Editor’s Note: This post has been updated since it was first published in 2017.
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, or MTHFR genetic mutations, can cause a wide array of health conditions, ranging from blood clots and cancer to autism and migraines.
Since MTHFR is important to so many of our customers, we decided to dig deeper into the published scientific literature to evaluate the evidence.
What is the MTHFR gene?
Here’s what we know about MTHFR.
The MTHFR gene contains instructions for making an enzyme 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.[1]
Two common naturally occurring variants in the MTHFR gene are C677T and A1298C.
When the MTHFR gene has either of these two variants, the resulting MTHFR enzyme is slightly less active, which can lead to decreased levels of folate and increased levels of homocysteine in the blood.[1]
Common misconceptions about MTHFR genetic variants
Some sources have spread the idea that having one or two copies of an MTHFR variant can lead to dozens of adverse health consequences. Over the past two decades, scientists have examined associations between the MTHFR C677T and A1298C variants and more than 600 medical conditions.[2] Across thousands of scientific publications, the evidence linking MTHFR to most of these health conditions is inconclusive or conflicting.[1]
For example, some studies report an increased risk of heart disease for individuals with two copies of the C677T variant,[3] while other studies report no association with heart disease.[4]
The same is true for cancer,[5][6] blood clots,[7][8] and many other well studied health conditions.[1][9][10]
It’s unlikely that variants in a single gene could cause dozens of unrelated health problems. And the C677T and A1298C variants are prevalent: more than 50 percent of people have at least one copy of one of these variants. That means it’s just as “normal” to have a variant as not. In general, disease-causing genetic variants are not this common.*
The exceptions
One health risk consistently associated with MTHFR variants is that people 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. But the overall risk is still very low.[11][12]
Research also consistently shows that MTHFR variants can lead to slightly increased levels of homocysteine. These increases are small: people with one copy of the C677T variant may have ~10% higher levels of homocysteine, and people with two copies may have ~30% higher levels, compared to people with no copies. On average, that still corresponds to normal or mildly elevated levels of homocysteine. The A1298C variant has not been consistently found to be associated with increased homocysteine levels on its own, but may have an impact when present alongside a C677T variant.[13][14]
These increases in homocysteine are small enough that they’re not likely to have a major impact on health for most people, but they may be relevant to know about as one factor that can contribute to high homocysteine levels. When homocysteine levels get too high, they can indicate an increased risk of certain health conditions, including cognitive decline and stroke. They may also be associated with cardiovascular disease risk, but the evidence for this is less clear.[15][16]
Misinformation about MTHFR and folate intake
The increased risk of neural tube defects in people with two C677T variants is an important point to keep in mind, because another false claim about MTHFR is that people who carry an MTHFR variant should avoid foods fortified with folic acid. However, there’s no evidence that individuals with an MTHFR variant should reduce their folic acid intake, and doing so could potentially lead to folate deficiency, which is linked to an increased risk of neural tube defects. On the contrary, according to the National Institute of Child Health and Human Development, as well as other countries’ national health programs, folic acid supplementation reduces the risk of neural tube defects in all pregnant people, including those with an MTHFR variant.[17][18]
There is also no convincing evidence that people with MTHFR variants should take modified forms of folate such as 5-MTHF.[19] People with MTHFR variants can still process all forms of folate, and 5-MTHF has not been studied in clinical trials.
The recommended daily amount of folate for everyone, including MTHFR carriers, is 400 micrograms of dietary folate equivalents (DFE). Most people can achieve this through a normal, varied diet that includes folate-rich foods like leafy green vegetables, eggs, legumes, and fortified breads and cereals. But some people may benefit from a folic acid supplement to get the recommended daily amount. Folic acid supplements are particularly recommended for all people who may become pregnant because they need higher daily amounts.[18][19]
The takeaway
We’re often asked, “Does 23andMe test for MTHFR mutations?”
The short answer is now yes. We’ve heard from our customers that they are interested in having this information about themselves, so we now report on the C677T and A1298C variants in the Homocysteine (MTHFR-Related) report, available to 23andMe+ Premium™ members.
While the connection between MTHFR variants and slightly increased levels of homocysteine in the blood is consistent, that connection has not been shown in well-run scientific studies to lead to higher risk of the health conditions claimed (with the exception of neural tube defects, as noted above). Based on the existing data, the common MTHFR variants alone should not be interpreted as having a significant effect on health. Most people with MTHFR variants are still expected to have homocysteine levels within the normal range. But for those who are concerned, a blood test can check homocysteine levels. And if homocysteine levels are found to be elevated, taking standard B vitamin supplements is an easy, safe, and effective way to lower them.
We 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.
Learn More
Find out if your genetics might increase your risk for certain health conditions with 23andMe.
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*Note:
Some rare variants in MTHFR can cause a severe condition called homocystinuria, affecting fewer than 1 in 200,000 people in most ethnicities.[20] These variants differ from the common ones described here and discussed throughout the 23andMe community and online.
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References:
Sources for Information
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:
• MedlinePlus https://medlineplus.gov/
• GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK1116/)
• Mayo Clinic (https://www.mayoclinic.org/diseases-conditions)
• Centers for Disease Control and Prevention (https://www.cdc.gov/)
• 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.
