Prenatal Vitamins and MTHFR: Choosing the Right Supplements for You

Prenatal Vitamins and MTHFR: Choosing the Right Supplements for You

Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Dr. Conor Sheehy - PharmD, BCPS

Medical Reviewer:

Dr. Conor Sheehy - PharmD, BCPS
Kari Asadorian - Bachelor of Science in Nursing

Edited By:

Kari Asadorian - Bachelor of Science in Nursing

Updated On:

March 23, 2025

Table of Contents

    Prenatal Vitamins and MTHFR: Choosing the Right Supplements for You

    Prenatal supplements are highly recommended for most women during pregnancy. For women with an MTHFR mutation, prenatal vitamins may be even more critical, and special consideration must be given to the exact form and quantity of vitamins within the supplement. This is due to the complications that MTHFR deficiency causes in metabolizing folate. Folate is crucial to the cellular differentiation and epigenetic changes that occur during fetal development, and a lack of folate can result in severe abnormalities.


    This article will discuss how MTHFR SNPs can negatively impact pregnancy and why pregnancy supplementation is essential, particularly regarding folic acid and folate. We will also explain which form of folate is best for pregnant women with MTHFR and other dietary recommendations.

    MTHFR Mutations and Pregnancy Outcomes

    Folate plays a critical role in fetal development; it is required for proper DNA synthesis and repair, control of gene expression, and many other biological processes involved in cell division. A lack of folate before conception and during pregnancy has been associated with numerous birth defects.


    The MTHFR (L-5-methyltetrahydrofolate) gene is responsible for converting folic acid into a usable form of folate. However, a mutation in the MTHFR gene impairs this conversion, resulting in insufficient folate. As a result, hundreds of enzymatic reactions that require folate cannot occur properly.


    There are several common variants1 of MTHFR mutations. Each of us inherits a copy of each MTHFR gene SNP (single nucleotide polymorphism) from each parent. Mutations can affect one (heterozygous) or both copies (homozygous). Homozygous mutations reduce MTHFR enzyme function2 even further, increasing the risk of health complications. MTHFR SNPs are also associated with an increased risk of infertility, miscarriage, and other pregnancy complications.


    Taking the correct form of folate before conception and during pregnancy can significantly improve the chances of a successful pregnancy.

    How Prenatal Supplementation Can Help

    Nutrient levels during pregnancy significantly impact fetal development. Pregnant women are usually prescribed specific prenatal vitamins by their doctor, namely folic acid and iron. However, because MTHFR is required for processing folic acid, those with the MTHFR mutation will be unable to benefit from folic acid supplementation. This can severely deprive both the mother and fetus of necessary folate, increasing the risk of neural tube defects.


    The best option for pregnant women with MTHFR SNPs is methylfolate. Methylfolate is one of the few folate forms that require no further conversion in the body and can bypass an MTHFR mutation. Prenatal vitamins that contain methylfolate can provide vital support during preconception and pregnancy.


    Other research suggests that supplements containing L-methylfolate and high-dose vitamin B(12) can help maintain hemoglobin levels and reduce the risk of anemia in pregnancy more effectively than standard prenatal vitamins3.

    Which Prenatal Supplements Should People with MTHFR Take?

    Methylfolate has been shown to increase the amount of “efficient” folate in the body more effectively than folic acid4. Supplementation with methylfolate may be an effective way to avoid the MTHFR-related problems of conception and miscarriages.


    Researchers also note that supplementing with methylfolate avoids the risk of Unmetabolized Folic Acid Syndrome (UMFA)5, which has been linked to serious diseases such as cancer6.


    Studies suggest that women with MTHFR may improve their chances of pregnancy success by supplementing with methylfolate7, even if they have suffered MTHFR-related miscarriages previously.


    Supplementation with methylfolate is also found to result in higher red blood cell and plasma folate8 concentrations than in the women supplemented with folic acid.

    Other Supplements for MTHFR Pregnancies

    Iron

    During pregnancy, demand for iron increases9 as the body must support the growing fetus and placenta while also increasing maternal red cell mass. Iron deficiency is common among pregnant women who do not take iron supplements.

    Calcium and Vitamin D

    Calcium and Vitamin D are both essential for proper fetal skeletal development10. Vitamin D also supports healthy immune function11 for both mother and baby.

    Omega 3

    Omega-3 fatty acids12 EPA and DHA are critical building blocks of the fetal brain and retina. They may also play a role in supporting a healthy gestation period and preventing perinatal depression.

    Iodine

    Iodine is critical to support increased thyroid hormone production13 in pregnancy and reduce the risk of congenital anomalies.

    B vitamins

    Vitamin B12 is essential for cellular growth and differentiation14, as well as for DNA methylation, and could be an independent factor for fetal development. Other B vitamins also play crucial roles in energy production and fetal growth.

    What You Eat Matters Too

    Eating plenty of folate-rich foods throughout pregnancy may also support pregnancy success. Folate is present in a wide variety of animal and plant foods, including liver, legumes, mushrooms, and leafy greens. Fermented foods such as sauerkraut and yogurt also contain higher amounts of folate. You can learn more about foods containing methylfolate here.


    While many packaged foods are fortified with synthetic folic acid, those with MTHFR defects must avoid them due to their inability to process the folic acid.

    Final Thoughts

    Managing nutritional requirements during pregnancy for women with an MTHFR mutation is crucial. Increased demands for folate must be met with methylfolate to bypass the MTHFR SNP and support the healthy development of the fetus. Additional supplementation of iron, B vitamins, and other nutrients is also critical during preconception and pregnancy.


    Unfortunately, most prenatal vitamins and fortified foods contain only synthetic nutrients, including folic acid, which must be avoided.


    For this reason, a quality prenatal supplement that contains tissue-ready nutrients is essential. A good example is Methyl-Life’s® Pregnancy Bundle, which includes L-Methylfolate 2.5mg, Vitamin B12 (as Hydroxocobalamin), and a methylation-supporting multivitamin. This bundle is formulated specifically for pregnant women with a heightened need for bioavailable folate and other nutrients due to MTHFR defects.

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    References

    1. Daniel Leclerc, Sahar Sibani, Rima Rozen; "Molecular Biology of Methylenetetrahydrofolate Reductase (MTHFR) and Overview of Mutations/Polymorphisms"; Madame Curie Bioscience Database [Internet].; 2000-2013

      https://www.ncbi.nlm.nih.gov/books/NBK6561/

    2. Stephan Moll, Elizabeth A. Varga; "Homocysteine and MTHFR Mutations"; Circulation; 2015 Jul

      https://www.ahajournals.org/doi/10.1161/circulationaha.114.013311

    3. Susan Bentley, Amy Hermes, Diane Phillips, Yahya A Daoud, Sylvia Hanna; "Comparative effectiveness of a prenatal medical food to prenatal vitamins on hemoglobin levels and adverse outcomes: a retrospective analysis"; Clinical therapeutics; 2011 Feb

      https://pubmed.ncbi.nlm.nih.gov/21440300/

    4. R Prinz-Langenohl, S Brämswig, O Tobolski, Y M Smulders, D E C Smith, P M Finglas, K Pietrzik; "[6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C-->T polymorphism of methylenetetrahydrofolate reductase"; British journal of pharmacology.; 2009 Dec

      https://pubmed.ncbi.nlm.nih.gov/19917061/

    5. Yves Menezo, Kay Elder, Arthur Clement, Patrice Clement; "Folic Acid, Folinic Acid, 5 Methyl TetraHydroFolate Supplementation for Mutations That Affect Epigenesis through the Folate and One-Carbon Cycles"; Biomolecules; 2022

      https://www.mdpi.com/2218-273X/12/2/197

    6. Karen L. Koenig, Stephanie Scarmo, Yelena Afanasyeva, Tess V. Clendenen, Per Magne Ueland, Anne Zeleniuch-Jacquotte; "Circulating unmetabolized folic acid and 5-methyltetrahydrofolate and risk of breast cancer: a nested case-control study"; European Journal of Clinical Nutrition; 2020 Apr

      https://www.nature.com/articles/s41430-020-0615-6

    7. Edouard J Servy, Laetitia Jacquesson-Fournols, Marc Cohen, Yves J R Menezo; "MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series"; Journal of Assisted Reproduction and Genetics; 2018 Jun

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086798/

    8. Amanda M Henderson, Rika E Aleliunas, Su Peng Loh, Geok Lin Khor, Sarah Harvey-Leeson, Melissa B Glier, David D Kitts, Tim J Green, Angela M Devlin; "l-5-Methyltetrahydrofolate Supplementation Increases Blood Folate Concentrations to a Greater Extent than Folic Acid Supplementation in Malaysian Women"; The Journal of nutrition; 2018 Jun

      https://pubmed.ncbi.nlm.nih.gov/29878267/

    9. Institute of Medicine (US) Committee on Nutritional Status During Pregnancy and Lactation; "Nutrition During Pregnancy: Part I Weight Gain: Part II Nutrient Supplements."; National Academies Press (US); 1990

      https://www.ncbi.nlm.nih.gov/books/NBK235217/

    10. M Fiscaletti, P Stewart, CF Munns; "The importance of vitamin D in maternal and child health: a global perspective"; Open Access; 2017 Sep

      https://publichealthreviews.biomedcentral.com/articles/10.1186/s40985-017-0066-3

    11. Eve Hornsby, Paul E. Pfeffer, Nancy Laranjo, William Cruikshank, Marina Tuzova, Augusto A. Litonjua, Scott T. Weiss, Vincent J. Carey, George O'Connor, Catherine Hawrylowicz; "Vitamin D supplementation during pregnancy: Effect on the neonatal immune system in a randomized controlled trial"; Biologics and immunotherapy Vol. 141, Iss. 1 p. 269-278; 2018 Jan

      https://linkinghub.elsevier.com/retrieve/pii/S0091674917305754

    12. Jaclyn M Coletta, Stacey J Bell, Ashley S Roman; "Omega-3 Fatty Acids and Pregnancy"; Reviews in obstetrics & gynecology; 2010

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046737/

    13. Christina Yarrington, Elizabeth N Pearce; "Iodine and Pregnancy"; Journal of Thyroid Research; 2011 Jun

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134395/

    14. Ralph Carmel, Ralph Green, David S Rosenblatt, David Watkins; "Update on cobalamin, folate, and homocysteine"; Hematology / the Education Program of the American Society of Hematology; 2003

      https://pubmed.ncbi.nlm.nih.gov/14633777/

    Katie Stone - Naturopath

    About the Author

    Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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