Methylfolate and Methyl B12 – Myths or Lies? Part 1

Written by Dr. Steve Chaney on . Posted in Methyl folate

How Did The Myths Arise?

Author: Dr. Stephen Chaney

 

methylated b liesHow did methylfolate become the center of a myth? 

How are the lies of the food supplement industry created? Some of them start innocently enough. They are often based on a kernel of truth which is misinterpreted by some well-meaning medical doctors. It’s not their fault. We teach future doctors what I call “metabolism light” in medical school. There simply isn’t room in the medical curriculum to teach all the details and nuances of human metabolism. We also try to teach them the basics of how to interpret the scientific literature. However, it takes years of experience to get really good at picking out the strengths and weaknesses of clinical studies.

The doctors form their hypothesis and test it on a few patients. If it works, they publish a paper. At that point their idea is picked up by the “sensationalist” bloggers. These are the bloggers who like to focus on the sensational. They delight in writing about “new findings” that go against what the medical profession has been telling you for years. The bloggers don’t stop there. They usually expand the claims. They ‘cherry pick” the scientific literature by quoting only studies that support their viewpoint, and ignoring studies that refute it. In short, they put together a very compelling story. Soon the story is picked up by other bloggers who embellish it further. After it appears in enough sites, people start believing it. A myth is born.

Then supplement companies get in the act. They sense there is money to be made. They manufacture supplements to provide nutrients supported by the myths. They embellish the mythology even more and put together a compelling story to market their products. This is where the mythology becomes deception. Companies have the responsibility to design their products based on the best science. They have an obligation to tell the truth about their products. They know, or should know, that all their claims are not true. When they make claims they know cannot be true, they are lying to you.

The saga of the methylated B vitamins is a perfect example of how observations based on a kernel of truth became myths and eventually became downright lies. Let me share that story with you.

 

The Kernel Of Truth About Methylfolate

 

methylated b folic acidLet’s start with the “kernel of truth” that launched the whole methylfolate saga. It started with a doctor who was having a very difficult time finding a solution for a patient with some significant health issues. The doctor ordered a genetic test and discovered the patient had a deficiency in the methylene tetrahydrofolate reductase (MTHFR) gene. The doctor remembered the reaction catalyzed by MTHFR, and a light bulb went off. “Eureka”, he said. His patient must be unable to make N5-methyltetrahydrofolate (commonly referred to as methyl folate), and methylfolate is required for some very important methylation reactions in the cell.

He gave his patient methylfolate, and the patient’s symptoms got better. The doctor leapt to the conclusion that other patients with MTHFR deficiency needed methyl folate as well. Many of those patients responded to methylfolate as well. He didn’t bother to check whether they responded equally well to folic acid. He just assumed methylfolate was the magic elixir. He wrote a paper on his clinical observations, and the methylfolate story was launched. It all seemed so logical. However, the story was not nearly as straight forward as the doctor and the people publicizing his findings assumed. Let me walk you through some “Metabolism 101”. Don’t worry. There won’t be a quiz.

 

Why The Original Assumptions About Methylfolate Were Misleading

 

MTHFR mutants only have a partial loss of activity.

  • Individuals with 2 copies of a mutation from A to C at position 1298 of the MTHFR gene(A1298C homozygotes) comprise about 5% of the US population. They have 60% enzyme activity and appear to be normal in clinical studies.
  • Individuals with 2 copies of a mutation from C to T at position 677 of the MTHFR gene (C677T homozygotes) have 30% enzyme activity. They comprise about 10% of the US population. C677T homozygotes often have elevated homocysteine levels. The homozygous C677T mutation is associated with depression, anxiety, and mood swings in some people, but not in others (I will come back to the significance of that qualifying statement later).
  • C677T heterozygotes (one mutant gene) have 65% activity and are normal.

We Don’t Need 100% MTHFR Activity

space shuttleOur human body is wonderfully designed. For many of our most essential metabolic reactions we have built in redundancy. We don’t require 100% activity of key enzymes. This helps protect us from bad effects of mutations as they arise.

The best analogy I can think of is the US space program. Most space vehicles had built in redundancy so that if one system failed, the mission could go on. For example, you may remember the Hubble space telescope. It was launched with four gyroscopes to keep the telescope pointed in the right direction. After a few years, one gyroscope gave out. That was not a problem because there were three left. A few years latter the second gyroscope gave out. Again, there was no problem because there were still two gyroscopes left. It was only after the third gyroscope gave out that Hubble became a bit “wonky”, and a space shuttle was sent up to replace the gyroscopes. It is the same with MTHFR. Only when you get down to around 30% activity, does it become a bit wonky”. (That’s about as non-technical as I get.)

Not Everyone With MTHFR Deficiency Experiences Symptoms

This is due to a phenomenon my geneticist friends refer to as penetrance. Simply put, that means that not everyone with the same mutation experiences the same severity of symptoms. That is because the severity of a mutation is influenced by diet, lifestyle, and genetic background. Let me start with genetic background. In terms of MTHFR mutants you can think of genetic background as being mutations in a related methylation pathway. People who have a mutation in both MTHFR and a gene in a related pathway will experience more severe symptoms and are more likely to require methyl folate. Once you understand penetrance, you realize that individuals requiring methyl folate may represent only a small subset of people with MTHFR mutations.

Penetrance is a concept that most proponents of the methylfolate hypothesis completely ignore. The most severe MTHFR mutation (C677T homozygote) increases the probability that individuals will exhibit symptoms, but some individuals with that mutation are completely normal. Now that you understand the concepts of redundancy and penetrance, you can understand why that is.

 

When Did The Kernel of Truth About Methylfolate Become A Myth?

 

methylated b mythsUp to this point the hype around methylfolate could be chalked up to an honest misunderstanding. The doctors who published the original papers may not have known that MTHFR mutations only resulted in a partial reduction in enzyme activity. They probably didn’t know the concepts of redundancy (our cells don’t need 100% enzyme activity) or penetrance (the same mutation may cause severe symptoms in some patients and have no effect in others). It seemed logical to assume that everyone with a MTHFR mutation might do better with methyl folate supplementation. That was incorrect, but it was an honest mistake.

However, the message was picked up by the bloggers who specialize in sensational stories, especially stories that contradict what experts have been telling you for years. They picked up the methyl folate story and distorted it beyond recognition. They knew that “natural” is a buzz word, so they told you that methylfolate was natural and folic acid is synthetic (I exposed that lie earlier). They told you that methylfolate was better utilized than folic acid. They told you that methylfolate was more effective than folic acid. They told you folic acid was toxic. It was going to increase your risk of heart disease and cancer. Suddenly, it was no longer about people with MTHFR deficiency. You were being told that everyone should avoid folic acid and use methylfolate instead.

methylated b folicOn the surface, these pronouncements should not have passed the “If it sounds too good to be true…” test, or in this case, the “If it sounds too bad to be true…” test. You were being asked the believe that folic acid, which has been in use for over 80 years and is backed by hundreds of studies showing it is safe and effective, was neither safe nor effective. You were asked to believe that the government was poisoning you by fortifying foods with folic acid.

However, to make their blogs sound more convincing, they listed clinical studies supporting their stories. The problem is they “cherry picked” the studies that supported their story and ignored the rest. Their bias was particularly outrageous when it came to the “story” that folic acid increases cancer risks. They ignored 10 or 20 studies showing no cancer risk and reported one suggesting it might increase risk. I call that deceptive.

Unfortunately, the myths created by the bloggers have been repeated often enough that many people now believe they are true. I will debunk their myths next week, but first let me touch on how their deceptions became downright lies.

 

When Did The Myths About Methylfolate and Methyl B12 Become Lies?

 

If you are writing a blog, you are covered by “freedom of speech.” You can say whatever you want. It doesn’t have to be true. However, if you are a supplement manufacturer, you are held to a higher standard. Ignorance is no longer an excuse. You can no longer cherry pick the “facts” you like and ignore the rest. You are ethically obligated to research all the available literature and be guided by the best scientific evidence.

Reputable companies have been guided by the scientific evidence and have not jumped on the methylfolate bandwagon. They know folic acid is both safe and effective in a wide variety of clinical situations. They also know that, while methylfolate may be just as effective as folic acid, its potential is largely unproven at this point. It has not been tested in many clinical situations.

Less reputable companies, however, sensed money to be made by capitalizing on the buzz around methylfolate. They repeated the myths of the bloggers to claim that their products were superior to others on the market. They call it marketing. I call it lying. They have an obligation to fact check their claims, and only make claims that are true.

It gets worse. Since lots of people already believed they needed methylfolate, why not extend the claim to one of the methylated B vitamins, methyl B12? That would boost sales even more. The claims for methyl B12 were even more outrageous than for methylfolate. There wasn’t even a “kernel of truth” like MTHFR deficiency to serve as a foundation. The claim was the methyl B12 was needed because of some sort of ambiguous “methylation deficiency”. The lies had become whoppers.

Next week I will debunk the methylfolate and methyl B12 myths. Stay tuned.

 

The Bottom Line

 

This week I have shared the story about how the myths about methylfolate and methyl B12 arose and how they eventually became lies. Next week I will debunk the myths.

 

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.

Trackback from your site.

Comments (3)

  • Caroline

    |

    I can remember in my DAOM doctoral studies one presenter was talking about methylation and everyone but me knew nothing, so he asked if our Shaklee was methylated and knowing how our B Complex is made, I said yes because I knew he would discuss it as not because of your article. Love our B Complex and sell lots of it, and I even call it a “cheap drunk” for lighting the spirit, energy and well being. I do enjoy your articles because of your educational teaching/history and that always helps me.

    Reply

  • Fran

    |

    I am a person who almost died because of MTHFR. Because my ability to detox was so poor, chemical pollution built up to extreme levels. All this happened while I was taking Shaklee B complex for thirty years prior to becoming sick. I contend that I would not have become so deathly ill if the B vitamins I was taking had been the correct methyl form!! I also will say that your “scientific” research is flawed and gives the wrong answer because you tested blood, not what actually gets into the cells. It does not matter what is in the blood, if it cannot get into the cells. That is the case with folic acid. Contact Dr. Ben Lynch. He has been researching this for many years. He has the correct answers. YOU do not.
    Thank you for giving me the opportunity to tell you about this. I’d be happy to speak directly with you regarding my severe experience with MTHFR, and how the methyl forms of folate and B12 saved my life.

    Reply

    • Dr. Steve Chaney

      |

      Dear Fran,

      I have consistently said that there are a few people who need methylfolate. These are individuals with several other mutations affecting pathways involving methylation reactions in addition to MTHFR. Situations like yours are exceedingly rare because multiple mutations are required. Published clinical studies show that most people with MTHFR deficiency do quite well with folic acid.

      Folic acid gets into cells quite easily and is immediately converted to folates, including methylfolate – even in individuals with MTHFR deficiency. Again, this is based on published clinical studies.

      I have been in touch with Dr. Ben Lynch and have pointed out the errors in his assertions. Many of his “answers” are contradicted by published clinical studies.

      Dr. Chaney

      Reply

Leave a comment

Recent Videos From Dr. Steve Chaney

READ THE ARTICLE
READ THE ARTICLE

Latest Article

Does Magnesium Optimize Vitamin D Levels?

Posted February 12, 2019 by Dr. Steve Chaney

The Case For Holistic Supplementation

Author: Dr. Stephen Chaney

 

Does magnesium optimize vitamin D levels?

magnesium optimize vitamin dOne of the great mysteries about vitamin D is the lack of correlation between vitamin D intake and blood levels of its active metabolite, 25-hydroxyvitamin D. Many people who consume RDA levels of vitamin D from foods and/or supplements end up with low blood levels of 25-hydroxyvitamin D. The reason(s) for this discrepancy between intake of vitamin D and blood levels of its active metabolite are not currently understood.

Another great mystery is why it has been so difficult to demonstrate benefits of vitamin D supplementation. Association studies show a strong correlation between optimal 25-hydroxyvitamin D levels and reduced risk of heart disease, cancer, and other diseases. However, placebo-controlled clinical trials of vitamin D supplementation have often come up empty. Until recently, many of those studies did not measure 25-hydroxyvitamin D levels. Could it be that optimal levels of 25-hydroxyvitamin D were not achieved?

The authors of the current study hypothesized that optimal magnesium status might be required for vitamin D conversion to its active form. You are probably wondering why magnesium would influence vitamin D metabolism. I had the same question.

The authors pointed out that:

  • Magnesium status affects the activities of enzymes involved in both the synthesis and degradation of 25-hydroxyvitamin D.
  • Some clinical studies have suggested that magnesium intake interacts with vitamin D intake in affecting health outcomes.
  • If the author’s hypothesis is correct, it is a concern because magnesium deficiency is prevalent in this country. In their “Fact Sheet For Health Professionals,” the NIH states that “…a majority of Americans of all ages ingest less magnesium from food than their respective EARs [Estimated Average Requirement]; adult men aged 71 years and older and adolescent females are most likely to have low intakes.” Other sources have indicated that magnesium deficiency may approach 70-80% for adults over 70.

If the author’s hypothesis that magnesium is required for vitamin D activation is correct and most Americans are deficient in magnesium, this raises some troubling questions.

  • Most vitamin D supplements do not contain magnesium. If people aren’t getting supplemental magnesium from another source, they may not be optimally utilizing the vitamin D in the supplements.
  • Most clinical studies involving vitamin D do not also include magnesium. If most of the study participants are deficient in magnesium, it might explain why it has been so difficult to show benefits from vitamin D supplementation.

Thus the authors devised a study (Q Dai et al, American Journal of Clinical Nutrition, 108: 1249-1258, 2018 ) to directly test their hypothesis.

 

How Was The Study Designed?

magnesium optimize vitamin d studyThe authors recruited 180 volunteers, aged 40-85, from an ongoing study on the prevention of colon cancer being conducted at Vanderbilt University. The duration of the study was 12 weeks. Blood was drawn at the beginning of the study to measure baseline 25-hydroxyvitamin D levels. Three additional blood draws to determine 25-hydroxyvitamin D levels were performed at weeks 1, 6, and 12.

Because high blood calcium levels increase excretion of magnesium, the authors individualized magnesium intake based on “optimizing” the calcium to magnesium ratio in the diet rather than giving everyone the same amount of magnesium. The dietary calcium to magnesium ratio for most Americans is 2.6 to 1 or higher. Based on their previous work, they considered an “ideal” calcium to magnesium ratio to be 2.3 to 1. The mean daily dose of magnesium supplementation in this study was 205 mg, with a range from 77 to 390 mg to achieve the “ideal” calcium to magnesium ratio. The placebo was an identical gel capsule containing microcrystalline cellulose.

Two 24-hour dietary recalls were conducted at baseline to determine baseline dietary intake of calcium and magnesium. Four additional 24-hour dietary recalls were performed during the 12-week study to assure that calcium intake was unchanged and the calcium to magnesium ratio of 2.3 to 1 was achieved.

In short this was a small study, but it was very well designed to test the author’s hypothesis.

 

Does Magnesium Optimize Vitamin D Levels?

 

does magnesium optimize vitamin d levelsThis was a very complex study, so I am simplifying it for this discussion. For full details, I refer you to the journal article (Q Dai et al, American Journal of Clinical Nutrition, 108: 1249-1258, 2018).

The most significant finding was that magnesium supplementation did affect blood levels of 25-hydroxyvitamin D. However, the effect of magnesium supplementation varied depending on the baseline 25-hydroxyvitamin D level at the beginning of the study.

  • When the baseline 25-hydroxyvitamin D was 20 ng/ml or less (which the NIH considers inadequate), magnesium supplementation had no effect on 25-hydroxyvitamin D levels.
  • When the baseline 25-hydroxyvitamin D was 20-30 ng/ml (which the NIH considers the lower end of the adequate range), magnesium supplementation increased 25-hydroxyvitamin D levels.
  • When the baseline 25-hydroxyvitamin D level approached 50 ng/ml (which the NIH says may be “associated with adverse effects”), magnesium supplementation lowered 25-hydroxyvitamin D levels.

The simplest interpretation of these results is:

  • When vitamin D intake is inadequate, magnesium cannot magically create 25-hydroxyvitamin D from thin air.
  • When vitamin D intake is adequate, magnesium can enhance the conversion of vitamin D to 25-hydroxyvitamin D.
  • When vitamin D intake is too high, magnesium can help protect you by lowering 25-hydroxyvitamin D levels.

The authors concluded: “Our findings suggest that optimal magnesium status may be important for optimizing 25-hydroxyvitamin D status. Further dosing studies are warranted…”

 

What Does This Study Mean For You?

magnesium optimize vitamin d for youThis was a groundbreaking study that has provided novel and interesting results.

  • It provides the first evidence that optimal magnesium status may be required for optimizing the conversion of vitamin D to 25-hydroxyvitamin D.
  • It suggests that optimal magnesium status can help normalize 25-hydroxyvitamin D levels by increasing low levels and decreasing high levels.

However, this was a small study and, like any groundbreaking study, has significant limitations. For a complete discussion of the limitations and strengths of this study I refer you to the editorial (S Lin and Q Liu, American Journal of Clinical Nutrition, 108: 1159-1161, 2018) that accompanied the study.

In summary, this study needs to be replicated by larger clinical studies with a more diverse study population. In order to provide meaningful results, those studies would need to carefully control and monitor calcium, magnesium, and vitamin D intake. There is also a need for mechanistic studies to better understand how magnesium can both increase low 25-hydroxyvitamin D levels and decrease high 25-hydroxyvitamin D levels.

However, assuming the conclusions of this study to be true, it has some interesting implications:

  • If you are taking a vitamin D supplement, you should probably make sure that you are also getting the DV (400 mg) of magnesium from diet plus supplementation.
  • If you are taking a calcium supplement, you should check that it also provides a significant amount of magnesium. If not, change supplements or make sure that you get the DV for magnesium elsewhere.
  • I am suggesting that you shoot for the DV (400 mg) of magnesium rather than reading every label and calculating the calcium to magnesium ratio. The “ideal” ratio of 2.3 to 1 is hypothetical at this point. A supplement providing the DV of both calcium and magnesium would have a calcium to magnesium ratio of 2.5, and I would not fault any manufacturer for providing you with the DV of both nutrients.
  • If you are taking high amounts of calcium, I would recommend a supplement that has a calcium to magnesium ratio of 2.5 or less.
  • If you are considering a magnesium supplement to optimize your magnesium status, you should be aware that magnesium can cause gas, bloating, and diarrhea. I would recommend a sustained release magnesium supplement.
  • Finally, whole grains and legumes are among your best dietary sources of magnesium. Forget those diets that tell you to eliminate whole food groups. They are likely to leave you magnesium-deficient.

Even if the conclusions of this study are not confirmed by subsequent studies, we need to remember that magnesium is an essential nutrient with many health benefits and that most Americans do not get enough magnesium in their diet. The recommendations I have made for optimizing magnesium status are common-sense recommendations that apply to all of us.

 

The Case For Holistic Supplementation

 

magnesium optimize vitamin d case for holistic supplementationThis study is one of many examples showing that a holistic approach to supplementation is superior to a “magic bullet” approach where you take individual nutrients to solve individual problems. For example, in the case of magnesium and vitamin D:

  • If you asked most nutrition experts and supplement manufacturers whether it is important to provide magnesium along with vitamin D, their answer would likely be “No”. Even if they are focused on bone health, they would be more likely to recommend calcium along with vitamin D than magnesium along with vitamin D.
  • If your doctor has tested your 25-hydroxyvitamin D levels and recommended a vitamin D supplement, chances are they didn’t also recommend that you optimize your magnesium status.
  • Clinical studies investigating the benefits of vitamin D supplementation never ask whether magnesium intake is optimal.

That’s because most doctors and nutrition experts still think of nutrients as “magic bullets.” I cover holistic supplementation in detail in my book “Slaying The Supplement Myths.”  Other examples that make a case for holistic supplementation that I cover in my book include:

  • A study showing that omega-3 fatty acids and B vitamins may work together to prevent cognitive decline. Unfortunately, most studies looking at the effect of B vitamins on cognitive decline have not considered omega-3 status and vice versa. No wonder those studies have produced inconsistent results.
  • Studies looking at the effect of calcium supplementation on loss of bone density in the elderly have often failed to include vitamin D, magnesium, and other nutrients that are needed for building healthy bone. They have also failed to include exercise, which is essential for building healthy bone. No wonder some of those studies have failed to find an effect of calcium supplementation on bone density.
  • A study reported that selenium and vitamin E by themselves might increase prostate cancer risk. Those were the headlines you might have seen. The same study showed Vitamin E and selenium together did not increase prostate cancer risk. Somehow that part of the study was never mentioned.
  • A study reported that high levels of individual B vitamins increased mortality slightly. Those were the headlines you might have seen. The same study showed that when the same B vitamins were combined in a B complex supplement, mortality decreased. Somehow that observation never made the headlines.
  • A 20-year study reported that a holistic approach to supplementation produced significantly better health outcomes.

In summary, vitamins and minerals interact with each other to produce health benefits in our bodies. Some of those interactions we know about. Others we are still learning about. When we take high doses of individual vitamins and minerals, we create potential problems.

  • We may not get the full benefit of the vitamin or mineral we are taking because some other important nutrient(s) may be missing from our diet.
  • Even worse, high doses of one vitamin or mineral may interfere with the absorption or enhance the excretion of another vitamin or mineral. That can create deficiencies.

The same principles apply to our diet. I mentioned earlier that whole grains and legumes are among the best dietary sources of magnesium. Eliminating those two foods from the diet increases our risk of becoming magnesium deficient. And, that’s just the tip of the iceberg. Any time you eliminate foods or food groups from the diet, you run the risk of creating deficiencies of nutrients, phytonutrients, specific types of fiber, and the healthy gut bacteria that use that fiber as their preferred food source.

The Bottom Line

 

A recent study suggests that optimal magnesium status may be important for optimizing 25-hydroxyvitamin D status. This is one of many examples showing that a holistic approach to supplementation is superior to a “magic bullet” approach where you take individual nutrients to solve individual problems. For example, in the case of magnesium and vitamin D:

  • If you asked most nutrition experts and supplement manufacturers whether it is important to provide magnesium along with vitamin D, their answer would likely be “No.”  Even if they are focused on bone health, they would be more likely to recommend calcium along with vitamin D than magnesium along with vitamin D.
  • If your doctor has tested your 25-hydroxyvitamin D levels and recommended a vitamin D supplement, chances are he or she did not also recommend that you optimize your magnesium status.
  • Clinical studies investigating the benefits of vitamin D supplementation never ask whether magnesium intake is optimal. That may be why so many of those studies have failed to find any benefit of vitamin D supplementation.

I cover holistic supplementation in detail in my book “Slaying The Supplement Myths” and provide several other examples where a holistic approach to supplementation is superior to taking individual supplements.

In summary, vitamins and minerals interact with each other to produce health benefits in our bodies. Some of those interactions we know about. Others we are still learning about. Whenever we take high doses of individual vitamins and minerals, we create potential problems.

  • We may not get the full benefit of the vitamin or mineral we are taking because some other important nutrient(s) may be missing from our diet.
  • Even worse, high doses of one vitamin or mineral may interfere with the absorption or enhance the excretion of another vitamin or mineral. That can create deficiencies.

The same principles apply to what we eat. For example, whole grains and legumes are among the best dietary sources of magnesium. Eliminating those two foods from the diet increases our risk of becoming magnesium deficient. And, that’s just the tip of the iceberg. Any time you eliminate foods or food groups from the diet, you run the risk of creating deficiencies.

For more details about the current study and what it means to you 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.

UA-43257393-1