Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans

Table 1

Some of the resveratrol biological effects reported in vivo and in vitro.

(a) Clinical trials (humans)

Article	Study type	Administered dose	Treatment time	Blood resveratrol	Dietary dose	Relevance
[37]	In vivo: human	Oral: 25 mg; intravenous: 1.5 mg	Once	<5 ng/mL	NO	Resveratrol is quickly metabolized
[49]	In vivo: human	Oral: 25 mg	Once	10 to 40 nmol/L	NO	In vitro anticancer and anti-inflammatory effects of the free polyphenols are irrelevant in vivo
[45]	In vivo: human	Diet: 300 mL (0.82 mg/L); 600 mL (3.2 mg/L); 600 mL (0.48 mg/L)	Once	Not detected	YES	The observed protective effect on cardiovascular diseases associated with a moderate consumption of wine may be due to the whole polyphenols contained in wine and not to resveratrol alone
[54]	In vivo: human	Oral: 2 times/day 2000 mg	16 days	1274 ± 790 ng/mL	NO	A high-fat meal decreases resveratrol absorption
[39]	In vivo: human	Oral: 1 g	Once		NO	A rapid, sensitive, and accurate method for the analysis of resveratrol and its metabolites in human plasma and urine
[50]	In vivo: human	Oral: 6 times/day; 25 mg; 50 mg; 100 mg; 150 mg	Two days	3.89 ng/mL; 7.39 ng/mL; 23.1 ng/mL; 63.8 ng/mL	NO	Repeated administration was well-tolerated but produced relatively low plasma concentrations of trans-resveratrol, despite the different administrated doses; trans-resveratrol pharmacokinetics showed circadian variation; bioavailability was higher after morning administration
[55]	In vivo: human	Wine in diet			YES	A moderate wine consumption (alcohol) may be one explanation for protection from coronary heart disease
[116]	In vivo: human	Oral: 1 g/day; 1.5 g/day; 2 g/day	28 days		NO	Resveratrol improves insulin sensitivity in subjects with impaired glucose tolerance
[117]	In vivo: human	150 mg/day	30 days	182.59 ± 30.33 ng/mL	NO	Resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction

(b) In vivo (animals)

Article	Study type	Administered dose	Treatment time	Relevance
[51]	In vivo: F344 rat	Oral: 200 μg/kg/day	100 days	A protective role of resveratrol in colon carcinogenesis.
[52]	In vivo: F344 rat	Orally or intraperitoneally: 1 mg/kg; 2 mg/kg	16 weeks; 20 weeks	Resveratrol may be a promising natural anticarcinogenesis agent for the prevention and treatment of human esophageal cancer
[53]	In vivo: Sprague Dawley rat	Diet: 200 μg/rat/day	120 days	Resveratrol suppresses 7,12-dimethylbenz(a)anthracene induced mammary carcinogenesis
[60]	In vivo: APfSD rat; In vitro: Cos-1 cells hER-α Yeast	Oral or subcutaneous: 0.03–120 mg/kg/day		Weak estrogenicity of the red wine constituent resveratrol
[62]	In vivo: weanling rat	Oral: 1, 4, 10, 40, and 100 μg/day	Six days	Resveratrol has little or no estrogen agonism on reproductive and nonreproductive estrogen target tissues and may be an estrogen antagonist
[103]	In vivo: streptozotocin-induced diabetes mellitus Sprague-Dawley rats	Oral: 0.75 mg/kg; three times a day	Eight weeks	Resveratrol improves energy metabolism and reduces protein wasting
[99]	In vivo: rabbit	Oral: 4 mg/kg/day	12 weeks	Resveratrol inhibits platelet aggregation
[115]	In vivo: Microcebus murinus	Diet: 200 mg/kg/day	21 months; 33 months	Resveratrol affects insulin sensitivity by improving glucose tolerance
[105]	In vivo: Caenorhabditis elegans; Drosophila melanogaster	Diet: 100 μM	Whole life	Resveratrol activates sirtuins in Caenorhabditis elegans and; Drosophila melanogaster and extends their lifespan
[108]	In vivo: Drosophila melanogaster	Diet: 50–500 μM	Whole life	Resveratrol extends lifespan
[109]	In vivo: Caenorhabditis elegans	Diet: 100–1000 μM	Whole life	Lifespan extension in C. elegans is mediated by sir-2.1
[82]	In vivo: Apis mellifera	Diet: 30–130 μM	Whole life	Resveratrol significantly affects gustatory responsiveness and prolongs lifespan under normal oxygen conditions

(c) In vitro

Article	Study type	Administered dose	Relevance
[63]	In vitro: MCF-7 cells; T47D cells; MDA-MB-231 cells	3–10 μM	Resveratrol exhibits variable degrees of estrogen receptor agonism in different test systems
[89]	In vitro: DU-145, PC-3, and JCA-1 human prostate cancer cells	25 μM	Resveratrol negatively modulates prostate cancer cell growth
[90]	In vitro: HL-60 cells; Hepa LcLc7 cells	11, 18, 21, 27 μM	Resveratrol is a potential cancer chemopreventive agent
[91]	In vitro: MCF7 cells	10 μM	Resveratrol blocks the aryl hydrocarbon receptor and has beneficial effects against some types of tumors
[92]	In vitro: MCF7 cells	10, 50, 100, 150 μM	The anticancer effect of resveratrol is via BCL-2 and NFκB
[93]	In vitro: human lymphoblast cells	2.5, 5, 10, 20, 40 μM	The anticancer effect of resveratrol is via p53
[94]	In vitro: L1210-R2 murine lymphoblastic leukemia cells; K-562 human myelogenous leukemia cells; P-815 murine mastocytoma cells	0.1–1000 μM	The anticancer effect of resveratrol is via inhibiting ribonuclease reductase
[95]	In vitro: murine 3T6 fibroblast	0.3–30 μM	Reactive oxygen species and arachidonic acid might be involved in the control of 3T6 fibroblast growth by resveratrol
[98]	In vitro: human platelets	0.1, 1.0 and 10.0 μM	trans-Resveratrol is an inhibitor of store-operated Ca^2+ channels in human platelets. This accounts for the ability of trans-resveratrol to inhibit platelet aggregation induced by thrombin
[104]	In vitro: Saccharomyces cerevisiae	0–500 μM	Resveratrol stimulates Sir2, thus increasing DNA stability and extending lifespan