The Science Behind Folate: Folic Acid vs. 5-MTHF
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Folate, also known as vitamin B9, is essential for DNA synthesis, cell division, and overall health. While many people get folate from leafy greens, beans, and fortified foods, supplements are a common way to ensure adequate intake—especially for those with increased needs or absorption issues. But not all folate supplements are created equal. The two most popular forms you’ll see on the market are synthetic folic acid and 5-MTHF (5-methyltetrahydrofolate). Here’s what you need to know about each.
What is Folate?
Folate is the natural form of vitamin B9 found in foods like spinach, lentils, and asparagus. It’s crucial for making red and white blood cells, converting carbohydrates into energy, and supporting healthy fetal development during pregnancy (1).
Synthetic Folic Acid
Folic acid is the synthetic form of folate used in most supplements and fortified foods. It’s stable, inexpensive, and has been added to cereals and grains in the U.S. since the late 1990s to help prevent neural tube defects (2).
How Does Folic Acid Work?
Once consumed, folic acid must be converted by the liver and other tissues into the active form, 5-MTHF, before the body can use it. For most people, this conversion is efficient. However, up to 40% of the world's population has a genetic variation (MTHFR polymorphism) that reduces their ability to convert folic acid efficiently (3).
Pros of Folic Acid
- Well-studied: Proven to reduce risk of neural tube defects in pregnancy (2).
- Widely available: Found in most multivitamins and prenatal supplements.
- Affordable: Cost-effective for manufacturers and consumers.
Cons of Folic Acid
- Conversion required: Must be converted to 5-MTHF in the body.
- Potential for unmetabolized folic acid: Some people, especially those with MTHFR gene variants, may accumulate unconverted folic acid, which has been linked to possible health concerns, though research is ongoing (4).
5-MTHF (5-Methyltetrahydrofolate)
5-MTHF is the active, methylated form of folate found naturally in foods and some supplements. It is sometimes labeled as "L-methylfolate" or "Quatrefolic®" on supplement bottles.
How Does 5-MTHF Work?
5-MTHF bypasses the need for conversion by the MTHFR enzyme, making it immediately available for the body to use. This is especially important for individuals with MTHFR gene variants (3).
Pros of 5-MTHF
- Bioavailable: Ready for use by the body without conversion.
- Better for MTHFR variants: Ideal for people with reduced enzyme activity.
- Lower risk of unmetabolized folic acid: Less likely to build up in the blood (5).
Cons of 5-MTHF
- Cost: Typically more expensive than folic acid.
- Stability: Slightly less stable than folic acid, but modern supplement technology has improved this.
Which Should You Choose?
- General population: Folic acid is safe and effective for most people.
- MTHFR gene variant carriers: 5-MTHF may be a better choice, especially if you have a family history of neural tube defects or elevated homocysteine levels.
- Pregnancy: Always consult your healthcare provider before switching forms, but both are effective at proper dosages.
Key Takeaways
- Folic acid is the most common supplemental form, but it is synthetic and requires conversion.
- 5-MTHF is the active form, ideal for those with certain genetic variations.
- Both forms support healthy folate levels, but your choice may depend on genetics, health conditions, and budget.
References
- National Institutes of Health. Folate Fact Sheet for Consumers
- Centers for Disease Control and Prevention. Folic Acid
- Bailey, L.B., & Gregory, J.F. (1999). Folate metabolism and requirements. The Journal of Nutrition, 129(4), 779-782. Link
- Pfeiffer, C.M., Sternberg, M.R., Fazili, Z., et al. (2015). Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults. The American Journal of Clinical Nutrition, 100(2), 490-497. Link
- Scaglione, F., Panzavolta, G. (2014). Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica, 44(5), 480-488. Link
