Epidemiological, in vitro and animal studies suggest that grape polyphenols, such as those present in wine, have favorable effects on the metabolic syndrome. However, controversy remains whether treatment with grape polyphenols is effective in humans. Here, we aimed to systemically review the effects of grape polyphenols on metabolic syndrome components in humans.
We systematically searched Medline, EMBASE and the Cochrane database for all clinical trials assessing the effects of grape polyphenols on insulin sensitivity, glycemia, blood pressure or lipid levels. We screened all titles and reviewed abstracts of potentially relevant studies. Full papers were assessed for eligibility and quality-rated according to the Jadad scale by two independent assessors.
Thirty-nine studies met the eligibility criteria. In individuals without component criteria of the metabolic syndrome, only low- and medium-quality studies were found with primarily neutral results. In individuals with the metabolic syndrome or related conditions, one of two high-quality studies suggested improvement in insulin sensitivity. Glycemia was improved in 2 of 11 lower-quality studies and 2 of 4 high-quality studies. Seven of 22 studies demonstrated a significant decrease in blood pressure, but only one was of high quality. Two of four high-quality studies pointed towards effects on total cholesterol while other lipidemic parameters were not affected.
No compelling data exist that grape polyphenols can positively influence glycemia, blood pressure or lipid levels in individuals with or without the metabolic syndrome. Limited evidence suggests that grape polyphenols may improve insulin sensitivity.
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Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR et al. The metabolic syndrome. Endocr Rev 2008; 29: 777–822.
Zimmet P . Globalization, coca-colonization and the chronic disease epidemic: can the Doomsday scenario be averted? J Intern Med 2000; 247: 301–310.
Renaud S, de Lorgeril M . Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992; 339: 1523–1526.
Koppes LLJ, Dekker JM, Hendriks HFJ, Bouter LM, Heine RJ . Moderate alcohol consumption lowers the risk of type 2 diabetes: a meta-analysis of prospective observational studies. Diabetes Care 2005; 28: 719–725.
Gillman MW, Cook NR, Evans DA, Rosner B, Hennekens CH . Relationship of alcohol intake with blood pressure in young adults. Hypertension 1995; 25: 1106–1110.
Gronbaek M . Alcohol, type of alcohol, and all-cause and coronary heart disease mortality. Ann NY Acad Sci 2002; 957: 16–20.
Andriantsitohaina R, Auger C, Chataigneau T, Etienne-Selloum N, Li H, Martinez MC et al. Molecular mechanisms of the cardiovascular protective effects of polyphenols. Br J Nutr 2012; 108: 1532–1549.
Pechanova O, Rezzani R, BABAL P, Bernatova I, Andriantsitohaina R . Beneficial effects of provinols: cardiovascular system and kidney. Physiol Res 2006; 55 (Suppl 1), S17–S30.
Hwang IK, Kim DW, Park JH, Lim SS, Yoo KY, Kwon DY et al. Effects of grape seed extract and its ethylacetate/ethanol fraction on blood glucose levels in a model of type 2 diabetes. Phytother Res 2009; 23: 1182–1185.
Pechanova O, Bernatova I, Babal P, Martinez MC, Kysela S, Stvrtina S et al. Red wine polyphenols prevent cardiovascular alterations in L-NAME-induced hypertension. J Hypertens 2004; 22: 1551–1559.
Quesada H, del Bas JM, Pajuelo D, Diaz S, Fernandez-Larrea J, Pinent M et al. Grape seed proanthocyanidins correct dyslipidemia associated with a high-fat diet in rats and repress genes controlling lipogenesis and VLDL assembling in liver. Int J Obes (Lond) 2009; 33: 1007–1012.
Li SH, Tian HB, Zhao HJ, Chen LH, Cui LQ . The acute effects of grape polyphenols supplementation on endothelial function in adults: meta-analyses of controlled trials. PLoS One 2013; 8: e69818.
Moher D, Schulz KF, Altman DG . The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Clin Oral Investig 2003; 7: 2–7.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17: 1–12.
Hozumi T, Sugioka K, Shimada K, Kim SH, Kuo MY, Miyake Y et al. Beneficial effect of short term intake of red wine polyphenols on coronary microcirculation in patients with coronary artery disease. Heart 2006; 92: 681–682.
Vinson J, Proch J, Bose P . MegaNatural(R) Gold grapeseed extract: in vitro antioxidant and in vivo human supplementation studies. J Med Food 2001; 4: 17–26.
Moreno-Indias I, Sanchez-Alcoholado L, Perez-Martinez P, Andres-Lacueva C, Cardona F, Tinahones F et al. Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients. Food Funct 2016; 7: 1775–1787.
Sapwarobol S, Adisakwattana S, Changpeng S, Ratanawachirin W, Tanruttanawong K, Boonyarit W . Postprandial blood glucose response to grape seed extract in healthy participants: a pilot study. Pharmacogn Mag 2012; 8: 192–196.
Queipo-Ortuno MI, Boto-Ordonez M, Murri M, Gomez-Zumaquero JM, Clemente-Postigo M, Estruch R et al. Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers. Am J Clin Nutr 2012; 95: 1323–1334.
Zern TL, Wood RJ, Greene C, West KL, Liu Y, Aggarwal D et al. Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress. J Nutr 2005; 135: 1911–1917.
Banini AE, Boyd LC, Allen JC, Allen HG, Sauls DL . Muscadine grape products intake, diet and blood constituents of non-diabetic and type 2 diabetic subjects. Nutrition 2006; 22: 1137–1145.
Sano A, Uchida R, Saito M, Shioya N, Komori Y, Tho Y et al. Beneficial effects of grape seed extract on malondialdehyde-modified LDL. J Nutr Sci Vitaminol (Tokyo) 2007; 53: 174–182.
Naissides M, Mamo JCL, James AP, Pal S . The effect of chronic consumption of red wine on cardiovascular disease risk factors in postmenopausal women. Atherosclerosis 2006; 185: 438–445.
Kar P, Laight D, Rooprai HK, Shaw KM, Cummings M . Effects of grape seed extract in type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity. Diabet Med 2009; 26: 526–531.
Chiva-Blanch G, Urpi-Sarda M, Ros E, Valderas-Martinez P, Casas R, Arranz S et al. Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid profile: a randomized clinical trial. Clin Nutr 2013; 32: 200–206.
Mellen PB, Daniel KR, Brosnihan KB, Hansen KJ, Herrington DM . Effect of muscadine grape seed supplementation on vascular function in subjects with or at risk for cardiovascular disease: a randomized crossover trial. J Am Coll Nutr 2010; 29: 469–475.
Zunino SJ, Peerson JM, Freytag TL, Breksa AP, Bonnel EL, Woodhouse LR et al. Dietary grape powder increases IL-1beta and IL-6 production by lipopolysaccharide-activated monocytes and reduces plasma concentrations of large LDL and large LDL-cholesterol particles in obese humans. Br J Nutr 2014; 112: 369–380.
Botden IPG, Draijer R, Westerhof BE, Rutten JHW, Langendonk JG, Sijbrands EJG et al. Red wine polyphenols do not lower peripheral or central blood pressure in high normal blood pressure and hypertension. Am J Hypertens 2012; 25: 718–723.
Barona J, Aristizabal JC, Blesso CN, Volek JS, Fernandez ML . Grape polyphenols reduce blood pressure and increase flow-mediated vasodilation in men with metabolic syndrome. J Nutr 2012; 142: 1626–1632.
Mori TA, Burke V, Zilkens RR, Hodgson JM, Beilin LJ, Puddey IB . The effects of alcohol on ambulatory blood pressure and other cardiovascular risk factors in type 2 diabetes: a randomized intervention. J Hypertens 2016; 34: 421–428.
Tome-Carneiro J, Gonzalvez M, Larrosa M, Yanez-Gascon MJ, Garcia-Almagro FJ, Ruiz-Ros JA et al. Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: a triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc Drugs Ther 2013; 27: 37–48.
Tome-Carneiro J, Gonzalvez M, Larrosa M, Yanez-Gascon MJ, Garcia-Almagro FJ, Ruiz-Ros JA 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. Am J Cardiol 2012; 110: 356–363.
Hokayem M, Blond E, Vidal H, Lambert K, Meugnier E, Feillet-Coudray C et al. Grape polyphenols prevent fructose-induced oxidative stress and insulin resistance in first-degree relatives of type 2 diabetic patients. Diabetes Care 2013; 36: 1454–1461.
Park E, Edirisinghe I, Choy YY, Waterhouse A, Burton-Freeman B . Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: a randomised, double-blinded, two-arm, parallel, placebo-controlled trial. Br J Nutr 2016; 115: 226–238.
Naissides M, Mamo JCL, James AP, Pal S . The effect of acute red wine polyphenol consumption on postprandial lipaemia in postmenopausal women. Atherosclerosis 2004; 177: 401–408.
Edirisinghe I, Randolph J, Cheema M, Tadapaneni R, Park E, Burton-Freeman B et al. Effect of grape seed extract on postprandial oxidative status and metabolic responses in men and women with the metabolic syndrome-randomized, cross-over, placebo-controlled study. Funct Foods Health Dis 2013; 2: 508–521.
van Mierlo LAJ, Zock PL, van der Knaap HCM, Draijer R . Grape polyphenols do not affect vascular function in healthy men. J Nutr 2010; 140: 1769–1773.
Hansen AS, Marckmann P, Dragsted LO, Finne Nielsen IL, Nielsen SE, Gronbaek M . Effect of red wine and red grape extract on blood lipids, haemostatic factors, and other risk factors for cardiovascular disease. Eur J Clin Nutr 2005; 59: 449–455.
Zilkens RR, Burke V, Hodgson JM, Barden A, Beilin LJ, Puddey IB . Red wine and beer elevate blood pressure in normotensive men. Hypertension 2005; 45: 874–879.
Karatzi KN, Papamichael CM, Karatzis EN, Papaioannou TG, Aznaouridis KA, Katsichti PP et al. Red wine acutely induces favorable effects on wave reflections and central pressures in coronary artery disease patients. Am J Hypertens 2005; 18 (Pt 1), 1161–1167.
Sivaprakasapillai B, Edirisinghe I, Randolph J, Steinberg F, Kappagoda T . Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome. Metabolism 2009; 58: 1743–1746.
Belcaro G, Ledda A, Hu S, Cesarone MR, Feragalli B, Dugall M . Grape seed procyanidins in pre- and mild hypertension: a registry study. Evid Based Complement Alternat Med 2013; 2013: 313142.
Clifton PM . Effect of grape seed extract and quercetin on cardiovascular and endothelial parameters in high-risk subjects. BioMed Res Int 2004; 2004: 272–278.
Naissides M, Pal S, Mamo JCL, James AP, Dhaliwal S . The effect of chronic consumption of red wine polyphenols on vascular function in postmenopausal women. Eur J Clin Nutr 2006; 60: 740–745.
Chiva-Blanch G, Urpi-Sarda M, Ros E, Arranz S, Valderas-Martinez P, Casas R et al. Dealcoholized red wine decreases systolic and diastolic blood pressure and increases plasma nitric oxide: short communication. Circ Res 2012; 111: 1065–1068.
Draijer R, de Graaf Y, Slettenaar M, de Groot E, Wright CI . Consumption of a polyphenol-rich grape-wine extract lowers ambulatory blood pressure in mildly hypertensive subjects. Nutrients 2015; 7: 3138–3153.
Ras RT, Zock PL, Zebregs YEMP, Johnston NR, Webb DJ, Draijer R . Effect of polyphenol-rich grape seed extract on ambulatory blood pressure in subjects with pre- and stage I hypertension. Br J Nutr 2013; 110: 2234–2241.
Ward NC, Hodgson JM, Croft KD, Burke V, Beilin LJ, Puddey IB . The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens 2005; 23: 427–434.
Razavi SM, Gholamin S, Eskandari A, Mohsenian N, Ghorbanihaghjo A, Delazar A et al. Red grape seed extract improves lipid profiles and decreases oxidized low-density lipoprotein in patients with mild hyperlipidemia. J Med Food 2013; 16: 255–258.
Vigna GB, Costantini F, Aldini G, Carini M, Catapano A, Schena F et al. Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers. Metabolism 2003; 52: 1250–1257.
Argani H, Ghorbanihaghjo A, Vatankhahan H, Rashtchizadeh N, Raeisi S, Ilghami H . The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia. Sao Paulo Med J 2016; 134: 234–239.
Preuss HG, Wallerstedt D, Talpur N, Tutuncuoglu SO, Echard B, Myers A et al. Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: a pilot study. J Med 2000; 31: 227–246.
Vazquez-Prieto MA, Renna NF, Lembo C, Diez ER, Miatello RM . Dealcoholized red wine reverse vascular remodeling in an experimental model of metabolic syndrome: role of NAD(P)H oxidase and eNOS activity. Food Funct 2010; 1: 124–129.
Hackam DG, Redelmeier DA . Translation of research evidence from animals to humans. JAMA 2006; 296: 1731–1732.
Kroon PA, Clifford MN, Crozier A, Day AJ, Donovan JL, Manach C et al. How should we assess the effects of exposure to dietary polyphenols in vitro? Am J Clin Nutr 2004; 80: 15–21.
ES and JW are supported by the Dutch heart foundation (2010T041).
The authors declare no conflict of interest.
Supplementary Information accompanies this paper on European Journal of Clinical Nutrition website
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Woerdeman, J., van Poelgeest, E., Ket, J. et al. Do grape polyphenols improve metabolic syndrome components? A systematic review. Eur J Clin Nutr 71, 1381–1392 (2017). https://doi.org/10.1038/ejcn.2016.227
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