Why You Don't Actually Need to Test for MTHFR Gene Variants

Depression. Autism. Breast cancer. Alcoholism. Type 1 diabetes. Heart disease. What do these supposedly have in common? Many alternative health websites like to talk about a supposed link between these conditions and a gene called MTHFR—but there's no indisputable evidence that the link really exists.

If you’re unfamiliar with the MTHFR gene, it stands for methylenetetrahydrofolate reductase, which is an enzyme the body needs to process certain substances. And if it doesn’t work properly, lots of people think it can cause all sorts of health issues, like those mentioned—but this is an extremely simplified way of thinking about MTHFR variations, and I’ll break it down much further for you.

As an epidemiologist, this subject isn’t new to me. But the topic of MTHFR gene variants and mutations seems to be having a moment in the wellness space.

I’m a researcher, so I keep tabs on what’s being talked about around the web, on social media, and in places like mommy forums with regard to health and wellness. And I notice that the fearmongering conversation surrounding MTHFR gene variants resurfaces every now and again.

I see threads on MTHFR gene variants and the alleged health problems they cause pop up almost daily in some of the forums I keep tabs on, as well as new blog posts on natural, holistic wellness websites (which I’d define as sites that tout medical treatments that generally are not viewed as part of mainstream medicine) warning that it’s crucial to get tested for a potential MTHFR abnormality. And it turns into a modern-day game of telephone.

What’s more, a number of alternative medicine sites even offer products like specialty vitamins or health programs marketed for individuals with MTHFR variants, with some treatments costing thousands of dollars. A number of outlets also suggest that having a MTHFR gene variant is a contraindication for vaccination—and they use this (unverified) assertion to justify avoiding vaccines.

The huge problem? There’s no convincing or conclusive scientific evidence to prove that all MTHFR variations are linked to health issues. So before you even worry about whether a MTHFR gene variant could be affecting you, here’s what you really need to know about the gene and the role it plays in your overall health.

What is the MTHFR gene, and how does it work?

As I mentioned, its normal function is to produce an enzyme called methylenetetrahydrofolate reductase in the body. And there are a few common variants, but they aren’t dangerous.

Methylenetetrahydrofolate reductase helps process amino acids, which are the building blocks of protein. More specifically, methylenetetrahydrofolate reductase converts the amino acid homocysteine to another, methionine. This is an important job because if the body can’t process homocysteine properly, it can lead to a buildup of homocysteine in the body, a condition called homocystinuria, which can cause health issues. But we’ll get to that.

Now, there are a lot of individuals who have variant in the MTHFR gene, meaning that there is some amount of alteration in the DNA sequence that makes up that gene. But it’s a common misconception that any amount of change in the DNA automatically implies that there will be health consequences associated with that variant.

For instance, lots of people have two common MTHFR variants: C677T and A1298C. While other variants exist, these two are the best-studied changes in the MTHFR gene, and “are very common in the Caucasian population,” Charis Eng, M.D., founding chairwoman of the Genomic Medicine Institute at the Cleveland Clinic, tells SELF. She adds that these variants are present in roughly 40 percent of people.

Dr. Eng also refers to them explicitly as “variants” and not “mutations,” as the latter suggests harm, which is actually very rarely seen in individuals carrying one of these two common variants. (Many websites/forums use these terms interchangeably, which is part of the problem, or they don’t specify if they mean a true mutation or are talking about these common variants.) In fact, having a single copy of these variants doesn’t decrease the activity of the enzyme. “Homocysteine levels have been measured in people with [one of these variants], and homocysteine levels are normal in [those] individuals,” Dr. Eng explains.

This is key when it comes to examining how common MTHFR variants affect a person’s health: An individual can function properly even with a lower-than-normal level of the enzyme, as long as there is enough of it to do its metabolic job of keeping homocysteine levels within a healthy range. So most people with these common variants would never even know they had one without genetic testing, as there aren’t any clear physical symptoms.

We don’t have definitive scientific research to suggest that these two MTHFR variants cause health effects.

To date, there are no large-scale, well-designed epidemiological studies that prove that either of these variants cause the health effects that these health forums commonly associate with them.

Take the claim that MTHFR variants up a person’s risk of developing heart disease, for example: Some older research suggested that those with some amount of C677T variation may be at a higher risk—while much newer, larger, and better-structured research actually found no evidence of an increased risk.

And there are thousands of studies that go back and forth like this in regards to hundreds of health conditions. It’s easy for media outlets, and in turn consumers, to fixate on any negative results, but this spreads worry and inaccurate health information when the definitive science just isn’t there.

There is an exception for which the research is more consistent: Some people with two copies of C677T may have elevated homocysteine, and research shows they could be at risk of having a baby with a neural tube defect. But, again that combination is uncommon. And for people who do have elevated homocysteine (which would be determined at the start of pregnancy via a blood test), it’s easily treatable with folate and/or B vitamin supplementation, and a doctor would help guide treatment.

MTHFR mutations, on the other hand, can cause health problems—but this is very rare.

As for people who do have a true MTHFR mutation, meaning a gene mistake large enough to cause clinical symptoms? “Extremely rare. Unicorns,” Dr. Eng says.

A serious MTHFR mutation implies that the mutation renders the enzyme completely inactive. There are 40 or so of these mutations that we know of. In individuals who do have one of these mutations, the enzyme deficiency it causes results in a potentially harmful buildup of homocysteine in the body, leading to a condition called homocystinuria. But again, this isn’t the case with all MTHFR variants, only these serious mutations. An estimated 1 in 200,000 people globally have homocystinuria, due to either MTHFR mutations or another condition called CBS deficiency.

Homocystinuria can lead to a number of health problems if left untreated, including developmental delays, seizures, and difficulty gaining weight or muscle. Because these can be serious issues, all states in the U.S. screen infants for homocystinuria in order to allow for early diagnosis and interventions. Also, the symptoms of homocystinuria related to an MTHFR mutation are generally observable (e.g. seizures, neurological issues). For these reasons, it’s very unlikely that someone with symptoms related to these clinically significant MTHFR mutations would be missed or go undiagnosed. Cases diagnosed later than infancy are possible, but they’re uncommon.

So what should someone do if they’re still worried about having a MTHFR variant?

Because people with serious MTHFR mutations are few and far between—and because genetic testing can cause a lot of unnecessary anxiety for people—current guidelines by many professional organizations explicitly note that they do not endorse MTHFR testing for their patients. This includes the American College of Medical Genetics and Genomics (ACMG), whose guidelines were adopted by the American Academy of Family Physicians; the Society for Maternal-Fetal Medicine; and the American College of Obstetricians and Gynecologists.

Even popular genetic testing company 23andMe does not recommend or offer testing for MTHFR variants. 23andMe states that, despite thousands of scientific publications examining common MTHFR variants, “the evidence linking MTHFR to most of these health conditions is inconclusive or conflicting.” The company goes on to advise “that people should not interpret their genotypes at the common MTHFR variants as having an effect on their health.”

For the majority of people with a common MTHFR variant, they won’t have any symptoms. And the overall health risks associated with a common variant are so small (or arguably nonexistent for many people) that they also likely wouldn’t need any special course of treatment. Simply put, having an MTHFR variant doesn’t mean you need medical treatment.

That being said, if you’re symptomless but still curious, rather than going the genetic testing route (unless you really want to, and that’s your choice to make), Dr. Eng suggests getting a blood test to check homocysteine levels, which is the real indicator of potential health issues. It’s less expensive and it can tell you if anything is actually wrong clinically. (Remember: Clinically significant MTHFR gene mutations would be indicated by abnormally high homocysteine levels.)

If your homocysteine levels are found to be abnormally high, treatment is also simple and straightforward: folate supplementation. Upping your folate via a supplement basically helps your body to bypass the need for the methylenetetrahydrofolate reductase enzyme produced by the MTHFR gene, and therefore reduces homocysteine levels. “Regular folate works; you don’t need anything fancy,” Dr. Eng notes. B vitamins such as B6 and B12 may also be recommended for some people. Your doctor can help determine what treatment and supplementation is best for you.

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