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.





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10 years ago

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.

9 years ago
Reply to  Dr. Ben Lynch

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,

7 years ago
Reply to  Josh

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.

7 years ago
Reply to  Josh

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.

5 years ago
Reply to  Matt

Wondering if anyone has an answer about Thorne’s form of L-5-Methyltetrahydrofolic acid

10 years ago

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!

8 years ago
Reply to  Alex

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

10 years ago

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?



10 years ago

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.

8 years ago
Reply to  Chris

Oops, this is where my reply was intended. .. sorry!

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

4 years ago
Reply to  Chris

Was this query ever addressed? I have similar concerns and questions.

10 years ago

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

8 years ago
Reply to  Chris

Chris…I found your post searching Gabapentin and Doxepin…I am trying to help my niece with her MTHFR- and she is on that same drug combo. I was wondering if you have found a winning supplement combo. You can email me at kim@drugtestyourteen.com. Thanks!

10 years ago

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,

9 years ago

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!!

9 years ago

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.

9 years ago

What do you think about the use of Rheumate?

[…] foods like bread, flour, processed foods, conventional pastas, etc. Dr. Lynch talks about the different forms of folate here. It is important to remember that you want to have an adequate intake of B12 as well in a form you […]

9 years ago

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.

9 years ago

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!!

9 years ago

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?

9 years ago

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?

9 years ago

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.

9 years ago
Reply to  Dr. Ben Lynch

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.

9 years ago
Reply to  Dr. Ben Lynch

Dr Lynch, can you explain something to me?
Husband has : c677t mutation is heterozygous a1298c was negative
Daughter has: c677t mutation is heterozygous a1298c is heterozygous
I was told I have no mutations…
I would have expected to have at least 1298c…

Samantha McRorie
9 years ago

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?

9 years ago
Reply to  Dr. Ben Lynch

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
2 years ago
Reply to  Dr. Ben Lynch

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

9 years ago

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.

[…] chlorine. Supplement with SAM. Consult with an MTHFR-knowledgeable doctor and figure out which methylfolate is right for […]

9 years ago

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

9 years ago
Reply to  Dr. Ben Lynch

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!

9 years ago
Reply to  ing

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.

9 years ago
Reply to  ing

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!

9 years ago
Reply to  Dr. Ben Lynch

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!

9 years ago

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.

9 years ago

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.
9 years ago

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.

[…] L-methyltetrahydrofolate. There is a nice write-up about the different supplemental forms of folate here.  Be aware, however, that some people can experience side effects from methylated folate because […]

Sherry Goeke
9 years ago

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.

9 years ago

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.

9 years ago

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

9 years ago
Reply to  Dr. Ben Lynch

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

9 years ago

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.


9 years ago

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?

9 years ago

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!

9 years ago
Reply to  Amanda

Hi Amanda,

Dr. Ben is a HUGE proponent of getting rid or all forms of folic acid (man-made form) in supplementation and fortified foods. He recently created a brief overview of the differences between folic acid and folate (found in nature) (https://www.youtube.com/watch?v=oZzR1NMg0hM). In short, there is really no reason to be taking folic acid.

There is also a post on pre-natal supplementation that you might find interesting: https://mthfr.net/prenatal-supplementation-optimizing-your-future-child/2012/01/20/

Hope this helps!

Terri Maxwell
9 years ago

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

9 years ago

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?

9 years ago
Reply to  Debbie

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!

[…] Fairhaven Health OvaBoost (contains CoQ10, 2000 mg Myo-Inositol, melatonin, 100 IU Vitamin E, Alpha Lipoic Acid, Grapeseed Extract, and 400 mcg Folate (there is a difference between Folic Acid and Folate!! Additionally, there is a difference between various types of Folate.) […]

8 years ago

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

7 years ago
Reply to  Dr. Ben Lynch

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

Afflicted grad student
6 years ago
Reply to  Dr. Ben Lynch

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.

8 years ago

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
8 years ago
Reply to  Sara

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

8 years ago

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

Dr. Aron
8 years ago
Reply to  Dominique

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
8 years ago

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!

7 years ago
Reply to  Amber Shull

My identical twin and I have Arnold Chiari, are we over methyilated or under. We also have many allergies.

Barbara Walsh
8 years ago

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.

8 years ago

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?

6 years ago
Reply to  Christina

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

4 years ago
Reply to  Jan

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
8 years ago

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!

Dr. Aron
8 years ago
Reply to  Jeff D

Jeff – Please read the article on Preventing Methylfolate Side Effects and listen to Dr. Lynch’s podcast “How much to take?”. In short, consider starting low and going slow. Of course, consult your physicians for what you ultimately decide. All the best!

8 years ago

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
8 years ago
Reply to  Terry

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.

8 years ago

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…

8 years ago

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
8 years ago

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?

8 years ago

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?

8 years ago

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!!

8 years ago

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

8 years ago
Reply to  ML

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.

8 years ago

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!

8 years ago

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,


8 years ago

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.

Dr. Aron
8 years ago
Reply to  heidi

Heidi – I recommend listening to this podcast by Dr. Lynch on “How much to take”: https://www.seekinghealth.com/index.php/natural-health-podcasts/26

8 years ago

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?

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