Hepatoprotective effects of silymarin in patients with alcoholic liver disease are controversial. For strict control, this was assessed in non-human primates.
Twelve baboons were fed alcohol with or without silymarin for 3 years with a nutritionally adequate diet.
Silymarin opposed the alcohol-induced oxidative stress (assessed by plasma 4-hydroxynonenal) and the rise in liver lipids and circulating ALT. Alcohol also increased hepatic collagen type I by 50% over the 3 years with a significant rise in mRNA for α1 (I) procollagen, both prevented by silymarin. There were corresponding morphologic changes: at 36 months, 2 of 6 animals fed alcohol had cirrhosis and 2 septal fibrosis, with perivenular fibrosis in 2, whereas with alcohol + silymarin, there was only 1 cirrhosis and 1 septal fibrosis, with perivenular fibrosis in 2, and virtually no lesions in the remaining 2.
Silymarin retards the development of alcohol-induced hepatic fibrosis in baboons, consistent with several positive clinical trials. The negative outcome observed in other trials possibly reflects poor compliance resulting in irregular or low silymarin intake. Thus, in view of the innocuity of silymarin, it might be advisable in future clinical studies to insure the controlled administration of sufficient amounts of silymarin.
From the Section of Liver Disease & Nutrition, Bronx VA Medical Center & Mount Sinai School of Medicine, Bronx, New York
Received for publication January 7, 2003; accepted May 6, 2003.
Supported, in part, by NIH grant AA11115, the Department of Veterans Affairs, the Kingsbridge Research Foundation and MADAUS AG, Cologne, Germany.
Reprints: Dr. Charles S. Lieber, VA Medical Center (151–2), 130 West Kingsbridge Road, Bronx, NY 10468 (e-mail: firstname.lastname@example.org).