PDF[?] (Download)
  • Liver
  • Milk Thistle (Silybum marianum)
  • Silymarin
    • Date: May 31, 2005HC# 110443-281

    Re:Silymarin in the Treatment of Liver Disease - A Conservative Meta-analysis

    Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver disease Drugs. 2001;61(14):2035-2063.

    Milk thistle (Silybum marianum) has been used for centuries as a treatment for liver diseases. Although a number of studies demonstrate that silymarin is efficacious for treating liver diseases, most studies enrolled only a small number of patients and do not use standardized silymarin preparations, doses, or outcome measures. This review is an attempt to overcome some of these limitations by using a systematic meta-analysis to assess the efficacy and safety of silymarin.

    All articles mentioning silymarin or silibinin (the most active compound in silymarin) were screened and weighed on the basis of methodological quality. Data Sources included bibliographic databases (TOXLINE, MEDLINE, HealthSTAR, AIDSLINE, CANCERLIT, Embase, AMED, Cochrane Col.), reference lists from pertinent review articles and books, and personal contacts with experts and manufacturers through March 2001. Efficacy studies needed to be double-blind, randomized, and controlled or randomized and controlled comparisons. The studies had to demonstrate good clinical practice standards and adequate statistical reporting. Safety studies could be unblinded.

    The authors identified 525 references; 84 papers containing human data were retained for closer inspection; and 36 were retained for analysis. From the studies, they determined that there is little evidence of a therapeutic effect of silymarin in toxic liver diseases other than mushroom poisoning. In addition, studies examining silymarin for the treatment of viral hepatitis were methodologically outdated. The majority of studies evaluated silymarin as a treatment for alcohol-induced liver diseases.

    None of the studies of alcoholic liver disease assessed clinical endpoints. They did report histological analysis, which showed normalization in the microscopic structure of the liver. The studies also reported an improvement in liver function. Patients with liver cirrhosis (a chronic liver disease caused by alcoholism) who consumed silymarin had a significant reduction in liver-related mortality (P < 0.01).

    The authors retained and evaluated pharmacological papers that used clinically relevant silymarin concentrations or dosages and clinically relevant pharmacological actions. They found the following pharmacological actions relevant. Silymarin is able to reduce the cellular absorption of poisonous xenobiotics (compounds foreign to the body) other than mushroom poisons. Silibinin may be an effective treatment for mushroom poisoning. Silibinin can inhibit the 5-lipoxygenase pathway, which is involved in the formation of free radicals. Silibinin can scavenge hydroxyl radicals. It can also inhibit tumor necrosis factor. The authors conclude that there are not enough dose-response data available.

    Overall the studies demonstrated that silymarin was safe to use. The most common side effect was upper GI symptoms. Two cases of silymarin-induced hives were reported.

    The authors state that the clinical trials published to date must be interpreted cautiously. Nonetheless, silymarin may improve the clinical course and survival rates from acute and chronic hepatitis and drug-, toxin-, and alcohol-induced hepatitis. Since silymarin has minimal toxicity and lack of adverse drug interactions, the authors conclude that silymarin may be used as adjunctive therapy in patients with liver disorders. Most controlled clinical studies have been published after decades of well-established use, in which clinical outcomes were ascertained in practice.

    —Heather S. Oliff, Ph.D.