The Straw Man of MTHFR

I’ve seen a number of mainstream articles lately claiming that MTHFR is “pseudoscience,” that “the existing scientific data doesn’t support the vast majority of claims that common MTHFR variants impact human health” (thanks, 23andMe), etc.  The biggest problem with these is that, by and large, they’re attacking a straw man.

What do I mean by that?  Well, the claim from the mainstream is that there isn’t evidence that MTHFR variants cause disease, and that MTHFR proponents are saying there is, so these folks (the MTHFR experts) are quacks.  But that isn’t really what the MTHFR folks are saying; it’s a straw man.  Misrepresenting the argument this way in order to “refute” it and dissuade people from learning more about how MTHFR can impact their health is, in my opinion, a violation of ethics.  (Note: MTHFR is not the only genetic variant for which the following information is generally true, but it’s one of the best-known, and is a good representative example.)

What is MTHFR?

I’ve written more extensively before about MTHFR, but let me briefly recap for those who haven’t read those posts (or have forgotten).  MTHFR stands for methyltetrahydrofolate reductase, which is the name of an enzyme.  This enzyme is part of the methylation cycle, a process within the body which has, in simple terms, three significant areas of function (with some overlap).  It’s necessary for detoxification, it’s necessary for the utilization of certain nutrients for other bodily processes, and it’s necessary for signaling certain genes to “turn on” or “turn off.”

MTHFR also refers to the genes that code for production of the enzyme.  And those with certain genetic variant produce less — sometimes significantly less — of this enzyme.

Why Does This Matter?

Well, MTHFR is not a disease (although “having MTFHR” is a shorthand way of saying you have the negative variants).  And it doesn’t cause disease — directly.  However, the key piece the naysayers are missing (and what MTHFR experts are really claiming) is that MTHFR variants can lead to disease.

Frankly, this shouldn’t even be a matter of debate.  It isn’t rocket science.  It’s fairly obvious that if our bodies need a given enzyme to run a detoxification process, and there’s a shortage of it, our detoxification will be less effective.  If we need a given enzyme to convert a vitamin into a form that can be used, and there’s a shortage of it, any process requiring that vitamin can be impaired.  And if we need a given enzyme to complete the process required for telling genes to “switch on” or “switch off,” we may end up with a lot of things “running” that shouldn’t be, or “not running” that should be.

I mean, really, this should be as abundantly obvious as saying that since plants need water to grow, a shortage of water can result in stunted plant growth.  It’s simple cause-and-effect.  So why the antagonism?  Besides simple philosophical differences, I think there are a few different road blocks here to greater acceptance of the fact that this gene (along with other, similar ones) matters.

1. The Historical Argument/It’s Common

This one is kind of a twofer, because these are pretty interrelated.  A large proportion of society has at least one MTHFR “mutation” (polymorphism).  The assumption is that if so many people have it, it can’t be bad, and that it can’t be contributing to health problems now if we weren’t seeing it contribute to health problems in the past.

This is overly simplistic, though.  First, that something is common doesn’t inherently make it healthy/optimal.  According to the National Institutes of Health, “approximately 39.6% of men and women will be diagnosed with cancer at some point during their lifetimes.”  Does that mean we should consider it “normal” to have cancer?  The CDC says, “as of 2012, about half of all adults…had one or more chronic health conditions. One in four adults had two or more chronic health conditions.” [Or see this quick-reference.]  Should we brush off chronic illness because it’s “common”?

Second, less than half the population has any mutation (of the type we’re talking about).  The estimates are “as many as 40 percent.”  That is certainly less than rare, but it isn’t even half — and even fewer people have a combination of mutations.  These all have varying degrees of enzyme non-production, so there’s a lot of variation here.  We’re talking about enough people to make this a significant issue, but not so many that we can necessarily call it “normal” to have a very low level of enzyme production.

Third, a common sense look at what MTHFR (the enzyme) does, and what has changed over the past several decades should make it clear that the increase in environmental toxicity could readily account for such a shift in symptoms.  If your detoxification is inefficient, but you have little to detoxify, you probably won’t show a lot of symptoms.  If your detoxification is inefficient and you’re bombarded with toxins, you’re likely to start having issues.  Other relevant changes have also occurred, such as the introduction of folic acid fortification of grains in the U.S.  Rodent studies have shown that high folic acid intake can mimic MTHFR deficiency even in those who don’t have an actual deficiency! 1

2. It’s Hard to Study

Because we’re not talking about a 1:1 correlation (“if  you have MTHFR mutations, you will have x disease”), it’s a hard thing to study.  Because really MTHFR is just one variable.  We’re talking about the volume of production of a necessary enzyme.  Even if 100 people all have exactly the same quantity of enzyme available, they may need the same amount.  Whether or not this leads to illness is entirely a matter of at what point the demand for the enzyme tips beyond the production, and there are hundreds or thousands of factors that can influence that.

3. We Assume Irrelevance Where Relevance Has Not Been Proven

What I mean by this is, how do we know MTHFR hasn’t made a difference in the frequency of, for instance, chronic illness?  You saw the numbers above.  About 40% of American adults are diagnosed with cancer at some point, and around half of American adults have at least one chronic illness (around a quarter have at least two).  We don’t know why.  It’s highly probable it’s a combination of factors, and one could very well be that a segment of the population is not able to keep up with the increasing demands on the body’s detoxification pathways.

Meanwhile, without the need for studies to demonstrate a causal relationship (direct or indirect) between MTHFR and a particular health issue, we can know simply from what we know it does in the body, what kinds of symptoms it has the ability to cause if it’s lacking.  Do we need studies that prove an increased number of traffic incidents in order to know that if the traffic lights go out, we might see accidents increase?  If the traffic lights go out and accidents increase, is it foolish to theorize that the increase is due to the lights being out, and work to get them running again?

What we’re looking at with MTHFR is a similar idea, and anecdotal evidence (or, read: clinical case studies) suggest(s) that in many cases this approach has, indeed, resulted in improved health.

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340065/