Photosensitization is related to the hypericin and pseudohypericin constituents in St. John’s wort. Consumers should be instructed to wear sunscreen and eye protection while using this product when exposed to the sun. Rarely, mild gastrointestinal symptoms, fatigue, sedation, restlessness, dizziness, headache, and dry mouth have been observed. Hypomania, mania, and autonomic arousal have also been reported in patients using St. John’s wort. When compared to SSRIs, St. John’s wort appears to be better tolerated when used to support medical treatment of major depression.
Inhibition of reuptake of various amine transmitters has been highlighted as a potential mechanism of action for St. John’s wort. Drugs with similar mechanisms (ie, antidepressants, stimulants) should be used cautiously or avoided in patients using St. John’s wort due to the risk of serotonin syndrome (see Chapters 16 and 30). The hyperforin constituent of St. John’s wort has been shown to activate the pregnane X receptor (PXR), which ultimately leads to many drug interactions by inducing hepatic CYP enzymes (3A4, 2C9, 1A2) and the P-glycoprotein drug transporter. Another constituent, hypericin, which may not be present in all commercial formulations, does not have any effect on PXR, CYP, or P-glycoprotein. Case reports involving the use of St. John’s wort have suggested the herb resulted in subtherapeutic levels of numerous drugs, including digoxin, birth control drugs (and subsequent pregnancy), cyclosporine, HIV protease and nonnucleoside reverse transcriptase inhibitors, warfarin, irinotecan, theophylline, and anticonvulsants. Without knowing which constituent is present in a St. John’s wort formulation, indiscriminate combined use with other medicines should be avoided.
The most common commercial formulation of St. John’s wort is the dried hydroalcoholic extract. Products should be standardized to 2–5% hyperforin, although most still bear the older standardized marker of 0.3% hypericin. The recommended dosing for mild to moderate depression is 900 mg of the dried extract per day in three divided doses. Onset of effect may take 2–4 weeks. Longterm benefits beyond 12 weeks have not been studied.
The active constituents in saw palmetto berries are not well defined. Phytosterols (eg, β-sitosterol), aliphatic alcohols, polyprenic compounds, and flavonoids are all present. Marketed preparations are dried lipophilic extracts that are generally standardized to contain 85–95% fatty acids and sterols.
Saw palmetto is most often promoted for the treatment of benign prostatic hyperplasia (BPH). Enzymatic conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase is inhibited by saw palmetto in vitro. Specifically, saw palmetto shows a noncompetitive inhibition of isoforms I and II of this enzyme, thereby reducing DHT production. In vitro, saw palmetto also inhibits the binding of DHT to androgen receptors. Additional effects observed in vitro include inhibition of prostatic growth factors, blockade of α1 adrenoceptors, and inhibition of inflammatory mediators produced by the 5-lipoxygenase pathway.