Myths of Methyl B12 and Methylfolate Benefits: Part 2

Written by Dr. Steve Chaney on . Posted in Methyl B12, Methyl folate, Methylfolate

Debunking The Myths

Author: Dr. Stephen Chaney


Now that I have shared the saga of how the methylfolate and methyl B12 stories progressed from a kernel of truth to myths and eventually to outright lies, let me systematically debunk the myths of the mehtyl B12 and methylfolate benefits.


Debunking The Myths of Methylfolate Benefits


Methylfolate Benefits Myth: Methylfolate is natural. It comes from whole food. Folic acid is synthetic.

Fact: I covered this earlier. Methylfolate is chemically synthesized from folic acid. It is physically impossible to extract enough from whole foods.


Methylfolate Benefits Myth: Methylfolate is better utilized by the body than folic acid.

Fact: This claim is based on levels of methylfolate in the blood after taking supplements providing equivalent amounts of methylfolate and folic acid. However, methylfolate has no biological activity in our blood. The measurement that matters is total folate levels (methylfolate plus other folates) in our cells. If you take equivalent amounts of folic acid and methylfolate, you end up with identical folate levels in your cells (B.J. Venn et al, The Journal of Nutrition, 132: 3333-3335, 2002 ). In short, there is no difference in our ability to utilize methylfolate and folic acid.


Methylfolate Benefits Myth: If you have a mutation in the MTHFR gene, folic acid isn’t effective.

Fact: MTHFR slightly increases the need for folic acid (from 400 ug to between 600 and 800 ug), but multiple studies show that folic acid supplementation is effective in people with MTHFR mutations. For example, homocysteine levels are easily measured and are a reliable indicator of methylfolate status. One study has shown that folic acid and methylfolate were equally effective at lowering plasma homocysteine in people who were MTHFR C677T homozygotes (I.P. Fohr et al, American Journal of Clinical Nutrition, 75: 275-282, 2002 ). That study also showed that folic acid was more effective than methylfolate at lowering homocysteine in people who were C677T heterozygotes and in people with normal MTHFR activity. Another study showed folic acid was just as effective as a diet providing equivalent quantities of folate from foods at lowering homocysteine levels in people with various MTHFR mutations (P.A. Ashfield-Watt et al, American Journal of Clinical Nutrition, 76: 180-186, 2002 ).

At present, lowering of homocysteine levels is the only indicator of methylfolate status for which methylfolate and folic acid have been directly compared. However, there are other studies suggesting that folic acid is likely to be effective for people with MTHFR defects.

For example, folic acid has been shown in multiple studies to be effective in preventing neural tube defects (L.M.De-Regil et al, Cochrane Database Systematic Reviews 2010 Oct 6;(10):CD007950. PMID: 20927767 ), which are highly associated with the C677T MTHFR gene defect. Three studies have shown that supplementation with folic acid, B12, and B6 slowed cognitive decline in older people with elevated homocysteine levels (J.Durga et al, The Lancet, 369: 208-216, 2007 ; A.D.Smith et al, PLoS ONE 5(9): e12244. doi:10.1371/journal.pone.0012244, 2010 ; G.Douaud et al, Proceedings of the National Academies of Sciences, 110: 9523-9528, 2013 ). In contrast, the one study that substituted methylfolate for folic acid showed no effect (J.A. McMahon et al, New England Journal of Medicine, 354: 2764-2769, 2006 ).


Methylfolate Benefits Myth: Folic acid causes cancer.

Fact: The studies suggesting that folic acid supplementation might increase the risk of cancer were all “outliers.”  By that I mean they contradicted many other studies showing no increased risk. Scientists are accustomed to this. We know that studies sometimes come up with conflicting results. In some cases, we can point to an error in experimental design or statistical analysis as the cause of the aberrant results. In other cases, we never methylfolate benefitsknow the reason for the differences, so we go with the weight of experimental evidence (what the majority of studies show). The weight of evidence clearly supports the safety of folic acid.

However, that is not enough. If there is the slightest possibility that something causes cancer, we investigate it further. Consequently, the scientific community followed up with larger studies. Those studies showed either reduced cancer risk or no difference in cancer risk with folic acid supplementation. None of the studies found any evidence that folic acid increased cancer risk. I have covered this in detail for folic acid and colon cancer risk in a previous issue of “Health Tips From The Professor.”

There have also been a couple of small studies suggesting that folic acid might increase the risk of prostate and breast cancer. Although these were small, individual studies, they have been widely hyped by the methylfolate advocates. Once again, the definitive study has been done (S.E. Vollset et al, The Lancet, 381: 1029-1036, 2013 ).

It was a meta-analysis of every placebo controlled study prior to 2010 that analyzed the effect of folic acid supplementation on cancer risk, a total of 13 studies involving over 50,000 subjects. The results were clear cut. Folic acid supplementation caused no increase in overall cancer risk, and no increase in the risk of colon cancer, prostate cancer, breast cancer, or any other individual cancer. Moreover, the average dose of folic acid in those studies was 2 mg/day, which is 5 times the RDA.

Of course, the bloggers and the companies selling methylfolate supplements ignore the definitive studies showing folic acid does not increase cancer risk. The myths and the lies continue.


Methylfolate Benefits Myth: Folic acid supplementation during pregnancy increases autism risk.

Fact: This myth is based on a recent study presented at an international meeting. There are two important things you should know about this myth.

#1: This study has not yet gone through the peer review process necessary for publication. We do not know if it is a valid study.

#2: The authors of this study are desperately trying to correct the misleading information that is being circulated on the internet about their study. They say their study does not apply to women taking a prenatal supplement containing folic acid during pregnancy. In fact, several studies  show that supplementation with 400 ug of folic acid during pregnancy decreases autism risk.

The authors emphasize that the increase in autism risk in their study was only seen in women with 4 times the recommended levels of folate in their blood at delivery. In other words, it only applies to women taking mega-doses of folic acid during pregnancy. Taking mega-doses of any vitamin during pregnancy is a bad idea.

Unfortunately, the best efforts of the authors have not deterred irresponsible bloggers and journalists from spreading the myth that folic acid supplementation during pregnancy may cause autism. That is incredibly bad advice because it may discourage some expectant mothers from taking prenatal vitamins with folic acid. Multiple studies have shown folic acid supplementation during pregnancy reduces the risk of birth defects.


Methylfolate Benefits Myth: Folic acid can mask a B12 deficiency.

Fact: True, but irrelevant if you use a supplement with folic acid and B12 in balance.

For more details and references, watch my “Truth About Methyl Folate” video in the Video Resources section of Health Tips From The Professor.


Debunking The Myths of The Methyl B12 Benefits

Along with the methylfolate myths have come the methyl B12 myths. Some supplement manufacturers are now claiming that methyl B12 (methylcobalamin) is more natural and more effective than the cyanocobalamin that has been used in supplements for the past 70 years. The arguments are essentially the same as for methylfolate, so let me briefly debunk the methyl B12 claims as well.


methylfolate benefits and methyl b 12Methyl B12 Benefits Myth: Methyl B12 (methylcobalamin) is more natural than cyanocobalamin. We get the methyl B12 in our supplements from foods.

Fact: As with methylfolate, it would be impossible to extract enough methylcobalamin from foods. In fact, most of the methylcobalamin in supplements is chemically synthesized from either cyanocobalamin or hydroxycobalamin. It can never be more natural than it’s starting ingredients. A small amount of methylcobalamin is made from genetically modified bacteria.


Methyl B12 Benefits Myth: Cyanocobalamin is toxic.

Fact: You get much more cyanide from common foods such as almonds, lima beans, any fruit with a pit such as peaches, and even some fruits with seeds, such as apples. For example, a single almond contains 200 times more cyanide than a supplement providing the RDA of cyanocobalamin.


Methyl B12 Benefits Myth: Because methylcobalamin is one of the active forms of B12 inside cells (adenosylcobalamin is the other), it is better utilized by cells than cyanocobalamin.

Fact: Cyanocobalamin and methylcobalamin are equally well absorbed by the intestine and equally well transported to our cells. At the cell membrane, the cyano and methyl groups are stripped off and cobalamin (B12) binds to a transport protein called transcobalamin II. Once inside the cell either a methyl group or adenosyl group is added back to cobalamin. In short, methylcobalamin offers no advantage over cyanocobalamin because its methyl group is removed before it enters our cells. Once the methyl and cyano groups have been removed, the cell has no way of knowing whether B12 started out in the methyl or cyano form.


Methyl B12 Benefits Myth: Methylcobalamin is better utilized than cyanocobalamin for people with methylation defects.

Fact: A methylation defect would affect methylation of cobalamin once it is released from transcobalamin II inside the cell. Because the methyl and cyano groups are removed before cobalamin binds to transcobalamin II, methylcobalamin offers no advantage over cyanocobalamin.


What Does This Mean For You?

MTHFR mutations only result in partial loss of activity. Most individuals with MTHFR defects remain symptom free with the RDA, or slightly above the RDA, of folic acid. However, there may be some individuals with a MTHFR defect and additional gene defects in metabolic pathways involving methylation who might benefit from methylfolate. This is due to a phenomenon that geneticists call penetrance and would likely represent a small subset of the population with MTHFR defects. The claims that everyone would benefit from methylfolate instead of folic acid are false. They are contradicted by human metabolism and published clinical studies.

The claims that everyone would benefit from methylcobalamin (methyl B12) instead of cyanocobalamin is even more outrageous. Anyone who takes the time to research how B12 enters our cells would realize that the claim is biochemically impossible.

In short, folic acid has been used for over 80 years and cyanocobalamin for 70 years. There are hundreds of clinical studies showing they are safe and effective, even in most individuals with a MTHFR deficiency. I can’t tell you whether the companies selling methylfolate and methyl B12 are ignorant of basic metabolism and the published studies refuting their claims or whether they are purposely trying to deceive the public—but neither is a good thing.


The Bottom Line


Last week I shared the story about how the myths about methylfolate and methyl B12 arose and how they eventually became lies. This week I debunked the myths of methyl B12 and methylfolate benefits.


These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.


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Comments (7)

  • Susan McNeil


    I Loved these information. Thank you. I just wish there was a way to share it on social media.


    • Dr. Steve Chaney


      You can share my post on my Steve Chanet Facebook page


  • Rose Mary Simmons


    I appreciate your 2-part explanation of methylfolate in such detail. I have celiac and also the MTHFR gene mutation so my nutritionist had me switch to her suggested vitamins and B’s. I knew Shaklee has no equal in quality so was concerned but had no information to go on. I have not felt any better taking other supplements and want to start back on all the things I was taken off of but wondering if someone with the gene mutation just needs to take extra to compensate for lack of absorption?


    • Dr. Steve Chaney


      Dear Rose Mary,
      Your situation is not unique. I have heard from many people with MTHFR mutations who have been put on methyl folate supplements and tell me they haven’t helped. The answer to your question is that MTHFR mutations slightly increase your need for folic acid, but 600 to 800 mcg/day should do it.
      Dr. Chaney


  • Louise Rees


    wish I could get these regularly. I get maybe one every few months.

    Louise Rees REES2380 password lered3d5


    • Dr. Steve Chaney


      Dear Louise,

      You are on the email list to receive “Health Tips From the Professor”. If you are not receiving it on a regular basis, check to see if it is going to your spam box on weeks you don’t find it in your In box. It goes out every Tuesday. If it is going to your spam box, set the “from” email address so it always goes to your In box.

      Dr. Chaney


  • Sarah


    I’m compound heterozygous for the MTHFR variant and have never had issues with supplements or other products containing folic acid or cyanocobalamin. In fact, I’m taking a really good B complex supplement right now that has a good balance of all eight B vitamins in reasonable doses (none over 250% of the RDA). It contains folic acid and cyanocobalamin. It really seems to make a difference in how I feel, and I hope future test results will confirm it. Thanks so much for the information, but it seems that the myths abound. Searching for MTHFR turns up sites and blogs that pretty much universally say that folic acid is harmful. I’ve had to restrict my research to the few sites like this one and Google Scholar to get the answers I’ve been seeking.


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Recent Videos From Dr. Steve Chaney


Latest Article

Is Our Microbiome Affected By Exercise?

Posted November 6, 2018 by Dr. Steve Chaney

Microbiome Mysteries

Author: Dr. Stephen Chaney

is our microbiome affected by exerciseIn a recent post,  What is Your Microbiome and Why is it Important,  of “Health Tips From The Professor” I outlined how our microbiome, especially the bacteria that reside in our intestine, influences our health. That influence can be either good or bad depending on which species of bacteria populate our gut. I also discussed how the species of bacteria that populate our gut are influenced by what we eat and, in turn, influence how the foods we eat are metabolized.

I shared that there is an association between obesity and the species of bacteria that inhabit our gut. At present, this is a “chicken and egg” conundrum. We don’t know whether obesity influences the species of bacteria that inhabit our gut, or whether certain species of gut bacteria cause us to become obese.

Previous studies have shown that there is also an association between exercise and the species of bacteria that inhabit our gut. In particular, exercise is associated with an increase in bacteria that metabolize fiber in our diets to short chain fatty acids such as butyrate. That is potentially important because butyrate is a primary food source for intestinal mucosal cells (the cells that line the intestine). Butyrate helps those cells maintain the integrity of the gut barrier (which helps prevent things like leaky gut syndrome). It also has an anti-inflammatory effect on the immune cells that reside in the gut.

However, associations don’t prove cause and effect. We don’t know whether the differences in gut bacteria were caused by differences in diet or leanness in populations who exercised regularly and those who did not. This is what the present study (JM Allen et al, Medicine & Science In Sports & Exercise, 50: 747-757, 2018 ) was designed to clarify.  Is our microbiome affected by exercise?


How Was The Study Designed?

is our microbiome affected by exercise studyThis study was performed at the University of Illinois. Thirty-two previously sedentary subjects (average age = 28) were recruited for the study. Twenty of them were women and 12 were men. Prior to starting the study, the participants filled out a 7-day dietary record. They were asked to follow the same diet throughout the 12-week study. In addition, a dietitian designed a 3-day food menu based on their 7-day recall for the participants to follow prior to each fecal collection to determine species of gut bacteria.

The study included a two-week baseline when their baseline gut bacteria population was measured, and participants were tested for fitness. This was followed by a 6-week exercise intervention consisting of three supervised 30 to 60-minute moderate to vigorous exercise sessions per week. The exercise was adapted to the participant’s initial fitness level, and both the intensity and duration of exercise increased over the 6-week exercise intervention. Following the exercise intervention, all participants were instructed to maintain their diet and refrain from exercise for another 6 weeks. This was referred to as the “washout period.”

VO2max (a measure of fitness) was determined at baseline and at the end of the exercise intervention. Stool samples for determination of gut bacteria and concentrations of short-chain fatty acids were taken at baseline, at the end of the exercise intervention, and again after the washout period.

In short, this study divided participants into lean and obese categories and held diet constant. The only variable was the exercise component.


Is Our Microbiome Affected By Exercise?

is our microbiome affected by exercise fitnessThe results of the study were as follows:

  • Fitness, as assessed by VO2max, increased for all the participants, and the increase in fitness was comparable for both lean and obese subjects.
  • Exercise induced a change in the population of gut bacteria, and the change was comparable in lean and obese subjects.
  • Exercise increased fecal concentrations of butyrate and other short-chain fatty acids in the lean subjects, but not in obese subjects.
  • The exercise-induced changes in gut bacteria and short-chain fatty acid production were largely reversed once exercise training ceased.

The authors concluded: “These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent of diet, and contingent on the sustainment of exercise.” [Note: To be clear, the exercise-induced changes in both gut bacteria and short-chain fatty acid production were independent of diet and contingent on the sustainment of exercise. However, only the production of short-chain fatty acids was dependent on obesity status.]


What Does This Study Mean For You?

is our microbiome affected by exercise gut bacteriaThere are two important take home lessons from this study.

  • With respect to our gut bacteria, I have consistently told you that microbiome research is an emerging science. This is a small study, so you should regard it as the beginning of our understanding of the effect of exercise on our microbiome rather than conclusive by itself. It is consistent with previous studies showing an association between exercise and a potentially beneficial shift in the population of gut bacteria.

The strength of the study is that it shows that exercise-induced changes in beneficial gut bacteria are probably independent of diet. However, it is the first study to look at the interaction between obesity, exercise and gut bacteria, so I would interpret those results with caution until they have been replicated in subsequent studies.

  • With respect to exercise, this may be yet another reason to add regular physical activity to your healthy lifestyle program. We already know that exercise is important for cardiovascular health. We also know that exercise increases lean muscle mass which increases metabolic rate and helps prevent obesity. There is also excellent evidence that exercise improves mood and helps prevent cognitive decline as we age.

Exercise is also associated with decreased risk of colon cancer and irritable bowel disease. This effect of exercise has not received much attention because the mechanism of this effect is unclear. This study shows that exercise increases the fecal concentrations of butyrate and other short-chain fatty acids. Perhaps, this provides the mechanism for the interaction between exercise and intestinal health.


The Bottom Line

A recent study has reported that:

  • Exercise induces a change in the population of gut bacteria, and the change was comparable in lean and obese subjects.
  • Exercise causes an increase in the number of gut bacteria that produce butyrate and other short-chain fatty acids that are beneficial for gut health.
  • These effects are independent of diet, but do not appear to be independent of obesity because they were seen in lean subjects but not in obese subjects.
  • The exercise-induced changes in gut bacteria and short-chain fatty acid production are largely reversed once exercise training ceases.

The authors concluded: “These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent on diet, and contingent on the sustainment of exercise.”

For more details and my interpretation of the data, read the article above.


These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.