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.

    Reply

    • Dr. Steve Chaney

      |

      You can share my post on my Steve Chanet Facebook page

      Reply

  • 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?

    Reply

    • 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

      Reply

  • Louise Rees

    |

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

    Louise Rees REES2380 password lered3d5

    Reply

    • 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

      Reply

  • 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.

    Reply

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Latest Article

Does Protein Supplement Timing Matter?

Posted May 15, 2018 by Dr. Steve Chaney

How Do You Gain Muscle Mass & Lose Fat Mass?

Author: Dr. Stephen Chaney

 

protein supplement timingMost of what you read about protein supplements on the internet is wrong. That is because most published studies on protein supplements:

  • Are very small
  • Are not double blinded.
    • Both the subjects and the investigators knew who got the protein supplement.
  • Are done by individual companies with their product.
    • You have no idea which ingredients are in their product are responsible for the effects they report.
    • You have no idea how their product compares with other protein products.
    • There is no standardization with respect to the amount or type of protein or the addition of non-protein ingredients.

Because of these limitations there is a lot of misleading information on the benefits of protein supplements timing and maximal benefit. Let’s start by looking at why people use protein supplements. Let’s also look at what is generally accepted as true with respect to the best supplement timing.

There are 4 major reasons people consume protein supplements:

  • Enhance the muscle gain associated with resistance training: In this case, protein supplements are customarily consumed concurrently with the workout.
  • Preserve muscle and accelerate fat loss while on a weight loss diet: In this case, protein supplements are customarily consumed with meals or as meal replacements.
  • Provide a healthier protein source. In this case, protein supplements are customarily consumed with meals in place of meat protein.
  • Prevent muscle loss associated with aging or illness. There is no customary pattern associated with this use of protein supplements.

How good are the data supporting the customary timing of protein supplementation? The answer is: Not very good. The timing is based on a collection of weak studies which do not always agree with each other.

The current study  (J.L. Hudson et al, Nutrition Reviews, 76: 461-468, 2018 ) was designed to fill this void in our knowledge. It is a meta-analysis that compares all reasonably good studies that have looked at the effect of protein supplement timing on weight gain or loss, lean muscle mass gain, fat loss, and the ratio of lean muscle mass to fat mass.

How Was The Study Done?

The authors started by doing a literature search of all studies that met the following criteria:

  • The study was a randomized control trial with parallel design. This means that study contained a control group. It does not mean that the investigators or subjects were blinded with respect to which subjects used a protein supplement and which did not.
  • The subjects were engaged in resistance training.
  • The study lasted 6 weeks or longer.
  • Reliable methods were used to measure body composition (lean muscle mass and fat mass).
  • The subjects were healthy and at least 19 years old.
  • There was no restriction on the food the subjects consumed.

The authors started with 2074 published studies and ended up with 34 that met all their criteria. They then separated the studies into two groups – those in which the protein supplements were used with meals and those in which the protein supplements were used between meals.

Both groups were diverse.

  • Group 1 included subjects who consumed their protein supplement with their meal and those who consumed their protein supplement as a meal replacement.
  • Group 2 included subjects who consumed their protein supplement concurrent with exercise (usually immediately after exercise) and those who consumed their protein supplement at a fixed time of day not associated with exercise.

Does Protein Supplement Timing Matter?

 

protein supplement timing workoutsBecause the individual studies were very diverse in the way they were designed, the authors could not calculate a reliable estimate of how much lean muscle mass was increased or fat mass was decreased. Instead, they calculated the percentage of studies showing an increase in lean muscle mass or a decrease in fat mass.

When the authors compared protein supplements consumed with meals versus protein supplements consumed between meals:

  • Weight gain was observed in 56% of the studies of protein supplementation with meals compared to 72% of the studies of protein supplementation between meals. In other words, protein supplements consumed with meals were less likely to lead to weight gain than protein supplements consumed between meals.
  • An increase in lean muscle mass was observed in 94% of the studies of protein supplementation with meals compared to 90% of the studies of protein supplementation between meals. In other words, timing of protein supplementation did not matter with respect to increase in muscle mass.
  • A loss of fat mass was observed in 87% of the studies of protein supplementation with meals compared to 59% of the studies of protein supplementation between meals. In other words, protein supplements consumed with meals were more likely to lead to loss of fat mass.
  • An increase in the ratio of lean muscle mass to fat mass was observed in 100% of the studies of protein supplementation with meals compared to 87% of the studies of protein supplementation between meals. In short, protein supplements consumed with meals were slightly more likely to lead to an increase in the ratio of lean muscle mass to fat mass.

The following seem to suggest protein supplement timing matters:

The authors pointed out that their findings were consistent with previous studies showing that when protein supplements are consumed with a meal they displace some of the calories that otherwise would have been consumed. Simply put, people naturally compensate by eating less of other foods.

In contrast, the authors stated that previous studies have shown that when foods, especially liquid foods, are consumed as snacks (between meals), people are less likely to compensate by reducing the calories consumed in the next meal.

The others concluded: “Concurrently with resistance training, consuming protein supplements with meals, rather than between meals, may more effectively promote weight control and reduce fat mass without influencing improvements in lean [muscle] mass.”

What Are The Limitations Of The Study?

Meta-analyses such as this one, are only as good as the studies included in the meta-analysis. Unfortunately, most sports nutrition studies are very weak studies. Thus, this meta-analysis is a perfect example of the “Garbage In: Garbage Out (GI:GO)” phenomenon.

For example, let’s start by looking at what the term “protein supplement” meant.

  • Because the studies were done by individual companies with their product, the protein supplements in this meta-analysis:
    • Included whey, casein, soy, bovine colostrum, rice or combinations of protein sources.
    • Were isolates, concentrates, or hydrolysates.
    • Contained various additions like creatine, amino acids, and carbohydrate.
  • As I discuss in my book, Slaying the Food Myths, previous studies have shown that optimal protein and leucine levels are needed to maximize the increase in muscle mass and decrease in fat mass associated with resistance exercise. However, neither protein nor leucine levels were standardized in the protein supplements included in this meta-analysis.
  • Previous studies have shown that protein supplements that have little effect on blood sugar levels (have a low glycemic index) are more likely to curb appetite. However, glycemic index was not standardized for the protein supplements included in this meta-analysis.

protein supplement timing workout peopleIn short, the conclusions of this study might be true for some protein supplements, but not for others. We have no way of knowing.

We also need to consider the composition of the two groups.

  • Protein supplements used as meal replacements are more likely to decrease weight and fat mass than protein supplements consumed with meals. Yet, both were included in group 1.
  • Some studies suggest that protein supplements consumed concurrent with resistance exercise are more likely to increase muscle mass than protein supplements consumed another time of day. Yet, both are included in group 2. We also have no idea whether the meals with protein supplements in group 1 were consumed shortly after exercise or at an entirely different time of day.

This was the most glaring weakness of the study because it was completely avoidable. The authors could have grouped the studies into categories that made more sense.

In other words, there are multiple weaknesses that limit the predictive power of this study.

What Can We Learn From This Study?

Despite its many limitations, this study does remind us that protein supplements do have calories. This is of relatively little importance for people whose primary goal is to increase lean muscle mass.

However, most of us are using protein supplements to lose weight or to increase our lean mass to fat mass ratio. Simply put, we are either trying to lean out (shape up) or lose weight. And, we want to lose that weight primarily by getting rid of excess fat. For us, calories do matter. With that in mind:

  • If we are consuming a protein supplement immediately after exercise or between meals we probably should make a conscious effort to reduce our daily caloric intake elsewhere in our diet.
  • Alternatively, we could consume the protein supplement with a meal, but time the meal so it occurs shortly after exercise.

 

The Bottom Line:

 

A recent study looked at the optimal timing of protein supplements consumed by subjects who were engaged in resistance exercise. Specifically, the study compared protein supplements consumed with meals versus protein supplements consumed between meals on weight, lean muscle mass, fat mass, and the ratio of lean muscle mass to fat mass. The study reported:

  • Protein supplements consumed with meals were less likely to lead to weight gain than protein supplements consumed between meals.
  • Timing of protein supplementation did not matter with respect to increase in muscle mass.
  • Protein supplements consumed with meals were more likely to lead to loss of fat mass.
  • Protein supplements consumed with meals were slightly more likely to lead to an increase in the ratio of lean mass to fat mass.

The authors pointed out that their findings were consistent with previous studies showing that when a protein supplement was consumed with a meal it displaces some of the calories that would have been otherwise consumed. Simply put, people naturally compensate by eating less of other foods.

In contrast, the authors said that previous studies have shown that when foods, especially liquid foods, are consumed as snacks (between meals), people are less likely to compensate by reducing the calories consumed in the next meal.

As discussed in the article above, the study has major weaknesses. However, despite its many weaknesses, this study does remind us that protein supplements do have calories. This is of relatively little importance for people whose primary goal is to increase lean muscle mass.

However, for those of us who are using protein supplements to lose weight or to increase our lean mass to fat mass ratio, calories do matter.  With that in mind:

  • If we are consuming a protein supplement immediately after exercise or between meals we probably should make a conscious effort to reduce our daily caloric intake elsewhere in our diet.
  • Alternatively, we could consume the protein supplement with a meal, but time the meal so it occurs shortly after exercise.

For more details, 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.

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