Investigation of the Effect on Photosensitivity following Multiple Oral Dosing of Two Different Hypericum Extracts in Healthy Men

Abstract

The naphthodiantrones hypericin and pseudohypericin, ingredients of hypericum extracts, are known as potent photosensitizers that may cause phototoxic effects in grazing animals after excessive ingestion of hypericum species and in some cases in higher concentrations of hypericum extracts oder pure hypericin in humans as well. Therefore, the objective of the present studies was to investigate the effect of two different hypericum extracts (STW 3, STW 3-VI) on photosensitivity with respect to minimal erythema dose (MED) after 14 days treatment. Both open, multiple-dose, one-phase studies were conducted in 20 healthy men, receiving one tablet per day. MED values were determined prior to hypericum extract administration (baseline) and after 14 days treatment using an erythem tester emitting a light very similar to sun light (main emission spectrum: 285-350 nm). Skin reactions with respect to MED were evaluated 12 h, 24 h (primary endpoint), 48 h and 7 days after irradiation. All volunteers reached steady-state of hypericin/pseudohypericin plasma concentrations before study day 14, when the irradiation under treatment conditions took place. In all subjects MED was measurable under baseline and under hypericum treatment conditions. With respect to the primary endpoint, in both studies, mean MED (24 h) were not significantly different between baseline and after 14 days hypericum treatment. However, individually photosensitivity of the skin could increase under treatment conditions, just as well photosensitivity could decrease or remain unchanged. There were no clinically relevant changes in the laboratory parameters, the vital signs, physical findings and other observations related to safety during the examinations. In one study (STW 3), two adverse events were reported, both described as hypersensitivity to light in mild Intensity. The two studies showed that treatment with the two hypericum extracts under steady state and under prescribed conditions were safe medications without significant increases of photosensitivity.

Hypericum perforatum : Pharmacokinetic, Mechanism of Action, Tolerability, and Clinical Drug-Drug Interactions

“…Although HP extracts appear to be well tolerated, the most frequently reported side effects are nausea, rash, fatigue, restlessness, and photosensitivity (Table ), which has been largely attributed to naphthodianthrones (hypericin and pseudohypericin) (Rodríguez‐Landa and Contreras, ; Schulz et al ., ) and typically manifests at higher‐than‐recommended doses. Although severe phototoxic reactions seem to be very rare events (only two cases of severe photo‐allergic reactions following ingestion of HP preparations have been reported in the literature; Schulz, ), patients should be informed that HP extracts, like some SSRIs, can increase light sensitivity (Doffoel‐Hantz et al ., ).…”

Photocontact Dermatitis due to Hypericum perforatum

“…One of the most popular herbs taken for depression is Hypericum perforatum, which contains the potential photosensitizer hypericin. 'Hypericism' is a term used to describe a state of skin sensitivity to visible light in animals following ingestion of hypericin-containing plants and feed [1,2] Recent investigations suggest an anti-inflammatory and antibacterial effect of hyperforin, which is a major constituent of Hypericum perforatum. In a halfside comparison study, it was assessed the efficacy of a cream containing Hypericum extract standardized to 1.5% hyperforin (verum) in comparison to the corresponding vehicle (placebo) for the treatment of subacute atopic dermatitis.…”

“…Remarkably, the effects seen from this product came from a single application [3]. The naphthodiantrones hypericin and pseudohypericin, ingredients of hypericum extracts, are known as potent photosensitizers that may cause phototoxic effects in grazing animals after excessive ingestion of hypericum species and in some cases in higher concentrations of hypericum extracts oder pure hypericin in humans as well [2].…”

“…Hypericum perforatum extract has been used to treat a variety of conditions, especially psychovegetative disorders, depressive disorders, anxiety, and/or nervous agitation. The main bioactive components of Hypericum perforatum extract for treatment of depression were thought to be hypericin and hyperforin [1,2,3,4,5,6,7,8,9,10,11]. We describe a patient with severe photocontact dermatitis caused by shortly after starting topical Hypericum perforatum therapy for osteoarthritis.…”

Amended Safety Assessment of Hypericum Perforatum-Derived Ingredients as Used in Cosmetics

“…In an oral study of 2 different H perforatum extracts (STW3, 80% ethanol extract, 612 mg, 1.4 mg hypericin; STW3-VI, 50% ethanol extract, 900 mg, 1.75 hypericin), male subjects (n ¼ 20) had no change in minimum erythema dose of irradiation after administration of the test substances for 2 weeks. 41 Plasma steady state of hypericin/ pseudohypericin was obtained before day 14 of treatment. The UV dose was adjusted for skin type.…”