Resveratrol levels and all-cause mortality in older community-dwelling adults.

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.

[1]  M. Garcia-Conesa,et al.  Resveratrol in primary and secondary prevention of cardiovascular disease: a dietary and clinical perspective , 2013, Annals of the New York Academy of Sciences.

[2]  Alberto Dávalos,et al.  One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. , 2013, Pharmacological research.

[3]  N. Møller,et al.  High-Dose Resveratrol Supplementation in Obese Men , 2013, Diabetes.

[4]  P. Elliott,et al.  A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma , 2013, British journal of haematology.

[5]  K. Schechtman,et al.  Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. , 2012, Cell metabolism.

[6]  M. Urpi-Sardà,et al.  Pharmacokinetics of resveratrol metabolic profile in healthy humans after moderate consumption of red wine and grape extract tablets. , 2012, Pharmacological research.

[7]  M. Garcia-Conesa,et al.  One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. , 2012, The American journal of cardiology.

[8]  J. Nicholson,et al.  Host-Gut Microbiota Metabolic Interactions , 2012, Science.

[9]  R. Lamuela-Raventós,et al.  High urinary levels of resveratrol metabolites are associated with a reduction in the prevalence of cardiovascular risk factors in high-risk patients. , 2012, Pharmacological research.

[10]  M. Garcia-Conesa,et al.  Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: a triple-blind, 6-month follow-up, placebo-controlled, randomized trial. , 2012, Molecular nutrition & food research.

[11]  J. Auwerx,et al.  The journey of resveratrol from yeast to human , 2012, Aging.

[12]  J. Auwerx,et al.  Targeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD+? , 2012, Pharmacological Reviews.

[13]  J. Auwerx,et al.  Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. , 2011, Cell metabolism.

[14]  P. Dandona,et al.  A resveratrol and polyphenol preparation suppresses oxidative and inflammatory stress response to a high-fat, high-carbohydrate meal. , 2011, The Journal of clinical endocrinology and metabolism.

[15]  T. Hsieh,et al.  Resveratrol: a cardioprotective substance , 2011, Annals of the New York Academy of Sciences.

[16]  V. Basevi.  Diagnosis and Classification of Diabetes Mellitus , 2011, Diabetes Care.

[17]  P. Dandona,et al.  An Antiinflammatory and Reactive Oxygen Species Suppressive Effects of an Extract of Polygonum Cuspidatum Containing Resveratrol , 2010 .

[18]  S. Bandinelli,et al.  Proinflammatory state, hepcidin, and anemia in older persons. , 2010, Blood.

[19]  R. Lamuela-Raventós,et al.  Resveratrol metabolites in urine as a biomarker of wine intake in free-living subjects: The PREDIMED Study. , 2009, Free radical biology & medicine.

[20]  C. Schmid,et al.  A new equation to estimate glomerular filtration rate. , 2009, Annals of internal medicine.

[21]  G. Rossi,et al.  Diagnosis and Classification of Diabetes Mellitus The information that follows is based largely on the reports of the Expert Committee on the Diagnosis and Classification of Diabetes (Diabetes Care 20:1183–1197, 1997, and Diabetes Care 26:3160–3167, 2003). , 2008, Diabetes Care.

[22]  H. Zhen,et al.  New enlightenment of French paradox: Resveratrol's potential for cancer chemoprevention and anti-cancer therapy , 2007, Cancer biology & therapy.

[23]  M. Blaut,et al.  Metabolic diversity of the intestinal microbiota: implications for health and disease. , 2007, The Journal of nutrition.

[24]  Irfan Rahman,et al.  Regulation of inflammation and redox signaling by dietary polyphenols. , 2006, Biochemical pharmacology.

[25]  P. Puigserver,et al.  Resveratrol improves health and survival of mice on a high-calorie diet , 2006, Nature.

[26]  M. Belvisi,et al.  Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF‐κB‐independent mechanism , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[27]  S. Bandinelli,et al.  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC only. TRIALS The , 2004 .

[28]  T. Walle,et al.  HIGH ABSORPTION BUT VERY LOW BIOAVAILABILITY OF ORAL RESVERATROL IN HUMANS , 2004, Drug Metabolism and Disposition.

[29]  Luigi Ferrucci,et al.  Subsystems Contributing to the Decline in Ability to Walk: Bridging the Gap Between Epidemiology and Geriatric Practice in the InCHIANTI Study , 2000, Journal of the American Geriatrics Society.

[30]  S. Renaud,et al.  Wine, alcohol, platelets, and the French paradox for coronary heart disease , 1992, The Lancet.

[31]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[32]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[33]  K. Magyara,et al.  Cardioprotection by resveratrol : A human clinical trial in patients with stable coronary artery disease , 2012 .

[34]  N. Møller,et al.  High-Dose Resveratrol Supplementation in Obese Men An Investigator-Initiated, Randomized, Placebo-Controlled Clinical Trial of Substrate Metabolism, Insulin Sensitivity, and Body Composition , 2013 .

[35]  P. Elliott,et al.  Resveratrol/SRT-501 , 2009, Drugs of the Future.

[36]  F Berrino,et al.  Relative validity and reproducibility of a food frequency dietary questionnaire for use in the Italian EPIC centres. , 1997, International journal of epidemiology.

[37]  Linda P. Fried,et al.  The Women's Health and Aging Study: Health and Social Characteristics of Older Women with Disability , 1995 .

[38]  E. Siemann,et al.  Concentration of the Phytoalexin Resveratrol in Wine , 1992, American Journal of Enology and Viticulture.