How Does Birth Control Interact with an MTHFR Gene Mutation?

How Does Birth Control Interact with an MTHFR Gene Mutation?

Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Dr. Nare Simonyan - PhD Pharmaceutical Science

Medical Reviewer:

Dr. Nare Simonyan - PhD Pharmaceutical Science
Kari Asadorian - Bachelor of Science in Nursing

Edited By:

Kari Asadorian - Bachelor of Science in Nursing

Updated On:

March 23, 2025

Table of Contents

    How Does Birth Control Interact with an MTHFR Gene Mutation?

    Birth control is a popular and effective form of contraception, used by around 14% of US women aged 15-49. Besides preventing pregnancy, hormonal birth control may be taken for a range of reasons, including regulating menstruation and balancing hormones.


    However, as with any medication, the contraceptive pill carries a few contraindications1, including blood clots, migraine headaches, high blood pressure, and high cholesterol.


    It has also been found that oral contraceptive use in women of childbearing age can lead to compromised folate status2. This may be problematic for women with an MTHFR gene mutation, particularly as folate is crucial in fetal development. A significant proportion of the population (more than 25% of Hispanics and 10-15% of North America Caucasians3) are estimated to be homozygous for the TT genotype MTHFR 677C > T.


    This article will discuss whether oral contraceptives may increase health risks for someone with an MTHFR gene mutation and whether MTHFR hinders contraceptives’ effectiveness. We will also discuss potential alternatives to oral contraceptives or whether supplementation may help reduce risks. 

    Do Oral Contraceptives Increase Risks for Someone with an MTHFR Gene Mutation?

    MTHFR is the critical enzyme for almost all biological processes that involve folate and methionine metabolism. However, those with an MTHFR genetic mutation have a defective MTHFR enzyme and cannot process folate effectively.


    Low folate levels4 are a common symptom of MTHFR mutations, along with higher levels of non-methylated forms of folate. Lower levels of vitamin B125 are also common in MTHFR mutations, particularly the C677T polymorphism6.


    A systematic review7 involving a total of 2,831 women in 17 studies showed that oral contraceptive use in women of childbearing age might significantly reduce folate levels.


    B12 and folate are both required for converting homocysteine to methionine8, red blood cell production, and nervous system maintenance. Deficiency of either nutrient may lead to elevated homocysteine levels, a significant risk factor for cardiovascular disease and many other chronic conditions such as diabetes. This is a common risk factor for those with MTHFR mutations9.


    Those with the MTHFR 677 TT genotype (this is considered a double mutation) have about 25% higher homocysteine levels10 than those with the 677 CC genotype (no mutation), but the impact of the MTHFR polymorphism varies according to folate status.


    The use of oral contraceptives by those with the MTHFR mutation may also increase the risk for venous thromboembolism11. One study highlighted that the presence of more than one of the prothrombotic polymorphisms, including MTHFR, was associated with a substantial risk of thromboembolism12.


    A 2005 study13 also showed that women with the C677T genotype were 50% more likely to have had arterial thrombosis. The same study noted that women with the C677T genotype who used oral contraceptives had a risk of ischemic stroke five times higher than women who had neither the factor V Leiden variant (a mutation of one of the blood clotting factors) nor an MTHFR genotype.


    Folate deficiency has been linked with an increased risk14 of neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction. Deficiency of B12 is a major cause15 of fatigue, neurological disorders, anxiety, nerve pain, and depression, along with pernicious anemia and megaloblastic anemia.


    For these reasons, women with an MTHFR mutation taking oral contraceptives may be at an even higher risk of health concerns associated with folate and B12 deficiency.

    Does an MTHFR Gene Mutation Impact Oral Contraceptives Effectiveness?

    When used correctly, the effectiveness of oral contraceptives is around 99%. However, missing a dose reduces the efficacy.


    Some medications can interfere with the effectiveness of contraceptives, including anti-seizure medications, the herb St John’s Wort, and the antibiotic Rifampin (other antibiotics do not affect the pill).


    However, there appear to be no reports of the MTHFR gene mutation affecting oral contraceptive effectiveness.

    Are There Safer Options?

    Women with a family history of thrombophilia, such as factor V Leiden (a mutation in one of the blood clotting factors), are advised to undergo screening for thrombophilic defects before taking the contraceptive pill.


    Women who have the C677T polymorphism are also at a higher risk of thromboembolism. For these reasons, alternatives to the oral contraceptive pill may be recommended. Options include:

    • Diaphragm
    • Cervical cap
    • Hormone-free IUD (copper/Paragard intrauterine contraceptive device)
    • Spermicide
    • Condoms
    • Sterilization

    How Could Supplementation Help?

    The impact on folate caused by oral contraceptives means it is highly advisable for women to take folate supplements while taking the pill. This is even more important for women with the MTHFR mutation and those who stop taking the pill to start a family.


    A 2009 study showed that around 45.7% of women16 who stop using the pill become pregnant within three months. These women may be at a higher risk of neural tube complications due to low folate status during the preconception period, especially if they have an MTHFR mutation(s) and are already at risk of being deficient in folate.


    Folate supplementation has been shown to reduce the risk of neural tube defects17 that occur in the first four weeks after conception. However, many women are unaware they are pregnant at this stage.


    During pregnancy, adequate supplementation with folate is crucial for proper methylation, which contributes to the healthy growth and development of the fetus18. Folate deficiency and impaired methylation have been linked to pregnancy complications19, including miscarriage, neural tube defects, preeclampsia, poor neonatal brain development, anemia, and peripheral neuropathy20.


    Supplementation with methylfolate has been shown to effectively improve folate biomarkers21 in young women in early pregnancy, which can prevent neural tube defects.


    Pregnant women with an MTHFR mutation are advised to avoid folic acid and instead supplement with active 5-methyl-THF22 (methylfolate). Studies show that methylfolate bypasses the MTHFR block, making it an effective treatment for women with MTHFR. Methylfolate is also shown to be more effective than folic acid23 in improving folate status and is recommended as an efficient and safe alternative.


    Some of the most stable and biologically active folate supplements are those that include ((6S)-5-methyltetrahydrofolate or (6S)-5-MTHF), ((6S)-5-methyl-tetrahydrofolic acid, calcium salt, or L-methylfolate) and ((6S)-5-methyltetrahydrofolic acid, monosodium salt, or L-methylfolate).


    These forms of methylfolate are used in Methyl-Life® products as Magnafolate® PRO. Studies have shown that Magnafolate® PRO offers superior particle size distribution, stability, dissolution, potency, bioavailability, and safety.

    References

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      https://www.ncbi.nlm.nih.gov/books/NBK430882/

    2. Yu Z, Zhang Y, Zhao M, et al.; "Role of folate metabolism in neural tube defects"; The American Journal of Clinical Nutrition; 2015

      https://pubmed.ncbi.nlm.nih.gov/26168104/

    3. National Institutes of Health; "Folic Acid"; NIH - National Library of Medicine; 2021

      https://www.ncbi.nlm.nih.gov/books/NBK66131/

    4. ScienceDirect; "Methylenetetrahydrofolate Reductase"; Medicine and Dentistry; 2016

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    5. Michael J. O’Leary, James E. Kearney, James F. Ruan, Peter L. McElroy; "The role of folate and its receptors in endothelial cell function"; American Journal of Physiology-Heart and Circulatory Physiology; 2007

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    6. Steffi G. M. Knapp, O. L. G. Meijer, H. M. M. V. Der Vleuten, A. M. B. D. Wesseling, P. F. R. Rombouts; "Vitamin B12 deficiency and its associated pathophysiology in human health and disease"; International Journal of Molecular Sciences; 2018

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294092/

    7. Mahvash Shere, Priya Bapat, Cheri Nickel, Bhushan Kapur, Gideon Koren; "Association Between Use of Oral Contraceptives and Folate Status: A Systematic Review and Meta-Analysis"; Journal of Obstetrics and Gynaecology Canada; 2015

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    8. Mahmood; Journal of Human Reproductive Sciences; 2014

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    10. J W Muntjewerff, R S Kahn, H J Blom, M den Heijer; "Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis"; Molecular Psychiatry; 2005 Sep

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    11. A. L. Jackson, et al.; "Homocysteine and cardiovascular disease: A review of the evidence."; BMJ; 2009

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    12. World Health Organization Regional Office for the Eastern Mediterranean; "Micronutrient deficiencies and public health implications"; Eastern Mediterranean Health Journal; 2009

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    13. "Oral Contraceptives May Raise Stroke Risk in Women with Migraine"; Neurology Today; 2005 Jul

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    14. Deth, R. C., & Muratore, C.; "The Role of Folate in Autism Spectrum Disorders"; The Journal of Alternative and Complementary Medicine; 2014

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    19. Mert Turgal, Fatma Gumruk, Ergun Karaagaoglu, Mehmet Sinan Beksac; "Methylenetetrahydrofolate Reductase Polymorphisms and Pregnancy Outcome"; Geburtshilfe und Frauenheilkunde; 2018 Sep

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    23. R. A. Pfeiffer, J. M. Caudill, D. L. Gunter; "Folate and vitamin B12 status in women of reproductive age in the United States: NHANES 2003-2006; American Journal of Clinical Nutrition; 2006

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    24. Banner Image Designed by FreePik

      https://www.freepik.com/

    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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