The methylenetetrahydrofolate reductase gene, more commonly known as MTHFR, is the most asked-about gene by 23andMe customers.
Some websites and products have made bold claims that common genetic variants in MTHFR can cause a wide array of health conditions, ranging from blood clots and cancer to autism and migraines. So we decided to dig deeper into the published scientific literature to evaluate the evidence.
Despite lots of research – and lots of buzz – the existing scientific data doesn’t support the vast majority of claims that common MTHFR variants impact human health.
Here’s what we know about MTHFR. The MTHFR gene contains instructions for making an enzyme that’s important for metabolizing folate (also called folic acid or vitamin B9). MTHFR also helps our cells recycle homocysteine, a chemical in the blood, into methionine, a building block for proteins. We also know that there are two common naturally occurring variants in the MTHFR gene, called C677T and A1298C.
When the MTHFR gene has either of these two variants, the resulting MTHFR enzyme is slightly less active, and this can lead to decreased levels of folate and increased levels of homocysteine in the blood. The hype
Some websites have spread the idea that having one or two copies of an MTHFR variant can lead to dozens of negative health consequences. There are a couple problems with this claim. First, it’s unlikely that variants in a single gene could cause dozens of unrelated health problems. Second, the C677T and A1289C variants are very common: in some ethnicities, more than 50 percent of people have at least one copy of one of these variants. Most disease-causing genetic variants are not this common.* Another claim about MTHFR is that people who carry an MTHFR variant should avoid foods that are fortified with folic acid. However, there’s no evidence that individuals with an MTHFR variant should reduce their folic acid intake.
The scientific evidence
Websites and blogs are filled with misinformation about MTHFR. When you’re looking for information about science and health, make sure you find trustworthy sources.
Here are a few of our favorite sites for information about genetics, health, and disease:
• Genetics Home Reference https://ghr.nlm.nih.gov/
• GeneReviews https://www.ncbi.nlm.nih.gov/books/NBK1116/)
• Mayo Clinic (http://www.mayoclinic.org/patient-care-and-health-information)
• Centers for Disease Control (https://www.cdc.gov/)
• US National Library of Medicine (https://www.nlm.nih.gov/medlineplus/)
• Disease-specific sites National Cancer Institute (http://www.cancer.gov/), the American Heart Association (http://www.americanheart.org/), and the American Diabetes Association (http://www.diabetes.org/)
• Understanding Health Research (http://www.understandinghealthresearch.org/), a tool to help evaluate the quality of health studies.
Over the past two decades, scientists have examined associations between the MTHFR C677T and A1298C variants and more than 600 medical conditions. Despite thousands of scientific publications, the evidence linking MTHFR to most of these health conditions is inconclusive or conflicting.
For example, some studies report an increased risk of heart disease for individuals with two copies of the C677T variant, while other studies report no association with heart disease. The same is true for cancer, blood clots, and many other well studied health conditions. There is one exception: women with two copies of the C677T variant appear to have slightly increased risk of having a child with a neural tube defect like spina bifida. However, according to the National Institute of Child Health and Human Development, as well as other countries’ nationwide health programs, folic acid supplementation reduces the risk of neural tube defects in all pregnant women, including women with an MTHFR variant.
Based on the existing data, scientists at 23andMe have concluded that people should not interpret their genotypes at the common MTHFR variants as having an effect on their health. In order for a connection between a genetic variant and a health condition to be considered real and clinically meaningful, well-run scientific studies need to show convincing and consistent evidence for that association. As statements from multiple scientific and medical organizations indicate,  that is currently not the case for the common MTHFR variants. Our team will continue to monitor research in this area – as we do for a wide variety of genetic research – and evaluate new information as it becomes available. *Note: Some very rare variants in MTHFR can cause a severe condition called homocystinuria, which affects fewer than 1 in 200,000 people in most ethnicities. These variants are different from the common variants described here and discussed throughout the 23andMe community and online. ____________________________________________________________________________