L-methylfolate has many different names which adds to confusion.

Those with MTHFR mutations scan labels, read websites or listen to their doctors rattle of conflicting terms for a nutrient they really need.

Update June 26, 2019:

Note how the label below illustrates:
Folate (this is where you need to pay attention – inside the paranthesis).

See how it shows (as Quatrefolic (6S) etc)?

That is the best form of methylfolate.

This is what you want.

L-Methylfolate Label
















I used to use Merck’s L-5-MTHF from calcium but I switched to Gnosis.

Be careful about other types of L-methylfolate are out there.

There are quite a few.

Understanding which form of methylfolate is best must be clear.

Why all the confusion?

Because there are so many different terms used for methylfolate.

By the end, you will understand everything you need to know about methylfolate.

More significantly – you will understand how to pick the right form of methylfolate.

Terms often used for methylfolate are:

  • Methylfolate
  • L-MTHF
  • L-Methylfolate
  • L-Methylfolate Calcium
  • D-Methylfolate
  • D-5-Methylfolate
  • Levomefolic Acid
  • Metafolin
  • 5-MTHF
  • 5-Methylfolate
  • 5-Methyltetrahydrofolate
  • L-5-MTHF
  • L-5-Methyltetrahydrofolate
  • 6(S)-5-MTHF
  • 6(S)-5-Methyltetrahydrofolate
  • 6(R)-5-MTHF
  • 6(R)-5-methyltetrahydrofolate
  • Quatrefolic (6S)-5-methyltetrahydrofolate
  • Quatrefolic

Are these forms of methylfolate all the same?

Are any of these forms of methylfolate the same?
Yes. The same forms are grouped together here. These forms are synonymous with each other:

  1. L-5-MTHF = L-5-Methyltetrahydrofolate = 6(S)-L-MTHF = 6(S)-L-Methyltetrahydrofolate
    • Good forms which are well absorbed
  2. L-Methylfolate Calcium = Metafolin = Levomefolic Acid
    • Good forms which are all well absorbed
  3. D-5-MTHF = D-5-Methyltetrahydrofolate = 6(R)-L-MTHF = 6(R)-L-Methyltetrahydrofolate
    • Avoid these (learn why soon…)

Then what are the other forms of methylfolate?

The other forms of methylfolate may or may not be 99% pure biologically active methylfolate.

  • 5-MTHF
  • 5-Methylfolate
  • 5-Methyltetrahydrofolate

How come these may or may not be 99% pure biologically active methylfolate?
These forms do not specify the L form (or 6(S) form) of methylfolate; therefore, you do not know what you are ingesting.

The forms of methylfolate not specifying L or 6(S) likely contain more than 1% of the D form of methylfolate.

What is the difference between D and L forms of Methylfolate?
In organic chemistry, one learns compounds may have the exact same molecular formula and sequence of bonded atoms but differ three dimensionally. These compounds are known as steroisomers.[1]

There are two common forms of sterioisomers:

  1. Enantiomers:
    • mirror images of each other, such as our hands.
    • same physical properties
    • may have different biological effects
  2. Diastereoisomers:
    • not mirror images of each other
    • rarely have same physical properties
    • have different biological effects

Methylfolate has stereoisomers in the form of diastereoisomers.

The forms of methylfolate that are biologically active are:

  • L forms
  • 6(S) forms
  • L-5 forms
  • Metafolin
  • L-Methylfolate Calcium
  • Levomefolic Acid
  • Quatrefolic

The forms of methylfolate that are NOT biologically active are:

  • D forms
  • 6(R) forms

The forms of methylfolate that may or may not be biologically active are the:

  • forms which do not specify L, 6(S) or trademarked name of Metafolin
  • 5-MTHF
  • 5-methylfolate
  • 5-methyltetrahydrofolate

From the package insert of Metanx, a prescription drug using biologically active Metafolin[2]:
“L-methylfolate or 6(S)-5-methyltetrahydrofolate [6(S)-5-MTHF], is the primary biologically active diastereoisomer of folate and the primary form of folate in circulation. It is also the form which is transported across membranes into peripheral tissues, particularly across the blood brain barrier. In the cell, 6(S)-5-MTHF is used in the methylation of homocysteine to form methionine and tetrahydrofolate (THF). THF is the immediate acceptor of one carbon units for the synthesis of thymidine-DNA, purines (RNA and DNA) and methionine. About 70% of food folate and cellular folate is comprised of 6(S)-5-MTHF. Folic acid, the synthetic form of folate, must undergo enzymatic reduction by methylenetetrahydrofolate reductase (MTHFR) to become biologically active. Genetic mutations of MTHFR result in a cell’s inability to convert folic acid to 6(S)-5-MTHF.

Metafolin® (L-methylfolate calcium) is a substantially diastereoisomerically pure source of L-methylfolate containing not more than 1% D-methylfolate which results in not more than 0.03 milligrams of D-methylfolate in Metanx®

D-methylfolate or 6(R)-5-methyltetrahydrofolate [6(R)-5-MTHF] is the other diastereoisomer of folate. Studies administering doses of 2.5 mg per day or higher resulted in plasma protein binding of D-methylfolate higher than L-methylfolate causing a significantly higher renal clearance of L-methylfolate when compared to D-methylfolate. Further, D-methylfolate is found to be stored in tissues in the body, mainly in the liver. D-methylfolate is not metabolized by the body and has been hypothesized to inhibit regulatory enzymes related to folate and homocysteine metabolism and reduces the bioavailability of L-methylfolate.”

Example of why all this is important to know
A supplement company has a supplement called, “5-MTHF”

Let’s say this supplement states it contains 10 mg of 5-MTHF.

One assumes this contains 10 mg of biologically active L-methylfolate.

Don’t assume.

The likelihood of it containing 99% of the biologically active form of L-methylfolate is slim to none.


Prescription drugs such as Deplin contain 99% active L-methylfolate as Metafolin. Deplin provides two potencies of L-methylfolate: 7.5 mg and a 15 mg

This much L-methylfolate is VERY potent and must be prescribed by a physician.

Merck does not allow any supplement company to provide more than 1 mg of their L-methylfolate in a stand-alone supplement. If L-methylfolate, as Metafolin, is included in a formula along with other nutrients, then a maximum of 800 mcg is allowed.

What amount of this 10 gram 5-MTHF supplement actually contains the biologically active L-methylfolate?
It is not known without requesting a lab report.

The likelihood of it containing a significant amount of the inactive D form of methylfolate is high.

Remember, the D form of methylfolate is undesirable and actually may reduce the bioavailability of L-methylfolate.

What to do?
Two things:

  1. Request a prescription from their physician to obtain drugs containing Metafolin.
  2. Look for supplements specifying the amount of active L-methylfolate.

Drugs containing Metafolin are:

  • Metanx
  • Deplin
  • Cerefolin
  • CerefolinNAC
  • Neevo
  • NeevoDHA

Supplements with Methylfolate
One must carefully evaluate supplements specifying the use of Metafolin, Quatrefolic or the L form.

If the supplement does not specify on the label that it uses Metafolin, Quartrefolic or the L form of methylfolate, then it is not recommended to use without first inquiring directly to the manufacturer. A manufacturer may have named their product as 5-MTHF and use the pure L form of methylfolate; however, one must inquire to be certain.

Quatrefolic: What is this?
This is a new form of methylfolate that uses glucosamine instead of calcium to bind the L-methylfolate. Quatrefolic is also a quality form of L-methylfolate.

This is the form of methylfolate that I use in all my formulations.

Key Points about Methylfolate:

  1. Not all methylfolate is the same
  2. The D form of methylfolate actually is undesired and should be avoided
  3. The L form of methylfolate is the desired form
  4. There are many names for the same thing. Understand them.


Supplements using the pure form of L-Methylfolate

Seeking Health uses purely the L-methylfolate as Quatrefolic by Gnosis.






  • Carie says:

    Hi, Dr. Lynch!
    Thanks for all your info from your research.
    My multi for women over 40 is listed as Folate(500 mcg as Calcium Folinate and 500 mcg as L-Methyltetrahydrofolate from L-5-Methyltetrahydrofolinic Acid, Glucosamine salt) 1 mg.
    I heard your webinar with Dr Christianson that hypothyroid patients are very likely to have the MTHFR mutation. I have been avoiding synthetic folic acid as a result.
    Would this Calcium Folinate be “safe”. Thanks.

    • Dr Lynch says:

      Hello Carie –

      Yes – calcium folinate can be very useful as it supports DNA base production. Methylfolate supports SAMe production and homocysteine recycling.

      Since the Methionine synthase enzyme is so picky, it is best, in my opinion, to support people with folinic acid a bit as well.

      If you are feeling good and your doctor agrees, then should be good to go.

      • Josh says:

        Dr. Lynch,

        I first want to commend and thank you for providing resources about MTHFR and the hard work and effort you are putting into the effort to spread awareness.

        I do have one follow-up question based on this post.

        The supplement (a Thorne product) that I am taking to help my own health issues has L-5-Methyltetrahydrofolate from L-5-Methyltetrahydrofolic Acid, Glucosamine Salt. Is this the same thing as the Quatrefolic you discussed in your post?

        If not, is this form of folate still effective (bio-available) for helping with MTHFR issues?

        Thank you so much!

        Best regards,

        • Shannon says:

          Did you get a reply to this questions. I just bought a supplement where the front reads: L-Methylfolate, but the back label reads: folate as (6s)-5-Methyltetrahydrofolic acid, glucosamine salt. My son is homozygous for MTHFR and I was told to get optimized folate and b12 and he also has a corn, soy and wheat sensitivities.

        • Matt says:

          I’m curious to know the answer to this question as well. My guess is that it is bio-available, since it is in a ‘methylated’ form.

  • Alex says:

    Hi Dr. Lynch. Thank you for all you do. The information on your website has helped me identify that I have a MTHFR mutation and I’ve been working with my primary care physician and taking a quality methylfolate supplement.

    In this article, you mention “steroisomers” and how we need a certain type of methylfolate to make sure we get the right form. I’m wondering if there are other vitamins/mineral supplements that could also have non-active, undesirable forms.

    I take a variety of supplements, and am curious if there are inactive forms of other nutrients – B12/methylcobalamin, B6/P5P, etc.

    Thank you!

    • SunnySky says:

      Unless I misunderstand your question, methylfolate is altogether different from B-12, though still one of the B vitamins. Don’t confuse the two.

  • Simon says:

    Dear Dr. Ben,

    I was wondering about the potency bioavailability of L-methylfolate as Metafolin , or whats used in Deplin vs Quatrefolic . If Quatrefolic is just as potent (or more) as you suggest, mg. vs mg. why is Quatrefolic alot less expensive?



  • Chris says:

    Dr. Lynch,

    I’m heterozygous A1298C. The person who diagnosed me and ordered the lab testing is a very well read nurse practitioner and she has a compound diagnosis herself. She wants me to go on Deplin and B12 (methylcobalamin form). I found an affordable and good formulation of methylcobalamin that I like. Unfortunately as you know, Deplin is VERY expensive, I still can’t figure why it is so expensive other than Merk took out a patent on it and there is only one “authorized” generic that is cheaper but still expensive. I asked her about several other products that appear to be legitimate to me and are much more affordable. She went to a conference of sorts for medical professionals and afterwards said, “There are no products that can be taken in place of Deplin or the generic L-Methyfolate Calcium made by Breckenridge… Now I have a hard time swallowing that and I have my doubts about that statement.

    I have looked at your guidelines above as well as in your introductory video at the home page of mthfr.net. I have tirelessly looked for other products with methylfolate and they are also expensive (like Deplin), illegitimate forms of methylfolate, or aren’t the dose my NP wants me on.

    I have found several products (see links below) called MethylPro. The methylfolate seems to meet your guidelines and criteria for the good form. They get their methylfolate from Gnosis S.p.A. They have both Quatrefolic and Extrafolate-S (both registered trademarks). I’m looking at the 10 mg dose. It looks like it’s based in Sisters, Oregon.


    My questions to you are:
    1. Are these legitimate forms of methylfolate?
    2. Knowing I already take B12, which MethylPro product, assuming these are legitimate, would you recommend (Extrafolate-S, Quatrefolic, Quatrefolic+cofactors)?

    If you would like there is helpful narrative about their products and a section on how it compares to Deplin: http://www.methylpro.com/more_info

    On another note, I guess Gnosis in the past had a labeling problem with the Extrafolate-S (see http://www.gnosis-bio.com/pdf/Corrective%20advertising%20letter%20for%20Extrafolate%20&%20Extrafolate-S.pdf) however, it appears they have corrected this under court order.

    I really appreciate any guidance you can offer on this matter to me. I also appreciate the wealth of information you have here and that it is free to all so that they may better their health.

  • Chris says:

    I forgot to mention I’m currently on Gabapentin, Doxepin, and methylcobalamin.

  • Val says:

    Hello Dr. Lynch,
    My understanding is that {6S} L-5 MTHF is processed from folic acid. It is a synthetic
    form of folate and that Formaldehyde is used in the distillation process to obtain this form of folate. Could you please clarify all of this!!! Of course my concern is in the possibility of ingesting any formaldehyde residue.

    Many Thanks,

  • Sucramdw says:

    So what does it mean for this whole foods Woman’s multi to have real Folate as 100% Organic?? http://www.herbalprovider.com/Wholefood-Womens-Multi-Organic

    Thank You!!

  • Michelle says:

    Seeking Health Kids Optimal Multivitamin lists Folate as 5-methyltetrahydrofolate. It doesn’t specify D or L and doesn’t mention Metafolin. You put that type on your questionable list.

  • Dale says:

    What do you think about the use of Rheumate?

  • rex says:

    I was hoping that you would have references to your statements about the biological activity and effectiveness of the various forms of folic acid so that I can share this info my wife’s physician. So I went onto PubMed.com and typed “folic acid and l-5-methyltetrahydrofolate ” in the search section. There are many studies showing that L-5MTHF supplements are effective. Some say that it is better or at least the same as a general form of folic acid supplementation. Obviously, L5MTHF would be far superior for those who have issues with folic acid. here are 3 articles that I found regarding L5MTHF effectiveness:

    1: Pietrzik K, Bailey L, Shane B. Folic acid and L-5-methyltetrahydrofolate:
    comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet.
    2010 Aug;49(8):535-48. doi: 10.2165/11532990-000000000-00000. Review. PubMed
    PMID: 20608755.

    2: Akoglu B, Schrott M, Bolouri H, Jaffari A, Kutschera E, Caspary WF, Faust D.
    The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total
    serum homocysteine level in orthotopic liver transplant recipients: a
    double-blind placebo-controlled study. Eur J Clin Nutr. 2008 Jun;62(6):796-801.
    Epub 2007 May 23. PubMed PMID: 17522618.

    3: Venn BJ, Green TJ, Moser R, Mann JI. Comparison of the effect of low-dose
    supplementation with L-5-methyltetrahydrofolate or folic acid on plasma
    homocysteine: a randomized placebo-controlled study. Am J Clin Nutr. 2003
    Mar;77(3):658-62. PubMed PMID: 12600857.

  • Catherine says:

    Hi, Dr. Lynch. Thank you so much for explaining about the different forms of folate. If the generic equivalent of Deplin 15 mg (L-Methylfolate Calcium manufactured by Virtus) states it has less than 1% of D-methylfolate, is this safe to take for someone who is compound heterozygous MTHFR? I had planned to take 1/4 of the tablet daily along with methyl b-12. Having just learned about the harmful effects of D-methylfolate on your website, I am not sure what to do. This stuff cost a lot of money, but should I throw it in the trash? Can you please advise? Thank you so much!!

  • Adrian says:

    My question is does anyone notice a recurring theme here with the companies manufacturing these supplements? Very few that I have found have actually been worth much.

    I suffer from mild depression and have had very bad experiences with anti depressants. They actually make the depression worse. I have a great doctor though who tested my genes and found several traits that predispose me to depression and not responding to serotonin reuptake inhibitors. He said that I was lacking certain chemicals that helped me to absorb folic acid. He told me that it was necessary to have the proper amount of folic acid in order for my body to create serotonin, dopamine and other chemicals that helped ones moods and depression. He put me right on L-Methylfolate Calcium and said that he wanted to give it a try. Within a few weeks, I was feeling a bit better. Within a few months I was happier in general than I have ever been. Great! I was able to get excited about fun things that were coming up and remain stable even in bad times.

    My girlfriend suffers from similar symptoms of light depression. Her doctor puts her on Anti depressants and she gets worse just like I did. She can see what the Deplin has done for me. She goes to her doctor to ask about L-Methylfolate and he tells her that she is crazy. He ups her dosage of anti-depressant and she gets even worse. I discuss this with my doctor who unfortunately does not accept my girlfriends insurance. He cant believe that her doctor wont just try the Deplin. The more I have read up on this though, the more I have found that there are LOTS of doctors out there who refuse to try L-Methylfolate. Why is this? People are being forced to find alternatives on the internet and other places that are nowhere near as effective as the prescription. These companies are getting rich and doing no good for their patients.

    Why are doctors so afraid to leave the confines of conventional Anti-depressants and try something that is mostly natural? We aren’t hippies trying to be All Natural just for the heck of it. This vitamin really does some good. Especially when you can get the purest form possible. I just don’t know why so many are so against helping us obtain that.

    My doctor is retiring soon and I have been left to find a new doctor. A lot of these new doctors would put me on just about any chemical that I want, but the second that I mention the Deplin they have all told me “No, Just take B-12″ or ” you can buy supplements online that has folate in it” HUH!?!?!?!

    I am asking you for a simple thing here. L-Methylfolate Calcium. How about some OXYCODONE Doc? “Sure thing Adrian, but I’m not writing a prescription for L-Methylfolate” Whats wrong with this picture?

  • Natasha says:

    Hi Dr, so here goes…long story short…I have suffered from sensorial neuropathy and anxiety since my plastic surgery procedure 5 months ago. I have been tested for everything imaginable and nothing to explain the neuropathy so my Neuro had me take Metanx. When I started researching the drug medication after experiencing itching, dizziness, and irritability I started reading about MTHFR. I had my PCP test me for it and found out I’m homozygous C677t. I tried to quit the Metanx and experiment with Country Life Coenzyme B Complex (anxiety, itchiness), Garden of Life Kind Organic Women’s Once a Day (instant Niacin-like reaction of red and itchy flush), Real Food Organics Prenatal Daily (anxiet, itchiness), Seeking Health Optimal Multivitamin Chewable (dizziness, depression, anxiety). Even taking supplements for my neuropathy such as acetyl l carnitine backfired by giving me dizziness and anxiety for 2-3 days. I have been juicing for about 2 months and noticed that adding the spinach makes me itchy! Therefore I am now down to just taking my Vitamin D and Omega 3 supplements and juicing. None of my doctors are knowledgable enough about my MTHFR to help me. Someone suggested that an added ingredient in the Metanx is causing the itching and being off of it so long with my MTHFR issue is not addressing the neuropathy. I have noticed feeling more neuropathy lately. Could you recommend a doctor for me to see in the Miami Rea that can help me get on track?

  • Deb says:

    I am looking for foods that have the active form of folate, my husband has one of the MTHFR defects and my daughter has both.mLooking for natural food source to supplement their diets. I live on a farm and if I can plant berries that have this will grow my own… But need to know if ALL berries have the active form… I have been told blackberries and raspberries do, just not sure about strawberries and blueberries. or any other types of berries. Any help would be appreciated.

  • Samantha McRorie says:

    I use a Thorne Multi – B product – easiest for me to get in Canada as I can get it from my naturopath and I don’t have to pay shipping.

    I have 2 of their multi-B’s right now. On one label it says: Folate (L-5-Methyltetrahydrofolic acid) – which I do not see on your list. Yes it has the L and the 5 but why would it say folic acid at the end?

    The other product says Folic Acid (5-Methyltetrahydrofolate). So this one doesn’t have the L. I am very confused by all of this and want to be sure I am using the correct folate since I am heterozygous for C677T.

    Do you have any advice on this?

    • Dr Lynch says:

      You need to have the L form or the 6S form. If they are not stating this, it may be racemic meaning that there are two forms in there of methylfolate. One of those forms is absorbed and used by your body and the other one is not.

      • Deb says:

        Husband and daughter had blood drawn, sent of to Clinical Pathology Labs, Inc. whom the Dr office uses. Mine was done by cheek swab. It was done by a company, DNASTAT Pharmacogenomic Testing Services.

        Would you expect mother to have one or these defects if child has both and father only has one?

      • Aleisha Phillips says:

        Is there a difference between L-5-methyltetrahydrofolic acid and L-5-methyltetrahydrofolate? I’ve seen both listed on labels.

  • Mara says:

    Would organic folate be tolerated as well as the good forms of folate for someone with MTHFR and COMT? Or could it still cause overmethylation. I’ve been taking an organic whole food multivitamin (Kind Organics), which say their folate (800mcg) is from organic lemon, but I’ve been feeling a bit off.

  • ing says:

    I just wanted to add my experience with different brands
    I tried three. Only one worked for me.
    Jarrow Quatrefolic had no effect at all.
    Solgar metafolin worked for some aspects of my health but caused irritability.
    Thorne 5-Mthf Extrafolate-S (uses Gnosis S.p.A.’s L-5-Methyltetrahydrofolate) works beautifully with added benefits on mood and sleep.

    Can you tell me why you say all active forms work the same when clearly all these different active forms work differently for me?

    Can you comment on Extrafolate-S, Im concerned over some things Ive read about it.

    thanks much

    • Dr Lynch says:

      Good points.

      They should work the same but clearly they do not with you.

      It also depends on the quality of the manufacturer – how do they handle the raw material, how do the encapsulate it, store it, how fresh, how seal it, delivery system?

      My company, http://www.SeekingHealth.com is switching to all Gnosis Quatrefolic and most of our products currently use that.

      I am not sure about Extrafolate-S but my first thought is that they use calcium salt vs glucosamine salt – like Metafolin. Also it may be racemic – I am not sure of the percentage of each isomer.

      • ing says:

        Thank you Dr Lynch for your response.

        I have done more research and seems Gnosis extrafolate-s is not recemic – from their website:
        “extrafolate-S® is the calcium salt of (6S)-5-methyltetrahydrofolate, and is suitable as a food ingredient.
        they also make “extrafolate – the calcium salt of (6R,S)-5-methyltetrahydrofolic acid.”

        I have found that the quatrefolic form of methylfolate gives me many of the negative symptoms listed as “side effects” on your website. For me personally -irritiblity, anxiety, racing heart, aching muscles, weak muscles, back pain) whereas extrafolate-s gives me only excellent results with added benefits on sleep and mood.

        I have found many people online commenting that this has been their experience as well with quatrefolic and would ask you to consider selling a supplement that contains extrafolate-s as an alternative to those who can not tolerate quatrefolic.

        Had I tried quatrefolic first I would not have believed that methylfolate therapy was for me and based on the negative reactions would not have continued supplementation nor would I have tried a different form of methylfolate because most websites claim all active form of methylfolate work the same.

        Thankfully my first try with a methylfolate supplement was with a brand that uses extrapolate-s and I had no side effects and could tell right away that it was indeed working for my symptoms.

        I fear many people who may be intolerant like I was may try quatrefolic first since it is what you and many other websites are endorsing based on the fact that it is the latest/fourth generation form of methylfolate and may give up based on negative symptoms, and not consider another form/brand of methylfolate.

        I feel like methylfolate in the form of extrafolate-s has given me back my life and I would hate for someone like myself to miss out only to not have found the right form of methylfolate that works for their personal chemisty.

        I would love to know what you think about my personal experience and would love for an article to be writen for those like me.

        Thank you very much for your response and consideration!

        • ing says:

          metafolin (solgar brand) was causing negative symptoms not quatrefolic.
          However quatrefolic (Jarrow) has no beneficial effect for me unlike like extrapolate-s.
          Sorry for the mix up.

          • Jeff says:

            Hi “ing”,
            Since you’ve tried various forms of active methylfolate I’m wondering if you have ever taken multiple forms of active methylfolate simultaneously on a daily basis?

            Do you know if the effectiveness of the folate is adversely affected or are there any safety concerns you’d have with taking multiple forms of methylfolate ?

            I’m planning on taking these two supplements when they arrive:
            L-5-MTHF 1000 from the “Seeking Health” company.
            and B-Complex #12 from “Thorne Research”.

            There is 200 mcg. of L-5-Methyltetrahydrofolic Acid, Glucosamine Salt and
            200 mcg. of Calcium Folinate in each of the B-Complex capsules by Thorne Research.
            1,000 mcg. of Quatrefolic(6S)-5-methyltetrahydrofolate, glucosamine salt contained in the Seeking Health L-5 MTHF capsules.
            Thank you very much!

      • Jeff says:

        I’m so glad to have found this excellent site. My physician suspected that I may have MTHFR mutations and ordered the blood lab test. I just received my test results back which show that I have both the C677T & A1298C mutations.

        I’m sure there’s a lot of factors that affect this question, but I’m wondering what is a good general starting dose of 5-MTHF for someone like me with both mutations?

        I ordered L-5-MTHF 1000 from your “Seeking Health” company.
        I also ordered B-Complex #12 from “Thorne Research”.
        I need to know if these three different forms of folate are safe to take together?

        There is 200 mcg. of L-5-Methyltetrahydrofolic Acid, Glucosamine Salt and 200 mcg. of Calcium Folinate in each of my B-Complex capsules by Thorne Research.
        I then plan on taking your L-5-MTHF 1000 from “Seeking Health” which contains 1,000 mcg. of Folate from Quatrefolic(6S)-5-methyltetrahydrofolate, glucosamine salt in the Seeking Health L-5 MTHF capsules.

        My doctor wants to prescribe me a large 15mg starting dose of folate, but after reading a little of the wealth of information on this site it sounds like this may be way too much with a high probability of causing adverse side effects.

        I’d sure appreciate your input on the recommended starting dose and to the effectiveness and safety of taking the multiple forms of folate I listed.

        Thanks in advance for your input, I appreciate it very much!

  • Bridget says:

    Dr. Lynch, can you explain the difference between just plain folate and methylfolate? (I understand the difference between folate and folic acid.) I am taking an organic, raw vegan vitamin formula that lists “folate” as one of the ingredients. But I am also taking a supplement that says “(6S-5)-5-Methyltetrahydrolic Acid.” A fiend says I shouldn’t take the vitamin with the folate because it could interfere with metabolizing the methylfolate. Thank you for your reply.

  • Pamela says:

    Dr. Lynch,
    Thank u for your remarkable information. My MD actually recommended it since I was diagnosed with heterozygous A1298c/A1298c. We discussed the methylation Plus that she recommends. But when I asked for a prescription instead, she said there wasny one available in a dose small enough. She mentioned 300 or 400mcg. I guess I’m wondering if you may know of one that she might not. She also mention the methylation plus will take care of my B 2, 6, &9 deficiencies all at once instead of having to take separate pills . I have very good prescription insurance. & would rathe go that route if possible due to finances. Will this be a lifelong requirement or would/could it resolve with the candida irradication ?
    Thank you

  • Judit B. says:

    Dear Dr. Lynch!

    I am MTHFR C677T homozygotes.I have polyneuropathia with a very late stage of chronic lyme disease ( + other lots of symptoms). I have been very ill for many years.I have done a Nutrahacker health info from my 23andme test. I am Hungarian and really can’ t imagine who could help me. I am 27 years old.
    I would like to ask you what kind of folate should I take if Nutrahacker “reports”me to avoid folinic acid and methyl donors! (methyl B12 too). I also have three kind of COMT gene and rs6922269, rs1801133, rs1805087, rs1802059, rs1801394 , rs7946, rs7925545, rs234706.
    A huge problem is nerve pain.I have tried taking Turmeric (300mg-600mg), but the pain increased insupportably so I have finished taking it.

    I just want you to help me a little bit.

    Thank you very much in advance: Judit B.

  • Sherry Goeke says:

    Dr Lynch,
    What about “folate” in whole food based vitamins, and more specifically Garden of Life raw vitamins?
    I have been unable to tolerate medium chain triglycerides in “Seeking Health” products.
    Thank you for your response.

    • Dr Lynch says:

      Sherry – if they don’t specify which form of folate it is, then I wouldn’t trust it. Medium chain triglycerides are derived from coconut oil – and the amount is very very small. Are you sure that’s the problem?

  • suzan says:

    Hi! Thank you for this article it is very helpful! I have been diagnosed with mthfr homozygous c677.. I am finding it hard to find methylfolate, can I supplement with folate ( pill not just naturally) and if yes what is the dosage? For folate or methylfolate. Would really appreciate some insight! Where i am from it seems lime they dont really consider mthfr as a problem! I have experienced already 2 miscarriages so i want to get it right this time. Thanks in advance.

  • sowmya says:

    Dear Dr.Ben Lynch
    Could you explain to me when does one use L5 MTHF or its various forms mentioned, versus Leucovorin? I understand that lack of 5mtf causes Cerebal Folate deficiency , but they supplement it with Leucovorin, I am trying to understand, what matters where? Thank you

    • Dr Lynch says:

      I’m not sure why they use folinic acid vs MTHF in those studies.


      As far as I know, folinic acid is needed to produce DNA bases and MTHF is needed for methylation – the general overview anyhow – they do other things as well – but those are the two major ones.

      Neurotransmitters need methylation to be formed and eliminated – the major ones –

      I need to research further if folinic acid plays a role specifically – as folinic acid – in neurotransmission. At this point, I am not aware of that but I could be just ignorant on the matter.

      • Sowmya says:

        Dear Dr.Lynch
        I got the answer from some of the moms who are working towards healing children with autism like me, from what I understood, Leucovorin would be converted to L5MTHF however if you have mutations etc, then the conversion would be affected or slowed down..here is what someone answered, I am sharing it incase someone else would be interested to know..Leucovorin does not contain methyl groups and thus, this form does not participate directly in the methyl cycle. However, it is a valuable player in generating pyramidines and it can be transformed into 5-MTHF. Of course, this is best accomplished if a child does not have an MTHFr polymorphism in which that enzyme is less efficient. The MTHF reductase will still transform Leucovorin into 5-MTHF, albeit somewhat slower. This can be especially hindered by homozygous polymorphism in that particular gene.

        Folinic acid (INN) or leucovorin (USAN), generally administered as calcium or sodium folinate (or leucovorin calcium/sodium),……..Folinic acid is a 5-formyl derivative of tetrahydrofolic acid. It is readily converted to other reduced folic acid derivatives (e.g., tetrahydrofolate), and, thus, has vitamin activity that is equivalent to that of folic acid. However, since it does not require the action of dihydrofolate reductase for its conversion, its function as a vitamin is unaffected by inhibition of this enzyme by drugs such as methotrexate.
        Folinic acid, therefore, allows for some purine/pyrimidine synthesis to occur in the presence of dihydrofolate reductase inhibition, so that some normal DNA replication and RNA transcription processes can proceed.

        Deplin is a trade name for 5-MTHF. Folapro is also the same thing, but in a low OTC dose, i.e., 800 mcg/tab. Deplin is the prescription version of this and my understanding of this is that it is much higher …in milligrams rather than micrograms. This is does have methyl groups attached. It is the only form that partakes directly in the Met cycle. This one can overcome the MTHF reductase blockade if it is present.
        thank you for all the inputs, it really brings in so much knowledge and so much hope that if there are solutions to problems and we can some way help our children to lead a normal life!
        Best Wishes
        Sowmya Fesenbeck

  • Zach says:

    Dr. Lynch,
    After countless hours of educating myself about L-5-Methyfolate and B12 (Methyl, Hydroxy), I want to personally thank you for your dedication to helping others. It gives hope to those of us who have suffered with chronic depression & anxiety over the years without any success to typical SSRI treatments. I wish more doctors and mental health professionals were aware of this as an alternative treatment when antidepressants simply do not work in some people, such as myself. There is hope in feeling “normal” again.


  • Zori says:

    Hello, D-r Ben. I thank you so much for your work?
    Can you tell me whether folate – as (6S)-5-methyltetrahydrofolic acid, is the same as folate – as Quatrefolic (6S)-5-methyltetrahydrofolate?

  • Amanda says:

    Thank you so much for this website and all the information! I was diagnosed with hypothyroidism and PCOS in 2009 just before we had our first daughter who was stillborn. Then we got pregnant with our second daughter with the help of Clomid which is also what we used for our first pregnancy. In 2010 i was diagnosed with MTHFR after the stillbirth of our first daughter and I was told to take 4 mg of folic acid. Now we are trying to conceive again and the Clomid isn’t working at all – I’m not ovulating. The only thing I have done different is taking the folic acid and I can’t help but think this is our issue! Could the folic acid be the culprit for my anovulation and causing the clomid to not work this time when it worked with both of our other pregnancies? What should I be taking in place of the folic acid? Thank you so much!

  • Terri Maxwell says:

    My dr prescribed Methylfolate 3 MG everyday, I went to the herb store and the gave me Methylation Complete by Neuro Biologix. Is this the same . 3.2 mg

  • Debbie says:

    Sorry about the typos. My daughter recently was diagnosed with the MTHFR gene problem and has been taking Folate as L-5-Methyltetrahydrofolate and many of her lupus-like symptoms have abated. Thank GOD.
    I recently was told, as her mom, to also begin taking it and I wonder if this product is what they say it is. Swanson Health Products has a Folate product that is labeled as: Folate (as Quatrefolic [6S]-5-methyltetrahydrofolic acid equivalent to 1.6 mg of [6S]-5-methyltetrahydrofolic acid, glucosamine salt).
    My question is-This is listed as folic acid instead of folate. Is that a problem? Is there any difference between the 2?

    • Aron says:

      Hi Debbie – I’m glad to hear that your daughter’s symptoms have abated. The naming conventions can be very confusing! There are many forms of folates, which is a general term. In this case, this particular Swanson product is using folate as Quatrefolic, which is the same form of highly bioavailable folate that Dr. Ben has used in his own formulations. Folic acid is the synthetic form that is not as bioavailable and potentially harmful in those with MTHFR gene mutations. See Dr. Ben’s post on this very topic: https://mthfr.net/folic-acid-awareness-week-2014-want-awareness-here-you-go/2014/01/08/.

      All the best!

  • Esther says:

    Is this ok?
    Folate (as (6S)-N5-methyl-tetrahydrofolic acid calcium salt (molar equivalent to 600 mcg of folic acid) and folic acid, USP 400 mcg)

    It is part of a prescription for iron due to pregnancy anemia. In prescription drug Feriva

    • Dr Lynch says:

      I dont believe anyone should take folic acid.

      I dont see why we cannot use more active forms of folate – folinic acid and methylfolate are the active forms.

      Folic acid is far from active.

      Please talk with your doctor about using more active forms of folate –

      Look at the folate on the label here in this prenatal vitamin:

      It shows the active forms of folate.

      You can use that as an example.

      Also learning more about folate is important – please review http://www.seekinghealth.org/gift

      Thank you

      • Joanne says:

        Dr. Lynch
        After many miscarriages I have been diagnosed with MTHFR deficiency. I am currently going through IVF. My doctor has prescribed me Folbic Tablets Folacin (Folic Acid) 2.5mg and Prenate mini Folate(as 6s-n5-Methyl-tetrahydrofolic acid calcium salt). Is this good? I am beating my head here! Please help

        • Dr Lynch says:

          Hi Joanne –

          Sorry to hear about your miscarriages. Good news is you may have identified a big potential cause of them – MTHFR – especially if homozygous. Please read this article on prenatal supplementation and MTHFR – and watch the video – it’s very informative and will provide you a ton of answers.

          I absolutely do NOT agree with any pregnant woman getting folic acid – regardless of her MTHFR status or not. Pregnant women need FOLATE – NOT folic acid.

      • Afflicted grad student says:

        I appreciate that you are trying to help people not take the wrong form of folate. However, I must point out that (6S)-N5-methyl-tetrahydrofolic acid calcium salt is indeed methylated folate. Folic acid does not contain any methyl groups. Methyl folate is literally folic acid with a methyl group added. (6S)-N5-methyl-tetrahydrofolic acid calcium salt is literally the same thing as methyl folate in terms of having a methyl group on folic acid.

        The simple answer is that this person can totally take that supplement if she is looking for methylated folic acid.

  • Sara says:

    Hi Dr. lynch. I am nearly 30 w 2 copies of the 1298c mutation. I have had several miscarriages and turned up positive for this after transferring a genetically normal embryo via IVF and suffering a blighted ovum. My doc prescribed fool guard but I take Thorne’s basic prenatal (1000 mcg folate) and 400 mcg of methyl folate.ive been doing so since Oct/Nov-ish. I am now pregnant again and will be 6 weeks tomorrow. I’m not sure if this one will make it, but due to a suspected sub chorionic hematoma (confirmed), I had an early scan at 5weeks3days and saw a sac and yolk sac, so already better than last time. After doing research today, I saw that my version of the mutation may only absorb 10% of the folate I take. I’m wondering whether I really need 4000 mcg? And whether I should up my vitamins or folate through food. That is a lot of green smoothies. Thank you.

    • Dr. Aron says:

      Hi Sara – Upping your intake of vitamins and methylfolate through food is usually the ideal way to get these essential nutrients…plus many other essential vitamins, minerals, and antioxidants. Leafy greens are great because they contain methylfolate plus 100+ other forms of folate! I’ll assume 4000mcg was a typo and you are wondering about 400mcg. 400mcg is not a lot of methylfolate. I like to tell patients that they should average 5-7 cups of vegetables per day making sure to eat a rainbow of colors. Colors represent different nutrients and eating a rainbow will make sure you get as much as you can from food. Supplementation makes up the difference.

      You might find Dr. Ben’s prenatal supplementation article helpful: https://mthfr.net/prenatal-supplementation-optimizing-your-future-child/2012/01/20/

      Please keep us updated on your progress!

      All the best,
      Dr. Aron

  • Dominique says:

    I was just wondering, if a supplement just says folate, is that acceptable? Thank you.

    • Dr. Aron says:

      Dominique – there are over 150+ forms of folate. The most common form in most supplements is synthetic folic acid. It’s important to know specifically which form.

  • Amber Shull says:

    Thank you for your work with MTHFR gene mutations and treatment for the same. I am a Physician Assistant practicing psychiatry and we have been doing the genetic testing revealing these mutations. I am curious to know if A poor MTHFR carrier’s family needs to be genetically tested before l methylfolate can be given for mood disorders noted in other family members. Is there a contraindication providing 7.5 milligrams of l-methylfolate calcium to a family member if they have not been tested? Incidentally, they have been proven to have Arnold Chiari malformation. Thank you for your time! Incidence lee, they have been proven to have I don’t care email from a shin. Thank you for your time!

  • Barbara Walsh says:

    Please confirm: If I understand your article correctly, the following L-Methylfolate supplement ingredients are OK. Thank you.

    Folate [as (6S)-5-Methyltetrahydrofolic acid, glucosamine salt]^

    1000 mcg

    Other ingredients: microcrystalline cellulose, dicalcium phosphate, croscarmellose sodium, silica, vegetable stearate, stearic acid.


    ^Quatrefolic® is a registered trademark of Gnosis S.p.A., Patent number 7,947,662.

  • Christina says:

    My son was recently prescribed deplin, my question is it contains soy lecithin(msg) and titanium dioxide wich I heard could be toxic if taken daily, is that true?

    • Jan says:

      I was just prescribed Deplin but am hesitant to take it bc of the soy and other dyes in it. I have thyroid issues and hormones issues. I don’t want anymore problems. Is there another L-Methylfolate ca out there that doesn’t contain these additives?Thanks

      • Mike says:

        Deplin is nothing more than active folate. Don’t bother taking that.
        You can find L methyl folate on Amazon for 15 bucks. I was suicidally depressed for years. Started taking Solgar 800 mcg L methyl folate and it was like the lights came on. Someone cleaned the windows from my eyes to my soul. Color existed again. I was back.
        trust me I’ve been thru all this. Tried a ton of stuff, you’ll get thru this. It’s just chemical, start exercise and diet. Eat better, feel better. It gets so much better. But yes. It starts with folate. Best of luck! You got this!

  • Jeff D says:

    I’m so glad to have found this excellent site. My physician suspected that I may have MTHFR mutations and ordered the blood lab test. I just received my test results back which show that I have both the C677T & A1298C mutations.

    I’m sure there’s a lot of factors that affect this question, but I’m wondering what is a good general starting dose of 5-MTHF for someone like me with both mutations?

    I ordered L-5-MTHF 1000 from your “Seeking Health” company.
    I also ordered B-Complex #12 from “Thorne Research”.
    I need to know if these three different forms of folate are safe to take together?

    There is 200 mcg. of L-5-Methyltetrahydrofolic Acid, Glucosamine Salt and 200 mcg. of Calcium Folinate in each of my B-Complex capsules by Thorne Research.
    I then plan on taking your L-5-MTHF 1000 from “Seeking Health” which contains 1,000 mcg. of Folate from Quatrefolic(6S)-5-methyltetrahydrofolate, glucosamine salt in the Seeking Health L-5 MTHF capsules.

    My doctor wants to prescribe me a large 15mg starting dose of folate, but after reading a little of the wealth of information on this site it sounds like this may be way too much with a high probability of causing adverse side effects.

    I’d sure appreciate your input on the recommended starting dose and to the effectiveness and safety of taking the multiple forms of folate I listed.

    Thanks in advance for your input, I appreciate it very much!

  • Terry says:

    I’m a 63 yo woman., test d for gene.
    Results of serum. Test..
    Heterozygous A. One allele. C677T
    Heterozygous mutant

    I’m so confused.
    Physchiatrist said to rake deplin. 15 mg

    I tried it a few weeks.
    Sleepless. Kind of. More anxious.

    Can I buy a methyl folate at the health store. Or on line that is less expensive, better suited.
    Do we have to buy from deplin mgr. ?

    This is all confusing to me.
    Someone said I needed methyl B12 too.
    My B 12 is 936. On my serum test
    Homocysteine is 8

    I’m concerned about the Deplin. He said just take it.
    He doesn’t know much, said its a new thing for him now. Testing patients. But he can’t exactly explain what works best.

    Please help.
    Is there a good low dose methy folate to buy on line.
    Who can help?

    Please. Thank you.

    • Dr. Aron says:

      Terry – This is confusing for health professionals too! Start by taking a look at Dr. Lynch’s Basic Protocol. The goal is to treat you as a whole person–diet, lifestyle, environment, exercise…in addition to supplementation. Next, look to consult with a physician who is both open to this and has completed training with Dr. Lynch in the physician directory. Wishing you the best.

  • Andrea says:

    I am homozygous MTHFR (the C677T), is (6S)-5-methyltetrahydrofolic acid okay for me? Can my body use it? I bought a bunch of it then noticed at the end it is “folic” instead of folate, so now I am worried…

  • Desiree says:

    My friend is trying to get me to purchase plexus through her. The company has N5-Methyltetrahydrofolate listed on its label is this an easily absorbed form. I don’t see it listed in the above article.

  • Ashley Cangelosi says:

    I am looking at a multivitamin supplement that has folate listed as Calcium N5 Methatetrahydrofolate. How does that compare to the L5 I am currently taking?

  • Niki says:

    Can you tell me, is Folinic a methyl form? I’m interested in a folate that has NO METHYLS. Folic Acid has a bad rep for blocking absorption at the BBB. Is there such thing as a non methyl Folinic?

  • Lindsay says:

    Dr Lynch-

    I have 5 kids-2 biological and 3 step- all five have mutations- the two babies (3 and 1) have double mutations on the C…and the three older have single mutations on both.

    My friend suggested a multivitamin for the older kids and my husband and myself that contains Calcium N5amethyltetrahydrofolate. I don’t see anything about the N form here. Is this a good source?

    We are also looking for practitioners in the Dallas area if anyone has suggestions!!

  • ML says:

    A folate supplement is something I’d like to try but I have difficulties finding supplements that don’t cause me problems. I’m gluten intolerant, with dairy and soy intolerances also. I see your product is free from soy protein but perhaps you can elaborate: vit e from soybean sources causes me problems also. Also minerals with “glauconate” as the salt. Are any of your products suitable for me? Your article on folate and folic acid interests me as I found I was unable to take folic acid (I think it was the solgar one so maybe it was folate) during my pregnancies after the first few weeks due to nausea (which would return even later in the pregnancy whenever I tried to return to it). Many thanks, ml

    • Christopher says:

      ML, I would suggest methylpro.com they have good formulations as well as GF and I believe they are soy and dairy free. They are also a very good value.

  • Kristen says:

    I was diagnosed 2 months ago with C677TT – B6, B12 and B9 out of whack. . Doc Rx MethylPro Complex 5mg.

    While I am not having negative side effects, I am still so tired, brain fog hasn’t lifted, concentration is limited.

    I have thyroid issues as well and we’ve addressed those issues and blood looks fine for that. Had a few other deficiencies, and other hormones out of whack. All being supplemented.

    I thought I felt a little better second week.. but now I feel it’s same ole. Is it possible that it can take several months for the dust to settle and see results – or do I need a change? Doc said, it could take some time, but I guess I just expected more?

    I have hardly touched your research as I find it overwhelming due to fog and fatigue – So I may not have gotten to this topic yet. If you point me in the right direction I can research.

    Also, have a company stating that they have biological methylation combo with lemon peel folic acid. Is there such a thing? I thought folic acid was from green leafy veggies?

    Thank you for your feedback and research in this topic!

  • helen says:

    Hi Dr Ben,
    I have not been tested yet for MTHFR but am just about 100% certain our family has this mutation based on all the congenital heart issues and mental problems in our family that go back many generations. I started on the methylcobalamin version of B12 (5000mcg) the first day and felt pretty good. The second day I cut the B12 tablet in half and only took 2500 mcg, and felt good. The third day I took the 2500mcg of B12 and added 800mcg of Country Life folate as (6S)-5-Methyltetrahydrofolate (glucosamine salt) and felt awesome! That night I started coughing and the next morning I felt like I got run over by a truck! Extremely achy, every joint hurts, coughing a lot and mucas in lungs, horrible headache, etc. What did I do wrong? Maybe I should have added in L-Glutathione? I eat an extremely good diet, huge amounts of dark green leafy greens, organic and havent even taken an aspirin in 20 years, grow a lot of my own food, chemical free. Would you have any idea what I should do differently?

    Thanks in advance for any help,


  • heidi says:

    If I add the liquid Glutathion to the methylfolate and the methylcobalamin B12, would that help with side effects?

    Im not sure what to do..

    Thanks in advance for any suggestions.

  • Lori says:

    Dear Dr Lynch, I am taking the Optimal Prenatal which as you know has 400 mcg quatrefolic and 400 mcg folinic acid. But I am also taking an extra 800 mcg Metafolin and 1000 mcg methylcobalamin (both solgar brand). I have both the C677T & A1298C mutations and had loss of pregnancy last July due to a neural tube defect. So that’s why I want to take the extra dose of methylfolate before trying to get pregnant again. I have been taking this same dosage since August 2015 and feel fine, but now I’m wondering, is it OK to be taking all 3 of these different kinds together? Or should I try taking extra quatrefolic instead? Or extra folinic? And if/when I do get pregnant is it OK to up my total intake to 2000 mcg?

  • Ricardo says:

    Dr Lynch, How do you feel about folate from lemon perl extract and would you recommend its use with the treatment of MTHFR, I am diagnosed by the DNA test as having severe folate deficiency, I have been taking 2400mcg daily and I have to say I ferl better along with taking a methyl-B complex, but the product I use is costly, so I have found lemon peel extract folate cheaper, would it be something I could try.
    Thank you.

  • Caren says:

    Thank you so much for this article! I’ve followed some of your writings and podcasts and always appreciate your highly schooled perspective. I was tested and found I was mthfr a few yrs. ago. I took Pure Encapsulations’ Homocysteine factors for several yrs., I don’t think it did much. I was just prescribed Deplin 15mg after a new Dr. and DNA test and wanted to learn more about it. You’ve put my mind at rest; good to know this is the right kind of folate. I’ve been sick for 30 yrs. and am very wary of Drs. Your advice is always very thoughtful and sound. God bless you! <3 C

  • Brooke says:

    Does anyone know of a good Dr in OKC, Edmond or anywhere near that is knowledgable in methylated folate (2D6 deficiency & adsorption issues)?

  • Autumn says:

    My son was diagnosed with MTHFR at age 11. I’m pressing to have this be a test at birth because he had a 10 on both apgars and seemed perfectly healtjy. Years of not knowing had more affect with time. I’ve been on a waiting list to see a child neurologist and should finally get to see one come fall, but my son is 15 years old now. My father’s 1 cousin’s son has MTHFR, and I question if my mom’s sister did, she died young at 36, she had skytsophrenia. They say skytsophrenia can result from the mutation. My son is currently taking Thorne 5-MTHF 5mg, I found a less expensive for but I think it’s weaker and I’m trying to find out how comprable the two are. The other one is by LifeExtension, it’s called Optimized Folate L-Methylfolate 1000mcg, Metabolically Active Forma of Folic Acid (is on the front of the bottle). The back says Folate [as (6S)-5-Methyltetrahydrofolic acid, glucosamine salt]^ 1,000mcg daily value 250%
    If anyone could please help me understand the comprablity. Unfortunately I never took chemistry in a loophole in high school, and in college I walked out the 1st day of class because I was lost. I have been trying to read and self teach myself some chemistry to understand better. Thank you

  • Mike C says:

    Dr. LYNCH! Thanks you for the awesome work you do, you are saving lives!!!
    what’s is the difference between (6s)- 5 – methyltetrahydrolfolic acid (glucosamine salt)
    Everything I’m looking at has the folic acid form at the end and is very confusing. Is it the same, is it kind of the same but 1 could potentially work better for an individual? I find 400mcg a day of the – 5 – methyltetrahydrolfolic acid (glucosamine salt), isn’t really working, in fact become quite irritable. Just like I did when I was accidentally takin a b complex years ago before 23nme, with folic acid in it.
    Want to try the other form, with out it saying folic acid, but am seeing that everywhere. Any ideas?
    Thanks you again doctor, you work is so important to so many. Sincere thanks!

  • Akhilesh Patel says:

    Can I eat L-5-methyltetrahydrofolate calcium 7.5mg in place of L-methylfolate 7.5mg

  • Sarah says:

    Hi there, I found a supplement with the following ingredients. I’m very curious on your thoughts on it. Thank you!

    Vitamin C (as ascorbic acid and calcium ascorbate 200 mg 333%
    Vitamin D (as cholecalciferol) 1000 IU 250%
    Vitamin E (as D-alpha-tocopheryl succinate) 30 IU 100%
    Thiamin (as thiamine hydrochloride) 3 mg 200%
    Riboflavin 3 mg 176%
    Niacin (as inositol hexanicotinate) 20 mg 100%
    Vitamin B6 (as pyridoxine hydrochloride) 10 mg 500%
    Folate (as calcium N5-methyltetrahydrofolate) 400 mcg 100%
    Vitamin B12 (as methylcobalamin) 500 mcg 8333%
    Pantothenic acid (as calcium D-pantothenate) 10 mg 100%
    Proprietary Blend – Patented aloe vera (aerial parts) blend, guar gum (fiber), New Zealand blackcurrant fruit extract (std. min. 35% anthocyanins) 390 mg

  • isabel says:

    I just had a 2nd miscarriage. Both my husband and I tested and have C677T MTHFR. The doctors stated not relevant. !!!After I miscarried, in a dream!!! yes a dream my OBGYN stated “you need a stronger prenatal”. I told a nurse that I had MTHFR and if there was a stronger prenatal available. I was given a sample of “Vita-MedMD One Rx with Quatrefolic” I read the ingredients it has (among other ingredients):
    “Folate Quatrefolic ((6S)-5-methyltetrahydroFOLIC acid, glucosamine salt)…600mcg”
    “Folic Acid 400 mcg”
    “Vitamin B-12 as cyanocobalamin”
    “Vitamin B6 as pyridoxine HCI”
    My gut says do not take. I had already ordered everything under the Prenatal protocol recommended by Dr. Lynch, just waiting for it to arrive. But was curious what the nurse had to offer.
    I just still wonder “what if” I’m not doing the right thing, not taking the right thing, etc. I already know if I have MTHFR do not take Folic Acid. This Rx has both Folate and Folic Acid. I am overwhelmed.

  • Jeannette Avila says:

    I am seriously confused. My son has epilepsy. Is is not controlled with medicines, actually thank God! The Modified Atkins controls the seizures but it is really hard on a 14 year old boy. He did Dr. Amy Yasko genetic test and I am still confused. I feel her supplements caused more seizures. He as double mutation for MTHFR C677T and a single for CBSA360A. His chiropractor has put him on Biotics ADB5-Plus (4 times a day) It has Folate in the form of calcium folinate and B12 in methlycobalamin. Can you tell me if this is ok? I am worried because I read that the wrong form of folate can eventually turn into cancer cells. He is also taking a kirkman multivitamin from the nutritionist at UCLA. I think this has the the wrong from of folate. Cam you recommend a multivitamin?

  • AdoreTu says:

    I do not know of any multivitamins for this but it’s best to not take one with folate in it. I recommend buying an optimized folate and something called 5-MTHFR. With MTHFR the body has difficulty processing the folate in regular vitamins. YOU can find these online or some stores sell them. I also was told to have my son take a B-12 supplement and Vitamin D. I hope this helps! Ebay sells a few optimized folates, but their 5-MTHFR is the weakest one and he’d need 5 a day to get what is necessary. There is a stringer grade one that I think is 5mg, he takes it once a day in the morning. I started taking it too because I don’t know if I have this genetic mutation, I lost 10lbs really fast! Not sure if related to it or just some lifestyle changes, but I think it had something to do with the weighteam loss. I had only a little to loose, but I think it may benefit a person trying to loose weight. I’m it positive on it, but it won’t hurt you. They are recommending 5mthfr to some pregnant women too.

  • Christy Parandi says:

    Dr Lynch,
    I was diagnosed homozygous MTHFR C677t & Pai-1 after my first 2 strokes in 2005. Up until now I have been given high does folic acid. I’m in the process of changing over but am wondering about about otc supplements. Is calcium n5-methyltetrahydofolate as found in Plexus xfactor the correct version of folate for me?

  • Melinda says:

    Hi. I am heterozygous for MTHFR A1298C (A/C). A supplement I’ve been taking says it’s Folate is “as calcium N5-methyltetrahydrofolate, 400mcg.” Curious about the N. ??

  • Arlene says:

    Dr. Lynch, I am taking METANX 2 caps a day, but I also take Methotrexate 6mg once a week. What are the problems taking these two drugs. My GP and my Rheumatologist have a disagreement over my taking both. I have fibromyalgia and polymyositis and polyneuropathy. The MTX is to treat the polyneuropathy and the METANX is to rreat for an MTHFR genetic mutation of a single gene of the pair. My doctors seem to be confused about this.

  • Lois says:

    This was the most helpful information I’ve found on MTHFR! Thank you!

  • Kathie says:

    I was wondering if Lamictal and Quatrefolic are contraindicated together.

  • Rachel R. says:

    I’m a little confused, Dr. Lynch. In reply to one comment you said that yes, calcium n5-methyltetrahydrofolate is a good form, but in another comment you said that if it lacks the L- or 6S-, methyltetrahydrofolate may be the racine version and, therefore, not good.

    I can’t find any information on what the “n5” stands for or how that n5 version compares to anything else. Can you clarify please?

  • Leslie McLea says:

    Thank you Dr. Ben for all your reasearch. I so need your imput. My journey has been difficult. Badk in Feb of 2015 I went to a Functional Medicine doctor, cost me my bonus check. I did find out under the MTHFR ( C677T) it shows C/T intermediate Risk. Mthfr ( A1298c).That falls under Optimal at A/A . The notes from the lab say; This patient is heterozygous for the MTHFR C677t Polymorphism(C/T) and has the normal or wild-type genotype for MTHFR A1298C(A/A). Ok, enough said, so now, my choesterol is off the charts and my body makes to much of it. THere is a lot to learn, and finiancally, I am now on Disibility and a very fixed income. I need to know what type of diet I need to follow inorder to bring my body back to where it needs to be. Hip surgery is somewhere out there, I have Osteoarthritis , now bone on bone. My BP is uncontrolled even on 300 mg of BP meds. I am on pain meds and 500 mg of naproxin twice a day. The diet concerns me the most, and supplements. I need a direction. Can you help? Thank you Leslie McLea Roanoke, VA

  • Jocelyn Mckervey says:


    I recently came across a post about how vitamins with food sourced folate is actually folic acid. They said that when the folate is processed for the vitamin it oxidates and thus becomes folic acid. Is this true?

  • Ayshea says:

    I’m looking at a multivitamin that claims to have the ‘most bioactive form of folic acid’ and ‘features bioactive 5-MTHF form of folic acid and then the label list it as Folate (as calcium N5-methyltetrahydrofolate). N5-etc. is not listed… Is is good, not good, or a maybe/maybe not?

    It also claims the aloe blend it contains (aerial parts) helps with optimal absorption, of course with the standard FDA disclaimer.

  • Erin says:

    When will seeking health optimal prenatal be back in stock?

  • Sonia says:

    hello I am currently taking MTHF 4th generation 1 mg every second day and folinic acid b9
    daily – should these be combined.

  • Alisha says:


    I just found out i have the MTHFR C677T gene from both parents. I’ve been extremely sick for the last 5 years. My Dr. Just found this and doesn’t know much. She’s starting me on Methyl folate 5000mg and L-Methyfolate. I want to make sure this is the correct dosages. I always seem to get all the bad side effects, so I’m worried to start taking these.
    Thank you,

  • Jen says:

    Hello! Great info 🙂 Quick question;I am taking a prenatal with L-methylfolate (800mcg) and I’m taking an additional 400mcg of quatrefolic. Is it ok to mix the two?

    • Mike says:

      It’s totally OK. They’re both active forms of folate. Stay away from straight folic acid. They’re both active but at different times in the methylation pathway. It’s a good combo. What else in in the prenatal?

  • Nurp says:


    I bought a prenatal vitamin that says:
    Folate (as Quatrefolic 5-Methyltetrahydrofolic acid, glucosamine salt 1.9mg).

    It doesn’t start with L- but it is Quatrefolic. What should I think of it?

    Best regards!

  • Stephanie Hammonds says:

    I think your site has a typo: “6(R)-L-MTHF = 6(R)-L-Methyltetrahydrofolate”
    I think you meant L to be a 5. Pretty sure you can’t be both 6(R) and L.

  • Sarah says:

    My mother has the MTHFR gene (as do I). She was taking a liquid vitamin containing Calcium L Methyl Folate 440 mcg [400 mcg as Folate], Adenosylcobalamin B12 250 mcg. However, the GP told her to STOP taking B12 supplements as her B12 is high. What’s causing her B12 to be high?

    • Sarah says:

      here is a list of ALL the ingredients: Choline Chloride 113 mg (83.3 mg as Choline), Dexpanthenol 25.5 mg (as Vitamin B5), Niacinamide 25 mg (as Vitamin B3), Thiamine Hydrochloride 16 mg (10.2 mg as Vitamin B1), Pyridoxal 5 Phosphate 16 mg (10.7 mg as Vitamin B6), Riboflavin 5 Phosphate 14 mg (10.4 mg as Vitamin B2), Potassium Carbonate 12.5 mg, Citric acid 4.5 mg, Calcium L Methyl Folate 440 mcg [400 mcg as Folate], Adenosylcobalamin B12 250 mcg, Methylcobalamin B12 250 mcg, Biotin 100 mcg [as Vitamin B7], Purified Water.

  • Brice Hagens says:

    My prenatal includes folate specified as simply “L-5-MTHF” (600 mcg), and I would like to take an additional supplement that specifies the folate as “Metafolin, L-5-MTHF” (800 mcg). Are these forms the same, and can they be taken together?

    Thank you!

  • Thanks for the pronunciation! I have been calling it Mothereffer. That’s what it looks like.

  • OK, I have had a duodenal ulcer since 2009, but had managed it with pepcid until 2015. I was careflighted to the ER and had 5 pints of whole blood and was still at a 10 (female) on my hgb. They had me on prilosec and said I could go off it in 2 weeks. Every time I tried I would vomit. And have regression. It is taking me since then to regain my strength (still not there- on the 90 essential nutrients, in optimal doses, Am tapering off prilosec, now about 8 mg. It is taking forever, also taking PQQ, and cayenne for mucous production (500 mg). AM on MCT oil and coconut oil, and many different things to try to rebuild my gut. Take grass fed butter for the butyric acid, have goats for raw milk, off grain and heavy carbs…knowing how wonky the gut can be, I just know the prilosec has to be a factor in destroying my mitochondria. And thus why I am low energy etc. How much more horrible is the prilosec interfering with my MTHFR? (23andme, says I am double for it). But I didn’t have problems until I retook my childhood vaccines to get into nursing school, I have just stopped chronic diarrhea from it with MSM and TMG in 2016.(from 2003) My Natural MD has given up and lets me research my own stuff and is supportive of anything I try that I need his help with.

    • I forgot one thing, I was feeling good enough to return to work in 2014, and had been on 5 mg of methylfolate, I was finally getting an appetite and losing weight at the same time (no special diet yet- except Real Foods). They put me on nights, and I began vomiting once a week immediately (my body hates nights but in nursing they are real bad about abusing their employees, My pleas went unheeded). At the end of a year I was not able to hold down solid food, then not even liquid food, and I had to quit. In spite of being on methylfolate and every nutrient I could. Now I’m on source of life Gold which is everything in liquid, but also take extras as their doses are too low on some things- one I have been able to take less of is vitamin C- I was on 9 grams before the liquid, and now I don’t have to take any except occasionally 1 or 2 grams. Other stuff, krill oil, astaxanthin, natural E 1000 IU, 10,000 IU D, MSM and TMG, …..etc. I am currently on plain folate.
      Also, when a supplement label says “folate as folic acid”, does that mean they have folic acid in it or does it mean it is actually folate and they are clarifying to the reader who doesn’t know the difference?

  • kathryn says:


    I have the A strain of MTHFR and I m 8 weeks along. I have been taking an organic prenatal with 800mg of Folate but my doctor has suggested another 400mg and recommended prescriptions which I’m not thrilled about.

    I’m finding methylfolate supplements available in 400mg and am wondering about the difference between folate and methylfolate prenatals, also wondering if I should be taking all methylfolate, and/or is the 800mg folate safe to take?

  • Cheryl says:


    I am a provider and my 80 year old female patient has the gene and is on the L-MTHR and taking 10mg since a month and started slow with 400mcg in January but since January has lost her hair in clumps also was started on synthroid 100mcg then too. Also lowered her DHEA troche from 25 to 20mg due to DHEA was too elevated.
    Which item do you think is the culprit?


    Cheryl A. FNP

  • Lindsay says:

    I have MTHFR and take folate daily. I recently bought more from the same place and realized I had been taking the reduced form and now have the active form of the folate. Is there a difference? It’s “bioavailable folate. Quatrefolic. Active form” I just feel a little different and that’s the only thing supplement wise I have changed so wanted to see what the difference between reduced form and active form are. Thanks

  • Jose Evaldo Williams says:

    Dear Doctor,

    Thank you very much for your excellent work.

    We just found out that our son has this mutation.

    He has several psychological and psychiatric symptoms.

    He takes several medices but none of them helps him.

    We are desperate.

    We are from Brazil.

    Could you please exchange email messages with us about that??

    Thank you very much indeed.

    Kindest Regards

    José Evaldo and Fabiellem

  • Susana Mora says:

    My Natural Pathic doctor prescribed me 1 pill of FolaPro(Folate as calcium l-5 methy) a day which is 800mcg. Is that normal?

  • Lara says:

    I tried taking methyfolate for the first time two days ago, immediately cleared up anxiety and depressive feelings i had been having on and off, only side effect is a tired feeling, or more like a heavy head feeling, does this mean i need to back it off? Or if tiredness is the only side effect does that mean i am ok to take it seeing as it reduced anxiety instead of causing it?

    I am low titre positive for anti nuclear antibodies but i do not feel that i have any problems with dairy or gluten, so does this mean i can still keep eating them?

  • Karen says:

    Dr. Lynch
    Thank you for this informative lecture. I’m watching it several times! I’m on Methotrexate and prescribed Leucovorin 10 Mg once a week to avoid the toxicity. Leucovorin, which is Folinic acid, I’m not sure if that is methylated. Do you know? Pharmacists don’t know. From all I can tell it is L and D folinic acid, presumably 1:1 ratio, but no proof of that and no literature to say if it’s methylated.
    Do you know if Leucovorin is methylated folinic acid?
    Thank you for all your knowledge!

  • Bru says:

    Re; [ c677t homo, 6s 5mthf]

    1: thank you for your passion and work 2: supplementing with 6s5mthf to mitigate symptoms. However, are we running the risk of increased cancer odds with supplementing with this type of folate ?
    Thank you.

  • Diamond says:

    What about Folate as calcium-l-5-methyltetrahdrofolate? 400mcg.

  • Doppelganger says:

    If these vaccine manufacturers hadn’t broken the MTHFR gene we wouldn’t need to rely on Merck and all their little Market capture and saturation tactics and variations for production and supply of methylfolate. This is no different than the old sharman trick of bringing the tribe member in supposedly curing their problem and then making them sick again so they become a return customer, rinse and repeat. These people are witches practicing your form of sorcery known as pharmakeia, And I hate to say it but all of these physicians, doctors and specialists who hold licenses to commit crimes with their lettered degrees and flattering titles, they are accessories during and after the fact.

  • Felicia says:

    This is great thank you! I have a supplement that has 6s-5-methyltetrafolic acid, glucosamine salt, (quatrewdolic) as the folate component. I didn’t see anything regarding the 6s 5 methyltetrafolic acid. Can you please comment on that version of folate please. Thank you

  • Konnie L McCullough says:

    Hello Dr. Lynch,
    Thank you for the very helpful information. My son’s Dr. prescribed 15 mg. tablets L-Methylfolate which my insurance doesn’t cover. I was told to request capsules instead. Is one better than the other when it comes to prescription strength?
    Thank you-

  • Lenka Ridley says:

    Hi. Thank you so much for your article. I am carrying 2 heterozygous mutations on my MTHFR gene. I am planing to get pregnant and my doctor recommended to take methylfolate 500ug/per day 3 months prior and during pregnancy. Which form/name of methylfolate should i take? Also if i buy 400ug or 800ug is it big difference? Thank you

    • Hi Lenka –

      A healthy pregnancy requires way more than just the right type of folate.

      It’s awesome you are aware that methylfolate is great – but you need more than this.

      This article on MTHFR and Pregnancy is very informative and thorough.

      I highly recommend you consider Optimal Prenatal with Plant Based Protein vanilla as it is easier to take, toss in a smoothie with your favorite milk and frozen organic berries and you’re solid.

      You can switch back and forth between Optimal Prenatal capsules and the shake.

      An optimal pregnancy is NOT just about taking a bunch of folate. It’s also about many other factors which is why I recommend the ProBiota HistaminX, Optimal PC, Optimal Iron Chewable, Optimal Fish Oil and Optimal Vitamin D Drops. It’s a comprehensive plan which supports all aspects of your pregnancy – not just folate.

      You will have way better success this way.

      Please read and watch my video here on this page and those supplements I recommended are all in the Prenatal Supplements category here.

      Have a fantastic pregnancy! 🙂

  • Amy says:

    Hello Dr. Lynch,

    You’re book Dirty Genes has been an incredible eye opener recommended to me by a personal friend and nurse practitioner. I recently (before reading you book) bought a supplement that contains”Folate as (6S)-5-Methyltetrahyofolic Acid, Glucosamine Salt and Quatrefolc” and I was wondering if this would be advisable to take? Based on this post, I would say yes, expect that the ending says “6S-5-mth..folic acid” instead of “6S-5-mth..folate” I have not had genetic testing done, but I do suspect I have some form of the MTHFR mutation seeing that my sister does.

    Thank you for this article and the opportunity to ask further questions.

    • Hi Amy –

      Yes that form is good – it’s the same one we use but we altered the name a bit with the ingredient manufacturer’s permission. It’s a quality form of methylfolate and I told the manufacturer they should not use ‘folic acid’ in the name.

  • Elena E. says:

    Dear Dr. Lynch,

    thank you very much for your amazing work!
    I’d like to ask if L-5-methyltetrahydrofolate calcium salt is a right form of folate. Unfortunately I don’t know whether my husband has MTHFR mutations or not so let’s assume he has them; he takes Two-Per-Day multivitamins by Life Extension which contain this specific folate. Thanks to these vitamins his homocysteine levels dropped from 10 to 7 mmol/L but now that I’ve read your article I’m worried L-5-methyltetrahydrofolate calcium salt probably isn’t any better than folic acid.


    • Hi Elena –

      Yes – that form is pretty good but it’s not my favorite. I prefer the Gnosis form of folate and that is what we use at Seeking Health.

      If he’s doing well with it, continue using it.

  • Jay says:

    What is MT-ja-Far? MTHR? You have said this over and over during the video. Confusing

    My doctor says I have to take “L”-Methylfolate with emphasis on the L. I am bipolar and genetic testing said I would most likely benefit from MethylFolate because I had only intermediate response to MTHFR. My doctor says I have to have “L” MethyFolate. Seems weird to me from everything I have read but because it is not cheap I want to know why it has to have “L” in front of it. I have seen many products without the “L”. He insists “L”

    • Hi Jay – It’s simply because I was talking fast – it’s MTHFR

      Your doctor is right. You need methylfolate as the L form – or the 6S form. If you get a racemic blend of methylfolate, it won’t work very well.

      You may find L-methylfolate supplements here if needed. We offer them in capsules and lozenges so you can choose how much you want at any given time.

  • Julie P. says:

    Is there a supplement that has ingredients equivalent to Meta NX? I cannot afford to take that on a long-term basis. I would like to take that for my neuromas in my feet, and the vitamin b supplement I was recommended by another genomics company had b vitamin levels in it that increased my anxiety.

    • Hi Julie –

      I just checked the ‘Ingredients’ of Metanx and it’s full of things that are unnecessary.

      Here are the full ingredients of Metanx:
      Silicified Microcrystalline Cellulose, Algae-S Powder [Schizochytrium Algal Oil (Vegetable Source), Glucose Syrup Solids, Mannitol, Sodium Caseinate (Milk), Soy Protein, High Oleic Sunflower Oil, 2% or less Sodium Ascorbate, Tricalcium Phosphate, Tetrasodium Diphosphate, Natural Flavors, Soy Lecithin, and Mixed Natural Tocopherols and Ascorbyl Palmitate (as antioxidants)], Pullulan, Pyridoxal 5′- Phosphate, L-methylfolate Calcium, Methylcobalamin, Titanium Dioxide (color), Magnesium Stearate (Vegetable Source), Caramel (color), Riboflavin USP, Shellac, Propylene Glycol USP. Contains Milk and Soy

      Consider HomocysteX Plus as it has the same active ingredients plus TMG which is very supportive of methylation. The potencies are less than Metanx but you can always take more if needed. The added TMG may make it more complete thereby requiring less of the other ingredients.

      Here are the full ingredients of HomocysteX PLus
      Riboflavin (as riboflavin-5’-phosphate sodium) 25 mg 1,923%
      Vitamin B6 (as pyridoxal-5’-phosphate) 15 mg 882%
      Folate [as Quatrefolic® (6S)-5-methyltetrahydrofolate, glucosamine salt] 1,360 mcg DFE (800 mcg) 340%
      Vitamin B12 (50% as methylcobalamin and 50% as adenosylcobalamin) 1,000 mcg 41,667%
      TMG (trimethylglycine) 700 mg **
      **Daily Value (DV) not established.
      Other Ingredients: HPMC (capsule), ascorbyl palmitate, silica, and medium-chain triglyceride oil.

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