Medication·Interactions & depletion·Reviewed June 9, 2026
Combined Oral Contraceptive interactions.
Combined Oral Contraceptive has 14 documented interactions in the NutriStack database, including 1 flagged to avoid or as a serious conflict. Prolonged use is also associated with lower Vitamin B6, Vitamin B12, Folate, and Magnesium. The full interaction list, depletion table, and replacement suggestions are below. None of this is a substitute for your prescriber's advice.
Combined Oral Contraceptive at a glance.
A quick, data-grounded summary. The full tables are below.
Combined Oral Contraceptive has 14 documented interactions in the NutriStack database, including 1 flagged to avoid or as a serious conflict. Prolonged use is also associated with lower Vitamin B6, Vitamin B12, Folate, and Magnesium. The full interaction list, depletion table, and replacement suggestions are below. None of this is a substitute for your prescriber's advice.
Substances that interact with combined oral contraceptive.
Every supplement and medication in the NutriStack database with a documented interaction with this drug, highest-severity first. Open any pair for the mechanism and sources.
| Substance | Interaction | What happens |
|---|---|---|
| St. John's Wort | Contraindicated | St. John's Wort induces CYP3A4, dramatically reducing levels of ethinyl estradiol and progestins. This causes contraceptive failure and unintended... details → |
| Inositol | Caution | Both combined oral contraceptives and inositol (myo-inositol) are used for PCOS, but for different reasons. COCs treat hyperandrogenism and regulate... |
| Coenzyme Q10 | Synergy | Combined oral contraceptive use significantly decreases serum coenzyme Q10 levels in premenopausal women, mirroring the drop seen with statins.... details → |
| Magnesium Glycinate | Synergy | Combined oral contraceptive use is associated with lower serum magnesium and altered mineral status in observational studies, contributing to... details → |
| Methylcobalamin | Synergy | Methylcobalamin is the active circulating form of vitamin B12 and is depleted along with other B vitamins during combined oral contraceptive use.... details → |
| Methylfolate | Synergy | Methylfolate (5-MTHF) is the active circulating form of folate and is the preferred supplement for women on combined oral contraceptives,... details → |
| Selenium | Synergy | Combined oral contraceptive use is associated with lower serum selenium and reduced glutathione peroxidase activity in several studies, contributing... details → |
| Vitamin B12 | Synergy | Combined oral contraceptives are associated with lower serum vitamin B12 levels in multiple observational and review studies. Although clinical... details → |
| Vitamin B2 | Synergy | Combined oral contraceptives modestly lower riboflavin (B2) status by altering hepatic enzyme turnover and erythrocyte glutathione reductase... details → |
| Vitamin B6 | Synergy | Combined oral contraceptives lower plasma pyridoxal-5-phosphate (active vitamin B6) and can contribute to low mood, irritability, and nausea. In a... details → |
| Vitamin B9 | Synergy | A systematic review and meta-analysis of 17 studies found that women using combined oral contraceptives had significantly lower serum and red-cell... details → |
| Vitamin C | Synergy | Combined oral contraceptives lower plasma and platelet vitamin C levels and increase oxidative stress, partly because estrogen induces hepatic... details → |
| Vitamin E | Synergy | Combined oral contraceptives reduce serum levels of lipid-soluble antioxidants including alpha-tocopherol and coenzyme Q10. In a controlled study of... details → |
| Zinc | Synergy | Multiple observational studies show that combined oral contraceptive users have lower serum zinc compared with non-users. The clinical impact is... details → |
What combined oral contraceptive can deplete.
Nutrients this medication is associated with lowering over time, with the mechanism, a suggested replacement where one applies, and the biomarker to monitor. Discuss any replacement with your prescriber first.
| Nutrient | Severity | How it happens | Replace with | Monitor |
|---|---|---|---|---|
| Vitamin B6 | Moderate | Estrogen-containing contraceptives can increase vitamin B6 turnover and lower circulating PLP in susceptible users. | Vitamin B6 | Plasma PLP |
| Vitamin B12 | Mild | Long-term oral contraceptive use is associated with lower measured B12 status, likely from altered binding proteins and absorption dynamics. | Methylcobalamin | Serum B12 + methylmalonic acid |
| Folate | Moderate | Estrogen-progestin contraceptives can lower folate status through altered metabolism and increased requirement in some users. | Methylfolate | Serum folate or RBC folate |
| Magnesium | Mild | Oral contraceptives are associated with lower magnesium status in some users, likely through altered renal handling and demand. | Magnesium Glycinate | RBC magnesium |
| Zinc | Mild | Estrogen-containing contraceptives can modestly lower zinc status, likely through altered hepatic protein synthesis and increased losses. | Zinc Picolinate | Serum zinc |
| Vitamin C | Mild | Some users show lower plasma vitamin C during chronic oral contraceptive use, likely from increased oxidative turnover. | Vitamin C | Plasma vitamin C |
| Selenium | Mild | Estrogen-containing contraceptives can modestly alter selenium handling and lower functional selenium status in some users. | Selenium | Serum selenium |
The full combined oral contraceptive profile.
Uses, typical dosing, side effects, and the cited evidence for this medication.
Common combined oral contraceptive questions.
Quick answers drawn from the tables above.
What interacts with Combined Oral Contraceptive?
In the NutriStack database, Combined Oral Contraceptive has 14 documented interactions. The most notable include St. John's Wort, Inositol, Coenzyme Q10, Magnesium Glycinate, and Methylcobalamin. Check any specific combination before taking it and confirm with your prescriber.
Which substances should I avoid with Combined Oral Contraceptive?
Combined Oral Contraceptive is flagged against 1 substance in the database, including St. John's Wort. These pairings carry a higher risk and should be reviewed with a clinician before combining.
Does Combined Oral Contraceptive deplete any nutrients?
Combined Oral Contraceptive is associated with lowering Vitamin B6, Vitamin B12, Folate, Magnesium, Zinc, Vitamin C, and Selenium with prolonged use. Useful biomarkers to monitor include Plasma PLP, Serum B12 + methylmalonic acid, and Serum folate or RBC folate. Ask your prescriber before adding any replacement supplement.
Is it safe to take St. John's Wort with Combined Oral Contraceptive?
NutriStack classifies the St. John's Wort and Combined Oral Contraceptive pairing as contraindicated: St. John's Wort induces CYP3A4, dramatically reducing levels of ethinyl estradiol and progestins. This causes contraceptive failure and unintended pregnancy. The FDA... Do NOT take St. John's Wort with oral contraceptives. Use alternative contraception (non-hormonal) if taking SJW. Multiple documented cases of... Always confirm with your prescriber.
Check your whole stack
See how combined oral contraceptive fits your supplements.
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