Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. Sources of resveratrol in food include the skin of grapes, blueberries, raspberries, mulberries, and peanuts.
Although commonly used as a dietary supplement and studied in laboratory models of human diseases, there is no high-quality evidence that resveratrol improves lifespan or has a substantial effect on any human disease.
Research
Resveratrol has been studied for its potential therapeutic use, with little evidence of anti-disease effects or health benefits in humans.
Cardiovascular disease
There is no evidence of benefit from resveratrol in people who already have heart disease. A 2018 meta-analysis found no effect on systolic or diastolic blood pressure; a sub-analysis revealed a 2 mmHg decrease in systolic pressure only from resveratrol doses of 300 mg per day, and only in diabetic people. A 2014 Chinese meta-analysis found no effect on systolic or diastolic blood pressure; a sub-analysis found an 11.90 mmHg reduction in systolic blood pressure from resveratrol doses of 150 mg per day.
Cancer
, there is no evidence of an effect of resveratrol on cancer in humans.
Metabolic syndrome
There is no conclusive evidence for an effect of resveratrol on human metabolic syndrome. One 2015 review found little evidence for use of resveratrol to treat diabetes. A 2015 meta-analysis found little evidence for an effect of resveratrol on diabetes biomarkers.
One review found limited evidence that resveratrol lowered fasting plasma glucose in people with diabetes. Two reviews indicated that resveratrol supplementation may reduce body weight and body mass index, but not fat mass or total blood cholesterol. A 2018 review found that resveratrol supplementation may reduce biomarkers of inflammation, TNF-α and C-reactive protein.
Lifespan
There is insufficient evidence to indicate that consuming resveratrol has an effect on human lifespan.
Cognition
Resveratrol has been assessed for a possible effect on cognition, but with mixed evidence for an effect. One review concluded that resveratrol had no effect on neurological function, but reported that supplementation improved recognition and mood, although there were inconsistencies in study designs and results.
Diabetes
Although animal experiments have found some evidence that resveratrol may help improve insulin sensitivity and so potentially help manage diabetes, subsequent research on people is limited and does not support the use of resveratrol for this purpose.
Other
There is no significant evidence that resveratrol affects vascular endothelial function, neuroinflammation, Alzheimer's disease, skin infections or aging skin. A 2019 review of human studies found mixed effects of resveratrol on certain bone biomarkers, such as increases in blood and bone alkaline phosphatase, while reporting no effect on other biomarkers, such as calcium and collagen.
Pharmacology
Pharmacodynamics
Resveratrol has been identified as a pan-assay interference compound, which produces positive results in many different laboratory assays. Its ability for varied interactions may be due to direct effects on cell membranes.
As of 2015, many specific biological targets for resveratrol had been identified, including NQO2 (alone and in interaction with AKT1), GSTP1, estrogen receptor beta, CBR1, and integrin αVβ. It was unclear at that time if any or all of these were responsible for the observed effects in cells and model organisms.
Pharmacokinetics
The viability of an oral delivery method is unlikely due to the low aqueous solubility of the molecule. The bioavailability of resveratrol is about 0.5% due to extensive hepatic glucuronidation and sulfation. Glucuronidation occurs in the intestine as well as in the liver, whereas sulfonation not only occurs in the liver but in the intestine and by microbial gut activity. Due to rapid metabolism, the half-life of resveratrol is short (about 8–14 minutes), but the half-life of the sulphate and glucoronide metabolites is above 9 hours.
Metabolism
Resveratrol is extensively metabolized in the body, with the liver and intestines as the major sites of its metabolism. Liver metabolites are products of phase II (conjugation) enzymes, which are themselves induced by resveratrol in vitro.