Can Folic Acid Be Harmful?

Can Folic Acid Be Harmful?
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New research on the human metabolism of folic acid suggests natural sources of folate are preferable.

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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

Folic acid supplements, which are recommended for all women of child-bearing age to prevent birth defects. Harmful, harmless, or helpful? In other words, vitamin and panacea, or genetic time-bomb?

I do not recommend folic acid supplements; I recommend folate—from the same word root as foliage—found in dark green leafy vegetables and legumes.

But everybody knows no one eats greens and beans every day, so the government started fortifying our food supply with folic acid in 1998. Folic acid, though, is not the same thing as folate. But it’s cheaper and more stable in pill form, and so that’s why they use it instead. In fact, folic acid is a synthetic chemical not found in nature at all. But, studies on rats found that there’s an enzyme in the liver that basically changes it into the natural form.

Studies keep coming out, though, linking folic acid supplementation with diseases like breast cancer and colon cancer. So yes, it lowers the risk of birth defects, but may raise our risk of cancer. But, wait a second; spinach doesn’t raise our risk of cancer. Beans and greens lower the risk of both birth defects and cancer. It was a big mystery until last year, when scientists figured out we’re not rats.

It’s hard to study human livers, because people tend to need them, but sometimes an organ donor dies, and there’s no one to take the liver. And so, scientists were finally able to see if what happens in rat livers actually happens in human livers. And it turns out that the enzyme that converts folic acid in pills into something our body can actually use, is 50 times less active than in rats. Less than 2% of the activity we thought it had, based on the animal studies.

So, because our enzyme is extremely slow, people who take folic acid pills have lots of this synthetic folic acid circulating in their bodies, and that’s what we think may be behind the elevated cancer risk. Whereas beans and greens every day offer the best of both worlds.

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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

Folic acid supplements, which are recommended for all women of child-bearing age to prevent birth defects. Harmful, harmless, or helpful? In other words, vitamin and panacea, or genetic time-bomb?

I do not recommend folic acid supplements; I recommend folate—from the same word root as foliage—found in dark green leafy vegetables and legumes.

But everybody knows no one eats greens and beans every day, so the government started fortifying our food supply with folic acid in 1998. Folic acid, though, is not the same thing as folate. But it’s cheaper and more stable in pill form, and so that’s why they use it instead. In fact, folic acid is a synthetic chemical not found in nature at all. But, studies on rats found that there’s an enzyme in the liver that basically changes it into the natural form.

Studies keep coming out, though, linking folic acid supplementation with diseases like breast cancer and colon cancer. So yes, it lowers the risk of birth defects, but may raise our risk of cancer. But, wait a second; spinach doesn’t raise our risk of cancer. Beans and greens lower the risk of both birth defects and cancer. It was a big mystery until last year, when scientists figured out we’re not rats.

It’s hard to study human livers, because people tend to need them, but sometimes an organ donor dies, and there’s no one to take the liver. And so, scientists were finally able to see if what happens in rat livers actually happens in human livers. And it turns out that the enzyme that converts folic acid in pills into something our body can actually use, is 50 times less active than in rats. Less than 2% of the activity we thought it had, based on the animal studies.

So, because our enzyme is extremely slow, people who take folic acid pills have lots of this synthetic folic acid circulating in their bodies, and that’s what we think may be behind the elevated cancer risk. Whereas beans and greens every day offer the best of both worlds.

Please consider volunteering to help out on the site.

Doctor's Note

Also check out these videos:
Some Dietary Supplements May Be More Than a Waste of Money
Risk Associated With Iron Supplements
Dietary Supplement Snake Oil

And check out my other videos on folate. If you’re worried about the gassiness of beans as a source of folate, check out my blog post Beans and Gas: Clearing the Air

For more context, also see my associated blog posts: Breast Cancer & DietSoy milk: shake it up! and Are Multivitamins Just a Waste of Money?

If you haven’t yet, you can subscribe to my videos for free by clicking here.

52 responses to “Can Folic Acid Be Harmful?

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  1. Please feel free to post any ask-the-doctor type questions here in the comments section and I’d be happy to try to answer them. And check out the other videos on folate. If you’re worried about the gassiness of beans as a source of folate, check out my blogpost Clearing the Air. Also, there are 1,449 other subjects covered in the rest of my videos–please feel free to explore them as well!




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    1. I have a genetic defect known as MTHFR, which makes it impossible for me to utilize folate from food or conventional supplements. I must take methylfolate supplements twice daily for life, as a result. Although I realize this does not entirely return me to “normal” health, I am extremely healthier with the supplement than without. Can you speak to those who have issues with folate utilization?




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      1. For those unfamiliar, humans have a gene that
        regulates the activity of an enzyme called MTHF-reductase. This enzyme is
        responsible for methylation or in layman’s terms, activation of several B
        vitamins, in particular folate. This is an important enzyme as the body only
        uses folate in the activated form and methylation is one method the
        body uses to remove toxic intermediaries of metabolism and other substances
        that might otherwise cause harm. Inability
        to activate folate can contribute to symptoms including fatigue, depression and
        elevated homocysteine that can contribute to cardiovascular disease. During pregnancy this enzyme helps provide
        L-methylfolate which is required for proper development of the neural tube or
        nervous system of a developing fetus. It is estimated that up to 30% of the
        population can possess one or more genetic variants of the MTHFR gene. If you have this genetic trait, the activity of MTHF-reductase can be reduced by 30%-70%. Taking a high quality supplement that
        contains folic acid as L-methylfolate and B12 as
        methylcobalamine, can address this deficiency and help reverse symtoms. For the majority of people who don’t possess this trait, getting most of your nutrients from food is always your first choice. You might like to check out these other interesting videos on supplementation: Vitamin Supplements Worth Taking and Should We Take a Multivitamin




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        1. Thanks for your excellent and detailed response. I wonder if the high prevalence of MTHFR mutations warrants more extensive screening testing for this mutation, at the very least in women who are pregnant or planning to become pregnant. Do you (or other NF viewers/readers) know the cost of this test and whether insurance generally covers the cost?




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          1. Linda provided some good resources! I’m not an expert on testing methods and unsure what insurance covers the testing. Perfect question for your doctor and healthcare team. Let us know if you find out anything.




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        2. Can MTHFR mutations be compensated for by increasing intake of Folate from food? My husband and I both have these mutations. Using CRON O METER I increased our Folate goal to compensate for the percentage that we are not Methylating. My deficit is reasonable to make up for with generous portions of greens and beans, but my husbands …far exceeds his appetite. Is it reasonable to assume that by consuming the extra % of Folate through food that the body isn’t able to grab that I am compensating for the mutation?

          Our Methyl Folate supplement bottle says “…if you are pregnant or tying to conceive consult your health care professional before taking…”. It seems that would be the time one would need it the most. Any insight into what the concern might be? BTW my healthcare provider has no clue about MTHFR mutations. Any advice on finding a knowledgeable professional to consult on this?




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          1. Hi D A, Unfortunately the folate in food must be converted into a usable form in the body. In people who have the MTHFR gene variant the enzyme responsible for this conversion has reduced function and for this reason those individuals need to take a methylated form of folate. By doing this you will bypass the step where the enzyme is needed. So the short answer to your question is no, you can not compensate for an MTHFR gene variant by taking more folate in your diet.
            The most likely reason your bottle says to consult a health care professional if you are pregnant or nursing is because pregnant or nursing women often have different nutrient requirements than the general population so most manufactures will put a similar warning on their labels. In addition pregnant women are at risk for having children born with neural tube defects if they don’t get adequate amounts of folate so it’s best for them to take folate under the direction of a healthcare provider to assure adequate amounts.
            Finally, you could try doing a search for a certified Functional Medicine Practitioner in your area by going to the website if the Institute for Functional Medicine http://www.functionalmedicine.org Click on the find a practitioner link and search by state or zip code. Any certified practitioner should be familiar MTHFR and with methylation related problems.




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    2. Could someone from the team…Darryl : ) please address Monica et al. regarding this MTHFR issue? I’ve never heard about it.

      thanks




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    3. Dear Dr. Greger,
      I have been taking vitamin supplements for more than 5 years. A multivitamins and a B complex so I think I’ve been taking about 500 mcg of folic acid a day. About 4 months ago I had my yearly blood test done and the result was scary. My folic acid levels (called here in Spain “folic acid erythrocytes”) were up to 1386 ng/mL when the normal parameters are between 112-508ng/mL. My doctor told me to stop taking the supplements and had me do another blood test about a month later. My levels had risen to 1637 ng/mL!! I don’t know what to do and neither does my doctor. She says she’s never encountered these results so of course now I’m worried!!
      What should I do? Am I at a big risk of getting cancer because of these folic acid levels? Is there a way I can cleanse my blood to get rid of the folic acid surplus?
      I stopped taking the supplements but do I need to eat less folate as well, at least until my levels return to normal? I usually have a green smoothie every morning.
      Many thanks for your help!!




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    4. I have rheumatoid arthritis and have been on Methrotrexate (25 mg injected once a week) for almost a year now. I have been given folic acid (1 mg/day, except on MTX day) to counter the side effects of the MTX. I recently came upon your piece on the problems with folic acid. For someone in my position, is there any reason I can’t get enough folate from what I eat to counter those side effects? Any reason not to use food instead of the folic acid supplements? I’ve been eating plant based/whole foods for the past five years and on the Paddison Program for RA for well over a year now. The Paddison Program involves a combination of exercise and food — plant based, whole foods, low fat — to control RA. I am largely pain free now though I still have some swelling and stiffness of joints — but much improved. I don’t want to jeopardize these improvements with rising AST/ALT levels (which folic acid is said to prevent). I’d really appreciate getting clear on this. My impulse having watched your video is to ditch the folic acid and keep eating those leafy greens and legumes. Thanks!




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  2. What about folic acid supplements for vegans during pregnancy? Healthy vegan diets are high in folate so it seems possible and certainly preferable to get this nutrient from food rather than supplements.




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    1. The fact that folic acid is attributed to the diseases mentioned in the video makes taking it as a supplement out of the question in my opinion. Its similar to taking a beta carotene supplement, what they have done is isolated a single carotenoid and super concentrated it in a pill. The prenatal supplements are truly not necessary, especially if one is eating as health a a plant based eater.

      Check our Dr. Greger’s video of the dangers of Iron during pregnancy and the vitamin supplements worth taking.

      http://nutritionfacts.org/videos/iron-during-pregnancy/
      http://nutritionfacts.org/videos/vitamin-supplements-worth-taking/




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      1. I’m also very interested in this manner.
        Since both question and answer were provided 5 years ago, is there any new information regarding this?
        Is there any significant finding in the last 5 years that is somewhat changing the stand on folic acid and pregnancy?




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  3. Should we avoid folic acid in supplements completely? I’m looking into B-complex supplements and almost all of them contain 1 mg of folic acid. Thanks for all the awesome videos!




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    1. The study measured folic acid at 1 mg or higher. 1 mg is considered the upper tolerable intake of folic acid. They note that .4 mg of folic acid in individuals gets metabolized to folate but higher than that and we get unmetabolized circulating FA which is harmful. If you are eating a well balanced plant based diet the only supplement you would need is vitamin b12. A B-complex is not necessary.
      http://nutritionfacts.org/videos/vitamin-b12-recommendation-change/




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      1. Thank you so much for the reply! Yeah I was also wondering if B-complex was necessary, I heard from some sources that your body really wants all the B vitamins to be taken together. But Dr Greger seems to recommend B 12 supplement only.




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        1. It is true that almost all whole plant foods contain a mix of the b vitamins, but just because they lack b12 doesn’t mean that the other b vitamins are ineffectively used, nor should we have any reason to believe so.




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          1. I guess when I really think about it, it makes sense that since we can get the rest of the B vitamins from a plant-based diet, the only supplement we need is B 12. Thanks again for your reply :)




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  4. There are food based vitamins such as MegaFood, which offer folate in the normal food form, from broccoli. 40 percent of population has MTHFR genetic mutations which affect the absorption of folate, to varying degrees. The synthetic folic acid is probably more harmful to these people and on top of that, they may need food based supplements-depending on the health of their gut and which mutation they have. It is insane that folic acid is added to everything.




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  5. I was on 5mg folic acid daily to offset harmful effects of methotrexate (for Rheumatoid Arthritis) I’m currently off the mtx but has the 5mg a day possibly done my body harm? I know the mtx probably has! :(




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    1. 5 MTHF is the folate that is actually used in the folate cycle to to make B12. If your folate is not able to be converted to 5-MTHF because of an enzyme deficiency (MTHF reductase) then this is the one that will keep your B12 levels up, your homocysteine levels down and keep your methylation happy. Folic Acid (provided by law in all enriched products) is not found in nature but is quite shelf stable in foods, and requires several more steps to turn into 5-MTHF. We are provided so much in our over consumption of enriched foods (think anything with flour that is not 100% whole wheat) that the build up of Folic Acid can be toxic and cause its own problems. And as chicavegana comefrutes commented above, a large segment of the population has the defective MTHF reductase enzyme which greatly puts them at risk.




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  6. Hi Dr. Greger: I was wondering about Perfect Prenatal by New Chapter Organics as is is a whole foods vitamin which includes “folate” not “folic acid”. Also, I am wondering about Seeking Health L-5 MTHF 1000 which claims to provide only folate as “metafolin” for people with the MTHR issue. In general, are vitamins containing “folate” no “folic acid” ok?




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    1. I think Dr. Greger would stick to his assertion that getting vitamins from whole foods and not pills, will serve our bodies better. Beans and greens are great, affordable sources of folate. :) Hope that helps.




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  7. Dr. Greger, you need a video on MTHFR defects. Some people do process folic acid, but 40% of the population have an MTHFR defect that causes them not to process folic acid into folate. So your recommendation that everyone eat beans and greens is right on target; however, people with MTHFR defects should take a multi and B-complex containing the natural form of folate. In fact, there are studies that link pregnant women who have this defect and take prenatal vitamins containing folic acid are at much high risk for premenopausal breast cancer. That’s 40% of women! (MTHFR polymorphisms, dietary folate intake, and
    breast cancer risk: results from the Shanghai Breast Cancer Study. Shrubsole MJ1, Gao YT, Cai Q, Shu XO, Dai Q, Hébert JR, Jin F, Zheng W. http://www.ncbi.nlm.nih.gov/pubmed/14973091)

    Since my entire family has one or two MTHFR defects, I’ve been reading more and more and am astounded by the statistics, some of which you state that are probably related to MTHFR people ingesting folic acid-fortified foods and increasing incidences of various types of cancer, but it’s more than that. It probably has a hand in every western degenerative disease. As you know, methylation is essential for the proper function of most body systems and cellular processes. It is also needed to support glutathione production which neutralizes free radicals, helps the body process toxins and supports proper DNA synthesis and repair and other metabolic processes. It is required for the creation of every cell in your body. Consequently, it is easy to see how this mutation could have a role in many conditions and diseases. And while I agree that if one is a vegetarian or vegan and eats beans and greens and does not take folic acid or eat fortified foods, their folate status will likely be good enough to not have problems with MTHFR; this is unfortunately not the case for the majority. Please do a video on MTHFR. 40% of the population is a lot of people. Get this, 98% of autistic people have this defect. No wonder they may have trouble processing toxins. Great site. Love the information. You do a great service to the many seekers of nutritional and medical knowledge! Many thanks!




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  8. Yes, I’m very curious to hear the Dr’s opinion on the MTHFR research out there. I asked my doc and she just said it’s “controversial”. I have compound heterozygous mutations and was taking methylfolate in very high quantities daily, but recently stopped because I’m wondering if it’s really making a difference. If I don’t need to be spending $40/month on those pills, that would be great!




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    1. I recently heard from a physician lecturer that preliminary research suggests *high* doses of methylated B-vitamins (methylcobalamin, methylfolate) may shift the cell reproductive cycle towards cancer formation. He said it’s really just a theory right now, but his current recommendation is to avoid *high* doses of methylated B-vitamins. Those with MTHFR mutations should still take *physiologic* doses of methylated B12 and folate, but avoid high doses.

      I would love to see Dr. Greger do a blog post or video on this issue as I have been unable to find the research the lecturer referenced in making his recommendation and as others have commented, MTHFR mutations are common.




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  9. Dr. Ben Lynch and Dr. Amy Yasko have a lot of information on line about the MTHFR genetic defects. Lynch says that those of us with MTHFR defects need to take 5-methyltetrahydrofolic folate. He says not to take the wrong kind – folic acid. Synthetic folic acid is not effective and the unmetabolized folic acid hangs around and reduces our T killer cells leading to immune issues. Also, I believe he says it fills up the folate receptors so the real stuff can’t get in. People can get raw genetic data from 23and me to see if they do have MTHFR (and many other) problems and then go to geneticgenie.com for help deciphering these very complex genetic issues.




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  10. Thanks for your great videos and articles Dr Greger. I mentioned your article on Folic Acid to someone and they said they had read the same studies and the problem with folic acid occurs when little to no vitamin E is ingested. She said that there is no problem with folic acid as long as they take vitamin E as well. Can you look studies again and comment on this. I was considering stopping all folic acid supplementation, but that is not an easy thing to do because nearly all multi-vitamins contain folic acid, not folate.




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  11. Hey :),

    nutritional yeast by some brands also contain high doses of folic acid. Which chemical form of folic acid do they contain? Folic acid or the naturally occuring chemical forms of folate? Is nutritional yeast consumption with high doses (or even low doses) of folic acid safe? I have concerns because as far as i know the growing medium of yeast is often fortified with vitamins to achieve such a high content of said vitamins. Therefore my subsequent question is whether the folic acid in yeast is converted into a naturally occuring form.

    Kind regards,
    Daniel




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  12. Hello, I have just received my blood test results. As expected urea and creatinine are low because I’m eating only plants. As expected my B12 is low so i will start supplementing this is the reason i went for the test). However, my folic acid is high at 20.5ug/L (the printout states that 3 to 20ug/L is the normal range). Is this a problem or a good thing? Is it merely a healthy side effect of eating a WFPB diet? I couldn’t find the answers to this query on google so if anyone here has some knowledge I’d love to hear it. Thanks, Alan




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  13. Should one worry about folic acid in nutritional yeast? How much is too much. The brand I use says is had 270% amount of folate, but lists folic acid at the very end of the ingredient list. It’s Bob’s Red Mill.




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  14. Hi Anna,
    b12 supplements often come with folate and b6 because these three B vitamins compliment each other and act as co-factors when being absorbed. As this video states however, the folic acid in a supplement, although may be absorbed is not usable by the body unless we convert it into the usable form with an enzyme. Since folate is abundant in green leafy vegetables I would try to use greens as my primary source of folate.




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  15. Possibly the introduction of folic acid into the US food supply to combat birth defects is related to the rise in colorectal cancer seen in younger adults(2/28/17 article in Medscape)




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  16. Dr. Greger,

    I moved to a plant-based diet a little over a year ago. Recently I learned that I have an elevated homocysteine level, 14.1 umol/L. I also have a low normal B12 level, 211 pg/mL. My methylmalonate is elevated at 0.6 umol/L. Lastly, my vitamin D is low; 25-HYDROXY is <5 ng/mL. My doctor recommended supplementing B12, Folic Acid and Vitamin D. I'm supplementing as follows:

    Vitamin D : 6,000 IU daily
    B12 : 3,000 mcg weekly

    I haven't started taking Folic Acid supplements. What do you recommend regarding Folic Acid? Also, do you agree with the supplementation above? We will redo these tests in 60 days.

    Any advice is very much appreciated.




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    1. Hi Eric, I am one of the dietitian volunteer moderators on this website. I am glad that you had your blood work done and you were given good advice by your dr to improve your B12 level and consequently that will bring your Homocysteine level down to normal. I don’t know what is your daily food intake however, from the high Homocysteine I could guess that sulfur containing protein food that contains methionine which is an essential amino acid(that means it has to be provided by the diet) might have been low. Therefore, given the essential role of methionine in metabolic processes, that means deregulating the transsufuration pathway, increasing homocysteine levels, and methylating homocysteine to make methionine.
      Having said that, Low level of methionine in vegan diet has been indicated to be protective of heart from oxidative damage as well! So, what would one do? The highest containing methionine nut is Brazil nut. I would recommend addition of Brazil nuts may be up to three per day. Other seeds and nuts also have some good percentage in them. I would suggest also keeping a food dairy and seeing a dietitian to assess your daily intake of all nutrients to make sure your food intake is balanced. I hope these explanation are helpful. I shall also ask you to see these below videos by Dr G. and if you needed any more information by all mean enquire in this forum.
      The Okinawa Diet: Living to 100

      Methionine Restriction as a Life-Extension Strategy

      Vitamin B12 Necessary for Arterial Health




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    2. Hi Eric,
      I’m one of the medical moderators here on the NF site. A I was formulating my response I noticed that one of our nutritionists also has given you an excellent response from a food based nutritional perspective. I’d like to highlight another factor that may be at play here which you can pursue if you have the resources available to you to do so. It is very likely that you have a genetic variant on a gene known as the MTHFR gene which is responsible in part for a very common and necessary chemical reaction known as methylation. People who carry this genetic variant can be very inefficient at methylation which often leads to B12 and folate deficiency and elevated homocysteine levels among other things. These individuals need to supplement with the methylated forms of these B vitamins in order to bypass the “methylation” step that they are inefficient at. In which case it would mean that you should be supplementing with methylcobalamin (B12) as opposed to another form, and L-Methyl Folate as opposed to folic acid. Your doctor can order the MTHFR blood test to see if you possess the genetic variant and how many copies you have. (You can potentially have a copy from each of your parents and these variants are quite common among the general population) This information would better assist you and your doctor in determining the best and most effective supplementation regimen for you.
      Hopefully this information will be helpful to you.




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