Wine Information Council

Background: Resveratrol is a polyphenol chemical that naturally occurs in many plant-based dietary products, most notably, red wine. Discovered in 1939, widespread interest in the potential health benefits of resveratrol emerged in the 1970s in response to epidemiological data on the cardioprotective effects of wine. Objective: To explore the background of resveratrol (including its origins, stability, and metabolism), the metabolic effects of resveratrol and its mechanisms of action, and a potential future role of dietary resveratrol in the lifestyle management of obesity.

Data sources: We performed a narrative review, based on relevant articles written in English from a Pubmed search, using the following search terms: "resveratrol", "obesity", "Diabetes Mellitus", and "insulin sensitivity". Results: Following its ingestion, resveratrol undergoes extensive metabolism. This includes conjugation (with sulfate and glucuronate) within enterocytes, hydrolyzation and reduction within the gut through the action of the microbiota (with the formation of metabolites such as dihydroresveratrol), and enterohepatic circulation via the bile.

Ex vivo studies on adipose tissue reveal that resveratrol inhibits adipogenesis and prevents the accumulation of triglycerides through effects on the expression of Peroxisome Proliferator-activated Receptor gamma (PPARgamma) and sirtuin 1, respectively. Furthermore, resveratrol induces anti-inflammatory effects, supported by data from animal-based studies. Limited data from human-based studies reveal that resveratrol improves insulin sensitivity and fasting glucose levels in patients with Type 2 Diabetes Mellitus and may improve inflammatory status in human obesity.

Although numerous mechanisms may underlie the metabolic benefits of resveratrol, evidence supports a role in its interaction with the gut microbiota and modulation of protein targets, including sirtuins and proteins related to nitric oxide, insulin, and nuclear hormone receptors (such as PPARgamma). Conclusions: Despite much interest, there remain important unanswered questions regarding its optimal dosage (and how this may differ between and within individuals), and possible benefits within the general population, including the potential for weight-loss and improved metabolic function. Future studies should properly address these important questions before we can advocate the widespread adoption of dietary resveratrol supplementation.

Moderate alcohol consumption in patients with nonalcoholic fatty liver disease (NAFLD) is common, yet the effects on cardiovascular and liver health are unclear. Moderate alcohol use is associated with improved insulin sensitivity and decreased cardiovascular mortality in the general population, but whether similar benefits would be observed in persons with NAFLD remains largely unstudied. There is significant overlap in the pathogenesis of alcoholic liver disease (ALD) and NAFLD, although studies of ALD have focused on pathological alcohol intake and few mechanistic studies of moderate alcohol use in NAFLD exist. We undertook a critical review of the effect of moderate alcohol use on cardiovascular and liver disease in patients with NAFLD. A total of seven observational studies met the criteria for inclusion (one for cardiovascular endpoints and six for liver endpoints). Insufficient studies have assessed the association of moderate alcohol use with cardiovascular outcomes. There was a positive association between moderate alcohol use and decreased NASH and fibrosis; however, heavy episodic drinking may accelerate fibrosis progression and moderate alcohol use may increase the risk of hepatocellular carcinoma in patients with advanced fibrosis. Significant methodological limitations were present, including incomplete adjustment for confounding factors and failure to measure lifetime use or the pattern of alcohol intake. Thus, a strong recommendation of benefit of moderate alcohol use in NAFLD cannot be made. There remains a need for additional high-quality longitudinal studies that evaluate both cardiovascular and liver outcomes among NAFLD patients with moderate or lesser degrees of alcohol use. (Hepatology 2017;65:2090-2099).

Ethanol consumption is associated with left ventricular dysfunction in heavy ethanol drinkers. The effect of moderate ethanol intake on left ventricular function in hypertension, however, is unknown. We investigated the relationship between ethanol consumption and cardiac changes in nonalcoholic hypertensive patients. In 335 patients with primary hypertension, we assessed daily ethanol consumption by questionnaires that combined evaluation of recent and lifetime ethanol exposure and examined cardiac structure and function by echocardiography. Patients with abnormal liver tests, previous cardiovascular events, left ventricular ejection fraction <50%, and creatinine clearance <30 mL/min 1.72 m2 were excluded. Left ventricular hypertrophy was found in 21% of hypertensive patients and diastolic dysfunction was detected in 50% by tissue-Doppler imaging. Ethanol consumption was comparable in hypertensive patients with and without left ventricular hypertrophy, whereas patients with left ventricular diastolic dysfunction had significantly greater consumption than patients with normal ventricular filling. Left atrial diameter, e' wave velocity, e'/a' ratio, and E/e' ratio changed progressively with increasing levels of ethanol consumption, and prevalence of left ventricular diastolic dysfunction increased with a change that became statistically significant in patients consuming 20 g/d of ethanol or more. The e' wave velocity was inversely correlated with ethanol consumption, and multivariate logistic regression indicated that ethanol consumption predicted diastolic dysfunction independently of age, body mass index, blood pressure, insulin sensitivity, and left ventricular mass index. In conclusion, ethanol consumption is independently associated with left ventricular diastolic dysfunction in nonalcoholic hypertensive patients and might contribute to development of diastolic heart failure

Background: Recommendations for moderate alcohol consumption remain controversial, particularly in type 2 diabetes mellitus (T2DM). Long-term randomized, controlled trials (RCTs) are lacking. Objective: To assess cardiometabolic effects of initiating moderate alcohol intake in persons with T2DM and whether the type of wine matters. Design: 2-year RCT (CASCADE [CArdiovaSCulAr Diabetes & Ethanol] trial). (ClinicalTrials.gov: NCT00784433).

Setting: Ben-Gurion University of the Negev-Soroka Medical Center and Nuclear Research Center Negev, Israel. Patients: Alcohol-abstaining adults with well-controlled T2DM. Intervention: Patients were randomly assigned to 150 mL of mineral water, white wine, or red wine with dinner for 2 years. Wines and mineral water were provided. All groups followed a Mediterranean diet without caloric restriction.

Measurements: Primary outcomes were lipid and glycemic control profiles. Genetic measurements were done, and patients were followed for blood pressure, liver biomarkers, medication use, symptoms, and quality of life.

Results: Of the 224 patients who were randomly assigned, 94% had follow-up data at 1 year and 87% at 2 years. In addition to the changes in the water group (Mediterranean diet only), red wine significantly increased high-density lipoprotein cholesterol (HDL-C) level by 0.05 mmol/L (2.0 mg/dL) (95% CI, 0.04 to 0.06 mmol/L [1.6 to 2.2 mg/dL]; P < 0.001) and apolipoprotein(a)1 level by 0.03 g/L (CI, 0.01 to 0.06 g/L; P = 0.05) and decreased the total cholesterol-HDL-C ratio by 0.27 (CI, -0.52 to -0.01; P = 0.039). Only slow ethanol metabolizers (alcohol dehydrogenase alleles [ADH1B*1] carriers) significantly benefited from the effect of both wines on glycemic control (fasting plasma glucose, homeostatic model assessment of insulin resistance, and hemoglobin A1c) compared with fast ethanol metabolizers (persons homozygous for ADH1B*2). Across the 3 groups, no material differences were identified in blood pressure, adiposity, liver function, drug therapy, symptoms, or quality of life, except that sleep quality improved in both wine groups compared with the water group (P = 0.040). Overall, compared with the changes in the water group, red wine further reduced the number of components of the metabolic syndrome by 0.34 (CI, -0.68 to -0.001; P = 0.049).

Limitation: Participants were not blinded to treatment allocation. Conclusion: This long-term RCT suggests that initiating moderate wine intake, especially red wine, among well-controlled diabetics as part of a healthy diet is apparently safe and modestly decreases cardiometabolic risk. The genetic interactions suggest that ethanol plays an important role in glucose metabolism, and red wine's effects also involve nonalcoholic constituents. Primary Funding Source: European Foundation for the Study of Diabetes.