The high prevalence of liver diseases such as chronic hepatitis and cirrhosis underscores
the need for efficient and cost-effective treatments. The potential benefit of silymarin
(extracted from the seeds of Silybum marianum or milk thistle) in the treatment of
liver diseases remains a controversial issue. Therefore, the objective of this review
is to assess the clinical efficacy and safety of silymarin by application of systematic
approach. 525 references were found in the databases, of which 84 papers were retained
for closer examination and 36 were deemed suitable for detailed analysis. Silymarin
has metabolic and cell-regulating effects at concentrations found in clinical conditions,
namely carrier-mediated regulation of cell membrane permeability, inhibition of the
5-lipoxygenase pathway, scavenging of reactive oxygen species (ROS) of the R-OH type
and action on DNA-expression, for example, via suppression of nuclear factor (NF)-kappaB.
Pooled data from case record studies involving 452 patients with Amanita phalloides
poisoning show a highly significant difference in mortality in favour of silibinin
[the main isomer contained in silymarin] (mortality 9.8% vs 18.3% with standard treatment;
p < 0.01). The available trials in patients with toxic (e.g. solvents) or iatrogenic
(e.g. antispychotic or tacrine) liver diseases, which are mostly outdated and underpowered,
do not enable any valid conclusions to be drawn on the value of silymarin. The exception
is an improved clinical tolerance of tacrine. In spite of some positive results in
patients with acute viral hepatitis, no formally valid conclusion can be drawn regarding
the value of silymarin in the treatment of these infections. Although there were no
clinical end-points in the four trials considered in patients with alcoholic liver
disease, histological findings were reported as improved in two out of two trials,
improvement of prothrombin time was significant (two trials pooled) and liver transaminase
levels were consistently lower in the silymarin-treated groups. Therefore, silymarin
may be of use as an adjuvant in the therapy of alcoholic liver disease. Analysis was
performed on five trials with a total of 602 patients with liver cirrhosis. The evidence
shows that, compared with placebo, silymarin produces a nonsignificant reduction of
total mortality by -4.2% [odds ratio (OR) 0.75 (0.5 - 1.1)]; but that, on the other
hand, the use of silymarin leads to a significant reduction in liver-related mortality
of-7% [OR: 0.54 (0.3 - 0.9); p < 0.01]. An individual trial reported a reduction in
the number of patients with encephalopathy of -8.7% (p = 0.06). In one study of patients
with cirrhosis-related diabetes mellitus, the insulin requirement was reduced by -25%
(p < 0.01). We conclude that available evidence suggests that silymarin may play a
role in the therapy of (alcoholic) liver cirrhosis. Silymarin is has a good safety
record and only rare case reports of gastrointestinal disturbances and allergic skin
rashes have been published. This review does not aim to replace future prospective
trials aiming to provide the 'final' evidence of the efficacy of silymarin.