Methylfolate Side Effects

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. The issue is methylfolate can cause more harm than good if not started at the right time or tapered up slowly in amount.

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.

Methylfolate Side Effects:

  • irritability
  • insomnia
  • sore muscles
  • achy joints
  • acne
  • rash
  • severe anxiety
  • palpitations
  • nausea
  • headaches
  • migraines

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 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.

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.

UPDATE November 25, 2014

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

  1. 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.
  2. Consider 1 to 2 capsules of 250 mg of 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.
  3. 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).
  4. Limit intake of leafy greens until side effects go away. This is because leafy green also contain methylfolate and nitrates.
  5. 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.
  6. Glutathione – as cells divide with more methylfolate, glutathione levels get further depleted. Restoring levels can help significantly. Do it SLOWLY though. Consider Optimal Liposomal Glutathione.
Tired of Guessing how much Methylfolate you need? Read this article, “How much methylfolate should I take?”

Questions for you to answer in your comment below – and please do – be sure to state which MTHFR mutation you have:

  1. What methylfolate side effects have you experienced?
  2. Did the niacin, hydroxocobalamin and curcumin help you resolve your methylfolate side effects?
  3. Did you suffer through the initial methylfolate side effects only to come out feeling great in the end? Or worse?
  4. Did your doctor start you on a 1 mg or more initial dose of methylfolate and that set you off?
  5. Did your doctor taper you up gradually and slowly on methylfolate? How’d that work for you?


1,096 Responses to “Methylfolate Side Effects”

  1. David March 1, 2012 at 10:28 am # Reply

    Hi Dr Ben,

    thanks for another interesting post.

    1. headaches, muscles and joint pain, fatigue and brain fog. Mild to moderate in severity. I should add that benefits from taking methylfolate include improved sleep,and resolution of a persistent sore throat.
    2. 100 mg of niacin appears to help.
    3. Hoping that this is the end result! I have been supplementing with 200 mg of methylfolate for 2 weeks. I think that the side effects are diminishing over time. Or that could just be the niacin helping out…..
    4. Yes
    5. No

    Is there any chance that niacin can completely offset the increased methylation produced by methylfolate? If so, what would that level be?



    • Kathy March 7, 2012 at 6:38 am # Reply

      Hi Dr. Ben,

      I just found out I am compound heterozygous. I was put on 7.5 mg of Deplin last week and am feeling terrible. I have brain fog , fatigue and some dizziness in the mornings, and I take it the night before. I told this to my naturopath and she remarked that she has never heard anyone complain of this before. I was told to go off of it for a few days and see how I feel. Any advice?

      • Dr Ben March 7, 2012 at 11:02 pm # Reply

        Definitely related to high amount of methylfolate.

        I see it ALL the time.

        Talk with your doctor about this article and how Niacin and Optimal Turmeric may help you.

        Being compound heterozygous, you likely do not need some much methylfolate. Some – yes – but not 7.5 mg of it.

        Talk with your doctor about this thought:
        I recommend you consider Optimal Multivitamin – 3 capsules with breakfast and 3 with lunch. This provides you about 300 mcg of methylfolate daily. If you need more, then you can take an additional 2 capsules at 2 pm with a snack and that brings the total methylfolate up to 400 mcg daily.

        If you still need more methylfolate, then I recommend you consider taking 1/4 tablet of Sublingual Active B12 with Methylfolate. This is easy to break apart and also contains methylcobalamin which is needed to allow the methylfolate to do its job.

        It is best to taper up with methylfolate than start on higher amounts.

        • Matina St. Sauveur October 19, 2013 at 1:17 pm # Reply

          My problem is irritableness on the Methylyguard folate with an anti depressant. Can one take the optimal turmeric and niacin if also on an anti depressant? I have been off of the methylguard folate dose for about a month now. Where would I start? Meaning how much and when do I take the turmeric, niacin, and then methylguard? I am trying to get balanced and well feeling to attempt withdrawing from the antidepressant one day. I do not get many responses is relation to anti depressants and folate. I also take vitamin C, calcium, magnesium, zinc, vitamin D, fish oil, and vitamin presently. Any comments on these?

          • Kathleen October 19, 2013 at 7:09 pm #

            Hi Matina. I’m on this forum as a C677T diagnosee. A few years ago I suffered from depression for a few years. Finally in 2004 I asked my doctor for Paxil, as I also had social anxiety disorder. After 6 months I went off (cold turkey) due to weight gain. The depression returned low grade off and on. My doctor told me about EFT for use on back issues. But it wasn’t until 10 years later when after seeing EFT referenced in just about every newsletter of Dr. Mercola to try it on anything that I finally checked it out. I was so impressed that I purchase the EFT video library and learned the techniques of the technique. You can teach yourself or you can go to and donate whatever you can to order the how-to videos (very worth it). I used it on social anxiety disorder with approx 95% success rate, depression with a 100% success rate, a uterine fibroid with 100% success rate, pain, anxiety, any many other physical and emotional issues. For treating my MTHFR defect, I’m having awesome success with Dr. Yasko’s multi vitamin together with Premier supplements for liver and kidney as well as 500mg of NAC 2-3x/day. This may or may not work for you, as everyone is different with regard to mutations. Hope this helps.

        • Madge June 5, 2014 at 4:40 am # Reply

          Can you explain why 5MTHF, which is the normal folate analogue found in food should do anything at all as far as side effects? Are you suggesting that if MTHFR people eat leafy green veggies they will get these side effects. That sounds very odd.

          • Roger November 16, 2014 at 8:37 pm #

            Folinic is the form of folate found in food. It can slowly break down to methylfolate. At least that’s my understanding.

          • Dr Lynch November 19, 2014 at 12:11 am #


        • Catherine March 30, 2015 at 11:33 pm # Reply

          Dr. Lynch,

          Can too many methyl donors halt methylation, or cause methylation to slow down?



    • Kathy Robison September 29, 2014 at 8:10 pm # Reply

      1. I feel so miserable on the methylfolate. It is fibromyalgia x 50. brain fog, aches, fatique,

      2. I just read this and will try niacin

      3. I felt good for 3 days and then, wham! I waited one week and tried again, it was exactly the same.

      4. I read about this and tried it.

      5. I really don’t know what to do now.

      • Dr Lynch September 30, 2014 at 3:50 am # Reply

        Methylfolate will push the mitochondria hard. Fibromyalgia – your mitochondria are tired. You need instead:
        – Optimal Electrolytes – 1 scoop once to twice daily in a liter of filtered water
        – Adrenal Cortex – 1 in AM after breakfast
        – NADH + CoQ10 – 1 upon rising and possibly another around afternoon
        – Optimal Start – as directed on the bottle.
        – 5-HTP – 1 capsule before bed
        – Magnesium Plus – 1 capsule before bed

        Do those for a month or so and then slowly add in Optimal Liposomal Glutathione

        These recommendations can be found at – which is my company (disclosure)

        I would stop the methylfolate and methylcobalamin at this point – need to do the above first.

        Evaluate your diet and lifestyle as well.

        • mjones January 31, 2015 at 3:27 am # Reply

          I have fibromyalgia as well and didn’t do well with methylfolate. I’d like to try this first, but how long do you do all this with the Optimal Liposomal Glutathione before adding in methylfolate again? And do you have to continue taking all these supplements with the methylfolate or can you begin to taper off the others and just take methylfolate?

          • Dr Lynch January 31, 2015 at 7:35 pm #

            Exactly what I see most of the time in those with fibro.

            Please read this:

            Yes – you need to prepare your body first.

            The key ones are:
            – liposomal glutathione
            – electrolytes
            – optimal start – multi without b12/folate

            You need to OPEN and get your biochemistry ready for folate/b12 – and this support really really helps a lot of people.

            You also use as needed – not daily.

            Need a well-trained doc.

            You may find them at

        • Carrie February 12, 2015 at 1:13 am # Reply

          Th advice to take 5htp can really mess you up. You must take L-Tyrosine with 5-htp. Otherwise you will eventually deplete your dopamine and be even worse off.

          • Donna February 12, 2015 at 2:00 pm #

            I am having problems with my dopamine levels and want to naturally boost. I can’t tolerate a lot of supplements including 5 HTP and now being treated with Ropinirole which mimics dopamine at the receptor sites. I was also told that I will need to go back on “ADD” meds which I don’t want to do. Any suggestions?

          • Rudi February 12, 2015 at 7:26 pm #

            Hi, this is in response to the question about dopamine levels. I have been doing some reading about b6 and it’s potential to help boost dopamine levels. There is pretty comprehensive information at this page:

  2. Kris March 1, 2012 at 2:18 pm # Reply

    GABA is already overexpressed in my son due to Trisomy 21 (homozygous C677T). Is there something other than Niacin that can be used to help quench excessive methylation?

    • Dr Ben March 1, 2012 at 4:43 pm # Reply

      Kris –

      Niacin appears to the best I have found so far.

      Niacin does not express GABA, it assists it crossing the blood brain barrier.

      Consider trying a small amount of niacin and seeing if there is benefit.

  3. Catherine March 1, 2012 at 4:15 pm # Reply

    I am homozygous for MTHFR C677T with normal homocysteine levels. I am healthy, happy, and fit… least I think so. After reading these posts, I’m not sure. Why should one take methylfolate? I’m reluctant to take a pill unnecessarily. I take 1 baby aspirin daily and super B vitamin.

    • Dr Ben March 1, 2012 at 7:24 pm # Reply

      Hi Catherine –

      I responded to you in another comment – on the MTHFR C677T Protocol article.

      • Jennifer April 8, 2015 at 4:02 pm # Reply

        I am unable to find that response and would find it useful.

    • Angie July 27, 2013 at 7:31 pm # Reply

      I was diagnosed yesterday. Dbl mutation of homozygous c677t. I took 5-mthf one pill with a bcomplex 6 with food yesterday. Slept well but feel sad today. Side effect? I’m not sure if I want to feel like this when I wasn’t feeling bad before diagnosis.

      • jill April 30, 2014 at 4:11 am # Reply

        could be the folic acid in the b complex..?

    • Gail September 23, 2013 at 5:41 am # Reply

      As Catherine stated, I am also homozygous for C677T with normal homocysteine levels. I didn’t know about this until a recent blood test by my integrative medicine physician. I have two normal children born to me 28 and 25 years ago. I have always taken a LOT of supplements that support cardiac health (a possible reason for the low homocysteine level). Do I really need to supplement with any more things?! I once took niacin because I had read about its wonders but I stopped when I couldn’t stand the flushing. This was all before I learned I had the gene defect. I am past child bearing years, and aside from Hashimoto’s thyroiditis and a knarly mycoplasma infection that caused me to test positive for lyme, I’ve had a fairly normal life. I am on the antibiotic protocal for the lyme/mycoplasma infection because the mycoplasma infection caused morphea (scleroderma family). I hesitate to take any more supplements. My habit already costs me about $200/month. My “D” levels are normal due to supplementation. So what now?? As long as the homocysteine levels are normal, do I really need more supplements?

    • Michael Dowdy October 31, 2013 at 10:19 am # Reply

      Hello Catherine. I’m not a doctor or expert about MTHFR. I’m just a patient trying to learn and survive. There’s an old saying, “If it ain’t broke don’t fix it.” Why were you tested for MTHFR and what symptoms did you have? If you really have 2 copies of MTHFR C677T your homocysteine levels should be a concern even if it checks normal for now. It shouldn’t hurt for you to use an activated (methylated) B complex and start out by trying a small amount of methylfolate supplement if you’re really homozygous for the MTHFR C677T mutation or even not. It’s worthwhile for you to research and study in case your metabolism changes all at once. Methylfolate is simply more easily metabolized than folic acid. Best Wishes, Michael Dowdy

      • gloria June 25, 2014 at 10:41 pm # Reply

        It’s NOT that folic acid isn’t as readily absorbed… it’s that it’s absorbed in preference over the natural and methylated forms… and (synthetic) folic acid then builds up to toxic levels in mthfr individuals, because we can’t convert it to useful forms.

        • Michael_Dowdy June 30, 2014 at 3:13 pm # Reply

          Hello gloria. I didn’t think that the synthetic folic acid was readily “absorbed” or used without proper MTHFR enzyme as a first choice over 5-L-MTHF/L-5-MTHF. Where exactly does the toxic levels of folic acid and methylfolate go? Apparently the methylfolate in excessive amounts causes bad side effects also just as does folic acid. Just where does each end up when taken in excessive levels since it’s basically impossible to prevent being force-fed folic acid because of it being a required food additive in some countries? Did you read the “Application A566″ documents regarding folate/folic acid food additives and the maximum tolerable levels? Did you know that the term “folate” can be used as the descriptive word for both synthetic and natural forms? Read about levomefolic acid in the metabolism cycles on Wikipedia. Methyl donors are critical in the fight against cancer. Is folic acid even needed when methylfolate is used?

          • Dr Lynch June 30, 2014 at 6:40 pm #

            Michael –

            I prefer people getting folate from:
            – leafy greens
            – methylfolate
            – folinic acid

            Folinic acid: use to support DNA base production and possibly also biopterin recycling – looking into this
            Methylfolate: use to support biopterin recycling and to recycle homocysteine into SAMe

            Folic acid should not be used in my opinion.

          • Lynn_M June 30, 2014 at 7:00 pm #

            Absorbed is not a specific enough term to describe what happens with folic acid metabolism. I don’t know if folic acid gets digested and into the blood stream any differently than MTHF (methylfolate). However, once folic acid or MTHF is in the blood, they each present to the cell membrane receptors to be taken up into the cell. There are a limited number of cell receptors, so when folic acid binds to the receptors, it competitively inhibits how much MTHF can bind.

            Also, once folic acid makes it into the cell, conversion to methylfolate requires four sequential reactions, as elucidated by Dr. Rich Van Konynenburg. The first two require NADPH, which is based on vitamin B3, and it requires some additional metabolism to form NADPH, including burning of glucose via the pentose phosphate shunt on the glycolysis chain. Magnesium is also needed. These two reactions convert folic acid to tetrahydrofolate (THF).

            Next, a reaction is needed to convert THF to methylene THF, and that is usually done using serine via the SHMT reaction. Then methylene THF must be converted to methylfolate via the MTHFR reaction, which requires vitamin B2 and NADPH. Using MTHF avoids all of those reaction pathways.

            Even people with homozygous C677T still have a very limited ability to make the MTHFR enzyme, using alternate pathways. So people with that mutation can metabolize some folic acid, but if they’re exposed to much, it will build up in the blood stream.

            I believe I get virtually zero folic acid in my diet, but then I don’t eat any processed foods and I eat gluten free. Folic acid is only found in processed foods. It can be avoided.

            Folic acid is totally synthetic. It is not needed when MTHF is available through diet or supplementation.

        • Michael_Dowdy August 2, 2014 at 5:16 pm # Reply

          Hello gloria. Where did you get this information and how do you know it’s accurate. You’re welcome to call me at any time. 321-443-6597. my phone isn’t working right now because i have no reception in the hospital I’m in. Try me in several days.

        • Michael_Dowdy December 15, 2014 at 6:09 pm # Reply

          Hello Gloria. I was wrong. You’re absolutely correct because folic acid is used before it gets into the portal vein of the liver. Folic acid needs to be avoided. Folic acid is converted into FormylTHF. I was unaware of this. Thank you. Respectfully, Michael M. Dowdy

  4. Karen March 1, 2012 at 5:13 pm # Reply

    Thanks for pointing out that taking too much methylfolate before inflammation is controlled is not a good thing. My son (heterozygous C677T) has been taking 800mcg methylfolate with no problems so I assumed I could handle 1 mg. I didn’t think about the fact that we have spent the last 3 years supplementing him with antifungals, probiotics, fish oil, multivitamin with P5P, TMG, and curcumin. His body was ready to handle it. Mine not so much. My son’s doctor actually wanted him and me to begin with 7.5mg! I took it once (Deplin) and felt awful, so I was afraid to give it to my son. I began to research and that’s when I came across this website.

    I experienced many of the side effects listed on days that I took just 1mg. I am awaiting my MTHFR test results. Maybe I have more mutations than my son? I followed Dr. Ben’s niacin recommendation and am feeling better. I will add the curcumin as well.

    Thanks Dr. Ben for all the info.

    • Dr Ben March 1, 2012 at 7:23 pm # Reply

      Karen – thank you for sharing your story here. Important for doctors and others to understand.

      • Marcia November 10, 2014 at 10:06 pm # Reply

        I’m curious what you think about this study, which suggests that folate deficiency makes inflammation worse…

        • Madge November 11, 2014 at 12:13 am # Reply

          well its pretty obvious that they don’t read much literature. Low folate, or low B12 leads to higher homocysteine, which is a precipitation factor in vascular disease, and in other conditions such as MS. Also low folate means low BH4. BH4 is an essential co-factor for nitric oxide synthase (NOS), the activity of which they say is low. So really the only surprise is the lack of knowledge of the authors, and also the people who reviewed the paper before it was accepted..

          • Marcia November 11, 2014 at 3:49 am #

            Thanks “Madge”, but your comment wasn’t helpful at all, actually quite patronizing and presumptuous.

            Of course low folate, b12, etc., leads to higher homocysteine. My point was this paper suggested that low folate equals more inflammation, so I was asking for Dr. Lynch’s take on it, as it seems like both low or high folate might could be a problem.

  5. Elizabeth March 1, 2012 at 9:18 pm # Reply

    Great information Dr. Lynch. I can relate to issues with taking methyl-folate… and well, ANY methyl donors! However, I am homozygous A1298C. I would tell you I react as your third scenario. Are there similar things for me to consider, such as getting the apparent inflammation under control?
    Thank you so much.

  6. Compound Heterozygous Daughter March 3, 2012 at 2:22 pm # Reply

    My 7 yr daughter (63 lbs) is compound heterozygous. She did very very well on .5 MG of 5MTHF at first (for a couple of weeks), but then started to experience symptoms of irritability, leg and joint pains, and has had dark circles under her eyes. We’ve stopped 5MTHF for a few days and she’s been a dream child and has no leg/joint aches. I’d like to try the Niacin — Can you give me the correct dosage for her age/weight?

    I’m a little confused on the overall protocol – when do I reintroduce methylfolate?

    Should we try the liposomal curcumin and Tumeric if the Niacin works? or just stick with the Niacin.

    Thank you for your help.

    • Dr Ben March 4, 2012 at 6:32 am # Reply

      Dea –

      I think she would do well on a multivitamin with methylfolate. Consider giving her 1/2 tablet of Optimal Multivitamin Chewable with breakfast and 1/2 with lunch for 2 weeks. Then increase to 1 tablet with breakfast and 1/2 tablet with lunch for 2 weeks. Then increase to 1 tablet with breakfast and 1 with lunch. This will provide her 400 mcg of methylfolate along with methylcobalamin – and other nutrients that she needs.

      I do not recommend giving her niacin right now if she is doing well. I use it only when people are having side effects – so i would have used it when she had dark circles under her eyes along with irritability and joint pain.

      I’d get a bottle of both Niacin and Optimal Turmeric on hand though in case she does get side effects again for any reason.

      • Compound Heterozygous Daughter March 4, 2012 at 1:39 pm # Reply

        Thank you Dr. Ben. We will try that. I should have mentioned this in the first post — I apologize — What about taking Bh4? I posted in the forum about this, but if you have any insight, it’d be appreciated.
        Here’s my forum post —
        “My 7 yr old daughter (compound hetero) and I (homozygous for a1298c) take a supplement called BH4 at the advice of our nutritionist. It seems to help me with mood and generally feeling better, and sometimes I think it’s helping my daughter in the same way and sometimes I’m not sure. Also I’m not confident that we have enough information on how much to take. It’s a supplement that is very hard to find and there is little information on it. Can anyone offer insight into using the supplement BH4 — it’s from Ecological Formulas BH4 Homeopathic 2.5 mg Capsules. The ingredients list only BH4 (2x) but the bottle also says “BH4 contains Biopterin, a cofactor to critical enzyme pathways in human physiology.” Thank you in advance to anyone who can assist me.”

        • Dr Ben March 4, 2012 at 7:55 pm # Reply

          Dea –

          BH4 is useful – and BH4 = tetrahydrobiopterin which many shorten and call Biopteriin.

          There are a few reasons why BH4 can be lower in people:
          – elevated neopterin caused by inflammation and an overactive immune system – which typically go hand-in-hand.
          – MTHFR A1298C
          – low ‘ingredients’ or precursors as we call them such as folate, magnesium, copper, vitamin B6 and vitamin C
          – low cofactors which are needed to make the reactions move forward in order to make biopterin such as niacin and iron.
          – elevated ammonia
          – high phenylalanine

          I am working on making BH4 easier to find.

          Dosage of BH4 is not known without labs and symptom evaluation by your doctor.

          • Katie August 25, 2012 at 10:06 am #

            Hi Dr Ben,

            I am trying to source BH4 in Australia, do you have any links for this at this point?


          • Dr Ben August 26, 2012 at 7:33 pm #

            Hi Katie –

            I do not recommend supplementing directly with BH4. I instead recommend the precursors for it. I need to write an article about it. BH4 is unstable, expensive and in such low amount via supplemental forms, that it doesn’t make sense to supplement with it.

    • Jessie December 30, 2013 at 1:13 pm # Reply

      Greetings! My son is compound heterozygous, and I am following the advice Dr. Ben gave you (1/2 tab twice daily of optimal multivitamin with 5-Mtfh). Can you tell me how your daughter did/is doing with this multivitamin? My son is terribly irritable and anxious, but I can’t tell if the vitamin has worsened his mood or if it’s just his “normal” irritability and I should increase to a full tablet twice daily or look for a different type of B12 altogether–perhaps a hydroxyB12. Anyhow, I’d love to know how your child is doing. Wishing you both the best of health! Jessie

      • Dr Lynch December 30, 2013 at 7:06 pm # Reply

        Hi Jessie –

        If you notice your son more irritable, moody after giving nutrients, it is likely due to those nutrients. Providing some Niacin will likely help him – along with reducing/stopping supplementation – but do talk with your doctor about that.

        These nutrients are effective and must be respected – and used properly.

        Please listen to this – in full – there are some great pointers here –

        • Jessie December 30, 2013 at 7:35 pm # Reply

          Thank you for your advice, Dr. Lynch. My son’s B12 labs came back in the normal range, so I’m wondering if he should just be taking the L-5-MTHF lozenge, since it contains no additional supplements. His thyroid doc was the one to spot the MTHFR and the normal B12, but he prescribed 15mg of Deplin. This caused aches and pains in my son, as did splitting the Deplin in half. This is what took me to this website and your advice to give 1/2 tablet twice daily of the Seeking Health multivitamin. However, I’m wondering now if we should just be using your L-5-MTHF lozenge, perhaps split in half to start. I am desperate for support here, so any advice you offer is greatly and warmly appreciated. Thank you, Dr. Lynch.


      • Rebekah December 30, 2013 at 8:23 pm # Reply

        Hi Jessie, I was mulling your problem over and I had an idea– For now you could concentrate on adding foods high in folate to his diet. Add a little at a time. At breakfast–give him some chopped up veggie and fruit pieces BEFORE any funner foods. Put it in a bowl and tell him you are still working on the rest of his breakfast. At lunch, always have some greens, this is a good time for a salad (or dinner if he is away at lunch). Always have a little fat in the meal. Make the food look appetizing and never give yucky bits (like check the berries so no gross ones get in). Slice up fruits and have them ready for just before he will want a snack. If he doesn’t want to eat the greens, remind him it is the healthiest part of his meal. Always try and get him to eat at least one piece, he will get used to it after a while. Never over cook the veggies so they always taste fine. Add some seasoning if that helps. Don’t give up and try and get other adults helping or at least not po-pooing your efforts in front of the child. Have him involved in preparing some foods, or growing some veggies if you have any place to do it this spring. Just because most Americans don’t eat enough veggies doesn’t mean your family has to follow suit. If you make a journal and write what he ate, how he felt and acted each day-you may find some patterns that will help you see what works for him. Make sure he gets plenty of sleep..that sort of thing. For the aggression, you could try finding an activity (very supervised) where he is helping others. Something he can easily do and doesn’t take too long. Be very positive about it. Good luck, Rebekah

  7. Aleina March 7, 2012 at 9:12 pm # Reply

    I am compound heterozygous and started out taking 2mg of methylfolate, then dropped to 1mg. I felt awesome at first, but started feeling off again recently. When I saw this, I realized I’ve been having most of these symptoms! When I started not being able to sleep, I knew something was going on because I have NEVER had that problem before. :)

    I was having headaches, joint pain (though that is still around since stopping?), irritability, insomnia, anxiety, palpitations, acne, and nausea.

    I stopped taking it about a week ago and have definitely been feeling better. The kind I have is in capsules though, so I’m not sure how I can reduce the dose? Should I keep taking it and add niacin/turmeric to counteract the symptoms? Or should I take turmeric for awhile to reduce inflammation first?

    • Dr Ben March 7, 2012 at 11:00 pm # Reply

      Aleina –

      Talk with your prescribing doctor what you’ve been feeling. If you self-prescribed then still talk with your doctor about how you’ve been feeling with the methylfolate.

      I recommend also that you stop taking it for a week or more until you get it out of your system. You may need the Niacin and Optimal Turmeric to help get your back more quickly.

      Taking Niacin and Methylfolate at the same time is like driving with one foot on the gas and one foot on the brake. Instead of doing that, find the optimal amount of methylfolate that is right for you.

      Taking something that has methylfolate in it but not 1 mg may be the best way.

      I recommend you consider Optimal Multivitamin – 3 capsules with breakfast and 3 with lunch. This provides you about 300 mcg of methylfolate daily. If you need more, then you can take an additional 2 capsules at 2 pm with a snack and that brings the total methylfolate up to 400 mcg daily.

      If you still need more methylfolate, then I recommend you consider taking 1/4 tablet of Sublingual Active B12 with Methylfolate. This is easy to break apart and also contains methylcobalamin which is needed to allow the methylfolate to do its job.

      • Cathi November 30, 2014 at 6:08 am # Reply

        I have been reading over the comments here to try to find additional answers. We are helping our son gradually ramp up his methylfolate amount. You said in the above comment from 2012, that you taking niacin and methylfolate at the same time is like driving with one foot on the gas and one foot on the brake. However, I’m confused because your optimal multivitamin has both niacin and methylfolate. won’t this cause a problem? Currently our son takes the optimal multivitamin, along with additional methylfolate in the form of 2 sublingual tabs of the active B12 with L-MTHF (from seeking health). Is the small amount of niacin he gets in his optimal multivitamin squelching any of the effects of the methylfolate?

  8. Kaethe March 21, 2012 at 9:31 pm # Reply

    Hi Dr. Ben,

    I got a call from my daughter’s doctor a few days ago saying that she was
    “positive” for the MTHFR gene mutation. I am in process of trying to obtain her lab results, because after reading the information on this website, I now realize there are several possibilities that she could have. I do not know which copy my daughter has, but the doctor ordered 5-MTHF (L-Methylfolate from Metabolic Maintenance)10 mg daily for her to begin now. The order arrived in the mail today. After reading some entries I am afraid this is too high a dose. I’m definitely going to go out and buy some niacin to have on hand in the event of side effects. I can only find non-timed release niacin. Is this OK? Do you think 10 mg is too high as a starting dose? I’m sorry I don’t have any more information.

    My daughter, age 19, 140 lb., is recovering from late-stage neurological Lyme. She was in treatment for two years with some improvement, but still has a terrible amount of brain fog and peripheral neuropathy. I asked the doctor to test her for MTHFR, and was a bit surprised to find out the result, but hopefully this discovery will lead her on the way to improved health. She has been on a detox diet for two weeks and doing well with that.

    Thank you for any advice you can give. I really appreciate this fantastic site.

    • Dr Ben March 22, 2012 at 4:49 am # Reply

      Hi Kaethe –

      10 mg of methylfolate as a starting dose in a 19 yr old woman with Lyme is pretty high – especially if she has only one copy of the MTHFR mutation or has the A1298C form.

      Is she taking any curcumin, alpha r lipoic acid or l-carnitine for the peripheral neuropathy? Vitamin B6? B12?

      If you have the form of niacin as nicotinic acid – that is good – anything else won’t work as well.

      Do let me know which form of MTHFR she has – and also ask the doctor why he/she feels that 10 mg is the appropriate starting amount.

      • Kaethe March 22, 2012 at 2:44 pm # Reply

        Thank you for your speedy reply.

        The nurse told me today my daughter has two copies of C677T and is homozygous. Does 10 mg daily of 5-MTHF sound appropriate for this? The doctor is not in today, so I could not ask why he is starting her on this amount. My daughter has an appointment with him next week.

        She has been taking B-12 1000 mcg S/L and Alpha Lipoic Acid 400 mg, for two years, prescribed by a different Lyme doctor. She was taking Acetyl-L Carnitine, but is supposed to stop that and start the L-carnitine soon, along with NAC 600 mg., Glyceine 500 mg, and Immunotix, introducing a new one every three days.

        Thank you for any insight you can shed!

        • Dr Ben March 22, 2012 at 7:02 pm # Reply

          Kaethe –

          There is no way to know if 10 mg is too much or not without testing for methylfolate levels or folate receptor antibodies.

          I know some doctors like to give the system a jolt; however, I prefer to ease into it as I don’t like side effects.

          Why is the doctor switching from acetyl-l-carnitine to l-carnitine? I’d like to hear the thought process behind that one – out of curiosity. I’ve wondered myself on that.

          If a person has a COMT mutation or CBS mutation or MAO A mutation and they take a high amount of methylfolate, it can cause some intense side effects.

          Please be prepared and get Niacin and Optimal Turmeric.

          I’d also share your concern with your doctor and ask to introduce methylfolate at a lower dose and gradually work up.

          • Kaethe March 23, 2012 at 8:53 pm #

            Thanks, I will ask the doctor about l-carnitne vs. acetyl-l-carnitine and let you know what he says. We have niacin and turmeric on hand as my daughter started the methylfolate 10mg yesterday. I’ll also ask the doctor about the other gene mutations you mention. Thank you for all your advice.

            We’re still in shock about the news of this, as we don’t seem to have a noticeable amount of people on either side of our family with the signs and symptoms of this type of gene mutation. We have two other kids and while one also has Lyme and co-infections, neither has any of what I am reading about on this site. Glad we caught this relatively early, however.

          • Dr Ben March 23, 2012 at 9:25 pm #

            Kaethe –

            I have the carnitine forms figured out.

            Acetyl-L-Carnitine is more for neurological support – yet it can also convert to L-Carnitine for mitochondrial support.

            L-Carnitine is more suited for mitochondrial support and does not readily convert to acetyl-l-carnitine.

            Thus, it depends what the issue is.

            Keep me posted how your daughter does on 10 mg methylfolate. I’ll be amazed if she does well long term – but it may be so.

          • Cathi November 30, 2014 at 6:12 am #

            Is it ok to be taking optimal turmeric and methylfolate on a regular basis together ? Does that create a problem?

  9. Sandy April 2, 2012 at 8:23 pm # Reply

    Hi Dr. Ben,
    So happy to have found your very informative website. My 23 yr old son is Heterozygous A1298c – recently diagnosed. His ND prescribed 7.5 mg Deplin per day. Does this seem like too much? He is attending college in another state, and after reading about the possible side effects, I am concerned about having him begin taking it. Would it be wiser to have him take just half a pill for a few weeks, to see how he reacts, and then go to the full dose, depending on if he has any side effects or not? A bit of background: He weighs 135. He has suffered with depression since age 14. He is also taking 20 mg. Lexapro, and 300 mg. Wellbutrin, and 20 mg Adderall XR. His ND also prescribed 2,000 mcg chewable methylcobalamin, and Pure Encapsulations B6 complex. (this has 400 mcg folate & 400 mcg methylcobalamin & 10 mg no-flush niacin as part of the formula)
    Thank you so much for any advice you can give.

  10. Heather April 3, 2012 at 7:12 am # Reply

    dr Ben,

    i haven’t yet been tested for mthfr because i can’t afford the test, as (relatively) cheap as it is, but my ND put me on 1 folapro/day (800 mcg methylfolate) because i muscle tested well for it. said ND is at least moderately well-versed in mthfr mutations. i have chronic lyme and coinfections and also take a number of other supps/herbs daily, including hydroxyB12 sublingual.

    in the day-to-day, on and off lyme treatment i am symptomatic and fatigued but functional to an extent (this was not always the case; at one point i was bedridden and near-death for about a year). i can now work part-time and take care of myself and my cats. i’m telling you this because as it turns out, even a tiny crumb of folapro knocks me for a loop, renders me totally nonfunctional. i started at 1 pill for a few days, felt strange, stopped, waited a week or so, started back at 1/2 pill, then 1/3, then a couple days later the symptoms hit me full force – excessive sleepiness, unbearable brain fog, feeling totally out of it and confused, feeling toxic/poisoned.. the reaction was horrible but there was some small seed of it that felt productive/healing. however, it left me completely unable to function or think or execute even the most basic of tasks.

    after that experience i quit the folapro for two weeks, then restarted at one tiny crumb. i thought for sure i’d have no trouble with such a negligible dose, but lo and behold, two days later all the same symptoms slammed me again. this time they were slightly less intense, but only slightly, and still debilitating.

    it’s been three days since i took my last folapro crumb and i’m mostly back to baseline.

    have you ever heard of anyone reacting so strongly to such a tiny dose of methylfolate? i know people who are symptomatically much sicker than me who are nonetheless able to tolerate much larger doses of folate with no additional problems. why might this be? i am so confused and would appreciate any insight you have to offer.

    thank you so much,

    • Dr Ben April 3, 2012 at 6:06 pm # Reply

      Heather –

      As surprising as it seems, yes, I have experienced a few with such intense side effects to methylfolate.

      I recommend getting these levels checked:
      – blood histamine
      – 24 hr urinary amino acids

      If you cannot afford those, then I’d focus on:
      – healing your gut
      – reducing inflammation
      – potentially reducing sulfur supplements (unless you do very well on them)
      – supplementing with molybdenum
      – probiotics
      – sauna at low temperatures for short duration and just keep increasing in duration as you can
      – colonics

      There are other mutations at play potentially – I am thinking the CBS gene mutation is playing a role here.

      When you experience these side effects, the Optimal Turmeric and Niacin can be life savers.

  11. AM April 4, 2012 at 4:15 am # Reply

    Hello Doctor,

    Long story short, mfolate and MB12 felt like a lifesaver at first… I finally felt normal!! And then I was hit with fasiculations and parasthesias and brain fog.

    We are working me up for autoimmune disease, but cannot pin it down yet. I still get these neurological episodes intermittantly… but I really really need the b vitamins. Zinc also gives me nerve issues, but in a different way.

    I am homozygous recessive for multiple MTHFR mutations and CBS.

    If I have autoimmune disease (my mom has sjugrens) will I ever be able to try mfolate again? Is it contraindicated? Maybe it will help?

    I don’t know if I should be taking curcumin because of my CBS sulfur issues, COMT downregulation and MAOA. (all confirmed by genetic testing).

    I have been having trouble all my life, and now finally with something that helps me I can’t take.

    Feeling hopeless. What can I do? Thanks

    • Dr Ben April 4, 2012 at 5:19 am # Reply


      You likely can start taking it again once you get your CBS mutation balanced. Gut health is critical.

      Have you read my C677T MTHFR Protocol article?

      You may have been taking too much – simply cut way back and start the amount you are taking in low amounts – and work up – slowly.

      Niacin is very handy when needed…

      • AM April 4, 2012 at 10:40 pm # Reply

        Thank you for your reply.

        I believe I have. Will take a look again.

        Do you find the the inflammation increase is persistant and or persistantly dose dependant, or (hopefully) does it peak inititally and then fall off once the body reaches homeostasis?

        • AM April 4, 2012 at 10:41 pm # Reply

          I mean to say: is there an initial inflammatory hump people have to get over or does it remain?

  12. Bryan April 19, 2012 at 11:38 am # Reply

    Hi Dr. Ben:

    I found your website when searching side effects of my wife’s supplement regimen.

    She was recently diagnosed being homozygous for MTHFR C677T by her doctor on Monday and told her to immediately start taking 1 pill daily of Metanx which provides 3mg l-methylfolate, 35mg p-5-p and 2mg methylcobalamin. She also told her to increase her vitamin D from the 4000iu she currently was taking to 8000iu. Her d levels previoulsy were 49 after being on 6000iu for about two months.

    On Monday when she started Metanx she didn’t have any symptoms.. On Monday she also increased her Vit D to 8.000 and started taking 1 baby Aspirin. On the following day she had no symptoms immediatley after taking Metanx, but in the evening after taking a few of her usual supplements- CoQ10 with 300 IU of Vitamin E, Magnesium 400 and Vit C 1.000 she felt light headed, weak, anxiety, panic and “weird” about 45 minutes after taking these.

    Yesterday, Wednesday she took Metanx together with other supplements after lunch and within half hour she started not feeling well, similar but much stronger symptoms than the day before. She developed nausea about 3 hours later and feels nauseous till now.

    She is 53 years old and is also on Coreg CR 80 (once daily) and Tambocor 100 (twice daily) for years for Paroxsymal Atrial Flutter.

    Do you have any advice or suggestions what she should do?

    Thank you so much for your help.


    • Lynn_M April 20, 2012 at 4:42 am # Reply

      She shouldn’t take Metanx or methylcobalamin within 40 minutes of taking Vitamin C. The Vitamin C cancels out the methylcobalamin.

      Sounds like she needs to start out with partial doses of the Metanx and build up to the full pill. As Dr. Ben has responded to other commenters, she could take niacin or turmeric to counter any symptoms from the Metanx.

      If your wife was replete in her folate and B12 levels, she wouldn’t notice any symptoms from the Metanx. Any change, good or bad, tells you that she needs it. She just needs to ease into it much slower.

      • Bryan April 21, 2012 at 3:17 pm # Reply

        Thank you for your response.

        She tried taking a 1/2 of Metanx and took it separately but she got a mild reaction like her throat was closing. Could it be the fillers and other ingredients causing the reaction? Would it be better to take the three components of Metanx separately and work up to a specific dosage?

        Also, I was reading about other forms of B12 like hydroxocobalamin and and adenosylcobalamin. How are these different, is one form recommended specifically for this condition over the other and what is the best method to take which is recommended, orally, sublingually, nasally or injection?

        Also, who makes the most pure form of the one recommended with the least amount or no non essential ingredients like fillers, food dyes, etc.?

        I look forward to hearing from anyone with any information and would also be appreciative of Dr. Ben’s feedback, if possible.

        Thank you for your time.


        • Lynn_M April 22, 2012 at 12:18 am # Reply

          According to, the nausea and anxiety can be due to a potassium deficiency. As the cells start to get the nutrients they need and heal, a demand is created for more potassium.

          The light headed, weak, anxiety, panic and “weird” feelings might be more attributable to the methylfolate, maybe the methylcobalamin. They work together, so it’s hard to separate out the effect of one from the other. Given the effects that people report on the Phoenix Rising B12 forums, I would think that your wife was reacting to the active ingredients of the Metanx rather than the fillers, unless she has a history of being very sensitive to fillers and inert ingredients. Some people have to start with crumbs and then build up. I think your idea of taking the components separately is a good one, to better identify which of the components is problematic for your wife. Hydroxycobalamin is not an active form of B12, and the body must further metabolize it into the active forms of methylcobalamin or adenosylcobalamin. With homo C667T, your wife has an impaired ability to convert and needs to bypass those conversion steps by taking only the active forms of B12 and folate.

          Methylcobalamin targets the neurological system and is constantly turning over in the body. Adenosylcobalamin targets the mitochondria and is needed for ATP production. The body uses ATP for energy, like a car uses gas.

          The best form of B12 is sublingual. B12 is a very large molecule and very poorly absorbed when taken orally. Read the website Daisy gives below for more information about how to take methylcobalamin. Nasally doesn’t work because there’s not enough contact time with the tissues. The problem with injections is that hydroxycobalamin and cyanocobalamin don’t help anyone with homo MTHFR. Methylcobalamin injections are very, very, very sensitive to light and I think they need to be compounded, so they’re quite problematic. I’ve taken mB12 for years, but I never realized any benefit until I followed the recommendations of the Active B12 Protocol Basics linked to below. It was after I started using Jarrow mB12, letting it sit under my upper lip for at least 45 minutes, and after I added adenosylcobalamin, that I really felt a discernable uplift in mood and energy.

          • Bryan April 22, 2012 at 2:43 pm #

            Dear Lynn,

            Thank you so much for your detailed, thoughtful and informative reply.

            I will read through the links carefully.

            I really appreciate your information,help and time.


          • Lynn_M April 22, 2012 at 11:28 pm #

            There wasn’t a reply option at your last post, so this may appear out of chronological order.

            If you want a better understanding of what happens when people with a deficiency start to supplement active forms of folate and methylcobalamin and other nutrients, read That thread is 254 pages long, and a long slog to get through, but much of it is a tale of how Freddd (who I think is the same Fred Davis that has commented here at was able to finally recover from his lifelong debilitating illness, and what he learned along the way. His recommendations are based on his empirical discoveries of what worked for him, and he certainly is to be commended for the zeal with which he endeavors to share that knowledge.

            Phoenix Rising is targeted to people with ME/CFS. One researcher, Richard van Konynenburg, PhD (richvank) believes ME/CFS is due to a glutathione deficiency, which then leads to methylation cycle block. I see the methylation cycle block as the element in common with those of us with MTHFR mutations, and thus I think there is much for us here to learn from Freddd and richvank and other commenters at Phoenix Rising.

          • Bryan April 23, 2012 at 6:55 pm #

            Thank you Lynn

            Based on my preliminary research with your help, I went to vitamin shoppe and bought Jarrow Methyl b12 1000mcg, solgar metafolin 400 mg and P-5-P 50 mg.

            However, my wife was reading on the internet about the side effects of these supplements at lower doses than these and she is concerned.

            She was wondering if we can split the b12 lozenges, the metafolin and the p5p. If so, what would be the ratios of them that you would recommend to start with, how much and when should she take them? Also, what roles does p5p play, if any, since I did not notice it on the active b12 protocols.

            She is already taking some supplements on the protocol but she is not looking to add others unless they are absolutely necessary. She is taking 3000mg C, 4000iu d3, 300mg r-alpha lipoic acid, 30mg optizinc, amongst others.

            She is also nervous about the side effect of hypokalemia since the results on her blood tests have been at the lowest level the lab considers normal (3.5). Should she also be taking potassium and if so, when and how much? We also read b12 and potassium may interfere with each other, do you have to separate them?

            In addition, we also read that the supplements may pose a clotting issue. She is particularly concerned since she was recently diagnosed with a G20210a mutation of the Prothrombrin gene. Any thoughts?

            We just realized that at the same time she started Metanx her doctor told her to double her D from 4000 to 8000iu and it appears online that this could cause similar side effects to the ones she was attributing to the Metanx. When she stopped Metanx she stop taking D for 2 days and is now taking 4000 again. Any thoughts?

            By the way, does anyone know a doctor who specialized in these gene mutations in NY?

            Also, Lynn are your recommending that she start with adenosylcobalamin in conjunction with the above and if so, when and how much?

            You also pointed out that in Phoenixrisng they are primarily dealing with ME/CFS. Are you homo MTHFR and what do you think of what they post is necessary for us?

            Thank you for your time.

          • Lynn_M April 23, 2012 at 9:32 pm #


            I believe we’ve reached the point where I can’t help you much more. I learned 3 weeks ago that I am homo A1298C MTHFR, and I have been studying this site and the Phoenix Rising forum intensively since then. Everything I share here I mostly learned at those two sites, but I don’t know any more than I’ve read. There is also more threads at Phoenix Rising that deal with B12 issues, including, and richvank’s Simplified Protocol.

            When your wife reads about side effects caused by the supplements, I suspect she is reading something addressing the general population and not something addressed to MTHFR people. Doses that might be excessive for the general population are necessary for those of us that need to bypass defective pathways.

            Your wife certainly can split the pills into smaller doses. Some people literally must start with crumbs. Some people dilute that crumb in a quart of water and drink one drop. Unfortunately this really is trial and error as to what doses your wife can tolerate as she starts out. You can read how other people have done it at Phoenix Rising.

            One research study found they could divide ME/CFS people into 5 or 7 subsets, can’t remember which. Just as there are differences between ME/CFS people, I’m sure there are differences between ME/CFS and MTHFR people, just as there are differences between C667T and A1298C people. I can’t tell you what of Freddd’s protocol is relevant for C667T or A1298C and what isn’t. Most of us here know we or a LO have some kind of MTHFR mutation, but we probably all have other hetero or even homo genetic mutations in addition to MTHFR, as well as different lifestyles and diets, so our responses and needed doses will be different.

            From what Freddd says, you definitely want potassium levels to be at least mid-range, and to supplement with potassium if they’re lower.

            I’m not sure when P-5-P is needed and when it isn’t. When I was taking adrenal support supplements, they had doses of B6 (pyridoxine) in them, so I’m playing it safe and taking P-5-P.

            Some people at Phoenix Rising needed adenosylcobalamin, but certainly not everyone. I found adenosylcobalamin to be the one supplement that really changed how I felt. Starting out at 2.5-3 mg. is probably good, and then it can be dropped down to even once a week. I found out 4 months ago that I’m homozygous for the non-celiac gluten sensitivity gene, so my deficiencies are probably caused by the combination of prior gluten exposure and my home A1298C genes.

            I don’t find the idea of trial and error and self-discovery on what to take and what doses to take to be satisfactory, but that seems to be current reality. I think there are tests like the organic acids test (OAT), or the methylation panel from Health Diagnostics and Research Institute (formerly Vitamin Diagnostics Inc.) of NJ, the company that richvank likes, that can tell a person how well they’re doing. Dr. Ben has talked about some tests like the ION tests. I hope he can work out a recommended way for each of us to know if we’re working around our mutations well enough.

            I hope you can work out a protocol that works for your wife.

      • Michael_Dowdy March 16, 2014 at 6:10 am # Reply

        Hello Lynn_M. How exactly does Vitamin C cancel out methylcobalamin? If this is true then any food or drink containing Vitamin C would cancel out the methylcobalamin and it would be very problematic taking methylcobalamin. Does this mean that drinking orange juice at the same time of taking methylcobalamin renders the methylcobalamin useless? Does this mean that you shouldn’t even take a multi-vitamin containing Vitamin C and methylcobalamin at the same time?

        • Lynn_M March 16, 2014 at 6:37 am # Reply

          Michael Dowdy,

          Dr. Lynch wrote about the interaction of Vitamin C and methylcobalamin at, starting just under Part II. He wrote: “When taking methylcobalamin, it is necessary to not exceed ingesting 450 mg of vitamin C concurrently. This is due to the destruction of methylcobalamin when in the presence of more than 500 mg of vitamin C.”

          I had read in a different blog that you should wait 30-40 minutes after taking Vitamin C before taking methylcobalamin. I don’t remember the reason.

          Perhaps Dr. Lynch will share with us why he included that caution in his protocol.

          • Lynn_M March 16, 2014 at 7:07 am #

            At, under the interactions segment, it says:
            “Vitamin C

            Early research suggests that vitamin C supplements can destroy dietary vitamin B12. It isn’t known whether this interaction is important, but to stay on the safe side, take vitamin C supplements at least 2 hours after meals.”

            Since this is the only reference of the 147 listed that had ascorbic acid or Vitamin C in its title, I suppose this is their reference for that assertion:
            Herbert V, Jacob E. Destruction of vitamin B12 by ascorbic acid. JAMA 1974;230:241-2.

            If you go to, there are 3 related and more recent citations to the issue of vitamin B12 and ascorbic acid. They are listed on the right hand side. I look forward to reading them tomorrow.

          • Lynn_M March 17, 2014 at 12:11 am #

            According to this article abstracted here, Stability of B12 in the presence of ascorbic acid in food and serum: restoration by cyanide of apparent loss, (also available in free full text), “B12 destruction by absorbic acid in vivo seems highly improbable.”

            This 1979 research reached a similar conclusion.

            Herbert had an article in the 1979 Nov 23;242(21):2265 JAMA, Ascorbic Acid and B12, but no abstract is available at PubMed, and the full text is behind a paywall, so I don’t know if he responded to the critiques of his work.

            So Michael_Dowdy, I’m glad you raised this question. It appears that the results of the original 1976 research, cautioning against combining B12 and Vitamin C concurrently, and now apparently discredited, are what has been repeated in time, and the research suggesting the improbability of those 1976 conclusions doesn’t get the light of day.

            So unless Dr. Lynch shares any more light on this subject, it appears one doesn’t have to be cautious about combining B12 and Vit C.

          • Dr Lynch March 18, 2014 at 5:40 am #

            Hi Lynn and Michael –

            The information I had was from that older study. If it has been discredited – that is interesting – did not know this.

            It is not is not that difficult, however, to keep these nutrients separate just in case you are finding your b12 levels are low.

  13. Daisy April 20, 2012 at 7:47 pm # Reply

    Hi there,

    I read on this CFS forum that sudden healing can cause potassium deficiency:

    From the link:
    “Potassium is far more critical than I realized with version 1 of this page. Most people starting the active b12s and Metafolin will have low potassium symptoms which can include unusual spasms, muscle weakness, mood and personality changes, nausea, heart palpitations and a long list of other possible symptoms which makes it difficult to identify. Many people misidentify low potassium symptoms as “detox”. This is a dangerous mistake to make.”

    I had all these symptoms creep up on me after taking methyl B12 & folinic acid. They abated the same day that I started the potassium supplements. I feel fine now. The worst thing was crippling depression and anxiety.

    • Dr Ben April 20, 2012 at 9:59 pm # Reply

      Daisy –

      Thank you for sharing. Gerson Therapy is all about potassium also. I will look into that further.

      • Daisy April 22, 2012 at 7:41 pm # Reply

        Glad to help. Here’s some more info from the same forum.

        • Dr Ben April 22, 2012 at 7:49 pm # Reply

          Daisy –

          This explains why Neutralize works with people who have side effects from detoxing. I knew potassium helps alkalanize and neutralize effects from environmental toxins – but I didn’t know that the body actually gets low in potassium during detox. I will have to research this further.

          • Kim April 24, 2012 at 3:29 pm #

            wont know mutation until I get results from you (should be any day)
            wondering if I should take potassium?

            1. fatigue, light headed,angry, just not myself on 3rd day of 1mg 5mthf.stopped it.
            then extreme anxiety, feeling crazy and panic attack with continued b12
            last night- b complex shot and made me worse

            Thursay, I switched from NAC to
            Liver X pills and 1mg mthf
            Vit E 40 iu
            b12 methyl 20 mcg
            NAC 400 mg
            Silymarin 100mg
            ALA 100mg
            Choline Bitartrate 100mg
            Picrorrhiza kurroa 25mg
            Andrograophis paniculata 25mg

            took it again friday and saturday

            saturday mid-day started feeling off, by evening I was getting anxiety and had distubed sleep.
            Sunday fatigue,woke, ate, took liver X pill and slept on & off til 2:00pm rest of day I felt not myself, angry, light headed, just weird. by evening I was feeling so bad that I foolishly took another Liver X pill. I became anxious, restless, running thoughts, sweating, felt out of my mind until I had panic attack at 4am. If I did fall asleep I’d wake from horrible nightmares. was not able to eat anything but an apple yesterday.
            Last night- I took no pills and got b complex shot at 6pm. felt down and anxious.weird sensations in back of head. took 125mg Niacin, drank Calm Magnesium drink but still was in and out of sleep with weird dreams and heart palpitations. took another Niacin in middle of night and again this morning. Still feel bad. taking nothing today.

            So, recap-
            Monday- B complex shot, NAC
            Tues & weds- NAC
            Thurs & Friday- 1mg 5mthf, Liver X,
            Saturday- 1mg 5mhtf, liver x, vit D3 1000mg,candidex, herbal UTI pill
            Sunday- Liver X AM & PM, vit D3, herbal UTI pill, candidex

            Curious what is causing reaction?

            should I wait until my results come in to continue or could I start slow on one of your supplements/vitamins?
            should I not take NAC or Candidex with my methyls?
            Should I start on potassium?
            How long until the shot is out of my system?

            feeling really bad right now.

          • Lynn_M April 24, 2012 at 7:27 pm #


            If you have amalgams or heavy metal toxicity, NAC and ALA can cause very nasty effects. I gather that your 20 mcg methyl B12 was in injection form, which makes it more potent. The half-life of B12 is 6 days. Either the methylB12 or the 5-MTHF can also cause start-up effects. If the niacin doesn’t help, I would suspect either the NAC or the ALA, but also possibly the 5MTHF.

            Try stopping everything until your symptoms go away, and then when you start up again, don’t take the NAC or ALA, but startup the mB12 and 5mthf one at a time, at reduced doses, adding the other after a week or so, and gradually build up those doses. Once you are doing okay, then you can try adding in the NAC or ALA, but one at a time, with no other changes going on.

          • Michael_Dowdy April 26, 2014 at 8:35 am #

            Hello Dr. Ben. I’ve used EDTA in the past with some slight apparent improvement for hardening of the arteries. When using EDTA orally for that purpose potassium is, I’m pretty sure, removed with metal toxins as well as other minerals when detoxing. Bad leg cramps and spasms were an issue for me when using EDTA but I did not take any any additional potassium because I think it reduces the effect of EDTA when removing metal toxins. I would be very surprised if potassium is removed by any other methods of detoxing. EDTA removes more than just lead and mercury which is the reason why some believe it is effective in cleaning up arteries. I’m curious to see your reply to Daisy.

    • Bryan April 25, 2012 at 4:29 pm # Reply

      How much potassium supplement did you take?

      • Dr Ben April 25, 2012 at 6:57 pm # Reply

        Bryan –

        Careful with potassium. I do not recommend taking more than 125 mg of potassium at a time unless advised by your doctor to do so. Neutralize by Seeking Health provides 125 mg of potassium along with sodium to help calm reactions down.

        • Bryan April 25, 2012 at 7:01 pm # Reply

          Thank you

        • Kelly November 5, 2012 at 3:32 am # Reply

          Why such low amounts? Aren’t most simple foods quite high in potassium?

  14. Jen April 21, 2012 at 3:44 pm # Reply

    I am Hetero C6776T. Last night I took my 3rd pill of NeevoDHA. I am TTC and am about 9 days past ovulation. Anyway, within about 10-12hrs. of the first Neevo pill I started with side effects that progressively got worse over the next two doses I took. They are Tachycardia, Palpitations, headache, dizziness, clammy hands and feet, shaky hands, and now anxiety because of all the symptoms. So my question for you is…. How long does it take for this to leave my body? and also, since I had such severe side effects, could it have harmed in any way a possible fertilized egg? I will not take it again. I have not tried niacin, as I may be pregnant and didn’t know if it was ok. I was/am also taking BA and a probiotic (which I’ve been taking for a long time). Any help would be great.

    • Lynn_M April 24, 2012 at 7:36 pm # Reply

      Niacin is Vitamin B3, and the two prenatal vitamins I looked at each contained 20 mg. niacin, so I think it’s quite unlikely it will cause you any harm. At worse, you may feel a temporary flush.

      Sounds to me like the doses in NeevoDHA are much too high for you, and you need to either just take part of a pill or take the non-prescription forms which are available in much smaller doses than what is in NeevoDHA.

      What is BA?

      • Jen April 25, 2012 at 4:20 pm # Reply

        BA is baby aspirin. I haven’t taken another Neevo pill, and feel much better now.

  15. Ky May 25, 2012 at 10:12 am # Reply

    Hi Dr Ben
    My normally placid son (ASD) has a fortnight ago started 1mg 5-mthf to assist his regular MB12 injections.

    We’ve had the great week / crap week scenario (extra talking, listening, thinking , switching quickly to weepy, clingy, hyperactive, punching me in the stomach). The 5-mthf dose wasn’t tapered up.

    Is it possible to use Inositol in place of Niacin to calm him?

    Thanks for your thoughts.

    • Dr Ben May 25, 2012 at 4:09 pm # Reply

      Ky –

      I have not used Inositol to help calm people down. Inositol can help some and hinder others. A doctor I know states that Inositol depends on levels of histamine whether it will be helpful or not. Problem is I don’t recall which way it is at the moment – I’ll look it up when I’ve a moment and edit my comment here.

      Given that I suspect your son is now too low in histamine, I’d rather see you use Niacin as I know that works.

      • Ky May 26, 2012 at 12:17 am # Reply

        Thank you so much for your quick reply.

        I was wondering about Inositol because he takes 700 mg of Inositol a day and it has a wonderful calming effect on him – all his OCD symptoms melted away. When tested 2 years ago he had a very high blood histamine level and our doctor diagnosed him as an undermethylator. He has responded well to zinc/mag/b6 therapy.

        I read your comments about using Niacin to soothe excess methylfolate, and thought that as Inositol is touted as ‘no-flush’ Niacin it might be useful in his case. I was worried advice I read elsewhere that Niacin is best for overmethylators and Inositol for undermethylators.

        Any advice you have on this will be useful for us.

        Thank you


        • Lynn_M May 26, 2012 at 2:30 am # Reply


          Niacin eats up methyl groups. Since the 5-MTHF wasn’t tapered up, your son’s body wasn’t accustomed to that dosage, and thus his symptoms of being overmethylated. The niacin will act as a sort of “rescue remedy” and calm his behavior down. You don’t want to give the niacin to him long-term, only to get through this episode. Then you can restart him on the 5-MTHF, but with lower dosages, which will allow his body to adjust to the changes in his methylation pathways. You can titrate the dose of 5-MTHF upward as he adjusts.

          • Ky May 26, 2012 at 3:47 am #

            Thanks for your advice Lynn

            Do you know if Inositol can perform the role of Niacin in your plan? He does well on Inositol normally.


          • Leona December 25, 2014 at 2:18 am #

            I know this is out of sequence and a reply to an old post; but I saw in another post of yours (which I couldn’t reply to) that you are A1298C homozygous, as I am. I’m struggling with getting my methylcobalamin levels up before beginning methylfolate, since I want to avoid side effects, especially since I have developed histamine intolerance and some anxiety and high homocysteine levels as a result of the B12 deficiency. Anything you have learned from your own experience would be extremely useful to me, if you are willing to share. Thanks.

        • Dr Ben May 26, 2012 at 7:21 am # Reply

          Ky –

          Lynn is correct.

          One has to keep in mind that methylation is dynamic and one can shift quickly from under and overmethylated – in a matter of an hr it is possible – or less – especially if utilizing potent nutrients such as methylfolate or methylcobalamin.

          We have to keep in mind that there may be other mutations on board – such as COMT. Niacin speeds up COMT which is one reason why it also may be useful. If one speeds up COMT, then things like dopamine and epinephrine get broken down faster. Niacin also is a ‘sponge’ for methyl groups, namely SAMe, because SAMe is required to metabolize niacin.

          Inositol is supposed to help reduce the flushing of niacin – not sure how that works – perhaps inositol reduces histamine?

          Two years ago and diagnosed as undermethylator doesn’t mean much currently – especially if he has been given methylcobalamin and/or methylfolate.

          The key is to use Niacin during times of overmethylation – that’s it.

          • Ky May 26, 2012 at 7:46 am #

            Good-o. Warm thanks to both for the advice. I’ll buy some Niacin for those overmethylated moments. Ky

          • Michael_Dowdy February 12, 2014 at 9:23 pm #

            Hello Lynn_M and Dr. Ben. I’m sure you know that I stumbled upon methylation more by accident than on purpose. The timing of the methylation is critical, as you already know, in the fight against cancer. I’ve seen enough death by cancer It’s not easy to trust in the knowledge of those who went before. DNA and gene expression is fascinating! Methylfolate has more impact than anything I’ve ever taken, except possibly the TMG. TMG (and a few nutrients) had a huge impact on my mother’s auto-immune system, psoriasis nearly disappeared and skin health improved. Dose dosage of 5 mthf vary with the patients weight? Why not just reduce the 5 mthf and wait it out instead of cascading treatments? Respectfully, Michael Dowdy

        • terri October 19, 2014 at 1:31 pm # Reply

          Ky….his symptoms sound like pyroluria.

          • Madge October 19, 2014 at 8:55 pm #

            If he has Pyoluria, he is most likely riboflavin deficient. This condition comes from incomplete synthesis of haemoglobin. The last step in the synthesis requires FAD, which come from vitamin B2, riboflavin.

      • Kathleen February 13, 2014 at 7:01 am # Reply

        Michael Dowdy,

        May I ask what dosage TMG your mother took to get her psoriasis to calm down? My friend has C677T Hetero and 1298 and has what the doctor thinks is psoriasis. He takes Betaine HCL with protein intake. I’ve been reading that TMG is exactly the same as HCL. Don’t now if the TMG dosage can be translated to dosage of HCL needed to clear up psoriasis. Any idea what dosage HCL would equal the TMG doage your mom took? Thank you!

        • Michael_Dowdy February 13, 2014 at 9:30 am # Reply

          Hello Kathleen. I’m not a healthcare professional. TMG and Betaine HCL are supposed to be the same. I give her 500mg morning and evening. She believes the extra virgin coconut oil added to her diet is the reason her skin improved. I think it’s the combination. I’m currently trying to find out if GSH levels are affected with use of TMG. For some reason her auto-immune system seems to have improved. I hope this helps!

          • Kathleen February 14, 2014 at 2:59 am #

            Hi Michael,

            Thank you for your reply. I checked for TMG to no avail. Which brand do you use for your mother? I found one by Source Naturals but the dose per pill is 750mg. That seems high and without the ability to incrementally increase.



          • Iatrogenia February 14, 2014 at 5:44 pm #

            TMG and betaine HCL are two different compounds.


            “What is Betaine? There is confusion about the terms TMG, betaine, and betaine HCL. TMG stands for “Trimethylglycine”, which is the chemical term for betaine. TMG is sometimes sold under the name “anhydrous betaine” (TMG without water), “betaine monohydrate” (TMG with one water molecule), “glycine betaine”, or “oxyneurine”. Betaine has a pH between 5 and 8, which is neutral. It is more than twice as soluble in water as Betaine HCL, has a lower molecular weight, and is manufactured differently…..

            Betaine HCL (betaine hydrochloride) is betaine with hydrochloric acid. It is sold as a digestive aid due to its strong acidity. Betaine HCL is usually synthesized, whereas TMG is made from sugar beets. There are no published studies on whether betaine HCL can function as a methyl donor to lower homocysteine and elevate SAMe. Although this is theoretically possible, its extreme acidity (a pH of 1) makes it an unlikely candidate for chronic use. Some clinicians have tried to use betaine HCL to lower homocysteine, but found that compliance was low, with most patients refusing to continue taking it. Several companies have been marketing betaine HCL as TMG (betaine HCL is cheaper), so one should be careful. Fortunately, the acidity of betaine HCL makes it easy to recognize…..”

          • Dr Lynch February 16, 2014 at 8:17 pm #

            Thank you for sharing this. Good information.

        • Michael_Dowdy February 17, 2014 at 2:55 am # Reply

          Hello Kathleen. Dr. Ben has posted the answer in part about the difference between Betaine HCL and TMG / trimethylglycine. Find his comment in answer to Iatrogenia’s description of the difference between Betaine and TMG. It doesn’t seem likely that anything will eliminate psoriasis but sometimes psoriasis will change or fade away. I believe psoriasis is an autoimmune disorder as I’ve had a couple of breakouts myself that were tested and found to be a psoriasis type skin condition. The TMG that I purchased was sold under the Swanson label and on the bottle in the Supplement Facts stated to be TMG (Trimethylglycine) (from BetaPower registered trademark Natural Betaine) 1 gram, with the dosage of two capsules. It also states on the bottle that BetaPower is a registered trademark of Danisco USA, Inc. I see no mention of HCL anywhere on the bottle. I’m not a healthcare professional so I recommend that you read Dr Bens comments and answers for the correct information. I am taking methyfolate as well and as I stated and I’m not sure of all the reasons for our improvements. I hope this is helpful. Thanks for sharing. Michael Dowdy

        • Michael_Dowdy February 17, 2014 at 5:51 am # Reply

          Hello Kathleen. Ray Sahelian, MD has an article about the differences in anhydrous TMG and Betaine HCL and discusses both. Search for it and I’m sure you will find what you’re looking for. The article is dated Feb 7 2014. I hope this helps.

  16. KarenT June 1, 2012 at 1:01 am # Reply

    Hi Dr. Ben, I am compound heterozygous C677T and A1298C.
    1. I am tired and foggy and have been having a few headaches. Tired is nothing new, I’ve recently been diagnosed with sleep apnea and have been sleeping with a cpap machine for ~2 months. I thought I was feeling better, but now I’m not. I’m also newly pregnant through IVF after several problems with pregnancies.
    2. I have not tried the niacin yet. There is already niacin, mostly niacinamide in my prenatal and B complex. 60mg altogether, so I’m leary of taking more.
    3. No. I felt great at first, but have just been tired now for quite a while, which is why I got the sleep study done, before becoming pregnant.
    4. My doctor started me on Folgard, or he said I could take 4mg folic acid and a B vitamin supplement. I read that it should be methylfolate and methylcoblamin and switched to those a few weeks ago at the same dose, which the dr. said was fine. I’ve actually been having a hard time finding a dr. who knows much about MTHFR, but I’m looking (Olympia, WA is the nearest big city and is over an hour away). I’m wondering if 4mg methylfolate is too much? Is it safe for pregnancy for me to cut this down?

    Thank you, Karen

  17. Bridgette June 17, 2012 at 9:24 pm # Reply

    Hi Dr. Ben,

    I have suffered from mild depression my entire life and have taken a variety of meds from prozac to effexor for the last 15 yeears. In March 2012 I discovered I have one copy of A1298 and my practioner prescribed 15mg of Deplin for 3 weeks. Within a week I had an improved sense of well-being and increased energy and felt better than I had in years. My homocysteine levels were still high so the practioner suggested I increase my Deplin dosage to 22.5mg, which I did. After reading through your site I recognize the agitation, headaches and irratability I have been experiencing since I increased the dosage as side-effects of too much Deplin.

    I stopped taking the Deplin for a couple of days to ‘level-set’ and plan to start again tomorrow but at 7.5mg and add Methyl B12. From what I’ve read on your site and others, BH4 would be a good thing to try as well, especially given my history of depression. How long should I wait before increasing my Deplin to 15 mg, if at all?

    Thank you for sharing your insights!

    • Dr Ben June 18, 2012 at 9:43 pm # Reply

      Bridgette –

      BH4 is something I would not take directly – rather supplement the precursors and recyclers of BH4 – I’ve yet to write a piece on this but will get it done. I’m pretty well versed on it now to do so.

      There are other nutrients needed to reduce homocysteine – besides B12 and methylfolate.

      These are:
      – B6
      – B2
      – Betaine

      Instead of taking more Deplin, consider 1 capsule of HomocysteX Plus in the AM. I’d take it away from the Deplin by 3 hrs. So if you take Deplin upon rising, then take 1 capsule of HomocysteX Plus three hours later or so. Do not take HomocysteX Plus within 5 hrs of bedtime.

      Make sure your doctor and lab are testing your homocysteine levels properly!

      Methylfolate helps produce BH4 – so you are getting some support now.

      If you are still struggling with other symptoms, consider a consult with me so we can address them.

      The biggest thing I can recommend is heal the gut.

    • Andrew December 6, 2012 at 7:17 pm # Reply

      Hi Bridgette, I am wondering how you are making out now with symptoms and your condition, as I was just diagnosed as Heterozygous 1298 as well. Thanks

  18. Sally July 21, 2012 at 9:09 am # Reply

    Hi Dr. Ben,
    I was just diagnosed with heterogeneous c677t and have no idea where to turn or what to do. My doctor recommended this website as well as gave me Deplin in 15 mg tablets. I just received my diagnosis yesterday and as I suffer from mood and anixety felt some relief that this mutation may be the cause of those things. This will be my second day on Deplin but am still worried about taking anything which may cause side effects. My doctor is very busy with patients and I’d feel bad having to check in all the time asking what to take. Should I stop Deplin and take other supplements? The protocol you wrote made me a little overwhelmed as I haven’t heard about most of these supplements, don’t know if all are safe for me to take together and don’t know the proper dosage or even where to begin to experiment safely with the dosage.
    I would love any input or recommendations. Thank you!

    • Dr Ben July 25, 2012 at 6:47 am # Reply

      Hi Sally –

      If you suffer from anxiety and you take all the Deplin 15 mg, it can push you over the edge. I don’t recommend taking such a high amount right out of the gate.

      Should you find that you need 15 mg of methylfolate – than fine; however, giving that all at once without testing a smaller amount first is not recommended. There are other genetic mutations which increase the risk of side effects caused by methylfolate – especially MAO A and COMT.

      Introducing one nutrient and/or one supplement at a time (every 3 days or so) is what I recommend typically.

      I cannot say that you should stop taking Deplin.

      What I can say is you should address your concerns with your doctor and let them know that you are now aware that taking such a high amount of Deplin may cause further anxiety and that you want to start with a lower amount first – such as 400 mcg –

      I typically start my clients on a 1/2 tablet of Active B12 with Metafolin in the AM upon rising. They stay on this for three days and do not increase unless they feel no difference or slightly better. If they feel worse, then we know not to use it right now and no harm no foul.

  19. Sara August 13, 2012 at 4:37 pm # Reply

    I am heterozygous for the MTHFR mutation: C677T. I also have a COMT mutation, prothrombin F2, and celiac disease.

    After a year on a gluten free diet, I was still suffering brain fog, difficulty concentrating, and fatigue. I noticed improvement in fingernail strength after taking methylcobalamin and folate (and other b vitamins), but still had the brain fog, attention issues, and fatigue. I then started taking SAM-e and felt much better. But a few weeks later, I am now geting a lot of the side effects listed above as overmethylation symptoms (namely, anxiety attacks as well as general increase in anxiety, throwing things, irritability, trouble going to sleep) about 8 hours after I’ve taken SAM-e. So it doesn’t seem to be related to the onset of increased methyl groups in my system, but to a fall in methyl groups. That is, if I skip my afternoon dose, or if I stay up too late, I feel raw (very similar to how I felt when going through tianeptine withdrawal), anxious, and panicky.

  20. Dolores Seames August 14, 2012 at 12:50 am # Reply

    I just read somewhere that you said the half life of Methyfolate is only 3 hours. I have started on a about 50 mcg by crushing a tablet, only in the mornings. When I tried 200 mcg, I got severe muscle and joint pain, so stopped for a couple of weeks. Now I am starting to get more pain again, with more fatigue, worsening in the afternoons and eveings. I do not get axiety, or any kind of irritability, etc. Should I try to muli-dose it? Can these symptoms be due to just detoxing? I actually started getting these symptoms, but more mild, when I started the methyl b12. I am taking Meriva, 1 with each meal. I tried taking a charcoal capsule at bedtime, and I think it helped, as I skipped it last night, and felt worse today.

  21. Sue August 29, 2012 at 8:10 pm # Reply

    Hi Dr. Lynch,

    I want to schedule a phone consult with you but wonder if you would advise me to have any additional panels done prior. I have tested homozygous for C677T and was put on Deplin by pdoc. In addition she has me on b12, fish oil, NAC and glutamine. I am 34 and have had a few bouts of recurrent depression and anxiety spread out by 5 or so years. In between which, I maintained my overall health by good diet and exercise. I found that I have MTHFR bc the bad feelings had returned and I wanted to go back on Lexapro that made me feel better in years past. However, my pdoc suspected MTHFR was my real issue.

    After finding out that I was homozygous for C677T, a lot of things made sense. My mom had a hard time carrying me to term as well has had a couple miscarriages. There is also a family history of depression and anxiety on both sides and autoimmune issues on one.

    So for the past 3 months, I have been taking 15 mg of Deplin without great relief. In fact, I have been highly reactive and had abnormal mood swings which I never had before. At least not to this extent.

    After scouring your posts, I realize that I probably need to adjust my dosage of methylfolate. I want a new protocol and your advice about how to proceed.

    Would you recommend I schedule a phone consult now or have some additional panels done?

    Thanks for your great work!



  22. Alan September 21, 2012 at 8:50 pm # Reply

    hich MTHFR mutation you have:

    I have homozygous 1298C

    What methylfolate side effects have you experienced?
    None so far (6+ weeks)
    When I tried Cerulin Forte, which has niacin, I got brain fog and a hung over feeling.

    Did the niacin and curcumin help you resolve your methylfolate side effects?
    I was already taking curcumin. Niacin in the Cerulin Forte may have made things worse.

    Did you suffer through the initial methylfolate side effects only to come out feeling great in the end? Or worse?
    No suffering

    Did your doctor start you on a 1 mg or more initial dose of methylfolate and that set you off?
    No., 800 ug, then 1600 ug after 4 weeks.

    Did your doctor taper you up gradually and slowly on methylfolate? How’d that work for you?
    Yes. Good so far.

  23. Katie October 3, 2012 at 1:03 am # Reply

    Hi Dr. Ben,

    I started your sublingual b-12 with methyfolate about 60 days ago after discovering I was compound heterozygous with MTHFR mutation following the loss of my baby boy at 20 weeks and then, 3 months later, the loss of another baby at 7 weeks. I have one son, and that pregnancy was completely normal. Anyway, for the past month, I have been noticing some of the symptoms you have listed here like anxiety, muscle/joint achiness, acne, and headaches. But I’ve also been experiencing throat tightness, soreness/achiness/fullness/tightness in neck (front and back, but mainly front), sore throat (but not where a normal sore throat would be…further down), shoulder and pectoral muscle tension, ache/soreness in left armpit, swollen glands in the neck, muscle weakness…especially in my neck and arms, occasional tingles on front of thighs and head, right eyelid twiching on and off, and major fatigue (MUST take a nap almost every single day). I was wondering if these things could also be attributable to the sublingual b-12 supplement. I was on Claritin for a couple weeks because a Dr. said I have post-nasal drip, but I didn’t take it today to see if that would relieve any symptoms. The only thing that seemed to be better was the fatigue. I know that I’ve had weird throat stuff with my anxiety issues in the past, but nothing as persistent as this. We could possible be pregnant again this month, and potentially in the months to come if not. I don’t want to stop taking the sublingual b-12 because I’m scared that I won’t be able to provide the folate that the baby/future baby needs.

  24. Jennifer Walls October 7, 2012 at 4:42 pm # Reply

    I am curious about dosing because I have been told by others at mthfr support that I am on WAY too much methylfolate. I actually posted in the forums section on this site and have not received a response, so I’m reposting here. Here’s what I said:

    In July I was diagnosed homozygous A1298C. I have suffered from depression, turned into bipolar disorder, anxiety, foggy headedness, horrible memory problems that appear to be dementia that were misdiagnosed (hopefully) as dissociative disorder. I also have cellular hypothyroidsm, chronic fatigue, allergies, shortness of breath, heart palpitations, hair falling out and brittle nails, numbness and tingling in my arms and legs.

    I was put on 20 mg methylfolate with 1 mg methylB12 for a month. Then they said they underestimated the dose and gave me 50 mg methylfolate with 2 mg methylB12 which is what I am on now. I had a couple of people on MTHFR Support say that is WAY too much methylfolate. I was concerned when I heard this but the only side effect from the supplements (I am also taking P5P, TMG, omegas) I have had is fatigue. I have gone from being dependent on 300 mg lamictal, down to ZERO! I am off my lamictal now!!!! THAT is a miracle because I had tried to come off it a couple times and could not.

    So, should I be concerned that the 50 mg is too much? Or credit coming off lamictal to the large dose and consider it safe?


    • Ashlee December 9, 2012 at 12:24 am # Reply

      Jen, you most definitely have all the symptoms of mercury poisoning. Do you have silver dental fillings? Dr. Andrew Hall Cutler’s (PhD Chemistry, Princeton) book Amalgam Illness: Diagnosis and Treatment helped me the most with my health. I was suffering from all your symptoms (actually 64 symptoms in total) and since I’ve had the fillings removed and detoxed using his protocol (he uses low-dose frequent chelation, which means you dose on the half-life of the chelator, which is completely mandatory for detox) I’m down to about 10 symptoms and my life is way more manageable. Dr. Cutler talks about the MTHFR mutation and how most of us are sick from mercury. Vaccines are also a huge source. He has another book Hair Test Interpretation: Finding Hidden Toxicities that can help you to diagnose the heavy metal toxicities that you may be suffering from.

  25. Laura October 9, 2012 at 7:06 pm # Reply

    Not sure if you are still responding to these posts, but I thought I’d put my response out there. I am homozygous A1298, diagnosed two years ago after two miscarriages. I was on a compounded MTHFR vitamin during the pregnancy and delivered a healthy baby. Since then I’ve only been on Folgard, which I recently learned is not doing anything of benefit for me. So my naturopath recommended 25 mg. mB12 injections which I started three weeks ago. Two weeks ago I started methylfolate, 1000mcg. Immediately had acne flare-up, headache, body aches and fogginess. Last week I backed down to 500 mcg. and no more fogginess but still persistent headache and body aches. Guess I back down more? I haven’t tried the niacin. I hate taking pills, I just want to find the right dose to feel good, not add on more pills. My main complaint is chronic fatigue, acne and anxiety. I’m 38 and have been dealing with all of the above for as long as I can remember.

    • Carly October 22, 2012 at 9:14 am # Reply

      Hi Dr Ben

      I have MTHFR hetero C677T and my naturopath recently put me on 1mg of methylfolate and I was fine for the first week and then I started to get hot flushes and burning in my chest and in my back.
      I have been off it now for a week and I still have to burning/hot flushes. Can methylfolate cause these symptoms?
      How can I stop it?

      • Teresa February 20, 2013 at 2:54 pm # Reply


        I have similar symptoms and wasn’t sure that it was caused by the 5-MTHFR, but now I think so. Mine started just after taking 1 mg for 3 days. I upped mine thinking it was something else, but maybe not. I am waiting for more mutant gene results and hoping that shreds some light. Your information has been useful; thanks for sharing. I wish that Dr. Ben had responded to you as he may have had some answers. Teresa

  26. Beckt Rubens October 28, 2012 at 5:57 pm # Reply

    My son has CFD but did not test positive for a C677T mutation. He’s low functioning autism and put EVERYTING in his mouth since starting methylfolate. Could this cause this excessive pica? His zinc level is fine so I know it’s not that.

    • Dr Ben October 29, 2012 at 9:04 pm # Reply

      Beckt –

      Could simply be too much overstimulation. Talk about this with your doctor. Perhaps decreasing the methylfolate and adding in a touch of niacin may calm him down. Checking serum ferritin and MCV, MCH are also important.

  27. Aaron Runfalo November 13, 2012 at 12:38 am # Reply

    Just received results heterozygous A1298C. MD put on generic L methylfolate 15mg daily. Started 3 days ago. No side effects at this time. Do you recommend decreasing dose? Was having joint pain, fatigue, brain fog and several other symptoms for last 5 years, not diagnosed with any other conditions. Also received results with pos. lupus anticoagulant this visit. Is this related in any way? Do you suggest decreasing dosage of methylfolate?
    Thanks, Aaron

  28. nona November 17, 2012 at 5:49 pm # Reply

    Hi DR Ben Please help … I was pregnant in the sixth month has died fetus Li said Dr. in Egypt taking folic acid 5 mg and I’m currently after abortion at 4 months and continuous p this drug, but I heard that methylfolate much better than folic acid, which Egypt has, but I did not knowdose did not know him anything with the knowledge that I have MTHFR C 677 ÇÔßŃß many that have been answered ….. Will take it if it happens carry with Aspusid

  29. Liz November 24, 2012 at 3:46 pm # Reply

    I have a hetero C677t mutation. I don’t have any (obvious) health issues and I have been working on cleaning up my diet for sometime (very similar to your diet recommendations) to hopefully help with a healthy pregnancy sometime in the future. I started taking 1,000mcg of L-5 MTHF and immediately I began getting headaches but no other symptoms that I have noticed. I haven’t had a headache in years before this supplement. I am going to drastically cut back on the dose and try to work my way up. Mostly I am just really surprised to have this reaction when I’ve been following an anti-inflammatory/healthy gut diet for over a year.

  30. Paulette Turner November 28, 2012 at 12:13 am # Reply

    I have Fibromyalgia and am so sore all over. My Rheumatologist
    has me on Savella, 100 mg, 3 times daily (2 in the morning, 1 at
    bedtime. I have been taking it for about a year and can’t tell it’s
    helping. I wondered if Methylated Folate might help me and how much
    should I take.

  31. Ara November 30, 2012 at 5:29 am # Reply

    The only side effect that I got when I tuck 1mg of 5-MTHF was extreme sleepiness.
    Am I the only one?

    • Andrea February 13, 2013 at 12:12 am # Reply

      I have that side effect too at 1 mg – but a lot of others, because I am homozygous comt

  32. Andrew December 6, 2012 at 5:37 am # Reply

    Hi, just one question… First of all I fall under your number 2 category for side effects. Heres my question:

    Ive got 1000mg tablets of ‘sustained released Niacinimide’ already in my home, are these okay to use as your explained ‘ time release niacin’?

    Thank you so much

  33. sue smith January 22, 2013 at 1:21 am # Reply

    This is an interesting article because my fatigue is overwhelming as well as brain fog. I’m dealing with alot of other issues like cfsids (but no relapse for 15 years) and thyroid but everything seems regulated except my vitamin deficiencies. When I seem to clean out my system, not from choice, I do feel better so this will definitely be a discussion with the doctor.

  34. douglas January 22, 2013 at 7:44 pm # Reply

    Hi Dr. ben
    Unfortunately I don’t believe I can tolerate L-methylfolate. I had a suspicion I was a ‘hyper-methylater’ years ago when I tried SAM-e.
    Last week I bought a bottle of Metafolin and took only 400 mcg. for two days along with my every other day dose of 10 mg. fluoxetine and my every night dose of 50 mg. doxepin. Started to get a down in the dumps feeling and strange dreams at night. Yesterday just took half of a 400 mcg. tablet and the same strange mood started to creep up on me. But all is not lost as this is helping me to put the ‘puzzle of my mind’ together.
    From now on I will consider myself a over-methylator and concentrate on things to quench methylation.
    Thanks for the great web-site…

    • Andrea February 13, 2013 at 12:14 am # Reply

      What are your comt mutations? Mine is homozygous ++ which makes me not process neurotransmitters correctly. I undermethylate and overmethylate at the same time.

  35. Katherine January 30, 2013 at 4:31 am # Reply

    In 2004, I was 31 and I started taking a pre-natal vitamin in the hope of getting pregnant. I took the supplement for 6 months and started feeling really awful. i was exhausted, lethargic. I felt toxic and was depressed. After several months of this, I was diagnosed with Inflammatory Breast Cancer. I underwent six months of weekly chemo, a mastectomy and radiation. I spent a lot of time in the years that followed working with a naturopath to recover my healthy in a variety of ways. I was always low on B12 and i received injections for years. They never seemed to work then, eventually, my naturopath said, “Oh, you’re one of those people” he found a kind of methyl b12 and folate in a capsule and said, “if these work for you and you feel better then you can only take this kind.” I took it for several years and felt a little better. He retired not long after that.

    About a year ago a friend started talking about MTHFR and I figured I had a mutation or two. I also figured my adopted daughter did as well and last summer we both took some of the methyl b12 and folate and we both did really well, we felt good. Then in the fall, I started feeling REALLY awful. Just like i had before my diagnosis and I told my oncologist and all my doctors. I am seeing a new naturopath now and I told her and I asked her to run the MTHFR test. She gave me an injection of folate before we even had the results. I felt AWFUL. Even worse than before. My test results showed I am compound heterozygous for C677T and A1298C. She said she wanted to give me these injections every week or few days. I told her no and recommended your site. Since then I have stopped taking all B12 and Folic acid supplements. I have started drinking 32 ounces of the MTHFR-ade you recommend and I sweat heavily 2x per week. I also take epsom salts baths, all focused on detoxifying my body and I feel so much better. I’ve been doing this for the last 3-4 months. I also discovered that the supplement I had been taking in 2004 contained methyl b12 and folic acid. I think my inability to clear my system of toxins may have been a contributor to my diagnosis.

    Thank you for providing all this information. I am currently 39 years old and cancer-free (as far as we know) and i have two adopted children (5 and 2). I hate to think what could have happened if I hadn’t come across your site.

  36. Aline February 4, 2013 at 2:51 pm # Reply

    My doctor who wrote a book on leaky gut, who makes appearances on the Dr. Oz show, prescribed me 1600 mcg of methylfolate right off the bat. I am compound heterozygous for MTHFR. Well, after a little more than a week I could not get out of bed – I was beyond exhausted and severely week. I was severely depressed and irritable. I was constipated and my joint and muscle pain became much worse. I realized it was the methylfolate and stopped taking it. I wouldn’t be that upset except that 2 weeks earlier I had flu like symptoms from the probiotic she gave me. She never told me that there could be any side effects from the two and she never told me to start off slow. I live in New York but do not know who to go to who will really care about my health. The visit was $750 and I’m sicker than when I went in. I would even do phone consults if there is someone out there who really cares about their patients. I know a few mistakes will be made but I don’t think this doctor understands my situation at all. Please help!

    • sue February 5, 2013 at 6:45 am # Reply

      I only take 800 mcg of methyfolate. I, too, have been having stomach problems but dealing with vitamin deficiencies, pancreatic and stomach issues. Can’t take protonix anymore because of osteosporosis. I do my research and I am doing well now and folate is normal. I had to get everything else stronger to deal with the mthfr gene, too, which doesn’t seem to effect me other than vitamin b12. I would recommend going to several doctors, a gene doctor, etc. to research individual problems.

  37. JK February 14, 2013 at 4:45 am # Reply

    Hello Dr, Ive recently increased methylfolate from 1.6mg per day to 3.2mcg per day because my dr wants me to ramp up to 10mg because of homozygous c677t (two copies of this mutation) My question is on irritability, mentally i feel fine but i feel uncomfortable in my own skin like my nerves are buzzing throughout body (itchy/cold). Side effect or no? Its always tough for me to tell because im always adding and changing things for my lyme protocol. Also, my body has an intolerance to taking small amounts of B6. It builds in blood and gives me tingling. Would that be related to MTHFR also?


  38. sue February 14, 2013 at 4:57 am # Reply

    I take (L-5- Methylfolate), along with b-6 and b-12. I believe (L-Methylfolate) is B-8. I have the C677T MTHFR mutation. Is this what everyone is saying causes side effects. I have been dealing with severe fatigue(I suspect from CFS) but my folate level did improve, as well as thyroid, vitamin D and B12 is high.

  39. Jeanie February 15, 2013 at 2:05 am # Reply

    Hi I have the MTHFR mutation +/- on all 3, and also CBS C699T +/+

    I took active b12 with L-5-MTHF

    The first two days I took a whole lozenge and felt an odd anxiety. I just started my menstruation cycle so wasn’t sure about the symptoms. I took 4 days off to be sure.

    Then I took 1/2 of a pill/lozenge. I felt fine for about an hour then throughout the day felt:

    insomnia that night
    sore muscles and achy joints
    headache by the end of the day
    tiny bit of hives
    my chest tightened in the evening
    at 3pm onward I was exhausted, napped, still exhausted.
    By the end of the night I was also unusually depressed, cried a bunch for no reason(several times), and felt hopeless. Luckily I realized where it was coming from.

    I need to clear my Sulfur channels I am guessing, and maybe unresolved inflammation. Just moved out of a mold infested house 4 months ago, and also got rid of h.pylori about 4 months ago. That’s what led me to study my genetics.

    Thanks for listening,

    • Dr Ben February 16, 2013 at 5:55 am # Reply

      Hi Jeanie –

      When you feel odd from taking any methylcobalamin or methylfolate, please do consider taking about a 1/10th of a tablet of Niacin every 30 minutes until the symptoms have relieved. Niacin acts very quickly.

      You may have increased hydrogen sulfide production along with increased stress hormone production. If you have CBS, you most likely increased your hydrogen sulfide production.

      Right now, use very little of the Active B12 with L-5-MTHF and focus on healing your gut and reducing sulfur-containing foods and supplements for a little bit.

      Consider a molybdenum supplement as well to support your sulfur pathways.

      Also consider ProBiota Sensitive – 1 capsule after dinner. It is a prebiotic-free probiotic.

      In health,
      Dr Lynch

      • Michael (MG) March 25, 2015 at 10:30 pm # Reply


        I am not MTHFR, but I am MTRR, MTR, NOS, CBS and VDAK, etc…. I’m taking Methly-B12, a co-enzyme B complex, vitamin D, etc….(previous ammonia, sulfite tests were normal)

        My co-enzyme B complex has about 400mcg of Methyl-Folate. And I’ve been doing fine with that. A few weeks ago I added 1000mcg Methly-Folate because my doctor said this would help increase BH4 production (actually she wanted me to possibly take 10,000mcg). Anyway, first few weeks I was fine, then about a week ago, I started getting SEVERE insomnia again. Felt wired all night long. Not sure if it’s the Methly-Folate or not. It could be. Not sure if it’s good to be taking more Methly-Folate if I’m not MTHFR defected. Not sure if I’m over methlyating or detoxing more or what.

        About a week after starting the increased Methly-Folate I added 400mcg of Chromium to help stabalize my blood sugars etc.. They weren’t that bad, but chromium definately gives me more energy (mental) and mental clarity. But, I tried chromium about 2 years ago when I was a lot more ill, and it made me feel good, but gave me SEVERE insomnia, couldn’t sleep. So, not sure if the addtional chromium is causing my insomnia issues now or not. The first two weeks were fine. So first I added more Methly-Folate, then Chromium, then I added 500mcg of adenosylcobalamin form of B12. That is supposed to increase energy in the cells, etc..I started this 5 days before the severe insomnia.

        So, I stopped the chromium, and adenosylcobalamin, and I might stop the methly-Folate (1000mcg) next. Maybe drop it down to 400mcg additional. Not sure.

        I do have adrenal fatigue, and I think I might be over stimulating them some how with these supplements.

        Anyway, just wondering if methly-folate could cause severe insomnia in those who don’t have the MTHFR mutation? My mood is still decent. But feeling more anxious at times (arm pit sweating) but overall stable.

        Thank you for any insights.


  40. Susie February 15, 2013 at 2:27 am # Reply

    My 6 yo son has Autism and is also compound hetero. He takes B12 shots once a week and can only handle the folate in his vitamin. Everytime we try to give him any other source of folate he gets very irritable. Can he take the B12 only with just the folate in the multivitamin? Or does he have to have some sort of additional folate for the B12 to work right?

  41. Mary February 17, 2013 at 5:30 am # Reply

    I had gene testing back in 2003 for a research study and they found the MTHFR gene revealed compund heterozygosity for C677T & A1298C, they also found heterozygosity for the thrombophilic Factor V Leiden with accompanying resistance to activated protein C, heterozygosity for the thrombophilic PL A1/A2 glycoprotein gene mutation, and homozygosity for the 4G/4G polymorphism of the PA1-1 gene.

    At the time it was recommended that I take Folic Acid 5mg per day, B6 100mg per day, B12 2000 mcg per day, Glucophage 1gm twice a day, and 10mg lipitor. I did this for a few years, but then kind of stopped. Recently met someone who actually heard about MTHFR and put me on 15mg Deplin which I started at full dose. Never had a side effect, but didn’t feel much different. Met another doctor who said that wasn’t quite right and I needed Metanx, and has started me on a 1/2 pill, working my way up to 2 pills per day. Currently at 1.5 pills. Not sure if this is a side effect but my mouth burns a bit, feel very thirsty all the time. Also have a period of difficulty staying awake approximately 1 hour after taking dose. No miracle drug effects, but nothing horrible either. Should I go back to taking any of the above vitamins?


  42. Molly Gibson February 19, 2013 at 2:49 am # Reply

    If niacin helps speed up COMT to breakdown neurotransmitters, then is it unnecessary to avoid methyl groups if you are homozygous COMT (as Yasko recommends)? Or can you just take niacin if you start getting over-anxious? I am also homozygous A1298C, and it seems like a bad idea to avoid all methyl groups, and unsafe to take methyl folate apart from methyl B12…What about less methyl B12 and some adenosyl B12?

  43. DK February 24, 2013 at 6:53 pm # Reply

    Hi Dr. Ben,

    I’ve found your website to be extremely helpful. I am homozygous (C677). I havent had any issues throughout my life other than several miscarriages as well as generalized anxiety. I did have one successful pregnancy on a regular multi-vitamin, folgard and Lovenox. I am pregnant again and, having found your valuable information, am avoiding folic acid this time around. I started taking Thorne prenatal two weeks ago and felt amazing right away! Much more alert and energetic. I have had some bouts of pretty intense irritability but I thought that was pregnancy hormones ;) This week, I tried taking half a pill of L-5-MTHF to get some additional methylfolate and within a few hours I could not stay awake. This is not normal sleepiness… I was basically asleep on my feet. Is this over methylation? Should I just stick with the Thorne prenatal and nothing else? Or try the lozenge with the combo methlycobalamin and methylfolate? Thanks!

  44. Donna G February 25, 2013 at 5:41 pm # Reply

    Dr. Ben, my son, age 9, is homozygous for C677t He had been on methyfolate 800 mcg daily by Metagenics. His functional medicine MD thought maybe increasing it might be good since he was having more behavior issues. He was increased to 1000 mcg daily and now to 1200 mcg daily, now on Thorne brand. He began having severe anxiety issues about 4 months ago, we assumed related to issues at school, but now I am wondering if it is related to the methylfolate. His anxiety comes in bursts lasting for days to weeks, then seems to calm. I have him on Niacinamide 500 mg daily as well, as I read this can help with aggression issues. He is diagnosed as severe ADHD, hypothyroidism, likely celiac disease (documented gluten intolerance) casein intolerant, and anxiety disorder, simple tic disorder and is being evaluated for high functioning autism. Can you help ?

  45. kate March 1, 2013 at 6:56 pm # Reply

    Hi Dr. Ben.
    Thanks so much for posting this info. It’s such a relief as it likely explains what I am going through. I have homozygous A1298C. I’ve been feeling quite good since my doc started me on Deplin about 3 weeks ago. I slowly raised from 3.75 to 7.5 and my sleep was getting increasingly worse. By day I was feeling great until the last couple days, in which anxiety and brain fog started creeping back in. I read somewhere today that Deplin dosing as taught to MD’s starts at a higher dose of methylfolate than other forms typically do. As I’m highly sensitive I think that’s gotten me into trouble, but Deplin is the only form my doc is familiar with. Once I can sleep better and I resume taking methylfolate, is there a particular form/ low dose that you would recommend I start at to avoid the same again? Thanks so much for the information you share.

  46. William Cooper March 2, 2013 at 5:27 pm # Reply

    Methylfolate can conflict with Depakote–a common seizure, epillepsy medicine. My compound hetero son (age 18) takes 2000 mcg of mthf. We slowly increased his dose to this level with methyl B12 also. More mthf increases his partial seizures. This is a known adverse interaction also reported by other sources. As Dr. Ben notes…increasing doses slowly helps identify such interactions before they are severe. The B12 and mthf definitely help son’s depression and fatigue.

  47. Tom March 12, 2013 at 12:48 am # Reply

    So glad to have found this comment section… I respond in the 3rd way as described by Dr. Ben. I can’t tolerate methylfolate at all, along with a host of other methylation supplements like methionine and TMG. I will have to try taking niacin with my supplements, and I KNOW I have some big issues with candida. I probably have inflammation that needs resolution, as well as a diet that needs transformation. I tried “The Candida Diet” for some time, and got some good results, but I think the sulfer-less diet is what I will focus on now.

  48. Pam March 16, 2013 at 5:43 pm # Reply

    I found out 3 weeks ago I was a Heterozygous A1298C. I was started on L-MethylFolate – 1000 mcg daily along with 5000 mcg methylcobalamin B 12. I was already on Reduced L-glutathion lotion 1 gm daily. Normal homocysteine levels. I responded in the 2nd way. The first week was fine. By the second week I had extreme anxiety, mental fogginess, muscle pain, constant headaches, some vision problems, and nausea and diarrhea. I have not taken Niacin as I am having a difficult time finding it in such low doses. I stopped taking the mfolate immediately, but continued on the mB12. The symptoms actually became worse over the next 6 days. Finally, in the last day or so the symptoms have become better, but still not gone. I am so new at this I am not sure what the next course of action will be. I am having further testing done to see if I have other mutations, but it is my understanding that those tests can take up to 3 months to get the results back. There was no taper nor at this point in time do I want to go back o the mfolate or mB12.

    • Teresa March 17, 2013 at 5:17 pm # Reply

      Pam I also had a bad time with the 5 MTHFR; I ended up in the emergency room. Nasty. I sent for more testing with Yasko and just received results. I have numerous mutants including CBS which causes a build up of Ammonia and sulfur in the body. I am reading the book on the disc Yasko sent with results trying to decide what to do (I am off all converted B’s) since I have CBS I decided to send for sulfur urine dip sticks and start a low sulfur diet and I am consider trying the yucca and charcoal to help detox the ammonia. It will take six weeks to see my naturopathic about the new mutants. So I am going to continue looking for a specialist or have Dr. Yasko evaluate the results which will take who knows how long. Frustrating that more doctors don’t understand the methylation pathway mutant genes. This process is so long and difficult since we all have probably suffered for a lifetime already. If I had the money I would have had Dr. Yasko evaluate the results in addition to just the results. Now it will take longer. I didn’t expect to have 11 mutations, 6 of which are +/+ and 5 +/-. Poor me. No wonder I haven’t felt well all my life.

      • Pam March 17, 2013 at 6:01 pm # Reply

        Teresa- Thank You for responding. I agree it takes to long to figure out what is going on. I am opposite in many aspects from where you are but this past year has been extremely trying and costly, so much wasted money trying to figure out what was wrong with me. I have finally found an excellent Integrated medicine doctor and he was the one who identified the MTHFR mutation in myself. I am in the medical field and have been for the past 30 years and had never heard of the MTHFR mutations. Kind of an eyeopener. My doctor is in Ann Arbor, Michigan…..and I am not. I know he does phone consults and cares for patients across the country. I am very lucky to have found him. He does not make you wait 6 weeks to see him, and is usually only hindered by how long the tests take to come back. His name is Dr. Tony Boggess, and he works out of his clinic which is called Natural Balance Wellness Center. His clinic has a website which is Insurance does not pay for his visits, but he is well worth it to me. I am so new to this information I could not even make a guess as to what I should be doing. I have started reading the information from D. Yasko’s site, but don’t have enough understanding of the information to start helping myself.

  49. Gabriela March 17, 2013 at 3:01 pm # Reply

    Due to panic attacks and severe OCD my psychiatrist put me on 100 mg of Luvox and 1 mg of clonazepan. Then a naturopathic doctor put me on 1000 mg of L-5-MTHF , p-5-p 50 mg and 1000 mg of methylcobalamin (all in one supplement), I tried it once and I felt like going to the ER because my heart felt like it would pop-out of my body. Next day, I decided, I would start slowly by my own choice and in separate supplementation. I started with 400 mg of metafolin. I felt great!! the anxiety was reduced a ton! It was so amazing that I got off of clonazepan. However, at the same time the OCD started increasing. The more I took it the better the anxiety got and the OCD worsened. However, during my period or ovulation the anxiety is enormous no matter what I take, and I feel all the side effects listed for methylfolate in the website. Then I doubled the mtfh and I started feeling a little side effects all the time, so I added the p-5-p and I felt the anxiety calm down ever more. Yay!!! but the OCD was getting brutal. I saw your presentation on youtube accidentally and I realized that I had to add the methylcobalamin. I added it and a couple of hours after I did the OCD got reduced by 50% but the anxiety increased!!! crazy huh? the day after I tried it again, the same thing happened. Third day I did not feel crazy anxious but I felt a little too Luvoxy. My psychiatrist told me to tapper down 25 mg and I felt a little (very little) better. I decided not to take it the next day, big mistake! I felt the way people feel when they discontinue an SSRI cold turkey!!! I saw a presentation by dr Jared Skowron and I emailed him. He suggested COMT and MAO testing. I will do that next week. So far, OCD is crazy and anxiety getting better.

    • Dr Ben March 18, 2013 at 7:47 pm # Reply

      Gabriela –

      Excellent post – thank you.

      Dr Skowron’s recommendation is valid. I’d consider 23andme testing as it is more complete – and you can have interpret the results for you.

      Consider Inositol Powder – that may help for the anxiety – along with a bit of Niacin- start with 50 mg or as recommended by your doctor. GABA may also support the anxiety.

      Your body needs to be able to convert the glutamate from the folate into GABA – and magnesium, B6 and GABA are useful for this – along with niacin.

      I would bet that you have COMT, MAO and/or GAD snps – along with potentially elevated estrogen levels. Guessing.

      In health,
      Dr Lynch

      • Dan March 19, 2013 at 6:26 pm # Reply

        Dr. Ben,

        I am 36 yr old, and I was in seemingly perfect health before taking Metafolin and methylcobalamin (B12). After taking those two supplements together, I suddenly started having severe panic attacks and anxiety — and I have zero history of anxiety or panic attacks before taking those vitamins. I was taking niacin at first, which helped a bit, but after two weeks of increasing anxiety, I started taking GABA and felt much better. My doctor said I could stop GABA after two or three weeks of feeling better. So, I stopped GABA once I felt better (3 weeks later) and the panic attacks resumed within a few days.

        So, now I am now back on the GABA and slowly starting to feel better. But, now I am worried that I have permanently screwed up my body. I just want to go back to the way I was before I started taking Metafolin and methylcobalamin. I feel awful without GABA, but I don’t want to be on GABA for the rest of my life.

        I happened to have a account and (right or wrong) it revealed the following results:

        VDR Taq ++, MAO A R297R +, MTHFR C677T ++, BHMT-08 ++, CBS C699T ++

        VDR Bsm +-, ACAT1-02 +-, MTRR A66G +-. BHMT-02 +-, BHMT-04 +-, AHCY-01 +-, AHCY-02 +-, AHCY-19 +-, NOS3 D298E +-

        My doctors don’t seem to understand this at all and I don’t want to start up complicated protocols that I don’t understand either. We tested calcium and found it to be 10.2 three weeks ago. Tested again this week by an endocrinologist and it was 9.8 (albumin corrected it’s 9.1) — everything else is “normal” in the complete metabolic panel and “normal” parathyroid hormone level of 25 as well.

        I find it odd that I went through life feeling perfectly fine until overmethylating and now I’m struggling to get back to normal. Clearly the GABA helps, but for some reason I can’t stop taking GABA or the panic attacks resume. Have I given myself a permanent panic disorder from taking Metafolin and methylcobalamin? Please help!


        • Teresa March 20, 2013 at 10:44 pm # Reply

          Dan it sounds like you need to see a specialist for methylation pathway mutant genes. With all your mutations it is complicated. I know with the CBS mutant (I have this one too) one produces too much sulfur and ammonia and that needs to come down before taking converted B’s or there is negative reaction. I ended up in the ER taking just taking a very small amount of the 5MTHFR. Now I am waiting for a doctor’s address that has a office a hour or two drive from me; he is a specialist. Then I will make an appointment. Did you have your testing done with Dr. Yasko? She included in depth information with her results. Look up her website and you can read about each mutant gene throughally. Plug in:

          • Kelly April 20, 2013 at 1:44 am #


            Seems like almost everyone goes through this extra anxiety (and sometimes extreme anxiety) at first, but believe me…it isn’t permanent, and it will eventually calm down. In addition, or possibly instead of gaba, you might consider trying some inositol powder. It really helps calm me down.

            Amy Yasko mistakenly says the CBS gene produces too much sulfur/sulfate/sulfite, but she has no research to back this up. I know people (including myself) who have done better by INCREASING sulfur foods (and taking small amounts of molybdenum to help convert the sulfites to sulfates.

            Unlike what Yasko says, sulfate is NOT toxic. Suflite is, but can be converted provided one has enough molybdenum in the diet or through supplementation.

        • Kreiss March 14, 2014 at 8:34 am # Reply

          Hello Dan,

          The same thing happened to me. after taking 15 mg of deplin for about 3 weeks, I experienced high anxiety. Unfortunately, just like you, I still suffer from the anxiety even though I stop taking the deplin 3 months ago. I tried GABA, but it did not work for me. Do you take other supplements to cross the brain barrier ? The only thing that calms my anxiety is Ativan, which I don’t want to take the rest of my life. I am wondering, just like you, what happened that made this change in my body. Did your anxiety went away with time ?

          Thank you.

          • Michael (NW) March 14, 2014 at 4:04 pm #

            Hi Kreiss,

            There are many things that can contribute to your anxiety. taking Ativan doesn’t cure anything, it just provides temporary relief, but then you may have side effects from it, become addicted, build tolerance so that you need more to make it work (better to only take it as needed not multiple times per day every day if you can avoid it), then you can have nasty withdrawal that can be worse than the symptoms you originally took it for (this is especially true if you take it every day, more so if you take it multiple times per day, and of course very true if you end up taking high doses of it every day)… Anyway, GABA (amino acid) has a hard time crossing the blood brain barrier. You can try Phenibut. It’s a derrivative of Gaba that the Russians discovered years ago. You can buy it as a supplement by a couple different companies. You can buy it on There is a product called Kavinace that has Phenibut in it, but it also has Taurine and B6 so if you can tollerate those items, then just buy the straight Phenibut product. And once again, you can build tolerance to Phenibut, and possibly have some withdrawal if you take too much for too long. But people use it for insomnia for years, although not sure if anyone has come off of it…..There are very few reviews of anyone having withdrawal, but not to say it couldn’t happen. I’ve heard taking brakes from it is good. Maybe try it 3 days on two days off. Anyway, there are other herbs that can help with anxiety, the best one I’ve found is Kava Kava, (Kava root). This really calms me, and no side effects that I’m aware of. The only issue you might hear about is liver damage, but the tests that were done from what I can tell were done on people who drank and also took high doses of it. And I’ve read that if you take the root only (which is what most of the Kava products are made from) then it shouldn’t be a problem. But, maybe you can rotate Kava with Phenibut. I like a liquid Kava product by Maui Medicinal Herbs. Works fast, taste good (coconut flavor). Also, Eclectic Insitute Organic Kava root is good. Also, Valerian Root is supposed to be good. It never helped me much but everyone is different. Supposidely it’s compared to Valium which is a Benzo like Ativan.

            The key here though is to find out what is causing your Anxiety and fix that, so you don’t need to take anything. But taking something for now will help you feel better until you can cure what it is that is causing your anxiety. Have you had all the basic tests done, CBC, Thyroid, Hormones, etc…? Low Serotonin can cause anxiety, panic, depression for sure, etc…Ask your doctor about trying out 5-HTP, I’d only recommend starting at low doses like 50mg a day and see how you feel in a week or two. If you can tolerate it without any side-effects keep it up for month and see if you start feeling better, it could take awhile. Another alternative would be taking l-tryptophan which converts to 5-HTP then Serotonin. But, you could have other neurotransmitters that are out of balance, and working with a ND would be a good idea to figure that out. Also, you could have Adrenal Fatigue, and so again I’d work with a ND to figure that out and treat it appropriately.

            If you look at Methylation as part of the issue, and deplin made you worse, then does that say you have enough Folate in your system, and have an issue with methylating B12? Maybe you need Methly-B12.. Hard to say, but you migth get the methylation test done to see where you might have issues. You might have some issues in the sulfation process of the methlyation cycle, which I’ve read could contribute to building up ammonia, sulfate/sulfites, which in turn could increase glutamate, which is an excitatory neurotransmitter…I’d get your methylation check and see if there is anything you can support there to help your anxiety/health.

            I hope you feel better.

            Michael (NW)

          • Michael_Dowdy June 1, 2014 at 11:49 pm #

            Hello Kreiss. Michael(NW)’s suggestion of trying 5HTP in the lower dose Is a suggestion I would agree with. I’ve only had good success with 5HTP. Since Ativan has been prescribed for you though I wouldn’t suggest that you do away with it unless you’re unhappy with the prescribing doctor and intend on not seeing that doctor anymore. You may jeopardize your options and choice of doctors. Until this new healthcare system has survived the test of time I’d be very careful about offending what is possibly a good doctor. If this new system hurts the doctors it will likely trickle down and hurt the patients as well. (I’m assuming you’re a US resident.) I strongly recommend following Dr Ben’s advice to start off very low (400 micrograms) 5-L-MTHF and slowly work up. 15 mg is a HUGE dose and will very likely mess with your brain in a negative way. Study this site a lot and be careful to not offend your doctors. I’m not a healthcare professional, only a patient with the MTHFR CT++ mutation and depression issues. Once again I’d recommend that you continue the Ativan as prescribed unless that doctor or another doctor takes you off of it or you have some very negative effects from the Ativan. Talk to your doctor about any problem. I can’t tolerate more than 2 mg’s of 5-L-MTHF. Ativan treats the symptoms and 5-L-MTHF treats the cause.

        • Fred C. January 25, 2015 at 8:13 pm # Reply

          After reading this I think I will stop what I am doing (taking SAMe and ACTIVE B12 with L-5-MTHF) until 23andMe testing and ND appointment. At 61 my problems are many. I was taking as I have SEVERE neuropthy in calfs and feet. Fells like they are in a freezer!!!!!! I to suffer from anxiety, being on some kind of benzos for THIRTY YEARS!!!! Off at this time but having a hard time. Have had thyroid problems for 5 years but no-one would listen. Now with TSH at .024 with free T3 free T4 normal they checked. Have massive amounts of non-cancerous nodules. Possable adrenal burnout with Test. level at .086, yes thats right! I believe my hormone problems were caused by having the mumps at 11 messing up my pituitary gland. Again I can’t get no-one to test hormone levels.
          Dr. Lynch
          Question: could high serum B12, folic acid, and homocysteine be caused by my body not processing causing neuropthy????
          Also wanted to say glad someone addressed high folic acid levels if taking multiple products. Thanks for massive info.

          • Dr Lynch January 27, 2015 at 8:00 am #

            Fred –

            Definitely need to see a doctor. Please see here:

            For neuropathy, consider:
            – Benfothiamine – 1 to 2 capsules a day – spread out
            – Alpha R Lipoic Acid – up to 4 to 8 capsules a day – spread out
            – Optimal Liposomal Glutathione – start at 1/4 teaspoon on empty stomach and work up to 1 tsp before breakfast and 1 tsp before lunch
            – Trace Mineral Complex

            These are available at

            I do think they will help- but as you said – you definitely need to see a doctor who will help you! :)

      • Amy Southorn June 8, 2014 at 12:02 pm # Reply

        Hey Ben.
        I just found out I am heterozygous C677T. I have Lyme disease. I was thinking of doing the 23andme test to see if there are other defects at play. Does 23andme test CBS, COMT, MOA etc. Epsom salt baths make me feel so much worse and I am wondering if sulfur is an issue. Would love to know for sure. This is all very knew to me. Thank you for the incredible information you share. I am excited to have found your supplements as well, they are the best I have come across.
        Thanks, Amy

  50. Renee March 19, 2013 at 6:20 pm # Reply

    I’ve had issues most of my adult life seems like it Got worse when I had to have my silver fillings redone after only getting them for six months then six months later they buckled and I had to have them redone again This is something I’ve been thinking about lately After learning about our bodies not being able to detox. Past 20 months. I use low-dose naltrexone 2.5 mg for my fibromyalgia pain does help with the inflammation So I have less joint pain. I also take magnesium Gly for muscle aches. But my energy level is still very very low After reading about MTHFR Issues I insisted my doctor run the two most common culprits and I did come back positive for the C677T. I am in the process of having the rest of my genes tested but appointment time has not arrived yet. In the meantime I had started doing Epsom salt detox baths 3 to 5 times a week, Also adding some methyl B12 I was feeling a little better that’s the reason why I insisted the doctor run the two main gene mutations right away. I started the methyl folate a week ago just doing a little bit at a time each day, And I do notice a difference today even more so. I’m happy I have hope once again And happy I may be able to leave this house without feeling exhausted! My sleep is still not right Never has been my entire adult life. I took Ambien for many years but I weaned off of it once I started the LDN. Ambien just did some weird things to me. I hope to get the. 677 protocol down and be able to regulate my sleep. Once I have the rest of the MTHFR issues ran in the lab I’ll know more but for now I see progress. I learned a lot from this website thank you so much. I have tried turmeric before in the past and he gave me bad stomach issues do you think that I could try it again, Maybe with a full stomach? I do try to remember to take my low-dose aspirin Daily as well. Reading on a group site I did buy some Immuno Rx whey protein powder With the hopes and boosting my glutathione if my pathways are going to be better taking the methyl B12 in the methyl folate. Got bless us all have a fast recovery! And thank you Dr. so much for all your time and help

  51. Julie Merlich March 23, 2013 at 1:54 pm # Reply

    I have developed severe restless leg syndrome, starting with my first dose of methylfolate. Even on a very low dose of 200 mcg, I am up all night. I have tried taking Niacin, iron and vitamin E with no improvement. Any suggestions are welcome because I feel great during the day. I am homozygous A1298C

    • Teresa March 27, 2013 at 3:05 am # Reply

      Julie, I have had restless for a few years now ever since I had surgery. There may be an underlying problem beside folic acid deficency; like a B12, calcium or magnesium deficiency on top of it. I am not on the 5MTHFR now, but when I took it and the other converted B’s, my restless leg was somewhat better. I have to wait to go back on because of other mutations. I am seeing a Dr. Rawlins in Richland, WA next month and hope to get the ball rolling. I am also homo 1298 and so are my two children. My husband has at least one. I couldn’t tolerate the 5MTHFR and now I know why because I have ten other mutant genes including CBS along the methylation pathway.

      • Deena October 17, 2013 at 9:32 pm # Reply

        Teresa, Were you able to get good results from Dr. Rawlins? I live in the same area and have been struggling to find a doctor to treat ALL my mutations, not just the MTHFR, so I am very curious as to your experience with Rawlins.

        • Teresa October 19, 2013 at 12:34 am # Reply

          Hi Deena,

          Well, He basically just gave me a sheet with a, b, c. basic instructions and didn’t address any of my other multiple mutants. I reacted badly to 5MTHFR in the past, so he wanted me to try deplin. But, my heart was pounding again within the two hour ride home. I talked to my naturopathic and she said she had been sorry she had referred me to him; evidentually she hasn’t had good reports on him. So I cannot recommend him. There is a Dr. Smith in the same area that has some knowledge, but I don’t know much about him. Sorry. My naturopathic is attending Dr. Lynch’s seminar this month and hopes to shed some light on my case. I had gotten my sulfur levels down to around 400 but, I still couldn’t tolerate the 5MTHFR. In fact I still occasionally start having heart paps still from the 5MTHFR (I don’t take it anymore) but not any where near the nightmare time which led me to the ER. I have heard it can take a year to stop having symptoms after a bad reaction to 5MTHFR. So I would tread carefully with starting 5MTHFR. I had only been taking 500mcg.

  52. Julie Merlich March 24, 2013 at 12:03 pm # Reply

    I am homozygous A1298C. My doctor started me on Thorne methylfolate 800 mcg along with 1 mg of Thorne methylcobaine. Within 48 hours I developed severe restless leg syndrome which started with a tightness in my chest and quickly spread to the creepy, severe restless, have to move my legs feeling. Upon her advice, I stopped the methylfolate for a week and the RLS stopped. I restarted methylfolate at 200 mcg (just emptied most of the capsule out) and the first night upon taking it, I experienced the chest tightness with the RLS again. I had read your articles on methylfolate side effects and had been taking niacin, vitamin E and iron all week and it still happened. I have chronic fatigue, fibromyalgia, osteoarthritis (s/p 2 total knee replacements) and felt fantastic during the day on the methylfolate. I was so happy to have finally found something to help me after years of fatigue. I am still working fulltime as a registered nurse and grateful that my integrative medicine doctor diagnosed my problem last month

    • Lenny April 7, 2013 at 3:05 am # Reply

      Julie, it may be a potassium deficiency caused by the methylation. Read up about it on Phoenix Rising and also google potassium deficiency and RLS.

      • Dr Ben April 8, 2013 at 5:03 pm # Reply

        Lenny and Julie –

        While I agree about Potassium deficiency caused by increased methylation, I also think that Magnesium deficiency is also possible because Magnesium is also an intracellular cation AND is needed to help potassium get into the cell.

        • Julie April 12, 2013 at 1:41 pm # Reply

          thank you for that information. I have been eating foods higher in K+ since reading this and it has definitely helped. I appreciate all the information given here. I have been taking Magnesium at night consistently too.

          • Jane March 14, 2014 at 9:37 pm #

            Hi Julie
            Just reading all the responses, and wanted to know if your RLS responded to the K+ and Mg? What type of mg do you take?

  53. Meg March 29, 2013 at 6:24 pm # Reply

    I am compound heterozygous and I just started using your methylfolate, I feel just fine, but my son’s seem to be bouncing off the walls after I give them 1/2 capsule of the kids multi. My 4 year old was acting very strangely (talking lots of jibberish, and just running around aimlessly. And my 2 1/2 year old (again only got 1/2 capsule 1ce a day) acted normal but was up for 3 hours past his bed time just unable to sleep.

    I don’t see hyperactivity in the symptoms above. I am very concerned, and wondering if I should not have them on this……any input?

  54. Mama April 1, 2013 at 1:23 am # Reply

    I believe my son had an asthma attack due to starting mb12 & methylfolate :( I’m still trying to get it under control (high dose vitamin C, vit E, molybdenum, and having to resort to asthma meds after being free of them for almost a year!). My understanding is it has to do with blocked SOUX pathway, so sulfur/sulfites are adding up too much. We are going to work on that pathway (cut out sulfur foods, add in more b6/molybdenum, liver and lentils a bit more often) before exploring methylation again.

  55. Erin April 13, 2013 at 5:49 am # Reply

    Hi Dr. Ben,

    First, I wanted to thank you for providing a website with so much valuable information.

    Second, I have a question about taking methylfolate. I recently found out I am homozygous for the C677. I ordered your B12 with methylfolate and started slowly increasing as per your protocol. I am now taking 2 capsules of homocystex in the morning and at lunch. It’ been about 5 weeks since I started taking the supplements. I also am taking the chewable multi 2 per day. I don’t really feel any difference, nor any side effects. Why do you think this is? Do I need a higher dose? My symptoms are generally anxiety, depression, low energy/ fatigue, and some brain fog and memory loss. I was really hoping that I had found the answer when I learned about my mthfr mutation.

    Any thoughts or advice would be much appreciated!


  56. Heather duggan April 13, 2013 at 5:00 pm # Reply

    Do you have any research on the effects of having both the defective MTHFR and UGT 1A1 (Gilbert’s Syndrome) genes? Thanks.

  57. William April 16, 2013 at 2:57 pm # Reply

    Dear Dr. Ben,

    My situation is very complicated.I have not been able to take many vitamins for years without experiencing significant anxiety & nervous system pain. It has been suggested that this could be due to lack of methylation factors but haven’t done the test yet. My mother has schizophrenia & my grandfather had lifetime epilepsy from a head injury in childhood so the genetic possibility is there. My neuro transmitters are crittically low, amino acid levels showed lots of variations (some too high & others too low), hormone levels low (testosterone, LH, FSH, Insulin), Homocystein at high end of spectrum13 (5-15 range), ect…

    Years ago my body went through major health challenges which trying to get better was a struggle, and now at 38years reacts to so many things now it’s hard to know what should be taken to help get better & what would harm me. Multi-vitamins, digestive enzymes, amino acid supplements, SAMe, ect… trigger pain that makes it difficult to function. However not taking anything I know I am missing something to feel alive & get better. Nausea, headaches, fatigue, & fear is a daily feeling as I drag myself through the day.

    I am currently seeing both a naturopath & physician who are trying to help.

    Any advice would be appreciated.

    Thank you,

    • Mara August 22, 2014 at 5:19 pm # Reply

      Try adding Gaia Herbs Adrenal Health

  58. PJ April 18, 2013 at 12:24 pm # Reply

    I was diagnosed with one copy mutation, unsure of which copy. My naturopathic physician recommended 50 mg of methylated folate.for 6 weeks, taper back to 25 mg and then 20 mg. I cannot find an over the counter with that mg or close to that mg. I found 400 mcg which I calculate it requires 125 tablets a day. What are your thoughts on that amount and where to find the proper mg?

    • Dr Ben April 19, 2013 at 1:32 am # Reply

      PJ – I believe that is very very high and potentially dangerous. I never recommend that to my clients – in fact, the opposite – start low and work up.

      • PJ April 19, 2013 at 2:21 am # Reply

        Thank you for the information. I was updated today specifically on the copies; I have two copies missing; C677T andn A1298C. I will confirm with them on the mg.

      • Michael October 15, 2013 at 9:15 pm # Reply

        Dr. Ben, Do you recommend trimethyglycine (TMG/Betaine) for people to reduce their homocysteine levels as an alternative to L methylfolate?

  59. William April 19, 2013 at 7:43 pm # Reply

    Dr. Dr. Ben,

    I had wrote earlier with many concerns, however now things seem to be more clear as the Methly-folate & Methly-b12 slowly work their magic. Finally some improvement in my situation after years of not knowing what was going on & what to do.

    The following are my gene markers:

    Homozygous MTHFR C677T, MTRR A66G, and CBS C699T

    Heterozygous – VDR Bsm, VDR Taq, and BHMT-08

    How much would you recommend I Methylize for the double MTHFR mutation, without triggering the Taurine upregulation from double CBS C699T?

    My Taurine levels checked in Aug 2012 was at 159%. How do I reduce this?

    I started this week taking 1 drop of Methyl-Folate & Methyl-Cobalamine (50mcg)

    Your advice would be greatly appreciated. :-)

  60. Lynnell May 20, 2013 at 4:00 pm # Reply

    I am 33 weeks pregnant and just went into preterm labor a few days ago. The labor stopped with nifedpine and a warm bath, thank goodness, and i’m now on bedrest. I have the A1298C mutation and started taking methylguard about a month ago. I was previously taking 4mg folic acid and a 80mg daily aspirin. My Ob said that it didn’t matter which I took and I went to a friend’s chiropractor who said that she usually starts on a lower dose. I was concerned I wouldn’t be getting enough and she was ok with me starting on 3 daily. I don’t know how many mg that is. I have begun having extremely high volume of amniotic fluid, insomnia, headaches, and severe cramping which may have caused my labor to start. I had no idea that there could be side effects from the methyl folate, especially after feeling so good the first week. I’m concerned that I might need to discontinue until the end of my pregnancy. I’m scared to keep taking it after reading this because I don’t want to risk the baby coming too early. What would you suggest?

    • Renee May 20, 2013 at 8:48 pm # Reply

      Hi, well, if you read up here you will see start slow on Methyl folate and work up, also may need to build up your methyl b12 first. WEALTH of info on the page… Dr so stupid, from what I read your body cant reconize folic acid, only methyl folate.. best of luck with the baby..

  61. Leanne May 21, 2013 at 4:41 pm # Reply

    I was recently diagnosed as compound heterozygous. Fortunately, I wave been taking a vitamin with methylfolate for years, but have recently added more methylfolate. I feel like it has helped my energy level but I am experiencing some mild to moderate irritability. Does this mean I should switch to a lower dose, or could this be a detox reaction that will pass with time? Thanks for this great website!

  62. Andre May 26, 2013 at 1:46 am # Reply

    Hello my wife suffers from CFS as a test we tried starting with one 5000mcg Methyl B12
    and she said she felt very sluggish for the rest of the day.
    What could be the cause of this

    • Renee May 28, 2013 at 12:26 am # Reply

      Try taking 1000 every 3 to 4 hours don’t take 5000 all once If you ask me that is. When I first started my methyl B12 treatment it made me very sleepy and I was taking 1000 MCGs. I slowly worked up to taking three or four throughout the day not all of the same time. After a couple months I added a small dose of 200 MCG’s methyl folate. I thought the 800 MCG and quarter to tablet. I start taking him for two weeks and I had body pain So I stopped taking that methyl folate for a week Headed back three times a week I continue to take 1000 mcgs of my methyl B12 every 3 to 4 hours until about 6 o’clock at night Work up to that don’t do it all at once. Best of luck read this website definitely will give you some great information everything I learned was reading here

  63. Leslie May 27, 2013 at 3:36 am # Reply

    I’m heterozygous for MTHFR C677T, Homozygous for COMT V158M ++, COMT H62H ++ , VDR Bsm and a slow metabolizer as well. After my father’s heart attack when I discovered I had high homocysteine, my cardiologist originally prescribed Folgard rx 2.2 twice a day. She also prescribed Niaspan 500 once a day. My homocysteine level did come down from 46.7 umol/L to around 12 umol/L. Later she doubled the Niaspan dose because I also have high LDL-P and Apo B (alas, I have the small dense particles). I’ve been on this regimen for 12 years or so. Recently after encountering your website, I asked if I could switch from Folgard to Metanx. She agreed. I am taking two tabs a day of Metanx. My most recent blood test has my homocysteine level at 8 umol/L, which is as low as it has ever been, so thanks! I’m also taking a low dose of Pravastatin, 20mg and I take thyroid medication for hypothyroidism, .075 mg. My blood pressure is 60-70/90-110, so that is not a problem, but recently I’ve developed a benign but annoying arrhythmia for which I’m taking magnesium, carnitine and ribose. I’m not sure why I developed the arrhythmia, but it possibly has to do with my being anemic, having too much caffeine and/or some nutritional supplements I was taking, DHEA and pregnonelone. I also exercise a lot.I’m now taking iron for the anemia. Is there anything else that I should consider taking given my genetic methylation profile? I’m also heterozygous for ACATI-02, MTRR C415T, MTRR A66G, AHCY-01, ACHY-02, AHCY-19 and CBS699T

  64. Autumn Casiglia June 3, 2013 at 12:35 pm # Reply

    Thank you, for all the information. I am just learning about MTHFR. I also have been diagnosed with:

    Lyme Stage III Autoimmune reaction
    Genetic Mutation Factor VI (homozygous A1298C)
    Irritable Bowel Syndrome
    Sjogrens Disease and hypothyroid
    Prolapse in intestine, bladder and rectal seal
    ovarian and uterine cysts
    slow gallbladder with gastric dumping

    I have thought all my symptoms were related to the Lyme or multiple food allergies (corn, soy, egg, milk). Also when I eat avocado I break out with little purple broken blood vessels all over legs and arms. I see now that many symptoms might be MTHFR related.

    I stopped all gluten 2 weeks ago. I am following your protocol as much as possible. Do you have any other recommendations for me? My Lyme doctor and my holistic doctor prescribed these supplements and medications (I have been on them since 2004):

    Biaxin XL 500 mg 2 tabs
    Hydroxychloroquinine 200 mg 2 tabs
    Thyroid Armor 90 mg 1 tab morning
    Nystatin 1/8 teaspoon at bed to manage candida

    B12 Hydroxoxobalamin 1000mcg 1 time a week injection
    DHEA 10 mg 1 tab morning
    Iodoral 8333% 4 tabs morning
    Potassium 200 mg 1 tab morning
    Pregnenolone 25 mg 1 tab morning
    Cytozyme AD 1-2 tabs
    Bio-D-Mulsion 2000iu 2 drops in morning
    Vitamin c powder 3917% 1 scoop morning
    Magnesium 87.5%
    calcium 35%
    potassium 3%
    Mg-zyme 100 mg 2 tabs at bed (50%)
    Ca/Mg plus
    Ca 300 mg 2 tabs at bed
    Mg 60 mg (30%)
    superoxide dismutase
    Super digest away As needed Aloe Vera Juice As needed IBS

    Milk Thistle

    B2 (Riboflavin) 50mg
    B12 (Methylcobalamin) 6mcg
    Dimethylglycine 150 mg
    Choline 50mg
    folinic acid (calcium folin) 800mcg

    Hydroxocobalamin 1,000 MC/ML injectable

    I had a hysterectomy in November due to heavy bleeding. I am currently experiencing fibromyalgia, fatigue, unavoidable desire to sleep, heart palpitations, clenching jaw, pain in bottom of feet and shines, bruising in shines, fullness in chest, out of breath, many gallbladder and stomach and digestion issues.

    Sorry this is so long I would appreciate any direction you can give me, because I just found out my kids have this mutation too. My husband’s sister is homozygous.

    • Michael Dowdy October 22, 2013 at 6:58 am # Reply

      Hello Autumn. Did you get the help both of you need? I’m not a doctor of a healthcare professional and in no other way financially benefiting from online sites. It sound like you may be over-medicating to me but seek the help of a good doctor with knowledge of genetic conditions. When taking a lot of medications the side effects multiply with each one, even up to ten times with each added medicine from what I’ve learned from my research. If the both of you are suffering with MTHFR mutations then you both could be malnourished, Eat well, but eat carefully, and find what supplements are beneficial for the both of you, including activated B vitamins and methylfolate. Don’t over do it. MTHFR mutations mean that your GSH and SOD may be at dangerously low levels and barely functioning. The Dr. Ben site provides a wealth of information on these relatively new findings and a lot of doctors, even very good doctors, are not familiar with them. Study, study, and study more! Inflammation in the gut and organs need treated correctly. Up to 50% of people have H Pylori and never know it, but it’s very easy to treat. People need to share knowledge to learn more. Try adding virgin coconut oil daily in place of dairy butter and in place of some cooking oils. It tastes great on whole wheat bread with a little honey. It becomes liquid at 76 degrees so it melts well on toast. It also adds a very nice flavor to shrimp scampi when used with half butter and half coconut oil. The benefits of coconut oil are huge to the vascular system. Extra virgin olive oil is very important in the diet also. Proper nutrients are so important to heal and eliminate gut inflammations. Best wishes, Michael Dowdy

    • Michael Dowdy October 22, 2013 at 7:38 am # Reply

      Oops, I got you confused with another member that had mentioned her daughter, but I hope the suggestion I made about using coconut oil is helpful to you. They removed my slow and inflamed gallbladder but I’ve been diagnosed with diverticulosis recently. I’m hoping that my GSH level is improving. I think you need methycobalamin and methyfolate if you have MTHFR mutations. This site provides a wealth of information on these newly learned findings.

  65. AMBER June 8, 2013 at 4:03 pm # Reply

    Hi Dr. Ben – I am C677T Homo….and I am having aweful side effects from the the methylfolate. I a working with a specialist who discovered the MTHFR mutation and also discovered I had a high yeast overgrowth in my intenstines. We decided to do a detox diet using a Yeast Busters kit for 2 weeks to get rid of some of the inflammation….I am also taking the niacin and tumeric you recommended. All that….and I am having aweful side effects AGAIN….the first week or so was fine and then I have a horrible anger. I am only taking 4000 mcg of methylfolate. Can you shed any light on what is happening to me. I cannot believe such a little amount of something so natural is having such a profound impact on my life. Please help. I have already tried taking it and had to stop….then I did everything mentioned above and I began again but the symptoms returned all the same. Any advice would be greatly appriciated….I am at the point where I am just about to give up taking it all together.

    • Julie June 10, 2013 at 9:26 pm # Reply

      Hi Amber,
      When my doctor first started me on methylfolate, I was having horrible restless leg syndrome and anger too. this was on a dose of 1000 mcg. 4000 mcg seems high for a starting dose. I went down to 200 mcg and stayed on that for a week and slowly worked up to 1000 mcg, where I am currently. It is always best to start low.

    • Teresa June 15, 2013 at 3:59 am # Reply

      Amber, what kind of side effects besides anger are you having. I started taking 400mcg and after three days ended up in the ER with horrid heart racing, squeezing, pounding, spasms, eradiating heat and severe anxiety episodes. I wanted to die. It wasn’t as bad the second time I tried. I am trying again. This time I am starting with a converted multi that contains 400mcg every other day. I may even start lower if things start up again. I don’t know if it is part of the detox or not. It took two weeks to normalize and I had to use a beta blocker to survive during both times. Wish me luck. I am going to need it. I was prone to anxiety and heart palps before taking the converted folic acid though. I have read B12 deficiency can cause heart stuff and I had been taking B12 so maybe it will be better this time. Have you been checked for other methylation path mutants?

  66. Samantha June 15, 2013 at 2:24 pm # Reply

    Dr Ben,

    This is my 3rd day of taking Metanx. I haven’t noticed anything from it yet. I also take niacinamide and have been for a couple of months now. Can I take it at the same time as Metanx or will it interact? I take 500mg 2x a day of niacinamide.

    Thanks, Samantha

    • Dr Ben June 15, 2013 at 9:24 pm # Reply

      Hi Samantha – yes you make take Metanx along with niacin. You may need more Metanx if you are taking so much niacin. Something to talk with your doctor about. Monitoring SAM/SAH ratios is important – and that can be done with a blood test.

  67. Donna June 19, 2013 at 12:56 am # Reply

    Hi, I recently learned I am homozygous MTHFR 677TT….via standard bloodwork my new family doc ordered. He was screening for “coagulation genetics”, and this was the only mutation that showed. He prescribed me 15mg of L-methylfolate, and after some pause and research I went ahead and filled it and started taking along with 2500mcg of B12 sublingual. I must be one of the lucky ones because my only side effects so far have been positive ones: increased energy, focus and concentration and improved mood.
    I’ve got otherwise good bloodwork (cholesterol, etc) though I do show some deficits in vitamin D and omega-3’s. So Im taking 1000mg flaxseed oil and 5000 IU D3. After reading the cautions here, I have also started adding more B vitamins (sans folic acid!) and niacin (slow release nicotonic acid 500mg). I feel great – just started this 3 wks ago, but wanted to share my experience so far. Other than low energy and poor concentration, I have not had significant health issues (I’m a 49 yr old female, mother of two). Will keep researching this site as I do have concerns for my two daughters, one who has struggled with memory/energy/social skills, the other one has anxiety/depression and past (fortunately) drug use. They are 15 and 17 and have not yet been tested. A little confused on where to start – it seems that expanded testing other than just MTHFR is warranted, but I expect it to be pricey (will try for insurance route though).

    • Renee June 19, 2013 at 1:31 am # Reply

      Go to the website 23 and me website you can order a full huge panel of DNA including all MTHFR mutations for only $99 if you order two you get a $15 off Best of luck

      • Julie June 20, 2013 at 12:50 am # Reply

        Hello. I was diagnosed with MTHFR about 6 months ago. I have struggled with chronic depression, IBS, chronic fatigue, fybromyalgia etc. for years. I don’t know if I am heterozygous or homozygous but I know that both 677 and 1298 are affected. Currently I am taking Deplin 15 and just started cerefolin. Next week we are moving to the Raleigh, North Carolina area and my Dr. is in Louisiana. This means I will need to find someone in Raleigh or nearby. Does anyone know of someone there who is knowledgeable about this that I could go to? I’m really nervous about leaving my Dr.

  68. Natalie K June 21, 2013 at 2:08 pm # Reply

    Hello all,
    Question, I recently found out that I am A222V heterozygote. My husband and I are trying to conceive so my dr put me on vitamed md plus rx with quadrifoliate. Within an hour of taking the mediciation I started having right chest pain, and then severe lower back pain to the point where I couldn’t sit down. I threw up, then broke out in a sweat and almost passed out. My question is this a normal side affect to taking this medication for the first time, or do you think it was an allergic reaction. THe dr gave me 3 different samples to try, but now I’m worried to try any of these. Additionally, he didn’t give me restrictions on when to take the medication so I took the vitamins with dinner. I did notice that you have advised to never take after lunch. Could that too have caused any issue? Any insights you are able to provide would be greatly appreciated.

  69. Pete June 28, 2013 at 1:21 am # Reply

    I’ve been taking 2 grams of Niacin (not time released) per day to lower cholesterol levels. It has worked well with total cholesterol now 188 and very good HDL / LDL nums as well. My question is this …… I have heterozygous MTHFR C677T and am considering starting a B12 lozenge (1000mcg) with L-5-MTHF (800mcg). Should I be stopping the niacin in order to start the lozenges ?

    • lahope June 28, 2013 at 6:51 am # Reply

      I don’t know what Dr Ben will say, but I can tell you my cardiologist has me taking B-12, B-6 and folate (I take Metanx) as well as niacin (I take Niaspan). They do different things. The niacin lowers LDL and free fatty acids whereas the folate, etc lowers your homocysteine. I am also heterozygous for C677T.

      • Pete June 29, 2013 at 12:21 pm # Reply

        Thanks for your reply. I had read on one of Dr. Ben’s post for someone to take niacin to reduce the effects of over methylation as niacin reduces the effects of methyl-folate. I deduced they must work against each other but if your doc is prescribing both that may not be the case. I’m going to give it a shot and see what happens.

        thanks again for responding….

    • Dr Ben June 29, 2013 at 9:54 pm # Reply

      Hi Pete –

      Please listen to the May 10th podcast on niacin.

      Typically, people with high levels of cholesterol have inadequate methylation.

      Consider supporting the cycle with choline, TMG, SAMe, folate, b12. Many of these nutrients are found in HomocysteX Plus.

      Taking fish oil is also useful along with phosphatidylcholine directly.
      This paper focuses on choline and healthy lipid levels – ie cholesterol.

      Niacin is a great nutrient – just be cautious that you are not worsening the situation by depleting your SAMe levels.

      I also don’t believe elevated cholesterol is much of an issue. What is an issue is what is causing the elevation along with inflammation. It is not the cholesterol that causes the issues – it is the oxidized cholesterol that is – esp lipoprotein little a.

  70. Dana Monk June 30, 2013 at 3:41 pm # Reply

    My Dr. Placed me on Methylguard Plus, any info you may have on this would be so helpful! I carry two copies of the A1298C. I am almost 48 and have suffered so much my entire life! So worried about my four children and my dad has Parkinson’s!

    • Teresa July 1, 2013 at 3:27 pm # Reply

      Dana, I am 57 and have also suffered much; in addition to anxiety and depression now I have osteoporosis, restless leg and fibromyalgia and tendon damage from Levaquin. I tried the 5 MTHFR three times and cannot tolerate even 400mcg. I have tried reducing my ammonia and sulfur levels and used a prescription Deplin but still no luck (because I have multiple mutants along the pathway). I have gone on the converted B12 hoping this will still my anxiety and heart symptoms (extreme with the 5MTHFR) before trying again. I am deficient in B12 tests said. The program just isn’t working for me; I think there just isn’t enough research and information available yet it seems. I too have two copies of the A1298C. That doesn’t mean the 5MTHFR won’t work for you though, so don’t let it stop you. Many people have had good luck with the 5MTHFR.

  71. Amy Duffield June 30, 2013 at 3:54 pm # Reply

    You talk a lot about side effects of methylfolate. What about side effects from just sublingual methylcobalamin? I tried 1000 mcg of sublingual methylcobalamin and felt awful in the head. Is this normal? (I didn’t take any methylfolate with the B12. I was just trying to start your protocol which you say is to start with the B12 and probiotics.)

  72. Emily Passic July 2, 2013 at 1:11 am # Reply

    I am heterozygous for C677T. I have found through much trial and error that I can only tolerate 5-MTHFR by IM injection or very small doses in oral form. i started at 800 mcg every 5 days and then every days, etc, until I could get to daily dosage w/o side effects.

    When I have taken too much oral MTHFR the side effect is very severe “stomach” cramping, which is just below my xyphoid, which is generally where my usual nausea and stomach pain originate from. My doctors have slowly increased the dose of the MTHFR both in my weekly IV (Meyer’s cocktail) and in my daily IM injections. And I am starting back on MethylGuard 1 capsule daily to see if I can start to tolerate that without side effects on a smaller dose (two capsules produces the severe stomach pain/nausea – the kind that makes you want to go to the ER but leaves you lying on the floor in the fetal position for 8-12 hours).

    I have had tremendous improvement in my symptoms (full body rash, nausea, systemic edema and headaches) since I started supplementing with MTHFR, B6 and Methylcobalamin. I do daily injections of all 3 because of the stomach cramping from the oral dose, and no side effects of IV or IM. My nausea went away completely for a few months after administration of IM B6, but has come back but with less severity. Skin rash is virtually gone UNLESS I am under a lot of stress combined with any amount of detoxification (sauna, spa, a lot of sweating, colonics), in which case I need to take more of these methylated B vitamins to buffer the “stress” on my liver.

  73. Clarissa July 15, 2013 at 1:43 am # Reply

    I am of the first group.
    I only discovered my heterozygous MTHFR (C67& A12..) a few months back. It certainly explained many things which I won’t go on about here because this is just to say that taking 10mg of 5 methylfolate makes me feel absolutely fabulous.
    I feel calm, composed, happy.. almost blissful. Its the feeling of inner peace I have been chasing most of my life. I have been a long time user of SAMe but there is no comparison. SAMe just kept me on track, if I didn’t take 400mg, I would get those ‘bad days’ back. Methylfolate gives me patience and love, something I need oodles of with five kids!
    My doc (in Sydney Australia) checked my B12 so I know that I am topped up there, she prescribed a pyrrole primer with folinic acid in it – didn’t really notice much difference from that. It was my son’s doctor who alerted me to the existence of Deplin, so I ordered 5mf and titrated it for my son and I. Didn’t notice much difference in my son, who is homozygous for C677T, but for me… wow. I only hope it lasts and I don’t develop side effects with time.
    I would also like to know just how it can make me feel so groovy??

    • Adam Will R July 23, 2013 at 1:58 am # Reply

      That’s Great for you Clarissa,

      In regards to your son, homozygous C677T is a bit more complicated. Speaking from experience here. ;-) Especially when combined with CBS 699T +/+.

      Hopefully Dr Yasko’s team can help me out of this mess.

      All The Best,

  74. jtex July 22, 2013 at 7:09 pm # Reply

    My son is 1298 heterozygous. His internist put him on Deplin 15mg. after his homocysteine was tested at 101 and then retested – still high but not that high – Dr put him on Methyl Guard Plus and L-Serine. Dr sent him to Baylor Adult Genetic lab who tested him and informed us that they don’t believe he has homocysturnia and that the heterozygous 1298 was of no importance. However, they couldn’t explain why a 25 year old would have pancreatitis (hospitalized 3 time last year) and high blood pressure.

    Is 1298 heterozygous alone something that could cause these problems? He also has 6/8 symptons of chronic fatigue syndrome (as published by Mayo Clinic).

  75. LMLyme July 24, 2013 at 7:42 am # Reply

    Hi Dr. Ben,

    Just got informed by my doctor today I am homozygous C677t. He recommended your site and said to start low with 5-mthf. He said we could talk about adding b-12 later. So I purchased Thorne 1mg 5-mthf and took 1 capsule. Felt a fleeting headache. I was curious so I waited 15 minutes and took another capsule. Another fleeting headache. A few hours later – irritability and VERY sore thigh muscles. Took 100mf niacin as that is all I had on hand at home. Still feel the thigh ache. So I see from your site you recommend taking b-12 first,

    Mom: Postpartum Depression

    1st pregnancy – sent to a hematologist and he found 8 had “super platelets” which I believe is a type of anemia caused by frolic acid deficiency, This was 2001. Healthy delivery.

    2nd pregnancy – healthy baby

    3rd pregnancy – miscarriage

    4th pregnancy – stillborn at 37 weeks. No known cause on autopsy.

    5th pregnancy – healthy baby. Delivered early by induction at 37 weeks.

    6th pregnancy – baby – overall healthy – born with feet a bit turned in

    Then got alyme Disease and it has been Hell. Bi-Polar symptoms ( high ammonia and quin acid). Did terrible with glutamate supplement. Closed my eyes and saw white flashes of light. Magnesium significantly reduced mood swings (shuts the NMDA receptor sites that are wide open). Magnesium defiency is across the board in all Late Stage Lyme Patients.

    Interesting to Note: after exercising 3 weeks in a row every other day I always have a massive attact of depression and anxiety. The last time I tried it Ai actually had internal tremors that lasted for a week or two. I had a Merametrix ION test done a few years before and I insisted on getting one done at that time I was having tremors. Very interesting to note results. VERY low potassium and magnesium. Very low arginine. High Quin. Looked on Metametrix site and these results indicate an ammonia problem. Researched a bit and ammonia is believed by some LLMD’s to be a primary toxin in Lyme Disease. When I began treating Lyme disease, I did coffee enemas to help detox because I was overcome with depression (beginning week 3 of treatment) and I would smell an ammonia (windex or urine) type smell as I flushed out my bowels which was weird to me at the time because I wasn’t detoxing urine but the colon. All that is just brain food.

    My question is?

    In Lyme Disease (late stage where the infection is systemic and there is an ongoing state of infection) do you still recommend m-thf supplementation with the b-12? Or is this case by case?

    I also don’t do well with liposomal glutathione. Within 5 minutes it makes me really irritable. Would this warrant further gene testing.

    Lately – do you consult/interpret Metametrix ION tests only as far as mthfr or can you offer insight to the whole.

    All the best!

    • LMLyme July 24, 2013 at 7:51 am # Reply

      Sorry – couple of corrections. Folate not “frolate”, I not “8” and glutamine not “glutamate supplements”, attack instead of “attact” and I instead of “Ai” and any other nutty typos in there! I have blurry vision from Lyme neurotoxin so sometimes I don’t notice my errors :-(. Sad!

    • Dr Ben July 25, 2013 at 6:34 pm # Reply

      Hello –

      I cannot give much advice here but I will say that Niacin in higher doses may be warranted. Look at using Nicotinic acid form – not the others.

      I have also changed my stance on dosing methylcobalamin and methylfolate. I feel now that they should initially be taken together for various reasons – one such reason is stated here at the 43rd Minute (just skip ahead).

      Mitochondrial support is needed – need to reduce oxidative stress prior to giving methylfolate and methylcobalamin.

      • LML November 9, 2013 at 5:25 am # Reply

        Hi Dr. Ben,

        I just want to thank you so much for replying to my post. I am re-referencing your answer to me today. I actually put my methyl folate away because I am in treatment for the Lyme and instead of the methyl folate making me feel better, I felt worse (as I wrote in my post). I have taken Zeolite Pure to help bind the ammonia from the Lyme and that has really, really helped me feel much more restful and peaceful and overall better. I was nervous to try it but was pleasantly surprised by the lack of side effects. That is helping me detox for now and I will look at the methyl folate in the future. Thanks so much for your help in this.

        All the best!

        • Michael (NW) November 15, 2013 at 10:19 pm # Reply

          Hi, I’ve used Zeolite before, a product called “Zeoforce by HealthForce Nutritionals”. carries this product. The reviews are great on it for detoxifying all sorts of stuff. I stopped using it a while back, I forget why…. My question would be, is it a sulfur containing product as I’m trying to avoid excess sulfur… I know it’s made from volcanic ash I think, or….? Thanks.

  76. Kristen July 25, 2013 at 12:14 pm # Reply

    Hello Dr. Ben,
    My blood work came back that I have a homozygous MTHFR129 mutation. My doctor gave me some samples of Deplin 15mg, which I took for two weeks and then ran out. I went to get my prescription filled and found out it was going to cost $400/bottle. I then went of off the Deplin for 4 days. I began to feel the symptoms I had before, muscle aches and extreme fatigue. I then got more samples and started to take the Deplin. It took about a week to feel better but then I started feeling dizzy. So I told my doctor and we agreed to cut back on the Deplin. He said he has never heard of anyone feeling dizzy with the Deplin. I took 7.5mg this past Tues. I then began to feel like I couldn’t concentrate and that I had “thing” floating in my head along with the dizziness. I haven’t taken the Deplin since Tues. I read your blog and took niacin and tumeric on tues. It took all day to feel better. It is now Thurs and I still feel dizzy. Do you have any suggestions?

  77. Amber July 28, 2013 at 9:20 pm # Reply

    Hi, Dr. Lynch,

    Below are some of my 23andme results:

    MTHFR 0677T rs1801133 GG -/-
    MTHFR 03 P39P rs2066470 AG +/-
    MTHFR A1238C rs1801131 GT +/-

    COMT V158M rs4680 +/-
    COMT HH rs4633 +/-
    COMT P199P rs769224 GG -/-

    CBS c699t RS234706 AG +/-
    CBS A360A rs 1801181 AG +/-
    CBS N212N rs2298758GG -/-

    Negative for 677 and only heterozygous for C1298P. Taking 7.5 mg Deplin (methylfolate) per my doctor has cause my acne to worsen x3 and caused insomnia and some brain fog.

    I believe it was in the article above you stated: “If a person has a COMT mutation or CBS mutation or MAO A mutation and they take a high amount of methylfolate, it can cause some intense side effects.”

    When you say that, do you mean temporarily as one is ramping up, or do you mean that COMT and CBS could cause permanent difficulty with methylfolate?

    • Lori Graham July 29, 2013 at 11:03 am # Reply

      I was just diagnosed homozygous for 677. I feel I was totally subclinical as I am a vegan, juice, don’t eat wheat, do a lot of live foods and am very athletic. Mild TPO, tho, but again subclinical.

      Started Folapro by Metagenics, and within on week started getting wierd floaters in left eye that didn’t resolve, so went to Optho and my eye checked out clear. Had craniosacral tx, and symptoms shifted. Now I have a “blob’ on the nasal side of my left eye and it’s like a circle of dark stuff and leaves me intact vision in the shape of a crescent moon in the position of a “C”…best I can describe. Emailed optho again, and am really concerned. Folalpro is the only new thing I have added to supplements. Any thoughts?

    • Renee November 10, 2013 at 2:19 am # Reply

      There is a wealth of info on a facebook group called mthfr I saw a lot of info about CBS and COMT there.. best of luck

  78. Dorene July 31, 2013 at 1:05 pm # Reply

    I am compound heterozygous and started the Thorne B-complex #12 I had in my cabinet and stopped other supplements with B vitamins in them like the Corvite the hemotologist prescribed for my ongoing anemia. I felt so much better I had been dealing with Epstein Barr for 5 weeks. But I did get a stomach ache soon after and had diarrhea and I have had it ever since like 6 weeks. Is this a normal reaction? I feel like the toxins are coming out. So felt great more alert and more energy. I stopped eating gluten also and now I am having migraines and muscle pain and fatigue I get bouts of this and doc previously said its fibromyalgia but I don’t know. So I stopped the Thorne B and I am taking Seeking Health Active B12 lozenge but I don’t feel as alert but still have diarrhea and pain.

  79. Michael G August 4, 2013 at 5:01 pm # Reply

    1. I was tested for the two common MTHF gene defects but it came back normal.
    2. I take whole tumeric poweder.
    3. It seems that 5-MTHF makes me feel more depressed??? So, I’ve shied away from it. But recently I increased from 1mg, to 2mg to 3mg, and started feeling slight improvements, then I increased methyl-b12 thought i was fine, but then yesterday felt very depressed and low energy/brain fog…. I was on 3mg 5-MTHF and 4mg Methyl-B12. I was also taking Methionine (for about 4 days) and DMG (past few weeks), but also take Betaine HCI for digestion. Maybe too much of everything? My blood tests who I have plenty of Folate (the level was in the 20’s I think or low 30’s). But for the past 1.5 years I’ve had very high B12 levels after taking B shots that had B12 in the cobalamin form. So, not sure why my body is not methylating the B12 and using it up, or peeing it out. A nutraeval test showed my body had a high need for B12 and Glutathione. So, what is going on? Do I need 5-MTH or Methyl-B12?

    The protocol I’m on with amino acids calls for 2mg-3mg of 5-MTHF. But as I mentioned I shied away from it as I heard folate can make depression worse for those who were undermethylated which it seemed like I was since I had all this B12 circulating, high/normal histamine and high normal homocystein. But maybe I need a lot more of it, but why did I feel so depressed yesterday?

    I started with 1mg of 5-MTHF, then 2mg feeling a little better then 3mg, continuing to feel better, then added more Methy-B12 2MG then 3MG then 4MG. Thought I was stlil feeling better, but now I’m more depressed….

    From what I gather, and online questionnaires I have enough Serotonin (no more OCD, anxiety low, no crying depression (never had that anyway) just low moods and low emotions…It seems I was low on Dopamine and Gaba.

    Niacin does give me a mood and energy boost at 50mg or even less…Flushing kind….

    Anyway, I’m repeating what I’ve shared on other posts. Just could use some insight as my doctors don’t know much about this methylation stuff. Thank you for your time and great work, I think you will end up helping many people are are stuck and not getting better due to some of these issues that you are helping people and doctors to figure out.

  80. Laura H August 6, 2013 at 8:10 pm # Reply

    Hi Dr. Ben,

    I REALLY need some help! I am taking Metanx after just being diagnosed with heterozygous MTHFR c677t gene mutation. I have miscarried 3 times all before five weeks. Anyways, Ive only been on Metanx one week and I feel TERRIBLE. I have no appetite, Im anxious and I just feel “off” all around. I only weigh 118 lbs. so Im thinking I must be overdosing. I do not want to miscarry again….but I dont think this medicine is for me. Any suggestions?? Thans so much!!!~ Laura

  81. Lea Ann Madison August 13, 2013 at 3:44 pm # Reply

    I am homo for c677t with high homocysteine. I just received my L-5 MTF (800 mcg.) on Saturday and because I have read about methylation issues, and problems I have with methyl donors, I crushed the tablet and took some throughout the day. I also started Hydroxy B12 (1000 mcg) and did the same thing. I have had a headache and my insomnia has worsened. I am reluctant to increase my dosage. I haven’t taken any Niacin, but I have it on hand. I don’t think my pain/inflammation has increased. I began taking Turmeric 320 mg. (for inflammation) about 1 month ago.
    I am reluctant to push the dosages on these because I’m pretty sure that I need to clear ammonia/sulfur (gut issues) first. I don’t have a doctor – I’m reading all that you’ve offered and gleaned info also from NutriGenomics. Any suggestions? I am going to call Paige Adams to see if I can make an appt. I live in So. Indiana and she’s in TN, so I could make that trip and certainly will if she will accept me. Thanks for all your information.

    • Blues August 16, 2013 at 11:40 am # Reply

      Dear Dr Ben

      Want your advice for this- I am not sure if i have MTHFR mutation as i have not tested for it. I live in Asia n my docs here dont have this on their radar. I had a miscarriage at 9 wks due to a subchronic hematoma bleeding. My docs did several tests like APS, lupus anticoagulant, ANA – all were negative except ANA positive moderate 1:320 specked pattern. As i said i didnt test for MTHFR but reading so much has caused me to think that also as a probable cause.

      I m already taking a folic acid supplement. got to continue with this as doc recommends.

      Now my question- can i take L-methylfolate also along with folic acid ?? Pl do let me know!!

      thanks !

  82. Erin T. August 21, 2013 at 6:40 am # Reply

    I am reading through all the comments/replies here. My 7 year old, also dx’d with ASD, recently had genetic testing that shows he is heterozygous for MTHFR C677T, COMT V158M and COMT H62H, hetero for CBS, as well as homozygous for MAO-A. His blood levels showed B12 levels through the roof..into the 1400’s, but his OAT showed normal B12 levels. His doc switched him to Klaires Vitaspectrum, which has methlyfolate in it, as well as methylb12. He has many other mutations as well. Doesn’t have ammonia problems so maybe CBS not expressing. I’m trying to navigate my way through all of this. We’re still working on his gut issues, but lab tests still show inflammation. He is gf/cf/sf tree nut free, no yeast, low sugar. We do probios, cod liver oil, aloe vera and so much more. For years. I read that you stated there is more of a risk for methylfolate side effects if you have MTHFR mutation along with COMT and es. MAO-A. My son is not always able to express how he is feeling, so this makes it even more challenging. I am wondering if i should even have him taking a methylfolate/methylb12 multivitamin. It’s all very confusing, our doc doesn’t really quite get the whole genetic mutation thing, and our financial situation is quite severe. Appreciate any suggestions/feedback you are able to offer. Thank you

  83. Florence August 22, 2013 at 1:57 pm # Reply

    I do not know if I have MTHFR yet, waiting on tests. I do have a B12 deficiency. My doctor started me on a high does of all b vitamins (methyl) orally. My main symptom of the B12 problem is neuropathy and joint pain. The high does of B vitamins made the joint pain and neuropathy very very much worse, so I stopped that. I tried three different oral brands with all the same result. We went to methyl B-12 shots and that works well. I am interested in your article as now I see maybe we should have done something about the inflammation I experience first.

  84. Terri Christie August 25, 2013 at 11:59 pm # Reply

    I started the Neuro-Immune Stabalizer cream (5-MTHF, methyl B12& 6) 1 week ago with just 1 pump in the morning and I took TMG 500mg. I felt ok the first few days I took it, but didn’t notice any great change. Maybe I had some more additional energy, which was nice.

    The 5th day I took it, I noticed a little extra anxiety about 7 hours after I took it and it lasted for a few hours and I was able to go to sleep. Then I took it the 6th day and 14 hours later had a BAD panic attack in bed.I got through it and had to get up 5.5 hours later and take my daughter to college. I didn’t take it the 7th morning thinking it must be the folate causing it. I felt very anxious before we left but then while she was driving, I had panic attack upon attack! It was completely awful! I felt like my body was about to explode with adrenaline and I was sobbing and couldn’t breathe.

    I called my doc and he told me I was overmethylating and it would stop soon or I could stop and get some niacin. It finally subsided and I haven’t had too much anxiety since. My doc said I may have other SNPS that cause me to not use the methyl groups and we have to stop rx for now.

    It wasn’t just too much folate as this is the cream that you give a 1/2 pump to babies and I was only started on 1 pump. I am trying not to be discouraged because I thought I finally found the answer to my 5 years of illness, but I am back to square 1 it seems until I fix other problems.

  85. Brigetta August 28, 2013 at 3:15 pm # Reply

    I am positive for both 677 and 1298 gene mutations. I tapered up over a week to L-5-Methytetrahydrofolate by Thorne and 1ml. sublingual daily of Methyl Factors by Biogenesis. I am also taking D-Ribose daily. Yet, after a month and a half I am experiencing zero change in my plantar neuropathy and fibromyalgia pain. I wonder if I am not being helped because I did not do the proper foundational prep before starting on the supplements. Should I stop and do a fasting cleanse before restarting? Seems like I should be experiencing something by now. Tired of spending so much money on these supplements with no effect. Also, feeling very depressed about my recovery at this point. Your help would be very appreciated at this point.

    • Renee August 29, 2013 at 3:19 am # Reply

      Hi I have the same frustrations I have Fibromyalgia/chronic fatigue syndrome and all that comes with it been fighting it for many years so it can take many years to even feel a lot better. I’m thankful that I found a drug that done in one 10th big dose of standard and help fibromyalgia joint pain Called LDN plus I added 800 mg of Magnesium Glyniate For a year and then tapered back to 600 this really did help my muscle pain. You can come join our group about LDN it’s on Facebook I put the website on the top by my name is ….You can Google LDN and fibromyalgia and you will see a lot of information Stanford medical school did a study on in 2009. It’s my website link isn’t working just go to Facebook Search GOT ENDORPHINS LDN, All capital letters and asked to join will be happy to have you. It is still very important to try to get your methylation straight. Hope to see you there

  86. Susan September 6, 2013 at 2:54 pm # Reply

    Hi Dr. Lynch

    I found out that I had 2 copies of C677T and my doctor started me on a capsule of 1mg of methylcobalamine and 20mg of methylfolate, 500mg of TMG and P-5-P. My diet was very clean prior to this and have not experienced any of the side effects listed. My digestive issues are clearing up! I was diagnosed with hypothyroidism about 6 years ago. One year ago, I started noticing that I had lost some hearing in my left ear and had an cat scan done and that showed no reason for the loss. My doctor adjusted my nature throid (3 grains/day) and I saw no improvement in my hearing. I also go to a chiropractor. No improvement. We did the test and found that I was homozygous for this defect and started the protocol but have not seen any improvement with hearing. I have recently started feeling a prickly sensation on the bottoms of my feet. Any suggestions?

  87. Martha Goudey September 8, 2013 at 10:23 pm # Reply

    I was diagnosed as “MTHFR T/T” on a genetic test…assuming that is the same as the C677T you refer to. The practitioner who administered the “advanced lipid test” that was also a genetic test I knew nothing about, saw high cholesterol and high ldls and told me to take folic acid. I went to another doctor who treats naturally and without explanation put me on Deplin and said, “You’ll feel better.”
    Then I saw a naturopath in Seattle who said, “you are homozygous, at high risk for blood clots, etc. Don’t take folic acid.” She prescribed Methylguard Plus by Thorne, which has 1 mg L-M per capsule. She said take two. I’ve been taking them for most of the last ten months.
    Recently I had a migraine (my first) and ended up in the hospital because I thought I was having a stroke. I am having panic attacks…feels like an adrenaline rush and out-of-control feeling. And have a sore place in my throat that’s new. (I also had a new crown put on five days before the migraine.)
    I was already following most of the protocols you recommend before the test because I knew I was genetically disposed because of family history. However, since being “diagnosed,” I’ve been confused…have no idea how much I’m really supposed to take. I’m tempted to do the optimal multivitamin or the chewable…but again, no idea what I’m reacting to or how much to take or who to even ask. I emailed the N.D. and she said, “go off the methylguard for two weeks and don’t do niacin.” However, I took 50 mg niacin this morning and had a panic attack along with the rush.

  88. Janice September 9, 2013 at 1:59 pm # Reply

    Hi there everyone and especially Dr Ben, Two copies C677T
    I have been taking methylfolate 200mcg everyother day for the past two weeks, and added methylcobalin 1000mcg last week. It is great to be out of the fog and to be pain free. I have had two side effects 1. Very mild headache (not doing anything about that). 2. Lots of questions from family members when I mention giving up wheat products, they all get defensive. I am hoping that Dr. Ben will have a presentation explaining all that I cannot.
    I have been following the slow carb diet (lost 40 lbs) for more than two years and it does not bother me not to have wheat.
    One last thing. Is there login to ? Can’t find it if there is one. I am entering though email.

  89. Kimberly September 11, 2013 at 7:09 pm # Reply

    The doctor prescribed 10mg Thorne 5-MTHF for my heterozygous C677T 14 year old daughter. I decided to start her out of 5mg at first. She became extremely anxious, hyper, agitated, irritable and impatient. It was as if she had 20 shots of espresso. She was bouncing off the walls, talking really fast, getting angry at little things, feeling like she needed to exercise off the extra energy (although that did not work), basically just freaking out. I thought it might be something else the doctor put her on, so I had her take 5mg a second day. I had her discontinue use after that. The third day, I gave her 25 mg niacin and she started to calm down. Now, four days later, she seems fine. Trying to figure out the next step and will probably order the Seeking Health chewable multi.

  90. Brian September 12, 2013 at 3:14 pm # Reply


    I’ll start by giving some history. I am currently 47 years old. During childhood I grew up with severe OCD and depression and was never diagnosed until age 26. I have been on antidepressants ever since, but about a year ago I decided to start tapering off my Citalopram and was finally off 3 months later…so I’ve been completely off of it for 10 months now. I did start getting a little bit of the depression back and OCD from time to time, but nothing even close to what it used to be like 20 years ago. I stopped the Citalopram because of health concerns and an enlarged prostate that diminished after quitting Citalopram.
    Since 10 months ago, I started doing research and experimenting with supplements. I knew that the Citalopram lessened my allergies and that there was a correlation between it and histamine and started to find out the correlation between histamine, over and Undermethylation and homocysteine. I noticed that the symptoms of Undermethylation was related to my family health history. Very strong heart disease on my dads side, Alzheimer’s, dementia, foggy head, low attention… and on.
    I then decided to try 500mg of TMG…at first I noticed that I had this strange feeling in my nose…sort of like the feeling you get when water goes up your nose. I’ve noticed this with high doses of D3 also. (6,000-10,000 iu). Anyway, I don’t take the D3 any longer and I keep experimenting with the TMG, MethylFolate, P5P, Methyl B12, Zinc, Acetyl L-Carnitine, B Complex, Magnesium….Anyway, I don’t seem to tolerate B Vitamins very well, even though I have signs of B12 deficiency (like the lines/ridges on thumbnails).
    The only thing I am taking now is L-Theanine and Inositol to try to help with my BIGGEST issue which is anxiety. I let little things get to me and always very nervous with a very nervous stomach. In the mornings I have to get out of bed immediately or else my stomache starts getting the jitters and I feel like I’m going to have diarrhea. I have always seemed to get mad VERY easily and if I’m on the phone with someone…like my cell phone carrier or utilities company, I seem to always get upset WAY too easy and get very mad. I’m not physically abusive at all but I get these sudden urges to feel like I could do something when I get mad. I’m so afraid that I will lose my job because of not being able to control my emotions. (It’s happened before :'( ).

    Currently, when I take TMG I seem to be a little more clear headed at 500 mg, but I seem more jittery and nervous. Even when I take 200mg or 300mg of Theanine I still have nervousness but it does help about 50%.

    I don’t have health insurance, so I’m trying to experiment on my own and getting very worried that I will lose my job before I get “fixed”. My nervousness wasn’t near as bad when I was on the Citalopram, BUT I still got angry way too easy and took everything to heart. No matter what I take I always wear my heart on my sleeve.

    Any suggestions would be SOOOOO appreciated.

    • Abby September 25, 2013 at 9:27 pm # Reply

      The first thing you should do is get off ALL caffeine and sugar. Even tea and chocolate. Try not to eat things that turn to sugar in your system like flour, potatoes, sweet potatoes, etc. Go on a good probiotic. If you need b12, try Hydroxy B12. It could take some time, but your emotions will definitely balance out.

      • Brian September 26, 2013 at 9:41 pm # Reply

        Thanks so much for your input Abby. Are you saying that it sounds like I should try Hydroxy B12? I forgot to mention I also am allergic to Wheat but also seem to have issues with high histamine foods. Sometimes I can tell when I eat something that my body doesn’t agree with…particularly when I am pushing a shopping cart and my ears make this strange noise from the vibration of the cart wheels…it’s like my ears are getting congested. It’s very strange and it also seems like my ears get extra sensitive to loud noise when this happens. I’ve correlated this all to whatever I have eaten.
        Is there anything I can take to lower my histamine so that I can have these foods from time to time or accidentally eat a high histamine food?

        Also, from all that I’ve told you…do I sound like a Undermethylator or Overmethylator? I have the OCD which correlates to “under” but TMG only seemed to help the first week and then seemed to over stimulate me.

        Thank you! :)

        • Brian September 26, 2013 at 10:05 pm # Reply

          Oh, I also forgot to mention. I don’t have caffeine very often because it makes me very irritable if I have more than a cup. Now, I have noticed if I have been staying completely away from caffeine for a long time, and then decide to have a cup, I feel great that first time and then get irritable if I have it the second day.


          • Abby September 26, 2013 at 10:37 pm #

            It’s good that you don’t have caffeine. Forgot to mention that fruit juice can be a major problem, too. Some people are sensitive to the Methyl B12 and Hydroxy B12 seems to work better for them. I found it on Amazon and at You sound like an undermethylator. It’s best to address the diet first, then add the methylfolate, etc. It can take adjusting from time to time if it starts bothering you. You may need to back off for a while, then increase it again later, depending on how you feel. If you don’t want to take an antihistamine after high histamine foods, you could try Innate Response Digestive Enzymes Clinical Strength. Those are great for taking with foods that could end up bothering you. Something else to consider would be taking Innate Response Plant Enzymes with 2 or 3 meals a day for about 3 months. Especially along with a probiotic, those would heal your digestive system and decrease food sensitivities. A fish oil supplement would also help your brain health. It can take months for natural solutions to fix these kinds of problems, so be patient, it works!

    • Vikiirna September 22, 2014 at 12:41 am # Reply

      Be very selective which B vitamins you take. For example, folic acic can be almost toxic to those that need methyl folate.

  91. Reeney September 14, 2013 at 1:21 am # Reply

    Hi Dr. Ben,
    I am homozygous for the c677t MTHFR mutation. A little background: My 17 month old was diagnosed at birth with Trisomy 21. 2 days after she was born, they found a DVT in my R iliac vein. Additionally, I have had a miscarriage in the past. I asked my hematologist to test me for MTHFR and it came back positive.
    I just found out I am pregnant (would be right at 4 weeks) and have been taking Metanx 1 capsule twice a day for the past few months. I also take CoQ10 and PQQ (for about a month).
    Is that dose enough? Is it safe? Is there anything else I should be taking during this pregnancy because of the MTHFR?
    Thank you!

  92. Kristen lynch September 14, 2013 at 10:21 pm # Reply

    My dr had me start 1mg of 5-mthf based on thoughts I was deficient but we are waiting on labs to confirm. It appears to be causing flutterings and issues with my heart, I am fatigued and when fatigued, often dizzy. I had some diarrhea but not too bad.I haven’t tried the niacin because my dr is on vacation and I’m worried about taking anything else. I only took two pills with two days in between and it’s been 6 days since i took the last pill and I’m still having side effects. It’s causing little muscle spasms too like in my right eye but other places too. How long does it stay in? I’m worried maybe about it causing a potassium deficiency? I was going to the sauna prior to this and having some fatigue issues with that. I am improving some but it’s slow.

    • lahope September 15, 2013 at 3:42 pm # Reply

      Has your doctor tested your iron levels? Your symptoms may be caused by anemia.

  93. Meggan September 22, 2013 at 10:08 pm # Reply

    Hi There,
    I was floxed by Cipro and since have horrible allergies Gastro and inflammation. I cut out all grains, GO GMO etc, and still have histamine responses. I ‘relapse’ about ever 2-3 months as well. I want to begin this, but I have zero support from my doctor, he does not beieve “Cipro can do that:. So, since I have mal absorption and allergies, how can I start? Any ideas? I really think this will help me.

    • Michael September 25, 2013 at 5:47 pm # Reply

      Hi Meggan, I also seem to have histamine responses to food. And i think it’s causing my anxiety, sweating, nervousness, terrible insomnia, etc… I’ve read that adrenaline is used to bring down histamine, and might be why I feel so awful at times… I’ve tried L-Methionine and it seemed to help for a while, but it’s also a sulfur, so if you have methlyation issues in the sulfur department, it might make me worse at some point, which I think it has. I have a methlyation test that I’m awaiting results for to hopefully find the area(s) where my methlyation might be messed up. As I’ve tried all the supplements for methlyation, 5-MTHF, Methly-B12, methionine, sam-e, TMG, DMG, NAC, and they all seem to help when you first take them, then I start feeling worse. So, I really need to find out what’s broken in my methlyation system….In the mean time, I’m going to try a product from called “histame” which contains the enzyme that breaks down histamine in foods…. Might provide some relief. (what is floxed by cipro)?

      I’m also have reactions to foods like sugar sensitivities, feeling anxious, panicky, light headed, stimulated after eating lunch in particular and even dinner….Don’t react as much with breakfast, but still can….I was tested with high noon insulin before, not sure why….Anyway, I hope you get better….

      • Abby September 25, 2013 at 9:19 pm # Reply

        Have you changed your diet? I used to have all of the same issues and changing what I ate was the only solution. I went on a low glycemic (and organic) diet so that my blood sugar stays even all the time. I don’t ingest sweeteners, corn, soy, dairy, gluten, coffee, chocolate, or much fruit. (I do eat Ezekiel 4:9 products. They don’t seem to bother me.) All of those contributed to my anxiety and not feeling well in general. I went through withdrawals when I went off of everything, but it was worth it. I also minimized environmental toxins.

        • Michael September 26, 2013 at 5:36 pm # Reply

          Hi Abby, I had been on a very low carb diet, feeling it would help my hypoglycemia, but also any adrenal fatigue. That didn’t help. Actually it doesn’t matter what I eat, I feel worse….I can actually eat a large dinner with carbs and feel fine. Some time not…I believe I have reactive hypoglycemia. years ago I went on a no carb diet and felt horrible. Went back on carbs and felt good, but lowered my carb intake and did okay. 2 years ago, I was told I might have celiac disease (I think it ended up just being gluten intolerance maybe wheat allergies) and so I went off all grains for a while. Then I tried a gluten free waffle with a little natural maple syrup (might have been agave) and felt really light headed. I started monitoring my glucose levels and noticed that when I ate, my blood sugars dropped, then went up slowly, then came down slowly then dropped fast. Something is not right….

          Now, I can go long periods without eating, feel better, then eat and feel worse for a while. That isn’t normal. My ATP system could be out of whack. coq10 could help and my ND said that I could add a little L-carnitine which both are needed for ATP production. I also read in a medical site that L-carnitine reversed reactive hypoglycemia in a test patient. So, I might try a little of it to see if it helps.

          I do not eat gluten, dairy or eggs. Don’t usually eat soy unless it’s added in something… I don’t do coffee, (never did), don’t eat chocolate any longer, don’t eat sweets, but doesn’t help… Well, I’m sure I’d be worse if I did eat those things…

          I’m a all natural guy, mostly organic foods, natural products at home, etc… Been that way for years. Something is just out of balance in my body. Hopefully my methalytion test will show where in the cycle I might have a defect.. I’m assuming it’s in the ATP cycle area, possibly the sulfation area… We’ll see.. I also have TONS of B12 in my blood not methlyating. But I don’t have a 5MTHFr defect, at least not the two common ones. So, we’ll see…. thanks for your input, I appreciate feedback!

      • Meggan September 26, 2013 at 2:41 am # Reply

        Hi Michael, first, to get it out of the way for you, Cipro caused a toxicity to my system, so I have autoimmune and systemic issues now. I am gettin the23andmetest to confirm if MFTHR was changed as well. I will check into the Iherb histame! One thing that has heled some is I removed all refined oils, sugars and gluten. Maybe try that? and see if it works for you. LOTS of people have reactions to gluten now, such as wheat, barley, rye. White sugar

        • Michael September 26, 2013 at 8:59 pm # Reply

          Hi, so Cipro is a anti-biotic? Have you tried probiotics? I would stick to a good brand that has common basic probiotics in them and start with that. If it killed all your good bacteria, you could have a candida (fungus) infection in your gut….which can wreak havoc on your digestive system, (whole body) and could trigger food allergies, inflammation, which could in turn cause an issue absorbing nutrients from food which in turn can cause mental health issues, etc…Also, GSE (grapefruit seed extract) is good at killing off fungus, and I believe it will not hurt the good bacteria. Glutamine is good also for healing the gut….Also if you have candida overgrowth there could be high levels of ammonia which you can take activated charcoal to remove (just don’t take at the same time as meds or vitamins). I am gluten dairy and egg free. I don’t eat desserts (refined sugars), and no bad oils. I do eat organic olive oils and coconut oil. So, that’s covered. :)….

          • Meggan September 27, 2013 at 3:25 pm #

            Hi Michael, Yes, Cipro is a fluoroquinolone. Too bad for me it attacked and mutated my mito DNA. (that is not uncommon btw). So, I am trying to work on the whole food absorption and changing to proteins thing. I do use pre and probiotics, whole foods etc. But for instance, NO folic acid, my body cannot use it anymore. And I do not absorb vits and mins right anymore.

            On to you… Have you been tested for IBS or stomach gastro issues? I went ‘practically’ paleo, but I DO eat eggs and use Goat milk. That helped me somewhat. Maybe it is your pre diabetic ugh

        • Teresa September 26, 2013 at 11:35 pm # Reply

          HI Meggan,

          I too am suffering from poisoning but from Levaquin (same family of drugs). It has affected all my tendons. Especially the ones in my feet and ankles. I can barely walk when I first stand up from sitting. Sometimes I wonder is it has caused some of my other problems like poor short term memory and heart palps. If you find anything that works to detox, please let me know. I cannot tolerate the 5MTHFR so cannot detox that way. Frustrating. I have a double A1298C and ten other mutants to boot. My doc is attending Dr. Lynches conference so she is hoping to discover some things that can help.

          • Michael September 27, 2013 at 3:16 am #

            Look into Zeolite for a detox. It removed heavy metals, pollutants, etc… Healthforce sells a good one, read the reviews on


          • Meggan September 27, 2013 at 3:29 pm #

            Hi Teresa, I am reading reading reading. And yes, check into the mem brain fog issue from Fluoroquinolones. Are you on FB? There is a group called Fluoroquinolone Toxicity group, they are a font of info and assistance. I have heard so many things, but one is FOR sure, your system was chelated on a massive scale, and now need I think, retraining to absorb nutrients right to repair or improve damages. I believe this with all my heart. Ask you doc about PQQ and regenerating the MITO Dna. I am asking mine in 2 weeks. PQQ is in egg yolk, parsley etc. Join the group on fb, LOTS of support and help.
            Sorry for any typos my hands now, are stiff.

        • Michael October 7, 2013 at 9:57 pm # Reply

          “Have you been tested for IBS or stomach gastro issues? I went ‘practically’ paleo, but I DO eat eggs and use Goat milk. That helped me somewhat. Maybe it is your pre diabetic ugh”

          I’ve seen Gastroenterologist, but no indicator that I have IBS. I might have Gastro issues. A ND has tested me multiple times of having low stomach acid. That can have the same symptoms of high stomach acid, but has it’s own other symptoms…I take Betaine HCI, but I worry that taking too much betaine could cause me to be over methlyated as supposedly it’s similar to TMG another form of Betaine. Anyway, I was tested as having a parasite and bacteria in my stools, but…They were both very common ones and the MD said shouldn’t be a problem. But the ND’s usually think otherwise. I’ve been on a special Oregano supplement from a ND for several months and just got done with it. I also use GSE now and then just in case. Not sure I really have candida overgrowth, but…Anyway, I suspected I might of had leaky gut, but hard to say now…. My blood sugars are all over the place, can’t tell if I’m just hypoglycemic or what….I don’t have HIGH blood sugar, so I doubt I’m diabetic, or pre-diabetic, although I have seen a couple of times elevated blood sugar after eating, but then it always comes down on it’s own. My fasting blood sugars are usually normal, but some times a little high like 110 or 105… Two different time recently, one hour after eating dinner I had blood sugar of 70. That is not normal and don’t quite understand why that would be. I ate plenty of food, but there weren’t a lot of carbs involved, just meat and veggies for the most part. Then I check it a couple of other times after, and it would go up to 80 then 90. Strange things like that. I have seen where my blood sugar would go down first then up then slowly come down then go down fast. I have a feeling after having years of mild anxiety, then 2 years of severe anxiety/panic that my body/cells are confused! Or, I could be low on a particular nutrient to help regulate insulin/glucose. I did try chromium for a while, got a huge mental energy and some what mood boosting effect, but also gave me severe insomnia. So, then I tried taking all my doses about 800mcg at breakfast, felt too stimulated (mental energy but not anxiety) and then crashed around lunch time. I’ve been tested as having high noon insulin. So, I’m not sure what is going on. I’ve read that l-carntinine can help with re-active hypoglycemia, and so can Biotin, and they help with ATP energy, and work with getting energy from foods…I hear vanadium might help, but, not sure I want to try it. I do see a new endocrinologist tomorrow. We’ll see what she has to say….Hopefully she’s got some good tests that might tell what is going on. My dad is type ii diabetic, so that worries me. But, he had years of bad diet, over weight a bit, stress from work/marriage, etc…So, hard to say if it’s hereditary or not. His dad got diabetes but not until he was like 80 or something.

  94. taiyo September 27, 2013 at 8:29 pm # Reply

    Hi Dr Erlich,

    I don’t know if someone already mentioned this, but did you mean to say phytosomal curcumin? The link you provide is Meriva which is a brand of phytosomal, not liposomal, curcumin. I figure people might benefit if you change that, even if you do provide the link, since people might try to find a different brand than you suggest.

    The brand you suggest makes sense. I would imagine phytosomal curcumin to be better since curcumin is fat soluble so if it is attached to phosphatidylcoline it absorbs into the gut better. Liposomes on the other hand are more useful for delivering water soluble medications since the nano spheres of phosphatidylcoline can hook to the cells of the gut wall and release the hydrophillic contents through it. Well, that is my understanding, I don’t know much about these things.

    thanks for all the great info,


    • taiyo September 28, 2013 at 7:25 am # Reply

      Hello Dr Ben,

      Oops, I don’t know why I called you by the wrong name before, doing too many things at once I suppose.
      I have two more questions, what do you think about using liposomes for say methyl b-12? Since intravenous injections of Methyl b-12 seems to be talked about by people so positively (don’t know if there is any research on whether it is good, just hearsay), and supposedly liposomal medications usually have a similar (sometimes better?) effectiveness than I.V. medications, and it is probably cheaper and more practical, I was wondering if that might be something worth researching.

      My second question is if a product does say liposomal curcumin (letstalkhealth has one), is that the same as phytosome curcumin? or is it different? From my primitive understanding of liposomes it seems it would either be hard (or impossible?) to make liposomal curcumin or unnecessary because of how liposomes form around hydrophillic things and deliver the contents into cells. If it is different, do you think liposomal would be very effective?

      Thanks again,


  95. Kathleen September 28, 2013 at 3:49 am # Reply

    Hi Dr. Ben,

    I have C677T. Will be doing the 23andMe to find out other issues, if any. I began taking your Optimum multi and could take it for about 3-4 days OK but not great experience, not horrible either, though. Day 1: 2 2x/day. Day 2: 2 2x/day; Day 3: 3/am 2/pm; Day 5 felt off and reduced caps to 2/am and 1/pm. Day 6 stopped taking them due to increased agitation/irritability, headaches and palpitations. When you say take B12 (I got yours) 1/4/tablet if you need more, how does one know they “need more”? I’m trying to quote what you posted somewhere on your site from memory and am not remembering much of what I want to quote at the moment. I’ve been working at reducing inflammation and am taking Premier Inflammacidin 1/4 tsp 2x/day, Optimal Turmeric 1 2x/day, sour cherry capsules. Inflammation is not completely under control but much better than it was a couple of months ago – I’ve been working to reduce severe inflammation for about 5+ months. Inflammation went way out of control (even inflammation in my brain) after an episode of severe bronchitis (worse I ever had, which was January 2013 – very strange that it was so severe). For some reason when I bump a bone it hurts very much, not sure that a result of inflammation. I tried WobeEnzyme but it didn’t help at all and I took 12/day in divided doses. Sleep has not been affected, as I’m fatigued all the time. For some reason my eyes became suddenly very blurry when the inflammation went out of control months ago. Otherwise, no other symptoms of over methylfolate dosage. Currently I’m taking 1 OptimalMulti after breakfast (after taking a break from the Optimal Multi for 2 days). The agitation returned with the 1 morning dose, though. Should I keep going with 1/day? Do I take 1/4 of Active B12 lozenge? What will the addition of B12 lozenge do?

    Thank you for your consideration of my issues. And thank you for this site and sharing what you know. I’ve been spreading the word but people look at me like a deer in the headlights, lol.


    • Kathleen September 28, 2013 at 4:17 am # Reply

      Forgot to state which C677T: heterozygous. Also, self-treating. No physician. No insurance. Probably wouldn’t be able to find a doc experienced in this area. Oh, I did find one doctor for $437/hr. Can’t pay that.

      • Kathleen September 28, 2013 at 4:23 am # Reply

        Does overcoming methyllation blocks mean that the risks associated with such mutations, such as the risk of thrombosis, go away? What happens to the risks when methyllation is corrected?

        • Kathleen September 28, 2013 at 4:27 am # Reply

          I also use bio-identical hormones: compounded 8mg 4 clicks/day estradoil and Dr. Lee’s ProgesterAll progesterone cream. Doe these compounds increase my risk of thrombosis per the C677T Hetero mutation? This has me worried, so please let me know how I should proceed with my hormone supplementation.

      • Renee September 28, 2013 at 7:06 am # Reply

        Click on my name and join the group that I admin private message me and I will help you find a lady who is very reasonable at 50.00 for few hours on Skype who can give you great great insight on your results from 23 and me.

    • Renee September 28, 2013 at 7:00 am # Reply

      Just want to say that you may have trouble with other issues like the CBS gene I read that has to be addressed first before you can successfully do the treatment on your methylation pathway. It’s all still very very confusing for me I could get my 23 and me results back and found out I do have CBS mutation. I kind of suspected it because I couldn’t have problems taking the methyl B12 but I did have problems after taking the methyl folate for a week I was only taking 200 MCG’s The folate and I had increased muscle pain and horrible irritability and emotional issues. I continue to take the methyl B12 but I avoid the folate for now until I can find somebody to help me address my CBS And other gene mutation issues. Best of luck, There are a few great Facebook support groups for MTHFR issues

  96. Pamela September 30, 2013 at 7:22 pm # Reply

    I don’t know where to begin,as I have a bunch of BIG “Catch 22″health challenges in addition. I have pernicious anemia and have been injecting 10,000mcg hydroxycobolamin weekly,, late stage chronic Lyme with co-infections, gluten sensitive celiac disease, PCO syndrome,Hashimoto’s thyroiditis, multiple GI surgeries, including hemi colectomy, resulting from being born with colon not attached to oementum, sprayed with defoliant/pesticide by a cotton crop duster,48 x-rays before birth, almost died of mercury toxicity from dental amalgams, and probably more that I’m too befuddled to think of right now. How do I know what symptom/side effect is from supplementation vs pre-existing conditions?? I have all the side effects of supplementation all the time to begin with. Do I need a different form of supplementation with the pernicious anemia? Thank you SO VERY MUCH for your website, I just don’t know where to begin and how to interpret results?? I have a great deal of anxiety and SEVERE pain EVERYWHERE!

  97. Beth Berner October 1, 2013 at 5:40 am # Reply

    I believe I have the Homozygous C677T mutation. This is all pretty new to me.

    Some of my side effects do not match anything I have seen so far. I started on 3 mg of Thorne methylfolate. Sleep was a tiny bit disturbed. Next day I did 6 mg (thank God I missed a dose). I noticed a couple-hour gap in my sleep and light sleep. Next day I again took 6 mg–my doctor had wanted me to be on 9 mg, but I decided to taper up. Good thing.

    That night, I had some of THE WORST side effects I have ever had. First, I starting becoming freezing cold shortly after getting in bed. My fingertips were turning purple; my teeth were chattering. I turned up the heat, put two housecoats on and curled up under the covers to try to get warm. This phase lasted about two hours.

    Then, almost instaneously, I became burning hot. I turned down the heat, kicked off the covers, took off the robes. I was still so uncomfortable I got up and splashed water on my face. Later, I got up and took a shower. This phase lasted about three hours.

    As I am peri-menopausal, some doctors lacking in creative thought might attribute it to this. I disagree. For one, I have had hot flashes and they weren’t like this. They were much more site-specific, for one thing. 2nd, I have not heard of menopausal women turning into human popsicles.

    Not only the hot-cold effects, but the insomnia were killers. I was already sleep-deprived. At one point I called my psychiatrist at 5 AM and asked her to put me in the hospital. Fortunately that passed.

    So, this time I am on Quatrefolic and I CHOSE THE DOSAGE. I have no idea why my doc put me on such a high dosage, especially when she knows I am sensitive to meds. The Quatrefolic starts at 400 mcgs. Even at that small dosage, I have been battling some insomnia. I think the longer I stay on it, the more likely it is to improve.

    I also have the problem–I can’t remember the name for it–where if you stand up too quickly you feel faint and can fall. The other day, I stood up to kill a bug–stood on tippy toes, promptly felt faint and spasmed and fell on my butt. Hit my head on something and have a pretty purple bruise.

    These are the only side effects I can think of. Unlike many of my meds seem to do, it doesn’t cause tremor and I am thankful for that.

    I haven’t tried the niacin or curcumin. I have been told I need to be on B6 and B12, so hope that doesn’t exacerbate side effects.

    I’m still going through the program.

    Yes, I think 6 mg set me off.

  98. Teresa October 8, 2013 at 10:12 am # Reply

    Dr,. Ben,

    My 15 year old daughter has been diagnosed with 2 different types of methylation mutations…not sure which ones. Our physician has put her on Neuro Biologix Neuro-Immune Stabilizer (1 pump in the morning and one at 7pm…the mg per dose are not given on the bottle…), adrenal cortex extract-500mg every morning, and L-Theanine- 100mg a day.

    Before starting these medications over a month ago, she had symptoms of severe weakness, fatigue, dizziness, nausea, pain in her arms and legs, high systolic blood pressure, low diastolic blood pressure, high pulse rate, tremors, clammy skin at times, heat sensitivity and cold sensitivity.’

    Almost 2 years ago, she was diagnosed with thyroiditis and has been taking .5mg of armour thyroid per day. That dosage was cut in half 2 weeks ago, and we have seen improvements with her blood pressure and pulse already.

    The headaches are more frequent and severe. The pain in her arms and legs in worse but not as frequent. The nausea is more frequent and severe. The dizziness is not as frequent or severe, but is still several times a day.

    Tests revealed that she has extremely low cortisol levels in the morning, normal levels around 6pm, and extremely high levels around 11pm. Due to this, she feels horrible until about 5pm every day…..please advise.

    She takes:

    Krill oil – 500mg qd
    Curamin – 902mg TID
    Ginger – 1.1g qd
    Zinc – 50mg qd
    Vitamin D3 – 10,000 five days a week (lab test revealed level of 59)
    Calcium – 1,000mg qd
    Turmeric – 450mg qd
    Iron – 50mg qd
    Magnesium Malate – 144mg qd
    Mitosynergy – 1 capsule am, 1 capsule pm
    Selenium – 200mg qd
    Glucosamine Chondroitin – 900 mg BID
    Prevacid – 15mg qd
    Probiotic – 20billion qd
    Gabapentin – 100mg am, 200mg pm
    Armour Thyroid – 30mg qd
    Singulair – 10mg qd
    Pulmicort – 2 puffs am, 1 puff pm
    Xopenex – 2 puffs before exercise or prn

    Her latest labs revealed High Folate, High Homocystein level, High B12, High B6

    I do not know what to do for her…. please help

    Thank you,


  99. Patricia E October 8, 2013 at 7:32 pm # Reply

    As I already have insomnia (unable to fall asleep but once asleep can stay asleep) for many years and get both migraine and cluster headaches (from age 18 onwards, and I’m 57), there is nothing new to report on those side effects – other than they are not worse.
    So far, on 8 weeks of 15 mg dl-methylfolate, i have no other side effects. I managed to find both multivitamin/mineral and b-complex supplements without folic acid (mv has 200mg folacin), so I have reduced my intake of folic acid. As I was already taking Omega-3 and Krill Oil, my inflammation is relatively under control (except for arthritis in one knee), so that may explain why nothing else has popped up.

    Anyway, my depression symptoms are better (the reason for taking dl-methylfolate along with antidepressents).

    And, a leg “tic” that I got when I sat (on the toilet) and went up on my toes (say when leaning forward) has disappeared. I did know that before taking a B-complex, that eye tics went away, but the leg one didn’t. So that is another positive that I attribute to the dl-methylfolate.

    According to the Inherent Health/Interleukin Genetics test I have MTHFR(+677) T,T and TCN2(+776)G,G, and 23andme came up with the same MTHFR(+677)T,T (listed under spinal defects – not hard to find the the info.)


  100. hank October 9, 2013 at 3:51 am # Reply

    Homozygous mtfhr.
    800 mg of metafolin a nightmare for me. Palpitations with light headedness that would be potentially incapacitating if driving. This and other side effects go away when stopped. Three retrials with same outcome.

    Are there people who have paradoxical reactions to metafolin? I am frankly afraid of trying again at Any dose. Not clear to me that good science supports benefit over risk for me. Roulette,either way.

    • Beth October 9, 2013 at 4:55 am # Reply

      I had a terrible night where I went from freezing cold to burning hot. Fingers were turning purple and teeth were chattering. Then, took off 2 robes I had put on. Lay in bed just miserably hot. Splashed water on face and even took a shower. Missed about 5-6 hours of sleep during this time. I was on a 6 mg dosage of L-methyl folate at time.

      • Dr Lynch October 9, 2013 at 5:14 pm # Reply

        Beth- was this your first dose ever taken or did these symptoms come on after taking 6 mg for a period of time? You still taking 6 mg?

    • Michael Dowdy October 17, 2013 at 1:29 am # Reply

      Hello Hank. I’m not a healthcare professional or a representative of any organization. Metyhlfolate had a profound effect on me also. Try a lower dose. Lab mistakes happen, but not likely. Maybe your lab results for MTHFR are not accurate. I added TMG to my diet because it’s a methyl donor. There are so many variables. Methionine synthase is not produced sufficiently by those with MTHFR mutations. The 677 and 1298 mutations are the most studied. Other mutations are possible. Try to locate a doctor who treats and is knowledgeable with inherited genetic problems. This site provides a wealth of knowledge. Study more. I wish you the best. Respectfully, Michael Dowdy cell 321-443-6597

  101. Michael October 12, 2013 at 6:37 am # Reply

    I’m fifty-four years old, an insulin resistant diabetic, and homozygous with the MTHFR 677 CT mutation. I also have Factor V Leiden so I’m at a pretty serious risk of stroke or blood clot. My weight is a problem. Within 48 hours of starting the 5 L-methylfolate I experienced severe paranoia, severe anxiety, inability to sleep, and my urine turned dark and felt like very hot water flowing. It was truly a nightmare to me. The 7.5 mg prescription dose was WAY too much for me. I studied a lot, experimented a lot, and now I take an activated B complex in the morning, a total of 2 mg of 5 L-methylfolate throughout the day, and 500 mg of TMG morning and evening. Sometimes I only take one of the 500 mg TMG’s if I feel a hot urine sensation coming on. The metabolism cycles are very tricky to deal with. I would seriously recommend that nobody do what I did at the start by treating their MTHFR mutation by taking either of the prescription strengths of the 5 L-methylfolate. I’m still experimenting but the doses I’m taking seem to be working alright for me judging from my blood lab work. I’ve added to my diet an organic whey protein that’s rich in branched chain amino acids but I use less than the suggested amount. Taking too much of even good things cause problems for the body to dispose of so I try carefully not to over-treat my conditions. I take a 325 mg aspirin and I use extra virgin coconut oil in my diet in an attempt to protect myself from clotting problems resulting from the combined MTHFR and Factor V problems. I suspect that the hot urine happens because of an excess ammonia problem in thetranssulphuration cycle. Can anyone tell me what causes this? Am Iover-methylated?

    • Michael October 15, 2013 at 9:30 pm # Reply

      Dr. Ben. Oops, I transposed the 5 and the L in my previous question. Please could you let me know why I experienced the very hot sensation when urinating after taking Metanx? It went away gradually and I reduced the amount of the L 5 methylfolate I was taking to around 2 mg by using a generic version. Also, what is the unexplained box that contains a check mark under the box asking for a website and what is needed in the box called “Website”? Respectfully, Michael Dowdy

  102. Debbie October 13, 2013 at 10:12 pm # Reply

    Hi Dr Ben: My husband has been battling depression for yrs, he is now 68, has been given numerous medications over the yrs with little or short term help, recently his dr recommended a totally different approach: take 15mg of methylfolate, B complex, a prohibotic 250mg bid, a low dose antibiotic along with the other meds he is on for diabetis and hypertension. What do you think of this approach and should I have niacin on hand?

    • Renee October 14, 2013 at 4:39 am # Reply

      Have the dr tell you way no methyl B 12 too. Has your husband had a DNA gene text? That can speak volumes with a DNA guru… Find them on mthfr Facebook support pages good luck

      • Debbie October 14, 2013 at 8:12 pm # Reply

        Dr Ben: my husband has not had DNA gene text, we live in very rural area and would need to travel a distance for this. I am very concerned for him to start taking such a high level of methylfolate(15mg) since with his depression he already has anxiety and irritibility. I do have niacin 500mg on hand and he is taking B complex vitamin. any suggestions what to watch for

        • Renee October 14, 2013 at 8:17 pm # Reply

          Hi Debbie this is not Dr Ben its Renee, I got my DNA testing from a great place called 23 and me here is a link best of luck.. join some facebook mthfr support groups.. please you will get lots of help there too..

          • Michael October 15, 2013 at 10:27 pm #

            Renee, how were you able to understand the report from 23andMe? After getting my report I learned almost nothing except that DNA is subject to change. I would have issues with recommending 23andMe. I’ve studied and learned that DNA changes for various reasons and can be repaired, even on a fetus. Respectfully, Michael Dowdy (cellular 321-443-6597)

          • Renee October 15, 2013 at 11:56 pm #

            I ran my raw data through a program at Your gene mutations don’t change your DNA does not change lets get that straight. Your DNA is your DNA. How on earth did you think your DNA can change?

            You can change the outcome Of the way you feel When you address these mutations be it in your Mitochondrial gene problems or methylation pathways or Detoxing issue, Etc. if you have one copy Of a gene mutation your running at 65% in that area if you have two copies you’re running it 10%…in that gene area. So In my opinion not yours it is important to find out That extra health information if you had chronic health issues most of your adult life yes I would recommend it and still do. There are DNA doctors out there who work off phine Consulting or Skype by reviewing your DNA gene raw data results, Along with medical history and past labs Etc. Kind of silly I’m still chuckling that you think that you can change your DNA. You can change the way you feel but you can’t change your DNA

          • Michael October 16, 2013 at 1:19 am #

            Hello Renee. Simply do a google search on DNA repair and you may change your mind. Respectfully, Michael Dowdy

        • Kathleen October 16, 2013 at 4:01 am # Reply

          Hi Debbie, Before I found this site and before I knew anything about methylation I began taking Niacin for good measure. I was experiencing bouts of depression. (Years ago I suffered from depression for several years until I learned about EFT and cured my depression with EFT (Emotional Freedom Technique)). Anyway, I learned about methylation when after I took a methyllateFolate pill I was severely nauseated for hours until I caused myself to vomit, then the nausea continued moderately for a few days. It was in my research that I found this site and learned why I became so sick – leading me to take the DNA test. Am positive for C677T Hetero. Anyway, I learned that the Niacin was causing my bouts of depression in recent weeks. I stopped taking Niacin (but would take it and should have taken one when I was sick from over methylation, if I ever feel that I am over-methylating). After learning that Inositol helps with depression, I began taking inositol powder in my water daily (a couple of times a day). That did the trick. No more depression. Dr. Lynch’s Optimal Multi does not agree with me. I ordered Dr. Yasko’s and this one better agrees with me. HOwever!, it wasn’t enough. Needed to assist my kidneys and liver using Premier brand supplements for liver and kidney (HepatoVen and RenaVen). But I get muscle tested for all the supplements that I take, including combinations thereof. With just the multi vitamin with the active B vitamins, of course, the detoxing wasn’t happening with just that alone and I was getting agitated and getting headaches. My elimination organs needed extra assistance. I also benefit from NAC, 500mg 3x/day. I’ve read others do not fair as well with NAC. Muscle testing is very helpful for finding out which is good for you. Hope this helps.

        • Michael (NW) October 16, 2013 at 6:38 pm # Reply

          Hi Debbie, I will call my self Michael (NW) as there is another Michael in this thread.

          I’m 44. I was hit with MAJOR anxiety/panic about 2.5 years ago out of the blue…After many months, I tried SSRI’s but made me MUCH WORSE. The last one I tried numbed all my emotions making more severely depressed. Nothing worked, nothing helped at the time… Funny thing is, I went off one SSRI, started a different older class Anti-depressant, and there was about 3 days where I felt normal. Then I relapsed. This happened twice. Anyway, I will leave out the details. But there did seems to be some sort of brain chemical issue.

          Anyway, I went on a amino acid protocol, and it did help to a point.

          And discovered where my defects are…I don’t have 5MTHF defects (so I don’t need folate), but I do in other areas that makes taking sulfur containing supplements like NAC, Taurine, MSM, etc.. NOT good for me…And could cause agitation as glutamate levels could arise because of it. Gaba is good for this and does help me.

          My methylation test does show I can’t convert B12 and require Methyl-B12. This makes sense since I have very HIGH levels of unmethylated B12 in my blood most likely from previous B12 shots I got. (I wish they were Methyl-B12 shots). Anyway, so Methyl-B12 is good for me, but not sure how much….Folate or Methyl-Folate (5MTHF) might not be good for me as I don’t require it, and have slightly elevated levels of it….I think low doses might be good, but high doses might be bad.

          Because of my other mutations, I could have high levels of ammonia and sulfite/sulfates. Hence why I need to stay away from sulfur containing supplements and foods, and lower my protein intake. (I need meat or I will starve so that is hard for me to do)…Also, because of my mutations a enzyme called BH4 could be depleted as it’s used up to detox ammonia, and it’s required for producing neurotransmitters like serotonin, and to help with NOS which I also have a defect in.

          In any case, before I took this test, I got on St. John’s Wort (Perika brand). And it seemed to calm my nerves. But, I’m still waiting for a depression lift. I am more motivated to do things, but I still don’t feel joy or happiness. Might be due to low BH4 levels and not producing neuros (serotonin) very fast.

          This is a bit complicated. I’d get the methylation test done before guessing which supplements to take. You could try a little 5-mthf, a little methyl-b12, etc.. but I wouldn’t over due it until you know if you really need it, otherwise you could cause some issues in other pathways. I would take some supplements, and started feeling better for a short time, but then would feel bad after a few days or week, but now I know which supplements help me, so I can avoid the ones that don’t and hopefully avoid any more relapses. I HIGHLY recommend the methlyation test from the link above. It’s expensive but worth it so you will know what is good and bad for you to take.


      • Michael_Dowdy April 6, 2014 at 3:28 am # Reply

        Hello Renee. I’ve looked at the LDN site linked to your name and wish you the best. MTHFR is certainly dangerous and and so are some supplements. I’m still studying and learning. DNA does get damaged by environmental causes. Neuropathy is a problem I have and some have thought it might be MS. I don’t have retinopathy that usually goes hand in hand with diabetic neuropathy. I am diabetic and MTHFR 677CT++ with Factor V Leiden heterozygous also. I’m using 5_L_MTHF. I’ve wondered if 5_D_MTHF was tested on humans like the syphilis tests done on the Tuskegee airmen. Food additives huh? I’m sick and I’d like to know why and what I can about it and how to treat it. Probably little I can do. Thank you very much for sharing. Again, I wish you the best. Michael M. Dowdy

  103. Matina St. Sauveur October 14, 2013 at 1:32 pm # Reply

    While still on a small dose of anti depressant I was started on just the folate at one milligram every week until I reached seven milligrams. I did not notice any side effects at that time due to other complications. I was put on the Deplin at a half a dose then upped it gradually to a full dose. At first I felt really hyper and irritable, withmuscle aches; but also really motivated on one task. I felt like I was on ridline. After about ten days I developed a severe neck/face rash. I went off it and the rash went away,along with the irritability and muscle aches; but my mood also fell. I restarted the deplin and the rash came back. I stopped it and I was started on the methylguard and made it up to two twice a day with no rashes, yet I was still irritable feeling with up and down mood swings. On both types I have sleep issues also.
    As mentioned I am on an anti depressant; but I have purchased the tumeric. One tablet has 350 milligrams. Is this safe to take with anti depressants so I can begin clearing some of the inflammation?

  104. Jen October 14, 2013 at 9:02 pm # Reply

    Dr. Lynch, I am homo C667T, and have worked my way up to 2.5 mg L methylfolate. My child’s doctor recommended this for her, and for me. Since it was my child’s doctor, I didn’t talk too much about myself. However, I am currently in physical therapy for four protrudings disc in my neck and arthritis. I am wondering–what do you mean when you say “inflammation?” I’m kind of in chronic neck pain, taking Advil for relief, trying to make progress with the physical therapy.

    • Michael Dowdy October 18, 2013 at 11:14 pm # Reply

      Hello Jen. I’m not a healthcare professional or part of any group. It sounds like you’ve got a good doctor there. Homozygous MTHFR 677 C-T is very serious and needs your attention. Metabolism problems this severe have to be treated. Methylation is necessary in so many ways. You’re basically malnourished. You are not digesting very needed amino acids efficiently. But one thing wrong that most people do is over-treating themselves. You need premethylated vitamins. If your body can’t use what you put in it it has to get rid of it and your organs and systems will stay inflamed dealing with excesses and toxins. You need proper nourishment to live and help prevent inflammation. STUDY this site because it will get you going in the right direction. You need something totally different than folic acid. Folic acid is bad for someone with severe methylation problems and you need to start using the right things starting off with small and careful doses including methylfolate instead of folic acid. People with poor methylation usually don’t have healthy levels of glutathione (GSH) and their immunities are usually impaired. DO NOT take things that deplete glutathione. Paracetamol is a very dangerous drug because it depletes glutathione. Look up paracetamol because it’s extremely common under different names and is added to many common prescription pain-killers. PROTECT YOUR LIVER! Eat well, pay close attention to how you react to different foods and drugs and get good help with treating your metabolism problems. Best Wishes, Michael Dowdy (321-443-6597)

      • Michael (NW) October 23, 2013 at 6:25 pm # Reply

        Hi, according to one test I have a high need for glutathione, but because of my mutations, MTRR/A66G +/+, MTRR/11 +/-, BHMT/1 +/-, CBS C699T +/+, VDR/TAq1 +/+, VDR/Fok1 +/-, and NOS/D298E +/+, that anything with sulfur is not good for me, so NAC would be bad. So, how do I get glutathione? I know you can get injections, but isn’t glutathione a sulfur? Thanks.

        • Dr Lynch October 23, 2013 at 7:52 pm # Reply

          As I say over an over:
          “Don’t treat the SNP. Treat the patient.”

          You cannot look at snps and develop a treatment plan. Simply because one has CBS 699 doesn’t mean they cannot tolerate sulfur – sulfur is incredibly important. Need a doc that understands this. I am working on increasing the awareness and training.

          • Michael (NW) October 23, 2013 at 8:28 pm #

            Hi Dr. Lynch,

            I appreciate your feedback/info. I’m basing my information on Dr. James C. Roberts website.

            I don’t have a local MD/ND that knows anything about this methylation stuff, and so I’m taking what i can put together from Dr. Roberts site to put together a wellness plan. It seemed due to my CBS, BHMT and NOS status that I would have high sulfur/sulfite/ammonia levels. It seemed that when I took supplements like methionine, I felt fine for a bit then it made me feel worse….Also, I was on a amino acid therapy which included large doses of MSM, I was constantly being over stimulated by it. Might have been the 5-htp and/or tyrosine, but too much sulfur due to my status could cause higher levels of glutamate, etc… (Again basing my info on Dr. Roberts info). I seem to be doing better after I stopped taking methionine, SAM-e, NAC, products with Glucosamine in it etc…I feel like I need to also avoid sulfur containing foods, as some times after eating nuts, or salsa, etc…I will have a bought of agitation/lower mood/brain fog-lethargy, etc… but limiting foods HIGHLY limits what I can eat since I have to already avoid gluten, dairy and eggs. I need meat, as I have hypoglycemic feelings and if I don’t eat a good meal, I get hungry easily, and too many carbs are bad so I try to eat a balance. I can easily avoid excess onions and garlic which are high in sulfur, and avoiding the sulfur containing supplements should all help.

            I’ve been taking activated charcoal as suggested to help remove ammonia…

            I’ve been taking Molybdenum to also help convert sulfites to sulfates, etc…

            I’ve read that my status depletes BH4 which is needed for the creation of neurotransmitters and might be why I’m not getting better very fast. I’m also taking St. John’s Wort now, which helps a little but not enough. I started taking some Ginko and also 5mg of Lithium Orotate to help stabilize how I feel. We’ll see if the Lithium Orotate works after a week.

            I’m a bit overwhelmed by my mutation status I have many. And I’ve read that it’s best to fix one area before others, etc…I just don’t know what to do and what supplements are best for me, etc….

            Anyway, I appreciate the good work you are doing and for your response.


          • Dr Lynch October 24, 2013 at 7:41 am #

            Hi Michael –

            That website is pretty informative but in my opinion, it treats the snp – not the patient.

            Expression of genes is far more important to evaluate rather than a snp.

            Also keep in mind that even if you dont have a snp in a gene doesnt mean it is working normally – for a whole slew of reasons.

          • Michael (NW) November 5, 2013 at 6:27 pm #

            My genetic testing results seem complex since I have multiple mutations…I don’t have a local doctor that really understands methylation….Well, I’m going to see someone tomorrow who might know more than anyone I can find, so we’ll see how that appointment goes….Do you know anyone in the NW (I’m from Oregon) who really understands this methylation stuff and can help me with my test results?

            Also, one of your videos shows these additional tests:

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

            Where can one get these tested?

            Thank you,

            Michael (NW)

          • Michael (NW) November 5, 2013 at 9:58 pm #

            You mentioned, “Expression of genes is far more important to evaluate rather than a snp”. What do you mean by evaluating expression of genes than SNP? I have my test results, and I have various mutations, so how do I go about treating myself. And I mean myself, since I have no doctors that know anything about this stuff to help me. I just saw one last doctor today, and they didn’t have a clue. They recommended a couple of products which were actually not recommended by the Cardiologist who knows a heck of a lot more about methylation that this doctor does. So, now I’m stuck, no one to help me. I don’t care so much about these mutations if I could just find something to help me feel better. I’m on Perika St. John’s Wort which is sorta helping. SSRI’s made me MUCH worse, so I’m hoping SJW will help. Once I get stable then I can look at methylation more, and hopefully some day not need something like SJW. I’m currently dealing with depression (lack of emotions, no joy, excitement, no feelings of looking forward to things), this got really bad after trying Lexapro which totally numbed my emotions and I never got better since, and that’s over 1 year ago. I also get agitated-anxious/brain-fog/low mental energy/ especially after eating food, mostly after lunch that time frame I feel the worse. I have terrible insomnia, waking up at 2am-ish every night, etc…. I need help, I’ve exhausted all my resources trying to get better. I’ve lost everything. If I can just get feeling better I can start rebuilding, but I continue to suffer…..

            Thank you for all that you do!

        • Renee November 6, 2013 at 2:19 am # Reply

          Michael, click on my name come look me up in my group, I can help you find a practicing DNA Dr who uses SKYPE and your medical history and labs and your tests results.. Ill help you find someone who can help you figure out whats up looking at your symptoms,history,labs,dna Renee Olive

  105. Wendy October 16, 2013 at 3:16 am # Reply

    Hi Dr. Ben,

    I am compound heterozygous and just started on Methyl-Guard which my Natural Path had recommended to take during times of stress. After 3 days I am feeling mild symptoms of headache and muscle soreness. I believe that I do have inflammation from some recent stress so may try adding Tumeric and will likely stop Methyl-Guard for a time and take the multi you recommend or perhaps Phyto Multi by Metagenics which my mom’s doc has recommended. My question is about the recommended dosage of potassium. You recommended only taking 125 mg at a time. I was thinking of trying your recommendation of water with Vit C and electrolytes. However, the dosage for potassium in the Bodybio concentrate (6 to 9 capfuls per liter) seems to be much higher than the recommended dosage of potassium in the previous posts. Could you help me understand how much potassium is best? Thank you, Wendy

  106. Tamsin October 16, 2013 at 10:46 am # Reply


    I am definitely in category 3. Answers:

    1) Severe anxiety, irritability, a rushing feeling (similar to the effect of high dose B6, but less panicked).

    2) Did not try niacin. 20mg propranolol resolved problems immediately.

    3) I tried 400 mcg 5-methyl folate on two occasions, several days apart. In both cases an intolerable reaction occurred within 2-3 hours of consumption. I have not tried ‘working through’ the side effects.

    4) No. I started on 400 mcg.

    5) No. See answer 4.

    I know my mutations and have read Yasko’s book. I take other supplements (currently, low dose methyl B12, magnesium, L-carnitine, and a standard multivitamin).

    Any thoughts or advice warmly welcomed. It seems this is not a common reaction.


  107. Eve October 16, 2013 at 3:49 pm # Reply

    I am compound heterozygous, 1 copy of each

    1.Methylfolate side effects include intense brain fog/confusion, intense mood swings and anger

    2.niacin and curcumin: Did not try as pregnant

    3.I had the side effects (after feeling great) when I switched from 1 mg straight MTHF to the Thorne Prenatal. After one week of taking I the had several days of side effects were to much and I was afraid of it affecting the pregnancy. Not sure if it is the methyl B12 which I don’t do well on or the half calcium foinate

    4.Initial experiments of 1 mg a day was too much.

    5.Had to taper up from 500 mg MTHF to 1 mg which seems to be a good base line for me but still don’t tolerate methyl B12 even starting at 500 mg

    • Renee October 16, 2013 at 10:08 pm # Reply

      Hi Eve, I’m working with a DNA familiar Doctor right now, NOT DR BEN. I just got my instructions today to do 200 MCG methyl folate BUT ONLY after 2 weeks of methyl B12 2000mg.. he wants me to start out SLOW and each week ad a bit more methyl folate till I find my perfect dose. for me and my gene mutations I do take niacin daily per my ACT mutations I believe and he said to double it if I over did the M folate. Once I find my best dose I stick to it! hope this helps. YOU DO see things are dosed out just for my gene mutations, not everyone is the same.. best of luck

  108. Michael Dowdy October 21, 2013 at 12:05 am # Reply

    Hello Dr. Ben Lynch. I’ve been unable to learn much about trimethylglycine (TMG/Betaine) and just how effective it is as a methyl donor compaired to the methionine synthase that I do not produce being that I’m homozygous for MTHFR C677T. How effective is it and what would a safe dose and when should it be taken in relation to meals?

    • Lynn_M October 21, 2013 at 2:23 am # Reply


      The MTHFR C677 gene encodes for methyltetrahydrofolate reductase. Being homozygous means that enzyme is reduced by roughly 60%. It is nothing to do with methionine synthase. Methionine synthase is an enzyme that is encoded by the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase).

  109. Michael Dowdy October 21, 2013 at 12:20 am # Reply

    Are there negative side effects of trimethylglycine compared to methylfolate and what are they?

    • Lynn_M October 21, 2013 at 2:57 am # Reply

      TMG is active only in the kidneys, liver, and the eye. So it contributes methyl groups in those locations but not in the rest of the body. Taking TMG favors the shortcut route to making methionine, but at the expense of the long route via the MTR and MTRR genes. If you look at the intersection of the folate and methionine cycles at the point where MTR and MTRR genes are involved, once methylfolate donates its methyl group, it then becomes THF, and from THF other reactions occur which lead to the formation of DNA and amino acids.

      So TMG contributes to a bypass of the long route, which ultimately may lead to reduced DNA and amino acid formation. If a person’s long route isn’t working, TMG can be a short fix to get some methylation going while working on getting the long route working.

      • Michael Dowdy October 21, 2013 at 3:48 am # Reply

        Lynn, thank you so much for your answers. You definitely gave me a lot to study. Respectfully, Michael Dowdy

      • Michael Dowdy October 22, 2013 at 5:57 am # Reply

        Hello Lynn_M. Since trimethylglycine use can interfere with with DNA formation and amino acids would it be more beneficial to skip every other day when using the TMG? What dosing would you suggest and how often? Would the correct dose be determined by my weight? Aside from the really bad side effects of taking methylfolate at first about six months ago, I feel like I’ve found the right dose for my methylfolate at around 2mg’s. I’ll know a lot more when I have my blood labs in December. I know I’m doing better because my insulin has become much more effective for some reason, possibly because of cimmamon, chromium, and L selenium. Whatever has happened I seem to be heading in a positive direction. Fatigue left at first but has returned some, but not as bad. Since I’m homozygous my mother would have to be at least heterozygous for the 677 C-T mutation. Her doctor seems to think that my mother requires no treatment for her MTHFR mutation. I think it should be treated, just much less aggressively. What do you think?

        • Lynn_M November 17, 2013 at 5:24 am # Reply

          Michael Dowdy,
          I am not a health professional so I will not give treatment recommendations. The understanding I’ve developed from reading the opinions of some doctors is that TMG is a short term fix, i.e. a crutch to use while a person is doing other measures to get their long-route methionine cycle working. Once the long-route is working, I have my doubts about whether TMG would still provide any benefit. It seems to me that at that point you want to encourage the long-route, and as some doctors advise, taking DMG would seem to provide that encouragement. Having ample DMG would provide a back-pressure to make the body choose the long-route over the short route.

          Unless her status has been verified by testing, your mother could be homozygous or heterozygous for C677T or compound heterozygous. Also, I think it’s too simplistic to look at just C677T or A1298C when 23andMe identifies something like 56 MTHFR snps. Unfortunately we don’t seem to know much about those other snps, but surely they also have an impact. Whether treatment is needed would depend on her diet, her lifestyle, her symptoms, and lab testing. I think it’s better to test than to guess.

          • Michael Dowdy November 17, 2013 at 8:09 am #

            Hello Lynn_M. Thank you for responding. I’m not a professional in healthcare either. A hematologist has just prescribed the testing for my mother so I should know soon her MTHFR and Factor V results. The reason I’m concerned is she recently was hospitalized with DVT and PE and she’s been placed on Warfarin permanently for clotting issues. These conditions affect others in my family and I have a daughter that I’m very concerned about. A very recent article is online from AAOS Now, June 2013, entitled; Aspirin vs Warfarin: Which Is Better At Preventig VTE? and concludes that Aspirin is much safer and better than Warfarin at preventing VTE and PE in patients that have had total joint replacements. I’ve been mostly researching anti-thrombolytics since my mother probably has both of these inherited conditions. There’s no way other than if it were an emergency I would allow a Dr. to put me on Warfarin and I would absolutely refuse to use it long term even though a doctor may advise it. That’s what I’ve been researching the most about right now. I’ve started trying to take preventative measures since I’m sure I’ll likely suffer the same problems. …. I started taking TMG before I really understood much of it’s uses and my blood labs improved in a huge way coming back good except for my sugar and A1C and even they were pretty good. I was shocked! My blood labs haven’t been this good in probably more than twenty years. I have liver fibrosis with some focal bridging so I was hoping that trimethylglycine might help my liver heal. I know it’s a long shot but I’ve never liked or eaten spinach, beets, and other foods that normally supply the body with it. My mother, on the other hand, normally thrives on these foods but they want her to avoid them now because she’s on Warfarin. I don’t think anyone will ever convince me that what is basically rat poison is good for humans. …. Thank you very much for your valuable input about TMG. I’ve only started treating these conditions over this past year but I’ve had some interesting and significant success. This site has helped me a lot. I haven’t had my raw data from 23andMe totally analyzed yet but I’m going to. I did see the large number of MTHFR snp’s and I know that they are currently studying only the 677 and 1298 locations. You’ve certainly made me take a harder look so I owe you some thanks and appreciation! Michael Dowdy (321-443-6597)

          • Michael Dowdy December 8, 2013 at 8:38 am #

            Hello Lynn_M. I agree that there’s still obviously a lot to be studied and learned since so many snp’s have yet to be studied. My mother’s test came back confirming that she is homozygous for the 677. They didn’t test my mother for the 1298 though. Doesn’t this mean that all of my siblings and my daughter have to be at minimum heterozygous for MTHFR 677? If I understand correctly there’s a very slight possibility for the 1298 also. I see the marker for the 1298 in my raw data. My mother is heterozygous for Factor V Leiden so at this time she and I share the exact polymorphisms. It’s extremely difficult to find a doctor willing to work with the methylation problems, and understandably so because it’s very complicated and has to be treated on a very personalized basis. It’s sort of a can of worms as the expression goes. I’m still very upset that my mother is permanently on warfarin, but that’s still the current protocol. My mother is going through problems that I will likely face in the future. Nobody will ever convince me that warfarin is a good treatment for people with the snp’s we have and I can guarantee you I will never use warfarin on a permanent basis. Warfarin is supposed to be basically rat poison. I’ll take my chances with aspirin and virgin coconut oil and improved nutrition. It seems to me that TMG to reduce damaging homocysteine levels and extra virgin coconut oil to promote vascular healing would be a much safer alternative. I haven’t found proof yet but I strongly believe that warfarin likely depletes glutathione and that would only severely compound the problems and lead to an earlier death. The whey protein found in Immunocal should be a huge help to anyone’s health because of the critical importance in maintaining good glutathione levels. The British seem to be ahead of the US in their views on warfarin. AAOS Now published an article in June 2013 about aspirin vs warfarin which showed that aspirin was much better and safer at preventing VTE than warfarin in patients undergoing total joint replacements so my logic tells me aspirin would be much better and safer than the current protocol of warfarin for my mother’s clotting problems due to the genetics she and I share. She’s not been put on methylfolate yet but I’m using methylfolate and it’s doing well for me. Actually it seems to be doing extremely well for me. Since neither you or I are healthcare professionals I’d love the opportunity to speak to you. Call me if you wish, please. You seem very knowledgeable to me and I’m really just learning but I’ve achieved some very good results for myself so far. I hope others can benefit from my experiences that I’m actually thrilled with. But I still have severe fatigue and 23andMe has let me know I have markers for narcolepsy. I’m still using 75mg of diphenhydramine morning and evening for my histamine problems which of course adds to my fatigue. By making adjustments in the methylfolate I use I’m no longer having what seemed to be excess ammonia in my urine causing burning sensation. The methylated B complex I take has inositol in it so I haven’t needed any additional niacin. I’m trying to keep my meds and supplements as conservative as I can yet enough for effective results and low enough to avoid over methylation problems. I’m glad I got my genome when I did and I hope 23andMe starts offering it again soon. There’s still a lot needing to be learned and people should be given that opportunity. Dr. Ben and 23andMe have both been a huge help to me. Respectfully, Michael Dowdy

      • Michael (NW) October 23, 2013 at 6:21 pm # Reply

        Hi, I started using TMG for about 2 weeks at 650mg a day. I put it in a 32oz bottle of water and drink it over the course of a day along with some other stuff. I started getting gut issues, bloating, heart burn, acid reflux, tight next muscles, worse insomnia, all things that others have complained about side-effects. But, it does work great without side effects for others. Anyway, I think it might be the TMG that is causing my issues. Anyway, I wanted to take TMG as I have the CBS/C699T +/+, BHMT/1 +/-, VDR/Taq1 +/+, VDR/Fok1 +/-, and NOS/D298E +/+ mutations. I don’t have a Doctor in my area that knows anything about these mutations, and so I’m just pulling info I read on the Internet to try and put together a wellness plan for myself. Anyway, TMG is noted to help stimulate BHMT and to help pull homocysteine away from CBS and lesson the burden of sulfur, etc….I don’t have a MTHFR mutation but I do have MTRR/A66G +/+ mutation, so I need Methyl-B12 which can also pull homocysteine away from CBS, but not sure if B12 or TMG is better for this….I also don’t want to over stimulate other areas. Anyway, I just don’t know what to do. I thought I’d also try some hydroxy-b12 but not sure if that is required. Also, I’ve read because of my mutations that BH4 is limited and this is need to create neurotransmitters, but the info said if I use BH4 I could spin things up too fast and cause problems. rrrrg. not sure what to do. I have depression anxiety and insomnia, and it REALLY bad for about 2 years. I’m on St. John’s Wort now which is helping some but not enough yet….. I could use any help possible. Thanks.

        • Michael (NW) November 22, 2013 at 6:25 pm # Reply

          The magnesium chloride shots with methyl-b12 seems to help.

          I am going to go on some antibiotics. They found Blastocystis Hominis more than once in my system. This can be problematic for some people. Could have been the root cause many of my symptoms, so I decided to finally eradicate it. They are going to give me Nitazoxanide. I hope it works and I will start feeling even better. We’ll see how it goes. I take it 3 x per day for 3 days. There is a gut/brain deal going on and if my gut is healthy, then maybe my well being will be improved. I hope it helps. :)

          • Ben P July 27, 2014 at 9:11 pm #

            Hi Michael,

            I hope you’re doing well, I was just curious how you’re treatment for Blastocystis Hominis went and if it has helped you. I’ve also tested for this and think it may be behind my ongoing health problems, but I’m concerned about taking strong antibiotics that might be worse!



      • Michael Dowdy November 10, 2013 at 1:49 am # Reply

        Hello Lynn_M and Ben Lynch. Thank you again. I started taking TMG because I understood that my MTHFR C677T ++ and Factor V Leiden put me at high risk for vascular damage from excessive homocysteine levels in the blood. I thought that TMG’s main target was the homocysteine first, the TMG changing into dimethylglycine after being a methyl donor, also producing methionine. It’s a bit confusing. I’ve had some decent results recently in that my diabetes has apparently improved some and some changes in my neuropathy. All along my eyes have been spared from damage from long-term diabetes and my eyes are in very good condition and show no visible damage from diabetes. Methylfolate negative side effects were serious at first but I seem to have reached some clear improvements. The things I’m daily using are methylfolate 2 mg, TMG 1 mg, a methylated B complex (Jarrow B-Right), extra virgin coconut oil and honey on whole wheat daily, cinnamon with chromium, and organic whey protein daily in addition to my current physicians’ prescriptions. I learned that leucine will make the pancreas secrete insulin and I can pretty much confirm that. I just very recently had to start taking magnesium for heart PVC’s. Histamine and fatigue are ongoing problems but I’m not really very concerned about these. I’ll get new labs in December and will know more then if any further improvements. I’m pretty happy and somewhat surprised with the improvements. Do you have any idea what may be causing my excessive nasal drainage which I assume is resulting from a histamine issue in my metabolism cycles? Respectfully, Michael Dowdy (321-443-6597)

        • Michael (NW) November 15, 2013 at 10:37 pm # Reply

          Hi Michael Dowdy…. I’ve taken TMG off/on. But I’ve been taking Betaine HCI for digestion, and I’ve heard it’s basically the same thing as TMG. In any case, I believe Methyl-B12 and TMG will pull homocystein away and convert it to methionine? If that is the case, I would assume that if your natural reserves of methionine build up, histamine would be more under control as methionine is anti-histamine….One doctor recommends taking methionine to reduce a high histamine person…I believe i have high histamine. I have had high/normal levels in my blood before…And I believe it could be causing some of my depression and tight band around my head. I was on Lexapro one time which totally numbed my emotions, but as soon as I got off it after 4 weeks and went on a low dose of Remeron, I slept great (had horrible insomnia), and after 7 days on Remeron which was 9 days off Lexapro, I felt 100% normal for the first time since i was probably a kid and I was 43 when this happened. But, I think as the anti-anxiety effect of lexapro wore off, I went into relapse and felt horrible. Remeron which is a old class of Antidepressent, at a low dose is a powerful anti-histamine. So I wonder if the combo of Lexapro and Remeron in my system if some how Serotonin was raised and histamine lowered making me feel better. I’m not sure. Remeron is known for it’s fast acting anti-depressent effects (but I was at such a low dose for only 7 days that I doubt it had that effect on me) that you can have a honeymoon effect for a day or so then it wear off and might become effective at a later date. I tried Lexapro one more time while still on Remeron, felt horrible again, after 4 weeks went off lexapro, started feeling great again but went off Remeron and went downhill and never recovered and now I’m trying to figure all this stuff out in regards to methylation etc… I’m doing St. John’s Wort now and some amino acids, etc… In any case, I keep wondering if those brief moments of feeling amazing were due to lexapro’s anti-anxiety effect (although it made me feel emotionally horrible) and remeron’s anti-histamine effect……I just don’t know. But, since I have some other mutations where sulfur products would not be good for me, taking methionine may not be a good idea for me. I have issues with CBS, etc…..But, if you don’t have CBS, BHMT, etc… Then taking methionine might help lower your histamine levels, but..I just wonder if taking Methyl-b12 and TMG get your body to make enough of it’s own methionine to lower histamine to levels that would make someone feel better? I’m not sure. I have taking methionine before and it seemed to help, but I was taking other sulfur products at the same time and i think I got overloaded as I started to feel worse I think. I don’t ever want to take Remeron again as I had too many side effects coming off it. Not sure what other natural ways I could lower my histamine levels enough to make a difference to see if that helps my depression. I have atarax (Rx) but it had a moderate interaction warning with SJW. Quercetin can help but not sure if it’s enough…Michael

          • Michael Dowdy November 16, 2013 at 10:20 am #

            Hello Michael (NW). If you haven’t had a sleep study done a bi-pap helps eliminate gut issues as a great side effect. I would recommend a sleep study to anyone. A bi-pap has enormous benefits which are not usually discussed. A bi-pap really protects against chronic sinus blockages. One’s a bit aggravating initially but very comforting in the long run. Once you’re used to it it’s invaluable. Thank you for sharing your information. I think TMG is more beneficial than is known with benefits to the vascular system. I hope it helps with chronic digestive system inflammation issues. Time will tell. Dosage is a big question to me. Respectfully, Michael Dowdy

          • Michael (NW) November 19, 2013 at 6:56 pm #

            Hi Michael Dowdy, Well, the following are my mutations….

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

            Kind of a mess. But, I had my ammonia levels checked and they were normal. And they should be high in regards to these mutations, but some how I guess I’m either taking something that is helping or my body is able to process ammonia somehow. I’m awaiting sulfur/sulfite urine test results. This should also be high. If not, then I’m not too worried about the CBS and BHMT mutations….I have been taking Methyl-B12 for some time so maybe that has helped lower ammonia etc…

            I just had a magnesium chloride and Methyl-b12 shot. I had two of them. They actually make me feel better I think. I assume sublingual Methyl-B12 is probably almost as good, but I figured I’d try a shot since it goes directly into the body/blood.

            I really feel that I need high amounts of methyl-b12 due to my mutations and due to my high/normal histamine and high/normal homocystein levels.

            But, I read somewhere that Methyl-b12 can increase histamine? Since Methyl-b12 pulls homocystein into methionine I would think it would reduce histamine since methionine is our body’s anti-histamine product, right?

            I really feel that lowering histamine would be huge for me. Not sure if high amounts of B12 will help that or not. Someone also mentioned on another area of this forum that from their research (or personal findings) that histamine pulls a methyl donor from SAMe? So, SAMe can be low. And they recommended taking Niacin at night to use up SAMe, so that it can be produced higher during the day? Not sure about all that, but thought it was interesting. So, taking larger amounts of B12 should create more methionine, reducing histamine and raising SAMe….???

            I wish someone out there knew all about these mutations and could direct us in how to treat them properly…..I don’t know of any doctors in my area.

            Again, I’m on 1200mg St. John’s Wort. I take some Tyrosine, 5-htp and/or Tryptophan, mucuna, to help build up my neurotransmitters. It’s been a long process and not sure why I’m not feeling really good by now. Do I have thyroid or adrenal issues? My thyroid keeps coming back normal although I just had a new test done and waiting for results. I still suspect high histamine levels…..

            Thanks for listening and any suggestions.

            Michael (NW)

          • Michael Dowdy November 20, 2013 at 7:59 am #

            Hello Michael (NW) Your questions go into areas that I am not familiar with but I’m glad to share what I’ve learned. I’m not a health care profession so I might not be correct. With regard to 5HTP I’ve tried using it in a lower dose and it was very calming to me. It’s very frustrating trying to treat snp’s. Dr. Ben please correct me where I’m wrong. TMG / Betaine is very useful in treating excessive homocysteine and I’ve heard that HomosysteX by Seeking Health brand has excellent quality control. I understand TMG is also may be available in a couple of prescription strengths. I use it because it is a natural substance derived primarily from beets and found in leafy greens so I don’t believe negative side effects are likely. I use diphenhydramine for histamine problems even though it will leaves me tired. I don’t believe that methylated B complex would be harmful to any individual, with or without MTHFR problems. Methylfolate though is not tolerated by many. I hope you find a doctor who is knowledgeable in nutrigenomics. Thanks for sharing. Michael Dowdy (321-443-6597)

          • Michael (NW) November 20, 2013 at 5:39 pm #

            Hi Mr. Dowdy, I think 5-htp is over stimulating to me, and if used for too many days, I get agitated, gut issues, etc… That’s what I’m assuming. If i don’t use it, and just use tyrosine during the day and tryptophan at night, that seems to work better. I was using 5-htp at 100mg a day, in the past I was told my by ND to use 1000mg during my amino acid treatment. Anyway, I tried 5-htp again the last couple of days, and had some discomfort. Not sure it’s the 5htp or not, but I will stop using it again and just stick to Tryptophan.

            I think Dr. Lynch mentioned that TMG and Betaine HCI were basically the same and can be used as a methyl donor. I use Betaine HCI for digestion as I was tested low stomach acid….They are 650mg pills, so if I take one per meal, I’m getting quite a bit of methyl donors. Not sure if that is good or not.

            You mentioned the sleep study (I forgot to comment). I thought about doing one. Not sure i have apnea or just issues with blood sugars dropping at night or depression related insomnia. Right now I can fall asleep just fine, but I wake up between 1-3am EVERY night, and then I usually snooze on/off after that. One ND said it could be my liver as the liver regenerates about 1am. (I think Chinese medicine will say the same thing).

            I’ve had some strange blood sugar issues these past 2 years and I can’t get any endocrinologists to listen to me. When I first came down with the out of the blue severe anxiety/panic adrenaline rushes, etc….., my blood sugars were all over the place, probably a normal issue due to the anxiety, but….I would have lower than normal readings for myself like 70’s which normally I would have fasting of 100, maybe 90’s. Then I’d eat, and some times my numbers would go down first, then go up slowly, then drop fast, etc…This is not normal. I only had above 180’s once or twice, maybe once in the low 200’s, otherwise it’s been pretty normal. But, I will have hypoglycemic like symptoms when my blood sugars are in the 80’s or 70’s but since that’s considered normal my Endo docs just ignore me. I did have a glucose tolerance test, 2 hour test. it was fairly normal. But after the 3rd hour I crashed (around 11am-noon), got into the 50’s. They just called it re-active hypoglycemia. I had a saliva test done and showed I had HIGH noon insulin. But no one can help me with that.

            I’m just now doing another saliva (adrenal stress index) test, which will test fasting insulin, cortisol, etc…I will be interested how things look now that my anxiety/panic is much lower. Although I’m still not feeling great.

            Michael (NW)

      • Michael Dowdy November 10, 2013 at 6:11 am # Reply

        Hello Lynn_M. I correct myself. I’m taking 1g of TMG a day, actually 500mg twice a day. I think I’ve made some significant improvement but it could change. Thanks again. Michael Dowdy

  110. Margaret October 23, 2013 at 6:39 pm # Reply

    My doctor put me on Methylation Balance which is B6 60mg, Folate 2,000 mcg and Vit
    B12 10000 mcg. Is this the same ingredients as Methylfolate?

  111. Dana October 28, 2013 at 4:30 pm # Reply

    Hi all,

    I have C677T heterozygous. I have had a lot of success taking Methylguard by Thorne. I only take one a day, because taking two causes me to experience almost all of the side effects. In addition, I take Krill oil 2X day, CoQ10, ALA, Vit E, D3. All in all this has been very successful for me. Good luck and remember to start slow…

    • Matina St. Sauveur October 28, 2013 at 11:50 pm # Reply

      I have tried taking only one a day of the Thorne Methylguard and still get the unbearable anxiety, hyper energy, and some irritability. I have not tried the niacin though. Also as mentioned above I am on an anti depressant and anti anxiety medication. Should that make a difference with such a small dose of methylguard? How much niacin should I take with just the one tablet of 400 mcg. methylfolate?

  112. Rebekah October 31, 2013 at 2:33 pm # Reply

    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 and mostly fine until around age 8-then different symptoms came and went. 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 think she may be developing something like MCAD. I put her on a low histamine diet, adding omegas, probiotics, and some 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 just yesterday 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. I’m trying to understand all of this information. I don’t want to make her worse. 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.

    • Kathleen November 2, 2013 at 6:34 pm # Reply

      Hi Rebekah,

      Have you seen Dr. Yasko’s webstie She specializes in children with mutations. I take Dr. Yasko’s All In One vitamin and tolerate it very well. She has a lot of formulations that are mutation specific.

      Best wishes.


  113. Beth November 2, 2013 at 6:23 am # Reply

    My homocysteine levels are a bit high–.6–so my doc started me on methylfolate. I took 3 mg the first day and 6 the next two. I had terrible reaction on third day with fingernails turning purple and teeth chattering, basically a hypothermic reaction. I did everything I could to warm up and was able to maybe an hour or two later. Then I instantly became uncomfortably hot–kicked off all the covers, but couldn’t stand to just lay there. Opened a window, splashed water on face, and took a shower. This, too, finally abated after a couple of hours. But I had missed 5 hours of sleep–from 2-7.

    I was a wreck. I called my psychiatrist at 5 AM. She said I needed sleep. True, since the folate had been giving me insomnia from the get-go.

    I took the dose down to 400 mcg. Still too disruptive. I even cut tablets into 200 mcg’s. Still too much sleep disruption.

    I have now been off the folate for maybe 2 weeks. My sleep pattern is now waking up every 2 hours. It wasn’t good before, but it was better than this. Could the folate still be in my system? I just read a note from Dr. Ben where he said folate could have long-term effects in those with bipolar. I do have bipolar II disorder.

    I also noticed that after the terrible night of side effects, I had a mini-version about 4 nights later. I was off of the folate–I think I quit the same day of the bad side effects!

    My question is, can folate stay in your system for awhile, especially if you are bi-polar? Also, if you are a psychiatrist who treats bi-polar, shouldn’t you know this?

    Thank you,

    • Renee November 2, 2013 at 6:40 am # Reply

      Beth as per Dr Bens info get some niacin asap it helps remove the extra methylation happening to you work UP not down.. Dr just dont know best to do your own research and be your own best advocate.. read all you can here.. Dr Ben has lots of info on here best of luck

      • Beth November 3, 2013 at 5:54 am # Reply

        Renee, thanks for your note and advice. I have been in the illness business so long, I’m surprised the combo of meds and doctors hasn’t killed me yet. Actually, all my docs are very good. Just expressing my occasional cynicism. :)

        • Renee November 10, 2013 at 2:24 am # Reply

          Beth, OH I am sick to death of decades of Dr not helping me, I finally took control and am treating myself!! I found LDN for my fibro and got my Dr to write me a script for it.. but pretty sure if I get my mthfr issues under control my fibro will be gone!!! I did my 23andme and got my Dr to send me to a Genetic Dr, we shall see if shes any good.. modern medicine has not grasp treat the illness not the symptoms!! SO FRUSTRATING! Im happy I took charge 3 yrs ago or I’d still be bed ridden.. best of luck I go to a group on facebook called mthfr heaps of info see you there.. also I found and admin a facebook group for LDN the link just click on my name, Cheers and good health

    • Renee November 2, 2013 at 6:42 am # Reply

      Sorry what I mean in working up not down, is start LOW with your methylation supplements and work your way up to a place you feel good not out right OUT OF IT! LISTEN TO YOUR BODY!!
      Best of luck

    • Michael Dowdy November 2, 2013 at 9:48 pm # Reply

      Hello Beth. I’m not a doctor or professional, only a patient. Why are you taking methylfolate? Betaine (TMG trimemhylglycine) will lower your homocystiene without the side effects of 5MTHF. Methylfolate did horrible things to me at first when I started with the prescription strenght dose. I require the methylfolate because I’m homozygous with MTHFR C677T. If you’re not diagnosed with MTHFR problems I would recommend that you not use methylfolate or if you do start at a very low dose. You’re welcome to call me at 321-443-6597. Michael Dowdy

      • Michael Dowdy November 2, 2013 at 9:55 pm # Reply

        Hello Beth. Sorry about my typing mistakes. You are at the best site about MTHFR. I misspelled trimethylglycine and strength in my previous note. Michael

  114. ana November 5, 2013 at 11:35 pm # Reply

    my testing has coming out MTHFR 677 T/T . is the protocol the same? i have just begun the methylfolate of yours and started on 1/4 tablet. it is making me feel terribly anxious even at such a small dose. please give your advice.

    • Renee November 6, 2013 at 2:44 am # Reply

      Read up on it, you do need to have you Methyl B 12 up a few weeks before you start the Methyl folate..

    • Kathleen November 6, 2013 at 2:53 am # Reply

      Hi Ana,

      I have C677T. Not sure if 677T/T is the same but from what I’ve read about supplementation for this mutation, methylfolate might not be the best. I was taking Dr. Lynch’s multi vitamin but could only tolerate it for 4 days. At 4 days I became agitated and got a headache. If you feel terrible, then it is because you might be over methylating. In that case, niacin is helpful. Dr. Lynch’s Niacin supplements are nice in that you can break them into quarters, and then split the quarter, if need be. Not knowing what to do about supplementation, I went to Dr. Yasko’s site, and bought her All-In-One multivitamin. It works great for me. But I also take with it each time Premier brand HeptaoVen for liver detoxing and RenaVen for Kidney detoxing, because those organs weren’t detoxing properly and the All-In-One wasn’t doing anything for me until I began taking those two products together with NAC 500mg by Jarrow. I can only take 2 (1-2/x day) of the All-In-One. I’ve been taking these for about 3 weeks. At this point in time I feel that something needs to be adjusted or I need to add something but don’t know what. I say this because I’m starting to get headaches and agitated, just slightly though. Could be some other irritant. I don’t know. Dr. Yasko’s All-In-One is only $29 and at the rate of 2 per day, will last 60 days. Since blood clotting disorders come with the C677T mutation, I’ve been taking Neprinol, a systemic enzyme. This is a must! It digests blood clots, cleans debri from the blood, and debris from joints, and debris from the brain. It should reduce the risk of thromboli and stroke.

      Hope this helps.

      • Renee November 6, 2013 at 3:17 am # Reply

        I am working with a DNA Dr and he had me start at 200 mcg, note mcg NOTE MG so you need to start low and go slow.. best and He had me taking Methyl b12 1000 mg twice a day.. for a few weeks first so again we are all different.. than keep on the Methyl B 12 and add the low dose of methyl folate cut them in quarters if you have to. If you feel over methylated like Dr Ben mentions take a nicine tablet right a way wait few days and try again lower dose.. best of luck ALSO go join facebook MTHFR group there are a few so much info for you to read and members you can ask personal stories..

  115. Kari November 11, 2013 at 6:48 am # Reply

    I was recently diagnosed with heterozygous c677t and a1298c. I had never had any symptoms and was only tested due to low b12 and high homocysteine. I usually have high energy. My doctor started me on metafolin 800mcg, methylcobalamin 800mcg, pyridoxal 5′ phos 50mg. My thorne prenatal has 1mg folate and 200 mcg vit b12. and after 5-7 days I felt awful so very tired and cranky which is very atypical for me. I stopped the vitamins and took 2 curcumin and after 2 days felt better. I started the methyl b’s again slower and the same thing happened. Now I am taking only the thorne prenatal and I am still feeling fatique, but not as bad as when I was taking all. I added ashwaganda, milk thistle and rhodiola to try to help. I took thorne prenatal with all kids and had no problems. I had spontaneous triplets 2 years ago and wonder if this changed how the vitamins affect me. Looking forward to info. Thanks!

  116. Debbie Hall November 14, 2013 at 1:46 am # Reply

    Hi Ben – I started with a stone bruise type of pain in the palms of my hands and bottoms of my feet about 7 years ago. Over the last few years has moved into the major joints – but since Jan. 2013, the pain in my feet and hands (in the tendons and tissues) has become chronic and much worse. After getting no help or a diagnosis from the specialists, I began seeing a Naturopath (Dr. Lisa Chambers Pate in Covington, LA) who tested me for MTHFR. We just found out I have 2 copies of C677T. I had been given Deplin 15mg about a year and a half ago for depression. Is it possible that the Deplin has made this situation worse? My folate RBC level is 1551 and she was happy about that. B6 is at 20.2 and B12 at 660. Until the remaining test results come in, her protocol is staying on the Deplin, gradually getting up to 200 mcg of B6 P5P and twice per week B12 injections (compounded). I am very new to this and is a bit over my head. I had pre-eclampsia with only pregnancy, endomitriosis, chronic migraines and now disabling pain. My thyroid is low and I went into menopause at 42 and am using bioidentical HRT. I am 48. Does it sound like all of this could’ve been from this mutation? Also, out of the blue after being healthy his whole life, my dad died of Primary Amyloidosis at the age of 62. Any thoughts or suggestions are appreiciated.

    • Kathleen November 14, 2013 at 10:38 pm # Reply

      Hi Debbie,

      I’m on this forum due to a diagnosis of C677T Hetero. I also have pain in my feet and joints. I would be willing to bet that I have Rheumatoid Arthritis. Have you been tested for this? With these mutations comes autoimmune diseases.

  117. Erin Egan November 16, 2013 at 12:42 am # Reply

    I am homozygous for a1298c and have had odd health problems for years. My doctor gave me 1000 mcg methylfolate & since adding just that to my daily vitamins, I’ve gained about 5 pounds. I have a lot of swelling, in my legs, hands & feet, my face seems puffy & my ears have been getting red too. I’m hoping that this will balance out, but I don’t know what else to try.

  118. Julianne November 16, 2013 at 8:09 am # Reply

    I am sitting here seething. I started Fola Pro at the end of August. I was told to titrate up- starting w/ 1/4 of a 800mcg tablet. For the first month, I tolerated it fairly well. But pretty soon I was having increased neurological symptoms, insomnia, EXTREME brain fog and cognitive difficulties, increased joint and muscle pain, irritability, depression, anxiety, you name it. And when my rheumatologist ran bloodwork on me in October, my sed rate was 51! And THAT was with 5mg prednisone in me! Btw, I am heterozygous for the C677T mutation, and negative for the A1298C mutation.
    I drive 2 hours to see this doctor, and I THOUGHT I was in good hands. But now I am throwing my hands in the air and cursing. The only thing I could do this evening, since I have no Niacin, and it is very late, I took a dose of Cholestyramine, which I had used to detox from the toxic mold I was exposed to last year. This is a hit I certainly did NOT need, and I am furious. My symptoms were so strange and unfamiliar, I was beginning to think we should rule out MS again (I do have Sjogren’s, a spinal cord lesion called Transverse Myelitis, secondary Addison’s, Hashimoto’s thyroiditis, and a few more dx-s. To increase the inflammation in my body is the absolutely WORST thing I can do. I never want to see another methylfolate tablet for the rest of my life, which hopefully hasn’t been shortened too much by this horrible experience! Any input you have will be accepted and appreciated. (ie., I won’t yell at YOU!) Oh…….and the reason I was to take this was to ultimately allow my B&T cells to return to normal levels by decreasing the slightly elevated homocysteine in my blood (11.7, with normal <10.4.) I'm reaching the end of my rope……………

    • Michael Dowdy November 17, 2013 at 3:32 am # Reply

      Hello Julianne. I’m only a patient who’s trying to deal with problems I know I have. I recommend following the old saying “If it ain’t broke don’t fix it.” If you’ve had only negative effects from methylfolate I would reduce or quit using it. The mthfr mutation affects the efficiency of your body’s use of amino acids. You may be doing alright since yours is only heterozygous. Some, women particularly, suffer serious problems with only one copy. If you believe you would benefit from better nutrition you might be able to boost you immunities with the addition of the precursors of GSH and SOD. This is pretty new territory even for most doctors and patients alike so be careful and study about whatever you decide to use. This site has been very helpful to me. Study telomeres! Respectfully, Michael Dowdy

    • Kathleen November 20, 2013 at 10:32 pm # Reply

      Hi Julianne,
      I’m on this site because I have C677T Hetero. Once I got the diagnosis I ordered Dr. Lynch’s Multi, Active B12, Niacin, and other supps that I thought would fix the problem. I could only tolerate the Dr. Lynch’s Multi for 4 days before I felt terrible with agitation and headache. I stopped and within a few days I returned to normal. Not wanting to do nothing, I remembered Dr. Yasko and went to her site to see what remedies she had. I ordered her All-In-One and it works like a charm when coupled with Premier Research HepatoVen and RenaVen for liver and kidney support and to get the detox activity moving. I also take NAC 500mg. I take all this with meals 2x day. I can only tolerate Yasko’s multi vitamin one-2x/day. More than that and I get a headache and feel slightly agitated. Today, though, I read Dr. Lynch’s recommendation of Hydroxo B12. I’m going to order that to see if it helps with taking more All-In-One multi. Plus, I have a slight headache that developed after being on the All-In-One for about 2 months. I think that the amount of supplements and adding different ones for other body systems and organ function is an ongoing thing that only we can know what is good for us, unless we take a bunch of tests and keep retesting. This is too costly. I’ll just use my intuition and listen to my body. I’m also fortunate to have someone muscle test me for supps that I feel that I might need. Also, I learned that Niacin can cause depression. It did that to me, so I stopped. When I feel low, I take Inositol. Inositol works great! It lifts the spirits by removing the downer feeling.

      • Dr Lynch November 21, 2013 at 8:57 am # Reply

        Hi Kathleen –

        Definitely use your intuition and listen to your body. I rarely take Optimal Multivitamin as I usually eat very well – however, there are days when I really feel I need it and I take it on those days. I haven’t taken it in a couple weeks now – however, I have taken a scoop of Optimal Prenatal Protein Powder and put it in a smoothie a couple times a week – I do very well with this one.

        Listen to this podcast on how to take supplements.

        I’ve learned today through a colleague that if niacin does not help someone, then Lithium should. They do opposite things. Something to consider.

        • Kathleen November 22, 2013 at 4:25 pm # Reply

          Dr. Lynch,

          Thank you for the podcast. It was informative. I will play around with frequency at which I take the multi. The Pre-Natal powder sounds like a good one to have on hand – easy to customize dosage. What will Lithium help with? Does fixing my reduced methylation (working at 60%, according to test results for C677T hetero) with the nutritional workaround reduce to any degree the risk for thrombosis and stroke? And if so, any idea on how much reduction in risk? How does one test for stroke risk? What should I be looking out for? Currently I take Neprinol systemic enzyme, and I’m hoping that with the multi, eating greens and healthy, and Neprinol that I reduce significantly, or completely, the risk for stroke and thrombosis. Thank you in advance for considering my question.

          • Kathleen December 7, 2013 at 7:04 pm #

            I’ll try your Multi again, taking one maybe every 4 days.

  119. Rebecca November 16, 2013 at 11:49 am # Reply

    I tested positive for the MTHFR gene mutation after having multiple miscarriages. I dont know much more about it other than what I have read online. My OBGYN told me to take 4 mg of folic acid every day, but after some research I found out that I probably need to take a folate suppliment instead. I have taken 4mg of the folate instead for about three months, but after reading this article, I’m not sure I’m doing the right thing. I haven’t been able to get a lot of answers about the MTHFR from my PCP or my OB. I am afraid I might be making matters worse.

  120. Mackenzie November 20, 2013 at 1:33 pm # Reply

    My daughter is heterozygous c677t and was prescribed Deplin 15mg right off the bat. She has never expressed any issues with taking this. I have now been recently diagnosed myself as homozygous c677t. My medical doctor admits having limited information on MTHFR so asked me to follow the recommendations for my daughter. She has recently been switched from Deplin 15mg to Metabolic Maintenance 5MTHR 10mg. I started taking this about a week ago and have felt extreme fatigue, nausea, and irritability (very emotional). I thought I had a bug?? I have never had success with multis in the past. When I take them I have chronic daily headaches. Therefore taking the Optimal does not appeal to me. Will these side affects go away after a while or should I stop taking the 10mg. It’s a capsule so I’m not able to cut it down for a smaller dose.
    I was so happy to be diagnosed because I thought I had finally found my missing link and would be feeling better but now I actually feel worse.
    I did read about the niacin but I’m concerned about the flushing and I simply just prefer to not take many supplements if I don’t have to.
    Suggestions? Thanks so much for your help.

    • Michael Dowdy December 22, 2013 at 6:47 am # Reply

      Hello Mackenzie. I’m not a healthcare professional. Always consult with a doctor first! I’m only a patient trying to learn to help myself stay healthy. I’m homozygous with MTHFR 677CT. According to some experts that I’ve spoken with when a parent is homozygous with MTHFR all of their children will be at very minimum heterozygous depending also on the other parent’s mutations. Be sure to study this site thoroughly. Metabolism problems can be complicated and dangerous to treat. Be careful and do not over-medicate and cause worse problems. Dr. Ben’s site and his information has helped me immensely. I’m 54 320 lb male and I’m doing great on just 2 mg of methylfolate. Before taking either of the prescription strengths of 7.5 or 15 mg I would advise getting a second opinion from a specialist in nutrigenomics. I had a few bad side effects including headaches at first. Some of my other side effects were very frightening to say the least. If I had treated my daughter I would have started her at 400 micrograms daily and from there very slowly adjusting upwards probably every couple of weeks and stop raising it immediately if a negative side effect started. Give the body some time to adjust to the strength where you first begin to notice a negative side effect. It took a long time for my body to adjust to different doses. Use patience and extreme caution with methylfolate. Mental issues can be huge and dangerous on high doses, and I’m speaking from my own personal experience. I think methylfolate may very likely cause suicidal thoughts or actions if started at the high strengths. ALWAYS consult with your doctor. Try to locate a doctor who is willing to work with nutrigenomics. Treatment of methylation problems is tricky but can be very effective. I totally agree with you and I try to stay on as little medications or supplements as possible. Again, I’m not a healthcare professional. Your decisions are your own. Respectfully, Michael Dowdy

  121. Howard November 20, 2013 at 2:48 pm # Reply

    I have the C677T mutation and the A1293C mutation. I believe my life long symptoms are low energy and ADD. I have been seeing a Chronic Fatigue specialist who just had the genetic tests performed. With those results — I started starting FolaPro 800mcg twice a day. I had also been taking a good Multivitamin and active form of b12.
    I was surprised at how the FolaPro hit me. With hours I become withdrawn, anxious, edgy, not able to tolerate interactions with other. I stopped the FolaPro. In a few days I was better. After reading and having a little understanding of the methyl cycle I tried the FolaPro again, Same side effects.

    Now trying at reduced dosages 400 mcg. still super anxious and non social but I want to keep trying until side effects go away ..
    Any suggestion or other info to help me understand these side effects would be greaqtly welcome.

  122. Kathy November 24, 2013 at 8:40 am # Reply

    Me and my son with down-syndrome took 5-mthf in a very low amount and it was an awful afternoon… we both got so emotional… irritable and we both cried easily because of frustration and anger. We have not been tested for MTHFR mutations but the side effects probably suggests we both have some of the mutation. We don’t have any other MTHFR related diseases much in our family (except this one DS kid of mine) so I first thought we probably don’t have it. Well at the moment I am afraid to give him any because of the side effects. – Kathy

  123. Meghan November 27, 2013 at 9:09 pm # Reply

    Hi Dr. Ben,
    Thank you so much for all of your helpful information! I am homozygous c677t and just started taking methylfolate. I started with 1mg l-methylfolate at night and the next morning I woke up itching all over. I have since reduced to 1mg every other day but still notice some itching and some eczema on my fingers. I had the flu the other week and went for an IV push two days ago- I made sure to get the methylated folate and B12, and since then I developed itchy rashes all over my hands and am itchy pretty much all over. I am not having any of the other side effects, in fact otherwise I feel great- do you think this has to do with taking too much methylfolate or is it more likely that I have another gene mutation that affects how I use methylated nutrients? Which method to reduce side effects would you recommend for just itching?

    • Renee November 28, 2013 at 1:50 am # Reply

      Hi, Im not Dr Ben but have read much on this since I have 677 too, well, you need to get down to only 200 mcg NOT MG and work your way up.. best that way you can judge best how its doing for your body.. and issues.. best of luck.. I have to cut my 800 mcgs into quarters started at 200 mcg and now only at 400 mcg best of luck

      • Meghan December 2, 2013 at 8:20 pm # Reply

        Thanks Renee. It’s been a week since the IV and I’m still itching all over, so there must have been a lot of methyl-B12 in there- I haven’t been taking my methyl-folate since then and even four days after the IV the rashes were getting worse. I started taking Benedryl since I couldn’t get a hold of timed-release niacin, and it’s been helping with the itching but not the rashes themselves. My main concern is whether or not I need to worry about another gene mutation that affects the way my body uses the methylated b-vitamins, since I feel fine other than the itching.

        • Michael Dowdy January 1, 2014 at 7:30 am # Reply

          Hello Meghan. I’m not a doctor or healthcare professional, I’m only a patient. Your itching problem is interesting to me because I used to suffer sever bouts of itching starting in my feet that was so bad it nearly drove me out of my mind. I had no rash though. If the rash happens in a certain areas that would provide a clue. If you’re experiencing the itching in a patch area, usually in the trunk area, and looks like small water blisters, I would guess shingles. If there’s no rash and it starts in the sock area of the foot and ankles I would guess that it may be related to diabetes resulting in nerve damage like neuropathy. There are medicines to help like atarax or hydroxyizine. I take imipramine for depression but it made my itching go away as a great side effect which I found out by accident. I ran out of imipramine a couple of times and the itching came back. As long as I do not miss a dose of my imipramine (twice a day 100mg in the AM and 150mg in the evening before bed, I don’t experience itching. Consult your doctor immediately about the itching. My itching was apparently linked to either liver damage or diabetic neuropathy. Allergies, parasites, mites, beg bugs, chiggers, nerve damage, pregnancy problems, hand soap, and other things can cause itching. I hope you figure out what the cause is. The starting in the hands is really confusing to me. Diphenhydramine is pretty good to stop itching. Do you have a mutation of the MTHFR gene or methylation problems that require methylated supplements? Respectfully, Michael Dowdy

          • Meghan January 4, 2014 at 11:57 pm #

            Thanks for the reply Michael! I have the homozygous c677t mutation and was taking 1 mg methylfolate for it. The itching cleared up after about a week, although I had to take Benedryl for about 3 nights before it started going away. I saw my doctor as it was going away and she thought it was most likely eczema caused by allergies/dry skin and exacerbated by the over-methylation. Since then I’ve started taking a natural allergy supplement (vitamin C and quercetin mostly), started using a humidifier, and stopped taking the methylfolate and instead am focusing on getting those vitamins naturally through food (mostly uncooked leafy greens). It seems to have helped for the most part, but the itching/rash started to come back again around New Years. I’m now completely baffled as to what could be causing it. I am gluten intolerant and had a little contamination over the holidays, but it was a very small amount and that has never caused such a response before, so I’m really confused as to what could be causing this now…

        • Michael_Dowdy April 6, 2014 at 8:39 am # Reply

          Hello Meghan. Have you recently or even in the past used a quinolone, l’quinolone, fluroquinolone, levoquinolone, 2-quinolone, 4-guinolone, Cipro, Ciprofloxacin, or Levoquin. Research those.

          • Meghan April 6, 2014 at 7:22 pm #

            Hi Michael,
            I haven’t taken any antibiotics in about 2 years but I have definitely taken Cipro before and I’m fairly certain I’ve also taken Levoquin… Is there an MTHFR connection? Or a connection to the bouts of itching? I’m not taking L-methylfolate or B12 right now and I’m still getting random hives (except not as much).

        • James March 17, 2015 at 3:31 pm # Reply

          Hi Meghan,

          Did you ever get to the root of what happened with the methylfolate? I have just experienced your exact situation. I stopped methylfolate supplementation about a four days ago and the rash is started to go away. Doctor said it was an allergic reaction, but he can’t be sure if it was really methylfolate unless I try it again. My hope is your much better.



  124. Susan December 2, 2013 at 3:44 pm # Reply

    Hi, I am a celiac and have been gluten free for 18 yrs. but energy levels and mild depression are constantly an issue. I began taking the optimal multivitamin and immediately felt better. I began with one per day and am now up to 3 per day after one month. Although I feel great, have energy and don’t feel blue I randomly break out in hives every day, all day long and even while sleeping….very uncomfortable. I have the following mutations and was wondering if you could offer some advice.

    Homozygous: VDR Bsm, BHMT-02, BHMT-04, BHMT-08, CBS A360A
    Heterozygous: COMT V158M, COMT H62H, MAO-A R297R, MTHFR C677T, MTHFR 03 P39P, MTHFR A1298C, MTRR A664A

    Thanks, Susan

  125. Selina December 5, 2013 at 3:44 pm # Reply

    I am homozygous c677t and my doctor started me on active B-12 with L-5-MTHF. I went through a massive weird detox where I would periodically get hives and random body parts would swell and turn bright red. Those symptoms are gone now but I have had some skin itching over the past couple days. I haven’t been able to determine whether it is due to the weather or the lozenge.

    • Paula December 6, 2013 at 6:51 pm # Reply

      Very interesting ladies. I took methylfolate and methyl B 12 at the beginning of this year for 4 months and broke out in hives periodically (never had them before) and facial flushing when exercising. I assumed it was an allergic reaction to the vitamins so I stopped them and they continued for a couple of more months then disappeared. I had wondered if could possibly be a detox reaction but didn’t think too much of it.

      I recently found out I am heterozygous c677t and purchased L-5 methylfolate 800 mcg and methyl B 12 1385 mcg. Been taking for about 1 1/2 weeks and while I’ve had no hives, the flushing is back in full force but only after exercising/sweating. Can’t determine if it’s a reaction to that substance or detox??

      • Selina December 6, 2013 at 11:10 pm # Reply

        Sometimes it’s so hard to figure out! I forgot to add that the hives disappeared after I started liver detox/gall bladder support supplements. Are you taking any liver nutrients?

        • Paula December 7, 2013 at 1:01 pm # Reply

          Only liposomal glutathione. It really seemed to help and I started it around the same time as the first round of B vitamins. Maybe they were working together to detox

  126. Deena Barselah December 9, 2013 at 11:10 pm # Reply

    I just started taking the L-5-mthf/b-12 combo from Seeking Health and in the past few days have also noticed nerve pain… in my wrists, fingers, feet, arms, etc. Could this be a side effect? I had been taking 1000mcg of methylated folate by THORNE prior to yours, but I know Seeking health is stronger and more bio-available. Should I stop for a few days and then ramp up more slowly or do you think this nerve pain is unrelated? It is something I’ve experienced in the past but not in a while. I am homozygous A1298c. Thanks!

  127. Jessie December 20, 2013 at 12:02 pm # Reply

    Greetings! My 10-year old son is compound heterozygous (labs confirmed yesterday) and just prescribed 15mg of Deplin by his endocrinologist. I’m very concerned that this is too high for his 79lb body. What do you recommend? He has a history of anxiety, mania, and rage, so I want to proceed slowly and carefully here. Thank you very much for any advice.

    • Michael Dowdy December 21, 2013 at 1:27 am # Reply

      Hello Jesse. I’m only a patient with 677CT homozygous. Dr. Ben provides a wealth of information. I’m 54 300+lbs and 2mg of methylfolate works well for me. 7.5mg was WAY too much for me and I can’t imagine what 15mg would have done to me. Be careful and do a lot of research and study. I’m not a healthcare professional but based on my personal experience I nearly went to the ER after taking only 7.5mg. I would be afraid if my daughter tried to take 15mg to start. I would study here about others’ experiences. I personally would not give such a large dose to such a small boy. I know nothing about compound heterozygous. But my experience was horrible at the prescription strength 7.5mg, in fact that’s an understatement. It took me to the edge, yes, right to the edge. You may want to get a second doctor’s opinion on such a large dose. Respectfully, Michael Dowdy

    • Eve December 21, 2013 at 1:33 am # Reply

      I have to second Michael on this. I am also only a patient, no medical background whatsoever. But my experience:
      I am also compound heterozygous. 120 lb female. Only a mere 1 mg was waaaaaaaay too much to start with. It gave me intense anxiety/panic attacks. Horrible. I had to start on 500 micrograms and let myself adjust before going up to 1 mg.

      It seems all of this is highly individual, but I found it was best for me to ease into anything rather than both feet in at a huge dose.

    • Rebekah December 21, 2013 at 2:11 am # Reply

      Hi Jesse, I’m not a dr, either, just a mom. I would also say start really much lower, and slowly add bit by bit if you choose to supplement–especially since your son is having emotional issues. I tried it with my daughter, only a tiny bit of a 400 microgram methyl folate supplement (after a week and a half of B12 supplementation) and after a few days she had quite a bit of itching. Every person is a unique chemical mix, of course. I hope you and your son find some relief. Omega 3’s are neuroprotective, and probiotics may help, too. Do whatever it takes to reduce his stress load for as long as it takes. I actually let my daughter just sit around reading, or whatever for a couple of months after she started having serious emotional issues. I fed her organic veggies, very low processed foods..whatever I could think of. She very slowly came mostly out of it. We did try a therapist to try and teach her coping skills though the therapist wasn’t very good-R

    • Michael Dowdy December 21, 2013 at 4:36 am # Reply

      Hello Jessie. I read some of the other responses to you and it looks like there’s a lot of agreement in the responses. I am not a healthcare professional so all I can say is what works for me. I’m 54 years old and overweight. I believe I read somewhere that Dr. Ben is compound heterozygous also. Study, study, and study more. More is constantly being learned all the time. I’ve done well on methylated B complex, methylfolate, TMG, ORGANIC cold processed whey protein, extra virgin coconut oil, and honey. I’m a type 2 diabetic with neuropathy, diverticulosis, and was diagnosed with fibrosis of the liver in 1996, and Factor V Leiden heterozygous. There’s more but I’ve made some significant improvements. I’m glad to see that others share similar feelings and I would like to caution all to not over-medicate and be careful and slow about making adjustments. I hope Dr. Ben gets time to respond to you soon. Methylfolate seems to be one of the most difficult substances to adjust to that I’ve ever taken, but it is paying off now I believe. I hope you all of the best success with your son and yourself. Most Sincerely, Michael Dowdy

      • Jessie December 24, 2013 at 2:17 pm # Reply

        Michael, Rebekah, and Eve, Thank you for your response. I really appreciate your time, as I feel fairly adrift in MTHFR info right now. I knew leaving the doc’s office that 15mg of Deplin was too high for my 78lb 10-yr old, and even 7.5mg of Deplin has triggered side effects of joint pains, insomnia, irritability, weepiness, and anxiety. He has a history of emotional instability, so it’s hard to know where his ‘normal’ ends and the Deplin side effects begin, but after reading your posts, I ordered Optimal Multivitamin Chewable With L-5-MTHF (recommended by Dr. Ben in earlier posts). Each tablet has 400mcg of L-5-methyl, along with B6 and B12. I saw in an earlier post where Dr. Ben recommended 1/2 of these tablets twice a day for a compound heterozygous 7-year old, so I may start there for my son. It’s just impossible to know what to do w/o a medical degree in bio-genetics. I am so reluctant to do anything to worsen my son’s problems, but I know at the same time that his quality of life can be so much better than this. I have to do something to help him, but I so wish someone could just tell me how much to give him for his age/weight being compound heterozygous. Man, this is tough stuff! However, thank you all for your input. It’s nice to not be alone! Warmest wishes during this holiday season- Jessie

        • Jessie December 24, 2013 at 2:19 pm # Reply

          I should also mention that my son has been gluten and casein free for over 6 months now, so I’m hoping to have set the stage nicely in terms of gut health. Again, many thanks! Jessie

  128. David December 21, 2013 at 2:16 am # Reply

    Recently diagnosed homozygous 1298, after 2 years of crazy symptoms. Taking 2 tablets of optimal multivitamin and quarter tablet active b12, the second day felt like had the flu ,Sore throat, headache,body pains.I’m on a very low dosage starting point, but feeling worse.

    • Michael Dowdy December 23, 2013 at 1:31 am # Reply

      Hello David. I advise you contact your doctor immediately about your concerns. I am not a healthcare professional. Being homozygous for the 1298 mutation is certainly reason for concern. Respectfully, Michael Dowdy

  129. Brent December 22, 2013 at 1:37 am # Reply

    Before I knew I had A1298c mutation and finding your web site I tried 400mcg methofolate and felt great the first day like my brain was waking up the and the next day I took a second dose and felt like I was going to lose my mind with extreame anxiety.

  130. Todd December 25, 2013 at 11:05 pm # Reply

    Hi, I recently found I had a pretty severe b12 defiency with no anemia.. I had some neurological effects occur in this time period that came on relatively quickly over a period of couple weeks…

    Luckily I caught it quite early and started mega dosing methyl b12 to raise my levels again.. Also adding potassium which seemed to tank with the supplements..

    I couldn’t find this answer elsewhere so I wonder if you would know?

    Supposedly adding folate too early or in place of b12 can create a worsening of neurological symptoms and increased damage, possibly its suggested to get b12 to normal levels before introducing folate for neuropathy.. However as a 23 yr old male I find it hard to think It would do much harm, I was deficient in both… I tried folate added to the b12 at 400mcg one day, 800 mcg, the next, and 400 the day after.. Felt adverse effects and worse but felt it was just the healing of nerves and potassium dropping..

    When would be a good time to add the folate without risking possible neuropathic damage? I need both

    • Michael_M_Dowdy January 25, 2014 at 2:03 am # Reply

      Hello Todd. I’m not a healthcare professional. Do you have neuropathy and what type of neuropathy do you have? Neuropathy often goes hand in hand with retinopathy if it’s tied to diabetes. Magnesium is a mineral that a lot of people don’t receive enough of and is lacking in a lot of OTC multi-vitamins. At 23 years of age it’s very unusual to have neuropathy. Have you been exposed to very high levels of organophosphates or chemicals like toluene? You must be seeing a doctor since you know your B12 levels. Your folate level may have been checked at the same time your B12 level was checked. You sound like you need serious and intense attention due to damage to your neurological system. Follow-up with a neurologist immediately. Respectfully, Michael Dowdy

  131. Valerie December 29, 2013 at 7:58 pm # Reply

    I was diagnosed with C677T and A1298C defects and given 1 mg 5-MTHF. Continued to take regular B Complex 50 as I wasn’t instructed not to. For five weeks I felt great with all positive symptoms and NO side effects. Then the Dr told me that I should not be taking the old form of B vitamins with the MTHF so I stopped. A few days later I experienced terrible shivers, thought I was going to throw up with symptoms of stomach flu and terrible headache. It took two days to recover. I was unable to return to 5MTHF without side effects.
    Later switched to B complex with MTHF 400 mcg, R5P 10 mg and P5P 10 mg. Felt great for 9 days then had same side effects but less. Have been unable to tolerate small amounts since.
    Would be interested in your comments. My doctor is not very helpful unless I pay her high fees every time I need help. Am considering returning to what actually worked!

  132. Jessie December 30, 2013 at 2:42 am # Reply

    Greetings! My 10-yr old son was recently diagnosed compound heterozygous and prescribed 15mg of Deplin. He reacted aggressively to this, so we dropped him to 7.5 mg of Deplin–still, he reacted poorly. Since then, I ordered the Seeking Health Optimal Multivitamin Chewable with L-5-MTHF (400 mcg). I’ve been giving him 1/2 of a tablet at breakfast and 1/2 tablet at lunch, which means he’s getting 200 mcg a day right now. He is pretty agitated and aggressive and demonstrating anxiety. I gave him niacin tonight, which seemed to move him from aggression to hyperactivity (happy but still over stimulated). What should I do? I know he needs methyl, so how should I be ramping him up safely? I thought the Seeking Health Multivitamin would be best for him as a compound heterozygous adolescent, but am I over methylating him? Any advice will be so greatly appreciated. Warmest regards, Jessie

  133. Alina January 1, 2014 at 6:06 pm # Reply

    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

  134. Adam January 1, 2014 at 7:04 pm # Reply

    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 January 2, 2014 at 8:38 am # Reply

      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 January 22, 2014 at 7:26 am # Reply

        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.

  135. Shauna January 4, 2014 at 6:41 pm # Reply

    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 January 5, 2014 at 10:24 pm # Reply

      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 January 6, 2014 at 3:45 pm # Reply

        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 February 27, 2015 at 10:55 pm # Reply

          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.

    • Kathleen January 5, 2014 at 10:44 pm # Reply


      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 January 6, 2014 at 4:14 pm # Reply

        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.

  136. Jessie January 4, 2014 at 9:59 pm # Reply

    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.

  137. Genevieve January 5, 2014 at 1:37 pm # Reply

    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!

  138. Maryanne January 7, 2014 at 3:59 am # Reply

    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.

  139. Dave Christensen January 9, 2014 at 7:38 pm # Reply


    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 January 19, 2014 at 6:59 pm # Reply

      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

  140. Amy Brekke January 10, 2014 at 3:02 pm # Reply

    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 January 13, 2014 at 5:26 am # Reply

      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 January 13, 2014 at 6:08 am # Reply

        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

  141. Iatrogenia January 11, 2014 at 11:07 pm # Reply

    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 January 12, 2014 at 3:34 am # Reply

      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.

      • Iatrogenia January 12, 2014 at 5:50 pm # Reply

        Thank you, Dr. Lynch.

        I have recently found about 150mg GABA with 130mg magnesium glycinate helps me get back to sleep. I take 100mg niacinamide every night.

        You may wish to clarify which, as I read it, says reduced MTHFR activity CANNOT be managed with dietary folate.

      • Kathleen January 13, 2014 at 5:04 am # Reply

        Dr. Lynch,

        That’s good to know. Please post a note when your B complex is available. In the past, GABA (I think it was GABA) has caused me to have headaches. Any idea why? What is a good alternative? In your opinion, is juicing just as good as ‘eating’ raw greens – say, in a salad?


    • Amy Brekke January 12, 2014 at 4:15 am # Reply

      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 July 15, 2014 at 5:52 pm # Reply

      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?

  142. Fiona January 18, 2014 at 9:53 pm # Reply

    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 January 19, 2014 at 5:58 pm # Reply

      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

  143. Joey Thompson January 19, 2014 at 2:38 am # Reply

    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?

  144. Rose CLaudia January 19, 2014 at 7:56 pm # Reply

    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

  145. Angeli L January 21, 2014 at 10:15 pm # Reply

    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 January 21, 2014 at 10:26 pm # Reply

      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 January 21, 2014 at 11:09 pm # Reply

        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!

  146. Wendi January 23, 2014 at 3:21 am # Reply

    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 January 23, 2014 at 2:09 pm # Reply

      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 January 26, 2014 at 6:38 am # Reply

      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 January 26, 2014 at 6:34 pm # Reply

        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 January 27, 2014 at 1:29 am # Reply

          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 January 27, 2014 at 5:30 pm #

            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 January 28, 2014 at 1:36 am # Reply

      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

    • Naomi March 17, 2014 at 6:58 pm # Reply

      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 March 17, 2014 at 8:09 pm # Reply

        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 March 17, 2014 at 8:31 pm # Reply

          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 March 17, 2014 at 9:13 pm #

            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 March 17, 2014 at 8:37 pm # Reply

          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 March 17, 2014 at 9:19 pm #

            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 March 17, 2014 at 9:23 pm #

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

          • Lynn_M March 17, 2014 at 10:01 pm #

            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 March 17, 2014 at 9:31 pm # Reply

          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 March 17, 2014 at 11:16 pm #


            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 March 18, 2014 at 12:00 am # Reply

          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.

  147. Kathleen January 23, 2014 at 5:30 am # Reply

    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 October 2, 2014 at 10:55 am # Reply

      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.

      • Dr Lynch October 2, 2014 at 5:10 pm # Reply

        If you take calcium with the leafy greens, it helps bind the oxalates. Also – if you have adequate stomach acid, this also helps reduce oxalates.

  148. Laurel January 24, 2014 at 6:34 pm # Reply


    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?


  149. Marcie Marwood January 26, 2014 at 12:24 am # Reply

    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.

  150. Rebekah January 28, 2014 at 2:32 am # Reply

    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.

  151. Chris January 29, 2014 at 8:53 pm # Reply

    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.

  152. Candi February 8, 2014 at 7:15 pm # Reply

    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 February 10, 2014 at 8:28 pm # Reply

      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.

  153. Brittany February 9, 2014 at 4:12 am # Reply

    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.

  154. Katherine February 12, 2014 at 3:38 pm # Reply

    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.

  155. Susanne February 13, 2014 at 2:46 am # Reply

    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?

  156. Tammy Tomek February 14, 2014 at 12:55 am # Reply

    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?????

  157. Colleen February 14, 2014 at 3:47 am # Reply

    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 .

  158. Jenny chandler February 14, 2014 at 4:32 pm # Reply

    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.

  159. Susan February 15, 2014 at 5:47 pm # Reply

    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 February 21, 2014 at 7:30 am # Reply

      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 March 31, 2014 at 3:42 am # Reply

        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.

  160. HJ February 18, 2014 at 9:11 pm # Reply

    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?

  161. Michael (NW) February 19, 2014 at 5:12 pm # Reply

    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 February 21, 2014 at 6:10 am # Reply

      Hi Michael –

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

      • Susan Davis February 21, 2014 at 7:23 am # Reply

        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 February 23, 2014 at 12:52 pm # Reply

          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) February 21, 2014 at 6:32 pm # Reply

        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 February 21, 2014 at 7:19 pm # Reply

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

          • ML February 21, 2014 at 7:49 pm #

            YES, I contacted Dr. Jess Armine and he has helped me immensely. Website is

            He and Shawn work together to help you as well. :)

        • Kathleen February 21, 2014 at 7:48 pm # Reply

          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 February 21, 2014 at 11:20 pm #

            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 February 21, 2014 at 7:51 pm # Reply

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

        • Michael (NW) February 25, 2014 at 4:52 pm # Reply


          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 February 25, 2014 at 8:14 pm #

            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) February 25, 2014 at 11:49 pm #

            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….

  162. AW February 20, 2014 at 12:25 am # Reply

    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!

  163. Stephen LaCorte February 21, 2014 at 8:22 pm # Reply

    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.

  164. Jodie McGuire February 22, 2014 at 5:56 pm # Reply

    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.

    • Dr Lynch February 22, 2014 at 11:12 pm # Reply

      Hi Jodie –

      I am glad your side effects have lessened with the Niacin. Be sure to let your doc know how the niacin has helped you and how you are dosing it.

  165. Sharon Elston February 23, 2014 at 6:25 pm # Reply

    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?

  166. Jaime February 24, 2014 at 5:16 am # Reply

    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 February 24, 2014 at 9:45 pm # Reply

      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 February 25, 2014 at 3:06 am # Reply

        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 March 17, 2014 at 8:25 pm # Reply

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

        • Michael_Dowdy March 21, 2015 at 10:20 pm # Reply

          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 February 24, 2014 at 9:48 pm # Reply

      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 February 25, 2014 at 2:55 am # Reply

        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 February 25, 2014 at 3:27 am # Reply

          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

  167. terri February 24, 2014 at 12:37 pm # Reply

    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 February 25, 2014 at 4:26 am # Reply

      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 February 26, 2014 at 1:13 am # Reply

        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 February 26, 2014 at 3:01 am # Reply

          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) February 26, 2014 at 11:36 pm # Reply

          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 March 1, 2014 at 7:16 pm # Reply

          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.

  168. Pamela February 25, 2014 at 3:43 pm # Reply

    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 February 25, 2014 at 9:16 pm # Reply

      Dr. Mullan is in my area. Please post how you like your visits and progress with her. She’s very expensive. There is also a doctor in Thousand Oaks – he is listed at

  169. Kathleen February 26, 2014 at 12:17 am # Reply

    Dr. Lynch, or anyone who might know:

    How does one increase Bh4?

    Thank you!

  170. Adrien February 27, 2014 at 10:12 am # Reply


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

    • Teresa March 2, 2014 at 6:04 am # Reply

      Hey Adrien,

      I know that my periodontal disease improved after magneium/calcium pushes.

  171. Terri March 1, 2014 at 1:03 am # Reply

    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.

  172. Terri March 1, 2014 at 6:30 pm # Reply

    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?

  173. Caroline March 2, 2014 at 2:33 am # Reply

    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 March 3, 2014 at 7:03 pm # Reply

      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.

  174. Adrienne March 3, 2014 at 1:25 am # Reply

    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 :)

  175. Adrienne March 3, 2014 at 1:27 am # Reply

    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 :)

  176. Ashlee March 5, 2014 at 10:27 am # Reply

    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 March 5, 2014 at 10:01 pm # Reply

      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 March 5, 2014 at 10:50 pm # Reply

      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.

  177. Jan March 6, 2014 at 9:41 pm # Reply

    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.

  178. Kreiss March 9, 2014 at 1:06 am # Reply

    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 March 9, 2014 at 8:00 am # Reply

      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 March 16, 2014 at 10:38 pm # Reply

      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