Resveratrol

Resveratrol is a naturally occurring polyphenolic compound found in foods such as grapes, red wine, peanuts and blueberries. ^[1] It is a stilbene molecule belonging to the polyphenol family, and is a constituent of red wine long suspected to have cardioprotective effects. ^{[2] [3]} Resveratrol has been reported to have diverse biological activities including anti-inflammatory, antioxidant, and antiaging properties. ^[4]

Resveratrol is the most potent natural compound able to activate SIRT1, mimicking the positive effect of calorie restriction. ^[5] By modulating signaling pathways such as the activation of sirtuin 1, resveratrol attenuates oxidative stress, regulates apoptosis, and promotes autophagy. ^[4] Its reported antiaging mechanisms mainly involve ameliorating oxidative stress, relieving inflammatory reactions, improving mitochondrial function, and regulating apoptosis. ^[1]

Resveratrol was reported to activate sirtuin deacetylases and to extend the lifespans of lower organisms, and a growing body of in vivo evidence indicates protective effects in rodent models of stress and disease. ^[3] Preclinical studies have demonstrated the potential of resveratrol in mitigating degenerative musculoskeletal disorders, cardiovascular diseases, cancer progression, and neurological diseases. ^[4] Over the last 20 years there have been almost 200 clinical studies evaluating resveratrol across at least 24 indications, yet there is currently no conclusive clinical evidence to advocate its recommendation in any healthcare setting. ^[6] Results from the available human clinical trials have been controversial concerning the protective effects of resveratrol against diseases, with differences in patient characteristics, doses used, and duration of supplementation proposed as possible causes. ^[7] In a systematic review and meta-analysis of women with polycystic ovary syndrome, resveratrol significantly reduced testosterone, luteinizing hormone, and dehydroepiandrosterone sulfate compared with placebo. ^[8]

Resveratrol consistently reduces inflammatory markers and improves aspects of a dysregulated metabolism, and the increasing weight of clinical evidence suggests it can benefit human health. ^[6] A major limitation is that resveratrol exhibits low bioavailability and interacts with multiple molecular targets, which has motivated development of new molecules with better bioavailability. ^[5] Resveratrol is generally well-tolerated at a dose of up to 1 g/day, but more large, high-quality clinical trials are required before its potential benefits to human health can be realized. ^[6] Toxicity and adverse effects have been reported following consumption of resveratrol, so extensive further study of its long-term and in vivo adverse effects in humans is needed. ^[7]