MTHFR Product Comparison

MTHFR Product Comparison

Many are asking me, “Dr Ben, I am taking this ________. Is that any good for C677T or A1298C or…?”

I am finding that I am answering, “No” too often.

I have here all the top homocysteine-lowering medications which are prescribed commonly by doctors. Keep in mind that many doctors do not understand nutritional biochemistry. Nutritional biochemistry is extremely important to know especially when people are dealing with MTHFR mutations.

I’ll tell you right now: I am NOT impressed by 99% of the prescription drugs used currently for those with MTHFR mutations.


Let me show you the top drugs prescribed by doctors for MTHFR mutations first. Then, I’ll explain why I am not pleased with the formulations. You’ll totally understand by the end of this rant – and if you have any questions – please do comment below.

Comparison of Homocysteine Support Products
Drug or Product Folic Acid & Amount B12 & Amount B6 & Amount Inactive Ingredients Rx Only Cost per Serving*
Folbee Folic Acid 2.5 mg Cyanocobalamin 1 mg Pyridoxine HCL 25 mg For Folbee Plus: Croscarmellose Sodium, Dicalcium Phosphate, Hypromellose, Magnesium Silicate, Magnesium Stearate, Microcrystalline Cellulose, Mineral Oil, Sodium Lauryl Sulfate, Stearic Acid, Titanium Dioxide and Triacetin Yes $0.93
Folplex Folic acid 2.2 mg Cyanocobalamin 1 mg Pyridoxine HCL 25 mg Dibasic Calcium Phosphate, Microcrystalline Cellulose, Modified Cellulose Gum, Crospovidone, Magnesium Stearate, Hypromellose, Titanium Dioxide, Polydextrose, Triacetin, Polyethylene Glycol, Iron Oxide Red, Iron Oxide Yellow Yes not found
CerefolinNAC L-Methylfolate Calcium (as Metafolin) 6 mg Methylcobalamin 2 mg N-Acetylcysteine 600 mg Microcrystalline Cellulose, Opadry II Blue 07F90856 (Hypromellose, Talc, Titanium Dioxide, Polyethylene Glycol, FD&C Blue #2-Aluminum Lake, Saccharin Sodium), and Magnesium Stearate (Vegetable Source) Yes not found
Deplin 7.5 mg L-methylfolate Calcium (as Metafolin) 7.5 mg none none Dibasic Calcium Phosphate Dihydrate, Silicified Microcrystalline Cellulose 90, Silicified Microcrystalline Cellulose HD 90, Opadry II Blue 85F90748 (Polyvinyl Alcohol, Titanium Dioxide [color], PEG 3350, Talc and FD&C Blue #2[color]),L-methylfolate Calcium, Magnesium Stearate (Vegetable Source), and Carnauba Wax Yes $3.19
Deplin 15 mg L-methylfolate Calcium (as Metafolin) 15 mg none none Dibasic Calcium Phosphate Dihydrate, Silicified Microcrystalline Cellulose 90, Opadry II Orange 85F43102, (Polyvinyl Alcohol, Titanium Dioxide [color], PEG 3350, Talc, FD&C Yellow #6[color], FD&C Yellow #5[color], FD&C Red #40[color] and FD&C Blue #2[color]), L-methylfolate Calcium, Magnesium Stearate (Vegetable Source), and Carnauba Wax. Yes $3.22
Folgard RX (Foltx, Homocysteine Formula (not sure which form) 2.2 mg 25 mg (not sure which form) 1 mg (not sure which form) Carnuba Wax, citric acid, corn starch, dicalcium phosphate, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, riboflavin, silicone dioxide, sodium benzoate, sodium starch glycolate, sorbic acid, stearic acid and titanium oxide Yes $0.83
Folgard Folic acid 800 mcg Cyanocobalamin 115 mcg Pyridoxine HCL 10 mg Dicalcium Phosphate; Microcrystalline Cellulose; Starch; Sodium Starch Glycolate; Hydroxypropyl Methylcellulose; Stearic Acid; Titanium Dioxide; Magnesium Stearate; Polyethylene Glycol; Sodium Citrate; Citric Acid; Riboflavin; Blue 1 Lake; Polysorbate 80; Sodium Benzoate; Sorbic Acid; Silicon Dioxide; Carnauba Wax. No $0.28
Metanx Metafolin which is L-methylfolate 3 mg Methylcobalamin 2 mg Pyridoxal-5-phosphate 35 mg Dibasic Calcium  Phosphate Dihydrate, Microcrystalline Cellulose 90, Microcrystalline Cellulose HD 90,  Pyridoxal-5´-Phosphate, Opadry II Purple 40L10045 (Polydextrose, Titanium Dioxide, Hypromellose 3cP, Hypromellose 6cP, Glycerol Triacetate, Hypromellose 50cP, FD&C Blue #2, FD&C Red #40, Polyglycol 800), Microcrystalline Cellulose 50, Opadry II Clear Y-19-7483 (Hypromellose 6cP, Maltodextrin, Hypromellose 3cP, Polyglycol 400, Hypromellose 50cP), Lmethylfolate Calcium, Magnesium Stearate, Methylcobalamin, and Carnauba Wax. Yes $1.48
FABB (brand name: Folgard RX) Folic acid 2.2 mg Cyanocobalamin 1 mg Pyridoxine 25 mg Dicalcium Phosphate, Microcrystalline Cellulose, Croscarmellose Sodium, Stearic Acid, Silica, Magnesium Stearate, Hydroxypropyl Methylcellulose, Polyethylene Glycol   Yes $0.73


Dr. Lynch’s Comments

All homocysteine support prescription drugs are loaded with artificial ingredients such as coloring, preservatives, flow agents, caking agents and others.

Costs vary tremendously between all of them.

The prescription drugs for homocysteine support which do not use the active form of folate (L-methylfolate which is Metafolin) or 5-MTHF, are vastly inferior and should not be used in my opinion. Most people with elevated homocysteine likely have the MTHFR mutation in some fashion. That said, it is imperative that these individuals only take active forms of folate (Metafolin form) otherwise the homocysteine levels will not drop effectively and the individual will have elevated levels of folic acid. Having elevated levels of folic acid is not good and obviously having elevated levels of homocysteine is not good at all.

Having elevated blood levels of folic acid, which are unable to be metabolized (processed by the body), increases the growth of existing neoplasms (cancers). So, in my mind, taking prescription drugs such as Folplex and Folbee and Folguard are not good ideas – especially those individuals with MTHFR C677T mutations are they are unable to process folic acid properly causing folic acid to buildup.

I also do not like prescription drugs utilizing only active folate even if it is the Metafolin form of L-methylfolate. Typically, when one takes only folic acid, the danger of creating a vitamin B12 deficiency is significant and even more serious is the potential to not only create a vitamin B12 deficiency, but not be able to see it! Thus, one may have a vitamin B12 deficiency while taking only folic acid but the doctor will not be able to tell if they order standard labs – and most doctors do only standard labs.

Research is suggesting that L-methylfolate ‘may be less likely than folic acid to mask vitamin B12 deficiency. Folate therapy alone is inadequate for the treatment of a vitamin B12 deficiency.’ This is taken right from the precautionary section from the package insert of Deplin, a well-known high-dose L-methylfolate prescription only product. The package insert is citing five research articles so their information is accurate.

Research is constantly evolving and finding new things out on a daily basis. If current research states that L-methylfolate ‘may be less likely than folic acid to encourage the rate of growth of existing neoplasms,’ that is great. But what is the true definition of ‘may be less likely?’

If the whole point of adding L-methylfolate, vitamin B12 and vitamin B6 is to reduce homocysteine levels in the individual, then I believe finding the lowest optimum amount of each ingredient is a necessity.

Homocysteine is also lowered by more than just L-methylfolate, methylcobalamin and pyridoxal-5-phosphate. Homocysteine is directly lowered by trimethylglycine known as betaine or TMG. Why don’t these prescription medications use TMG? I don’t know.

It is also known that riboflavin, vitamin B2, is required to help reduce elevated homocysteine levels in those with homozygous C677T MTHFR mutations. One may say that adding riboflavin is not needed because the homozygous C677T mutation is not significant in the population. I absolutely disagree.

Riboflavin is inexpensive and if one is going to such an expense to help lower their homocysteine levels, then why not add the most active form of riboflavin possible?

My key point is this:
The main goal here is to lower homocysteine levels safely and effectively with the lowest cost to the individually financially and physically.

That said, if a homocysteine formula contains nutrients which enhance the breakdown of homocysteine from all possible angles, wouldn’t that be the safest option?


Why take more of L-methylfolate if it is not needed? L-methylfolate can only process so much homocysteine as it approaches homocysteine metabolism from one angle.

Adding TMG is a great idea as TMG completely reduces the need for high dose L-methylfolate as TMG bypasses the genetic mutation in MTHFR and is able to lower homocysteine directly. This means, that if a formula has added TMG, then the ability to lower the amounts of L-methylfolate and active B6 is possible to do.

Not only is the potential risk lessened, but the out of pocket expense is lessened as well. L-methylfolate is very expensive. TMG is not very expensive.

An often overlooked issue with prescription drugs for lowering homocysteine is they contain a ton of ‘garbage’ ingredients. These ‘inactive ingredients’ do not benefit the body at all and, in fact, may do harm especially for individuals who have problems in their methylation pathway. I know that MTHFR mutations cause defects in methylation pathways. If there is a defect in methylation, then toxins do not get metabolized well and they end up accumulating in the cells, nerves, fat and bones of the individual. The last thing a person suffering with MTHFR is more chemical burden.

Let’s summarize what we know about standard folic acid:

  • taking only high levels of folic acid now is dangerous as it may speed the rate of growth in existing cancer cells.
  • taking folic acid in the inferior forms is not smart as all who have the C677T MTHFR mutation cannot do anything, or if they can, very little gets processed.
  • a vitamin B12 deficiency may be hidden by taking high levels of folic acid tops it off as a no-no to take alone.
  • Keep in mind how many foods are fortified with standard folic acid. A ton. Breads, cereals, drinks, formulas and more.

Let’s summarize what we know about L-methylfolate:

  • taking high levels of L-methylfolate is safer than standard folic acid or folinic acid in terms of enhancing the growth of neoplasms.
  • L-methylfolate is rapidly utilized by those with MTHFR mutations as this form of folic acid readily bypasses the genetic mutation thereby lowering homocysteine levels. This is outstanding.
  • is less likely to mask a vitamin B12 deficiency when compared to standard folic acid

Let’s summarize what we know about lowering homocysteine:

  • inactive standard form of folic acid doesn’t work well at all for those with MTHFR mutations – especially the C677T mutation
  • active L-methylfolate works very well in lowering homocysteine as it bypasses the genetic defect of the MTHFR C677T mutation
  • TMG, also known as Betaine or Trimethylglycine, works well in lowering homocysteine safely and effectively
  • Vitamin B2, known as riboflavin, is needed by homozygous C677T MTHFR mutations in order to lower homocysteine effectively.
  • Vitamin B12 is needed in order to prevent a vitamin B12 deficiency and to also help lower homocysteine by donating a methyl group. This is why methylcobalamin is the preferred form of vitamin B12. If the individual takes an already methylated form of vitamin B12, the ability for it to help donate a methyl group in the reaction to lower homocysteine is immediate. Basically, methylcobalamin helps transform homocysteine to methionine. There is a less commonly known MTHRR mutation (MTRR A266G) which requires methylcobalmin in order to get homocysteine levels dropped.
  • Vitamin B6, the active form, is the backbone to get L-methylfolate and vitamin B12 to actively lower homocysteine. Without vitamin B6, this reaction does not take place. That said, vitamin B6 helps lower homocysteine.

If I had to choose one prescription drug to help lower homocysteine: Metanx.

However, I prefer getting the job done of lowering homocysteine with the least force possible and covering all angles in as pure and inexpensively as possible.

Optimizing homocysteine levels may be obtained with the above nutrients. HomocysteX Plus provides all the above supportive nutrients in one – and it is completely without synthetic folic acid.

Please do share which prescription drugs you are taking to lower homocysteine and to reduce your MTHFR symptoms. I will add them to the comparison form above.


Dr Lynch

Sources updated on 9/12/2011

  1. Folbee and Folbee Plus
  2. Deplin
  3. Folguard RX
  4. Folplex
  5. FABB
  6. Metanx
  7. CerefolinNAC

*Pricing sources found at and 


  • MTHFRgrl says:

    Dr. Ben,

    I just found out last year, at 26 years old, that I had a Pulmonary Embolism (blood clot in my lung). Before I even knew it, was lying at home feeling i was having a panic attack and felt totally weird i.e.: out of body, everything was going in slow motion, and some chest pains.

    The next thing i know I wake up in an ambulance (I had a seizure) and i cannot even recall what season it was or when my birthday was, when they asked me these questions (normal after a seizure). I have never had a seizure in my life prior to this.

    I then was stabled in the hospital and my hematologist put me on Coumadin hoping it would dissolve the clot. She also checked my blood and told me I have MTHFR, but in a low case, whatever that means. I was also on birth control which apparently made the clot with MTHFR a lot worse.

    Now, i suffer from severe anxiety bc of all of the trauma I went through. I tried Lexapro which made me feel EXTREMELY weird and had an outer body experience, and the panic was worse. My doc concluded i was allergic to SSRI’s and i should never take them again.The only thing that helped me was Klonopin.

    Finally i researched that MTHFR can cause anxiety and depression…and that Deplin could be a good choice. I took one tonight, after consulting with my doctor, and haven’t felt anything yet. I know it takes time, but how much time before the Deplin will start doing its work?

    Please let me know! Thankyou!

  • Heather S. says:

    Dr. Ben,

    I’m somewhat confused, can you please clarify…are you stating that a homozygous individual should take an RX of the L-methylfolate in addition to the supplements that you’ve listed because those persons need more folate than a heterozygous? I would greatly appreciate your insight.

    Best Regards,
    Heather S.

  • Rebekah says:

    Please adjust the ads on this page so the full table is visible.


  • Michaela says:


    I am new to this site, and only beginning to learn. From my lab report I gather that I have the double mutation of the C677T. It is listed in red as positive with the marker “T/T”. I have been prescribed Deplin, Armour thyroid, B12 SHOTS, and a host of other supplements. I have been feeling a lot better, but not 100%. At my last check a few weeks ago my homocystein levels were finally in the green.
    I have not yet had a chance to surf this site extensively, but from what I have read so far, I have not seen B12 shots listed as an alternative to oral B12. I cannot absorb oral B12, therefore the shots.
    Are you able to fill me in?
    I am also ready to stop taking the Deplin and try your alternative instead.
    I look forward to hearing from you.

    • Dr Lynch says:

      Shots work for B12 for many people – I find them overkill for many people – not necessary. Why can’t you absorb B12? Studies show that even with pernicious anemia, high dose B12 lozenges elevate B12 levels. Yes, T/T = the risk alleles for the MTHFR 677 variant. The alternative I formulated is not nearly as potent as Deplin but I also dont believe Deplin is the right choice for many people. If you feel good on it, great – it may be for you; however, if you start getting side effects, then time to reconsider. Some people do well for a while with methylfolate at high dose and then need to drop down very low. HomocysteX Plus is the formula I’ve designed to support the methionine cycle.

      • amy says:

        Dr Lynch I am hetero c677t, also apoe 3/4 and high lpa (135 nmol) so i take homocystex plus .. i have read recently that TMG can raise cholesterol levels do you see it as an issue as lpa is hard to modify the current protocol is to lower ldl as much as possible (with a very strict diet and daily hitt cardio) my ldl is still 123mg

  • Melinda Roman says:

    Based on complete genetic profile it seems that some people tolerate hydroxyl b12 better than methyl b12. Is there a product, multivitamin that contains hydroxyl instead of mehyl b12?

  • Paula says:

    Hello, Dr Ben,

    I recently had extensive lab tests done that revealed info under the “Coagulation Genetics” category regarding 2 subgroups:
    1. Subgroup: MTHFR (A1298C) rs 1801131, revealed “Intermediate risk,” @ an estimated genotype frequency: A/C (~ 30%)

    2. Subgroup: MTHFR- C677T (rs1801133; Methylenetetrahydrofolate Reductase) revealed “Optimal,” @ an estimated genotype frequency: C/C (~ 49.3%).

    3. As a history, I am 65 years old, and about 25 years ago I started having some mild blood coagulation problems that manifested themselves when I was donating blood. It would come out slower and eventually stop, so I could not donate the full pint, and had to stop giving blood. I never checked into this, but it can still happen when a doctor draws blood for testing. If they need alot, it ends up slowing down considerably and they get the blood but it takes awhile. With these new lab test results for #2 subgroup above, the doctors office recommended l methylfolate to improve brain functioning and help prevent blood clots.

    Also, about 25 years ago I started having extensive digestive issues that manifested itself in diverticulitis, IBS, leaky gut, fibromyalgia, chronic fatiguea, thyroid issues / inflammation, autoimmune type things, and some brain fog and memory issues. Recently through all the research I have done, I put 2 + 2 together about the digestive/leaky gut problems, and how the thinning of the intestinal walls c created an environment were foods/bacteria could leak and cross the blood/brain barrier. Seven months ago I had a severe attack of IBS and small growth bacteria and this ended up resulting in healing with antibiotics/non gluten wheat diet and non processed foods (which I have been doing for 7 months). Whereas, 25 years ago I noticed brain fog and minor memory issues that have lingered, this eposode I noticed another level lower in my memory challenges, which greatly concerns me.That, combined with the above lab finding regarding subgroup 1, hence, I am writing you.

    My doctor just prescribed “podiapn, which is a medical food. She relayed that this was methyfolate, a less expensive one. Can you please provide your view on my lab numbers, and this prescription and what it is? There was no written documentation with it, maybe because it is described as a medical food? Thanks in advance for your help.

  • Laura says:

    Hi Dr. Ben,

    I’m 7 weeks pregnant and seeing a Reproductive Immunologist who just prescribed me to take Metanx, once daily. I was dx with MTHFR 677T (heterozygous) mutation but also a PAI-1 heterozygous mutation (not sure if you’re familiar with this one). She has me on a prescription prenatal called vitaPearl, which has the activated folic acid (4mg?) and now wants me to take the Metanx. I’ve been trying to find research saying whether this is safe to take during pregnancy, but really there’s not much out there about it, and everything says it’s unknown whether it’s safe to take. What are your thoughts on taking Metanx if pregnant?

    Thank you,

  • brother's keeper says:

    I read the following quote in one of you’re replies. Please help me understand. If I can buy a supplement, then I should be able to get its elements from what the supplement is made of. Some item in creation, or you couldn’t put it together to sell it. It doesn’t make sense that there it’s no food or substance somewhere I can take in some form of you can get it to make your formula.

    “You cannot ‘create’ L-methylfolate through B12, B6, B2, etc – can’t happen.

    You have to buy it sadly.

    Cannot even get it from food.

    But you do need to have B12, B6, methylfolate, TMG and B2 to effectively reduce homocysteine and balance the deficiency caused by the MTHFR mutations.

    • Dr Lynch says:

      Hello –

      You CAN get methylfolate from food – leafy greens. That statement is old and incorrect. Love to know where that statement is so I can fix it.

      • Hanna says:

        It’s higher up on this page, posted on Sept 16, 2011.

      • Elizabeth says:

        Dr. Lynch,
        I am compound heterozygous for MTHFR. Would your Optimal Prenatal contain all I need for pregnancy or should I also add something extra?? Please help. Thank you!

      • Kelly says:

        Just to let you know Dr. Lynch — it still says above that you can’t get methylfolate from food.

        My quick question: Can one take too much TMG? And if so, how would that affect methionine synthase and folate metabolism?

        Thank you for all your work!

      • Apryl says:

        If we can get already methylated Folate from food then why the need to supplement?…. This mutation seems irrelevant then. And more of a problem of poor diet and the addition of synthetic folic acid in the food supply. But is the mutation effects ones ability to convert naturally occurring folate then his mutation seems very relevant… Hence the need for supplementation. This is not made clear enough

  • Christi says:

    I had to ask my DR to test me after my brother tested positive. I have the 677 and the 1298. I’ve had cancer 3 times, been diagnosed with CFS and fibromyalgia among other things. I’ve always taken b12 injections since I was 18 but not the methyl b12. I’ve ordered a couple things from Thorne but I really dont know what I should be doing. I would love to feel better! My doctor said ‘yes, you have it but theres really nothing you can do about it’. Where do I start??

    • Reda Nafso says:

      I don’t do well on Thorne. I’m heterozygous 677 & 1298. I started feeling ill about 10 yrs ago not knowing why my body kept rejecting my multivitamins and I always felt ill. I had to get shots of b12 non methylated. I would feel sick afterwards so I stopped. I have adopted mainly a vegan diet and will do lean meat once or twice a week. I react to meats, dairy, eggs and gluten. I do a lot of quinoa and some vegetables. My b12 is too high so now I’m only taking b minus supplements by Dr. Lynch’s Seeking Health. I would like to take the optimal start but there is herbs in that formula and almost always have an allergic reaction to most herbs. I just ordered the probiotic formula.

      Dr. Lynch – will you please make an optimal start vitamin without the herbs?? I just think a lot of us with this genetic disorder or whatever its called would be more than happy to purchase.

      Thank you


  • Heather says:

    Hi Dr. Ben,

    I just found your website. I am specifically interested in what to do for my 11-year-old daughter who was diagnosed as homozygous for the A1298C mutation when she was 6-years-old. I have been giving her 400mcg of 5-mthf since then, but wonder what else I should do. Her pediatrician tested her for the gene defect because she has severe anxiety, proprioceptive sensory dysfunction, dyslexia, and visual sensory integration.

    I just wonder if there’s anything else I should be doing to increase her ability to function normally. It’s such a difficult thing to measure without a baseline. Most of the info I’ve found on your site addresses the other (677) mutation.

    Is there a typical supplement recommendation for the homozygous 1298?

    Thanks so much,

    • Dr Lynch says:

      Heather –

      Use the same info which discusses 677 – it’s basically the same thing – in fact it is. Just lower amounts of methylfolate are needed – but not always – some people need more or less methylfolate regardless of their MTHFR status – for various reasons.

      • Elizabeth says:

        Hello Dr. Ben,

        I saw a great doctor about my compound heterozygous MTHFR. He suggested I take 1000 mcg of methylfolate a day and 500 mcg of methylcobalmin twice a week to start out, and work up to 500 mcg three times a week if tolerated. I have experienced anxiety issues in the past, but since eliminating gluten and dairy I have felt great. I am really trying to avoid getting overmethylation symptoms b/c I don’t want to feel anxious. My questions are-

        Will 500 mcg of methylcobalmin twice a week along with 1000 mcg of methylfolate a day prevent the methy blocking I read about that can occur if you don’t have enough B12?

        Since we are getting ready to start trying to have another baby (after 4 losses), I would like to start taking your prenatal multivitamin. I think the doses of folate and B12 in it are pretty close to what my doctor told me. The methylfolate is 200 mcg less per day, but that wouldn’t matter much right??

        Thank you!

  • Amy says:

    Hello, I am homozygous C677T, with depression since childhood plus other symptoms, my doctor gave me samples of EnLyte, which has 8 mg or so of folic acid in various forms, and 25 mcg of other b vitamins. I started taking the pills, but then was warned by others that it may be too much folic acid. So I stopped. Now I want to get my homocysteine tested but don’t know how long to wait after stopping the EnLyte to get a good baseline reading. Your thoughts?

  • Bob says:

    Hi Ben, hear about you through Sean Croxton. I tested positive for the MTHFR A1298C G/G homozygous and my wife tested positive for MTHFR C677T A/A homozygous.

    1) I am trying to understand what these letters G/G & A/A mean then I see CC, AC etc. I have been searching for days for an answer, what is G/G for me, then A/A for my wife? have a link that explains this in layman terms?

    2) Can we both take the same supplementation? not clear on that. Then do you have a product/supplement for this? What would you suggest we take?

    3) We had two children, It sound like that they could be Compound Heterozygous or Compound Homozygous. They are 25 & 30 yrs old now and one is Type 1 diabetic and the other has been diagnosed with Celiac. I suppose they should get tested or since we both have the mutations it is pretty much guaranteed they have it right? its just a matter of Homo or Heter & I suspect being compound, right?

    Thanks for your help in clarification on this.

  • Ashley says:

    Hi Dr. Ben,

    I have heterogenous mutations. Is the Homocystex Plus supplement safe to take while breastfeeding? I took Folgard RX throughout the pregnancy and for the first 5 months of breastfeeding per my RE. Or should I stop supplementation and resume when I stop breastfeeding? Thank you!

  • Samantha says:

    Dear Dr. Lynch,

    I wanted to order the HomocysteX Plus and I noticed that it said Turmeric was useful if too much was taken. How does Turmeric affect those with MTHFR in general? I make a “golden milk” with Turmeric in it because I thought it was healthy, but it sounds as if it may have a negative affect? Is that the case?

    Thank you for your time and expertise,


    • Aron says:

      Hi Samantha – Turmeric is an extremely safe anti-inflammatory. It is the HomocysteX Plus you must use carefully. Dr. Lynch recommends turmeric to quench inflammation if you experience side effects from taking methylfolate. He wrote an article about minimizing the chance of methylfolate side effects here:

      Turmeric is perfectly safe and beneficial to have on a daily basis.

      -Dr. Aron

  • Meghan says:

    After reading this comparison of homocysteine support products, I just wanted to recommend the product that I take, which is available without a prescription. I am homozygous for MTHFR c677t; I use Methyl-Guard Plus by Thorne Research. It contains Riboflavin 5-phosphate sodium, Vitamin B6, L-5-methylfolate, methylcobalamin, and TMG (Betaine Anhydrous). It’s working well for me!

  • brenda says:

    We are taking Metagenics Vessel care

  • irishgirl says:

    Hi there Dr Ben/Anyone else who can advise

    I love your website and have been fascinated since discovering it a few weeks ago

    A bit about me, and I’ll try to keep this brief as no doubt you’re inundated with queries from people.

    My story is, I’m, 37 and struggle (quite literally) with borderline personality disorder. It’s a diagnosis I agree with unfortunately. My emotions are so extreme that they come out of my skin and I am floored with depression and hyper-sensitive to people’s treatment towards me and I experience such anxiety, social anxiety, depression, hurt, disbelief and rejection at others’ insensitivity. It results in my plotting revenge in my head (something I never actually carry-out though). I cry very very easily also.

    I am getting therapy for it, and last week, I discovered methylation through your site and learned more and more as time went on. To point out, I live in Ireland and there is nobody that tests for this bar one person, and I don’t have $500 unfortunately. It’s out of the question for me as money is tight also.

    So I emailed a professor here in one of the universities who researches molecular science. She emailed me back and told me to go ahead and get the vitamins. So I bought; Solgar 400ug (mcg in the United States I think) of Methylfolate (as Metafolin) and Solgar Vitamin B12 Sublingual cyancobalamin 1000ug vitamins. After three days, it was almost a miracle happened; I felt calmer, the obsessive thoughts and anxiety almost diminished and I could have bathed in the relief. However, I had a weekend away and forgot to bring my vitamins and the symptoms came back. I also started an antipsychotic drug from a psychiatrist here called Risperadol 0.5mg but I cut it in half and I am taking 0.25mg therefore. I just wanted to start on a low dose. So, I am back on the vitamins, but the improvement is slower this time? if at all? This methylation is SO interesting and I know I have it. I know. I just haven’t the money to get tested. My mum has high blood pressure. Her sisters (my aunties) all have chronic rheumatoid arthritis and one of them has associated heart failure and COPD with it. Her daughter (my cousin) actually died three years ago aged 33 from Spina bifida, a condition she was born with. I really want to shout this discovery from the rooftops to them that it could be the B12 and folate deficiency. I also come from my father’s side where they were all academic geniuses but chronic, albeit functioning alcoholics.

    I realise that it’s quite difficult for you to advise without my data. However, is there anything I can do to optimise? What else would you recommend I take? Is there something I could introduce? I have since ordred the Jarrow B12 Methyl vitamins and I am waiting on them to arrive. I also have bought the Dr Udo’s Choice Probiotic with 42million bacteria for the gut.

    Honestly, it feels like my brain is isolated and for some reason (up until now) no tablet could reach it and fix whatever neurotransmitters that were broken.

    Many thanks in advance from across the Atlanic

    IrishGirl 🙂

  • Susie says:

    Hi Dr. Ben, I am heterozygous with one copy of the A1298C and one copy of the C677T MTHFR mutations. I am taking METHYL-GUARD by Thorne Research. It is not a prescription medication. It is a supplement recommended to me by a naturopath. Have you heard of this one? Thank you so much. Thank you for all you do!

  • Michelle says:

    With all the talk on getting homocysteine down to a safe level, has anyone experienced low <5 homocysteine with homozygous C677T +/+ and negative A1298C -/- ? Could this be from a CBS upregulation issue and if so, would methylation support of any kind be needed or is just keeping an eye on sulfur and ammonia good enough? As far as I can see, this scenario is not discussed anywhere on Dr. Lynch's protocol pages. Thank you in advance.

    • Anna says:

      Michelle, did you ever find any information about your question? I had the same thought about whether CBS upregulation offsetting (potential) low methylation levels.

      I am in my early 40s, found out that I am homozygous C677, CBS, MTRR, SOD2, MAO-A, GSTP1 and heterozygous for a number of other snps. The thing is, other than occasional hormonal acne, being a shy “worrier”, and not liking smell of chemical clearners, I don’t have any major health issues (yet!). I had two textbook pregnancies with zero issues with fertility. I do eat very healthy (leafy greens, no processed sugar, no caffeine, no dairy, no alcohol, no excess salt, no red meat, etc) and I do exercise. I try to reduce my stress levels too now.

      Am I a walking time bomb with these multiple genetic mutations? I’ve read through hundreds of these comments and most of these people are ill. I’m not sure whether I should get my levels tested at this point, start taking basic supplements (B Minus, etc) and see if I feel any different, or just hold off.

      Being a very healthy conscious person, now that I know this information, it’s hard to ignore.

  • alexis says:

    First of all I have been studying MTHR and homocysteine levels for 3 years now since I was diagnosed and this has Been by far the most helpful page yet. So thank you for that. Next, after having 4 miscarriages in a row I was diagnosed and put on foltx, baby aspirin, and a homocysteine formula by bluebonnet, as well as put on a strict diet with zero dairy and soy products. After doing this for 6 months I finally became pregnant with my now 1 year old healthy baby boy. We are now wanting baby number 2, but I have not only learned my magic combo from before was not the perfect combo, but my son is still nursing so the baby aspirin is out of the question. I saw a specialist who recommends taking the prescription podiapn. He seems to think one pill twice daily is my cure all that this will allow me to continue to nurse while trying to conceive all safe for breastfeeding and will help prevent miscarriage as well as keep baby number 2 healthy as far as receiving folate for defects…….. what are your thoughts on this particular medical food? ?? I appreciate any information and advice very much as I am terrified of any more miscarriages. Thank you so much!

    • Monica says:

      Wanting to know your thoughts on PoDiaPN. Does it supply the correct dosage of supplements?

      • Dr Lynch says:

        It provides some good nutrients. It does not provide TMG which is also supportive of homocysteine metabolism. Vitamin B2 is also useful as a cofactor for MTHFR which is a main enzyme in homocysteine metabolism.

        Thus, I recommend a formula I developed called, HomocysteX Plus.

        Please discuss with your healthcare professional.

  • Sierra says:

    I think the MTRR gene is A66G (not A266G), as mentioned in article

  • i am buying some supplements in that igredients is

    microcrystalline celloluse

    hydroxypropyl methylcellulose



    and i have done a test for 23andme and waiting for result,

    this all for my son 5 years old who have hasimotos

  • I just ordered the optimal multivitamin that already has the l-metholfolate in it. I am heterozygous. I have been taking Metanx, but consider it a little too strong. My question is: Should I also be taking Homosytine formula along with the multivitamin? I am still trying to figure all of this out. Thank you!

  • Delia love says:

    Please can I schedule a consultation? ? I have been suffering for about 10 yrs. now. I have been test for everything but this.Just got tested for the MTHFR. I have both C677T and I believe C677TT. And the A1298C. My ANA levels elevated. And I have hashimotos. SO confused! !!! I take care of my 84 My 22 yr. daughter which is been diagnosed with everything under the sun! And my thirteen year old son. Please help I spend more and more time trying to find a way or just a minute to get in bed.
    My life is wasting away in front of my eyes. And u r the only light I can find!!!!,please. ..

    • Dr. Aron says:

      Delia – Dr Lynch can no longer provide consultations. Please reach out to a doctor on the Physician Directory. Some also do phone consults. Dr. Eric Balcavage and Dr. Bernarda Zenker are excellent. I recommend reaching out to them. Wishing you the best.

  • Megan says:

    I am positive for 2 copies of the A1298C mutation. My doctor has me on a Metafolin vitamin, as well as the methylated versions of B12 and B6. However, the vitamin does have folic acid in it as well…. when I asked her if I should stop taking that and avoid folic acid at all cost – she said that folic acid is a water soluble vitamin and our body will convert it into urine and we will pee off the excess that we don’t use. Also, I read that if you have a lesser severe version of the MTHFR mutation it only reduces your ability to convert folic acid by a percentage – for example with my mutation I read that I still have 40% ability….. are either of these things true?

  • Bobbie Sue says:

    I currently am taking ProdiaPN b.i.d.
    and it is not covered by insurance, which the cost is around $40 per month.

  • Vicki says:

    My doctor has prescribed Enlyte for my methylated folate needs. I had medical genetic testing which showed I have the MTHFR mutation. I am taking this for assistance managing depression and anxiety. The problem for me is that the Enlyte formulation contains 1.5mg elemental iron, and I also have thalassemia and should not have iron.

    I am looking for a formulation of methylated folate that does not have iron.

  • Danielle says:

    Dr. Lynch
    I am homozygous for C677T. I am currently taking 15mg deplin daily in conjunction with depression medications. Am I reading this correctly to the fact that you are saying that is not a good idea? I have just had labs done to check my B levels, but you think that they will not correctly show my true B levels because deplin masks it? Just wanting to get this right. Thank you.

  • Denise Belk says:

    Hi! My doctor gave me some Deplin 15 samples to take to bridge the gap while I was waiting to place and receive my Homocystex order. I felt amazing! It took me a little while to get around to placing my order and I felt great on the Deplin. When my Homocystex arrived, I stopped the Deplin and just took the Homocystex. After a week, I wasn’t feeling as “bright” as I had on the Deplin. I added the Deplin to the Homocystex. So far, the combination seems to be working well for me. I had my vit B-12 levels tested when I was on the Homocystex, they were fine. (I am heterozygous for both MTHFR mutations.)
    Thanks for your terrific website!!!
    ~ Denise

  • Daniele Ponzini says:

    Good morning Dr Lynch,

    I’m following your MTHFR C677T Mutation: Basic Protocol but I’m a bit confused .
    I realised that B12 and Methylfolate has to be assumed sublingually becouse of absorbition problems.
    So , why your HomocysteX product is not sublingual ?
    Thanks a lot


  • Ann says:

    Since this article has been written there is a newer drug called EnLyte that has come out that has L-Methyfolate and some of the necessary B vitamins for proper Homocysteine in the Methylation process. Do you have any thoughts on this prescription supplement? Would Mentanx still be your one of choice?

  • Julie says:

    Can you please tell me how I can lower my folic acid levels? I take l-methl avoid folic acid but my levels are still off the charts high. My homostiene levels are normal and vit B is normal. So what am i missing?

  • Amanda Hutchinson says:

    I am taking Metnx and vitamin D. Is there something I should take in addition to this medication to make it more effective?

  • Amanda Hutchinson says:

    I am homozygous for C677T I am extremely tired all the time. I am taking Metanx and Vitamin D. Is there something I can take with the Metanx to enhance the effects?

  • Jennifer says:

    Dr. Lynch,

    My 21 year old daughter has one copy of A1298C (+/-) and one copy of C677T (-/-)? Can you tell me what your recommendation would be and what health risks she needs to be most worried about? She has always had mental health related issues. She had hers tested through Prescient Medicine for pharmacogenics, while in residential treatment. However, they gave us NO RAW data, only a printout, so i am trying my hardest to decipher.

    So, if I go to 23andme, which selection is better, and what is the difference (in terms of submitting the RAW data to have the genes analyzed). The $99 or the $199 package?

    I would like to have mine done, then eventually, the rest of the family. Please help recommend which to pick.

    Thanks, because this can get very confusing, although VERY interesting.

  • Kathryn says:

    Hi. I had an RIND 15 years ago and just had a BRAO a month ago. My homocysteine level was 30 at that time. I was immediately prescribed a statin and Plavix. I’d already been on aspirin therapy since the earlier event. Fortunately I have identified the three Functional Medicine docs in my area quickly–but they all seem to have different areas of expertise: hormones/thyroid, allergies/gut, and liver detox. I just got my genome data back this week so am able to stop guessing about my MTHFR status and several other things as well. However, I’m going to have to work with all three docs to get all of my needs met, I think.

    The thyroid/hormone doc just recommended I wean off the statin and go on Metanx. But since I’ve had such dramatic allergic reactions to all B-vitamins in the past, I looked it up on your site first and found your response here…so I’m thinking I will take one tonight and see if my face breaks out into a rash or not–and also order your HomocysteX Plus. I think my doc would be fine with that–he’s always concerned about the high cost of the Rx meds.

    Here’s my status: homozygous for C677T of MTHFR = 10-20% efficiency in processing folic acid = high homocysteine, low B12 and folate levels; Carrier of Medium-Chain Acyl-CoA Dehydrogenase Deficiency; rs6025(A;G) bad:3.40 1.19%(rare) Prone to thrombosis.

    I’ve just found out about all of this at the old age of 63 with many medical issues my whole life. So I’m excited to know there’s something to DO that’s not toxic to help!!! Thank you for your research and commitment~you are appreciated. _/\_

    • Dr Lynch says:

      Hi Kathryn –

      Glad you’re empowered to get to the bottom of your health concerns. Definitely MTHFR C677T homozygous is playing a part. I highly recommend running your 23andMe raw data through so you can see what other key SNPs are present.

      Finding a doctor who is a skilled GENERALIST and knows about SNPs is key. Going to three docs is not going to be fun here. Your body is one – and cannot be split up amongst three docs. Here is a great directory of professionals I’ve trained over the years -and many do online consults as well.

  • bryan says:

    my doctor gave me folbee which lowered my homocysteine every 4 weeks from 12.5 to 11.8 to 11.0. then i started taking homocystex plus for 5 weeks 1 per day and my level went up to 12.4. have you heard of this before?? i have both mthfr mutations so i’m a little confused if i should go back to folbee or take them both together? any advice would be greatly appreciated.

    • bryan says:

      I have to add that i feel great with homocystex plus.

    • Dr Lynch says:

      Hi Bryan –

      Great question. First I am pleased to hear you felt great on the HomocysteX Plus.

      Yes – I get why. There are a few variables at play.

      1) Did you have the same size meal the night before your blood draw?
      2) Were you fasting?

      If yes and yes, then you simply weren’t taking enough of the HomocysteX Plus. I would consider taking 1 capsule with breakfast and 1 at lunch. Folbee has 2.5 mg of folic acid while HomocysteX Plus has 800 mcg of methylfolate plus another 700 mg of TMG which is great – and the active B12’s and B6 and B2. Start there – with 2 a day and see how your homocysteine levels do. If you need another capsule, give another a shot. You may need to load up for a bit and then taper back down again.

      Do watch your protein intake – to about 1 gram of protein per 2 lbs of body weight or so.

      Note that with Folbee – the folic acid is lowering your ‘extracellular homocysteine’ but not helping your intracellular levels – and that is a major difference. Research shows this.

      Do watch this when you’ve a moment.

      You may also need to read this ‘Preventing Methylfolate side effects’ – and prepare yourself better with electrolytes and glutathione. If low in either, not only will you not feel optimal, but you may have side effects from the methylfolate.

      • Debby Smith says:


        I am on Deplin 15 can I take your product with it? I have two forms of MTHFR mutations. Ni side effects but worried about the lowering of b12 ect.

  • I have heterozygous C677T. My OBGYN gave me a prescription for L-Methyl-B6-B12. I am not sure the brand or anything like that, but that is what it says on the prescription bottle. Should I be taking that. I am new to MTHFR and am trying to learn what I should be doing and what I can do for my 11 month old.

  • wolf max says:

    please make chewable lozenges for B complex +, B minus, and Homocystex +

  • Tehra says:

    Hi there, I am a compounding technician at a pharmacy, and just wanted to chime in that having your supplements compounded is always an option…. though price wise, you would need to have a pharmacist list all the ingredients for your medical plan (if you have one) if you want to see about coverage. I make a lot of P5P, 5MTHF, methylcobalamin combos. Some also include oxaloacetate–supports citric acid cycle. Cheers

  • Jessie says:

    Hi Dr. Lynch-

    I am 27 weeks pregnant. I have suspected for a long time that I am a carrier of the MTHFR genetic mutation, therefore I immediately started methylated vitamins when I found out I was pregnant. I asked my OBGYN to test for it and she said it was positive, but she didn’t tell me which mutation(s) I have. Shouldn’t she know that? Where can I get that information? What kind of doctor do I need to be seeing to help me manage my MTHFR mutation?

    I have MCTD (Mixed Connective Tissue Disease), unbelievable fatigue, awful brain fog, Prinztmetal Angina, Mast Cell Degeneration, Alcohol allergy, severe anxiety, digestive issues, shortness of breath, muscular and joint pain, sever sensitivity to light and smells, migraines, Reynaud’s, TONS of food allergies (ironically, my food allergies IgE, IgG etc. are almost all foods to avoid on the low-histamine diet…and no doctor has ever out 2+2 together that I may be MTHFR positive. I have been gluten-free going on 8 years now. A concern is I am on medications that apparently exacerbate the MTHFR and lack of breaking down histamine. Suggestions? I take Plaquenil, low-dose aspirin, EPA/DHA, Smarty Pants Prenatal and Homocystex daily.

    I was living in a home filled with Stachybotrys mold (seller’s didn’t disclose previous water damage). I have been mold ill since.

    Any suggestions are greatly appreciated! I am so tired of feeling horrible everyday.

  • Macauley says:

    Hi all. I am currently taking Podiapn (1 per day) for MTHFR mutation. The twice daily sent me into panic attacks. Once daily has worked well for me but looking for a cheaper solution. Can this be replaced by the Homocystex?

  • Debra Lane says:

    I have mthfr c677t. I am now taking 1 tablet of metnax at night and “seeking health” active B-12 with L-5-MTHF – 1 tablet in the morning. I take 3 soft gels of nortic naturals ultimate Omega ( 1280 mg Omega-3) in the morning + a low dose aspirin (81 mg) once a day. Should I be doing anything different?

  • Debra Lane says:

    I have MTHFR-C677T . I am now taking 1 metnax at night and 1 (Seeking Health) Active B-12 with L-5-mthf, 1 tablet of low dose 81mg a day..also 3 soft gels of Ultimate Omega 3 (1280 mg Omega-3) should I be doing anything else?

  • Traci Hill says:

    Where can I get tested for mutations? Online
    Direct customer testing available? What exactly is the tests called? About how much? Thank you

  • Lisa says:

    What is your opinion of podiapn? That’s is what I was prescribed.

  • lori says:

    Hi. This article is 8 years old. Do your recommendations hold or f not, can you update your article? thank you.

  • Charlotte says:

    Dr. Lynch-
    I’ve had multiple miscarriages. I just found out that I’m homozygous MTHFR with 2 copies of A1298C. I’ve been prescribed Metanx and Neevo DHA (prenatal.) I exercise and eat KETO. Is there anything else that I should be taking to increase changes of having a healthy baby?

    • Hi Charlotte –

      Metanx and Neevo DHA are pretty incomplete. They’re ok but far from optimal.

      You definitely need more support and I’d start now.

      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.

      If you prefer capsules, you can switch back and forth every other day or so 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! 🙂

  • Katrina says:


    I am in Australia and using a brand called Metagenics if you’d like to add this to your supplement list above. Metagen Methyl-Active Ingredient List: Serine, Pyridoxal 5-phosphate monohydrate (B6), Riboflavin sodium phosphate (Riboflavin 5-phosphate sodium), Equivalent Riboflavin (B2), Mecobalamin (Co-methylcobalamin + B12), Levomefolate calcium, Equivalent Levomefolic acid (5-methyltetrahydrofolate).

    Also, can you please advise if it is safe for women to use Mirena if they have two copies of the gene mutation? I have been off birth control for 7 years and recently had to get the Mirena due to heavy clotting during my cycle. I’ve since been experiencing lethargy, bloating, and brain fog (which I had under control previously). Side note: I also had an iron infusion earlier this year because my ferritin stores were quite low and I was experiencing dizziness and feeling tired.

    Thank-you for your work and time.

  • Melissa Jackson says:

    What’s wrong with metanx for compound heterozygous?

    • Melissa –

      First of all, one shouldn’t prescribe medications for MTHFR based on genetic results. The prescription should be done based on more factors than this.

      Metanx contains a lot of filler ingredients which are not needed and require more work from your liver to process.

      These are the ingredients of Metanx:
      Each METANX® capsule contains 3 mg of L-methylfolate Calcium (as Metafolin®)*, 90.314 mg of Algae-S Powder (Schizochytrium), 35 mg of Pyridoxal-5´-Phosphate and 2.0 mg of Methylcobalamin *CAS#151533-22-1

      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

      I prefer people using HomocysteX Plus as it’s cleaner, is less potent so better chance of helping the person vs experiencing side effects from taking too strong of a formulation, and is more comprehensive as it contains TMG which helps support methylation significantly which reduces the need for pushing such high amounts of MTHF and vitamin B12 which are known to cause side effects at high amounts.

      • wolf says:

        “high amounts of MTHF and vitamin B12 which are known to cause side effects at high amounts” can you expand with some detail on that for those of us too pain/fatigue-challenged to investigate every nuance deeper?

  • Yvonne says:

    How does the FDA approved “drug”, Enlyte compare. I have a milder case of MTHFR. Not sure if it effects me.

    • Hi Yvonne – I don’t like Enlyte because it contains Folic Acid – plus Enlyte is very expensive because it’s prescription. Supplements which may support MTHFR are way less expensive. Here are some MTHFR supplements which may help you – but I highly recommend reading Dirty Genes – first! 😉

  • Nancy Gingrich says:

    Thank you for sharing your knowledge about MTHFR, how prescription drugs don’t do the trick, and for your recommendation for Homocystex Plus. I have been taking this supplement for years and found it extremely helpful but just a few weeks ago I found it unavailable thru Seeking Health or any other website. For lack of know what to do I did without it for a couple of weeks and noticed I was “hitting a wall” by mid day every day, unable to function. So I went on a web search and found Methyl B Complete by Pure Therapro. Are you familiar with this substitute for Homocystex Plus and would you recommend it or have other alternatives to suggest?

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