St John’s wort (Hypericum perforatum) has been used for thousands of years for its medicinal properties.1 Today it is most commonly used as a dietary supplement to treat depression, obsessive-compulsive disorder, attention-deficit hyperactivity disorder, and menopausal symptoms, though the data supporting these indications are mixed at best.

Studies of St John’s wort and cancer have primarily focused on drug absorption and metabolism, but some in vitro studies have evaluated its potential anticancer effects. One pilot study evaluated its effect on non-melanoma skin cancer.

Two analyses of the Vitamins and Lifestyle (VITAL) prospective cohort study found no association between supplementation with St John’s wort and cancer incidence compared with no use.3,4

Drug Absorption and Metabolism

St John’s wort is known to alter the metabolism of multiple different medications. One study demonstrated that St John’s wort activates the pregnane X receptor, resulting in induction of cytochrome P450 (CYP) 3A4, which is responsible for the deactivation and elimination of many different anticancer agents, and P-glycoprotein, which is an efflux pump that limits drug uptake.2

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Activation of these enzymes can reduce drug levels. A small randomized study, for example, demonstrated that plasma levels of SN-38 — the active metabolite of irinotecan and a substrate of CYP3A4 — was reduced by 42% when patients were supplemented with St John’s wort compared with patients who were not.5 Patients who receive irinotecan and St John’s wort also experienced myelosuppression more frequently than patients who received only irinotecan.

Another study found that plasma levels of docetaxel also substantially decreased and clearance increased after adding St John’s wort supplementation, which resulted in fewer toxicities.6