Table 3.
The results of resveratrol from clinical research.
| Population | Targeting Diseases | Study Type | Sample Size (Valid Data) | Resveratrol Dose and Duration | Main Findings: Resveratrol vs. Measurements/Risk Factors/Biomarkers |
Ref. |
|---|---|---|---|---|---|---|
| Healthy and slightly overweight | CVD—atherosclerosis | Randomized, parallel | N = 48 (male, 24; female, 24) | Resveratrol supplement, 500 mg/day (30 days) |
Favorable: Increased serum SIRT1 concentrations from 1.06 ± 0.71 to 5.75 ± 2.98 ng/mL, p < 0.0001 Null: Did not influence the various metabolic parameters (BW, BMI, WC, HR, BP, HDL, LDL, TG, BG, estradiol, estrone, insulin, hsCRP, and TAC) Unfavorable: Increased TC, ApoB, and HOMA-IR score |
[114] |
| Asymptomatic hypercholesterolemics (AHCs) and normohypercholemics (NC) | CVD—atherogenesis | Randomized, placebo-controlled | N = 40 (male, 21; female, 19) | Resveratrol supplement, 150 mg/day (4 weeks) |
Favorable: Increased TAC (mean value increased to 136.7% after consumption, p = 0.035) in healthy NC individuals and facilitated an increase in vitamin E (7.18 μmol/l, i.e., 35.72%) in AHC Null: No differences found in TC, TG, HDL, LDL, TAC (in AHC), and vitamin E (in NC) |
[113] |
| Overweight and slightly obese volunteers | CVD—endothelial function | Randomized, double-blind, placebo-controlled | N = 45 (male, 25; female, 20) | Trans-resveratrol supplement,150 mg/day (4 weeks) | Null: Did not improve endothelial function (FMD, arterial stiffness, and other endothelial activation markers), inflammation (IL-6 and TNF-α), glucose and lipid metabolism (BG, insulin, and serum TG) | [122] |
| 65 years or older with peripheral artery disease (PAD) | CVD—PAD | Randomized, double-blind, placebo-controlled | N = 66 (male, 45; female, 21) | Trans-resveratrol supplement,125 and 500 mg/day (6 months) |
Favorable: 125 mg/day improved the outcome of 6-min walk test results statistically significant (95% CI: −5.7 to 39.5) but not clinically meaningful Null: 500 mg/day showed no significant improvement |
[123] |
| Patients in primary cardiovascular disease prevention | CVD—atherogenesis | Triple-blind, randomized, placebo-controlled | N = 75 (male, 34; female, 41) | Resveratrol-enriched grape extract, 350 mg/day (6 months) |
Favorable: Decreased LDL-C (−4.5%, p = 0.04), ApoB (−9.8%, p = 0.014), oxidized LDL (−20%, p = 0.001), and oxidized LDL/ApoB (−12.5%, p = 0.000); increased ratio non-HDL-C/ApoB (8.5%, p = 0.046) Null: No clinically significant effects on hepatic, thyroid, and renal function (GGT, AST, ALP, bilirubin and albumin; TSH, T4; CPK, creatinine, and urate) |
[115] |
| Healthy aged men | CVD | Randomized, double-blind, placebo-controlled | N = 27 (male) | Trans-resveratrol supplement, 250 mg/day (8 weeks) |
Null: No effects on SIRT1 protein concentrations or cardiovascular parameters (BG, TC, and HDL), and VCAM-1 Unfavorable: Abolished the exercise training-induced improvement in maximal oxygen uptake, BP, and lipids (LDL, TC/HDL ratio, and TG) |
[58] |
| Women at increased breast cancer risk | Cancer—breast cancer | Randomized, double-blind, placebo-controlled | N = 39 (male) | Trans-resveratrol supplement, 10 or 100 mg/day (12 weeks) |
Favorable: Decreased the methylation of RASSF-1α (p = 0.047) Null: Did not significantly alter PGE2 |
[124] |
| Patients with type-2 diabetes | Type 2 diabetes | Randomized, double-blind, placebo-controlled | N = 192 (male, 126; female, 66) | Resveratrol supplement, 40 and 500 mg/day (6 months) |
Favorable: Prevented bone density loss (500 mg/d) (whole-body BMD (0.01 vs. −0.03 g/cm2, p = 0.001), whole-body BMC (4.04 vs. −58.8 g, p < 0.001), whole-body T-score (0.15 vs. −0.26), and serum phosphorus (0.07 vs. −0.01 μmol/L, p = 0.002)); decreased CRP (not significantly) Null: BW, BMI, WC, BP, FBG, HbA1c, insulin, HOMA-IR, C-peptide, FFAs, ALT, AST, GGT, uric acid, IL-6, and adiponectin Unfavorable: Slightly increased TC and TG (500 mg/d) |
[116] |
| Patients with diet-controlled type-2 diabetes | Type 2 diabetes | Randomized, double-blind, placebo-controlled | N = 14 (male) | Resveratrol capsules, 1000 mg/day (5 weeks) |
Favorable: Modestly decreased FBG and HbA1c Null: No significant effects on GLP-1 secretion, gastric emptying, glycemic control (HbA1c, BG), energy intake, and BW |
[121] |
| Obese men | Obesity | Randomized, placebo-controlled | N = 24 (male) | Trans-resveratrol tablets, 500 mg/day (4 weeks) |
Null: Did not improve insulin sensitivity, BP, BG, insulin, HOMA-IR, HbA1c, lipids (TC, HDL-C, LDL-C and TG), liver and skeletal muscle lipid content, or inflammatory biomarkers (IL-6, TNF-α, and MCP1) and some metabolic markers Unfavorable: Insignificantly deteriorated insulin sensitivity |
[120] |
| Overweight/obese with insulin-resistance subjects | Obesity | Randomized, double-blind, placebo-controlled | N = 108 (male, 54; female, 54) | Resveratrol supplement, 150 mg/day (12 weeks) | Null: Did not significantly impact liver fat content or cardiometabolic risk biomarkers (FBG, HbA1c, BP, TC, HDL, LDL, TG, AST, ALT, GGT, hsCRP, and IL-6) | [119] |
| Overweight/obese with NAFLD | Obesity—NAFLD | Randomized, placebo-controlled | N = 75 (male, 52; female, 23) | Resveratrol capsules, 600 mg/day (12 weeks) |
Favorable: Significantly reduced BW (95% CI: −1.61 to −0.38) and BMI (95% CI: −0.54 to −0.12) Null: Did not significantly change ALT, AST, and lipid profiles (TG, TC, LDL-C, HDL-C), hepatic steatosis grade (ALT and AST), serum glycemic parameters (FBG, insulin, and HbA1c), and SIRT1 levels |
[117] |
| Obese men | Obesity—bone health | Randomized, double-blind, placebo-controlled | N = 66 (male) | Trans-resveratrol tablets, 1000 or 150 mg/day, (16 weeks) |
Favorable: Dose-dependently benefited bone by stimulating formation or mineralization as significantly increased BAP (R = 0.471, p < 0.001), and BMD (BAP and lumbar spine volumetric BMD were positively correlated: R = 0.281, p = 0.027) | [16] |
| Individuals with mild/moderate Alzheimer disease (AD) | Aging—AD | Randomized, double-blind, placebo-controlled | N = 119 (male, 51; female, 68) | Resveratrol supplement, 500–2000 mg/day (52 weeks) |
Uncertain: Resveratrol and its major metabolites were detectable in plasma and CSF, suggesting CNS effects; CSF Aβ40 and plasma Aβ40 levels declined less than those in the placebo group; brain volume loss was more compared to placebo Null: No effects on plasma Aβ42, CSF Aβ42, CSF tau, CSF phospho-tau 181, hippocampal volume, entorhinal cortex thickness, MMSE, CDR, ADAS-cog, NPI, or glucose and insulin metabolism Unfavorable: The most common adverse events were nausea and diarrhea, but similar to placebo |
[118] |
| Elderly participants | Aging—memory | Randomized, double-blind, placebo-controlled | N = 53 (male, 25; female, 28) | Resveratrol pills, 200 mg/day, (26 weeks) |
Favorable: Non-significant trend for stable performance in a pattern recognition task Null: No significant changes in CVLT performance, HbA1c levels, hippocampus volume, microstructure, and functional connectivity Unfavorable: Increased serum cholesterol, weight, body fat, FBG, and inflammatory markers; decreased physical activity and neurotrophic factors Adverse events: Two dropouts (a sudden decrease in eyesight and a skin rash), and others (case no.): Diarrhea (n = 3), skin changes (n = 3), stomach aches (n = 1), dizziness (n = 1), improved mood changes (n = 1), loss of hair (n = 1) |
[15] |
Abbreviations used in the table: ADAS-cog, Alzheimer’s Disease Assessment Scale–cognitive; AHC, asymptomatic hypercholesterolemics; ALP, alkaline phosphatase; ALT, aminotransferase; ApoB, apolipoprotein B; AST, aminotransferase; Aβ40, amyloid β40; BAP, bone alkaline phosphatase; BG, blood glucose; BMC, bone mineral content; BMD, bone mineral density; BMI, body mass index; BP, blood pressure; BW, body weight; CDR, clinical dementia rating; CNS, central nervous system; CPK, creatine phosphokinase; CRP, C-reactive protein; CSF, cerebrospinal fluid; CVLT, California Verbal Learning Task; CVR, cerebrovascular responsiveness; FBG, fasting blood glucose; FFAs, free fatty acids; FMD, flow-mediated vasodilation; GGT, γ-glutamyl transferase; GLP-1, glucagon-like peptide 1; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; HOMA-IR, the homeostatic model assessment—insulin resistance; HR, heart rate; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin-6; LDL-C, low-density lipoprotein cholesterol; MCP1, monocyte chemoattractant protein 1; MMSE, mini-mental state examination; NAFLD, non-alcoholic fatty liver disease; NC, normohypercholemics; NPI, neuropsychiatric inventory; PAD, peripheral artery disease; PGE2, prostaglandin E2; SIRT1, sirtuin 1; T4, thyroxine; TAC, total antioxidant capacity; TC, total cholesterol; TG, triglycerides; TNF-α, tumor necrosis factor α; TSH, thyroid-stimulating hormone; VCAM-1, vascular cell adhesion molecule 1; WC, waist circumference; WHR, waist-hip ratio.