The founders of SNPedia are often asked questions about MTHFR. This page provides our response to the most commonly asked questions.

There only scientific consensus about the impact of MTHFR variants is that certain very rare mutations can cause a disease called Homocystinuria. How rare are these mutations? Less than 1 person in a million has homocystinuria due to MTHFR mutations. We know you are unique, but you are very, very unlikely to be that 1 person in a million.

The questions we most commonly receive are not about these rare mutations; instead, they are about the very common variants (aka polymorphisms). The variants are usually called C677T and A1298C; in SNPedia, these are represented by rs1801133 and rs1801131, respectively.

There is scientific consensus about these common variants as well. The consensus is that (1) there is no medical reason to test these common variants, and (2) there no recommended actions based on the results of such genetic tests.

Why not? Basically, most claims about these common MTHFR variants are snake oil. They are unfounded claims offered by those who will profit from selling you supplements. The publications that seem to support MTHFR-based testing and supplementation are prime examples of poor science: small sample sizes, poor study design, conflicts of interest and publication bias.

Of course, some people may benefit from taking supplements, so let’s be clear about who.

Pregnant Women [ edit ]

Many experts feel that it makes sense for all pregnant women to take a multivitamin with folate - regardless of their MTHFR status in order to reduce the (low) risk of neural tube defects even further.

Those with High Homocysteine Levels [ edit ]

There is some evidence that people with very little folate in their diet may be at higher cardiovascular risk due to high homocysteine (Hcy) levels. These individuals are usually those in nutrient-poor countries or in some cases vegetarians with limited food choices.

If you have had a clinically validated test showing high homocysteine levels or low folate levels in your blood, supplementation with vitamins such as B6, B12, and folate or folic acid might be recommended by your health-care provider. Homocysteinaemia is classified according to fasting plasma Hcy levels, as moderate (fasting plasma Hcy levels 15–30 umol/L), intermediate (fasting plasma Hcy levels 30–100 umol/L), or severe (fasting plasma Hcy levels > 100 umol/L). However, be aware that in countries where folate-enriched food is common (which means most countries in the world) there is little to no proof showing that lowering these levels through folate supplementation actually reduces your disease risk.

Everyone Else [ edit ]

The rest of you are most likely perfectly healthy and normal, no matter what common MTHFR variants you carry. While there’s little harm (other than to your pocketbook) in taking supplements just to see if you notice positive effects, there is currently no scientific basis for doing so based on whatever common MTHFR variants you carry.

Other Posts About MTHFR We Recommend [ edit ]

comments from a genetic counselor (originally posted on Reddit])

Genetic counselor here-- Please be aware that genetic counselors are trained medical professionals; part of our job is explaining very complex biological information and integrating it into people's health care.

You will have difficulty finding a board-certified genetic counselor who will recommend supplements outside of the general recommendation for women of childbearing age to take a prenatal vitamin before they become pregnant. The whole MTHFR- supplement industry is not evidence-based, and is seen as quackery by genetics experts. Yes, there are many "functional medicine" practitioners who will tell you that this is the answer to all medical problems. Interesting that only 10-20% of the population are "normal" (aka "wildtype") for MTHFR, so apparently 80-90% of the population are in need of supplements... according to these folks (who are also very happy to sell you the supplements). If you have a particular medical problem that you are concerned about, then a genetic counselor can certainly help you.

Basically, a whole industry has sprung up that involves looking at people's methylation pathways, and then selling supplements to "fix" whatever deficiency is predicted. But, there is really no solid evidence base that having common (and I mean really common) variations in the MTHFR is a problem that needs fixing. The best summary on the issue is here: https://www.sciencebasedmedicine.org/dubious-mthfr-genetic-mutation-testing/

Being proactive and wanting to optimize health are good things, and we absolutely encourage our patients to take an active role in their health. But this is one area where the actual evidence just doesn't add up. Good luck!



http://www.genetics.edu.au/health-professionals/FS64-MTHFR-GENE-TESTING-FOR-PATIENTS.pdf

https://www.washingtonpost.com/news/wonkblog/wp/2015/09/11/the-powerful-argument-for-not-learning-too-much-about-your-genes/

https://blog.23andme.com/health-traits/our-take-on-the-mthfr-gene/

http://genomemag.com/mthfr/