Cardioprotective Effects of Resveratrol in the Mediterranean Diet: A Short Narrative Review
Abstract
:1. Introduction
2. Methodology
3. RSV Effects on Atherosclerosis Progression and Lipid Metabolism
3.1. RSV Effects on Lipid Metabolism and the Progression of Atherosclerosis: Studies on Animal Models
3.2. RSV Effects on Lipid Metabolism and Progression of Atherosclerosis on Humans: RCTs and Prospective Cohort Studies
3.3. RSV Effects on Atherosclerosis Progression by Regulating the TMAO Synthesis via the Remodeling of Gut Microbiota
4. Concluding Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Author, Year of Publication | Study Design | Study Duration | Sample Size | RSV Supplementation, Antioxidant Activity, Lipid Profile, and Atherosclerotic Risk |
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Maura Floreani, 2003 [39] | Case control | Follow-up: 16 days | 13 Dunkin–Hartley male guinea pigs | Effect of RSV on Vmax and Km of DT-diaphorase from guinea pig cardiac tissue: RSV treatment vs. controls Vmax: 75.47 ± 3.87 vs. 57.08 ± 9.02, p < 0.05 Km: 0.23 ± 0.03 vs. 0.25 ± 0.02, p = NS Effect of RSV on the antioxidant enzyme activities of cardiac tissue: RSV treatment vs. controls Gpx: 46.49 ± 2.61 vs. 45.10 ± 1.60, p = NS GR: 18.21 ± 2.97 vs. 16.62 ± 1.93, p = NS CAT: 32.20 ± 2.39 vs. 25.14 ± 3.85, p < 0.001 Cu/Zn SOD: 32.69 ± 3.86 vs. 27.75 ± 4.15, p = NS Mn–SOD: 31.87 ± 3.55 vs. 32.70 ± 1.86, p = NS Menadione-induced ROS generation by cardiac tissue from the control and resveratrol-treated guinea pigs. RSV-treated guinea pigs: significantly lower ROS production with respect to controls (p < 0.001, data not shown) Positive inotropic effect induced by increasing the concentrations of menadione in the left atria isolated from control and RSV-treated guinea pigs. RSV-treated guinea pigs: no inotropic action of menadione at 5 M concentration; effect was 54% lower than that observed in controls (p < 0.001, data not shown) |
Gyeong-Min Do, 2008 [40] | Case control | 20 weeks | 4-week-old male apo/E-deficient mice | Effects of resveratrol supplementation on the plasma levels (mmol/L) of the total cholesterol at 20 weeks (p < 0.05): Control diet: 9.60 ± 0.50 0.02% clofibrate-supplemented diet: 7.73 ± 0.36 0.02% resveratrol-supplemented diet: 6.33 ± 0.41 0.06% resveratrol-supplemented diet: 7.78 ± 0.51 Effects of resveratrol supplementation on the plasma levels (mmol/L) of Triglycerides at 20 weeks (p < 0.05): Control diet: 1.51 ± 0.17 0.02% clofibrate-supplemented diet: 1.10 ± 0.11 0.02% resveratrol-supplemented diet: 1.00 ± 0.11 0.06% resveratrol-supplemented diet: 1.42 ± 0.16 Effects of resveratrol supplementation on the plasma levels (mmol/L) of the LDL at 20 weeks (p < 0.05): Control diet: 8.1 ± 0.5 0.02% clofibrate-supplemented diet: 6.1 ± 0.4 0.02% resveratrol-supplemented diet: 4.8 ± 0.3 0.06% resveratrol-supplemented diet: 5.9 ± 0.5 Effects of resveratrol supplementation on the plasma levels (mmol/L) of the HDL at 20 weeks (p < 0.05): Control diet: 1.07 ± 0.10 0.02% clofibrate-supplemented diet: 1.41 ± 0.12 0.02% resveratrol-supplemented diet: 1.36 ± 0.11 0.06% resveratrol-supplemented diet: 1.87 ± 0.12 Effects of resveratrol supplementation on the plasma levels of the HDL/cholesterol (%) at 20 weeks (p < 0.05): Control diet: 11.7 ± 0.9 0.02% clofibrate-supplemented diet: 18.4 ± 1.5 0.02% resveratrol-supplemented diet: 20.9 ± 1.7 0.06% resveratrol-supplemented diet: 22.3 ± 1.5 Effects of resveratrol supplementation on the plasma levels of the atherogenic index (ratio) at 20 weeks (p < 0.05): Control diet: 7.0 ± 0.5 0.02% clofibrate-supplemented diet: 4.6 ± 0.4 0.02% resveratrol-supplemented diet: 3.9 ± 0.4 0.06% resveratrol-supplemented diet: 3.8 ± 0.3 Effects of resveratrol supplementation on the hepatic HMG-CoA reductase activity (pmol/min/mg protein) at 20 weeks (p < 0.05): Control diet: 282.15 ± 15.62 0.02% clofibrate-supplemented diet: 148.20 ± 31.38 0.02% resveratrol-supplemented diet: 113.73 ± 6.20 0.06% resveratrol-supplemented diet: 152.97 ± 11.45 Effects of resveratrol supplementation on the hepatic ACAT activity (pmol/min/mg protein) at 20 weeks: Control diet: 49.99 ± 4.17 0.02% clofibrate-supplemented diet: 52.81 ± 2.86 0.02% resveratrol-supplemented diet: 55.92 ± 2.78 0.06% resveratrol-supplemented diet: 59.77 ± 3.43 |
Jimmy F.P. Berbée, 2013 [41] | Case control | Run-in period: 5 weeks; Drug intervention period: 14 weeks | 10–12-week-old female APOE*3- Leiden.CETP (E3L.CETP) transgenic mice | Total atherosclerotic lesion area: Resveratrol vs. control: −52% (p < 0.01) Atorvastatin vs. control: −40% (p < 0.05) Resveratrol plus atorvastatin vs. control: −47% (p < 0.01) Collagen/macrophage ratio as marker of plaque stability: Resveratrol vs. control: +108% (p < 0.05) Atorvastatin vs. control: +124% (p < 0.01) Resveratrol plus atorvastatin vs. control: +154% (p < 0.001) Reduction in the plasma VLDL levels: Resveratrol vs. control: −19% (p = 0.08) Atorvastatin vs. control: −22% (p < 0.05) Resveratrol plus atorvastatin vs. control: −21% (p < 0.05) |
Liyu Zhou, 2020 [42] | Case control | 20 weeks | 7-week-old male apo/E-deficient mice | HFD + LPS vs. control after 20 weeks (data not shown): TC, LDL-C, non-HDL-C serum levels: increased (p < 0.001). TG serum levels: increased (p < 0.05) HDL-C serum levels decreased (p < 0.05) Atherosclerotic plaque area ratio: increased (p < 0.01) CD4+ T cells in PBMC: increased (p < 0.01) Simvastatin + LPS vs. HFD + LPS after 20 weeks (data not shown): TC, LDL-C, serum levels: decreased (p < 0.01) TG, non-HDL-C serum levels: decreased (p < 0.05) HDL-C serum levels increased (p < 0.05) Atherosclerotic plaque area ratio: decreased (p < 0.05) CD4+ T cells in PBMC: decreased (p < 0.05) Resveratrol + LPS vs. HFD + LPS after 20 weeks (data not shown): TC, LDL-C, serum levels: decreased (p < 0.01) TG, non-HDL-C serum levels: decreased (p < 0.05) HDL-C serum levels increased (p < 0.05) Atherosclerotic plaque area ratio: decreased (p < 0.05) CD4+ T cells in PBMC: decreased (p < 0.05) |
Lei Xu, 2020 [45] | Case control | 3 months | 24 three-month-old New Zealand male white rabbits | Serum levels (mmol/L) of the total cholesterol at 3 months in RFG vs. FDG 11.84 ± 2.78 vs. 30.32 ± 5.74, p < 0.001 Serum levels (mmol/L) of the HDL at 3 months in RFG vs. FDG 1.58 ± 0.35 vs. 3.28 ± 1.61, p < 0.001 Serum levels (mmol/L) of the LDL at 3 months in RFG vs. FDG 6.23 ± 1.53 vs. 16.45 ± 3.16, p < 0.001 Serum levels (mmol/L) of Lp-PLA2 at 3 months in RFG vs. FDG 953.20 ± 96.66 vs. 1928.88 ± 385.78, p < 0.001 Serum levels (mmol/L) of the TG at 3 months in RFG vs. FDG 0.76 ± 0.28 vs. 0.90 ± 0.42, p = 0.232 Measurements (μm) of the aortic arch thickness observed under a microscope at 3 months in RFG vs. FDG Intima: 52.44 ± 14.94 vs. 124.76 ± 6.83, p < 0.001 Intima/media ratio: 0.30 ± 0.09 vs. 0.64 ± 0.04, p < 0.001 Smooth muscle layer: 173.48 ± 4.05 vs. 194.16 ± 10.2, p = 0.65 |
Author, Year of Publication | Study Design | Duration of Study | Sample Size | RSV Intake, Atherosclerosis, and Inflammatory Biomarkers |
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Amirhossein Sahebkar, 2015 [47] | Meta-analysis from 10 randomized controlled trials | Treatment duration range: 60 days to 12 months | 600 subjects: 344 in RSV group and 256 controls | Effect of RSV supplementation on the plasma concentration of the CRP and selected predictors of CVD risk. CRP (mg/L): WMD = −0.144; 95% CI = −0.968–0.680; p = 0.731 TC (mg/dL): WMD = 1.49; 95% CI = −14.96–17.93; p = 0.859 LDL (mg/dL): WMD = −0.31; 95% CI = −9.57–8.95; p = 0.948 HDL (mg/dL): WMD = −4.18; 95% CI = −6.54–1.82; p = 0.001 TG (mg/dL): WMD = 2.67; 95% CI = −28.34–33.67; p = 0.866 Glucose (mg/dL): WMD = 1.28; 95% CI = −5.28–7.84; p = 0.703 SBP (mm Hg): WMD = 0.82; 95% CI = −8.86–10.50; p = 0.868 DBP (mm Hg): WMD = 1.72; 95% CI = −6.29–9.73; p = 0.674 |
João Tomé-Carneiro, 2013 [48] | Triple-blind, randomized, placebo-controlled study | Follow-up: 1 year | 75 stable-CAD patients | Serum levels of the inflammatory markers after 12 months vs. baseline in placebo group: Interleukin-10 (pg/mL): 18.3 ± 12.2 vs. 19.6 ± 12.4; p = 0.03 Adiponectin (μg/mL): 9.6 ± 4.4 vs. 11.0 ± 5.8; p = 0.01 PAI–1 (ng/mL): 25.9 ± 15.0 vs. 18.7 ± 14.4; p < 0.001 hs-CRP (mg/L): 4.0 ± 1.8 vs. 3.3 ± 2.2; p = 0.66 Serum levels of the inflammatory markers after 12 months vs. baseline in RSV group: Interleukin-10 (pg/mL): 23.3 ± 16.9 vs. 23.05 ± 16.7; p = 0.45 Adiponectin (μg/mL): 13.6 ± 5.2 vs. 12.4 ± 5.6; p = 0.01 PAI–1 (ng/mL): 14.0 ± 7.0 vs. 17.2 ± 10.3; p = 0.05 hs-CRP (mg/L): 3.2 ± 2.1 vs. 3.9 ± 4.1; p = 0.17 Activation status of the inflammation-related transcription factors genes in the PBMCs in the RSV group after 12 months: KLF2: Activated Ap-1: Inhibited JUN: Inhibited ATF-2: Inhibited CREBBP: Inhibited |
G.C. Batista-Jorge, 2020 [49] | Prospective case–control study | Follow-up: 12 weeks | 25 subjects aged 30 to 60 years old | Anthropometric and biochemical parameters of the subjects treated with the physical activity program + diet + placebo before and after the 12-weeks intervention Bodyweight (kg): 102.7 ± 12.9 vs. 95.9 ± 12.1, p = 0.006 BMI (kg/m2): 35.0 ± 3.0 vs. 32.8 ± 3.6, p = 0.003 WC (cm): 105.0 ± 9.4 vs. 96.3 ± 8.6, p = 0.001 TC (mg/dL): 198.4 ± 33.1 vs. 193.7 ± 44.1, p = 0.568 LDL (mg/dL): 123.3 ± 38.3 vs. 117.7 ± 42.0, p = 0.483 HDL (mg/dL): 47.2 ± 6.6 vs. 50.6 ± 5.8, p = 0.253 VLDL (mg/dL): 24.1 ± 6.7 vs. 27.4 ± 9.5, p = 0.209 Triglycerides (mg/dL): 120.4 ± 33.1 vs. 137.1 ± 47.4, p = 0.203 Insulin (IU): 56.7 ± 91.7 vs. 13.9 ± 6.1, p = 0.194 Glycemia (mg/dL): 87.1 ± 9.1 vs. 89.4 ± 5.7, p = 0.363 HBA1c (%): 5.5 ± 0.7 vs. 6.2 ± 0.4, p = 0.005 Leptin (mg/dL): 36.3 ± 24.2 vs. 22.7 ± 16.2, p = 0.031 Uric acid (mg/dL): 10.6 ± 15.9 vs. 4.8 ± 0.7, p = 0.345 ALT (mg/dL): 30.2 ± 14.4 vs. 30.6 ± 14.5, p = 0.948 AST (mg/dL): 33.3 ± 19.4 vs. 35.3 ± 34.1, p = 0.874 Fibrinogen (mg/dL): 97.0 ± 136.9 vs. 5.1 ± 5.7, p = 0.535 Urea (mg/dL): 30.0 ± 12.2 vs. 30.3 ± 6.5, p = 0.933 Creatinine (mg/dL): 0.9 ± 0.3 vs. 1.6 ± 2.3, p = 0.344 Albumin (mg/dL): 4.5 ± 0.4 vs. 7.8 ± 11.3, p = 0.371 Anthropometric and biochemical parameters of the subjects treated with the physical activity program + diet + RSV (250 mg/day) before and after the 12-week intervention Bodyweight (kg): 105.4 ± 13.0 vs. 98.1 ± 11.7, p = 0.000 BMI (kg/m2): 36.1 ± 4.5 vs. 33.6 ± 3.5, p = 0.000 WC (cm): 109.6 ± 8.3 vs. 102.2 ± 7.8, p = 0.000 TC (mg/dL): 221.0 ± 48.6 vs. 192.1 ± 43.9, p = 0.031 LDL (mg/dL): 127.8 ± 33.3 vs. 108.1 ± 38.1, p = 0.241 HDL (mg/dL): 42.7 ± 7.6 vs. 48.1 ± 6.2, p = 0.026 VLDL (mg/dL): 49.3 ± 25.6 vs. 39.1 ± 14.3, p = 0.025 Triglycerides (mg/dL): 294.9 ± 191.8 vs. 189.9 ± 73.2, p = 0.094 Insulin (IU): 46.6 ± 69.9 vs. 15.6 ± 4.1, p = 0.154 Glycemia (mg/dL): 138.8 ± 66.3 vs. 117.1 ± 45.9, p = 0.116 HBA1c (%): 11.3 ± 15.0 vs. 11.7 ± 15.6, p = 0.343 Leptin (mg/dL): 35.8 ± 27.9 vs. 28.0 ± 25.5, p = 0.014 Uric acid (mg/dL): 10.1 ± 14.8 vs. 5.4 ± 1.6, p = 0.302 ALT (mg/dL): 34.9 ± 12.4 vs. 29.3 ± 11.0, p = 0.099 AST (mg/dL): 46.1 ± 27.4 vs. 37.7 ± 23.5, p = 0.440 Fibrinogen (mg/dL): 82.1 ± 151.9 vs. 3.7 ± 1.2 p = 0.199 Urea (mg/dL): 35.9 ± 8.8 vs. 28.9 ± 6.3, p = 0.046 Creatinine (mg/dL): 1.0 ± 0.1 vs. 0.9 ± 0.2, p = 0.021 Albumin (mg/dL): 4.8 ± 0.6 vs. 4.0 ± 0.4, p = 0.000 |
Henry Montero Salazar, 2022 [50] | Prospective cohort study | Mean follow-up: 10 years | 2318 subjects from cohort of AWHS | Risk of presence of at least one plaque in the femoralarteries according to a higher dietary polyphenol intake: Stilbenes: OR = 0.62; 95%CI = 0.46–0.83; p trend = 0.009 Flavonoids: OR = 0.62; 95%CI = 0.48–0.80; p trend < 0.001 Risk of presence of at least one plaque in the carotid arteries according to a higher dietary polyphenols intake: Stilbenes: OR = 0.89; 95%CI = 0.67–1.18; P trend = 0.536 Flavonoids: OR = 0.80; 95%CI = 0.62–1.02; P trend = 0.094 Risk of presence of at least one plaque in the femoral arteries according to each 1 mg/day intake of stilbenes or each 100 mg/daily intake of flavonoids: Stilbenes: OR = 0.97; 95%CI = 0.95–0.99 Flavonoids: OR = 0.94; 95%CI = 0.90–0.98 Risk of presence of a positive coronary calcium Agatston score (CACS > 0) according to a higher dietary polyphenol intake: Stilbenes: OR = 0.75; 95%CI = 0.55–1.03; P trend = 0.131 Flavonoids: OR = 0.88; 95%CI = 0.67–1.15; P trend = 0.346 |
Tamires Miranda Santana, 2022 [55] | Review from 27 randomized clinical trials | Treatment duration range: 28–360 days | Average sample size: 26 subjects | Changes in atherosclerosis biomarkers according to Cluster II (RSV dose: 454.14 ± 129 mg): SBP (%): −6.76 ± 1.06, p < 0.001 DBP (%):−4.51 ± 1.77, p = 0.026 TC (%): −6.04 ± 1.51, p < 0.001 TG (%): −10.13 ± 5.01, p < 0.001 LDL (%): −4.81 ± 3.40, p = 0.036 HDL (%): −1.16 ± 1.42, p < 0.001 Changes in atherosclerosis biomarkers according to Cluster III (RSV dose: 263.75 ± 88.07 mg): SBP (%): −0.95 ± 1.19, p < 0.001 DBP (%): −1.39 ± 0.87, p = 0.026 TC (%): −3.28 ± 1.39, p < 0.001 TG (%): −3.51 ± 2.12, p < 0.001 LDL (%): −4.35 ± 2.38, p = 0.036 HDL (%): 6.23 ± 1.35, p < 0.001 |
Qian Zhou, 2022 [56] | Meta-analysis and systematic review from 25 randomized controlled trials | Treatment duration range: 4–26 weeks | 1171 subjects: 578 in placebo group and 593 in RSV intervention group | Effect of RSV supplementation on the lipid, glucose, and anthropometric parameters (SMD). Best duration of intervention: more than 17 weeks; best intake of RSV: 200–500 mg/day) TC: SMD = –0.15; 95% CI = –0.01–−0.3; p = 0.003 LDL-C: SMD = –0.42; 95% CI = –0.27–−0.57; p < 0.001 HDL-C: SMD = −0.16 95% CI = –0.02–−0.31; p = 0.03 HbA1c: SMD = –0.48, 95% CI = –0.2–−0.69; p < 0.001 WC: SMD = –0.36; 95% CI = –0.14–−0.59; p = 0.002 TG: SMD = 0.06; 95%CI = –0.12–0.23; p = 0.53 Body weight: SMD = 0.12; 95%CI = –0.05–0.28; p = 0.18 BMI: SMD = 0.02; 95%CI = –0.13–0.17; p = 0.83 HOMA index: SMD = 0.14; 95%CI = 0.04–0.31; p = 0.13 Insulin: SMD = 0.1; 95%CI = –0.06–0.25; p = 0.42 Leptin: SMD = 0.11; 95%CI = –0.13–0.36; p = 0.38 Fasting glucose: SMD = –0.10; 95%CI = –0.24–0.03; p = 0.14 Fat percentage: SMD = –0.26; 95%CI = –0.54–0.01; p = 0.06 Adiponectin: SMD = 0.02; 95%CI = –0.22–0.25; p = 0.89 |
Nazanin Mohammadipoor, 2022 [57] | Meta-analysis and systematic review from 17 randomized controlled trials | Treatment duration: 90 min–24 weeks for evaluating FMD; 4–54 weeks for evaluating fibrinogen, PAI-1, ICAM-1, VCAM-1 | Effect of RSV supplementation on FMD (%), ICAM-1, VCAM-1, fibrinogen, PAI-1 (WMD). FMD in cross-over studies: WMD = 1.59%; 95% CI: 1.05–2.13, p < 0.001 FMD at dosages <100 mg: WMD = 1.69%; 95% CI:1.30–2.08, p < 0.001 FMD on acute intervention: WMD = 2.28%; 95% CI: 1.80–2.76, p < 0.001 FMD on patients with CVD: WMD = 2.60%; 95% CI: 1.95–3.26, p < 0.001 ICAM-1: WMD = −7.09 ng/mL, 95% CI: −7.45–−6.73, p < 0.001 VCAM-1: WMD = −15.04 ng/mL, 95% CI: −37.52–−7.45, p = 0.19 Fibrinogen: WMD = 0.25 g/L, 95% CI: −0.36–0.86, p = 0.42 PAI-1: WMD = −0.94 ng/mL, 95% CI: −3.51–1.62, p = 0.47 |
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Capurso, C.; Bellanti, F.; Lo Buglio, A.; Vendemiale, G. Cardioprotective Effects of Resveratrol in the Mediterranean Diet: A Short Narrative Review. Dietetics 2023, 2, 174-190. https://doi.org/10.3390/dietetics2020014
Capurso C, Bellanti F, Lo Buglio A, Vendemiale G. Cardioprotective Effects of Resveratrol in the Mediterranean Diet: A Short Narrative Review. Dietetics. 2023; 2(2):174-190. https://doi.org/10.3390/dietetics2020014
Chicago/Turabian StyleCapurso, Cristiano, Francesco Bellanti, Aurelio Lo Buglio, and Gianluigi Vendemiale. 2023. "Cardioprotective Effects of Resveratrol in the Mediterranean Diet: A Short Narrative Review" Dietetics 2, no. 2: 174-190. https://doi.org/10.3390/dietetics2020014
APA StyleCapurso, C., Bellanti, F., Lo Buglio, A., & Vendemiale, G. (2023). Cardioprotective Effects of Resveratrol in the Mediterranean Diet: A Short Narrative Review. Dietetics, 2(2), 174-190. https://doi.org/10.3390/dietetics2020014