L-Methylfolate (5-MTHF): Your Must-Read Beginner’s Guide

L-Methylfolate (5-MTHF)- Your Must-Read Beginner’s Guide

[Last Updated 6th December 2017]

Folate and folic acid are nutrients required for many critical functions in the body.

Unfortunately, many who have a genetic MTHFR mutation are unable to utilise these nutrients properly.

L-Methylfolate (5-MTHF) has emerged as a popular alternative, and has been used as a complementary medicine in several recent clinical trials.

This article covers what you need to know about it, but explained in human terms.

What is L-Methylfolate (5-MTHF)?

What is L-Methylfolate?L-methylfolate is the biologically active form of vitamin B9.

That means it is the form the human body can actually use in circulation.

It goes by several other common names including:

  • Methylfolate
  • L-Methylfolate calcium (refers to the calcium salt molecule it is attached to)
  • Metafolin and Deplin
  • 5-MTHF and L-5-MTHF (in this article 5-MTHF refers to L-5-MTHF)
  • Levomefolic acid
  • 5-methyltetrahydrofolate
  • (6S)-5-methyltetrahydrofolate and Quatrefolic.

The letters or numbers before the name refers to the 3D chemical structure of that compound.

In this case all you need to know is that L- and 6(S)- indicates biologically active L-Methylfolate (helpful). D- and 6(R)- indicate non-biologically active L-Methylfolate (not helpful).

Some products may only list Methylfolate or 5-MTHF, without specifying if which form it contains. If the label does not state L-Methylfolate, Metafolin or Quartrefolic then it may not be the biologically active form.

Summary: L-Methylfolate, also commonly known as 5-MTHF, is the active form of vitamin B9 the human body can actually use. L- and 6(S)- forms are biologically active, while D- and 6(R)- are not.

L-Methylfolate vs Folic Acid v Folate

The other forms of vitamin B9 you should know are folic acid and folate.

These are the forms we eat, although L-methylfolate is also found naturally in some high-folate food too.

Folate is often called the natural form of vitamin B9, but it actually refers to a family of different compound that occur naturally in some vegetables.

Folic acid is the supplemental or “synthetic” form of vitamin B9 and is typically the first line of treatment for folate deficiency and related health conditions, such as high homocysteine and Neural Tube Defects (1, 2).

In fact, it has been so beneficial for the general population that the addition (fortification) of folic acid to wheat flour is now mandatory in Australia, USA, Canada and several other countries (3).

But note that folic acid is also found naturally in foods, as it is just another compound of folate.

Any folic acid we ingest must be metabolised (converted) into Dihydrofolate (DHF), Tetrahydrofolate (THF), and then finally into L-methylfolate (5-MTHF) to be used in the body. Once in this form it can be transported into cells, tissues and even across the blood-brain barrier.

This is what they look like alongside each other… you can see they are almost identical:

folic acid, tetrahydrofolate and 5-MTHF structure

Image source.

But issues can arise during metabolism for those with an enzyme issue, such as an MTHFR mutation.

These individuals cannot complete the final metabolic step that converts folic acid to the active form L-methylfolate (5-MTHF) (4).

L-Methylfolate (5-MTHF) has emerged as a popular alternative to folic acid. This article covers what you need to know about it, but explained in human terms.

Note that the last step (the last black arrow) requires the MTHFR enzyme and Vitamin B2 to convert 5,10 methylene-THF to L-methylfolate.

This leaves folic acid supplements somewhat useless to you and potentially harmful in the long run (5).

Summary: Any folic acid or folate we ingest must be converted into its active form (L-methylfolate) to be useful. However this becomes a problem if you cannot do this conversion effectively, such as those with an MTHFR mutation.

Benefits of L-Methylfolate (5-MTHF)

Supplementing with L-methylfolate bypasses the entire folic acid metabolism cycle, which is good news if you have an MTHFR mutation.

Think of it like receiving a cooked meal instead of all the raw ingredients. An MTHFR mutation is equal to not having the pots and pans to cook with.

Studies show that L-Methyfolate supplementation is equally (if not more) effective than folic acid for increasing circulating folate in those with an MTHFR mutation. It is also highly effective at reducing homocysteine levels in healthy people (6, 7).

It is also better absorbed and interacts with fewer medications than folic acid (8).

What should I eat with an MTHFR mutation?

Get your free guide here:

Or click here to download the guide.

Summary: Research shows it is just as effective as folic acid, if not better absorbed and tolerated.

L-Methylfolate During Pregnancy

L-Methylfolate During PregnancyActive folic acid is highly protective against Neural Tube Defects.

This is why all national and international health organisations advocate for folic acid supplementation before and during early pregnancy.

For those who do not metabolise folic acid well, supplementing L-Methylfolate is the clear alternative while pregnant. Especially if you have a homozygous C677T or A1298C mutation, which is thought to increase your folate requirements even more.

The link with miscarriage

Understanding why miscarriage occurs at all is still an active area of research.

Many large observational studies have found a link between MTHFR mutations and increased risk of miscarriage, at least for those of Asian decent (9, 10).

Not all studies found the link, and observational studies do not prove cause and effect, so we cannot say if it’s true for certain. Considering the important role of active folate in fetal growth and development, ensuring adequate L-Methyfolate intake should be your top priority.

Summary: Supplementing with L-Methylfolate while pregnant is the clear alternative for those who suspect an issue with metabolising folic acid.

Other L-Methylfolate Benefits

There are several other areas of health where it has been trialled or used successfully in treatment:

L-Methylfolate (5-MTHF) in depressionL-Methylfolate (5-MTHF) in depression

L-methylfolate is becoming widely recognised as an effective complementary medicine for patients with severe depression. That is, using it alongside pharmaceutical drugs (SSRI) to enhance the overall effectiveness of treatment (much like fish oil and depression).

Several randomised clinical trials have shown that 15 mg/day of L-methylfolate calcium is a safe, effective and well-tolerated treatment for patients with major depressive disorder who experience partial or no response to SSRIs (11, 12).

It appears to be particular effective in those with certain genetic variations (including MTHFR) and those with elevated inflammatory markers (13, 14).

L-Methyfolate (5-MTHF) in patients with diabetic neuropathy

Diabetic neuropathy is nerve disorder that develops over time in those with poorly managed type 1 or type 2 diabetes.

In a recent study, 544 patients with diabetic neuropathy were given Metanx (L-methylfolate-methylcobalamin-pyridoxal-5-phosphate) to trial for over a year. Based on self-reported surveys, overall pain rating decreased by 32% those previously treated with medications reported a 52% improvement in medication satisfaction (15).

Metanx is a combination vitamin B supplement, so this study did not test the effects of L-methylfolate on its own.

Summary: Early studies show L-Methylfolate supplementation may be beneficial in treating severe depression and diabetic neuropathy.

Important Considerations and Side-Effects of L-Methylfolate

Side-Effects of L-MethylfolateThere are several important factors to consider before starting L-methylfolate (5-MTHF).

  • Supplementing L-methylfolate bypasses the body’s natural checkpoints for preventing over-methylation. So we must be incredibly cautious with the dosage, as unnatural levels of folate is linked with several issues including cancer risk (16, 17, 18).
  • As with almost any supplement, this is not something you should take forever. Nor even everyday in most cases, but rather as a complementary medicine prescribed by your doctor. L-methylfolate also exists naturally in foods, so that should be your preferred source.
  • Your vitamin B levels – particularly vitamin B12 (cobalamin) – must be adequate before taking L-methylfolate. Otherwise homocysteine (not good) cannot be broken down and transformed, even with adequate folate. Think of L-methylfolate as the fire, and vitamin B12 as the firewood.
  • Minimise intake of folic acid. That means store-bought bread and anything else made with fortified wheat flour.
  • L-methylfolate (or any other form of vitamin B9 supplementation) can interact with numerous drugs and medications, so be sure to speak with your doctor first.
  • If you have been diagnosed with depression, you must first be screened for risk of bipolar disorder. Folate can enhance antidepressant effects of known antidepressant drugs, and is believed (although not clinically proven) to potentially trigger mixed/manic episodes in those with bipolar.

Potential side effects

As with any biologically active supplement or drug, certain people may experience unwanted side effects.

Unfortunately it is quite common with L-Methylfolate.

These are the most common symptoms and may appear after 2 weeks, 1 week, or even 1 day:

  • sore muscles and aches
  • acne or rash
  • insomnia and irritability
  • severe anxiety
  • nausea, headaches and migraines

If you experience this then you should speak with your doctor as soon as possible to reduce the dose or take a break. Persistent supplementation through symptoms can be dangerous.

There are also reported steps you can take to relieve some of the L-methylfolate side effects. This includes a small 10-50 mg dose of niacin, or a glutathione supplement (which I’m sceptical actually helps).

Additionally, the idea of taking more supplements to offset side effects of another is the same as taking more pharmaceutical drugs to offset the side effects of another drug.

Summary: There a very important factors to consider before taking L-methylfolate. Side-effects are also common and potentially dangerous if you do not address the problem immediately.

Recommended L-Methylfolate Dosage and Product

The FDA and European Food Standards Agency have approved L-methylfolate (5-MTHF) calcium supplements (16).

It can be obtained with or without prescription, but for non-prescribed supplements ensure the label specifies the amount of active L-methylfolate.

Prescription folate is available in 7 mg and 15 mg dosages which is very high. Unless recommended by your doctor, starting at less than 1 mg (1000 mcg) and then re-assessing is much more sensible if you are using because of an MTHFR mutation. 500 mcg (0.5 mg) or less appears to be the safest starting point.

If this is you, I recommend this supplement (disclosure: this is an affiliate link). The reason is because it contains 800 mcg of L-methylfolate (start with half) plus 1 milligram of vitamin B12 per pill.

It is also gluten, dairy and soy-free for those concerned, but always check with your doctor before taking any new supplements.

Again, there are a lot of risks associated with L-methylfolate supplementation, and it’s not recommended as a long-term solution.

You can get L-methylfolate from natural foods too.

MTHFR ebook ipad

More on MTHFR and other genetic variations

L-Methylfolate (5-MTHF) has emerged as a popular alternative to folic acid supplementation. This article covers what you need to know about it, but explained in human terms.


  1. Pennie Farrell says:

    Because I have two mutations (MTHFR), my doctor recommended 15 mcg of L-Methylfolate. The side effects were a nightmare. I was anxious, irritable and cried for no reason. Tears would just be streaming down my face and I had no power over it. In addition, I could not sleep and was totally uncomfortable in my own skin. I would be sobbing to my poor husband and could think of no reason why. In addition, I felt mean and hostile. Finally, I did the research and found out that this product is nothing to play with. So, I am taking a week off. I plan to go back on it but follow the product you recommended.with B-12. I want to say how much I appreciate your article. You gave me far more information than my own doctor. Thanks again

    • Thanks for the feedback Pennie and kind words!
      Yes it seems your dose was too high, and/or your other vit b levels might be sub-optimal.
      Good luck, go very slow with it.

    • Hi Pennie

      Did this end up helping you? i.e. taking the b12 with methyl folate?

      I experienced the same symptoms you have with but had been taking high doses of p5p and a bit of folic acid in another concoction prescribed by a holistic doctor.

      • I see this so often, people get too much bioavailable B6 and then they can develop Serotonin Syndrome.
        P5P is the incorrect form of B6. We need pyridoxine because it can enter the cells where it is THEN converted to P5P for use by the cells mitochondria to make ATP. ATP is the molecule which the cell then uses for fuel, ie energy production . P5P can not enter the cell, that molecule will not fit into and pass through the cell walls transport gateway. It can even block the gate. Thus it will cause big problems in the brain, triggering anxiety, depression, sleep problems, from a LACK of B6 inside the brain cells. The body has to do something with all that B6 floating in your bloodstream, so it starts converting it into serotonin. Thus the symptoms of too much serotonin. Many people with the MTHFR gene mutations are told by physicians and nutritionists to take P5P ( since it is the most bioavailable form of B6 ) because they are not familiar with how B6 is actually transported into the cell and what the conversion process in the cell itself involves. Or they may have learned about it in medical school but promptly forgot about it after taking and passing the tests in school.
        Folic acid should.NEVER be taken by a person with methylation system defects, such as we who have the MTHFR gene mutations.
        The medical profession used to think only 3-5 percent of the population had a methylation system defect, but the latest studies show that 50-60 percent of the population has a MTHFR gene mutation. That means if two people get together, one of them will have the defect. That means billions of people have it, that is not a minor problem when our environment is becoming filled with chemicals dangerous to us, which MUST be be converted and/or detoxified.

        • Lynn Bakeman says:

          Aelxa, It sounds like you have dialed in exactly what has been mis-prescribed for my son. In the beginning of 2016 we tried Dr. Hinz’s Amino-Acid Therapy and his expensive lab testing and proprietary supplements. My son has refractory ulcerative colitis and we’ve tried literally everything but he’s been in misery for almost 7 years.

          He has MTHFR A1298C plus other methylation snps issues. It seemed like we were making progress with the protocol then he got into the nausea phase and he was on high P-5-P and D5Macuna.

          In any event, we are considering enlisting the aid of Dr. Amy Yasko’s protocol but it sounds like you’ve gotten both educated and connected with a knowledgeable doctor. Is it possible for me to connect with you to learn more?

        • Bart VANGHELUWE says:


          As I have the MTHFR genetic mutation and also have a too high score for homoscysteine, I am quite interested in the whole subject of methylation.

          I read your message on the dietvsdisease site saying that you object against the P5P form of vitamin B6 as it cannot enter the inner cell and starts accumulating causing a serotonin overload

          But I learn everywhere that all other forms of vitamin B6 are all converted in the liver into P5P before entering the bloodstream. Therefore I do not understand your objection against taking directly P5P because too big to enter the cell. After all in the bloodstream it is the only form of B6 available as all the other are metabolized in the liver anyway and as such are not present any more.

          I would appreciate a comment.

          Thanks in advance

    • It sounds like you could also have a problem with COMT V158M, which cause a problem when supplementing with methyl compounds, including coffee and chocolate and tea. You can run your raw data from 23andme through the Sterling’s App or other programs to find out. See the youtube video https://www.youtube.com/watch?v=deVGXuEXZuk&spfreload=5.

      • A Bunny says:

        try taking Riboflavin. I did not see any positive effect of the methylfolate for months and experienced bad moods which I attributed to another medicine prescribed for EBV. But then I stopped that med. I took methylfolate along with B2 (riboflavin) and was in a much better mood – much more alert, less fatigue. I am wondering if the importance of B2 should be stressed much more to people with MTHFR mutations.

    • I’m compound heterozygous for MTHFR (+/- for C677T and A1298C) and have discovered that I can’t take the methyl form of B12, but the adenosyl and hydroxyl forms work well. My methylation pathway testing through Holistic Heal confirmed that methyl form is not optimal for me. Methyl makes me irritable, mean, and difficult to live with.

      • I have same two mutations and have to go without same two forms of b12….but I’m having a hard time keeping b12 levels up …have you or anyone had that problem?

        • Yes, many people with two copies of the MTHFR gene mutation can only use the hydroxocobalamin form of B12, and it must be injected since we have such a problem absorbing it in the gut with all our lack of enzymes which come from the lack of bioavailable vitamins in body to make the enzymes.It is like the chicken or the egg problem, which came first? In our case we know it all started with the MTHFR gene.
          My physician is finding it hard to get the injectable hydroxocobalamin, has to get it from a veterinary supply source.

    • gail martin says:

      Hello Pennie,
      Are you sure you were taking mcg instead of mg? Because that would be a very low dose if you were taking mcg. Thank you. Gail

    • Hi Pennie
      Just saw your post and would like to share some misconceptions that many doctors and Heath professionals are u aware of.
      William Walsh PhD wrote a book called Nutrient power.
      He is the foremost authority on Orthomolecular medicine. Patients who experience issues with mental health and have Methylation defects should not be genetically placed on Methylfolate!!
      It’s not just the MTHFR gene that regulates methylation. There are approximately 20 other genes that are play here. There is a specific blood test that we use to determine global methylation status and without it, one is prescribing blindly. It’s imperative to determine if a patient is an under methylator an over methylator or a normal methylator. If a patient is an under methylator and takes Methyl folate it will actually lower their serotonin level despite common thought. If this is your status this is the reason you experienced the reported symptoms. The answer to why is based upon molecular biochemistry and too in depth to report here. Over methylator as thrive on Folates.
      Dr. Marks

  2. I’m taking a prenatal containing 1mg of folate (500mcg as calcium folinate and 500mcg as L-5-methyltetrahydrofolaye from L-5-methyltetrahydrofoluc acid) and b12 (100mcg as adenosylcobalamin and 100mcg as methylcobalamin). Should be fine in terms of possible side-effects? Not been tested for MTHFR but pretty sure it runs in my family and my daughter is heterogenous though not sure for which mutation so just covering bases.

    • Should be fine for the average person (but there is always exceptions).
      Was it recommended by your doctor?

      • Thank you. No, I haven’t seen a doctor about this as I didn’t think it necessary. I do know that my naturopath green-lighted this for use by a friend who has MTHFR mutation.

        • Just be mindful if you take any other medications that may interact 🙂

          • Lynn Bakeman says:

            Joe, I understand how dangerous it is to enter into a methylation defect protocol without having the guidance of someone who can understand all the medications their patients are on.

            Since my son is on a host of immunosuppressive drugs (prednisone, Azathioprine, Lialda, Remicade) and even the doctors don’t know what the possible side effects are with these drugs in combination, who can we possibly see who has this knowledge?

            Getting desperate and need support!

    • Do mind sharing the name of the prenatal? Did you do well with it?

  3. Scott Salzman says:

    The Seeking Health supplement you recommend has 1 mg (1000 mcg), not 1 g of B12.

    And one of the other commenters said she was taking 15 mcg (really low dose), when I think she meant 15 mg (really big dose).

    Thanks for the helpful info. Ben Lynch @ mthfr.net has a great article on SLOWLY testing your tolerance for Methylfolate. And another couple of articles on Methylfolate side effects.

  4. My Doctor gave me this to help with Vitimin B absorption. It made me feel awful from the first of seven days I took it. I had a general sense of being unwell. I had extremely sore muscles making it hard to even walk upright and I am perfectly fit. It was weird. It felt like I was carrying someone on my upper back. I became easily out of breath when just moving around the house. I tried to exercise more, walking it off and using more asthma meds than normal but I never could find the right combo to start feeling better so I stopped taking it. I immediately felt back to my normal great self. I never had a change in my mood but feeling suddenly sick from a vitimin supplement that was supposed to help my body was frightening. L-Methofolate is not for me and I would caution anyone considering adding it to your regiment to improve your health. I vote F-!

    • This is a common side effect of too large a dose, and/or not taking with cofactor b-vitamins that work in tandem.
      But some people just do not do well with it, regardless of other factors, seems you are one of them!

    • Same symptoms. What do people do that can’t take Metho supplements yet need to get B’s absorbed in ones body?? Frustrated

      • A Bunny says:

        I am taking Jarrow 400 mcg – seems to be OK when accompanied by B2. That was the lowest dose I could find, lower than my Doc recommended – because I am very sensitive to supplements and medications.

  5. I’m homogenous c1298c and have a severe mercury poisoning after full mouth restoration last October 2015 and so many health problems my red blood cell count was so high doc tested for genetic mutation and low and behold. Problem is I can’t get stable. Between folate and b vitamins. I had such severe immune response with candida, lichen planus, dermidex outbreak, you name it after teeth issue and keep having folic acid side effects no matter my b vitamin etc. Eating very well no sugar very little carbs no processed foods.I got doen to 98lbs. Up to 105 now. I’m not sure my doctor knows what to do and I spend hours on the Internet searching for answers. Help

    • What folic acid supp do you have?

    • Terese elkins says:

      I’m curious to hear more about your experience including answers to your questions. After having 7 amalgam teeth fillings removed in a 3-day period ten years ago, It eventually lead me to testing for MTHFR, which I am positive for the heterozygous A1298C mutation. Finally after a decade of severe Neuro-malfunctions, I have been on Methyl-folate for one month and my mood finally seems stabilized. Although something is triggering restless leg (coincidently?) since I started a higher dose product.

    • You can use Vitamin C, start at 500mg a day and slowly increase by adding another 500mg every four days until you either start having diarrhea ( then you go back to the lower dose ), or get up to 3grams a day.This will help the body by binding the mercury into a molecule the body can excrete. Take the vitamin C in 500mg doses you space out over the day, do not take 3gm all at once. Drink lots of water , sip it over the day. Do not drink a full glass all at once, this can dilute stomach acid too much and make absorbing nutrients from food and vitamins hard to do.
      Trans-Resveratrol 500-600mg before sleep helps the body repair and detoxify. If the bottle only says “Resveratrol” it will mostly be cis -Resveratrol which your body can not use, and a waste of money.
      You can also use reduced Glutathione, 250mg of it right before sleeping. If you take it during the day you will feel tired and not so great as it puts all its energy detoxifying while it has the glutathione available. Nighttime is when your body naturally devotes most of its energy into the process of repairing and detoxifying while you sleep.
      Your body normally makes and uses glutathione to detoxify, but with the MTHFR gene mutations it is not making enough glutathione, just use the reduced glutathione. If the bottle only says “glutathione ” then it will not be in a form your body can use and a waste of money.
      Restless legs can be a symptom of low magnesium or even low B12 . We have to take vitamins in balance, you can not raise your L-methylfolate and not raise your B12 and B6 , etc. Remember to balance your vitamins and minerals.

      • Aelxa Hill says:

        Just found that reduced glutathione does not survive stomach acid well, so I a switching to acetyl glutathione. Acetyl glutathione and liposomal glutathione are the only forms that are absorbed well from what the studies show.

  6. Breanne says:

    Please help. I’m struggling with my diagnosis of MTHFR. I have two mutations, one from my mom, one from my dad. In addition to this I also found out I have PCOS. I have gained a ridiculous amount of weight over the last 6 months. My hematologist just told me she is pretty sure she won’t allow me to take birth Control, which is one of the only “treatments” for PCOS because of the fact that I have two mutations. Is this accruate? Would birth control put me at serious risk for stroke? Should I be more worried about the MTHFR. My doc didn’t seem as concerned with my mutations.

  7. Blenda Braswell says:

    What is the difference between methylfolate and L-methylfolate? Does it matter which I take to help with depression?

  8. Travis Marttila says:

    If Folic Acid and Dietary Folate are broken down the same way, should one also avoid Dietary Folate as much as possible?

  9. I’ve been taking a prescription for L-Methylfolate Calcium 15 mg per day for about 3 years. I was recently contacted an told my insurance would no longer cover this due to it not being FDA approved. The prescription is quite expensive. Does anyone know if the prescription is similar to some of the online vitamins for L-Methylfolate? Thanks

    • My insurance also denied the prescription, but I found a coupon through GoodRx.com. Good rx.com can direct you to a pharmacy in your area with the least expensive price. The savings were remarkable!

      • My pharmacy charges me $44.00 for a 30 day supply. Which i dont think is tjat bad! But i seem to be having some moderate side effects.

  10. Momma Megan says:

    My doctor prescribed 2 Folgard tablets per day because I have MTHFR. I know taking methylfolate is better so I’ve been taking 3mg daily. Is this an accurate conversation? I am also taking 800mg of folic acid that are in my prenatal vitamins as well. I also recently read to reduce the folate dose after 12 weeks? What is the recommendation for that?

    • Hi Megan you have to speak to your doctor about that. It depends on your med history and other medications, sorry I can’t give more useful advice.

    • My dr prescribed lmethylfolate calcium 15 mg. 1 everyday. For an indefinite time. There are several refills on the script. Is this normal? Seems like i should be a week on a week off or something like that. Im now experiencing bowel issues but ive also been taking 3000 iu of vitamin d and 1000 of calcium. Ive become so constopated although i dont eat much due to stress im wondering if all of this is causing the constipation? Please help!

  11. Can I take L-Methylfolate (5-MTHF) even if I don’t have the gene mutation but I am planning on getting pregnant or just folate? Is 800mg ok? Thanks!

  12. My daughter has bipolar disorder. She takes wellbutrin and lamotrigine for the bipolar. Her homocysteine is normal but her Vit B-12 in blood tests is always high, highest was 1600. She was tested for MTHFR mutation and it came back homozygous A1298C. She started taking the L-5-MTHF 5mg but after reading we decided to stop and figure out the right way to do it. Because she has the mutation does the high B-12 mean her body is not using it? For some reason they didn’t check folate. Should we check that also? We were going to try the product you suggested to restart and slowly increase. Is it okay to take the methyl B-12 if her B-12 in the blood is high? Also what is the precaution with bipolar disorder for taking these supplements?

    • Could be she is not using the B12.

      But there is risk with l-methyfolate and bipolar. Because it can greatly affect mood, up or down.

      You need to do this with your doctor.

      • Hello, I’m new here & that’s me exactly. High B-12, 1500 in my blood work yet, I’m a shaky, angry, irritable mess on Metnx, low dose or Deplin. Seems no health practitioners get it. I’m spinning as I get worse & my memory, cognitive function is suffering.

  13. I recently subscribed to your articles and am quite relieved to find one place to get this information. Thank you for this terrific service.

    I am heterogygous and my 14 yo daughter is homozygous for the C677T mutation and are currently taking psychiatrist-prescribed Deplin (L-Methylfolate), 15 mg/day for me and 7.5mg/day for her, as well as supplementing with B12. Both of us has suffered from depression and are currently stable with the Deplin and SSRIs.

    After reading your article, I am concerned that the Deplin doses we are taking may be too high. How would we know? Also, I was a bit confused by your statement that “as with any supplement, this is not something you should take forever.” If we don’t have the enzymes to break down folate//folic acid to its usable form, isn’t that a permanent condition requiring permanent supplementation?

    • Deplin is a high dose, but the side effects are severe. So if it was too high you would know about it.
      Your psychiatrist knows best in any case.
      I recommend extra low to people taking l-methylfolate on their own.
      You are right, I’m referring to any one particular supplement or drug, and anyone particular dosage. I will re-phrase

  14. Suzi mclean says:

    I have a toxic level of b6…?
    I do not use a supplement..
    Being tested for the mthfr mutation ..waiting for results..
    Pain, muscle cramps, tremor, bilat. foot pain,

    What am I supposed to eat?!?!

  15. Mimi Cox ND says:

    Folic acid is the synthetic form of B9, and is not absorbable for those that have the MTHFR polymorphism. It is artificial and inactive. It will NOT have any good effects for these people. If someone who is positive for the MTHFR gene mutation were to take this artificial form of folate, once it adheres to our receptors it actually stops enzyme production. Please stop reporting about folic acid that it is ok. It is important individuals who have this mutation eliminate anything with folic acid in it.

    • Dulce Andrade says:

      are you stating this artil is wrong and people should not take L-Methylfolate.
      I have MTHFR (dual mutation) and Dr has me on prescribe Folic Acid.
      was considering switching to L-Methylfolate.

      • You have a genetic mutation called MTHFR where your body cannot breakdown anything synthetic. You should not be taking ANY form of synthetic vitamin. Synthetic vitamins are: Riboflavin, Niacin, D-Biotin, Folic Acid, Cyanocobalamin. To clarify, Folic Acid is synthetic. L-Methyfolate is not synthetic and therefore you can take this form of folate and your body will be able to use it.

        • Wait, I take a B complex with B12 (1000mcg methylcobalamin) and 400mcg Folate (5-methyltetrahydrofolate) but it also has Biotin, niacin, B2 (as riboflavin) You are saying the last 3 are not good for me? I have the double MTHFR mutation. All B Complex even the one I take which is for people like me has them. So should I just take a vitamin like this one whiich only has B12 and Folate? My Doc said to take it easy with the dark greens (1 handfull daily) just in case. Not sure about that. ;-(

          • Btw, I forgot to mention that I have not seen any improvement at all and my B’s are normal and my B12 is perfect. Still, I’m extremely weak all the time. ;-(

            • Aelxa Hill says:

              If your B12 is normal or high and you have symptoms of deficiency then it is a sign that the B12 in your blood is inactive form. You have two copies which means your methylation system is only 10-20 percent efficient. This system is involved in the conversions of all chemical vitamins, not just folic acid, and minerals into bioavailable form. Your body uses these vitamins to make the enzymes and hormones your body needs to function. It also detoxifies heavy metals, pesticides and other chemicals that get into your body through eating, drinking, inhaling, and absorbing through your skin. You need an organic whole food multivitamin supplement or a bioavailable multivitamin supplement. You need to avoid chemicals, eat organic fruits and vegetables, and organic grass-fed meat. For energy you can take Niagen by HPN , I have two copies and it helps my energy immensely. Have your lead, mercury, copper blood levels checked as these are often high. If you read through the posts on these MTHFR pages, I have listed many other things you can do.

  16. I only just heard there is a difference between folic acid and folate. i have been taking at least 1.8mg of folic acid for years as recommended by my arthritis doctor because he has me on Methetrexate. should I switch ti folate? The dose is supposed to lessen hair loss.

  17. My doc currently has me on 5-MTHF Optimizer w/ AstraGin and BioPerine for optimal absorpiton… i take 2 a day (8mg)… I have a hard time swallowing pills and wanted to switch to Superior Source Methylfolate microlingual tablets… each is 1000 mcg… would that do the same and/or be okay? the doc tells me i need the broken down folic acid as my body doesn’t break it down… thanks for any help.

  18. Ana Rodriguez says:

    I find your site to be so thorough and informative that I feel compelled to assist in making it even more complete and informed.
    B-12 is, as you put it, The Firewood. Therefore your site could stand to have much more information on this vital and important nutrient.
    Thanks for all you do!!!

  19. Susan Price says:

    I am going on a cruise next month and I am very concerned about what to eat. Any suggestions on how to survive a 7 day cruise when I have so many dietary restrictions due to MTHFR. I’m aLSO a congestive heart failure patient and I require a low sodium diet. Thank you ahead of time for any light you can shed on this for me.

  20. Great article, learned a ton! Would you mind attaching your sources please? Thanks!

  21. I am homozygous A1298C. I began titrating your B12 sublingual tablet – 1/4 for four days, then 1/2 tablet for a week. I immediately noticed a lift in energy and spirit. My urine was noticeably potent but is now normal. After 8 days on the 1/2 tablet my headaches and fatigue returned so yesterday I added another 1/4 at lunch time. Today I feel lousy with a continued headache that may well need migraine medication (injectable Imitrex) to stop. I don’t seem to have any other other symptoms listed like irritability, anxiety, insomnia – although I have not slept as soundly the last three nights.

    Do I increase to a whole tablet or just stop for a period? I am basically gluten and dairy free and have not eaten processed foods in years.

    I was feeling so good at the beginning and thought I had a new lease on life!

    Hope you can suggest where I go from here. I have a new order for the Optimal Multivitamin and more B12 sublingual tablets backordered – wonder if I should cancel it.

    Thank you for any ideas.

  22. MARY JONES says:

    Douglas Laboratories B-Complex with Metafolin® and Intrinsic Factor — 60 Vegetarian Capsule
    Is this a good product to take for this?
    Thank you

    • I made DNA test and found that I have MTHFR, Vitagine.com recommended me B-Complex vitamin and they recommended Douglas Labs products.
      My B-12 was low and LDL cholesterol was high.
      After using B-Complex, everything balanced and my LDL cholesterol level went down without medicine.

      Thanks Doctor for this artcle.

  23. i am supposed to be starting methotrexate treatment for rheumatoid arthritis. my rheum has me on 5 mg’s of folic acid daily (as you need to take it with mtx),
    i would rather take the l-methylfolate. unfortunately deplin isn’t available out in Canada, so I’d have to do this with the supplemental form. any recommendations for equivalent dose?

    thank you!

    -Charlie Sacks.

  24. In September of last year I was prescribed Cetefolin NAC by my integrative M.D. I was not tested for the MTHFR mutation. At that time I was also taking Lexapro. Within about two weeks I had a severe panic attack. My doctor advised me to go off of the Lexapro. For the next four months I felt great even though I was going through a very stressful time in my life. About one month ago I started to experience what I think is a tension headache. I get pressure mainly in the back of my head and sometimes between my temples. In addition, I’ve had several panic attacks too. When I went to the emergency room they did take a CAT scan and that came back negative. Since then I went back to my chiropractor to see if this was originating from a neck issue. I also went to an ENT and I’m having a CAT scan of my sinuses performed tomorrow. I even have an appointment with my eye doctor because I really haven’t been wearing my glasses and I do squint a lot. When I called my doctor about a week ago he told me to stop taking the Cerefolin for a week. It’s been six days since I’ve been off of it but I’m still experiencing similar symptoms. I decided as of yesterday to go back on the Lexapro. Based on all the research I’ve been doing my best guess is that I am over methylated. Is it possible that my ymptoms are being caused by this? If so, would it take longer than six days for the symptoms to go away?

  25. I did the genetic test with 23 and me and found I had a problem with MTHF. I took the supplement but ended up breathless, fatigue, muscle pain etc… all the side effects that can bring your functioning to a halt. However, I found that if I took Coq10 and Glutathione as well, I handle the 5-MTHF supplement perfectly and now I feel great all the time.

    • My functional said not to take Coq10 with the MTHFR mutation. Not sure why. ;-(

      • Aelxa Hill says:

        If you buy CoQ10 it will be very likely a form that is not usable by people with the MTHFR gene mutations. The only CoQ10 form that is usable is called Ubiquinol, and you need to take 200mcg of selenium and 500 mg of Vitamin C with it.

  26. Questions:
    1. Does the time of day make a difference when taking the pills? Ex: Does taking the pills at night instead of the morning increase the risk for insomnia?
    2. If you are taking a SSRI in the morning should you take the supplements at the same time or in the evening to lessen the stress on the body processing everything at once?

  27. Is it true I should avoid Niacin supplements with MTHFR? I already take 500 mcg methylfolate, a P5p supplement and Methyl B12 (moderate dose) without too big a problem of side effects. I like to take Niacin for my mood at night sometimes. I just took it, and now read that possibly I should not take it?

  28. DIANE COLWELL says:

    My Naturopathic physician recommended Methyl Folate due to a potential for the inability to process folic acid. Within three days I felt like a cloud had lifted. I was able to concentrate for longer periods of time and feelings of sadness disappeared. I took 15 Mg for approximately 8 months and stopped for the same period of time. I feel like it is time to start taking it again. If I experience the same results I will be 100% behind this supplement.

  29. Dianne R. says:

    I have been taking methotrexate for the past 2 years. My rheumatologist had also prescribed Leplin. I’ve just found out that my daughter tested positive for the MTHFR gene. I have not been tested yet. My doctor recently called after a blood test where liver tested very high, so off of methotrexate. I just called my pharmacy. The Deplin I was supposed to be given all this time is NOT l- methylfolate!!. Just folic acid. My daughter sent me a bottle of the l-metjygolate, I stopped all folic acid. I feel great! Going to my endocrinologist and rheumatologist soon. I will try to get tested (i’m very due I’m positive) for the mutation. I also take metformin and Humira. I need to clean up my health!. Thanks for the plain English version!

  30. Thanks for your terrific website. Not a lot known in Australia still I found. I’m have a MTHFR C677T + MTHFR A1298C (compound heterozygous) mutation but as fortunate to find a GP who advised take 2 x (6s) 5-methyltetrahydrofolate at 500ug each, Bioactivated B12 1000mg AND 1x Folinic Acid (activated vitamin B9) 540mcg. Just wondering why the bio form of B9 is needed if I’m already taking the 5-MTHF tablets? Aren’t they the same thing? Or is there a reason for taking both. Also, wold adding in a B6 supplement be beneficial and would that have to be the bioactivated form also? Many thanks for considering this query.

    • Aelxa Hill says:

      The problems are with all chemical vitamins, if you have MTHFR gene mutations., so all vitamins you take should be in bioavailable forms your body can use without conversion. If you are taking B12 and folate it should be balanced with B6. Pyridoxine is the correct form of B6 to use because it can enter cells, through the cell wall ports specificly keyed to Pyridoxine alone. Once inside it is then turned inside the cell into P5P which the mitochondria use to make ATP. Do not take B6 as P5P, because it can not enter the cell from the bloodstream and will be of little use to your body’s cells for energy production.
      I am not certain why your physician has you taking folinic acid, folinic acid needs to go through too many conversions to get it to the (6s) L-methylfolate form that your body can actually use. To call folinic acid bioavailable is a misnomer. You have two MTHFR gene mutations so your methylation system will only be working at 10- 20 percent. If you had only one gene mutation then it would be capable of 60-70 percent and might be able to convert the folinic acid to L-methylfolate , as long as it was not overloaded with other chemicals, like pesticides, inorganic chemical vitamins, etc. I would suggest talking to your physician about the extremely poor ability of your methylation system to convert the folinic acid and about stopping taking that form of folate. If your physician wants you to get more folate that your body can use she/ he should increase the (6s)folate you are taking, as it is bioavailable and needs no further conversions. You should also check what form your B12 is in, if it needs as many conversions as the folinic acid then it will be a waste of good money to purchase it. The most bioavailable form is hydroxocobalamin and it needs to be injected, as the oral form is poorly absorbed by people with two MTHFR gene mutations. This is due to the body not making enough of the enzymes to absorb B12 in the digestive system.

      • Can you provide a reference-link that supports your statement:
        “Do not take B6 as P5P, because it can not enter the cell from the bloodstream and will be of little use to your body’s cells for energy production.”

        This link confirms the efficacy of P-5-P (PLP):
        (the plasma levels numbers require some calculation, but clearly P5P plasma levels increased after administration of active B6 (P-5-P) and at a better rate than pyridoxine hydrochloride.)

  31. I have diabetic neuropathy, type 2 diabetes, my foot dr. told me to take L-methyl folate (optimized folic acid) and vitamin B complex. He didnt say how much. I am taking the vitamin B complex but am confused on the methyl folate. Does both come in one pill. I really need help. The gabapentin (900 mcg) is just not enough and my insurance doesnt cover lyrica.

  32. I was just prescribed L-Methylfolate 15mg daily because I have the genetic mutation as well. I suffer from chronic anxiety and I’ve only been taking it for 3 days now. I’ve noticed the possible side effects include “extreme anxiety”, and I have noticed my adrenaline spiking these past few days. I do have a chronic condition so this does happen from time to time, but I don’t want to make my condition any worse. Today was exceptionally difficult – pressure in my head and inability to focus and adrenaline rushes. Anyone experience anything like this?

    • Why do doctors keep prescribing high dose vitamins in isolation? There is a balance, if you raise one you need to raise the others or you get an imbalance that can cause problems.
      Yes, I have experienced this, then I learned about the need to take bioavailable vitamins in balance and to start with the RDA amounts, then increase slowly, if needed. Sometimes just getting the RDA is enough.
      Our bodies have been trying to function with chemical vitamins it can not use. When it finally gets vitamins it can use, it makes the enzymes and hormones we need. Our bodies do not need mega doses to function properly, it needs all vitamins taken to be in the correct bioavailable vitamin forms which it can use.

      • This also means that if you have the MTHFR gene mutation and are on a SSRI antidepressant, you may very well experience Serotonin Syndrome. Your body’s serotonin levels will naturally increase once your body has bioavailable vitamins to make normal levels of serotonin with. Taking a SSRI on top of normal serotonin levels, will make you sick. In this case,once your body is making enough serotonin, the answer is NOT to stop taking bioavailable vitamins. The answer is to wean the patient off the SSRI which the patients body no longer needs to keep serotonin levels high enough. The depression comes from the body’s serotonin level being too low, not from a lack of the antidepressant.

  33. I have the mutation, and have been taking Deplin for 3 months, but reading about how I shouldn’t be on it permanently, makes me wonder – how long should one be on it? It’s expensive, so I’d like to stop if I can. Didn’t notice a difference with or without it, except maybe a bit less insomnia. Thanks for any suggestions you may have.

  34. I think it’s still best to be careful and skeptical at this point with this mutation. Quite a few people are showing up with it and having no adverse effects. The science is still unclear and the research needs more time. I think the advice to use low plused (taking time off) doses is the best approach for most people with the mutation until more is known. On the other hand, Increased risk of blood cancers from prolonged high doses of b vitamins is a real thing.

    • Jeff, if you have only one copy of the MTHFR gene mutation, your methylation system will function at 60- 70 percent so it will take a while for problems to show up. But believe me,when the chemicals build up in the body that person will get sick fast and more and more illnesses will develop.
      A person with two copies has a methylation system that functions only at 10-20 percent efficiency. This person will get sick fast in our society’s chemical filled environment, sometimes as very little children. But it will all depend on chemical exposure.
      Huge amounts have been learned in just the last five years alone. For example, if the mother has high blood levels of the chemical vitamin folic acid then the baby will be born with Autism. Autism rates went from 1 in over 2,000 births in 1990, to the latest information being 1 in 46 births in the US. It was in 1991 when the government had physicians tell their pregnant to take folic acid to prevent spinal cord defects. Spinal cord defects in the same time period only went down less than 5 percent.
      All this information can be found on the NAH.gov website, if you read the studies posted there on pubmed. But they are STILL telling pregnant women to take folic acid.
      The facts are 40- 60 percent of people have the MTHFR gene mutation, and these people can not convert chemical vitamins into bioavailable forms which the body needs to make the enzymes and hormones it needs to function properly in adequate amounts. If we could not convert them at all,then we would just die. That is why women with the defects have so many miscarriages. The fetus is unable to deal with all the chemicals and it dies. All these are known facts, go look at the studies. It is heartbreaking, especially from us would have had miscarriages and autistic children.
      We do not need high doses of vitamins, all we need is ALL our vitamins to be in bioavailable vitamin forms our bodies can use, since our bodies can not process chemical vitamins into bioavailable form.

  35. Antriksh says:

    Hi There,
    This article is so informative, really appreciate the detailed information. I started reading about Folate as recently i went for full body check up and it has been identified that my homocysteine level is 58.5 and doc adv me to take it very seriously so i started reading about it and came across to this article and thinking on taking MTHF supplement. Surely i’ll discuss about this supplement with my doc but any suggestion form your side please.

    • There is no MTHFR supplement, the MTHFR gene mutation can not be fixed. All we need is ALL our vitamins to be in bioavailable forms. Taking just one vitamin in bioavailable form and then giving it at high doses will make your body’s vitamin balance off and can make you ill.
      The problem is NOT with just folic acid, your body can not convert ALL the chemical vitamins into bioavailable forms. Physicians and nutritionists need to STOP giving people high dose L-methylfolate. You need a complete bioavailable multivitamin and mineral supplement giving the RDA amounts. Then if additional amounts are needed, to increase all vitamins unless there is another problem affecting only one nutrient .

      • Diane Mastromatto says:

        You seem to be well educated with this mutation. Are you a functional wellness Dr? I’m in desperate need of help. So many health issues.

  36. The article said if you’re taking methylfolate to limit the products you eat with folic acid… could you please explain why

  37. Katherine says:

    3 yrs ago I was diagnosed with compound heterozygous for both mutations, C677T & A1298T. Nothing was said to me about anything. Every other year my system seems to crash and I have to get Vitamin B shots, the doc says its almost like I haven’t eaten in way too long. Despite these genes and thyroid I am pretty healthy. I do have some concerns and hope someone / doc would give me some advice. I am 50 lbs overweight and have been borderline diabetic for years – now on metphormine, I have hypothyroidism so I take Synthroid, I take a vitamin B and Vitamin D supplement daily (blood tests show too low when I don’t), I sleep at most 35 hrs a week and go non-stop! work, kids, and I am in college. I recently found a lump in my right breast and after family history was called back to do a saliva test to be sent out for BRCA 1 & 2. I saw that the MTHFR and the BRCA genes have some relationships that cause patients to be at a higher risk for cancer. I need to lose weight to get off the Metphormine, I am worried about the BRCA genes, I am trying to walk over 12,000 steps a day and my husband and I switched to a plant based diet over a month ago,,,,help please

    • You have a few concerns, but I believe the cancer tendency is what is causing the most anxiety.
      From Mutation Research- Genetic Toxicology and Environmental Mutagenesis. Volume 496 Issue 1-2 Sept 2001 pigs 171-180.

      “Resveratrol, a natural phenolic compound, inhibits Cell Proliferation and Prevents Oxidative DNA Damage”
      Resveratrol reduced nuclear DNA fragmentation, as assessed by single cell electrophoresis ( comet test ).
      ….our results suggest that Resveratrol can act as an antimutagenic- anticarcinogenic agent by preventing oxidative DNA damage which plays a pivitol blood role in the carcinogenic activity of many genotoxic agents.

      I personally take 100 mg of Resveratrol a day and will be iincreasing to 200 mg Resveratrol a day. Right now I can not find the information I wrote down, but in another study they found Resveratrol caused cardiac infarcts ( dead areas of the heart tissue caused by heart attack) to be repaired by the body. All these studies are to be found at the National Institute of Health website ( NIH.gov ) if you are interested in reading them.
      Hope this info helps you.

      • That is Trans-Resveratrol that I take. Most Resveratrol is cis-Resveratrol that the human body can not use. If the bottle only says “Resveratrol” on the ingredient list, then it will have little Trans-Resveratrol in it.

  38. i was prescribed this because of a genetic test result. thank you for the info as it helped me shop for a cheaper but effective supplement. knowing the proper labeling terminology helped me navigate the myriad of search results. thanks!!

  39. Hi my question is, if L metyhlfolate bypasses the checkpoints putting you in danger of overmethyiating, does eating folate in plants also put you in danger of over methylating? I have comt gene also, my dr is working on it so far we are looking at hormones first (other issues) and then she said we’d look at methylation, which she reckons is complicated wiht those two genes.
    anyone got any comments? can we do this naturally?

    • The folate in plants comes in all three forms, folic acid, folate and methylfolate. The amounts of each vary from plant to plant type, ie corn levels are different from bean levels. When you have the MTHFR gene mutation your body can only use the methylfolate. Your body will absorb the other 2 forms but can not convert them to methylfolate, so they will stay in the bloodstream for a long time since the same methylation system that converts folic acid and folate also removes chemicals from the body to excrete them. One copy of the gene and the methylation system can convert close to only 60 percent efficient, two copies and it is only 10-20 percent efficient. So you can have a normal or high blood test level of folate but only a very small amount of the folate in the blood will be usable methylfolate.
      The same thing with B12, most of that B12 will be unusable cyanocobalamin. Alot of people with the MTHFR gene mutation will not be able to use methylcobalamin either. Always suspect inactive B12 if blood levels are high, but you have symptoms of low B12. The only bio-available form of B12 that is bioavailable for certain is injectable hydroxocobalamin. There is an oral hydroxocobalamin but due to gut absorption problems in people with the MTHFR gene mutation it is rarely absorbed.
      This problem of high blood levels but low usable vitamin is due to consuming chemical vitamins. The best vitamin for us with the MTHFR gene mutation is a whole food source multivitamin supplement, the one I use is made by Garden of Life. Called My Kind Certified Organic Whole Food Woman’s Multi 40 Plus. Whole food vitamins will go bad fast in comparison to chemical vitamins, so keep them in a cool dark place. NOT the refrigerator since they get too cold when you open the cold bottle and humidity in the air will coat the tablets, thus helping to degrade the vitamin potency.
      I do not sell vitamins and have no monetary interest in the Garden of Life company. Always start low with vitamins, especially bio-available forms, to avoid over methylation problems.

    • As regards your hormone problems, your body uses the vitamins to make your body’s hormones and enzymes. This is why we who have the MTHFR gene mutations develop hypothyroidism, hyperparathyroidism, low testosterone, gallbladder problems ( due to not having the vitamins to make enough bile which is stored in the gallbladder) , and the list goes on.
      Your physician can try to correct your hormone levels with medication, but if the medication is not a bio-identical form your body will not be able to use most of it. Remember that with one copy your methylation system can only convert about 60 percent, you have two copies and can only convert 10-20 percent.
      Meanwhile all that medication your body can not convert it also can not excrete. It stays in the blood stream and your body will then start storing it in any cell that will accept it. This is how we get toxic.
      Chemicals which that cell can not use are sitting in the cell and over time they start to degrade by interacting with other chemicals stored in the cell. All these stored chemicals start interfering with the normal cell processes and you start getting more and more ill.
      So make certain your physician orders bioidentical hormones for you, you may have to get it from compounding pharmacy. Make certain the pharmacy knows you have a severe methylation problem and you need the least amount of inactive ingredients in the medication. Pharmacies will add so-called inactive chemicals to make the capsule full. I have one nutrient capsule I take that is only one third full, but all it contains is the active nutrient.
      So-called “inactive” ingredients are not inactive in our bodies since we have trouble excreting them and they wind up stored in our cells, adding to the toxicity we experience.

  40. I am homozygous MTHFR A1298C and have been taking Deplin 15mg (or OTC version) for a while. I just had bloodwork done and my folate is > 24 which is apparently OK, but my B12 is very high at 1780. Most everything I read online about the mutation and Deplin seems to suggest that I should have a B12 deficiency, not an elevated level. Any thoughts? Thanks.

  41. When you have the MTHFR gene mutation your body can not convert the chemical vitamin into the bio-identical form your body uses to make the hormones and enzymes it needs to function. The MTHFR mutation affects the methylation system your body uses to detoxify and render harmless any chemical you eat or absorb through your skin, making it hard to excrete the chemicals. In effect, the body can not convert the chemical vitamins into a useful form but it also can not get rid of it. The blood tests will show you have a high blood level of B12, but the B12 can not help you because it is still in the unusable chemical form.
    People with one copy of the MTHFR mutation ate able to convert 60-80 percent of chemicals, those of us with two copies can only convert 10-20 percent of chemicals and are at a huge disadvantage and become very ill over time as our toxic load increases. Our physicians see the blood levels look good but do not understand that the vitamin level is deceptive, that the vitamin is unconverted and is sitting there because the body can not excrete it either.

  42. Our 9 year old daughter tested positive for the heterozygous genotype MTHFR gene mutation ( C677T and A1298C ) three years ago, and on a doctor’s advice, we purchased the Seeking Health Active B12 w L5 MTHF. She began taking immediately, and has taken every day for three years. We did not gradually introduce B12. She is now almost 13 years old, and has quite a bit of acne, depressed immune system, and is often times tired/exhausted. Colds last 3-5 weeks, allergy symptoms have gotten much worse, and she just does not have sparkle. As soon as I read about the side effects of this product (and specifically about our mistake of starting it without ramping up in dosage) I discontinued her use of it. Besides the obvious of having a new blood test done, what would you recommend we do? Start niacin supplements? Any B vitamins? Any other advice? Thanks a lot for any suggestions.

    • Your daughter will need a good bioavailable multivitamin supplement, the MTHFR gene mutations affects all vitamins and minerals, not just B vitamins. I have two copies myself, I use Garden of Life organic whole food multivitamin supplement. It gives me the RDA amounts and that is adequate for me with the addition of calcium, magnesium, zinc bioavailable supplements at the RDA. I also take 300mcg lithium, 100mg Ubiquinol (CoQ10), biotin, 200mcg selenium because these are all found to be low in people who have the MTHFR gene mutations. Zinc when low causes poor wound healing and acne.
      Taking high amounts of single vitamins can cause many problems, I am still trying to find out where this protocol came from. Its very important to test for high lead, mercury, copper, etc since these are found to be high in people with MTHFR gene mutations. This methylation system detoxifies chemicals and metals also, in addition to converting all vitamins into bioavailable vitamin forms the body uses to make the enzymes and hormones it needs to function properly. With two copies methylation system efficiency drops to 10-20 percent. For this reason I eat organic fruits and vegetables, and organic grass-fed meats, along with gluten-free.
      The exhaustion, acne, depressed immune system, and allergies are common disorders found in people with the MTHFR gene mutations according to the studies I have read on the nih.gov PubMed site.

      • Thank you, Aelxa! I will have the mercury-copper-lead testing done and switch to bioavailable multivitamins.

    • Joe Leech, Dietitian says:

      Hi James, unfortunately I cannot give out medical advice regarding supplements. Best to check with your daughters doctor.

  43. HI Alexa-

    Do you have an email address I can email you some questions for my mom(66 yr old) who just found has she has heterozygous MTHFR and have been having multimple health issue for years( mainly pain related all over her body) and not a single type of doctor has been able to figure out any solution?



    • Aelxa Hill says:

      I would be happy to have your mom write to me. I have been dealing with the allover pain since 1992, after being on folic acid for a year (before, during, and after pregnancy). I have done many different treatments over the years and now have a program that works for me. I will need to know how her pain came on, that can give clues as to what is going on. Just email me at aelxahill@gmail.com

  44. Hi,
    I’m currently taking 500 mcg of Methyl B12, twice a day to combat deficient level of B12. The vitamin also contains 200 mcg of Folate and 8mg of Vitamin B6. This means I’m getting a totla of 1,000 mcg of B12, 400 mcg of Folate and 16mg of B6. Is this to much Folate everyday?

    • Aelxa Hill says:

      In the US they recommend people get 400mcg of folate daily, so you are taking what they call 100% of the Daily Value of Folate.
      16mg of B6 is approximately 700% of the Daily Value of B6.
      And 1000 mcg of B12 is approximately 20,000% of the Daily Value of B12.

      • Aelxa Hill says:

        Do you know if you have one copy of the MTHFR gene? If your B12 is low, then most likely that is your MTHFR gene status. With one copy your body can convert and use almost all the B12 that it is able to absorb. If you go over to “MTHFR genes C667T and A1298C explained in plain English” I posted a long explanation of how B12 is absorbed by the human body. It starts with the saliva in my mouth, if the B12 is in tablet form it will not be absorbed. It needs to combine with the saliva enzyme TCN1 in order to survive the stomach acid, and then unhook from TCN1 in the small intestine where it goes through five more steps before it gets to the liver where it is stored and dispensed into the bloodstream as needed.
        For you a sublingual form of B12 where it can mix with saliva may work better. Also recent studies on the NIH.gov PubMed site show your body can only absorb a small amount of B12 every 4-6 hours. They think it may be due to the small intestine making only very minute amounts of intrinsic factor every 4-6 hours. It may help to take your B12 in a sublingual form and divided into 4 doses a day, and see if that helps increase your B12 levels.

    • Joe Leech, Dietitian says:

      Hi Chris, Please check with your doctor as I cannot give medical advice online. Thanks!

  45. I have a high level of B6 in the blood ( I don t take any supplement ) and numbness in feet and arms. I have an homozygoute on MTHFR 677. You wrote that this defect can prevent the B6 to go into the cell and to stay in the blood. You recommend to use Pyridoxine that is a useful form of B6 to be use in the cell. You mentioned also a problem with detoxifacation to explain why the B6 get stock in the blood. What do you recommend to help to expel the extra B6 from the blood to get it to a normal level? Thanks

    • While you are not taking any vitamins, you may be getting them from your processed packaged foods. Look in your kitchen cabinets and read the ingredients list on the side of the box. In the USA they list all the added ingredients, and the vitamins will be in the list.
      While pyridoxine is active inside the cells, it is unable to enter the cells since the P5P molecule will not fit into the B6 cell wall transport port. P5P has to be made inside the cell itself in order for the cell to use the P5P. L- methylfolate is the molecule that will fit into the B6 cell wall transport port.
      Numbness in the feet and arms is a symptom of B12 deficiency. The body’s nervous system uses methycobalamin and hydroxocobalamin, both forms, to correctly function. You need to take methycobalamin, and for the hydroxocobalamin the body’s methlyation system needs 400mg of the alpha form of Vitamin E in order to convert the methylfolate into the hydroxocobalamin form. It is possible to get hydroxocobalamin, but it needs to be the injected form, as the oral form taken by mouth is destroyed in the stomach by the stomach acid.
      And needless to say, I hope you are seeing your doctor about this numbness. I assume you are since you know you blood level of B6 is high.
      I was able to discontinue the injectable hydroxocobalamin by adding the 400Mg of alpha Vitamin E, and it is working well. After one week my pain level has gone down so far, that in one day I went from taking four of the Nucynta 75mg every day to taking just half a Nucynta 75mg four times a day. That’s half the medication .
      Before starting the alpha Vitamin E my pain level, on the higher amount of Nucynta, was between 6 and 9, now with the lower pain medicine my pain level is between 1 and 3. I also did a few other changes, but they were all natural substances that support the methlyation system, like taking 600mg of NAC once a day. Also, I stopped all vitamins and anything else that contained titanium dioxide.
      In nature we never encountered titanium in any but tiny minute amounts, now it is being used as a food coloring and is even used in milk to make it whiter. It is also in toothpaste, anything white or pastel-colored could have Titanium in it. The reason I did this was because Titanium is a metal. And anytime you consume a substance, the body will try to use it. This is how people with Lead poisoning wind up with Lead in their bones. The body will use Lead instead of Calcium to build bones , if it is available in the body.
      Anyway, I have been reading studies on the internet and Titanium was not so big a problem until they started making nanoparticle sized Titanium dioxide. Nanoparticles have many useful purposes in industry, however in the human body they have the ability to cross the blood/brain barrier that protects our brains from substances that can damage the brain. One study found these Titanium dioxide Nanoparticles, when fed to salmon, caused massive holes in the salmon’s brains. Can anyone say “Alzheimer’s!” ??? Other studies done with rats show the same results, holes developing in the rat brains. And hundreds of tons are manufactured each year., Alot is used in sunscreens, since Titanium dioxide Nanoparticles are transparent to our eyes and works as well as Zinc oxide which is thick and white. All those tons are going into the sea, now I do not like the taste of fish but if any of you do, your fish may die out since Titanium nanoparticles combined with sunlight are being found in studies to kill algae. And algae is the very beginning of the ocean foodchain. Not to mention, the algae in the ocean make most of our atmosphere’s oxygen. Can anyone say “Soylent Green!!!” ???
      Well, I quit Titanium because I figured it is one less foreign metal that my methlyation system has to deal with, if it can even deal with nanoparticles at all. I was looking it up on the Table of Elements trying to figure out what the body might do with it, however the action of an element changes drastically when it is at nanoparticle size. Sort of the difference as between Newtonian Physics and Quantum Physics. What you do with this information is your choice.
      Remember, I am not a physician and can not diagnosis or treat any medical condition. However, more than one of my doctors are taking notes and asking me for the web addresses of the studies I have read since they are dumbfounded at the huge reduction in pain and being able to cut my pain medication in half overnight. I am just f___ING thrilled myself, especially since just the co-pay for the Nucynta is almost $200 a month. I will now have more money for other things, like HEAT now. Having to keep my house at 55 degrees Fahrenheit during the winter in order to afford my pain medication has been very hard these last six years. Now if I can only get completely off the pain medication, I will be able to have a nice glass of Moselle white wine with dinner occasionally, it has been 20 years since my last glass.

      • Aelxa Hill says:

        Please excuse me, I made a big mistake (due to a chemical exposure which caused a brain glitch) in the first 2 paragraphs of what I posted above this post. Pyridoxine is the correct form of B6 to take. Pyridoxine will fit in the B6 cell wall transport port, the P5P form of B6 will not fit. The P5P form of B6 is made inside the body’s cells by organelles that live only inside the cells. The organelles convert the Pyridoxine into P5P.
        Ignore what I posted about methylfolate, it was incorrect.
        The only way for chemical forms of B6 to get out of the body is through being detoxified by the body’s methylation system. The only way to improve the methylation system is to decrease the amounts of chemicals you get in your body. You need to eat clean organic vegetables also eat organic and grass-fed meats. Avoid packaged processed foods which contain many added chemicals. All these things will help.
        Avoid chemical cleaners, use old-fashioned soap and water to clean. Do not use so-called air fresheners, the less chemicals in your home, the less chemicals your body’s methylation system has to detoxify.

        • Thank you very much for all your good information. so if I understand pyridoxine will go into the cell. so is it possible for me to take a pyridoxine supplement to help my numbness in feet and arm ? If yes do I need pyridoxine alone or do I need to associate it with B12? THANKS

    • Joe Leech, Dietitian says:

      I don’t have any specific recommendations for B6 sorry

  46. Pami Coakley says:

    I have sever depression and anxiety..been on meds for 20 plus years..not much help.
    My psychiatric suggested the l methylfolate..15 mg daily.
    Some of the side effects seem to sound worse than the benefits? I’m confused.
    Now knowing that I need the l methylfolate…if I start trying to eat foods high in it..won’t that be too much? Sounds like it might do more harm than good

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