Table 1.

Studies of resveratrol bioavailability and pharmacokinetics in the last 10 years *.

Metabolite (form of RV)	Sample	Type of Study	(n)	Dose	Participants’ Health Status	Effect	Ref.
RV and six metabolites: two monosulfates, one disulfate, two monoglucuronides, and one glucuronide-sulfate	Urine and feces	Clinical trial	40	After a five-day washout, 10 subjects received a 0.5 g dose, which was escalated sequentially to 1, 2.5, and 5 g	Healthy	An intake of up to one dose of 5 g of RV was safe, with minor adverse events in some cases; 77% of urinary excretion of RV and its metabolites occurred within four hours after the lowest dose. RV underwent enterohepatic recirculation.	[43]
tRV	Plasma	Randomized, crossover, open-label, and single-dose	24	Two treatments with a single dose of 400 mg tRV after a high-fat meal or eight hours without breakfast, separated by a washout of seven days or more.	Healthy	The rate of absorption of tRV was reduced by the presence of a meal	[35]
tRV	Plasma	Phase I, randomized, double-blind, placebo-controlled, and single-center	40	25, 50, 100, or 150 mg, administered at four hours intervals (six times/day) for 48 h (13 doses in total)	Healthy	High daily doses of tRV were well tolerated but produced low plasma tRV levels; tRV bioavailability was higher when it was administered in the morning.	[39]
tRV	Plasma	Open-label and single-arm	8	tRV 2000 mg twice daily for seven days and tRV 2000 mg with quercetin 500 mg twice daily for seven days, with a two-week washout period	Healthy	tRV 2000 g twice daily had adequate exposure and was well tolerated by subjects. Moreover, combined intake with quercetin did not influence its exposure	[34]
RV glucuronide and sulfate conjugates, RV glucoside, piceid glucuronides, sulfates, DHR, glucuronide, and sulfate conjugates	Plasma and urine	Randomized and crossover	10	After a three-day washout period, three people were chosen for the pilot study in which they consumed 15 grape extract tablets (total RV 4.72 ± 0.07 mg) with 400 mL of water within 10 min. In parallel, seven people were selected randomly to drink 375 mL of red wine (total RV 6.30 ± 0.09 mg) with 400 mL of water consumed within 10 min.	Healthy	Statistically significant differences between grape extract tablets and red wine treatments were obtained for some metabolites, mainly due to the different composition of RV and piceid from both sources. The grape extract tablets delayed RV absorption compared to the red wine treatment.	[31]
Free RV and conjugated RV (monosulfate, disulfate, and glucoronide)	Plasma	Clinical trial	15	Single dose (40 mg) of tRV in soluble formulation or dry powder	Healthy	Bioavailability was higher with soluble formulation compared to dry powder.	[29]
tRV, DHR, 3,4′-dihydroxy-trans-stilbene, and 3,4′-dihydroxybibenzyl (lunularin).	24 h urine and feces	Controlled intervention	12	Following a washout period, all the subjects received a single oral dose of 0.5 mg tRV/kg body weight in the form of a grapevine-shoot supplement (7.7% tRV as well as other stilbene mono- and oligomers [14.6%-ε-viniferin, 3.4% ampelopsin A, 1.8% hopeaphenol, 0.6% trans-piceatannol, 1.6% r-2-viniferin (vitisin A), 2.5% miyabenol C, 2.5% r-viniferin (vitisin B), and 2.4% iso-trans-ε-viniferin].	Healthy	The human gut microbiota produced pronounced interindividual differences in tRV. Slackia Equolifaciens sp. and Adlercreutzia Equolifaciens sp. were identified as DHR producers, but the bacteria that produce dehydroxylated metabolites were not determined.	[40]
tRV	Plasma	Pilot study	2	146 +/− 5.5 mg tRV per 2000 mg of lozenge mass, containing about 46% ribose, 46% (fructose/sucrose mixture), and 8% tRV	Healthy	A mixture of ribose and RV oral transmucosal administration achieved a much higher and quicker RV release compared to the reported traditional free RV capsules.	[36]
Free and conjugated RV	Plasma	Randomized and three-way crossover	15	Oral doses equivalent to 50 mg or 150 mg of tRV or plant-derived RV (150 mg) on three occasions separated by seven-day washout periods.	Healthy	150 mg dose of tRV showed higher total and free levels than 50 mg dose	[46]
tRV, RV, 3-O-sulphate, RV 4′-O-glucuronide, and RV 3-O-glucuronide	Plasma	Randomized, double-blind, and placebo-controlled	23	250 mg of tRV or 250 mg of tRV with 20 mg of piperine on separate days at least a week apart.	Healthy	Piperine co-supplementation with 250 mg of tRV or 250 mg of tRV; piperine enhanced the absorption of the polyphenol leading to an increase in cerebral blood flow.	[23]
tR4G, cR4G, tR3G, cR3G, tR4S, cR4S, tR3S, cR3S, tR34dS, RV-SG, tpiceid, cpiceid, Pic-G, Pic-S1, Pic-S2, DHR, DHR-G1, DHR-G2, DHR-S1, DHR-S2, and DHR-SG	24 h urine	Randomized, double-blind, placebo-controlled, crossover, and intervention study	26	Consumed twice a day (with breakfast and dinner) for 15 days (per each phase) 187 mL of: a control placebo and a functional beverage (4280 g/L of hydroxycinnamic acids, 16 mg/L of anthocyanins, 96 mg/L of flavanols, 83 mg/L of hydroxybenzoic acids, and 5.7 mg/L of stilbenes)	Healthy	The whole profile of the 21 RV metabolites increased after acute and chronic consumption of the functional beverage with respect to the control-placebo beverage and to the baseline.	[30]
Phenolic acids including, 3-hydroxyphenylacetic acid, 3-hydroxyhippuric acid, 4-hydroxyhippuric acid, and Hippuric Acid,	24 h urine	Randomized, placebo-controlled, and crossover	35	Six placebo gelatin capsules consumed with 200 mL of water (control) Six capsules containing 800 mg polyphenols (141 mg anthocyanins, 24 mg flavan-3-ols, 16 mg procyanidins, 10 mg phenolic acids, 9 mg flavonols, and 1 mg stilbenes) derived from red wine and grape extracts, or the same dose of polyphenols incorporated into one of the following: 200 mL of water (positive control), 200 g of dairy drink, 200 g of soy drink, 200 g fruit-flavored drink, or protein-free drink.	Healthy	Bioavailability of polyphenols and the excretion of their phenolic metabolites were not significantly affected when polyphenols were consumed in protein-rich soy or dairy drinks.	[37]
Total RV	Plasma	Randomized and double-blind	9	5 g/day of SRT501 for approximately 14 days	IV colorectal cancer and hepatic metastasis subjects scheduled to undergo hepatectomy.	RV treatment was well tolerated by the patients. The peak plasma after ingestion of SRT501 was 1.942 ng/m, higher than that of an equivalent dose of non-micronized RV supplementation.	[33]
tR4G, cR4G, tR3G, cR3G, tR4S, cR4S, tR3S, cR3S, tR34dS, RV-SG, tpiceid, cpiceid, Pic-G, Pic-S1, Pic-S2, DHR, DHR-G1, DHR-G2, DHR-S1, DHR-S2, and DHR-SG	24 h urine	Randomized, crossover, and controlled clinical trial	59	15-day run-in period in which they consumed neither grape-derived products nor alcoholic beverages. Afterwards, they consumed every day for four weeks: 272 mL of RW (red wine) with 30 g ethanol/day or 272 mL of DRW (dealcoholized red wine), following the same background diet.	High cardiovascular risk	The whole profile of the 21 RV metabolites increased after RW and DRW consumption, and no differences between them were presented	[38]

cpiceid: cis-3,4′,5-trihydroxystilbene-3-β-d-glucopyranoside, cR3G: cis-RV-3-O-glucuronide, cR3S: cis-RV-3-O-sulfate, cR4G: cis-RV-4′-O-glucuronide, cR4S: cis-RV-4′-O-sulfate, DHR: Dihydroresveratrol, DHR-G1: DHR glucuronide 1, DHR-G2: DHR glucuronide 2, DHR-S1: DHR sulfate 1, DHR-S2: DHR sulfate 2, DHR-SG: DHR sulfoglucuronide, Pic-G: piceid-glucuronide, Pic-S1: Piceid sulfate 1, Pic-S2: Piceid sulfate 2, RV: resveratrol, RV-SG: RV sulfoglucuronide, SRT501: microparticular RV of particle size less than 5um, tpiceid: trans-3,4′,5-trihydroxystilbene-3-β-d-glucopyranoside, tRV: trans-RV, tR3G: trans-RV-3-O-glucuronide, tR3S: trans-RV-3-O-sulfate, tR4G: trans-RV-4′-O-glucuronide, tR4S: trans-RV-4′-O-sulfate, and tR34dS: trans-RV-3,4′-O-disulfate, * Studies which identified resveratrol or some metabolite of resveratrol in plasma, urine, and/or feces.