MTHFR and Birth Control Pills.

Naturally, MTHFR and birth control pills interact. It's not like this is an easy mutation to live with in other senses; why would it leave our contraceptive options untouched? Complaining aside, I could have saved myself years of miserable experiences with the pill if I had known this when I was in University.

Birth control pills and MTHFR - it's complicated.

Birth Control Pills Deplete Folate

Birth Control Pills are known to deplete folate levels in women and have been known to do so since the '80s.  This is a problem for all women, but especially those who have compromised folate metabolism in the first place (that's us MTHFR folks). This folate depletion is part of the reason for some of the most common side effects of birth control pills, including fatigue, mild depression, and even acne.  It's also linked to an increased risk of neural tube defects in babies born to women who have recently stopped using birth control pills.

The nutrients depletions apply not only to oral contraceptive pills, but also hormone-secreting implants and the ring. Any contraceptive that uses hormones to affect fertility, with the exception of the Mirena IUD, which secretes progesterone into the uterus and to date is not known to cause significant nutrient interactions.

Due to the risk of neural-tube defects in women who become pregnant after recently stopping birth control pills, many folate-fortified pills have been developed.  Well-known examples include Beyaz, Safyral, and Yaz Plus. In good news, they are supplemented with an active form of folate, called levomefolate calcium, which is a calcium salt of L-methyl folate. If you're an MTHFR gal and you absolutely must take oral contraceptive pills, these three are better options for you.

If you don't tolerate birth control pills and can't figure out why, it could be because you have an MTHFR mutation, especially if you have signs of a folate deficiency even though you're taking your birth control pills WITH a multivitamin or folate supplement.

Birth Control Pills Deplete B12, Magnesium, and Other Nutrients

Not only is folate depleted, but crucial-for MTHFR riboflavin and B12 are depleted too.  While Riboflavin and B12 are the most crucial for methylation on this list, B6, and Zinc are not far behind. Ironically, magnesium and vitamin E are both pivotal in estrogen metabolism, so really, an excellent multivitamin is a must for all birth control users, with or without MTHFR.

The nutrients that are depleted by birth control pills and other hormone-secreting contraceptive options are:

• Folate

• B12

• Magnesium

• Vitamin C

• B2 - Riboflavin

• B6 - Pyridoxine

• Zinc

• Vitamin E

• Selenium

Birth Control Pills Also Affect Serotonin

In related bad news, Birth control pills may also affect your Serotonin metabolism. Birth control pills are known to increase women's risk of depression, so this is a well-studied topic. Research published by Larsen et. al. shows that women taking oral contraceptive pills have 9-12% lower binding capacity in seratonin receptors than women who are not taking the pill. Other reserach shows that the levels of both seratonin and norepinepherine are reduced in the brains of women on birth control pills.

Birth Control Pills, Stroke Risk, and MTHFR

A study published in 2005 made it clear that while oral contraceptives increase the risk of a thromboembolic stroke (strokes caused by blood clots) in everyone, the risk is especially high in women with the MTHFR C677TT mutation. Specifically, the risk is 5.4 times higher than in the average population. MTHFR mutations generally are correlated with higher risk of blood clots, as are birth control pills, so it makes sense that having both would be a double-whammy. A 2013 meta-analysis published in the European Journal of Epidemiology, however, showed that the combination of MTHFR and oral contraceptives did not increase clotting risk, so the evidence is not conclusive.

What Type of Contraceptive is Safest for MTHFR Mutants?

Hormone-based contraceptives carry additional risks for MTHFR mutants, as outlined above, but the following options are safe relative to MTHFR (although each has risks not related to MTHFR, so do your research):

• Condoms, Female Condoms

• Copper IUD (non-progesterone-secreting)

• Mirena IUD (progesterone-secreting, but seems not to cause nutrient deficiencies).

• Vasectomy or tubal ligation

How To Make Your Birth Control Pills or Hormone-Based Contraceptives Safer

If you prefer to use a hormone-based contraceptive, here are some simple guidelines to help make it as safe as possible:

• Ask your doctor for a prescription that includes active folate. The most common are Beyaz, Safyral, and Yaz Plus.

• Always take your pills with a good multivitamin that includes minerals (magnesium, zinc, and selenium), plus an additional vitamin C and vitamin E.

• If you experience constipation, restless legs, or sleep difficulties with hormone-based birth control, you may also need additional magnesium.

• Avoid using injections, pellets, or implants simply because once they're in, you can't get them out.  That means if your body doesn't tolerate it, you're stuck with the side effects until the dose wears off.

• If you're considering getting pregnant, please stop all oral contraceptives at least a year before you start to try and make sure you work diligently during that year to boost your levels of all of the nutrients that may have been depleted.

References

DrugBank. (n.d.). Levomefolic acid (DB11256). In DrugBank Online. Retrieved July 24, 2026, from https://go.drugbank.com/drugs/DB11256

Palmery M, Saraceno A, Vaiarelli A, Carlomagno G. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013 Jul;17(13):1804-13. PMID: 23852908.

Basciani S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022 Jul;26(13):4846-4862. doi: 10.26355/eurrev_202207_29210. PMID: 35856377.

Simone B, De Stefano V, Leoncini E, Zacho J, Martinelli I, Emmerich J, Rossi E, Folsom AR, Almawi WY, Scarabin PY, den Heijer M, Cushman M, Penco S, Vaya A, Angchaisuksiri P, Okumus G, Gemmati D, Cima S, Akar N, Oguzulgen KI, Ducros V, Lichy C, Fernandez-Miranda C, Szczeklik A, Nieto JA, Torres JD, Le Cam-Duchez V, Ivanov P, Cantu-Brito C, Shmeleva VM, Stegnar M, Ogunyemi D, Eid SS, Nicolotti N, De Feo E, Ricciardi W, Boccia S. Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls. Eur J Epidemiol. 2013 Aug;28(8):621-47. doi: 10.1007/s10654-013-9825-8. Epub 2013 Jul 31. PMID: 23900608; PMCID: PMC3935237.

Larsen SV, Köhler-Forsberg K, Dam VH, Poulsen AS, Svarer C, Jensen PS, Knudsen GM, Fisher PM, Ozenne B, Frokjaer VG. Oral contraceptives and the serotonin 4 receptor: a molecular brain imaging study in healthy women. Acta Psychiatr Scand. 2020 Oct;142(4):294-306. doi: 10.1111/acps.13211. Epub 2020 Jul 21. PMID: 33314049; PMCID: PMC7586815.

Parry BL, Rush AJ. Oral contraceptives and depressive symptomatology: biologic mechanisms. Compr Psychiatry. 1979 Jul-Aug;20(4):347-58. doi: 10.1016/0010-440x(79)90006-3. PMID: 37042.