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) spec ies through stimulation of polymerise 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 wel l 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 acut e Amanita (deathcap mushroom) poisoning. Primary efficacy data from 3 trials which examined the therapeutic potentia l of silymarin in patients with cirrhosis, and included patient survival as an endpoint, demonstrated that silymarin had no significant beneficial eff ect on patient mortality. However, upon subanalysis, silymarin 420 mg/day h ad a significantly beneficial effect on patient survival rate (compared wit h patients receiving placebo) in 1 randomised, double-blind trial in patien ts with alcoholic cirrhosis. Silymarin 420 mg/day was also shown to improve indices of liver function [A ST, ALT, gamma -glutamyl transferase and bilirubin] in patients with liver disease of various aetiology, including those exposed to toxic levels of to luene or xylene; however, it was largely ineffective in patients with viral hepatitis. Reports of adverse events while receiving silymarin therapy are rare. Howev er, 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. Conclusion: The antioxidant properties of silymarin (a mixture of at least 4 closely related flavonolignans, 60 to 70% of which is a mixture of 2 dias tereomers of silybin) have been demonstrated in vitro and in animal and hum an studies. However, studies evaluating relevant health outcomes associated with these properties are lacking. Although silymarin has low oral absorpt ion, oral dosages of 420 mg/day have shown some therapeutic potential, with good tolerability, in the treatment of alcoholic cirrhosis. Moreover, sily bin 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 o f treatment are needed to clarify its role in this indication. Studies in p atients with the early onset of liver disease may demonstrate the liver reg eneration properties that silymarin is promoted as possessing.