Silymarin: a review of its clinical properties in the management of hepatic disorders.

The mechanisms of action of silymarin involve different biochemical events, such as the stimulation of the synthetic rate of ribosomal RNA (rRNA) species through stimulation of polymerase I and rRNA transcription, protecting the cell membrane from radical-induced damage and blockage of the uptake of toxins such as alpha-amanitin. Studies in patients with liver disease have shown that silymarin increases superoxide dismutase (SOD) activity of lymphocytes and erythrocytes, as well as the expression of SOD in lymphocytes. Silymarin has also been shown to increase patient serum levels of glutathione and glutathione peroxidase. Silybin 20 to 48 mg/kg/day has shown promise as a clinical antidote to acute Amanita (deathcap mushroom) poisoning. Primary efficacy data from 3 trials which examined the therapeutic potential of silymarin in patients with cirrhosis, and included patient survival as an end-point, demonstrated that silymarin had no significant beneficial effect on patient mortality. However, upon subanalysis, silymarin 420 mg/day had a significantly beneficial effect on patient survival rate (compared with patients receiving placebo) in 1 randomised, double-blind trial in patients with alcoholic cirrhosis. Silymarin 420 mg/day was also shown to improve indices of liver function [AST, ALT, gamma-glutamyl transferase and bilirubin] in patients with liver disease of various aetiology, including those exposed to toxic levels of toluene or xylene; however, it was largely ineffective in patients with viral hepatitis. Reports of adverse events while receiving silymarin therapy are rare. However, there have been accounts of nausea, epigastric discomfort, arthralgia, pruritus, headache and urticaria. Silymarin has also been reported to have possibly caused a mild laxative effect.

CONCLUSIONS

The antioxidant properties of silymarin (a mixture of at least 4 closely related flavonolignans, 60 to 70% of which is a mixture of 2 diastereomers of silybin) have been demonstrated in vitro and in animal and human studies. However, studies evaluating relevant health outcomes associated with these properties are lacking. Although silymarin has low oral absorption, oral dosages of 420 mg/day have shown some therapeutic potential, with good tolerability, in the treatment of alcoholic cirrhosis. Moreover, silybin 20 to 48 mg/kg/day has shown promise as an antidote for acute mushroom poisoning by Amanita phalloides; however, further studies paying attention to the amount of ingested mushroom and time elapsed before administration of treatment are needed to clarify its role in this indication. Studies in patients with the early onset of liver disease may demonstrate the liver regeneration properties that silymarin is promoted as possessing.