MTHFR and Birth Control

MTHFR and Birth Control

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Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Kari Asadorian - BSN, RN

Medical Reviewer:

Kari Asadorian - BSN, RN
Dr. Nare Simonyan - PhD Pharmaceutical Science

Edited By:

Dr. Nare Simonyan - PhD Pharmaceutical Science
Last updated:

How Does Birth Control Interact with an MTHFR Gene Mutation?

The MTHFR gene mutation reduces the function of the MTHFR enzyme, which can lead to reduced folate levels and higher homocysteine. Both are associated with increased risk of thrombosis (blood clots) and vascular dysfunction.1
Homocysteine causes vascular endothelial dysfunction, activates the clotting system, and inhibits the fibrinolytic system.2 Oral contraception can also increase risk of thrombosis by increasing coagulation factors.3

Previous research has also suggested that birth control reduces intestinal reabsorption of folates and vitamin B12. Low folate and B12 can then increase homocysteine, potentially leading to hyperhomocysteinemia and megaloblastic anemia.4

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

A 2025 study concluded that combined oral contraceptives (COCs) increase the risk of venous thrombosis and potentially also arterial thrombosis due to changes in clotting factors. Oral contraceptive pills (OCPs) that contain estrogen increase plasma concentration of clotting factors II, VII, X, XII, factor VIII, and fibrinogen. The pill also decreases anti-clotting factors. Both of these effects can increase risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism.5

The MTHFR gene mutation is also associated with an increased risk of venous thromboembolism as it affects the metabolism of homocysteine, an amino acid that causes vascular endothelial dysfunction, activates the clotting system, and inhibits the fibrinolytic system.6

Women with MTHFR genetic mutations who take birth control may therefore have a higher risk of thrombosis or other clotting disorders. A 2022 case report suggests that carriers of a combined mutation in heterozygosity for the C677T and A1298C of the MTHFR gene who use oral contraceptives have an increased risk of venous thromboembolism. This study concluded that further research is needed to assess the relationship between the MTHFR genotype and the use of oral contraceptives that can potentiate their prothrombotic effect, and that genetic testing may be important to assess thrombotic risk before starting oral contraceptives.7

Does an MTHFR Gene Mutation Impact Oral Contraceptives' Effectiveness?

While there is no specific evidence that MTHFR gene mutations can reduce the effectiveness of oral contraception, women taking birth control may be advised to monitor their levels of B-vitamins and homocysteine. Both folate and B12 play important roles in fertility and healthy fetal development, and research has suggested that birth control use may be associated with lower serum B12 levels.8

Folate is also often low in women with MTHFR mutations, which can increase risk of neural tube defects in children.9

Risks of Taking the Pill With an MTHFR Mutation

Risks associated with birth control and MTHFR are mostly related to blood clots (thrombosis) and stroke. Combined oral contraceptives are generally associated with a higher risk of thrombosis, with some research showing they may increase risk of myocardial infarction or ischemic stroke by 1.6x in all women, not just those with MTHFR. The risk was highest for birth control that contains more than 50 mcg estrogen.10

As the MTHFR genetic mutation also increases risk of vascular issues, women with MTHFR taking contraceptive pills may have an even higher risk especially if B vitamin levels are already low, particularly folate, B6, and B12. Other factors linked to blood clots include age, high BMI, smoking, personal/family history of thrombosis, and other health issues.

Nutrient Depletion and Oral Contraceptives

A 2015 systematic review and meta-analysis involving 17 studies found that OCPs significantly reduced women’s folate levels. Because folate is essential for early fetal neural development, folate‑fortified oral contraceptives were introduced around 2010 to help maintain folate levels around the time of conception.11


A 2025 study involving 752 women found that those taking OCPs had slightly smaller increases in serum B12 than women who were not taking OCPs, but concluded this was not a significant association between contraceptive use and low B12.12

Previous studies have shown that OCP users had significantly lower serum B12 levels than non-users, which was not explained by a lack of dietary intake or lifestyle factors.13 Other studies have also reported that women taking the OCP tend to be lower in vitamins B6, B12, and folate than non-users.14


Birth control formulations have also been found to reduce vitamin B6 levels, which increase risk of B6 deficiency in early pregnancy if women stop taking the pill and become pregnant.15

Alternatives to Oral Contraceptives

  • Contraceptive implants and intrauterine devices (IUDs) are generally more effective at reducing unintended pregnancy than short-acting contraceptives, and also more cost-effective.
    For women at higher risk of thrombosis or other clotting disorders, alternatives to oral contraceptives may include non‑estrogen methods. IUDs (copper and levonorgestrel‑releasing) do not contain systemic estrogen. Research has not shown that levonorgestrel‑releasing IUDs increase risk of VTE, and they are often considered suitable for women with a history of clotting issues.16
  • Progestin‑only pills and etonogestrel implants have not been shown to increase VTE risk in the general population. Some studies suggest that depot medroxyprogesterone acetate (DMPA, the Depo‑Provera shot) may be associated with a slightly higher VTE risk, particularly in women with underlying thrombogenic conditions.17

MTHFR supplementation and contraceptives

Women with MTHFR genetic mutations who want to take contraception should consider their thrombotic risk and monitor their folate and homocysteine levels. They may also be advised to supplement with active folate (methylfolate) and active B12 (methylcobalamin) to support one-carbon metabolism and methylation. 

Currently, there is no specific research on taking MTHFR supplements alongside the oral contraceptive pill. However, OCPs that contain folate in the form of levomefolate calcium (L-methylfolate or 5-MTHF) are shown to increase folate levels more effectively than taking folic acid supplements alongside the OCP. The methylfolate OCP also helped to maintain higher levels after discontinuation.18 Beyaz is a combined oral contraceptive that contains 3 mg drospirenone, 20 µg ethinylestradiol, and 0.451 mg levomefolate calcium (providing about 0.416 mg L‑5‑methyltetrahydrofolate).

Stopping Birth Control and MTHFR

Women who want to start a family should focus on optimizing their health before getting pregnant. Folate and B12 are two of the most important nutrients involved in fetal development, and folate deficiency in the first trimester significantly increases risk of neural tube defects. 

Mutations in the MTHFR gene can impair enzyme activity, which then affects folic acid conversion and homocysteine metabolism.

Taking methylfolate may be recommended as it requires no further conversion in the body. 

A 2026 study found that supplementation with methylfolate, rather than folic acid, can increase tetrahydrobiopterin (BH4), reduce superoxide production, and support nitric oxide synthase activity, thus improving endothelial cell function in pregnancy. These findings suggest that methylfolate may be beneficial in reducing hypertension in pregnancy and has advantages over folic acid, although more research is pending.

Women with MTHFR should consult their doctor or other health professional before starting any new supplement regimen.

MTHFR and Birth Control

Key takeaways

  • Icon Both MTHFR mutations and the oral contraceptive pill can increase the risk of blood clots (thrombosis).
  • Icon Oral contraceptives may reduce B‑vitamin levels, including B12 and folate, which is particularly concerning for people with MTHFR.
  • Icon People with MTHFR are advised to consider non-estrogen birth control options as well as folate/B12 supplementation when starting a family.

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L Methylfolate 15 mg - A Mood-Boosting Supplement

$76.00

  • Professional Strength - Ask Your Doctor
  • High-Dose L Methylfolate 15 Mg for Natural Mood Support²
  • 3rd-Party Tested for Purity, Potency & Safety
  • 90 Vegan, Non-GMO, Chewable Mint Tablets

Frequently Asked Questions about MTHFR and birth control

Is it safe to take birth control pills with MTHFR?

Women with MTHFR mutations should consider risks associated with birth control pills and blood clots, as well as their own risk of blood clots/thrombosis (including folate levels and homocysteine). Oral contraceptive pills increase thrombosis risk even in women without MTHFR, and the risk may be higher in people with MTHFR. A healthcare professional can help determine whether estrogen‑containing pills are appropriate or whether non‑estrogen contraception is safer.

Can people with MTHFR take birth control?

Yes, people with MTHFR can safely take birth control if it does not increase their risk of thrombosis. This may mean examining their personal and family health history, their folate intake, and their homocysteine level.
Progestin‑only contraception methods such as IUDs, progestogen-only pill (POP), or copper implants have significantly lower thrombotic risk, which may be suitable for those with MTHFR. If overall thrombotic risk is high (due to health history, smoking, obesity, age), it may be best to avoid estrogen‑containing methods.

Why are oral contraceptives not recommended if you have MTHFR?

Oral contraceptives that contain estrogen are not recommended for people who have MTHFR and a high risk of thrombosis. Combined OCPs can increase coagulation factors and reduce some anticoagulants, which can be problematic in people with MTHFR if they also have a family history of cardiovascular issues and/or elevated homocysteine.

What medications should be avoided with MTHFR?

People with MTHFR mutation should be cautious with medications that impair folate metabolism or significantly lower folate levels. These include antifolate drugs such as methotrexate and some chemotherapy agents.
Contraceptives that contain estrogen increase thrombotic risk and may be less suitable for people with MTHFR.
Synthetic folic acid is also not advised for those with MTHFR, although it is recommended in general health guidelines. Antacids that impair B12 absorption can also affect B12 uptake and cause methylation issues if used long term.

Can MTHFR cause high estrogen?

MTHFR mutations do not directly increase estrogen production. Reduced MTHFR activity can increase homocysteine and affect methylation, which may impair COMT activity. COMT is required to methylate catechol estrogens into methoxyestrogens. If methylation is impaired, catechol estrogens are not properly inactivated. They can then accumulate and become oxidized into highly reactive estrogen quinones.20

References

  1. Shanel Raghubeer, Tandi E Matsha; "Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks"; Nutrients; 2021 Dec

    https://pmc.ncbi.nlm.nih.gov/articles/PMC8703276/

  2. Hieronim Jakubowski, Łukasz Witucki; "Homocysteine Metabolites, Endothelial Dysfunction, and Cardiovascular Disease"; International journal of molecular sciences; 2025 Jan

    https://pmc.ncbi.nlm.nih.gov/articles/PMC11765536/

  3. Jamilya Khizroeva, Victoria Bitsadze, Gennady Sukhikh, Maria Tretyakova, Jean-Christophe Gris, Ismail Elalamy, Grigoris Gerotziafas, Daredzhan Kapanadze, Margaret Kvaratskheliia, Alena Tatarintseva, Azaliia Khisamieva, Ivan Hovancev, Fidan Yakubova, Alexander Makatsariya; "Combined Oral Contraceptives and the Risk of Thrombosis"; International journal of molecular sciences; 2025 Nov

    https://pmc.ncbi.nlm.nih.gov/articles/PMC12652158/

  4. Soudabeh Fallah, Vajihe Nouroozi, Morteza Seifi, Ali Samadikuchaksaraei, Elaheh Mokhtarned Aghdashi; "Influence of oral contraceptive pills on homocysteine and nitric oxide levels: as risk factors for cardiovascular disease"; Journal of clinical laboratory analysis; 2012 Feb

    https://pubmed.ncbi.nlm.nih.gov/22467328/

  5. Jamilya Khizroeva, Victoria Bitsadze, Gennady Sukhikh, Maria Tretyakova, Jean-Christophe Gris, Ismail Elalamy, Grigoris Gerotziafas, Daredzhan Kapanadze, Margaret Kvaratskheliia, Alena Tatarintseva, Azaliia Khisamieva, Ivan Hovancev, Fidan Yakubova, Alexander Makatsariya; "Combined Oral Contraceptives and the Risk of Thrombosis"; International journal of molecular sciences; 2025 Nov

    https://pmc.ncbi.nlm.nih.gov/articles/PMC12652158/

  6. Elvira Giurranna, Francesca Nencini, Serena Borghi, Ilenia Barbaro, Niccolò Taddei, Claudia Fiorillo, Matteo Becatti; "Homocysteinylation of Fibrinogen: A Post-Translational Link to Thrombosis"; International journal of molecular sciences; 2025 Jun

    https://pmc.ncbi.nlm.nih.gov/articles/PMC12193665/

  7. Marcia Machado, Daniela Neto, Silvia Nunes, Cristina Cunha, Carlos Fernandes, Glória Alves, Jorge Cotter; "The Importance of MTHFR C677T/A1298C Combined Polymorphism in Deep Vein Thrombosis: A Case Report"; Cureus; 2022 Sep

    https://pmc.ncbi.nlm.nih.gov/articles/PMC9576123/#sec4

  8. Jennifer O McArthur, HoMan Tang, Peter Petocz, Samir Samman; "Biological Variability and Impact of Oral Contraceptives on Vitamins B6, B12 and Folate Status in Women of Reproductive Age"; Nutrients; 2013 Sep

    https://pmc.ncbi.nlm.nih.gov/articles/PMC3798926/

  9. Nuzhat Nauman, Samina Jalali, Sajjad Shami, Shireen Rafiq, Greta Große, Alina C Hilger, Rhong Zhang, Saira Mansoor, Michael Ludwig, Heiko Reutter; "Low maternal folate concentrations and maternal MTHFR C677T polymorphism are associated with an increased risk for neural tube defects in offspring: a case-control study among Pakistani case and control mothers"; Asia Pacific journal of clinical nutrition; 2018

    https://pubmed.ncbi.nlm.nih.gov/29222906/

  10. Rachel E J Roach, Frans M Helmerhorst, Willem M Lijfering, Theo Stijnen, Ale Algra, Olaf M Dekkers; "Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke"; Cochrane Database Syst Rev; 2015 Aug

    https://pubmed.ncbi.nlm.nih.gov/26310586/

  11. Mahvash Shere, Priya Bapat, Cheri Nickel, Bhushan Kapur, Gideon Koren; "The Effectiveness of Folate-Fortified Oral Contraceptives in Maintaining Optimal Folate Levels to Protect Against Neural Tube Defects: A Systematic Review"; J Obstet Gynaecol Can; 2015

    https://www.jogc.com/article/S1701-2163(15)30229-2/pdf

  12. JNAID, Hussam et al.; "The Effect of Hormonal Contraceptive Use on Vitamin B12 Levels among Adult Females in Saudi Arabia"; Medical Research Archives; 2026 AUg

    https://esmed.org/MRA/mra/article/view/7059

  13. Jennifer O McArthur, HoMan Tang, Peter Petocz, Samir Samman; "Biological Variability and Impact of Oral Contraceptives on Vitamins B6, B12 and Folate Status in Women of Reproductive Age"; Nutrients; 2013 Sep

    https://pmc.ncbi.nlm.nih.gov/articles/PMC3798926/

  14. Federico Lussana, Maddalena L Zighetti, Paolo Bucciarelli, Massimo Cugno, Marco Cattaneo; "Blood levels of homocysteine, folate, vitamin B6 and B12 in women using oral contraceptives compared to non-users"; Thrombosis research; 2003

    https://pubmed.ncbi.nlm.nih.gov/15013271/

  15. Stephanie Mc Wilson, Brittney N Bivins, Katelyn A Russell, Lynn B Bailey; "Oral contraceptive use: impact on folate, vitamin B6, and vitamin B12 status"; Nutrition Reviews; 2011 Oct

    https://academic.oup.com/nutritionreviews/article-abstract/69/10/572/1866655

  16. Naomi K Tepper, Maura K Whiteman, Polly A Marchbanks, Andra H James, Kathryn M Curtis; "Progestin-only contraception and thromboembolism: A systematic review"; Contraception; 2024 Apr

    https://pmc.ncbi.nlm.nih.gov/articles/PMC11034842

  17. Naomi K Tepper, Antoinette T Nguyen, Maura K Whiteman, Kathryn M Curtis; "Progestin-only contraception and thrombosis: an updated systematic review"; Contraception; 2025 Aug

    https://pmc.ncbi.nlm.nih.gov/articles/PMC12381897/

  18. Zohra S Lassi, Zulfiqar A Bhutta; "Clinical utility of folate-containing oral contraceptives"; Int J Womens Health; 2012 Apr

    https://pmc.ncbi.nlm.nih.gov/articles/PMC3346209/

  19. Ruihua Yang, Guanghui Li; "The roles of folate, MTHFR genetics, vitamin B12 in pregnancy outcomes"; Frontiers in nutrition; 2026 Mar

    https://pmc.ncbi.nlm.nih.gov/articles/PMC12995692/

  20. Lucia Janacova, Michaela Stenckova, Petr Lapcik, Sarka Hrachovinova, Pavla Bouchalova, David Potesil, Roman Hrstka, Petr Müller, Pavel Bouchal; "Catechol-O-methyl transferase suppresses cell invasion and interplays with MET signaling in estrogen dependent breast cancer"; Scientific Reports; 2023 Jan

    https://www.nature.com/articles/s41598-023-28078-1

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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