LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].
Resveratrol is a plant polyphenol found in high concentrations in red grapes that has been proposed as a treatment for hyperlipidemia and to prevent fatty liver, diabetes, atherosclerosis and aging. Resveratrol use has not been associated with serum enzyme elevations or with clinically apparent liver injury.
Resveratrol is a natural plant polyphenol (3,5,4’-trihydroxystilbene) that is found in highest concentrations in the skin of red grapes and other fruits (mulberries, blueberries, blackberries). In cell culture, resveratrol has antiinflammatory, cytoprotective, and antineoplastic properties which can be reproduced in several animal models. In model systems such as yeast (S. cerevisiae), worms (C. elegans) and fruit flies (Drosophilia), chronic administration of resveratrol extends lifespan in a manner similar to caloric restriction. These results were somewhat controversial, but subsequent studies in several mammalian species supported the finding to some extent. Thus, resveratrol extended lifespan in mice fed a high fat diet (but not in normal mice), seemingly by counteracting the detrimental effects of the diet, and improving insulin sensitivity and mitochondrial function. The bases for the beneficial effects of resveratrol are unclear. Resveratrol has direct antioxidant effects, but also stimulates expression of antioxidant enzymes and the activity of sirtuin 1 (Sirt-1) and adenosine monophosphate activated protein kinase (AMP-K), both of which have major effects on glucose and fat metabolism and may play a role in aging. Resveratrol is available without prescription as a nutritional supplement in multiple preparations and doses. In human trials, doses of resveratrol have ranged from 20 mg to 5 g daily; but a typical over-the-counter recommended dose is 500 mg twice daily. Importantly, the purity of commercial products is rarely well defined, its oral bioavailability is poor and the form responsible for its activity is not known. Thus, resveratrol exists in both trans and cis configuration and the major form found in plasma is a sulfated or glucuronidal conjugate rather than free resveratrol. At present, there is no conclusive evidence that resveratrol has beneficial effects in humans. On the other hand, it has few if any side effects. Side effects may include minor gastrointestinal upset, nausea, headache and fatigue and possible supplement-drug interactions with estrogens and anticoagulants.
Liver injury attributable to resveratrol has not been reported. In trials of resveratrol in human subjects, there have been no reports of serum enzyme elevations or clinically apparent liver injury. Thus, hepatotoxicity due to resveratrol must be rare, if it occurs at all.