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 Sublingual Active B12 with Methylfolate.


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

  1. alison February 10, 2013 at 6:38 pm # Reply

    Hi- I am currently on 20mg of 5-mthf as per my doctor. Could this amount cause diarrhea? Thanks so much!

    • Aaron January 15, 2014 at 7:08 pm # Reply

      I have the same question. I am taking 30 mg / day and wonder if it is causing diarrhea.

    • Monique July 30, 2014 at 11:12 pm # Reply

      I just started 1 mg today. My Dr. suggested I start low and build up because I’m sensative to meds. I was going to email her today and ask if diarrhea was a side effect because I have been to the bathroom twice since I took the pill…… So more than likely, yeah.

  2. Sue June 9, 2013 at 2:15 am # Reply

    Hi Ben, thanks so much for this site and all the information here.

    I know this question is probably a little along the lines of “how long is a piece of string,” but is there any kind of recommendation for how many days you should leave between ramping up your intake? I began adding 200mcg of 5-MTHF one week ago to my regimen of supps and am totally jazzed to find that it is a large piece of my personal jigsaw puzzle. I feel so much better – less depressed and less poisoned as well. I’m feeling a bit nervous about increasing my dosage, even though I have niacin on hand to negate any side effects. Is a week between doubling the dose enough time? Thanks.

  3. Michael G August 4, 2013 at 4:15 pm # Reply

    Hi, can increasing 5-MTH cause depression instead of agitation? I don’t have the two common MTHF mutated genes, so I would assume 5-MTH would benefit me, although do I need it if I don’t have the mutated genes? I had my folate levels check and although they don’t provide a high end reference range, the number was elevated I think…I think it was in the 20’s, or low 30’s. Not sure if that is excessive or not. I mentioned in other posts that I have HIGH B12 circulating in my blood for over 1.5 years after B shots, and so I’m not sure if Methyl-B12 is good or not. If my body isn’t using it then maybe Methyl-B12 is required. But, if I have folate in my blood and I take 5-MTHF wouldn’t that get rid of my elevated B12? Unless something else is going on… Anyway, I recently increased my 5-MTHF to 3mg, (1mg to 2mg to 3mg) over a period of several days and felt a bit of mood increase, then I increased methyl-b12 felt okay, then at 3mg 5-MTHF and 4MG Methyl-B12 I started feeling more depressed. Not sure what caused it. I was also taking Methionine, and DMG. And I take Betaine HCI for digestion. Maybe I over did something, so I’m removing Methionine and DMG to see how it goes.. Thanks.

  4. Michael G August 4, 2013 at 8:07 pm # Reply

    Hi Doctor,

    So, I’ve been thinking…Why does Niacin help so much? I’ve read in a couple of places on your web site that it helps with over methylation by absorbing or using up methyl donors? Also, you mentioned it’s good for breaking down glutamate…

    Does over methylation cause an increase or a reaction with glutamate?

    I’ve posted my history in other places on this site, so I don’t want to go into too much detail but if you want more info from this particular posting site, let me know. Anyway, I’ve had bad anxiety, panic, then insomnia and depression. Now, it’s more of a agitated depression at times, low mood, feeling a bit panicky or impending doom kinda feeling, but more of a agitated feeling in the brain, not an overall whole body anxiety feeling. It’s mostly in my brain. I thought it could be high histamine, as the old school anti depressant seemed to make me feel 100% normal after 7 days at a low dose which is where it works as a strong anti-histamine. But that feeling only lasted part of a day, then 3 days later I was bad again….(I had just come off of Lexapro for four weeks which numbed my emotions but seemed to calm the anxiety a bit).

    Anyway, my anxiety, and panic have very low at this time overall. I’ve been taking Kavinace at night, theanine and taurine….

    I usually wake up in the morning feeling pretty good, some energy, mood okay but not great, then after breakfast, or lunch I go down hill. This is also after taking my amino acid mix. Which at different times contained different things. More recently I had added methionine, (before was doing SAM-e), DMG, etc… Anyway, I can be feeling half way stable not normal but better than the misery I was in a few months ago, then all of a sudden I can feel a drop in my mood coming on, and the agitation yukky feelings begin. Kinda feels like the feeling you get just before you get really nauseated when you have the flu, you just have this something isn’t right feeling and you may feel a bit depressed and hopeless feelings then once you throw up you feel really good. That’s kinda how it feels. Almost this slight dizzy, ill feeling, slight pressure maybe, and low mood.

    But, I noticed if I take a Taurine 500mg, that will give me a boost in mood and energy, as I feel some tingly euphoric feelings in my brain like something is lifting or clearing up. I hear that Taurine can help with glutamate. NIACIN the flushing kind does the same thing, helps with mood and energy even at 25MG or 50MG….

    So, am I dealing with over methylation, or glutamate issue? I’ve been eating a high protein diet due to wanting to limit my carbs, as there was some notion I could have some candida, but also some adrenal fatigue. But, I some times feel better eating carbs but not all the time. If I eat a high meat meal, with some veggies, I can feel worse. Why is that? Glutamate is a amino acid found in protein, so is this a glutamate response? I also was eating this chickpeas with some sort of Indian spices, and although it didn’t have MSG there were some other flavorings that might be similar. I also had some Thai food one time and a couple of days later I went into massive head fog, low mood, etc…. Was it a glutamate response?

    So, if Niacin breaks down glutamate, and that is my issue, what can cause high glutamate levels or an issue with glutamate to begin with, as I never had this issue before 1 year ago, unless it slowly built itself up.

    So, if I were to take 50mg of Niacin maybe with each meal, and found relief, would my depression lift? I’m worried I’d burn up too much methyl donors, although I did drop taking methionine and DMG, since I do take Betaine HCI for digestion which is TMG. Actually when I re-introduced taking Betaine HCI after a break, I seemed to have less issues of feeling more low energy and brain fog after eating protein. Is that because i wasn’t breaking down protein well, or was it because I was donating more methyl donors with it? But when I added Methionine, along with the DMG, and increased my 5-mTHF and Methyl-B12, things seemed okay for a short while then I got more depressed. I didn’t take methionine today, or DMG, at went down to 2mg 5-MTHF and 3mg Methyl-B12 and so far so good.

    So if Taurine and Niacin both give me some sort of mood boost and energy (mental) then it might seem Glutamate might be an issue? And might be why taking Kavinace (phenibut), taurine, theanine is helping with anxiety as it’s helping to lower glutamate and raise Gaba….

    I’m starting to wonder if glutamate could be my source of brain fog, low energy (mental), low mood, agitation (mental)…..I will experiment with low doses of Niacin…the flushing kind. I have the other form, but it doesn’t seem to have the same effect.

    I also read that L-Theanine can totally reverse Glutamate…was it damage or whatever in the brain…It can also increase gaba…So, I’m on Theanine, but I don’t feel any immediate reduction in anxiety or increase in mood by taking it like I do taurine or niacin, but I’m sure in the long run it can help heal and improve things.

    Sorry, I always write so much, but just want to provide as much info as possible as I’ve been ill for way too long and need some relief. Just trying to figure out what is the culprit.


    • Ben January 2, 2014 at 4:10 am # Reply


      I have been having the exact same problems as you. All my problems started after a bad reaction to Lexapro. Did your problems start after Lexapro? I never had any problems before Lexapro. Just mild anxiety. Thanks -B

    • Ben January 2, 2014 at 4:23 am # Reply

      Hello Michael G,

      Please email me @ I have been having the exact same symptoms…. Thanks -B

  5. Sara kaye August 27, 2013 at 9:35 pm # Reply

    I have 2 copies if the gene mutation. I have not started treatment yet. Where is the place to order methyl folate and methyl B12? What dose do I start with? How long will I be taking this regimen? I’m also waiting for this info from my physician.

    • Dr Lynch August 28, 2013 at 2:57 am # Reply

      Hi Sara –

      Please read this article on MTHFR protocol. It is generally helpful.

      The underlined products in the article will take you to product pages when clicked.

  6. HD August 31, 2013 at 9:45 pm # Reply

    Hi! I have not been diagnosed with a mutation that would require this treatment. I haven’t tried to get one yet for reasons listed below. But I have been diagnosed with IBS, fibromyalgia, problems with gluten and multiple food sensitivities, depression, and anxiety, which, from the research I’ve looked at, are all on the list as possible indications of a methylation problem. Many other things on the list run in my family, like schizophrenia, alcoholism and sugar addictions, and CFS. (pulling here both from your list and the presentation on MTHFR that I found by Dr. Neil Rawlins on YouTube. I was referred there by a friend of mine who is related to him). I took low-dose Cymbalta for the fibro for a few months, until my strict diet got my symptoms under control. But other than that, I have had a hard time pursuing treatment because we have moved states, and the doctors that took years for me to convince that I was really in pain and not just a head case are no longer around. I’ve started over with new doctors who, for all I can tell, don’t believe Fibromyalgia exists at all. The Dr. I just left didn’t even believe I could be sensitive to so many foods. How on earth could I convince him to help me get treatment trough a vitamin, or give me a blood test?

    So I tried starting it on my own the other week, with 1 mg methylfolate and methyl B12. Yes, now I know that was too high. After about 3 (really awesome, happy, and energetic) days, my fibro symptoms suddenly kicked up (mostly aching joints). Then I got nauseous, and cranky, and headaches. I found your site, saw that I had probably overdosed, and saw the niacin recommended to help. I only took 100 mg–a fifth of a capsule–but after the first time, I got nauseous. After the second time, I was nauseous and burning up, lying on the floor and moaning. And then I got really tired. At least I slept well for once! But I had low-grade nausea and was just out of sorts for several days after stopping all supplements. So, I’m thinking no more niacin for me, and starting again with 100 or 200 mcg methylfolate. I was like this with the Cymbalta too; VERY sensitive, taking only half of the lowest dose because anything higher gave me severe full-body spasms. My question is, why? Why am I reacting so much to such small amounts, even of the niacin? You said that most people don’t experience these reactions, and that most reactions stop within 24 hours. Well, most people don’t get convulsions from just 30 mg of Cymbalta, or obtain benefits from just 15. Something’s up, and I’d love to know what.

  7. Eric October 15, 2013 at 1:08 am # Reply

    I have a question regarding the bipolar snippet. I have had one doctor say iI am bipolar and one who says no. I am also heterozygous A1928 and starting at the recommended low dose of methylfolate and methyl b12. So….. If I am bipolar should I take more niacin, try another route, or what. I don’t want this making things worse. Thank you

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

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

    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”.


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

    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

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

    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 # Reply

      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 # Reply

        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!!

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

    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?


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

    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!

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

    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,


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

    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

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

    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 # Reply

      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.

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

    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 # Reply

      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 # Reply

        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 # Reply

          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.

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

    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 # Reply

      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 # Reply

        Doesn’t niacin increase histamine?

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

    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!


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

    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?

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

    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!

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

    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.

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

    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???

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

    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

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

    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!

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


    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.

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

    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.

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

    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 # Reply

      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.

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

    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 # Reply

      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.

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

    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 # Reply

      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 # Reply

        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 # Reply

          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.

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

    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.

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

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

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

    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 # Reply

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

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

    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


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