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AASLD 2011: Milk Thistle Extract Did Not Improve Liver Inflammation or Quality of Life for Hepatitis C Patients


Oral silymarin, an extract from the milk thistle plant, was well-tolerated but did not reduce alanine aminotransferase (ALT) or HCV RNA levels or improve quality of life for hepatitis C patients who did not respond to interferon, researchers reported at the 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011) last month in San Francisco.

Interferon-based therapy for chronic hepatitis C virus (HCV) infection is not always effective, and even if it is, liver damage may persist. Patient and providers have explored numerous alternative and complementary therapies for liver disease, with milk thistle (Silybum marianum) among the most common. Silymarin is a mix of milk thistle flavonoids (including silybin A and B) with anti-oxidant, anti-inflammatory, immunomodulatory, and antiviral properties in vitro.

In the present study -- funded by the National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Center for Complementary and Alternative Medicine (NCCAM) -- Michael Fried from the University of North Carolina Liver Center and colleagues evaluated oral silymarin in hepatitis C patients who did not achieve sustained virological response to interferon-based therapy.

A total of 154 adult participants at 4 U.S. centers were enrolled; a majority were men, about 75% were white, and the median age was 54 years. Most (about 90%) had hard-to-treat HCV genotype 1 and 40% had liver cirrhosis, but people with decompensated cirrhosis, moderate or worse steatosis (liver fat accumulation), and HIV or hepatitis B coinfection were excluded. At baseline they had elevated ALT (> 65 IU/L or 1.5 x upper limit of normal; median 106 IU/L), a biomarker of liver inflammation.

Participants were randomly assigned to receive 420 mg or 700 mg of Legalon brand silymarin 3-times-daily (3 to 5 times higher than the doses typically used) or placebo or 24 weeks.


  • 138 out of 154 enrolled participants completed the study.
  • Adherence was good, with more than 90% reporting that they took silymarin as directed at least 80% of the time.
  • Although ALT levels declined somewhat more in the 420 mg and 700 mg silymarin groups compared with the placebo group (-4.3, -14.4, and -11.3 IU/L, respectively), the difference did not reach statistical significance (P = 0.75).
  • At 24 weeks, only 2 people (4%) each in the 420 mg and 700 mg silymarin groups saw their ALT level fall to 45 IU/L or lower compared, with 1 (2%) in the placebo group.
  • 1 person (2%) in the 420 mg silymarin group and 2 (4%) in the 700 mg group saw their ALT decrease by at least 50% to < 65 IU/L, compared with 2 (4%) in the placebo group.
  • HCV RNA viral load did not change significantly in any group (+0.07, -0.03, and +0.04, respectively).
  • Quality of life measures and symptom scores (including CES-D, SF-36, and CLDQ) were not significantly different across groups.
  • Silymarin was well-tolerated, with mostly mild-to-moderate adverse events that were similar across groups.

The investigators concluded that although it was well-tolerated, higher than usual oral doses of silymarin "did not significantly reduce serum ALT levels more than placebo in participants with HCV infection who previously failed interferon-based therapy."

In response to a question about whether even higher doses might have an effect, given the need for alternatives in areas of the world that have no access to new HCV drugs, Fried replied that higher doses would necessitate too great a pill burden -- even the higher dose used here required 5 capsules 3-timesdaily -- and attempts to boost silymarin with other botanicals were unsuccessful.

Investigator affiliations: UNC Liver Center, University of North Carolina at Chapel Hill, Chapel Hill, NC; Thomas Jefferson University, Philadelphia, PA; Beth Israel Deaconess Medical Center, Boston, MA; University of Pittsburgh, Pittsburgh, PA; Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC; NIDDK, National Institutes of Health, Bethesda, MD; NCCAM, National Institutes of Health, Bethesda, MD; University of Pennsylvania, Philadelphia, PA.



MW Fried, VJ Navarro, NH Afdhal, et al. A Randomized, Placebo-Controlled Trial of Oral Silymarin (Milk Thistle) For Chronic Hepatitis C: Final Results of the SYNCH Multicenter Study. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 228.