PMID 24819981 Resveratrol levels and all-cause mortality in older community-dwelling adults Prospective cohort study (InCHIANTI) · JAMA Intern Med, 2014 783 adults aged 65+, 9-year follow-up - dietary resveratrol (urinary metabolites) levels were not associated with mortality, inflammation, cardiovascular disease, or cancer. Directly rebuts the 'red wine longevity' belief.
Key summary
A prospective cohort study (InCHIANTI) in 783 community-dwelling adults aged 65+ in the Chianti region of Italy, measuring 24-hour urinary resveratrol metabolites and following them for 9 years (1998-2009). The primary endpoint was all-cause mortality. Over follow-up, 268 (34.3%) died, but the proportion who died across quartiles of urinary resveratrol metabolites was 34.4%, 31.6%, 33.5%, and 37.4%, with no statistical difference (P=0.67), and the mortality hazard ratio for the lowest versus highest quartile was 0.80, not significant. Resveratrol levels were also unrelated to inflammatory markers such as CRP, IL-6, and TNF, and to cardiovascular disease and cancer. The authors concluded that resveratrol levels achieved with a Western diet did not substantially influence health status or mortality risk. It is a landmark study that rebuts, with human data, the central premise of 'red wine, anti-aging, and longevity' marketing.
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IMPORTANCE: Resveratrol, a polyphenol found in grapes, red wine, chocolate, and certain berries and roots, is considered to have antioxidant, anti-inflammatory, and anticancer effects in humans and is related to longevity in some lower organisms. OBJECTIVE: To determine whether resveratrol levels achieved with diet are associated with inflammation, cancer, cardiovascular disease, and mortality in humans. DESIGN: Prospective cohort study, the Invecchiare in Chianti (InCHIANTI) Study ("Aging in the Chianti Region"), 1998 to 2009 conducted in 2 villages in the Chianti area in a population-based sample of 783 community-dwelling men and women 65 years or older. EXPOSURES: Twenty-four-hour urinary resveratrol metabolites. MAIN OUTCOMES AND MEASURES: Primary outcome measure was all-cause mortality. Secondary outcomes were markers of inflammation (serum C-reactive protein [CRP], interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]) and prevalent and incident cancer and cardiovascular disease. RESULTS: Mean (95% CI) log total urinary resveratrol metabolite concentrations were 7.08 (6.69-7.48) nmol/g of creatinine. During 9 years of follow-up, 268 (34.3%) of the participants died. From the lowest to the highest quartile of baseline total urinary resveratrol metabolites, the proportion of participants who died from all causes was 34.4%, 31.6%, 33.5%, and 37.4%, respectively (P = .67). Participants in the lowest quartile had a hazards ratio for mortality of 0.80 (95% CI, 0.54-1.17) compared with those in the highest quartile of total urinary resveratrol in a multivariable Cox proportional hazards model that adjusted for potential confounders. Resveratrol levels were not significantly associated with serum CRP, IL-6, IL-1β, TNF, prevalent or incident cardiovascular disease, or cancer. CONCLUSIONS AND RELEVANCE: In older community-dwelling adults, total urinary resveratrol metabolite concentration was not associated with inflammatory markers, cardiovascular disease, or cancer or predictive of all-cause mortality. Resveratrol levels achieved with a Western diet did not have a substantial influence on health status and mortality risk of the population in this study. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 15333514 High absorption but very low bioavailability of oral resveratrol in humans Pharmacokinetic human study · Drug Metab Dispos, 2004 6-person pharmacokinetics - oral resveratrol is over 70% absorbed but only trace intact drug (<5 ng/mL) reaches blood. Rapid conjugation makes systemic bioavailabilityThe fraction of an ingested substance that actually reaches the blood and tissues to act. very low.
Key summary
A classic pharmacokinetic study giving 14C-labeled resveratrol orally and intravenously to six healthy volunteers to measure absorption, metabolism, and bioavailabilityThe fraction of an ingested substance that actually reaches the blood and tissues to act.. Absorption of a dietary-relevant 25-mg oral dose was high at at least 70%, with a peak plasma resveratrol-plus-metabolite level of 491 ng/mL and a half-life of about 9.2 hours. However, only trace amounts of intact (unchanged) resveratrol (<5 ng/mL) were detectable in blood. Extremely rapid sulfate and glucuronide conjugation in the intestine and liver was the rate-limiting step for bioavailability. The authors noted that although systemic bioavailability is very low, accumulation in aerodigestive epithelial cells or active metabolites might still produce some effects. Contrary to the assumption that 'what you swallow acts in the body,' it shows a large gap between the dose taken and the amount that actually reaches circulation.
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The dietary polyphenol resveratrol has been shown to have chemopreventive activity against cardiovascular disease and a variety of cancers in model systems, but it is not clear whether the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans. In this study, we examined the absorption, bioavailability, and metabolism of 14C-resveratrol after oral and i.v. doses in six human volunteers. The absorption of a dietary relevant 25-mg oral dose was at least 70%, with peak plasma levels of resveratrol and metabolites of 491 +/- 90 ng/ml (about 2 microM) and a plasma half-life of 9.2 +/- 0.6 h. However, only trace amounts of unchanged resveratrol (<5 ng/ml) could be detected in plasma. Most of the oral dose was recovered in urine, and liquid chromatography/mass spectrometry analysis identified three metabolic pathways, i.e., sulfate and glucuronic acid conjugation of the phenolic groups and, interestingly, hydrogenation of the aliphatic double bond, the latter likely produced by the intestinal microflora. Extremely rapid sulfate conjugation by the intestine/liver appears to be the rate-limiting step in resveratrol's bioavailability. Although the systemic bioavailability of resveratrol is very low, accumulation of resveratrol in epithelial cells along the aerodigestive tract and potentially active resveratrol metabolites may still produce cancer-preventive and other effects. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 33480264 Resveratrol supplementation and type 2 diabetes: a systematic review and meta-analysis Systematic review and meta-analysis · Crit Rev Food Sci Nutr, 2022 30 studies - resveratrol significantly lowered insulin resistanceA state in which cells respond poorly to insulin, so blood glucose does not fall as it should. (SMD -0.34) and HbA1cGlycated hemoglobin, a blood marker reflecting average glucose over the past 2-3 months; used to gauge diabetes control. (-0.64); fasting glucose fell significantly only in people with diabetes (-0.85). High heterogeneity (I2 70-90%).
Key summary
A systematic review and meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of resveratrol's effect on diabetes-related markers (fasting glucose, insulin resistanceA state in which cells respond poorly to insulin, so blood glucose does not fall as it should., HbA1cGlycated hemoglobin, a blood marker reflecting average glucose over the past 2-3 months; used to gauge diabetes control.). Excluding observational and non-randomized trials, it reviewed 30 experimental studies, about 60% of which reported a significant effect on at least one marker. In meta-analysis, insulin resistance (standardized mean difference -0.34) and HbA1c (-0.64) fell significantly, while fasting glucose fell significantly only in people who had diabetes (-0.85). However, heterogeneity was very high at I2 70-90%, so results varied widely. The authors summarized that resveratrol has protective effects on diabetes parameters, but this must be read alongside the effect size and the consistency of the findings.
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This study aimed to review the literature on studies that evaluated resveratrol's effects supplementation on parameters of diabetes in humans. We conducted an online search in the following databases: Pubmed, Lilacs, Scielo, Scopus, Web of Science, Embase, and Cochrane. It included experimental studies that investigated the effects of resveratrol supplementation for diabetes treatment or prevention and its relationship with fasting blood glucose, insulin resistance, and glycated hemoglobin. Observational, non-human studies and non-randomized clinical trials were excluded. We conducted a meta-analysis to evaluate the effects of resveratrol supplementation on fasting blood glucose, insulin resistance, and glycated hemoglobin. Thirty studies were included in the review. Almost 60% demonstrated at least one significant effect of the resveratrol supplementation related to diabetes. In the meta-analysis, there was a significant effect on the reduction of insulin resistance [SMD: -0.34; CI 95%: -0.64, -0.04; p = 0.01; I2 = 70%] and glycated hemoglobin [SMD: -0.64; CI 95%: -1.22, -0.07; p = 0.01; I2 = 90%]. For fasting blood glucose, the results were significant only for individuals with diabetes [SMD: -0.85; CI 95%: -1.49, -0.21; p = 0.01; I2 = 90%]. This systematic review with meta-analysis demonstrated that resveratrol supplementation has protective effects on diabetes parameters. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 35685602 Effects of Resveratrol on Metabolic Indicators in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis Systematic review and meta-analysis · Int J Clin Pract, 2022 19 studies, 1,151 patients (diabetes) - high dose (1,000 mg/day+) lowered fasting glucose by 18.76 mg/dL; systolic and diastolic BP also fell. But waist circumference, triglycerideA type of fat in the blood; high levels raise cardiovascular risk.s, and HDL unchanged.
Key summary
A recent meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of resveratrol's metabolic effects in people with type 2 diabetes, pooling 19 randomized controlled trialA high-reliability trial randomly assigning participants to compare effects (RCT).s (1,151 patients; 584 resveratrol, 567 placeboAn inert dummy treatment used as the comparison baseline.). High doses (1,000 mg/day or more) lowered fasting glucose by an average of 18.76 mg/dL, and systolic (-7.97 mmHg) and diastolic (-3.55 mmHg) blood pressure were also lower than placebo. By contrast, waist circumference, triglycerideA type of fat in the blood; high levels raise cardiovascular risk.s, and HDL cholesterol did not differ from placebo. The authors concluded that resveratrol can reduce blood pressure in diabetic patients and that high doses can reduce fasting glucose. The conditions for interpretation are that the population is limited to diabetic patients and the benefit appears mainly at high doses.
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BACKGROUND AND AIMS: Previous studies on the effects of resveratrol on metabolic indicators reported contradictory findings, and these indicators have not been frequently studied in patients with type 2 diabetes. In this study, we aimed to examine the effects of resveratrol on metabolic indicators in a specific group of people with type 2 diabetes using the most recent literature. METHODS: We used RevMan 5.4 and Stata 14.0 software to identify randomized controlled studies on the impact of resveratrol on metabolic indicators in patients with type 2 diabetes using relevant search terms and keywords such as "resveratrol" and "type 2 diabetes" in the China National Knowledge Infrastructure, PubMed, Cochrane, and Embase. Data were expressed as the weighted mean difference (WMD) and 95% confidence interval (CI). RESULTS: This meta-analysis included 19 studies involving 1151 patients with type 2 diabetes, including 584 patients treated with resveratrol and 567 patients who received placebo. Compared with the control data, large doses of resveratrol (≥1000 mg) reduced fasting blood glucose levels (WMD: -18.76 mg/dL, 95% CI: -23.43, -14.09; P < 0.00001). Additionally, resveratrol reduced systolic blood pressure (WMD: -7.97 mmHg, 95% CI: -10.63, -5.31; P < 0.00001) and diastolic blood pressure (WMD: -3.55 mmHg, 95% CI: -5.18, -1.93; P < 0.00001) in patients with type 2 diabetes but did not improve waist circumference (WMD: 0.05 cm, 95% CI: -1.77, 1.88; P=0.95), triglyceride levels (WMD: -4.49 mg/dL, 95% CI: -24.23, 15.25; P=0.66), or high-density lipoprotein cholesterol levels (WMD: -1.05 mg/dL, 95% CI: -2.44, 0.33; P=0.14) in patients with type 2 diabetes. CONCLUSION: This systematic review and meta-analysis updated the most recent literature and provided new evidence, proving that resveratrol treatment can reduce systolic blood pressure and diastolic blood pressure. High-dose resveratrol can reduce fasting blood glucose in patients with type 2 diabetes, although it has no effect on waist circumference, triglyceride, and high-density lipoprotein cholesterol. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 29359958 Effect of resveratrol on blood pressure: A systematic review and meta-analysis of randomized, controlled, clinical trials Systematic review and meta-analysis · Crit Rev Food Sci Nutr, 2019 17 trials - resveratrol did not significantly change systolic, diastolic, or mean BP versus placeboAn inert dummy treatment used as the comparison baseline.. Signal only in high-dose (300 mg/day+) and diabetic subgroups.
Key summary
A 2019 systematic review and meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of resveratrol's blood-pressure effect (17 randomized trials). Overall, neither systolic blood pressure (weighted mean difference -2.5 mmHg, p=0.116) nor diastolic (-0.5 mmHg, p=0.613) nor mean pressure nor pulse pressure changed significantly versus placeboAn inert dummy treatment used as the comparison baseline.. However, significant differences appeared in the high-dose (300 mg/day or more) and diabetic subgroups, and meta-regression found a positive association between baseline body mass index and the systolic-pressure-lowering activity. The authors cautiously noted a possible use for promoting cardiovascular health in high doses and in diabetic patients. Overall, no clear effect on blood pressure was confirmed.
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Introduction: Results of previous clinical trials evaluating the effect of resveratrol supplementation on blood pressure (BP) are controversial. Purpose: We aimed to assess the impact of resveratrol on BP through systematic review of literature and meta-analysis of available randomized, controlled clinical trials (RCTs). Methods: Literature search included SCOPUS, PubMed-Medline, ISI Web of Science and Google Scholar databases up to 17th October 2017 to identify RCTs investigating the impact of resveratrol on BP. Two review authors independently extracted data on study characteristics, methods and outcomes. Overall, the impact of resveratrol on BP was reported in 17 trials. Results: Administration of resveratrol did not significantly affect neither systolic BP [weighted mean difference (WMD): -2.5 95% CI:(-5.5, 0.6) mmHg; p=0.116; I2=62.1%], nor diastolic BP [WMD: -0.5 95% CI:(-2.2, 1.3) mmHg; p=0.613; I2=50.8], nor mean BP [MAP; WMD: -1.3 95% CI:(-2.8, 0.1) mmHg; p=0.070; I2=39.5%] nor pulse pressure [PP; WMD: -0.9 95% CI:(-3.1, 1.4) mmHg; p=0.449; I2=19.2%]. However, significant WMDs were detected in subsets of studies categorized according to high resveratrol daily dosage (≥300 mg/day) and presence of diabetes. Meta-regression analysis revealed a positive association between systolic BP-lowering resveratrol activity (slope: 1.99; 95% CI: 0.05, 3.93; two-tailed p= 0.04) and Body Mass Index (BMI) at baseline, while no association was detected neither between baseline BMI and MAP-lowering resveratrol activity (slope: 1.35; 95% CI: -0.22, 2.91; two-tailed p= 0.09) nor between baseline BMI and PP-lowering resveratrol activity (slope: 1.03; 95% CI: -1.33, 3.39; two-tailed p= 0.39). Resveratrol was fairly well-tolerated and no serious adverse events occurred among most of the eligible trials. Conclusion: The favourable effect of resveratrol emerging from the current meta-analysis suggests the possible use of this nutraceutical as active compound in order to promote cardiovascular health, mostly when used in high daily dose (≥300 mg/day) and in diabetic patients. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 24731650 Effect of resveratrol on blood pressure: a meta-analysis of randomized controlled trials Meta-analysis · Clin Nutr, 2015 6 trials, 247 people - no significant reduction in systolic or diastolic BP overall. Systolic pressure fell -11.90 mmHg only in the high-dose (150 mg/day+) subgroup.
Key summary
An early meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. quantitatively evaluating resveratrol's blood-pressure effect (6 randomized trials, 247 people). Overall, resveratrol did not significantly lower systolic or diastolic blood pressure. In subgroup analysis, only the high dose (150 mg/day or more) lowered systolic pressure by an average of 11.90 mmHg (95% CI -20.99 to -2.81), while lower doses had no significant effect. Diastolic pressure did not change significantly at any dose, and meta-regression found no dose-dependent effect. The authors stated that systolic pressure falls significantly only at high doses and that further high-quality studies are needed for causal conclusions.
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BACKGROUND & AIMS: The results of human clinical trials that have investigated the effects of resveratrol on blood pressure are inconsistent. We aimed to quantitatively evaluate the effects of resveratrol on systolic blood pressure (SBP) and diastolic blood pressure (DBP). METHODS: We conducted a strategic literature search of PubMed, EMBASE, MEDLINE, and the Cochrane Library (updated to January, 2014) for randomized controlled trials that evaluate the effects of resveratrol on SBP and DBP. Study quality was assessed using the Jadad scale. Weighted mean differences were calculated for net changes in SBP and DBP using fixed-effects or random-effects models. We performed pre-specified subgroup, sensitivity and meta-regression analyses to evaluate potential the heterogeneity. Dose effects of resveratrol on SBP and DBP were estimated using meta-regression analyses. RESULTS: Six studies comprising a total of 247 subjects were included in our meta-analysis. The overall outcome of the meta-analysis indicates that resveratrol consumption can not significantly reduce SBP and DBP. Subgroup analyses indicated that higher-dose of resveratrol consumption (≥ 150 mg/d) significantly reduces SBP of -11.90 mmHg (95% CI: -20.99, -2.81 mmHg, P = 0.01), whereas lower dose of resveratrol did not show a significant lowering effect on SBP. The meta-regression analyses did not indicate dose effects of resveratrol on SBP or DBP. CONCLUSIONS: The present meta-analysis indicates that resveratrol consumption significantly decreases the SBP level at the higher dose, while resveratrol has no significant effects on DBP levels. Additional high-quality studies are needed to further evaluate the causal conclusions. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 31264084 The Effects of Resveratrol Supplementation on Endothelial Function and Blood Pressures Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Systematic review and meta-analysis · High Blood Press Cardiovasc Prev, 2019 28 trials - flow-mediated dilatation (FMD) rose significantly (SMD 1.77). But heterogeneity was extreme at I2 96.5%, and there was no effect on systolic or diastolic BP.
Key summary
A meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of resveratrol's effect on endothelial function and blood pressure in people with metabolic disorders such as metabolic syndrome (28 randomized trials, 33 findings). Resveratrol significantly raised flow-mediated dilatation (FMD, a surrogate marker of endothelial health) (standardized mean difference 1.77, 95% CI 0.25 to 3.29), but heterogeneity was extremely high at I2 96.5%, so results varied widely between studies. There was no significant effect on systolic or diastolic blood pressure. The authors concluded that FMD rose significantly while noting that prospective studies at higher doses and longer durations are needed. Whether a rise in the FMD surrogate translates into actual clinical outcomes cannot be determined from this analysis alone.
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INTRODUCTION: There are current trials investigating the effect of resveratrol supplementation on endothelial function and blood pressures among patients with metabolic syndrome (MetS); however, the findings are controversial. AIM: This systematic review and meta-analysis of randomized controlled trials (RCTs) were carried out to summarize the effects of resveratrol supplementation on endothelial activation and blood pressures among patients with MetS and related disorders. METHODS: We searched systematically online databases including: PubMed-Medline, Embase, ISI Web of Science and Cochrane Central Register of Controlled Trials until October, 2018. Two independent authors extracted data and assessed the quality of included articles. Data were pooled using the fixed- or random-effects model and considered as standardized mean difference (SMD) with 95% confidence intervals (95% CI). RESULTS: Out of 831 electronic citations, 28 RCTs (with 33 findings reported) were included in the meta-analyses. The findings showed that resveratrol intervention significantly increased flow-mediated dilatation (FMD) levels (SMD 1.77; 95% CI 0.25, 3.29; P = 0.02; I2: 96.5). However, resveratrol supplements did not affect systolic blood pressure (SBP) (SMD - 0.27; 95% CI - 0.57, 0.03; P = 0.07; I2: 88.9) and diastolic blood pressure (DBP) (SMD - 0.21; 95% CI - 0.52, 0.11; P = 0.19; I2: 89.8). CONCLUSIONS: Resveratrol supplementation significantly increased FMD among patients with MetS and related disorders, but did not affect SBP and DBP. Additional prospective studies are needed to investigate the effect of resveratrol supplementation on endothelial function and blood pressures, using higher-dose of resveratrol with longer durations. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 30569644 Effect of Resveratrol on Blood Lipid Levels in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis Systematic review and meta-analysis · Obesity (Silver Spring), 2019 10 trials, 363 patients (diabetes) - 6+ months lowered triglycerideA type of fat in the blood; high levels raise cardiovascular risk.s, but total cholesterol rose in the obesity range and LDLLow-density lipoprotein cholesterol - the so-called "bad" cholesterol. rose in obese or lipid-drug-cotreated patients.
Key summary
The first meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of resveratrol's effect on blood lipids in people with type 2 diabetes (10 randomized trials, 363 people). Long-term use of 6 months or more lowered triglycerideA type of fat in the blood; high levels raise cardiovascular risk.s (TG), but total cholesterol rose in patients in the obesity range, and LDLLow-density lipoprotein cholesterol - the so-called "bad" cholesterol. cholesterol actually rose in diabetic patients who were obese or who also took lipid-lowering drugs. The authors' conclusion went only as far as the limited statement that resveratrol can improve triglycerides in people with type 2 diabetes. Overall, the benefit of use aimed at improving lipids is not clear, and it shows that some lipids may actually rise depending on the population.
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OBJECTIVE: Few studies have considered the effect of resveratrol on blood lipid levels, and the results of these studies are inconsistent. In this study, the first meta-analysis on the effect of resveratrol on blood lipid levels in patients with type 2 diabetes was conducted. METHODS: This study used keywords such as type 2 diabetes, total cholesterol, triglyceride (TG), high-density lipoprotein, low-density lipoprotein, and resveratrol and their abbreviations, free words, and related words to search PubMed, Cochrane Library, and Embase. The Cochrane risk of bias tool was used to evaluate the risk of bias, and Review Manager 5.3 and Stata 13.0 were used for data merging and statistical analysis. RESULTS: Ten randomized controlled trials involving a total of 363 patients with type 2 diabetes were included in the analysis. The results show that longer resveratrol intervention time (≥6 months) can reduce TG levels. But resveratrol increased total cholesterol in patients within obesity range. In type 2 diabetes patients with obesity and in those who took lipid-lowering drugs, resveratrol increased low-density lipoprotein levels. CONCLUSIONS: Resveratrol can improve TG in patients with type 2 diabetes. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
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