Objectives:

This evidence report summarizes studies of efficacy and adverse effects of milk thistle in humans with alcohol, viral, or toxin-related liver disease.

Search Strategy:

English and non-English citations were identified through December 1999 from 11 electronic databases, references of pertinent articles and reviews, manufacturers, and technical experts.

Selection Criteria:

Selection criteria regarding efficacy were placebo-controlled trials of milk thistle. For adverse effects, all studies in humans were used.

Data Collection and Analysis:

Abstractors independently abstracted data from published reports. Relationships between clinical outcomes and methodologic characteristics were examined in evidence tables and graphic summaries. Exploratory meta-analyses were used to examine possible patterns of effects.

Main Results:

Sixteen prospective placebo-controlled trials were identified.

Interpreting the evidence was difficult because of inadequate reporting and study design regarding severity of liver disease, subject characteristics, and potential confounders. Outcome measures, dose, duration, and followup widely varied among studies.

Four of six studies of chronic alcoholic liver disease reported significant improvement in at least one parameter of liver function or histology with milk thistle.

In three of six studies that reported multiple outcome measures, at least one outcome measure improved significantly with milk thistle compared with placebo, but there were no differences between milk thistle and placebo for one or more of the other outcome measures in each study.

Three studies evaluated the effects of milk thistle on viral hepatitis. The acute hepatitis study showed no improvement in liver function. Improvement in aspartate aminotransferase and bilirubin was significant in the study of acute hepatitis. Two studies of chronic viral hepatitis showed improvement in aminotransferases with milk thistle in one and a trend toward histologic improvement in the other.

There were two studies of patients with alcoholic or nonalcoholic cirrhosis. In one study, milk thistle showed a positive effect, but no data were given. In the other, milk thistle showed a trend toward improved survival and significantly improved survival for subgroups with alcoholic cirrhosis or Child's Group A severity.

Two trials specifically studied alcoholic cirrhosis. One showed no improvement in liver function, hepatomegaly, jaundice, ascites, or survival but did show nonsignificant trends favoring milk thistle in the incidence of encephalopathy, gastrointestinal bleeding, and death in subjects with hepatitis C. The other reported significant improvements in aminotransferases with milk thistle.

Three trials evaluated thistle as therapy or prophylaxis in the setting of hepatotoxic drugs; results were mixed.

Meta-analyses generally showed small effect sizes, some statistically significant and some not, favoring milk thistle.

Available evidence does not define milk thistle's effectiveness across preparations or doses.

Little evidence is available regarding causality, but evidence suggests milk thistle is associated with few, generally minor, adverse effects.

Conclusions:

Milk thistle's efficacy is not established. Published evidence is clouded by poor design and reporting. Possible benefit has been shown most frequently, but inconsistently, for aminotransferases, but laboratory tests are the most common outcome measure studied. Survival and other clinical outcomes have been studied less, with mixed results. Future research should include definition of multifactorial mechanisms of action, well-designed clinical trials, and clarification of adverse effects.