Key messages

• Due to a lack of data on outcomes of importance to people with MASLD as well as to doctors, the benefits and harms of silymarin in adults with MASLD are still unclear.

• Silymarin appears to be safe and may improve liver enzyme levels, but the evidence is very uncertain.

• Further larger, well-designed trials that consider people-related clinical outcomes are needed to better evaluate the benefits and harms of silymarin in adults with MASLD.

What is MASLD?

MASLD, a common chronic liver disease, has emerged as the most prevalent liver disease globally. It is defined as the presence of excessive fat accumulation in the functional tissue of the liver, that is, parenchyma (> 5% of the main cells of the liver, called hepatocytes) in people without any history of significant alcohol consumption (i.e. a daily alcohol intake of ≤ 20 g for females and ≤ 30 g for males) or any other aetiology of hepatic steatosis. The nomenclature has evolved from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD), and more recently to MASLD. This shift reflects how the disease is closely connected to common metabolic problems, like obesity and diabetes.

How is MASLD treated?

At present, no medicines are approved for the treatment of MASLD. Lifestyle modifications are, however, recommended. Silymarin, a common herbal agent, is considered by some to be effective for MASLD due to its potential antioxidant, anti-inflammatory, and antifibrotic properties.

What did we want to find out?

We wanted to know if silymarin is an effective and safe treatment choice for MASLD.

What did we do?

We searched for studies that investigated silymarin monotherapy or silymarin complex (compound preparation consisting of silymarin combined with solubilising agents, such as vitamin E, phosphatidyl choline, etc.) compared with no treatment, placebo (dummy pill), or other interventions in adults with MASLD.

We explored the effect of silymarin on adults with MASLD based on the following outcomes: proportion of people with serious adverse events, death due to any cause, health-related quality of life, liver enzymes (i.e. alanine transaminase, aspartate aminotransferase, and gamma glutamyl transpeptidase), and the proportion of people with non-serious adverse events.

We compared and summarised the results of relevant studies and rated our confidence in the evidence based on how well the studies were performed and reported.

What did we find?

We found 17 studies that involved 2069 adults with MASLD, which formed four comparisons. These studies were conducted in different regions, including 12 in Asia, four in Europe, and one in North America. Silymarin monotherapy was administered in nine studies and silymarin complex in eight studies. None of the trials reported death due to any cause or health-related quality of life.

Only one study on silymarin monotherapy versus no intervention or placebo reported five serious adverse events, but none of which were attributed to the medicine. Silymarin monotherapy versus no intervention or placebo may make little to no difference to serious adverse events. Silymarin monotherapy versus no intervention or placebo may decrease alanine transaminase (ALT) and gamma glutamyl transpeptidase (GGT), but we are very uncertain about the results. It is unclear if silymarin monotherapy versus no intervention or placebo has an effect on aspartate aminotransferase (AST) and non-serious adverse events.

We do not know if silymarin monotherapy versus other interventions has an effect on serious adverse events, ALT, AST, GGT, and non-serious adverse events.

It is unclear if silymarin complex versus no intervention or placebo has an effect on serious adverse events, ALT, AST, GGT, and non-serious adverse events.

Three trials with 920 participants reported zero serious adverse events. Silymarin complex versus other interventions probably makes little to no difference to serious adverse events. Silymarin complex versus other interventions may make little to no difference to GGT. We do not know if silymarin complex versus other interventions has an effect on ALT, AST, and non-serious adverse events.

What are the limitations of the evidence?

We have moderate-to-very-low confidence in our results for several reasons. First, the studies did not provide sufficient information to adequately assess their study quality in design and reporting. Second, the results varied significantly across the studies. Third, most studies had a small sample size. Fourth, none of the studies reported death due to any all-cause or health-related quality of life, and plenty of studies failed to report serious adverse events. In the future, our results may change if further studies with a high quality of conduct and reporting are published.

How up-to-date is this evidence?

This evidence is up-to-date as of 15 May 2024.