Folic acid v Methylfolate for Pregnancy?

Understanding Folate Supplementation for Fertility and Pregnancy

If you're planning to conceive or are pregnant, you're likely aware of the advice to take folate supplements to support a healthy pregnancy. While synthetic folic acid has traditionally been the go-to recommendation for preventing neural tube defects (NTDs) for decades, recent research into genetics and folate metabolism suggest that natural alternatives like methylfolate (5-MTHF) and folinic acid may be better options for many women.

Here’s what you need to know about folate, its role in fertility and pregnancy, and how to choose the best supplement for your needs.

Folic Acid: Still Essential for Some

For women with a personal or family history of NTDs, high-dose folic acid remains the only approach supported by extensive research. The World Health Organization (WHO) has established optimal red blood cell folate levels necessary for NTD prevention, and whilst this can be a good guide to follow when supplementing with methylfolate or folinic acid, it hasn’t yet been proven in clinical trials to give the same outcomes as folic acid supplementation in reducing NTD. For women with a history or high risk of NTD, daily supplementation with 4-5 mg of folic acid for 3 months before conception and in early pregnancy lowers the chance of NTD by 50-75%.

However, for women without this direct history, alternatives like methylfolate and folinic acid have abundant research supporting their benefits for fertility and pregnancy outcomes.

Methylfolate and Folinic Acid: Superior Alternatives

For most women, natural forms of folate provide a safer and more effective option compared to synthetic folic acid. These alternatives are easier for the body to utilize and don’t accumulate as unmetabolized folic acid in the bloodstream—a compound linked to potential health risks like cancer and immune dysfunction.

Benefits of Folinic Acid

Folinic acid supports:

  • DNA synthesis and repair.

  • Blood cell production.

  • General cellular health, making it suitable for nearly everyone.

Benefits of Methylfolate (5-MTHF)

Methylfolate supports:

  • The methylation cycle, which is critical for detoxification, neurotransmitter production, and hormone metabolism and DNA replication.

  • The regulation of homocysteine levels, which, if elevated, can harm fertility and increase cardiovascular risks.

The Methylation Cycle, MTHFR, and SLC19A1

Folate plays a key role in the methylation cycle, which supports:

  • DNA repair and synthesis.

  • Detoxification of toxins, heavy metals, and hormones.

  • Neurotransmitter balance.

Mutations in the MTHFR gene reduce the body’s ability to convert folic acid into its active form, methylfolate, impairing methylation. Similarly, the SLC19A1 gene helps transport folate into cells, and synthetic folic acid can block its function.

Understanding these genetic nuances can help personalize folate supplementation to optimize health outcomes for you and your baby.

The WHO and MTHFR: Insights on NTD Prevention

A key 2015 study by Stover et al. examined the role of the common 677C>T MTHFR polymorphism in folate metabolism and NTD prevention. The WHO’s guidelines emphasize the importance of maintaining optimal red blood cell folate levels, particularly for women with MTHFR mutations, who may require tailored folate intake.

The 677C>T polymorphism significantly impacts both folate status and metabolism. While folic acid supplementation effectively raises folate levels even in women with MTHFR mutations, it’s important to note that methylfolate’s ability to prevent NTDs has yet to be conclusively studied. Despite this, methylfolate offers other proven fertility and pregnancy benefits, making it a valuable alternative for women without a history of NTDs.

Final Thoughts

Folate is essential for fertility, pregnancy, and overall health. But not all forms of folate are created equal. For most women, natural forms like methylfolate and folinic acid are safer and more effective, supporting critical processes like DNA synthesis and methylation without the risks associated with synthetic folic acid.

Remember: "FOLIC ACID = BAD." If you missed my earlier article on folate, revisit it to understand why this distinction matters—even if you don’t have MTHFR gene mutations. Choosing the right form of folate is a small but vital step toward a healthy pregnancy and baby.

References

  1. Pfeiffer, C. M., et al. (2015). Unmetabolized Folic Acid Is Detected in Nearly All Serum Samples from US Children, Adolescents, and Adults. The Journal of Nutrition.
    Link

  2. Menezo, Y., et al. (2011). Folic Acid, Folinic Acid, 5-Methyl TetraHydroFolate Supplementation for Mutations That Affect Epigenesis through the Folate and One-Carbon Cycles. Journal of Assisted Reproduction and Genetics.
    Link

  3. McGowan, E., et al. (2021). Association Between Folate Metabolites and the Development of Food Allergy in Children. Allergy.
    Link

  4. Samaniego-Vaesken, M. de Lourdes, et al. (2017). Supplementation with Folic Acid or 5-Methyltetrahydrofolate and Prevention of Neural Tube Defects: An Evidence-Based Narrative Review. Nutrients.
    Link

  5. Stover, P. J., et al. (2015). Bringing Clarity to the Role of MTHFR Variants in Neural Tube Defect Prevention. The American Journal of Clinical Nutrition.
    Link

  6. World Health Organisation. (2015). Guideline: Optimal Serum and Red Blood Cell Folate Concentrations in Women of Reproductive Age for Prevention of Neural Tube Defects. https://www.ncbi.nlm.nih.gov/books/NBK294192/

Clare Pyers