Resveratrol has been studied for its potential therapeutic use,[13] with little evidence of anti-disease effects or health benefits in humans.[6][10][14]
There is no evidence of benefit from resveratrol in people who already haveheart disease.[10][15] A 2018meta-analysis found no effect onsystolic ordiastolic blood pressure; a sub-analysis revealed a 2 mmHg decrease in systolic pressure only from resveratrol doses of 300 mg per day, and only indiabetic people.[16] A 2014 Chinese meta-analysis found no effect on systolic or diastolic blood pressure; a sub-analysis found an 11.90 mmHg reduction insystolic blood pressure from resveratrol doses of 150 mg per day.[17]
There is no conclusive evidence for an effect of resveratrol on humanmetabolic syndrome.[10][19][20] One 2015 review found little evidence for use of resveratrol to treatdiabetes.[21] A 2015 meta-analysis found little evidence for an effect of resveratrol on diabetesbiomarkers.[22]
Resveratrol has been assessed for a possible effect oncognition, but with mixed evidence for an effect. One review concluded that resveratrol had no effect on neurological function, but reported that supplementation improved recognition andmood, although there were inconsistencies in study designs and results.[27]
A 2022 meta-analysis provided preliminary evidence that resveratrol, alone or in combination with glucose andmalate, may slow cognitive decline inAlzheimer's disease.[28]
Although animal experiments have found some evidence that resveratrol may help improveinsulin sensitivity and so potentially help manage diabetes, subsequent research on people is limited and does not support the use of resveratrol for this purpose.[14][29]
Resveratrol has been identified as apan-assay interference compound, which produces positive results in many different laboratory assays.[31] Its ability for varied interactions may be due to direct effects oncell membranes.[32]
As of 2015, many specificbiological targets for resveratrol had been identified, includingNQO2 (alone and in interaction withAKT1),GSTP1,estrogen receptor beta,CBR1, andintegrin αVβ. It was unclear at that time if any or all of these were responsible for the observed effects in cells and model organisms.[33]
The viability of an oral delivery method is unlikely due to the low aqueous solubility of the molecule. Thebioavailability of resveratrol is about 0.5% due to extensivehepaticglucuronidation andsulfation.[34] 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.[35] Due to rapid metabolism, thehalf-life of resveratrol is short (about 8–14 minutes), but the half-life of the sulphate and glucoronide metabolites is above 9 hours.[36]
Resveratrol is extensively metabolized in the body,[6] with the liver and intestines as the major sites of its metabolism.[37][36] Liver metabolites are products ofphase II (conjugation) enzymes,[38] which are themselves induced by resveratrol in vitro.[39]
Resveratrol (3,5,4'-trihydroxystilbene) is a stilbenoid, a derivative ofstilbene.[6] It exists as twogeometric isomers:cis- (Z) andtrans- (E), with thetrans-isomer shown in the top image. Resveratrol exists conjugated to glucose.[40]
UV irradiation to cis-resveratrol induces further photochemical reaction, producing a fluorescent molecule named "Resveratrone".[43]
Trans-resveratrol in the powder form was found to be stable under "accelerated stability" conditions of 75% humidity and 40 °C in the presence of air.[44] Thetrans isomer is also stabilized by the presence of transport proteins.[45] Resveratrol content also was stable in the skins of grapes andpomace taken after fermentation and stored for a long period.[46]lH- and13C-NMR data for the four most common forms of resveratrols are reported in literature.[40]
Only a few human studies have been done to determine theadverse effects of resveratrol, all of them preliminary with small participant numbers. Adverse effects resulted mainly from long-term use (weeks or longer) and daily doses of 1000 mg or higher, causingnausea,stomach pain,flatulence, anddiarrhea.[6] A review of 136 patients in seven studies who were given more than 500 mg for a month showed 25 cases of diarrhea, 8 cases of abdominal pain, 7 cases of nausea, and 5 cases of flatulence.[52] A 2018 review of resveratrol effects on blood pressure found that some people had increased frequency ofbowel movements and loosestools.[16]
Resveratrol is aphytoalexin, a class of compounds produced by many plants when they are infected by pathogens or physically harmed by cutting, crushing, or ultraviolet radiation.[53] Plants that synthesize resveratrol includeJapanese knotweed,pine trees (includingScots pine andEastern white pine), Concord grape vines, raspberries, mulberries, peanut plants, cocoa bushes, andVaccinium shrubs that produce berries, including blueberries, cranberries, and bilberries.[6][8][53]
Resveratrol concentrations in red wines average1.9±1.7 mg trans-resveratrol/L (8.2±7.5 μM), ranging from nondetectable levels to 14.3 mg/L (62.7 μM)trans-resveratrol. Levels ofcis-resveratrol follow the same trend astrans-resveratrol.[54]
In general, wines made from grapes of thePinot noir andSt. Laurent varieties showed the highest level oftrans-resveratrol, though no wine or region can yet be said to produce wines with significantly higher concentrations than any other wine or region.[54]Champagne andvinegar also contain appreciable levels of resveratrol.[9]
Red wine contains between 0.2 and 5.8 mg/L, depending on the grape variety. White wine has much less because red wine isfermented with the skins, allowing the wine to extract the resveratrol, whereaswhite wine is fermented after the skin has been removed.[6] The composition of wine is different from that of grapes since the extraction of resveratrol from grapes depends on the duration of the skin contact, and the resveratrol 3-glucosides are in part hydrolysed, yielding bothtrans- andcis-resveratrol.[6][55]
Though its extraction (i.e. from wood chips or other sources) during artificial ageing, resveratrol is added in red wines to improve the color and sensory properties.[56]
Ounce for ounce, peanuts have about 25% as much resveratrol as red wine.[6]Peanuts, especiallysprouted peanuts, have a content similar to grapes in a range of 2.3 to 4.5 μg/g before sprouting, and after sprouting, in a range of 11.7 to 25.7 μg/g, depending on peanutcultivar.[9][53]
Mulberries (especially the skin) are a source of as much as 50 micrograms of resveratrol per gram dry weight.[57]
Most US supplements of resveratrol are derived from the root ofReynoutria japonica (also called Japanese knotweed, Hu Zhang, etc.)[6]
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