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Background: St John's wort (SJW) is widely used as a treatment for depression. A phototoxic reaction, due to its content of hypericin, can occur in animals and in cell culture, and has been reported in humans. Hypericin displays absorption within the ultraviolet (UV) A1 spectrum and there may therefore be a potential for phototoxicity if taken during high-dose UVA1 therapy., Objectives: To assess the phototoxicity risk of SJW ingestion., Methods: Eleven adult volunteers of skin types I and II were exposed to a geometric dose series of UVA1 irradiation from a high-output source (Dermalight Ultra 1; Dr Hönle, Martinsreid, Germany; irradiance 70-77 mW cm(-2)) on the photoprotected lower back skin at eight 1.5-cm(2) test areas. Irradiation was carried out at baseline and after 10 days of SJW extract 1020 mg (equivalent to 3000 microg of hypericin) daily. Four, 8, 24 and 48 h after each exposure, the minimal erythema dose (MED) and the presence or absence of pigmentation were recorded visually and erythema was assessed objectively with an erythema meter., Results: The median MED and D(0.025), an objective measure of MED, were lower at all time-points after SJW ingestion. The visual erythemal peak (lowest median MED), which was seen at 8 h postirradiation, was lower after SJW (median 14 J cm(-2), range 10-56) than at baseline (median 20 J cm(-2), range 14-56) (P = 0.047). Similarly, the median D(0.025) at 8 h postirradiation was lower after SJW (median 22.0 J cm(-2), range 15.2-53.9) than at baseline (median 33.7 J cm(-2), range 22.9-136.0) (P = 0.014). The MED and D(0.025) were also significantly different at the 48-h and 4-h time-points, respectively. Significance was not reached at the 24-h time-point. Median intensity of postirradiation erythema increased at all time-points after ingestion of SJW. Despite these differences, the maximum slope of the dose-response curve was not increased after SJW ingestion., Conclusions: These data suggest that SJW extract has the potential to lower the erythemal threshold to UVA1 irradiation in a significant proportion of individuals and highlight the importance of ascertaining a full drug history, including herbal remedies, before initiating UVA1 phototherapy.

Extract of St. John's Wort (Hypericum perforatum) is commonly used as natural remedy for treatment of mild to moderate depression. However, it contains a powerful photoactive component, hypericin, which can cause a severe photodermatitis when eaten by grazing animals (hypericism). In humans, there is evidence that supplementation with St. John's Wort can reduce the minimal erythemal dose (MED) in patients undergoing high dose UVA-1 phototherapy. This is a recent development in phototherapy where the most erythemogenic parts of the UVA spectrum are filtered out, allowing delivery of higher doses of the longer wavelengths of UVA. Although current published evidence suggests that the plasma levels of hypericin are unlikely to cause clinical phototoxicity, it has been established that photoactive compounds can cause DNA damage at sub-toxic and sub-erythemal doses, the effects of which might not be apparent for many years after the event. The present study used HaCaT keratinocytes to investigate the photoclastogenic ability of hypericin on irradiation with UVA. The results show that although the combination of hypericin and UVA light increased the genotoxic burden, when all factors are taken into account, the risk of significant photogenotoxic damage incurred by the combination of Hypericum extracts and UVA phototherapy may be low in the majority of individuals.