Oral milk thistle has been used to treat acute and chronic viral hepatitis, alcoholic liver disease, and toxin-induced liver injury in human patients. A systematic review of 13 randomized trials involving 915 patients with alcoholic liver disease or hepatitis B or C found no significant reductions in all-cause mortality, liver histopathology, or complications of liver disease with 6 months of use. A significant reduction in liver-related mortality was claimed using the data from all the surveyed trials, but not when the data were limited to trials of better design and controls. It was concluded that the effects of oral milk thistle in improving liver function or mortality from liver disease are currently poorly substantiated. A recent multicenter, double-blind, placebo-controlled clinical trial in patients with hepatitis C refractory to interferon treatment failed to show a benefit with 24 weeks of milk thistle, 420 mg/d and 700 mg/d, on reduction of serum alanine aminotransferase levels. Milk thistle also had no effect on mean serum hepatitis C virus (HCV) RNA levels at 24 weeks. In contrast, the intravenous use of silybinin succinate has shown some benefit in reducing HCV RNA levels and alanine aminotransferase levels in patients with treatment-resistant hepatitis C infection. Prospective pilot studies have also shown benefits with intravenous silybinin before and after liver transplantation treatment in patients with HCV cirrhosis. Potent antiviral activity was demonstrated with significant reductions in HCV-RNA levels during treatment compared to placebo or nontreated controls when given for at least 14 days before transplantation and 7 days after liver transplantation. HCV-RNA relapsed, however, after silibinin withdrawal. This suggests that formulation and poor oral bioavailability may influence treatment outcomes.
Although milk thistle has not been confirmed as an antidote following acute exposure to liver toxins in humans, intravenous silybinin is marketed and used in Europe (Legalon SIL) as an antidote in Amanita phalloides mushroom poisoning. This use is based on favorable outcomes reported in case-control studies.
Milk thistle has rarely been reported to cause adverse effects when used at recommended doses. In clinical trials, the incidence of adverse effects (eg, gastrointestinal upset, dermatologic, headaches) was comparable to that of placebo. At high doses (>1500 mg), it can have a laxative effect caused by stimulation of bile flow and secretion.
Drug Interactions, Precautions, & Dosage
Milk thistle does not significantly alter the pharmacokinetics of other drugs transported by the P-glycoprotein transporter or metabolized by cytochrome enzymes. In a recent review, the impact of the herb was listed as “posing no risk for drug interactions in humans.” Recommended oral dosage is 280–420 mg/d, calculated as silybin, in three divided doses.
ST. JOHN’S WORT (HYPERICUM PERFORATUM)
St. John’s wort, also known as hypericum, contains a variety of constituents that might contribute to its claimed pharmacologic activity in the treatment of depression. Hypericin, a marker of standardization for currently marketed products, was thought to be the primary antidepressant constituent. Recent attention has focused on hyperforin, but a combination of several compounds is probably involved. Commercial formulations are usually prepared by soaking the dried chopped flowers in methanol to create a hydroalcoholic extract that is then dried.