Folate vs. Folic Acid and the MTHFR Gene Mutation

When you think of folate, what comes to mind? If you’re like most folks, the nutrient probably sparks thoughts of pregnancy and prenatal vitamins. And hey, you’re not wrong; adequate folate intake is super important when you’re pregnant or trying to conceive (TTC). However, even if you’re in neither boat, it’s still crucial to get enough for optimal health. 

The world of folate can be confusing, though. Folate is often used interchangeably with “folic acid”, even though they’re different forms. Furthermore, a common genetic variant—called the MTHFR gene mutation—may determine the best choice for achieving optimal intake. 

Blue Pink Abstract Colors Clouds

Folate vs. Folic Acid: What’s the Difference? 

Folate (vitamin B9) is a water-soluble vitamin that’s essential for making red blood cells, DNA, and neurotransmitters, including serotonin and dopamine. Without enough folate, you’re more likely to feel tired, weak, and down in the dumps. Plus, our bodies can’t synthesize the nutrient, so it’s important to include it in the diet. Adult men and women both need 400 micrograms (mcg) of folate each day.

You can find folate in dietary sources like leafy greens, citrus fruits, and beef liver. But here’s the catch: Folate is destroyed through preparation methods like cooking, canning, and freezing. The bioavailability of food folate is also 50%, which means only half is absorbed and metabolized by the body.

Folate can also be synthesized for use in supplements and fortified foods, including enriched cereals and grains. The most common synthetic form is folic acid, which has a higher bioavailability (85%) than food folate. (Folic acid is more stable, so it’s less likely to be destroyed by the intestinal tract.) That rate jumps up to 100% if you take it with water on an empty stomach. 

Needless to say, it may be worth taking folate supplements. The only problem? Not all supplements are equal. Specifically, folic acid—the common synthesized format—may not be the best option due to a common gene mutation. This mutation, which involves the methylenetetrahydrofolate reductase (MTHFR) gene, makes it difficult for your body to properly use folic acid. In this case, you’ll want to be extra mindful of the folate supplements you consume.

Folic Acid and the Gene Variation

The MTHFR gene codes for methylenetetrahydrofolate reductase, an enzyme. When you take a folic acid supplement, MTHFR converts the folic acid into L-methylfolate, also called 5-methyltetrahydrofolate (5-MTHF). This is the biologically active form of folate; in other words, it’s the type of folate our cells can use.

However, if you have an MTHFR gene mutation, your body might have a hard time making this conversion. The most common genetic variant is the MTHFR C677T mutation, which is found in 20 to 40% of white and Hispanic individuals and 1 to 2% of black individuals in the United States. 

Another variant, called the MTHFR A1298C mutation, is the second most common type. According to the journal Circulation, it’s found in 7 to 12% of people in North America, Europe, and Australia. It’s also found in 4 to 5% of Hispanic individuals, 1 to 4% of Chinese individuals, and 1 to 4% of Asian individuals.

Having a MTHFR gene mutation means your body is unable to efficiently code for MTHFR enzymes. This decreases normal enzyme function, or in some cases, totally turns it off. The result? Folic acid gets “stuck” and isn’t converted into a usable form. 

With high doses, unmetabolized folic acid can accumulate in the blood. (Generally, this isn’t a cause for concern—except for the fact that your cells aren’t getting the folate they need.) Single doses, on the other hand, are quickly cleared by the kidneys, resulting in some very expensive pee for women supplementing with folic acid. 

Do I have a MTHFR gene mutation?

Typically, doctors don’t test for MTHFR mutations unless you have high levels of homocysteine, an amino acid. (The MTHFR enzyme works to break it down, so low MTHFR function would increase homocysteine levels.) It involves a test that checks for different variants of the MTHFR gene. 

Talk to your doctor if you’re curious about your MTHFR status. They might recommend the test, depending on your overall health and family history.

Marea PMS Elixir - Multivitamin for PMS

Best Folate Supplement for the Gene Variation

Most traditional supplements contain folate as folic acid. But if you have a gene variation, your ability to convert folic acid into L-methylfolate is compromised—making it harder to reap the intended benefits of those supplements.

Luckily, it’s possible to take folate supplements as L-methylfolate. By using the form that’s already biologically active, you can bypass the need for enzyme conversions. In turn, this can help you achieve ideal folate concentrations (and avoid buildup of unmetabolized folic acid) if your body is unable to convert folic acid.

The takeaway? When possible, look for a supplement with L-methylfolate, rather than folic acid. For example, in one serving of our PMS Elixir, you’ll find 250 micrograms of folate as calcium L-methylfolate. It’s part of a cocktail of essential B vitamins, including thiamine (B1) and cobalamin (B12). Together, this B complex helps support your mood, energy, and blood formation, especially around that time of the month. 

If you’re wondering how folate or the MTHFR gene plays a role in your health, reach out to your doctor. They can offer guidance based on your personal health, needs, and family history.



Kirsten NunezLearn more about Kirsten at

1 comment

I have the gene mutation and got 5mg folic acid by my doctor. The first week i took them i felt like a new person. But now i feel no difference. I have also tried methylfolate 500mcg and 5mg. Dont feel anything.. How come i felt it so much the first week when i took folic acid and now im going back to feel bad again?

Hampus Olsson January 15, 2021

Leave a comment

All comments are moderated before being published


I have noticed a significant amount of joy and an energy return to my life. Something that has felt so difficult for me to experience in the last few years. I am amazed at the effectiveness of Marea and am so grateful I stumbled upon it.

-Danielle C.