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.

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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

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Latest Article

Do Omega-3s Lower Blood Pressure in Young, Healthy Adults?

Posted August 14, 2018 by Dr. Steve Chaney

What Is The Omega-3 Index And Why Is It Important?

Author: Dr. Stephen Chaney

 

Do omega-3s lower blood pressure in healthy adults?

omega-3s lower blood pressure young adultsThe literature on the potential health benefits of omega-3s is very confusing. That’s because a lot of bad studies have been published. Many of them never determined the omega-3 status of their subjects prior to omega-3 supplementation. Others relied on dietary recalls of fish consumption, which can be inaccurate.

Fortunately, a much more accurate measure of omega-3 status has been developed and validated in recent years. It’s called the Omega-3 Index. Simply put, the Omega-3 Index is the percentage of EPA and DHA compared to 26 other fatty acids found in cellular membranes. Using modern technology, it can be determined from a single finger prick blood sample. It is a very accurate reflection of omega-3 intake relative to other fats in the diet over the past few months. More importantly, it is a measure of the omega-3 content of your cell membranes, which is a direct measure of your omega-3 nutritional status.

A recent extension of the Framingham Heart Study reported that participants with an Omega-3 Index >6.8% had a 39% lower risk of cardiovascular disease than those with an Omega-3 Index <4.2% (WS Harris et al, Journal of Clinical Lipidology, 12: 718-724, 2018 ). Although more work needs to be done, an Omega-3 Index of 4% or less is generally considered indicative of high cardiovascular risk, while 8% or better is considered indicative of low cardiovascular risk. For reference, the average American has an Omega-3 Index in the 4-5% range. In Japan, where fish consumption is much higher and cardiovascular risk much lower, the Omega-3 Index is in the 9-11% range.

Previous studies have suggested that omega-3 fatty acids lower blood pressure to a modest extent. Thus, it is not surprising that more recent studies have shown an inverse correlation between Omega-3 Index and blood pressure. However, those studies have been done with older populations, many of whom had already developed high blood pressure.

From a public health point of view, it is much more interesting to investigate whether it might be possible to prevent high blood pressure in older adults by optimizing omega-3 intake in a young, healthy population, most of whom had not yet developed high blood pressure. Unfortunately, there were no studies looking at that population. The current study was designed to fill that gap.

 

How Was The Study Done?

omega-3s lower blood pressure young healthy adultsThe current study (M.G. Filipovic et al, Journal of Hypertension, 36: 1548-1554, 2018 ) was based on data collected from 2036 healthy adults, aged 25-41, from Liechtenstein. They were participants in the GAPP (Genetic and Phenotypic Determinants of Blood Pressure) study. Participants were excluded from the study if they had been diagnosed with high blood pressure and were taking medication to lower their blood pressure. They were also excluded if they had heart disease, chronic kidney disease, other severe illnesses, obesity, sleep apnea, or daily use of non-steroidal anti-inflammatory medications.

Blood samples were collected at the time of their enrollment in the study and frozen for subsequent determination of Omega-3 Index. Blood pressure was also measured at their time of enrollment in two different ways. The first was a standard blood pressure measurement in a doctor’s office.

For the second measurement they were given a wearable blood pressure monitor that recorded their blood pressure over 24 hours every 15 minutes during the day and every 30 minutes while they were sleeping. This is considered more accurate than a resting blood pressure measurement in a doctor’s office because it records the variation in blood pressure, while you are sleeping, while you are exercising, and while you go about your everyday activities.

 

Do Omega-3s Lower Blood Pressure In Young, Healthy Adults?

omega-3s lower blood pressure young adults equipmentNone of the participants in the study had significantly elevated blood pressure. The mean systolic and diastolic office blood pressures were 120±13 and 78±9 respectively. The average Omega-3 Index in this population was 4.6%, which is similar to the average Omega-3 Index in the United States.

When they compared the group with the highest Omega-3 Index (average = 5.8%) with the group with the lowest Omega-3 Index (average = 4.6%):

  • The office measurement of systolic and diastolic blood pressure was decreased by 3.3% and 2.6% respectively
  • While those numbers appear small, the differences were highly significant.
  • The 24-hour blood pressure measurements showed a similar decrease.
  • Blood pressure measurements decreased linearly with increasing Omega-3 Index. [In studies of this kind, a linear dose-response is considered an internal validation of the differences observed between the group with the highest Omega-3 Index and the group with the lowest Omega-3 Index.]

The authors concluded: “A higher Omega-3 Index is associated with statistically significant, clinically relevant, lower systolic and diastolic blood pressure in normotensive, young and healthy individuals. Diets rich omega-3 fatty acids may be a strategy for primary prevention of hypertension.”

 

What Does This Mean For You?

omega-3s lower blood pressure young adults questionPerhaps I should first comment on the significance of the relatively small decrease in blood pressure observed in this study.

  • These were young adults, all of whom had normal or near normal blood pressure.
  • The difference in Omega-3 Index was rather small (5.8% to 4.6%). None of the participants in the study were at the 8% or above that is considered optimal.
  • Liechtenstein is a small country located between Switzerland and Spain. Fish consumption is low and omega-3 supplement consumption is rare.

Under these conditions, even a small, but statistically significant, decrease in blood pressure is remarkable.

We should think of this study as the start of the investigation of the relationship between omega-3 status and blood pressure. Its weakness is that it only shows an association between high Omega-3 Index and low blood pressure. It does not prove cause and effect.

Its strength is that it is consistent with many other studies showing omega-3 fatty acids lower blood pressure. Furthermore, it suggests that the effect of omega-3s on blood pressure may also be seen in young, healthy adults who have not yet developed high blood pressure.

Finally, the authors suggested that a diet rich in omega-3s might reduce the incidence of high blood pressure by slowing the age-related increase in blood pressure that most Americans experience. This idea is logical, but speculative at present.

However, the GAPP study is designed to provide the answer to that question. It is a long-term study with follow-up examinations scheduled every 3-5 years. It will be interesting to see whether the author’s prediction holds true, and a higher Omega-3 Index is associated with a slower increase in blood pressure as the participants age.

 

Why Is The Omega-3 Index Important?

 

The authors of this study said: “The Omega-3 Index is very robust to short-term intake of omega-3 fatty acids and reliably reflects an individual’s long-term omega-3 status and tissue omega-3 content. Therefore, the Omega-3 Index has the potential to become a cardiovascular risk factor as much as the HbA1c is for people with diabetes…” That is a bit of an overstatement. HbA1c is a measure of disease progression for diabetes because it is a direct measure of blood sugar control.

In contrast, Omega-3 Index is merely a risk factor for cardiovascular disease. However, if it is further validated by future studies, it is likely to be as important for predicting cardiovascular risk as are cholesterol levels and markers of inflammation.

However, to me the most important role of Omega-3 Index is in the design of future clinical studies. If anyone really wants to determine whether omega-3 supplementation reduces cardiovascular risk, high blood pressure, diabetes or any other health outcome they should:

  • Start with a population group with an Omega-3 Index in the deficient (4-5%) range.
  • Supplement with omega-3 fatty acids in a double blind, placebo-controlled manner.
  • Show that supplementation brought participants up to an optimal Omega-3 Index of 8% or greater.
  • Look at health outcomes such as heart attacks, cardiovascular deaths, hypertension, stroke, or depression.
  • Continue the study long enough for the beneficial effects of omega-3 supplementation to be measurable. For cardiovascular outcomes the American Heart Association has stated that at least two years are required to obtain meaningful results.

These are the kind of experiments that will be required to give definitive, reproducible results and resolve the confusion about the health effects of omega-3 fatty acids.

 

The Bottom Line

 

An accurate measure of omega-3 status has been developed and validated in recent years. It’s called the Omega-3 Index. Simply put, the Omega-3 Index is the percentage of EPA and DHA compared to 26 other fatty acids found in cellular membranes.

Although more work needs to be done, an Omega-3 Index of 4% or less is generally considered indicative of high cardiovascular risk while 8% or better is considered indicative of low cardiovascular risk.

Previous studies have shown an inverse correlation between Omega-3 Index and blood pressure. However, these studies have been done with older populations, many of whom had already developed high blood pressure.

From a public health point of view, it is much more interesting to investigate whether it might be possible to prevent high blood pressure in older adults by optimizing omega-3 intake in a young, healthy population, most of whom had not yet developed high blood pressure. Until now, there have been no studies looking at that population.

The study described in this article was designed to fill that gap. The participants in this study were ages 25-41, were healthy, and none of them had elevated blood pressure.

When the group with the highest Omega-3 Index (average = 5.8%) was compared with the group with the lowest Omega-3 Index (average = 4.6%):

  • Both systolic and diastolic blood pressure were decreased
  • Blood pressure measurements decreased linearly with increasing Omega-3 Index.

The authors concluded: “A higher Omega-3 Index is associated with statistically significant, clinically relevant, lower systolic and diastolic blood pressure in normotensive, young and healthy individuals. Diets rich omega-3 fatty acids may be a strategy for primary prevention of hypertension.”

Let me translate that last sentence into plain English for you. The authors were saying that optimizing omega-3 intake in young adults may slow the age-related increase in blood pressure and reduce the risk of them developing high blood pressure as they age. This may begin to answer the question “Do omega-3s lower blood pressure in young, healthy adults?”

Or even more simply put: Aging is inevitable. Becoming unhealthy is not.

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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