mycoplasma high, EBV old infection present. Where as it is hard to find a dr. in my plan that is knowledgeable enough on this. I am doing my own research, as I see this is all connected some way. I want her to start supplement for the MTHFR. Will the HomocysteX Plus be ok for her to take. Just wondering with the B12 being high. and if so what is ideal dose. Thank you

  • Laura says:

    Dr. Lynch,

    What happens when you discover homocysteine is now too low? My 19 month old son is hetero C677. He also has CBS,MAO,NOS,MTRR. He has a speech delay but no other noticeable problems.

    He’s been on l-methylfolate 1/5th of your capsule, along with one capsule of the kids optimal multi (in addition to other supplements) for about 5 months now. He just got labs done- ammonia was excellent, folate and b12 were great, but homocysteine was 3.8. Is he on too much methylfolate?

    The doc here recommended l-carnitine 100mg and 5htp 25mg and when he had those today (his third dose) he cried about 20 mins later for several minutes and signed to me that his head hurt. Not sure what to do now, or how to raise that homocysteine to a healthy level. I basically was told to make my own decision on what to give him by his doc’s office, which was not helpful. We eat a plant based diet, by the way, but I have started giving him a couple eggs a week.

    • Dr Lynch says:

      Laura – 3.8 is a normal level in a young child.

      100 mg of L-carnitine and 25 mg of 5-HTP is quite a bit for an 18 month old – not crazy high but more than I’d use. It’s hard to gauge though with speech delay. Sometimes it may break through.

      I would increase his protein intake – as that is where homocysteine comes from.

      I would put him on Optimal Electrolyte along with some more added Optimal Creatine. 1 serving each. Put in his water bottle and let him drink.

      Which MAO does he have? Which allele? T or G?

      Look at his RBC Fatty acids as well.

      I’d also consider Optimal Liposomal Vitamin C – to start – 1/2 tsp. Then work into Optimal Liposomal Glutathione – drops at a time.

      Don’t introduce the glutathione – yet. Wait until the other things are on board first – for about 2 weeks.

      I should add that a plant based diet is low in choline. So increasing choline is going to be very important for him. Maybe critical actually. Consider Optimal PC – mix with some honey or something. Keep it out of the fridge. Start low – say 1 tsp – with food.

      • Laura says:

        Dr Lynch,

        Thanks so much for replying. For MAO A he is +/+ for T. On Amy Yasko’s test that appears to be his only homozygous mutation.

        Some more details- the doctor had him on Sam-e 1/5th of a 200mg capsule starting at 15 months old- we discontinued that about two months ago after concerns about giving that to him at such a young age.

        He currently takes one capsule of your Probiota 12, one capsule of Nordic Naturals Pro EFA, vitamin d, a little bit of aqueous zinc a few times a week, the multi and folate previously mentioned, Yasko’s RNA drops for CBS+ and MAO, and has also taken the drops for SHMT but is out of them currently.

        His ammonia last week was 20, homocysteine was 3.8, folate was 1218. methylmalonic acid was 0.10. Recommendations were the aforementioned l-carnitine and 5htp, as well as pycnogenol 25mg and grape pip 50 mg. I have yet to buy those last two as my husband is seriously questioning having our son on so many things at such a young age.

        My son is a hearty eater of quinoa and a variety of beans and lentils. I’m open to whatever we need to do to keep him healthy and hopefully bring his speech out soon. Although it is too early to diagnose, I am somewhat concerned about the possibility of apraxia. He does say words randomly, only to never hear them again.

        • Laura says:

          I have all the products you recommended set aside in my shopping cart. How many drops of the glutathione?

        • izzy says:

          Hi Laura, I am +/+ for MAO-A (TT) and can’t handle 5-HTP (30mg) at all because it causes serotonin syndrome.

          • Laura says:


            Thanks a lot for letting me know that. He got one 25 mg dose that one day and I’ve not given it to him since- and definitely won’t be now! This is why we are nervous about giving him supplements- he’s too little to tell us exactly how they make him feel. Since Dr.. Lynch knew to ask me about that, I’ll be going with his recommendations from now on.

          • Laura says:


            Do you know what that means for sam-e? He was on that for about 3- 4 months I think…

      • Laura says:

        Dr. Ben- I am confused about your prior comment to only take the methylcobalamin and mthf when sluggish. My issue is anxiety, I am homogeneous for the C gene and have been on high doses of folic acid for years. (Stopping now) does this mean that it won’t help me? I took a half a dose of Homocystex and did feel some anxiety. Thanks.

        • Laura says:

          This is a different Laura than the one posting on 12/14, sorry for the confusion

        • Dr Lynch says:

          Laura –

          That comment was old. Sometimes people with anxiety do better with methylfolate and sometimes they do worse – it depends on what the reason for the anxiety is.

          If you feel anxiety from the HomocysteX, do try the 50 mg of Niacin every 30 minutes until relieved. Magnesium and B6 should also help – not all – but quite a few people. Glutamate levels can also increase from methylfolate – which is why I recommend these three other nutrients (they lower the glutamate).

          • Laura says:

            Dr. Lynch- Thanks for your reply. I will try the niacin and other recommendations. Is any of this contraindicated for breastfeeding? Also, does all the folic acid which is still in my system prevent me from properly absorbing methlyfolate or dietary folate? Lastly, for people who can’t tolerate or have to slowly move up on the methlyfolate, do you suggest that they increase their diet of greens to make up for the folate or does this make things worse? Thank you. This is all new for me and I’m trying to wrap my head around it.

  • Windingdown says:

    I am pretty sure Roy is an internet troll.. he loves getting all of your goats.. ignore him
    Get it? A troll loves to get goats just like the childrens story.. Many are up for for DNA testing and learning how to get well with trial and error since GPs are worthless to many who have been ill for decades.. bye Roy.. I hope this is your last post I think he is 23andme jealous..

    • Roy says:

      You certainly are different people. Do you not believe any science just because someone is trying to help and gives free advice? Is that how bad it is over there? No-one can actually accept free information from people who are trying to help, and who actually may have done the science to back up their comments. You blindly accept comments from people who are trying to sell product yet do not believe the comments and opinions of people who are trying to GIVE free advice and hope. Obviously the good samaritan is long dead over there. I would not say that I am religious, but really God help you all if that is the case.
      It is such a terrible statement on the condition of humanity.

      • Marcia says:

        Oh come on Roy, no one knows who you are, so why should we accept your advice, especially when you provide no links or references to back it up?

        I have a feeling you’re probably “Greg” and “Madge” as well, although Madge was constantly pushing b12 “oil”.

        Anyway, I’ll stick with Dr. Lynch, and I suggest others do so as well. He has the references and studies to back up his claims.

        • Roy says:

          So who are you Marcia? Do we need to know?
          For Pete’s sake, if you don’t believe me about the incidence of the alleles, why don’t you just look on SNPedia. Plug in your allele into google, that is easy enough. Cross reference it with SNP for say rs1801133. When google finds the link, just hit enter, you will see the SNP come up. Then scroll down the page. There you will find a graph of frequency of the alleles. You will see by eye that the frequency of the CC, CT and TT alleles varies depending upon country of origin. You will also see that generally (and not always) the CT is about the most common. So to have the CT allele is the “norm”. I don’t know why you would bother getting your 23andme SNPs if you didn’t understand what they mean, it would just be a waste of money. As for the references you simply go to PubMed, a free on-line reference base of the scientific literature that is factually based and check out the data on your SNP there.
          Here is the link
          You can believe what you want to believe, but at least be educated in it.
          As for the nutrition, it is just common sense, something that does not appear to be common. Thus if you have energy excess to your needs you put on weight. Vitamins are by definition critical to your health (ie vital). If you are low on vitamins you are suffering malnutrition of the vitamins. Thus if you are low on vitamin C you get scurvy. It doesn’t matter what you eat. If you are low on vitamin D, you all know that you get osteoporosis. IF you are low on folate you don’t methylate or perform the other functions of the folate cycle. If you are low on methyl B12 you don’t methylate. You can believe it or not. There are 100s of references on it. If you don’t want to believe the science, that is your business, but I would think that it might actually be nice NOT to live in ignorance. Knowledge is a gift that can be acquired, all I am trying to do is to help you get it. I haven’t pushed anything but knowledge and have given it freely, despite the abuse..

          No I don’t know either Madge or Greg, hopefully one day I will get to meet them. It would be an honor to know them. At least they seem to know the science.

          • Michael_Dowdy says:

            Hello Roy. Don’t attack Marcia. You know who I am. Why is chirality missing on 5MTHF. Call me. Michael M. Dowdy cell 321-443-6597 or home 407-847-7061

          • Michael_Dowdy says:

            Hello Roy. According to this article, , the answer to my question is still not fully known. 5MTHF is racemic but is apparently converted into 5-L MTHF, although not fully known. The unused remaining portion seems to me to likely cause problems, which is stated in the conclusion of this article. Michael M. Dowdy

      • Michael_Dowdy says:

        Hello Roy. You say “over there” twice in you comment. Where are you referring to? Where are you? You capitalize the word God so you likely recognize God as a supreme being or creator and I’m not embarassed to say I believe you’re right. Exactly what are you trying to say? I’m very transparent and I live in central Florida USA. Respectfully, Michael M. Dowdy

      • Michael_Dowdy says:

        Hello Roy. I love your comment! Striking things I notice in it, very revealing. Where are located you when you’re saying “over there” twice? I’m also impressed that you capitalize “God” so that says to me that you must recognize God as a supreme being. So do I, of which I’m not embarassed. We seem to agree on something major. It’s pretty hard to believe we just popped out of the water and dust. Methylation, demethylation, and enzymes are pretty complicated stuff to happen all by chance, far too complicated in my belief. I have genuine concern over others and I think these things need discussion. The “good samaritan” is not dead, but certainly very scarce. My questions are for the right reason, and also for my own understanding. Sincerely, Michael

        • Marcia says:

          Michael, you seem like a really kind man. I think you’re being too easy on Roy, too trusting perhaps.

          He said above: “Similarly many people who develop CFS/FM were perfectly fine on their “bad genetics” and probably would have died with their bad genetics if a major crisis had not occurred. Curiously too, many of these get better when their nutritional status is improved, despite these “bad genetics”.”

          That statement has so many errors in it I don’t know where to start, but to say that people who have CFS/FM are “perfectly fine on their bad genetics” is not only an insult to those of us very sick, but actually proves Dr. Lynch’s point — that a ‘major crisis’, like infections, chemical exposures, etc., will of course affect genetic expression and cause problems with methylation.

          I thought the studies you posted were great, and especially the first one showed that “folic acid” isn’t utilized like the active forms are.

          Anyway, seems like Roy has left the building, so to speak, so we can get back to talking 21st century science, and not about the folic acid that has contributed to our problems.

          Take care,


  • Tammy says:

    Hi, I have been on Homocystex for about 3 weeks, the main problem I’m having is an increased allergic reaction to things I’ve never had allergies to, both food and environmental. Is this possibly a side effect of the homocystex?

  • izzy says:

    Laura, Sam-e is related to other SNPs and I have never tried it.

  • T Brown says:

    I am homozygous A1298C. Three months ago I was started on 1mg methylfolate combined with 5mg methylcobalamin. I was not tapered up. At the same time, I started an adrenal supplement for adrenal fatigue. I have had occasional palpatations, nervousness and insomnia but not to an alarming degree. I figured it had more to do with healing the adrenal glands. Regardless, I will continue to use both. I have niacin on hand in case I need it.

  • claire says:

    I starte taking yyour multivitamin powder (just half dose) and on the days I take it I get a tight chest feeling. Could this be from the folate?

  • Trina Elsasser says:

    Hi Dr. Lynch,

    First off, let me say thank you for this website, and all that you have done to help those of us with the MTHFR gene mutation. I am 58 years old, and was diagnosed with Hashimoto’s hypothyroid this summer. I have since had my SNP’s identified, and have discovered that I am homozygous C677T, heterozygous COMT V158M and H62H, am homozygous DAO.& MAO A R297R. I also am homozygous SOD3 and am heterozygous SOD2 & 2 A16V. I also have numerous other homozygous and heterozygous SNP’s. My functional medicine practitioner started me other on Synthroid, compounded T3, methylcobalamin shots once a week, and active B12-Folate daily. At first I felt wonderful, and then I began having anxiety, joint aches, and heart palpitations. I stopped the methylcobalamin and B12-Folate. She then added liposomal glutithione with a pulsing dose of 1 teaspoon 3 x’s a week. I developed even worse anxiety and depression. She also added Gaba twice daily and Ashwaganda once a day. I also added your Optimal Start over the last few weeks. I went off the glutithione, ashwaganda a week ago. My anxiety and depression diminished, but I continued to feel nausous with little appetite. I stopped the Gaba supplements a few days ago and am feeling better. I am now only taking Synthroid, T3, Optimal Start, omega 3’s, ubiquinol, D3, and calcium daily. I have just ordered 50 mgs of niacin, your optimal electrolytes, and sensitive probiotics. After reading your page on how to prevent side effects, I am wondering if I should also order and start taking NAC, hydroxocobalamin and/or adenosyl B12, and the SOD supplements. My Dr seems to be agreeable to following your protocol since I reacted so negatively to the 1st two attempts that she suggested. I am a bit overwhelmed to say the least, which is why I am hoping for a response from you. I am nervous about beginning the glutithione again, but will do so when I have received the niacin tablets to offset any negative reaction. Thank you so much for any help you can give me. Sincerely, Trina

  • John Lorscheider says:

    I am seriously stumped on how to move forward with my methylation and folate cycles. I have a Hcy level of 16 and do not tolerate methyl donors well at all.

    Methylfolate, methylcobabamin, folinic acid and TMG get me wired, grumpy and brain fogged even in low doses. 2,000 mcg of Hydroxocobalamin agrees with me as does low dose B6 and 100 MG of phosphatidylserine (for BHMT) . All 14 of my MTHFR genes are -/- which is good.

    ++ COMT rs6269 and rs165722
    ++ VDR rs1544410 and rs731236
    ++ MTHFS rs6495446 – is this folinic acid intolerance?
    ++ BHMT-02, 04, 08
    ++ MTRR A66G
    +/- MTRR-11 A664A
    +/- MTRR rs10520873 and rs1532268
    + MAO A R297R
    + MAO A rs6323
    + MAO B rs3027452
    + MAO B rs1799836

    How would I go about getting a form of folate that will agree with me and help me reduce my Hcy? Is folic acid advisable since all MTHFR genes are intact? Just eat a lot of greens?

    Thank you.

    • Greg says:

      Hi John, you have some pretty strong SNPs there. Do you know what your serum B12 levels are, and moreover have you had an OAT analysis of your metabolism? This will help to tell you how to move forward.

      • Donna says:

        Does anyone know how to get rid of excess folic acid in blood? I am having a hard time with methylated folate and b12. I have just started P5P with magnesium and hoping this will help me open pathways. I need to get additional testing as I only know I am hetero C677T at this point. Which ones are the most helpful as I am very sensitive to meds and am celiac as well. Money is tight so I have to be specific on most important testing.

        • Michael_Dowdy says:

          Hello Donna. Just watch carefully and reduce or eliminate your intake of folic acid. Always use the smallest amount of supplements until you determine what works for you. Pay close attention to how you respond and try to judge from trial and error. Most people vary their diet so you’re going to see different levels when tested so if you’re close that’s probably very good. Stress is so damaging so do what you can to reduce stress. Sleeping well is crucial and a sleep study is a good idea if you feel like you’re not getting enough quality sleep. Dr. Ben’s recommendations are very helpful and I believe his concern is genuine and not greed driven. Some people say you don’t need to treat a heterozygous MTHFR mutation. I think they’re wrong, especially when it comes to women of child bearing age. Best Wishes, Michael M. Dowdy

          • Claire says:

            I’m still learning about this whole topic on this site. I too have very elevated serum folic acid. In all my last 3 blood tests over the past 4 years. I was pregnant and taking small amounts of folic acid at the time of 2 of the blood tests. But I still had high serum folic acid after a miscarriage where i hardly took much folic acid and then switched to a folate supplement (5 MTHF or similar I think) for that pregnancy which ended at 11 weeks.

            No one ever told me there is something wrong with high serum folic acid. What does this mean? I haven’t tested myself for MTHFR genes. But will have to look into that. Perhaps I’ll do the 23andme test. Would that give information about the MTHFR genes too?

            My last serum Vit B12 tested was middle of the range.

          • Donna says:

            Hi Michael,

            I have been watching my diet very closely over the last seven months since I was diagnosed Celiac. My folic labs are still coming in over 20 which above the high range and has been there for over seven years. I hope that it will go down soon. I asked my doctor to test RBC folate and he looked at me like I had two heads.

            I suffer from chronic muscle spasms/pain and insomnia with a recent diagnosis of Restless Leg Syndrome by my neurologist and was put on Ropinerole to help my dopamine levels. I want to use natural products as possible. Maybe I should schedule that sleep study…these last three years have been torture.

            Thanks again…

        • Roy says:

          Hi Donna,
          Have you had your B12 levels tested and do you know if you have thyroid issues?

          • Donna says:

            Hi Roy,

            Serum B12 was 1198,
            TSH 0.38 (0.27-4.2uIU/ml),
            FT4 was 1.2 (0.9-1.8ng/dl) and
            T3T was 180 (80-200ng/dl)
            on 12/8/2014.

            TSH was .38
            FT4 was 1.3
            T3T was 140
            on 12/19/2014.

            My doctor also tested TSI <89 (<140) to check for Graves. He thinks I am border hyperthyroid and is rechecking again in about 10 days.

            Any ideas???? I am taking 6000iu (was taking 4000iu over summer) of vitamin D as my levels as still borderline at 40 (dropped from 49 over summer), Ferritin 27 (10-291ng/ml) which dropped from 47 over summer.

            I feel like I am getting better, but not where I was before I hurt my back 9/3/2011 and was treated with so many steroid injections that I feel like a pin cushion… I ended up having back surgery on 10/3/2012, but it didn't help.

            I would appreciate any suggestions or comments from fellow bloggers!

          • Roy says:

            Hi Donna,
            Your T3 levels certainly look high, which is probably why your doctor thinks you are hyperthyroidic.
            May I ask what sort of diet you are on? Do you have plenty of eggs and dairy? It looks like you are either supplementing with high dose B12 or getting injections. If you are, what form of the B12 are you taking, and why did you start?

          • Donna says:

            I was on Metanx .75mg which was 1/2 pill, but trying to split them was not easy. I tried to take Seeking Health HomocysteX Plus, but couldn’t tolerate so tried HomocysteX and still couldn’t tolerate. I am now taking P5P with magnesium as Dr. Ben had discussed this as a possible solution if not tolerating the methylated folate and B12. I can’t even take his multi’s with the methyl vitamins as it would cause my pain and spasms to increase.

          • Donna says:

            I forgot to mention the diet: Gluten Free and I do not eat many eggs and I use Almond Milk in place of milk. I do eat a lot of plain greek yogurt though.

          • Roy says:

            Hi Donna,
            If you are on a gluten free diet you will almost certainly be B1 (thiamine) deficient.. Whoever put you on the diet should have warned you of this. This is very common in hyperthyroidism. Have you had an OAT, this would tell you. Do you have elevated blood glucose? B1 deficiency can cause peripheral neuropathy similar to that seen in diabetes. This is going to become an increasing problem as people avoid a natural diet.

          • Donna says:

            Hi Roy,

            My blood sugar is fine, but have been diagnosed with neuropathy after my back surgery due to mechanical compression from injury. I had it prior to surgery, but got worse after surgery.

            I will discuss with my doctor about the OAT testing panel and see what he says. I asked him to do more testing, but he said insurance is not good about paying for these types of tests unless he can link it to a diagnosis… I think Celiac would qualify.

            I will buy B1 and give it a try-what is a good dose to start with??? Should I back off on the B6? I would like to just take an overall multi, but the one with methyl vitamins seem to aggravate pain and spasms…

  • Joanne says:

    Dr. Ben, I started taking your Active B-12 with L-5-MTHF about a week ago and within a few days started feeling joint pain, especially in my hips and knees — and, now I have a black & blue bruise on the upper outer quadrant of each of my thighs, both with significant soreness. Each thigh bruise looks the same and measures approximately 2-1/2″ wide and 1″ high. This is scary… What’s going on here? I have stopped taking the supplement and