Methylfolate: Taking too much a problem?

I recently received an excellent pair of questions from a client of mine and wanted to share the dialogue with you.

To bring you up to speed, I urged caution in providing 800 mcg of methylfolate to younger children or immediately starting at a higher dose as it can cause side effects. Instead, I mentioned that he should start with a small amount and work up gradually in order to avoid side effects.

This caused some concern among his family members making them not want to take methylfolate at all – yet they all suffer from the MTHFR mutation.

Here is his question to me:

I am enjoying this tablet. It makes me feel grounded and secure. I have most of my relatives taking it now. I have two more questions that will help specific relatives:

1) Is the Metafolin portion of this supplement absorbed sublingually, like the B-12 component is? Or does the Metafolin portion mainly get absorbed by the stomach when it is swollowed?

2) You say that getting too much methylfolate can be “too much of a good thing”, or as bad as not getting enough. This worries people. So we want to know, how dangerous is this? Is the resultant agitation and irritability just a feeling of discomfort? Or is the body suffering from an imbalance as much as it would be harmed by a deficiency? I have not been able to find where you clarify this disturbing concern anywhere on your site.

Thanks! Dave

Hi Dave –

Great questions.

Let me quickly say that the population that I work with is very ill and highly sensitive so I am extra careful in my recommendations. The general population is not likely to experience any ill effects from taking methylfolate in higher amounts.

According to the Alt Med Review:
Side Effects and Toxicity of Methylfolate: In doses typically administered for therapeutic purposes, 5-MTHF is considered non-toxic. At doses of up to 50 mg daily, gastrointestinal complaints, insomnia, irritability, and fatigue have been mentioned as occasional side effects. Folic acid and 5-MTHF are considered safe during pregnancy, with a recommended intake of 800 mcg daily.

To answer your questions:
1) The metafolin is going to be directly absorbed just like the methylfolate – sublingually.

2) Taking too much of anything is not good. Is taking too much methylfolate dangerous? In most people, no. It is not going to cause long term issues or death or a serious health concern – and not even any side effects.

People take upwards of 50 mg of methylfolate daily for their depression or other mental dysfunctions.

I am very conservative when it comes to dose suggestions as I don’t like people being ‘macho’ and thinking that if they take 10 mg of methylfolate, that will be better than 1 mg. Sometimes yes it will and sometimes it won’t.

What could you experience if you do take too much methylfolate?
– Irritability
– Anxiety
– Nausea
– Headaches
– Insomnia

Will these symptoms go away upon reducing the levels of methylfolate or stopping it?
– Yes

Will these symptoms go away quickly?
– In most people – yes – these symptoms will stop within 24 hours if not earlier.

Can you ‘neutralize’ these side effects faster if they occur?
– Many times, yes.

– By taking niacin as niacin binds methyl groups and also increases the breakdown of glutamte – which is the excitatory neurtransmitter.

– By taking vitamin B6 – for many people – as B6 converts glutamate to GABA and GABA is the inhibitory neurotransmitter.

As a physician, it is my job to:
– Inform
– Educate
– Do no harm

That said – I encourage people to start low and work up carefully to avoid these side effects.

If I have ‘scared’ you – in a way, that is good – because you – and others – will take my recommendations to go slowly seriously.


Methylfolate in high doses appears to be much safer than taking folic acid in high doses.

As of now, research does not show any long term ill effects of excessive methylfolate – except in those who are bipolar.

Why bipolar?

Those with bipolar already have issues breaking down glutamate which is why they do so well on high doses of vitamin B3 (niacin) and I bet they’d also do very well on vitamin B6 and magnesium.

I hope this has been informative and has reduced the anxiety of your relatives. My apologies for making your desire to help your family more difficult. I admire your kindness and desire to help them.

Dr Ben

PS – the ‘tablet’ that Dave is enjoying is Active B12 with L-5-MTHF.


106 Responses to “Methylfolate: Taking too much a problem?”

  1. Jessie January 5, 2014 at 1:30 am #

    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.

    • patricia December 17, 2016 at 8:32 pm #

      Dear Jessie, and parents of a young person. Consider the effects of vaccinations and the heavy metals they contain. Also, check to see if your water is fluoridated. These can be heavy contributors to upsetting the already delicate balance.

      Seaweeds, especially Atlantic red dulse is supposed to help chelate metals out.
      Heavy metals and radiation are cumulative. Consider dentistry influences. Fluoride and mercury are both Haz Mat designated but the AMA considers them safe to put directly into humans, even children who are much more affected.

  2. Jean January 31, 2014 at 11:09 am #

    Hi Dr. Ben,
    I am a bit upset (not with anything about what you have taught). Long story but I’m almost positive my side of the family has this defect. My 23 and me test has not come back yet. I told my brother – who lives in another state- that I would like for him to ask his psychiatrist to do a MTHFR test. I gave him the lab, your web site, etc. My brother called last night and said his doctor said yes the methylfolate could possibly help SO he gave him enough for a month 15 mg, no explanation, didn’t explain anything about MTHFR, nothing about that he has to take the methylcobalamin. I told him to wait to take it – too late. He had already taken a dose. Of course I know what could happen if you take too much. He already has emotional issues, severe migraines, possible even bi-polar. I was freaking out. I told him to go get some niacin just in case his symptoms worsened. I also told him to stop taking it until he has some of the right kind of B-12. His didn’t say methylcobalamin. I also said that when he starts again he should only sprinkle of tiny bit of the capsule out – maybe 1 mg.

    I’m hoping I told him right.
    Thank you so much for all you do. I am so praying that your protocol is what my brother needs. He has so many of the markers for this defect and has tried everything and is taking so many pills. He always seems to be “drugged up”.


  3. Julien Y Perrette February 22, 2014 at 7:00 pm #

    Hi there,
    I have Bipolar and am medicated with lithium, lamictal, clozaril and Klonopin as well warfarin for blood clots, but I struggle with ongoing anxiety and am curious about Eric’s question about how much Niacin is helpful and also how much Folate too, as I took the 7.5 of Deplin on the advice of my Dr. for a while and it didn’t feel good. Thank you so much!
    – jyp

  4. Meliss March 8, 2014 at 5:55 am #

    Hi there. So last year I had the 23andme profile done and now I can see the raw data for my genome. When I search it for mthfr I get lots of results, but nothing with the numbers you give. All locations are listed as very long numbers. Any help on finding the right gene to check?? Any help is appreciated. Thanks!!

    • Dr Lynch March 8, 2014 at 6:31 pm #

      Hi Meliss –

      Please take your 23andMe raw data and run it through this reporting tool:

      This way you will be able to find out what MTHFR variants you have – along with others. It is a very useful tool.

      • Meliss March 11, 2014 at 2:48 am #

        Thanks for the reply… I was worried since there hasn’t been a post since 2012 that you had abandoned the site! I ran it through geneticgenie first and then did the one you suggested… not too surprised that I am homozygous for 677ctoT. I was put on Deplin 15mg as a “EH what could it hurt” by my psychiatrist to supplement the Vyvanse I have to take to mentally function and it was life changing. I felt NORMAL for the first time in forever, but the company switched from calcium salts to glutamate salts and it isn’t working the same. Both are 10mg… so many little tweaks with huge consequences. Do you know of any research groups out there? I would love to contribute to furthering this study!!

  5. Sue April 1, 2014 at 5:18 am #

    If you don’t have a MTHFR gene defect, can you still take the Sublingual Active B12 with Methylfolate as part of your health protocol?


    • Kyle March 2, 2017 at 10:34 pm #

      I’d like to know this also, as I took it and now I have continuing side effects.

  6. Sybil April 8, 2014 at 6:03 pm #

    My GP doctor put me on Ortho Molecular Products Methyl CpG recently when my blood test for MTHFR showed C677T and A1298C…one copy of the varient for each (not sure of the proper way to express that) along with elevated homeocysteine . First time homocysteine has ever been tested (I am 57 and this is a new GP for me) so I don’t know if it’s a new development or ongoing. Started feeling bad within days of starting the supplement, trouble focusing/brain fog, very tired (actually “tired and wired” simultaneously) and then progressed to feeling noticeably depressed a couple weeks later so I stopped taking it altogether. Was several days before I felt “normal” again . So then I called my doctor and said I thought I might be reacting to the supplement she said she had not ever heard of these reactions (presumably why there was no mention of possible reactions) but agreed that halving the dose might help. It made no difference…same reaction though I stopped this time after a couple days and took niacin as I have read on yours and other sites. Have also since tried your Active B12 with L-5-MTHFR and even at half the lozenge the reaction seems the same and it takes me a couple days to feel completely normal again when I stop. At 1/4 of the lozenge that I took today, I feel some negative reaction but maybe not as strong. I am wondering if should I keep trying progressively smaller amounts or is there something else that might be help to control the elevated homeocysteine which seems to what concerns her the most at this point. Also, is there a problem associated with MTHFR with taking niacin daily for cardiovascular health? She suggested last visit that it might be necessary . Seems I read something on your site related to that but cannot find it right now. My diet is better than the average person for the last 3 years…I cook daily (no processed foods) …almost entirely organic, organic grassfed/pastured meat/egg/dairy sources etc. and more recently lower carb along with more fish (3 times a week either wild salmon or sardines is what I aim for) and leafy greens daily, some raw, some cooked. I can’t help wondering if it is it even possible to make a positive impact relative to the potential health effects of these MTHFR gene varients through diet…or are we simply trying to avoid the chemicals/toxins mainly to avoid making things worse? The more I read, the more confusing MTHFR seems to get!

  7. Michael (NW) April 15, 2014 at 3:55 pm #

    Hi, can you over methylate with TMG? If so, is it the same symptoms?

    I take Betaine HCI. I’ve heard it can act as a methyl donor like TMG since they are similar… If that is the case, I take 660mg of Beataine 3 x per day (one with each meal) to help with digestion. Often when I go to bed, I have strange reactions, almost like pre panic attack symptoms, pulse increases, maybe heart palps, muslce spasms possibly, but in any case, I’m wired, like I had coffee, and cant sleep all night. Some times I can feel the stimluation happen before I go to bed, some time after dinner, but I definately feel symptommatic when I get into bed and lay there….Could this be overmethylation symptoms? I’m not doing any methylfolate, I have elevated folate/folic acid in my blood anyway… so not sure I need any. I don’t have MTFR mutation, although I have MTRR which I take methylb12 for. Tyring to determine what is causing these symptoms and terrible insomnia…. The only other thing that I do some times when these symptoms occur was taken some tryptophan, or 5-htp. so, I thought, hmmm, maybe too much serotonin, light serotonin syndrome? I was tested low magnesium, (spectracell test) and I’m taking liquid magnesium chloride. In any case, trying to figure out if Betaine HCI is causing me to over methylate, and what symptoms could it present itself as….
    I did take a little niacin (flush kind) and thought things calmed down, then they came back.

    Thank you,


  8. Kyle Crawford July 2, 2014 at 12:17 am #

    Hello. First, what a great site!
    My wife is bipolar and her Dr has just told her to start on MethylPro, 10mg. This also contains several B vitamins. I noticed your comment above on bipolar and want to know your thoughts on this product.

    Thank you, Kyle

  9. Nancy August 21, 2014 at 8:55 pm #

    I am homozygous MTHFR C677T++, COMT158M++ & COMT H62H ++, VDR taq++. I eat lots of green leafy vegetables every day and my diet is healthy, I worked up to 2 tablets of your Active B12 w/5-MTHF, and did not notice any difference in my energy, I did this for a couple of months and then had a blood test done RBC folate, and was surprised that my RBC folate was 2263 ng/ml – where the reference range is 499 – 1504. Do you know what the optimal RBC folate range should be? I did an internet search and found articles that suggest that too high RBC folate can shut off the tumor supressing genes and can take up to 10 years off of your life but did not say how much RBC folate is too much. If I eat a lot of green leafy vegetables, is it really necessary to supplement with 5-MTHF???

    • Dr Lynch August 26, 2014 at 6:51 am #

      It may not be necessary to supplement with L-5-MTHF, Nancy, if you are eating – and absorbing your folate from greens.

      Keep in mind that RBC folate is showing ALL folates – which does not mean your MTHF levels are fine. It may mean that your other forms are high while MTHF is low.

      You may need phosphatidylcholine (non-soy, non GMO) to support your cell membranes.

  10. Mirjam September 4, 2014 at 1:55 pm #

    Dear Dr. Ben,

    Help! How to reverse methyl trapping?
    You mentioned here and there that you should always take methylcobalamin with the folate. I read that way too late and listened to the wrong specialist.
    I made the stupid mistake of taking 1200mcg Methylfolate for a while without additional Methylcobalamin (maybe a tiny bit from food). I think this means methyl trapping.

    Now I experience severe brain fog and mental dysfunctioin, memory loss, confusion.. I cannot study anymore and find myself really sad. At first I thought I had a brain tumor.. it’s really horrible. Now have taken 400 mcg Methylfolate and 500 mcg Methylcobalamin for weeks but I really don’t feel any better. Should I stop Methylfolate for a while? Do I need to take Niacin in this case as well? I cannot find any usefull information anywhere on the internet on symptoms of methyl trapping only on how to prevent it from happening. I am really desperate for your advise. Especially on what to do about methyl trapping, how to reverse the symptoms.

    I would be extremely grateful to get a reply. Many thanks in advance.
    Thank you for all your great information. My naturopath and me find it very useful on this complicated subject.

    Grtz. Mirjam

    • Dr Lynch September 6, 2014 at 10:09 pm #

      In this case, I would stop the methylfolate and methylcobalamin.

      Try some Niacin 50 mg every hour until you feel better. Then stop.

      Also taking L-Tyrosine 250 mg (open the capsule and mix in juice) to 500 mg in the AM may help along with 5-HTP 50 mg in AM and at bedtime.

      One always needs to adjust what they are taking and how much.

      Please discuss with your doctor.

      • Sarabeth Matilsky September 7, 2014 at 12:58 am #

        Hi Dr. Lynch,

        Regarding your advice to Mirjam, above, concerning “methyl trapping,” I have an additional question: Once a person has stopped methylfolate/B12 for a period of time, and symptoms have abated, when is it appropriate to try to take them again? And, what is an appropriate way to titrate up the dose?

        Thanks so much for taking the time to read/respond to these comments! They are very useful for me.


        • Dr Lynch September 9, 2014 at 6:17 pm #

          Please listen to this:

          The easiest way to titrate is with a lozenge – which you can split into quarters. The formula I’ve designed contains methylfolate and two forms of B12 (methylcobalamin and adenosylcobalamin) – called Active B12 with L-5-MTHF.

          Before you do that though, you may need to support downstream pathways – and upstream. Typically those with side effects have deficiencies in other nutrients. This caused me to formulate a product for such situations. Optimal Start provides all key nutrients except B12, folate, calcium, copper along with some calming herbs to help focus and reduce stress. They do not cause fatigue – but rather calmed focus. Consider taking Optimal Start for one month and then restarting with a small amount of Active B12 with L-5-MTHF.

    • Mandy September 11, 2015 at 10:32 am #

      I had a similar but milder experience as Mirjam – I was doing great until I raised my methylfolate dose (from about 1200mcg to 3000mcg). I got brain fog and my cognitive function got worse. Most alarming was the complete disappearance of my motivation – I just had no motivation to do anything at all! Very weird for me as I’ve always been super interested in life, work, and everything. Not all was bad though – at such high levels of MTHF – my food sensitivities decreased, my skin cleared up, no more runny nose/congestion, and I was much calmer than before (I used to be slightly anxious and had mild insomnia).

      I didn’t like how I was feeling psychologically (“flat”) so I cut out methylfolate completely for a month. Fortunately, the brain fog disappeared and my cognitive function improved. However… my motivation never came back 🙁 Also, the physical benefits above disappeared as well.

      Fortunately – thank GOD – I decided to try this 50mg of niacin per hour strategy and it worked like a CHARM. Within the first dose I felt … “alive”. It was subtle initially but it felt like something in me just “woke up”. I took about 2-3 more doses before leaving work, and for the first time in two months, I regained the motivation to read a book on the train home!! (This moment, plus the first methylb12 dose I ever took, are the most magical moments I have had – no kidding)

      I wanted to post this to share – as I have benefitted from everyone’s sharing here – a couple of interesting observations (experiential only) to add to this resource:

      1) It did not matter that I was off methylfolate for one month already – adding niacin helped instantly – therefore I would suggest anyone troubled by a symptom to give it a shot, rather than wait it out – it might help. (I also suspect it could be a plain niacin-deficiency, as I take only 25mg niacin daily in a multi)

      2) My symptoms of too much methylfolate seemed different from most people – I was not edgy/anxious/irritable. In fact, I felt very grounded and calm, but stripped completely of motivation (apathy). Because my symptoms were so odd (almost opposite), it took me a long time to pinpoint increased methylfolate as the cause. I did so only after ruling out everything else, and reviewing my supplement diary many, many times. I think journalling symptoms and supplements is so, so useful.

      3) I am finding a balance in terms of dose- I think methylfolate does wonderful things for me physically but I am since very careful of its psychological effects. So far, I have found that not only I have to keep its dose low (about 1200mcg daily), I also have to add niacin (about 250 mcg daily).

      I have no idea why this combination works for me. Over time I have lost interest in the theoretical / physiological explanations. I do what works. Theoretically, niacin is just mopping up my methyl groups and is counter-productive to the methybl12 and methylfolate I take. But without niacin I don’t have motivation. And without methylfolate I just don’t feel good either. So I just take all 3 on a daily basis.

      Cannot figure out why, don’t care, and just happy to feel motivated again 🙂

      • Lance April 13, 2016 at 4:23 pm #

        Mandy, I wanted to respond to your post because it so closely echoes my own experience. I absolutely need methylfolate to be at my best, but if I take even a little bit too much, my cognition stalls out, I lose all motivation, and want nothing more than to be left alone to stare at the wall. Niacin is the silver bullet and brings me back to life. These days I find that I get the best result by pairing niacin with methylfolate.

        The common wisdom is that methylfolate/niacin is an either/or proposition, but I wonder if this doesn’t overlook the benefit of taking both together.

      • Scott March 12, 2017 at 8:26 am #

        I read your post with great interest because I went through the same thing, though I was not taking methylfolate at the time of my health crash but I was taking injectable methyl B12. Brain fog, reduced cognitive function, inability to plan or organize, it feltlike my IQ had dropped 20 pts, and as you said most distressingly was the complete disappearance of my motivation. I was totally apathetic and prior to that I was at the other side of the spectrum, almost hyperthyroid. I was also falling asleep during the day after eating.

        This change in brain function and complete apathy totally derailed my life. At the time I thought it was due to an antibiotic protocol I was doing (the marshall protocol)and also exposure to a moldy building. It still might be becuase of either of these, but I had also just prior increased the amount of methylB12 injections I was taking. I was on them not because of MTHFR issues, but because blood test showed I was low in B12 and had high homocyteine levels. My doc put me on 1 a week cyanocobalamin and some folic acid tabs. I never noticed any difference on these, and at some point read up about methylated B12 and gave that a go, unfortunately I forgot about folic acid,but I dont know if that was the reason for my cognitive& motivation decline. My doctor had diagnosed me as an under methylator so taking methyl b12 if anything should have boosted my brain energy function.

        I too have found benefit with vitamin b3 but with the niacimamide version rather than the flush version. the trouble is the benefit runs out after a month. I have taken methylfolate before, the first time I felt worse so dropped it. the next year I took it I noticed nothing, and now when I tried at triple the dose from before I am getting more motivation,though its not enough to get me back to what I was. I had asked others online about the methyl b12 possibly ruining my cognition and motivation and everyone doubted it, so it was interesting to read your post were you had the same issues as me but on methyl-folate. and you also benefited from B3, which is the opposite of what most people experience.
        Mucuna Puriens also helps (boosts dopamine),me but the trouble with that is your transmitters can down regulate to it quickly and you have to space it out when you take it.

  11. Carol September 29, 2014 at 6:27 pm #

    Dr Lynch,
    Thanks for this website. I am Bipolar 2.
    I hesitated to take Sublingual Active B-12 with L-5-MTHF after I learned about it because 3 of my doctors don’t seem to be aware of what it is, or what it does. One is my Primary Physician, another my Psychiatist, and the third a well-known Physician who works with patients that have Mental Disorders.
    I was actually frightened to take this product. I have a bottle now and feel confident after reading this blog that it will not hurt me with low doses.

    I am presently and have been taking high doses of Depakote & Zoloft for 14years now. Mania & Depression still sneak through at times. Especially Depression, feeling hopelessness lately. For the first several years before I was diagnosed with bipolar, I mostly experienced Manic Episodes that were productive, like working hard at my job & overly organizing my belongings, constant cleaning around the house, rapid speech…

    I read the information on this blog. But I am still confused on how many tabs to start with.
    Thank-You so much for this website.
    Carol, Dave’s sister

    • Dr Lynch September 30, 2014 at 4:10 am #

      Hello –

      Be careful.

      You should be cautious with Active B12 with L-5-MTHF. If you take it and feel great, then stop. Skip a day or two. If you feel you need more, then take a bit more.

      Always have a bottle of Niacin handy so you can neutralize the side effects.

      I’d start low with a quarter tab of the B12/MTHF and take it after your food in the AM.

      I’d also consider supporting your moods/cognition with:
      – Magnesium Plus – a combination of magnesium and active B6
      – Optimal Adrenal – a combination of herbs and some nutrients to balance your adrenals – very needed for many people
      – Optimal Liposomoal Glutathione – start low and work up – many times oxidative stress causes mental dysfunction – MANY TIMES.

      Eliminate gluten and dairy.

      I would read this lady’s blog – high histamine is a major issue – and reducing histamine foods could really help you.

      We have ‘Histamine Block’ which helps reduce histamine in the gut – from food. It’s expensive so the best thing to do is just reduce those foods.

      Taking vitamin B1 also helps remove sulfites – and that is important to do many times.

      These recommendations can be obtained at which is my company – disclosure.

      Do talk with your doctor about this.

      I’d also journal when the mania takes over – likely when your blood sugar drops and cortisol/norepi spikes. Balancing blood sugar is very important – and balancing adrenals is as well – they go together.

      • Marcia April 7, 2015 at 9:11 pm #

        Doesn’t niacin increase histamine?

  12. Rachel October 27, 2014 at 3:01 pm #

    Hi Dr. Lynch,

    I feel so lost! I live in a state where there are no physicians that completely underdtand MTHFR. I discovered my own mutation after ordering 23 and Me and also after demanding some lab just to confirm.
    I am heterozygous A1298C and have SLE and high homocysteine levels. I am currently on NeevoDHA. My physician also prescribed Metanx in addition. I am not sure if I need to take both. How do I know if my levels are in normal range with NeevoDHA supplementation? Is there a specific lab test? I am also confused as to whether or not I should be consuming spinach, kale, orange juice etc. I have read that consuming natural folate will even inhibit methylfolate consumption, is this true?? Also, I have 10 amalgam fillings in and I am having them removed soon. What heavy metal detox program do you recommend? Natural detox with cilantro, chlorella etc? Or DMSA DMPS chelation? I am wanting to start my family soon, so the detox is really concerning to me also!


  13. Bethany November 29, 2014 at 6:55 pm #

    I have been trying to get pregnant for over 3 years with one successful pregnancy 5 years ago with help of fertility treatments. Last year I found out I have one copy of the A1298C mutation. I never thought much of it until I had a miscarriage 2 months ago. Now my reproductive specialist wants to give me Folgard and baby aspirin but my primary physician wants me to take Thorne Research basic prenatal plus 1 Methyl Guard plus everyday. I don’t think the Folgard is correct but the Thorne supplements put together are 1.5mg methylfolate and 0.5mg folic acid which is too much for a pregnant woman according to your website. Only having one copy of the mutation, I’m not sure whether to worry about it at all. Do you have any advice?

  14. Ellie January 8, 2015 at 10:09 pm #

    I had initial hormone testing (as well as gut and neuroadrenals and cortisol testing) done thru an integrative medicine dr. she explained that i was defficient in methylation. i started a lot of supplements, one of which is orthomolecular methyl cpg. it has 2,000mcg of folate and she initially had me taking one tablet 3 times a day.

    i was feeling great for 1 week and then started experiencing a horrible speedy/anxious feeling with a rapid heart rate and increased bp in the morning, and then flu like symptoms every afternoon…could not get my head off the pillow. she took the methyl cpg down to 1 pill a day and i have felt much better.

    i just started my menstrual cycle last week and have always had heavy ones but this one sent me to my obgyn. i was bleeding terribly heavy, like after a miscarriage, and saw blood clots in the toilet every time i had to urinate. i passed out this morning, so i called my dr. and saw him today. he did a biopsy of my uterus (horribly painful), ordered a pelvic ultrasound, did bloodwork, put me on iron, and on a huge dosage of a birth control pill (9 pills a day for 3 days, then 2 pills a day for 6 days, then 1 pill daily for 21 days). he said i was in danger of “bleeding out” and would need a blood transfusion if i didn’t follow his protocol.

    does this “hemmoraging” have anything to do with my new supplements? my cousin is studying to be a naturopath and she has said from the beginning that my integrative medicine doc has me on way too much methyl folate and vitamin d3. my integrative medicine doc. disagrees, except she did take me down from 3 pills to 1 pill of methyl cpg. i also take effexor which the IM doc says she will start weaning me off of in a few weeks. Any thoughts? Is there just a bad combination of supplements/meds going on for my body? I am scared and feel like i may be one of those people that gives up on trying to treat MTHFR because of the side effects.

    Thanks for you help!

  15. whisperingsage January 11, 2015 at 1:13 am #

    I am MTHFR and Hashimotos and Adrenal insufficiency, I am a hot mess in other words. It began when I retook my childhood vaccines to get into nursing school. So vaccine injury- thimerisol and aluminum. The mercury is currently detoxed but the injury remains.

    So I have doubts about it being purely “genetic”. I think genes are damaged through life and I may have had some damage from my mother being fetal alcohol.

    My mes is that i became obviously adrenal insufficient in 2011 when I threw up for 30 days and have been fighting to regain some semblance of health since then. My gut is my #1 issue- continue to have daily pain, gas and diarrhea. The diarrhea has been since the vaccine injury in 2003. That has cascaded into all the other things. Can’t heal if I can’t absorb nutrients. The gut issue is adrenal- and I fight it with 16 species probiotics, magnesium, vitamin C ironically, oxy powder, pHenomenal water,pancreatin with meals, gas enzymes with meals, cumin with meals (stimulates gall bladder), i am not gluten intolerant (tested 5 times including saliva and biopsy), not lactose intolerant, ( problem began when abstaining from milk, but I have been tested at least 5 times there too), methylfolate 4 mg began a great healing- such that I could (had to ) reduce raw adrenal and thyroid pills, began to work but work nights, had to drastically increase methylfolate, lost many improvements methylfolate first helped. Nights upset the circadian rhythm, but in my field, that is where the need is so here I am. No work, no money for testing or going to my doc. Nights really screw up my guts.

  16. Heamardon January 17, 2015 at 3:38 am #

    Dr. Ben! I need help!

    A few years ago, I’ve was told I’m B12 deficient and have tried B12 shots and Deplin, but both made me feel like the Incredible Hulk, irritable and anxious. So I stopped.

    But now I’ve had 2 early miscarriages and I’m concerned it’s related to my B12 deficiency. My reproductive endocrinologist refuses to test me for MTHFR because she feels it’s “pointless.” I would like to try supplementing myself to prevent another miscarriage, but I have no idea the differences between the methylcobalamin and methylfolate and all of the other forms. Can you please tell me what I should take???

  17. Carrie English February 2, 2015 at 3:06 am #

    My name is Carrie. I’m 16 and my doctor said I have MS two years ago, because my feet were num. my mom didn’t believe this and started looking online what else it could be. She found this thing called mthfr and had my doctor test me for it – he didn’t want to, never heard of it. The report came back that I have 2 of 1298. Can I fix this? My doctor still says it MS and not this, just keep taking Copaxone drug. Help? TY -Carrie

  18. Nicole February 6, 2015 at 9:55 am #

    Hi Dr Lynch

    My name is Nicole and would very much appreciate your advice. I have tried to keep the message as short as possible, but had to explain my background a bit.

    I have always had the symptoms of an undermethlator, but these symptoms weren’t severe and allowed me to excel in life. However this changed about 3 years ago when I went on roaccutane to clear my skin. Shortly after starting my dosage was increased, as the roaccutane seemed to have no therapeutic effect on me (so I ended up taking a very high dose). Within the next few months of starting roacctuane I went dramatically downhill. I developed severe depression, severe anxiety, extreme phobias, delusional thinking, racing thoughts and struggled to function at all. I had no idea what was happening and sought help via a psychiatrist. He put me on sertraline (50mg) and risperidone (0.375mg). When I first started risperidone, I reacted very badly to it. Now three years later I am tapering off both medications very, very slowly, as it decreasing it even a small amount seems to have a major effect on me. I still struggle with anxiety, phobias, etc and have become chronically fatigued. I still have the physical side effects of roaccutane – dry skin, sun sensitivity and bruise easily. I have done a 23 and me test and have listed the main results – CYP2D6 S486T ++ SOD2 ++, SOD2 A16V ++, GAD1 rs12185692++, GAD rs3828275 ++, MTHF A1298C ++, MTRR ++, MTHFS.

    I was wondering what supplements you recommend for firstly overcoming the CYP2D6 S486 mutation and hence eliminating the accutane, sertraline and risperidone from my liver. I heard that activated charcoal can do this? What dose and for how long would you recommend?

    Secondly I was wondering what supplements you would recommend for me for methylation? I have recently started methylfolate, but stopped, as even just taking 200mcg gives me nauesa, fatigue and totally knocks me out (the same happens with 200mg of SAMe but to a lesser extent).

    (I am also supplementing with Mg, K, vit B12, Vit C, vit E, zinc, activated B6, activated B2, NAC, GSH, Max DHA, milk thistle, probiotics, phospatidyl choline and inositol (as well as saffron, iron, DHEA and progestrone, vit D3))

    Any advice at all would be a great help – thanks!

  19. Michael (NW) February 13, 2015 at 7:34 pm #


    I’m MTHFR — . But, I’m MTRR/A66G ++ and MTRR/11 +- which I’m not exactly sure which each one means for certain, but from what I gather, I don’t have the ability to convert/make Methyl-B12. So, I take Methyl-b12. Since this is a Methlyfolate post, I have a question about taking Methlyfolate. If I’m not MTHFRR ++, is taking extra Methlyfolate benefical? Will it help make more neurotransmitters? I’m assuming since I am MTRR ++ that methlyfolate can’t help with B12 at all, so what will it do? My co-enzyme B complex has about 400-800mcg methlyfolate. Will taking more help? I’m still dealing with some depression, even after being on SJW, Tryptophan, Methly-B12. (I was also dealing with some adrenal fatigue which has greatly improved recently). Thank you.

  20. Michael (NW) February 13, 2015 at 7:35 pm #

    Oops, one other question. You mention using Niacin if you over methlyate….I’m believe you are referring to the nicotinic acid , the flushing niacin? Also, if it helps break down glutamate, which I was tested high before, how much niacin can you take to help without causing an undermethylation scenario? Thanks.

  21. Meg February 27, 2015 at 8:08 pm #

    Hi Dr Lynch,
    I started the Optimal Start, and I feel horrible 🙁 IDK why could it be b/c I have MTRR and MTR as well as others causing problems? I have been using a combo of Aden and Hydroxy b12 fine, as well as niacin alone, Riboflavin alone, and Thiamine alone. I use Vitamin C, your electrolyte drink 🙂 and glutathione presursors but something in this makes me headachey and fatigue with a headache. IDK why, as it does not have Cobal B12 or folic acid in it. I am just wondering if something in it is being blocked. ps. I have atypical PKU from slcssa1 qdpr and a bunch of others snps = low bh4. But, none of the 6 mthfr docs I have seen can figure this out. This is such a hurdle. Should I try a folinic instead?

    • Dr Lynch March 1, 2015 at 7:28 am #

      Hi Meg –

      It is hard to say without more information – but definitely stop taking it – or reduce the amount to just 1 capsule a day – then increase to 1 capsule twice a day after a week or two – go slowly. Not good to ‘kick’ your metabolism too fast.

      Testing may be needed and likely so.

      RBC Essential and Toxic Elements by Doctors Data OR T Lymphocyte Testing by Spectracell or Nutreval by Genova may be some things to consider – along with a comprehensive digestive stool analysis and other tests.

  22. dm7 February 27, 2015 at 11:01 pm #

    Dear doctor,

    I am deficient with all b vitamins. So my doctor gave me b complex + 5gr of mthfr.
    first i felt great but than i atarted feeling bad. I told the doctor but she said its just like that and that i should keep on taking them. I was taking them for 4 weeks, when i realised something is very wrong. My skin became yellow, liver was showing problems, i had dark curclez under eyes, tinntus in ears, muscle pain, bone pain, headech, irritability, depression, aggressive behavior , delusioons.

    To cut the story short, i was overdosed for 3 weeks. Yhey wanted to put me in mental hoital for behavior. In 24h when i stopped taking supplements, my mood improved and i started feeling better.But still i have problems with speaking, forgetfullnes and tinntus in my ears After 5 days of stopping. should i be worried ?

    • Dr Lynch March 1, 2015 at 7:59 am #

      Hello –

      Sorry to hear about this.

      It is ALL TOO COMMON and this is why this article is the #1 read article.

      Please consider:
      Optimal Liposomal Glutathione – start low – few drops – and work up
      Optimal Electrolyte – 1 scoop in a tall glass of water and drink over about 15 minutes or so
      Optimal PC – 1 capsule with lunch to help your liver
      Liver Nutrients – 1 capsule with lunch – to help with liver

      Please do try and find a doctor near you – has a list of physicians.

      The above should help support your liver. I believe your methylation became quite unbalanced – especially if you were not eating enough protein.

      Be sure you are eating adequate protein – about 1 gram per 2 lbs of body weight. So about 90 grams of protein a day if you weigh 200 lbs – spread throughout the day.

      Please do find a good doctor to work with.

  23. Jen March 11, 2015 at 1:26 am #

    Dr. Lynch
    On October 16,2014 we had our first baby, she had anencephaly and deletion 13. The doctors put me on 4 mg of folic acid. They said that’s all I needed to do but recently we found out about MTHFR. My husband sibling both have Heterozygous 677. We have been to a genwtiat and high risk OBGYN and they say MTHFR didn’t contribute to our babies birth defect. We just found a doctor willing to test us. I’m now on 4 mg of methylfolate and my husband is taking 400 MCG. Does my husband need to be on methylfolate for a certain amount of time before we try to get pregnant again? Is 4 mg what you recommend for neural tube defects? I’m currently taking prenatal vitamin, fish oil, probiotic and the methylfolate. Do you think that is sufficient. Thank you so much for your help. It has been so difficult to find answers.

    • Dr Lynch March 11, 2015 at 5:29 pm #

      Hi Jen –

      I am pleased to hear that you are making some good changes in supporting methylation.

      It’s not just about MTHFR here – but more about methylation in general.

      Please read this article:

      I also highly recommend that you and your physicians watch this prenatal conference course -it gets into details – many of which you’d understand as well as a lay person.

      I’d like to see you consider some phosphatidylcholine – and your husband. You are absolutely right that your husband needs to support his methylation as well.

      The phosphatidylcholine is available in the Optimal PC capsules -also in meat – red meat specifically.

      If you find yourself anxious, irritable or in pain, you may be taking too much methylfolate. As you continue taking it, and improving your lifestyle, diet and overall environment – and supplement protocol, you may find that you need less methylfolate.

      Methylation is all about demand – and pregnancy is HIGHLY demanding of methylation – so preparing now is key – for both you and your husband.

      I HIGHLY recommend the Optimal Prenatal Protein Powder – over the Optimal Prenatal capsules – at least some of the time.

      Mixing 1/2 scoop twice daily in some coconut/almond milk is a great way to drink your prenatal vitamins along with complete protein.

      • Jen STolz March 11, 2015 at 10:11 pm #

        Dr. Lynch,
        Thank you very much for your quick reply. I will look at the supplements you suggested as well as the articles/course.

        I noticed this comment in an article on the Seeking Health Learning Center
        What happens if you have too much methylfolate? Methyl trapping!
        More is not always better and having too much methylfolate without adequate
        B12 will block the methionine cycle. This can set off a cascade of problems
        including increased homocysteine levels and inhibition of methylation. It also has
        the potential to increase strand breaks in DNA due to an increase in uracil and
        decrease in thymidine.

        How much B12 is save to take when trying to get pregnant and when pregnant, also how much B12 and Niacin should I take if I’m taking 4mg of Methylfolate?

        My husband has taken folic acid in his multivitamin for 9 months and then this past month he was on methylfolate instead. I was on folic acid during pregnancy and then 4 mg of folic acid for 4 months and 1 month of methylfolate in place of folic acid. Do you feel 2 months of us both being on methylfolate is enough time before trying to get pregnant?

        We eat a gluten free diet as my husband has celiac. We also stay away from refined sugars and try to only use olive oil, grapeseed oil, grassfed butter and coconut oil. We eat organic with the dirty dozen and our meat and chicken.

        We know we will need to trust for future pregnancies but would like to do everything we can do with what we eat and supplements.

        I appreciate your time and help.

        • Dr Lynch March 12, 2015 at 5:09 pm #

          I am not sure how much time is needed -there is no setting for that as we are all different and require different amounts and those requirements change daily even given the circumstances.

          I do recommend you take some folinic acid – around 400 mcg – not just methylfolate.

          I would consider being on those recommendations I made for a couple months – all of them – and both of you – and then consider trying to conceive.

          Evaluate how you and your husband are feeling as well – that’s key. If you feel tired and drained, either of you, then don’t try.

          If you both feel amazing, that’s the time to try as your body is ready.

  24. Shannon April 1, 2015 at 9:54 pm #

    I am currently following the Gerson Therapy protocol for breast cancer. All scans and tumor markers have been good for the past year. I began the therapy after a lumpectomy in Dec. 2013. The diagnosis was stage 1 grade 2 with no lymph node involvement. I am taking large doses (relative to the standard) of B12 (methyl form) via injection twice per week, 1 gram total and tolerate it well. After discovering the world of methylation I believe it is very relevant to my cancer. My MCV and MCH have remained at high normal and above normal respectively since before I began the therapy. Is it possible the issue may be a folate deficiency? I certainly should not be B12 deficient at this point as I have taken injections for over a year now. So, I have added 1mg of the Thorne methylated folate and feel great so far taking it. I am wondering if you feel this is a sign my body is starved for folate despite my consumption of 4 8 oz organic green juices per day. Is it possible. I have not been tested specifically for MTHFR mutation however genetic expression tests of my tumor classified me as high risk for distant recurrence within 10 years. I assume because the link between methylation and cancer has been established, this gene is one of the 70 considered in the mammaprint genomic test performed on the tumor tissue. Any help you can provide would be brilliant! My ND and Gerson practitioner know little concerning this subject and seem relatively uninterested in researching with/for me. I am more than happy to consult with you if necessary. Please advise.

  25. Shannon April 1, 2015 at 9:56 pm #

    I’m sorry…I mg of B12 per week via injection not 1 gram!

  26. Gillian April 3, 2015 at 5:23 pm #

    I am currently experiencing a bad reaction to the methyl supplements. Initially I believe I was having potassium crashes. My heart would race, blood pressure would sky rocket, hands and feet would go cold and my body would shake. Now symptoms of overmethylation are racing heart and anxiety. I was taking a lot of B 12 Methylcobalamin and a moderate amount of methylfolate. I have been off all supplements for 4 days, and am still experiencing symptoms of overmethylation. They have reduced in intensity each day, but are still pretty agonizing. On top of that, I believe I was suffering from a deficiency in B12. I would like to supplement it but I don’t think methylcobalamin agrees with me. I have bi polar disorder in my family, and may also have some bi polar tendencies. Will the overmethylation symptoms ever end?

    • Aron Choi April 13, 2015 at 6:13 pm #

      Gillian, this post on methylfolate side effects is a place to start . Definitely see your doctor if the symptoms have not improved.

    • Vanessa June 9, 2016 at 7:06 pm #

      If you want a good source of information on the topic of overmethylation I can recommend a good book for you. It is called Nutrient Power: Heal your biochemistry Heal your brain, By William Walsh. This is probably one of the best sources of information on the topic of methylation and the common imbalances that lead to mental health issues and other health problems. He has developed a panel of tests through Direct Healthcare Access II Labs which can be very helpful.

      Walsh has a lot to say about overmethylation and bipolar and what kinds of treatments are helpful for that. He’s got a lot of great Youtube videos on this topic if you don’t want to get the book. If you are overmethylated, as far as I’ve understood you should not be taking any supplements that add extra methyl groups, you already have too much. There is a specific list of supplements for overmethylation. I had to look into this myself because I found out that I am overmethylated with copper overload a while ago. A lot of Dr.’s and Naturopaths are not well informed about overmethylation and many of them are recommending these genetic tests which are not actually going to be helpful for detecting this problem. I don’t think Dr. Lynch talks much about this specifically, so you might want to go elsewhere for information.

      It is also very important to find a doctor or naturopath that is methylation literate that you can work with, you should not be trying to treat yourself for this problem. I know that Walsh trains physicians across the USA and has a list on his website on who to look up for help. Another good source would be Dr. Albert Mensah, and I’m pretty sure you can book over the phone consults through his clinic Mensah Medical.

      Wishing you well on your healing journey.

  27. Alyson April 7, 2015 at 9:06 pm #

    I think it might be time to add to this article, because there are a ton of truly severe side effects from taking too much methylfolate. This is what I learned the hard way

    -“Upper limit” is a truly individual thing, so judge how much you should take based on how it makes you feel, not what your doctor says is the maximum a person can take. If you’re not tolerating it, don’t take it

    -Side effects can be SEVERE- I don’t think this is really given enough attention

    I say this because when I started, I saw the list of side effects and thought, “those don’t sound so bad, people report those even with a placebo.” Then the side effects hit me – hypokalemia, severe muscle cramps, spasms, STRONG palpitations, cystic acne, thickened painful rashes, psychotic anger, disabling confusion and dreadful depression to the point I would practically hide under my bed, full body pain, hyperventilation, etc It felt like I had poisonous fire through my whole body and could not get it out. It was bad. Most definitely SEVERE. It did not go away quickly, but took 8 months.

    tl;dr dose tolerance is an individual thing, side effects can be SEVERE

    • Melissa October 3, 2015 at 2:20 am #

      Hi Alyson,
      Were you having injections of b12 or supplement? Also did you have insomnia? If so did it get better? Thanks Melissa

      • A October 5, 2015 at 9:07 am #

        Hi Melissa, at first I was on methylfolate and methylb12 sublinguals. That was hell.

        Now I take pure hydroxocobalamin liquid. I try to take as much as I need for symptom relief.

        I have terrible insomnia. With the methyls I was.awoken throughout the night by tremors a 92nd palpitations. Those are better now but I still don’t sleep.

        Epsom salt footbaths help sleep if you are deficient in magnesium. But overdoing it causes diarrhea.

        • Vic December 15, 2015 at 9:08 pm #

          Hi Alyson, how are you doing now?

          I’m writing for you because I’m now suffering from over methylation symptoms
          It’s terrible! I can’t deal with 0 stress. Can’t get off home. I have hyperventilation, depression, insomnia, confusion and a weird feeling of being out of my body.
          I HADN’T THESE THINGS BEFORE. I can’t deal with that, I was thinking about suicide. Seriously, i’m passing through a hell. I don’t know if I’ll get better.

          I don’t know if I’m dealing with folate trap, or overmethylation or excess of ammonia firing my NMDA receptors. There isn’t a way to check these possibilities, so I’m totally lost.

          • Amanda January 31, 2017 at 3:26 pm #


            How are you doing now? I am new to this site but I have been through what you are going through. It started for me about a year ago. Did you ever get any answers?

  28. Jackie April 29, 2015 at 1:46 am #

    Dr. Lynch,
    Everyone in our family has one or two copies of the MTHFR mutations. I have been reading and researching this subject for the past 8 months and need some clarification regarding Methyl-Folate VS Folic Acid. I keep reading that if you are homozygous for these mutations that you must avoid all food and supplementation containing folic acid and use alternative types such as L-Methyl folate or folinic acid. Is there any research that verifies this claim? A lot of foods we eat contain folic acid, as do some of the supplements we are taking. I am concerned, but would appreciate if you could direct me to the research that you have done or has been done to confirm this.

    Thank you,

  29. Cara May 22, 2015 at 6:47 pm #

    Hi Dr Lynch,
    I have been taking your active b12 and L-5-MTHF, 1 lozenge a day and your optimal prenatal for about 3 months. I went to go have blood work done, my vit b 12 level came back over the high limit of >1999. My primary told me to stop taking any b12. What would you recommend? I bought the L-5-MTHF lozenges and started them. What prenatal should I take now? Should I be concerned about the high level?

  30. Angela McDougall June 3, 2015 at 12:05 pm #

    Hi Dr Lynch,
    I have been taking 400mcg of folate daily since being confirmed as homozygous C677T mutation. I was already taking 100mg of Zoloft daily and was hoping to slowly reduce this after being on this for 15years for depression. I have been stable on Zoloft but wanted to hopefully wean of this and just use methyl folate. I tried to reduce to 75mgs and do not feel good. Can taking Zoloft antidepressant and folate at the same time cause too much serotonin which can make you depressed and very fatigued? I have found these symptoms have taken over and now need to stop taking folate just try to get stable again on the 100mg Zoloft. Any suggestion or information would be very helpful and appreciated.
    Thanks Angela

  31. Katie June 5, 2015 at 7:03 pm #

    Hello Dr. Ben,
    I am 33 years old have been dealing with chronic health issues since for over 10 years…food sensitivities, anxiety, etc. We learned about mthfr after my 5th baby was born with down syndrome. My husband and I have both had 23&me testing. Something that I have always wondered is could we have prevented this genetic mutation from happening? I always thought that it was interesting that after having a baby with ds, the risk factor for more children with ds goes up. That tells me that the state of the mother’s body has a effect on the baby while he/she is being formed. I saw that you have a presentation about healthy pregnancy, but I just don’t have the $55 right now. Also, I am having a very difficult time finding a practitioner to help me. I have seen so many that seem to know a lot, but then are not helpful. I know that healing the gut it the 1st step. I currently have a very limited diet of meat and very few vegetables. I still seem to tingle no matter what I eat. I have been trying broth fasts, but then I get histamine with that too. I take d3, seleniumethionine, quercetin, zinc/b6. I have 5methylfolate but am nervous to add another methyl group in there. ( I think that I am already over methylating). b12 (adeno) is important, but it’s hard to find one with no added sweeteners and flavorings. I just don’t know what to do anymore. We have spent so much money trying to find someone to help, and we are tapped out. I am trying to understand all of this and am a bit overwhelmed. Thank you for pioneering the way in this field. So many docs don’t value this. We recently went to the Museum of Science and Industry in Chicago. Their human body section had a huge area on genetics and the value of understanding your SNPS. My husband and I were encouraged that they were “speaking our language”, and we weren’t off-base in getting tested. Thank you again.

    • Vanessa June 9, 2016 at 10:25 pm #

      If you are in Chicago there is a clinic that helps people specifically with methylation issues and other particularly confusing health problems – its called Mensah Medical, you can look it up online. This clinic takes a different approach to evaluating methylation issues, different from looking at genetic tests (these are seen as inherently problematic by a number of experts on this topic, because they are not assessing end products.There is no way to know the dowstream effect with genetic testing alone). Dr. Mensah trained under Dr. Walsh, of the Walsh research institute. Walsh is one of the best information sources available on methylation and other biochemical imbalances that cause mental health issues, sensitivities, fatigue etc… He has written a book on this subject titled ‘Nutrient Power’. Both Walsh and Mensah have quite a few educational videos on Youtube that you can check out to get more information. If you think you are overmethylating, then you definitely should not get any more methyl groups in your system. But the only way to know is to get properly tested for this, the panel that walsh recommends is fairly inexpensive and available through Direct Healthcare Access II Labs (Metabolic Panel).

      I think all of this genetic testing is just creating a huge amount of confusion for people, especially when they can’t find good practitioners to work with and then end up on internet forums out of desperation. A lot of practitioners are ONLY familiar with undermethylation and think the MTHFR test is the only one to do, but this will not tell you everything you need to know as there are many other genes and pathways involved.

      Hope this helps, take care 🙂

  32. VM July 23, 2015 at 7:44 pm #

    Hi Dr. Ben,

    I am finding the information on different sites very confusing with regard to MTHFR and something called ‘overmethylation’.

    Is there any way to discern the difference between overmethylation and undermethylation from an MTHFR test? I have not had any MTHFR testing done, but plan to in the next few weeks.

    I suspect that I may be an ‘overmethylator’ based on symptom profile – (copper overload, chronic insomnia, hypersensitivity/anxiety, mood fluctuations, low libido, creative personality type, intolerance to SSRI’s and SAMe etc..). I am trying to figure out what the best protocol is to follow, I don’t want to start taking the wrong supplements and end up getting worse.

    Can you recommend any good sources for further reading on this topic?


    • Vanessa June 9, 2016 at 6:49 pm #


      I was in the same boat, I suspected I was overmethylated and wanted to find out more. The best source of information on this topic is Dr. William Walsh and also Dr. Albert Mensah. Walsh has a number of Youtube videos on this topic as well as a very informative book titled: Nutrient Power: Heal your biochemistry, Heal Your Brain. He trains physicians in the USA and Australia.

      I can tell you that his point of view on this is that genetic testing is not 100% useful for detecting methylation imbalances – he recommends a panel of tests that look at end products rather than genes, as well as a number of very common nutrient imbalances that can also develop. The gold standard test for overmethylation according to Walsh and Mensah is called the SAMe/SAH ratio. But whole blood histamine can also be a useful way to screen for this.

      I realize your posted this a year ago, so I hope you get this message notification. I think reading the book or listening to some of his talks on Youtube will really clarify things for you.

      Take care and wishing you well on your healing journey.

  33. Melissa October 3, 2015 at 2:09 am #

    Hi,A month and a half ago my dr offered me a b12 shot after I mentioned it being lil low months ago and actually level was 450 should have never received a shot and I did. Since I have had high heart rate over adrenaline of energy and insomnia. I was a big sleeper so this has been a living nightmare. Is there anything to take to reverse these effects? Has anyone had this reaction and have long lasting side effects? Will they go away if haven’t yet?

  34. Christina October 11, 2015 at 7:51 pm #

    I’m homozygous for MTHFR C677T. My GYN put me on 5 mg folic acid, B-Complex and fish oil. I’m thinking to become pregnant, I may be right now (still waiting for my period). Is it safe to stop taking the high dose of folic acid and start with Seeking Health Active B12 with L-MTHF? Or could the detoxification reaction resulting from taking methylfolate do harm to the fetus (if I’m pregnant)? Please help me. I live in a very small town and knowledge on MTHFR is very poor.

  35. John February 29, 2016 at 3:11 am #

    Please help. I’m heterozygous for both mutations. I have one copy of both mutations. I was put on 15 mg of Deplin and it kicked me into overdrive, along with the other medications I was taking. I have gotten off of the other meds. When I try to lower the Deplin I get bad heart palpitations (PVCs). Magnesium helps a little bit. This is ironic because usually when you go on Methylfolate you get PVCs and when you go off it, they go away, but I’m the opposite. Can anyone explain that. Also, I have tight calves and pain in my hamstrings and abs. Please give me advice.

  36. leela February 29, 2016 at 4:41 pm #

    My name is leela and i was taking Metnax but now I stopped. I am having dizeness and lost my balance. Do you have any idea it is because of not taking Metnax

  37. Ariel March 8, 2016 at 2:02 am #

    Hi Dr. Ben,
    I am homozygous a1298c. I’ve started taking your seeking health prenatals and those seemed to work alright. After about a month I had my folate levels and b12 levels checked by a doctor. Folate was at 20 (I was on normal prenatals with FOLIC acid before my diagnosis) and b12 was at 359 so I ordered the active b12 and L-5-MTHF as well as we felt my b12 should be in 600-900 range if I want to conceive. I also take baby aspirin 81mg just to see if it helps. Homocysteine levels were at 7.

    Since I found out about all of this and have started supplementing and such.. I’ve had symptoms. My period is irregular (very unusual for me, it is always regular and on time, just very clotty). I have had severe headaches. And I’ve noticed rash like breakouts on my face and I’ve always had clear skin with no problems. Am I taking too much or what do you think may be causing these symptoms?

    Thank you in advance,

    • Dr Lynch March 8, 2016 at 6:36 am #

      Hi Ariel –

      I suspect you should stop taking the additional B12/folate and just take the prenatal.

      Try that and see how it goes.

      Also do read the ‘Methylfolate side effects‘ article.

      Taking 50 mg of niacin may help reduce the headaches also.

      Glad you are taking the right prenatal – folic acid is not what anyone needs.

      Do talk with your doctor about these thoughts above.

  38. Laurie Kowalski March 9, 2016 at 9:42 pm #

    I have just found out that I have both of the MTHFR mutations. My B12 blood level is pretty high (1800) is this related? My doctor has given me three injections of high dose b 12 and now I am a bit nervous that it was too much.

  39. Diane J March 25, 2016 at 3:57 pm #

    Hello and thank you for all you do.

    It was recently discovered that I have the MTHFR mutations C677T, homozygous, with elevated homocysteine, etc. Based on my research, it looks like I probably have severe histamne challenges as well. Have been chronically ill for years AND ALSO TAKING PLAQUINEL for that long for “undifferentiated connective tissue disease”.

    My PCP ordered 15 mg L Methylfolate from Methyl Pro. I took one two days in a row and developed “serotonin syndrome’ as per my PCP. VERY shakey, running a temp, out of sorts, very flushed. Felt like I was “on fire”. Still feeling the effects three days later after stopping them. Trying to decide what to do.

    My sense is that the long term dose of Plaquinel is really stirring up the pot, so to speak. Based on my research, I am attempting to taper off the Plaquinel all together. I feel like I am in over my head on all of this, though my PCP is supporting me as best he can. Am searching for an ND who is well-versed in methylation, etc.

    Would you suggest taking the L-Methylfolate every other day, and perhaps cutting in half or thirds? I just don’t know where to begin. And please don’t suggest taking niacin, as that is contraindicated with a histamine intolerance problem.

    • Dr. Aron March 28, 2016 at 9:38 pm #

      Diane – Dr. Lynch has a podcast titled How Much to Take? that addresses this question. Maybe this article onHistamine Intolerance will give you some ideas on where to start.

  40. Terri April 14, 2016 at 12:11 pm #

    In your discussion, Methylfolate: Taking too much a problem?, Michael G. asked a question about GLUTAMATE that went unanswered. I would be interested to hear your answer to his question and more about the relationship between glutamate, folate and niacin. I’ve also read on your site where you have stated that Niacin helps reduce/block glutamate, but you provide no additional information or references. Could you please answer Michael G’s question and address the issue of glutamate. Thanks

  41. Marie May 10, 2016 at 6:16 pm #

    Dr. Lynch, Can you please help? I am so confused. For years I have “minor” but strange symptoms and so my Dr. would send me to different specialists and all would say it’s from anxiety. Then the anxiety would get worse and now I just worry all the darn time. Well, I’ve had four kids and of course taken the normal OTC multi-vitamins. I found out after my 4th baby that I have a MTHFR mutation. I was referred to a hematologist that said “of the three types of mutations you have the middle one.” He tested my homocysteine and it was 5 or 6. He told me not to worry and that was over. But now that I am reading about it, most of my symptoms are on the MTHFR list. A friend that is a dr. wrote me a prescription for the generic Deplin (Breckenridge.) She said take the higher dose, your body will get rid of what it doesn’t need. I would much rather just start with a multi-vitamin with the right stuff in it. What is the easiest way to start? Would jumping right in at 15 be too much. I read this entire chain on “methyl trapping” and I’m not interested in that business. Thanks so much for reading this!

    • Vanessa June 9, 2016 at 6:39 pm #

      If you want a good source of information on this topic I can recommend a good book for you. It is called Nutrient Power: Heal your biochemistry Heal your brain. By William Walsh. This is probably one of the best sources of information on the topic of methylation and the common imbalances that lead to mental health issues like anxiety. There may be more to the picture than just a genetic mutation.

      Unlike you, I did not go the genetic testing route. Walsh makes the case that this will not actually tell you what is really going on, he advises an affordable panel of tests that looks at end products rather than genes. He has a lot of talks on Youtube as well, if you want to check him out for more info on common problems associated with methylation imbalances.

      From one woman to another, I would also advise you to be careful with those multivitamins. When I did Walsh’s testing panel I found out I’m overmethylated with copper overload and zinc deficiency. I used to feel way worse after taking multis – and now I know why, it was because of the added copper. Most people take multis and think they are going to improve their health, when in fact you might be making things worse. It is better to find out what your actual needs are before starting to supplement. If you’ve had a few kids, that is one factor that can certainly raise copper levels in the body (high levels of eostrogen does this), so it may be worthwhile to get tested and read more about it. Here is one article on how copper overload/zinc deficiency can affect mental health, cause anxiety, fatigue, hypersensitivity, insomnia and number of other issues.

      Here is an article written by a psychiatrist about the problems associated with copper overload. There are a lot of other good ones on this topic on the internet.

      Wishing you well and hope you can turn things around 🙂

  42. Tawnee Temple June 6, 2016 at 2:20 pm #

    Hello, I have read your article and wondered what the ill effects are for those with bipolar are? I saw you mention this a bit at the end, and I was diagnosed with cyclothymia, a slight case on the bipolar spectrum. I have been taking Deplin 15 for this per my psychologist. I have been on it for about 1 year and was searching for reactions to too much of it, since I have been taking it so long. I have read on other articles that I should be taking a good b-complex as all the B vitamins are needed with this particular one? Thank you for your advice.

  43. J June 12, 2016 at 7:12 am #

    Please help! I almost died from severe methyl trapping with meth12 injections 3 yrs ago, it activated life-threatening chronic illnesses,including tick-borne infections, CVID, etc. of which I am still recovering. I’ve been on a methylation protocol since then. About 2 months ago my Dr. raised me from 5mg 5-MTHF to 50mg 5-MTHF (no B12 at all, I have the B12 mutation too). I felt amazing for a while, then started to get some weird acute symptoms, then things got progressively worse and if I didn’t know what was happening, I’d be in the hospital right now. I have severe neurotoxicity and neuroexcitation, that create almost constant seizure like episodes. It’s getting progressively worse, I have a severe autoimmune, immune and biochemical reactions. I’ve been taking Niacin at 100mg for three days every two hrs to no avail. I have tried all the things in both your articles, Hydroxyb12, Curcumin, Glutatione, etc. 5-HTP makes me worse. Even though according to my SNP’s I’m not supposed to take methyl b12, I’ve read that is the only way to reverse this. Is this true? If so, what dosage? Or what should I do? Your help will be endlessly appreciated. Thank you!

    • Kelly November 28, 2018 at 1:52 pm #

      Methyl-trapping happens where one has too much folate and not enough B12, period.

      Your doctor should NEVER have raised your methylfolate dose so high, especially with ‘no B12 at all’. You’ve probably cut way back on your supplements by now, but for others, it’s wise to try small amounts of each supplement ONE AT A TIME, so you know what’s causing what.

      Anyway, methyl-trapping occurs because of insufficient B12 to handle the folates.

  44. Frank August 6, 2016 at 8:37 pm #

    Hi Ben, very interesting about the niacin and glutamate/ gaba relationship.

    I recently was taking a supplement high in glutamic acid (collagen) along with other amino acids…
    I noticed a huge spike in anxiety. Would b6 and niacin help reduce this? Is my reaction an indication of anything in particular?


  45. Jan September 21, 2016 at 7:46 pm #

    Hello Dr Lynch,

    I will try to keep this very brief, I’m compound heterozygous for MTHFR.
    I have been feeling very miserable for the last 5 years with no desire to do anything and just going through the motions of just going to work, ( fortunately i can drag myself there).
    On my most recent visit to the doctor he gave me for the past 3 days, Hydroxy B12 Lozenge and NADH + CoQ10 and L-5-MTHF Lozenge, with no great change in my state of mind i suddenly got an itchy rash on the insides of my arm and now starting down my legs.
    I did take some niacin but that has not really done anything for me, my dr at work recommends zyrtec, should i try the zyrtec to see if it helps or should i just try and wait it out?
    any advice would greatly be appreciated.

  46. whisperingsage September 21, 2016 at 9:50 pm #

    Hi folks;

    I was excited to learn about MTHFR and what I could do about it, I took methylfolate OTC before I actually got my 23 and me results back. I felt better on 5 mg of methylfolate. My results came back double positive.

    I have been questioning the rarity of MTHFR for some time however. One of the MTHFR docs found that 90% of her pts were positive and showed improvements with methylfolate.

    Then this year (2016) i read that they just discovered that rats are quite able to process folic acid and humans are not. So that solves that problem. Simply being human makes us not process folic acid well, so no big surprise. Now I suppose it will take another 50 years for docs and vitamin suppliers to get the memo.

    So I have dumped my favorite Whole Food Multi, and notified the company of the new info and urged them to provide natural folate instead of folic acid, as that is probably clogging up the works. On the plus side, I am no longer bound to buy expensive methylfolate- I can buy cheaper folate and use whole food sources like bee pollen and nutritional yeast, and liver without fear now.

    Another new thing I tried that helped is something i learned in the Homocystiene revolution that a different thing was happening- in addition to the fake folate. A coauthr is a veterinarian and without naming Round Up as the culprit, noted that the livestock industry had created TMG- TriMethylGlycine- specifically to detox them from a GMO feed (Round Up Ready corn or alfalfa or sprayed onto wheat, oats or barley to dry it) , and I am tankful e mentioned it, it has cleared up a lot of my problems I have been struggling with for years. The implication that he didn’t want to outright say was that the glyphosate (Round Up) messes with our folate metabolism. Just as I suspected.

  47. Jaime McMullin September 24, 2016 at 5:17 pm #

    Hi Dr. Could you lead me to an article on what methylation trapping is. I recently started seeing someone who lead me to to the gene mutation, which i have, methylfolate and b12 (injections), but my blood work just came back as being extremely high in folate amd b12. It’s also high in choline. I have felt totally miserable before and after I started her supplements so no clues there. I’m also somewhat low in iron, d, and magnesium, but not to the Standard clinical levels but almost. Everything else seems okay although my reverse t3 wasn’t tested. I’m completely and utterly exhausted at all times. Frequently can’t think straight and have no motivation. Any info you can give me to help balance my body out would be greatly appreciated. Thank you!

  48. Carolyn September 29, 2016 at 5:33 am #

    Its interesting to me how people see things- I am one of them! Water is necessary-daily for good health, but watching someone standing on a beach while a tidal wave comes in, shows that there CAN be too much! Same as Vitamin D. We need it, and can handle a fairly high dose for awhile… but in the doses that help our bodies, it can kill rodents. Does that mean its poison or bad? Nope! It means we need to take the right amount. And this could be a different amount for each person depending on their circumstances, job, lifestyle, & genetics. It just makes sense. Let your fear drive you to find the answers.

  49. Leah Langowski January 8, 2017 at 12:53 am #

    The link seems to be incorrect, but I believe I found the product at

  50. Jean February 13, 2017 at 3:02 pm #

    Hi, I have the C677T mutation so started on l methyl folate, I cannot tolerate it, I ache and feel sick. So I thought I would try NAC a few months later and have the same side effects as I did on l methyl folate.

    I was dx’d with Hashimoto last year and want to heal my body with the help of diet and supplements. What should my next supplement be? I have read that sometimes we need to fix something else before we take l methyl folate. I thought of trying l thiamine next. Thanks in advance for your response.

  51. Leslie LeCornu February 16, 2017 at 8:41 pm #

    I want to buy methyl folate and don’t know which one to buy. I am getting Methyl cobolomin shots right now and want to add to that with methylfolate. I am MTHFR a1298c and hyper sensitive to everything including vitamins. Isn’t there a methylfolate that is 400mg that I can cut in half? I can’t find it.

  52. Garrett February 22, 2017 at 10:16 pm #

    Hi Dr. Lynch

    I am homozygous for the MTHFR mutation. I have major depression and depersonalization. I’ve been taking l-methylfolate and 2,000mcg of active B-12 for about 2 months now. I moved up to 30mg on the l-methylfolate about 3 weeks ago and definitely noticed an improvement. Can I keep going up in dosage and see if I continue to feel better? Would it be completely crazy to go to 45mg or even higher?


    • Dr Lynch February 24, 2017 at 1:47 am #

      Have you stopped dairy?

      Have you stopped folic acid?

      Both are needed to help clear the folate receptors. They may be blocked by antibodies and synthetic folic acid thereby requiring higher doses of MTHF.

  53. Robert March 4, 2017 at 3:43 pm #

    I started to take Cerefolin NAC about 5-6 months ago. I am working with an integrative MD to improve my cholesterol & other factors. At the time I was taking 10 mg of Lexapro. Within about 2 weeks I had a panic attack. My doctor said to go off of the Lexapro which helped. For the next several months I felt great. About a month ago I started to feel anxious & experience pressure headache mainly in the back of my head. Since then the symptoms have worsened & my anxiety level is off the charts. I’m having panic attacks more often. For my pressure headache I tried a chiropractor thinking it may be a Neck issue. I went to an ENT think it’s my sinuses. I’m going for a catscsn of my sinuses on Monday. I’m even going to my eye doctor on Monday thinking it’s from not wearing my glasses & squinting too much. I spoke with my integrative MD last week and his theory is that I may be “over methylated”. So as of Monday I stopped taking the Cerefolin cold turkey but the symptoms have not improved. I’ve been reading a lot on the Internet and I seem to have a lot of the symptoms of being “over methylated” but I’m perplexed because I stopped taking it now for six days. I ended up in the emergency room yesterday with a bad panic attack and the ER doctor says it could be many things but he felt that it may be a high dosage of either the methyl folate or certain B vitamins in the Cerefolin. He feels it would take more than six or seven days to get this all out of my system. As of last night I started to take my Lexapro again but as of this morning I’m still having symptoms. The only thing that seems to help is Clonazepam. Any help or advice would be appreciated.

    • Dr Lynch March 8, 2017 at 5:32 am #

      It could be that you need niacin – as explained here – Methylfolate Side effects

      Also may need molybdenum support from the NAC – as it may have increased sulfites.

      Do talk with your doctor about these recommendations.

  54. sharon March 12, 2017 at 6:17 pm #

    I have several MTHFR gene mutations – i’ve had to gradually increase my t3/t4 thyroid med. i’ve never been able to tolerate methylB12 – i take hydroxy and adenosylB12. recently a functional med doc told me i needed to start taking methyfolate if i wanted to improve my health. i cut the 1000mcg tablet into 3rd so got a probably 300mcg and also took about 125mg P5P. i was already having a severe insomnia problem – getting no more than 3-4 hours of sleep per night for 2 years already. within 2 days i was having severe panic attacks and not sleeping at all. my understanding is this could have swung my into a hyperthyroid situation although the doctor is insistent low doses and only for 2 days couldn’t cause this. i feel horrible and don;t know what to do. would you expect someone to have to downtitrate their thyroid med quickly if they are going to try to endure getting methyl vitamins on board?

  55. Jog March 29, 2017 at 2:04 pm #

    Hello Dr. Lynch.

    Could Tinnitus be Methylfolate side effects?

    I take this :

    I take 55 capsules in 5 months, at first take more.

    Thank you
    Best regards.

  56. Lexi M. April 2, 2017 at 6:45 pm #

    Dr. Lynch,

    My psychiatrist informed me that I have the C677T mutation 3 years ago. the only things I was told, and thus prescribed was L-Methylfolte 15 HTP in order for my body to absorb my psych meds. Nothing further was discussed w/ me about the multiple nutritional areas that needed to be addressed.

    Recently, I decided to see a nutritionistime. She discussed with me the importance of methylated versions of my B vitamins. She also added to my regimen Methylfolate 400 mcg. Im still researching the difference between L-methylfolate and Methylfolate. Is that too much folate? My migraines have increased to almost daily w/ nausea daily. What am I missing?

    • Dr Lynch May 29, 2017 at 5:15 am #

      You are likely experiencing migraines due to too much methylfolate. I’d talk with your doctors and stop using it for a few days.

  57. Joshua April 9, 2017 at 10:05 pm #


    I have recently been taking L methyl after having a test done… My problem is, if I don’t take enough, I begin to get palpitations. I take glutathione and niacin which also seems to help curve this as well as lemons. But I am not sure what is the root cause of all this?

  58. Tasha May 21, 2017 at 7:36 pm #

    Dr. Lynch, I experienced extremely severe side effects from taking a small amount of methylfolate over the last 7 months. Ended up in the emergency room. Doctors had no idea my symptoms were from l-methylfolate and they thought I was having a stroke. Then, my doctor actually advised me to keep taking it even after I told him about the emergency room visit. In the last week I finally realized that methylfolate was the source of my extreme issues. I’ve stopped taking methylfolate and have been taking niacin since I figured this out with the help of your website. How long should I continue the niacin? Do the side effects from taking too much l-methylfolate ever go away? Could it have caused permanent damage?


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