Resveratrol does not influence metabolic risk markers related to cardiovascular health in overweight and slightly obese subjects: a randomized, placebo-controlled crossover trial

Sanne M van der Made, Jogchum Plat, Ronald P Mensink, Sanne M van der Made, Jogchum Plat, Ronald P Mensink

Abstract

Background: In vitro and animal studies have shown positive effects of resveratrol on lipid and lipoprotein metabolism, but human studies specifically designed to examine these effects are lacking.

Objective: The primary outcome parameter of this study in overweight and slightly obese subjects was the effect of resveratrol on apoA-I concentrations. Secondary outcome parameters were effects on other markers of lipid and lipoprotein metabolism, glucose metabolism, and markers for inflammation and endothelial function.

Design: This randomized, placebo-controlled crossover study was conducted in 45 overweight and slightly obese men (n = 25) and women (n = 20) with a mean age of 61 ± 7 years. Subjects received in random order resveratrol (150 mg per day) or placebo capsules for 4 weeks, separated by a 4-week wash-out period. Fasting blood samples were collected at baseline and at the end of each intervention period.

Results: Compliance was excellent as indicated by capsule count and changes in resveratrol and dihydroresveratrol concentrations. No difference between resveratrol and placebo was found in any of the fasting serum or plasma metabolic risk markers (mean ± SD for differences between day 28 values of resveratrol vs. placebo: apoA-I; 0.00 ± 0.12 g/L (P = 0.791), apoB100; -0.01 ± 0.11 g/L (P = 0.545), HDL cholesterol; 0.00 ± 0.09 mmol/L (P = 0.721), LDL cholesterol -0.03 ± 0.57 mmol/L (P = 0.718), triacylglycerol; 0.10 ± 0.54 mmol/L (P = 0.687), glucose; -0.08 ± 0.28 mmol/L (P = 0.064), insulin; -0.3 ± 2.5 mU/L (P = 0.516)). Also, no effects on plasma markers for inflammation and endothelial function were observed. No adverse events related to resveratrol intake were observed.

Conclusion: 150 mg of daily resveratrol intake for 4 weeks does not change metabolic risk markers related to cardiovascular health in overweight and slightly obese men and women. Effects on glucose metabolism warrant further study.

Trial registration: ClinicalTrials.gov NCT01364961.

Conflict of interest statement

Competing Interests: The funding we received from TI Food and Nutrition and the capsules that were given by DSM Nutritional Products Ltd. does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Subject flow chart.
Fig 1. Subject flow chart.
Fig 2. Individual total resveratrol (RES) and…
Fig 2. Individual total resveratrol (RES) and total dihydroresveratrol (DHR) concentrations at day 28.

References

    1. Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA. 1986;256: 2835–2838.
    1. Assmann G, Schulte H, von Eckardstein A, Huang Y. High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport. Atherosclerosis. 1996;124 Suppl: S11–20.
    1. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977;62: 707–714.
    1. Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, et al. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2001;104: 1108–1113.
    1. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357: 2109–2122.
    1. Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365: 2255–2267. 10.1056/NEJMoa1107579
    1. Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367: 2089–2099. 10.1056/NEJMoa1206797
    1. Boekholdt SM, Arsenault BJ, Hovingh GK, Mora S, Pedersen TR, Larosa JC, et al. Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk of cardiovascular events among statin-treated patients: a meta-analysis. Circulation. 2013;128: 1504–1512. 10.1161/CIRCULATIONAHA.113.002670
    1. Nicholls SJ. Apo a-I modulating therapies. Curr Cardiol Rep. 2011;13: 537–543. 10.1007/s11886-011-0223-0
    1. Hovingh GK, Bochem AE, Kastelein JJ. Apolipoprotein A-I mimetic peptides. Curr Opin Lipidol. 2010;21: 481–486. 10.1097/MOL.0b013e3283404507
    1. Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet. 1993;342: 1007–1011.
    1. Manach C, Mazur A, Scalbert A. Polyphenols and prevention of cardiovascular diseases. Curr Opin Lipidol. 2005;16: 77–84.
    1. Fan E, Zhang L, Jiang S, Bai Y. Beneficial effects of resveratrol on atherosclerosis. J Med Food. 2008;11: 610–614. 10.1089/jmf.2007.0091
    1. Iannelli P, Zarrilli V, Varricchio E, Tramontano D, Mancini FP. The dietary antioxidant resveratrol affects redox changes of PPARalpha activity. Nutr Metab Cardiovasc Dis. 2007;17: 247–256.
    1. Inoue H, Jiang XF, Katayama T, Osada S, Umesono K, Namura S. Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice. Neurosci Lett. 2003;352: 203–206.
    1. Erlund I, Koli R, Alfthan G, Marniemi J, Puukka P, Mustonen P, et al. Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol. Am J Clin Nutr. 2008;87: 323–331.
    1. Sacanella E, Vazquez-Agell M, Mena MP, Antunez E, Fernandez-Sola J, Nicolas JM, et al. Down-regulation of adhesion molecules and other inflammatory biomarkers after moderate wine consumption in healthy women: a randomized trial. Am J Clin Nutr. 2007;86: 1463–1469.
    1. Poulsen MM, Vestergaard PF, Clasen BF, Radko Y, Christensen LP, Stodkilde-Jorgensen H, 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. Diabetes. 2013;62: 1186–1195. 10.2337/db12-0975
    1. Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011;14: 612–622. 10.1016/j.cmet.2011.10.002
    1. Yoshino J, Conte C, Fontana L, Mittendorfer B, Imai S, Schechtman KB, et al. Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab. 2012;16: 658–664. 10.1016/j.cmet.2012.09.015
    1. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18: 499–502.
    1. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28: 412–419.
    1. Hansen HC, Chiacchia FS, Patel R, Wong NC, Khlebnikov V, Jankowska R, et al. Stilbene analogs as inducers of apolipoprotein-I transcription. Eur J Med Chem. 2010;45: 2018–2023. 10.1016/j.ejmech.2009.12.076
    1. Sahebkar A. Effects of resveratrol supplementation on plasma lipids: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2013.
    1. Dash S, Xiao C, Morgantini C, Szeto L, Lewis GF. High-dose resveratrol treatment for 2 weeks inhibits intestinal and hepatic lipoprotein production in overweight/obese men. Arterioscler Thromb Vasc Biol. 2013;33: 2895–2901. 10.1161/ATVBAHA.113.302342
    1. Brasnyo P, Molnar GA, Mohas M, Marko L, Laczy B, Cseh J, et al. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr. 2011;106: 383–389. 10.1017/S0007114511000316
    1. Bhatt JK, Thomas S, Nanjan MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res. 2012;32: 537–541. 10.1016/j.nutres.2012.06.003
    1. Csiszar A, Smith K, Labinskyy N, Orosz Z, Rivera A, Ungvari Z. Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells: role of NF-kappaB inhibition. Am J Physiol Heart Circ Physiol. 2006;291: H1694–1699.
    1. Agarwal B, Campen MJ, Channell MM, Wherry SJ, Varamini B, Davis JG, et al. Resveratrol for primary prevention of atherosclerosis: clinical trial evidence for improved gene expression in vascular endothelium. Int J Cardiol. 2013;166: 246–248. 10.1016/j.ijcard.2012.09.027
    1. Wong RH, Berry NM, Coates AM, Buckley JD, Bryan J, Kunz I, et al. Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults. J Hypertens. 2013;31: 1819–1827. 10.1097/HJH.0b013e328362b9d6
    1. Bode LM, Bunzel D, Huch M, Cho GS, Ruhland D, Bunzel M, et al. In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. Am J Clin Nutr. 2013;97: 295–309. 10.3945/ajcn.112.049379

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