Resveratrol

Resveratrol is a natural phenol of the stilbenoid family, produced by plants such as grapevines as a phytoalexin, a compound made in response to attack by bacteria or fungi ^[3]. It is found in grape skins, red wine, peanuts, and various berries; red wine contains more than white wine because it is fermented in contact with the grape skins ^[3]. The compound exists in two geometric forms, cis and trans, and the trans form can convert to the cis form on exposure to ultraviolet light ^[3]. Most commercial resveratrol is extracted from Japanese knotweed ^[3].

Interest in resveratrol grew after laboratory reports that it activates sirtuin enzymes, in particular SIRT1, and mimics some effects of calorie restriction, prompting speculation about anti-aging and heart-protective potential ^[2]. This idea was popularized alongside the French paradox, the observation of relatively low rates of heart disease in populations with high wine consumption ^[2]. The compound was commercialized through a company co-founded by the researcher David Sinclair, which was acquired by a major pharmaceutical firm and later closed without producing a successful drug ^[2].

Despite extensive study, high-quality evidence that resveratrol improves lifespan or meaningfully treats human disease is lacking ^[3]. A significant limitation is its very low bioavailability; although well absorbed, it is rapidly converted in the intestine and liver into sulfate and glucuronide metabolites, so little unchanged resveratrol reaches the bloodstream ^[1]. An umbrella review of trials in type 2 diabetes, metabolic syndrome, and fatty liver disease found that most reported effects were small and rested on low-certainty evidence ^[4]. Resveratrol is sold as a dietary supplement rather than an approved drug, and expert reviews have cautioned that current evidence does not justify its use beyond the amounts found in food ^[3].

Generally well tolerated; higher doses can cause GI upset, loose stools, or nausea. It can inhibit certain cytochrome P450 enzymes and has mild antiplatelet (blood-thinning) effects, so caution with anticoagulants or before surgery. It may have weak estrogenic activity, which is worth noting for hormone-sensitive situations. Very high doses studied in trials sometimes caused more GI complaints without clear added benefit.