Table 1.

Outcome of clinical studies involving intake of resveratrol.

Type of the Study/Number of Probands	Clinical Outcome	References
Healthy volunteers (N = 20) tested before and after 15 days of controlled wine consumption (300 mL/day)	Increase in resveratrol concentration in plasma after wine consumption. Enhancement of platelet NO synthase (NOS) activity, decrease in phosphorylation of p38 MAPK and reduction in NADPH oxidase activity after treatment of platelets with resveratrol in vitro	[126]
Healthy volunteers (N = 22) who received orally placebo and two doses of resveratrol (250 and 500 mg) on separate days	Enhancement in cerebral blood-flow after resveratrol intake (cognitive functions stayed not affected)	[127]
Patients with mild-to-moderate Alzheimer’s disease (N = 119) randomized to placebo or resveratrol group and treated for 52 weeks (the latter group was receiving orally 500 mg of resveratrol once daily with dose escalation until a final dose of 1000 mg twice daily)	Presence of low nanomolar concentration of resveratrol in the cerebrospinal fluid of resveratrol- treated group; a 50% decrease of MMP-9 level and increase in activation of microglia/macrophages; reduced plasma levels of proinflammatory interleukin (IL)-1R4, IL-12p40, IL-12p70, and TNF; weight loss in resveratrol-treated group	[128]
Healthy obese men (N = 11) treated with placebo and subsequently with 150 mg/day resveratrol for 30 days	Significant reduction in sleeping- and resting metabolic rates due to resveratrol-treatment. Activation of AMPK, enhancement of SIRT1 and PGC-1α protein levels in muscle, and decrease in plasma glucose, triglycerides levels and inflammation markers	[129]
Pooled analysis of 21 clinical studies that included overweight and obese human	Resveratrol-treatment significantly decreased total cholesterol, systolic blood pressure and fasting glucose, effects more pronounced in individuals ingesting more than 300 mg of resveratrol per day	[130]
Meta-analysis of 28 randomized controlled trials	Significant reduction in body weight, BMI and waist circumference; effects of resveratrol most prominent in obese patients and in trials longer than three months	[131]
Meta-analysis of 36 randomized controlled trials	Significant reduction in body weight, BMI, fat mass and waist circumference; no significant effect of resveratrol intake on leptin and adiponectin levels	[132]
Meta-analysis of 17 randomized controlled trials	Intake of resveratrol did not significantly affect systolic, diastolic or mean blood pressure. However, significant blood pressure lowering effects were found in individuals treated with resveratrol daily at dosage ≥ 300 mg per day and in diabetic patients	[133]
Meta-analysis of 21 randomized clinical trials	Resveratrol could not significantly change total cholesterol, LDL and HDL cholesterol levels, but it might decrease blood triglycerides levels	[134]
Meta-analysis of 10 randomized clinical trials	No changes in C-reactive protein (CRP) blood levels. In addition, no alterations in total cholesterol, LDL cholesterol and triglycerides plasma levels upon resveratrol treatment	[135]
A randomized placebo-controlled clinical trial including middle-aged men (N = 74) with metabolic syndrome receiving daily 1000 mg, 150 mg of resveratrol, or placebo for 16 weeks	No lowering of CRP, interleukin 6, or soluble urokinase plasminogen activator receptor plasma levels. No change in analyzed inflammatory gene expression in adipose and muscle tissues. No effect on blood pressure. A striking increase in total cholesterol and LDL cholesterol plasma levels in resveratrol-treated compared to placebo-treated men	[136]
Meta-analysis of 15 randomized clinical trials (N = 658)	Resveratrol decreased serum CRP levels; no significant change in serum IL-6 and TNF-α levels	[137]
Meta-analysis of 17 randomized clinical trials (N = 736)	Significant reduction in CRP- and TNF-α levels; no significant change in IL-6 in serum upon resveratrol treatment	[138]
Type 2 diabetes mellitus and hypertensive patients consuming daily resveratrol’s enriched (8 mg) grape extract	Reduced expression of pro-inflammatory cytokines CCL3, IL-1β and TNF-α; modified pattern of inflammatory-related microRNAs in peripheral blood mononuclear cells due to resveratrol enriched grape extract consumption	[139]
Obese human subjects (N = 10) treated with resveratrol for 30 days	Decrease in postprandial glucagon levels due to resveratrol’s intake, no changes in fasting plasma glucagon levels	[140]
A randomized clinical trial including a three month treatment of type 2 diabetic patients (N = 62) with 250 mg per day of resveratrol or placebo	Reduction in systolic blood pressure and total cholesterol levels, no change in body weight and LDL and HDL cholesterol levels in comparison with placebo group	[141]
Type 2 diabetic patients taking resveratrol orally (1 gram per day for 45 days) in the presence of standard antidiabetic treatment (N = 34 resveratrol, N = 32 placebo)	Reduction in systolic blood pressure, fasting blood glucose and HbA1c levels and improvement in insulin resistance in the resveratrol group	[142]
Meta-analyses of six randomized controlled clinical trials of type 2 diabetes mellitus patients (N=104 resveratrol, N = 92 placebo)	Reduction in systolic blood pressure, HbA1c, and creatinine levels in the resveratrol group. No change in other clinical parameters (fasting glucose, insulin resistance, triglycerides, LDL and HDL cholesterol)	[143]
Meta-analysis of 10 randomized clinical trials including patients with type 2 diabetes mellitus (N = 363)	Prolonged treatment of diabetic patients (≥ 6 months) with resveratrol reduced triglyceride levels	[144]
Meta-analysis of nine randomized clinical trials including patients with type 2 diabetes mellitus (N = 283)	Significant improvement of the fasting plasma glucose and insulin levels (especially at a dose of resveratrol ≥ 100 mg per day) as well as reduction of blood pressure. No significant changes in HbA1c, LDL and HDL cholesterol	[145]
Meta-analysis of six studies involving patients treated with resveratrol (N = 247)	No significant reduction in systolic blood pressure in the whole resveratrol group. Reduction in systolic blood pressure in a subgroup treated at a high dose of resveratrol (≥ 150 mg per day). No changes in diastolic blood pressure	[146]
Healthy physically inactive 65 years old men subjected to eight week exercise training and additionally taking 250 mg per day of trans-resveratrol (N = 14) or placebo (N = 13)	In the trained placebo group: a ~45% higher increase in maximal oxygen uptake when compared to the trained resveratrol group. Reduction in the mean arterial pressure detected only in the trained placebo group. Lower interstitial levels of vasodilator prostacyclin and higher levels of muscle thromboxane synthase in the trained resveratrol group than in trained placebo group. Reduction in LDL, total cholesterol/HDL ratio and triglyceride concentrations in the blood detected only in the trained placebo group (not in the trained resveratrol group)	[147]
Healthy physically inactive 65 years old men subjected to eight week intense exercise training and additionally taking 250 mg per day of trans-resveratrol (N = 14) or placebo (N = 13). Non trained group received 250 mg per day of trans-resveratrol (N = 9) or placebo (N = 7)	In the trained placebo group: a ~20% increase in the ratio of capillary to muscle fibers as well as increase in levels of VEGF, VEGF receptor-2, and tissue inhibitor of matrix metalloproteinase (TIMP-1). In the trained resveratrol group: no increase in the ratio of capillary to muscle fibers as well as no increase in VEGF levels	[148]
60 sedentary persons aged > 65 years will be exercising three times weekly during three months. Participants are being/will be assigned to three groups: consuming 1) placebo, 2) 250 mg/day resveratrol, or 3) 1000 mg/day resveratrol.	This running clinical trial should provide an important information on the skeletal muscle mitochondrial function induced by a combined use of resveratrol and exercise in older sedentary persons	[149]