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Effects of grape seed extract on dyslipidaemia: a systematic review and dose–response meta-analysis of randomised controlled trials

  • Javad Anjom-Shoae (a1) (a2), Alireza Milajerdi (a1) (a2), Bagher Larijani (a3) and Ahmad Esmaillzadeh (a2) (a4) (a5)


Data on the effect of grape seed extract (GSE) on lipid profiles are inconclusive. We undertook a systematic review and meta-analysis of randomised controlled clinical trials on the effect of GSE on serum lipid profiles. The online databases of PubMed, ISI Web of Science, Scopus, ProQuest, Science Direct and Embase were searched for relevant publications until March 2019, using MeSH and non-MeSH keywords. Study selection, data extraction and quality assessment were completed independently by two investigators. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. Assessment of study quality was conducted using the Jadad scale. Eleven randomised clinical trials involving 536 participants were included in the present meta-analysis. Combining effect sizes from earlier studies, we found that GSE supplementation significantly decreased serum levels of LDL-cholesterol (−0·17 mmol/l; 95 % CI −0·34, −0·01) and TAG (−0·11 mmol/l; 95 % CI −0·18, −0·05). Although no overall significant effect of GSE supplementation on circulating total- and HDL-cholesterol levels was observed, there were significant reductions in these lipids in studies with <10 weeks of intervention and those that had administered the dosages of <300 mg/d of GSE. In conclusion, GSE supplementation seems to favourably affect serum levels of LDL and TAG concentrations, but it did not affect total- and HDL-cholesterol concentrations.


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*Corresponding author: Ahmad Esmaillzadeh, fax +98-21-88984861, email


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1.Hertog, MG, Feskens, EJ, Hollman, PC, etal. (1993) Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 342, 10071011.
2.Corder, R, Mullen, W, Khan, NQ, etal. (2006) Oenology: red wine procyanidins and vascular health. Nature 444, 566.
3.Sánchez-Moreno, C, Cao, G, Ou, B, etal. (2003) Anthocyanin and proanthocyanidin content in selected white and red wines. Oxygen radical absorbance capacity comparison with nontraditional wines obtained from highbush blueberry. J Agric Food Chem 51, 48894896.
4.Shi, J, Yu, J, Pohorly, JE, etal. (2003) Polyphenolics in grape seeds – biochemistry and functionality. J Med Food 6, 291299.
5.Viana, M, Barbas, C, Bonet, B, etal. (1996) In vitro effects of a flavonoid-rich extract on LDL oxidation. Atherosclerosis 123, 8391.
6.Frankel, EN, Kanner, J, German, JB, etal. (1993) Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 341, 454457.
7.Miyagi, Y, Miwa, K & Inoue, H (1997) Inhibition of human low-density lipoprotein oxidation by flavonoids in red wine and grape juice. Am J Cardiol 80, 16271631.
8.Aviram, M & Fuhrman, B (1998) Polyphenolic flavonoids inhibit macrophage-mediated oxidation of LDL and attenuate atherogenesis. Atherosclerosis 137, S45S50.
9.Bagchi, D, Bagchi, M, Stohs, SJ, etal. (2000) Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology 148, 187197.10.1016/S0300-483X(00)00210-9
10.Bagchi, D, Garg, A, Krohn, RL, etal. (1997) Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Res Commun Mol Pathol Pharmacol 95, 179189.
11.Bumrungpert, A, Kalpravidh, RW, Chuang, CC, etal. (2010) Xanthones from mangosteen inhibit inflammation in human macrophages and in human adipocytes exposed to macrophage-conditioned media. J Nutr 140, 842847.
12.Adisakwattana, S, Moonrat, J, Srichairat, S, etal. (2010) Lipid-lowering mechanisms of grape seed extract (Vitis vinifera L) and its antihyperlipidemic activity. J Med Plant Res 4, 21132120.
13.Vigna, GB, Costantini, F, Aldini, G, etal. (2003) Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers. Metabolism 52, 12501257.
14.Preuss, HG, Wallerstedt, D, Talpur, N, etal. (2000) Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: a pilot study. J Med 31, 227246.
15.Razavi, SM, Gholamin, S, Eskandari, A, etal. (2013) Red grape seed extract improves lipid profiles and decreases oxidized low-density lipoprotein in patients with mild hyperlipidemia. J Med Food 16, 255258.
16.Kar, P, Laight, D, Rooprai, HK, etal. (2009) 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 26, 526531.
17.Hansen, AS, Marckmann, P, Dragsted, LO, etal. (2005) Effect of red wine and red grape extract on blood lipids, haemostatic factors, and other risk factors for cardiovascular disease. Eur J Clin Nutr 59, 449455.
18.Moher, D, Shamseer, L, Clarke, M, etal. (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4, 1.
19.Jadad, AR, Moore, RA, Carroll, D, etal. (1996) Assessing the quality of curcumin in non-alcoholic fatty liver disease: a randomized controlled trial. Drug Research 67, 244251.
20.Borenstein, M, Hedges, LV, Higgins, JP, etal. (2011) Introduction to Meta-analysis. Hoboken, NJ: John Wiley & Sons.
21.Hozo, SP, Djulbegovic, B & Hozo, I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5, 13.
22.Fan, J & Gijbels, I (1996) Local Polynomial Modelling and Its Applications: Monographs on Statistics and Applied Probability 66. Boca Raton, FL: CRC Press.
23.Green, S & Higgins, J (editors) (2008) The Cochrane Handbook for Systematic Reviews of Interventions. Chichester: Wiley.
24.Clifton, PM (2004) Effect of grape seed extract and quercetin on cardiovascular and endothelial parameters in high-risk subjects. J Biomed Biotechnol 5, 272278.
25.Park, E, Edirisinghe, I, Choy, YY, etal. (2016) 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 115, 226238.
26.Yubero, N, Sanz-Buenhombre, M, Guadarrama, A, etal. (2013) LDL cholesterol-lowering effects of grape extract used as a dietary supplement on healthy volunteers. Int J Food Sci Nutr 64, 400406.
27.Sano, A, Uchida, R, Saito, M, etal. (2007) Beneficial effects of grape seed extract on malondialdehyde-modified LDL. J Nutr Sci Vitaminol (Tokyo) 53, 174182.
28.Argani, H, Ghorbanihaghjo, A, Vatankhahan, H, etal. (2016) The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia. Sao Paulo Med J 134, 234239.
29.Sivaprakasapillai, B, Edirisinghe, I, Randolph, J, etal. (2009) Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome. Metabolism 58, 17431746.
30.Brooker, S, Martin, S, Pearson, A, etal. (2006) Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration. Radiother Oncol 79, 4551.
31.Edirisinghe, I, Randolph, J, Cheema, M, etal. (2012) 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. Func Foods Health Dis 2, 508521.
32.Natella, F, Belelli, F, Gentili, V, etal. (2002) Grape seed proanthocyanidins prevent plasma postprandial oxidative stress in humans. J Agric Food Chem 50, 77207725.
33.Vinson, JA, Proch, J & Bose, P (2001) MegaNatural((R)) gold grapeseed extract: in vitro antioxidant and in vivo human supplementation studies. J Med Food 4, 1726.
34.Yugarani, T, Tan, BK, Teh, M, etal. (1992) Effects of polyphenolic natural products on the lipid profiles of rats fed high fat diets. Lipids 27, 181186.
35.Wilcox, LJ, Borradaile, NM, de Dreu, LE, etal. (2001) Secretion of hepatocyte apoB is inhibited by the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP. J Lipid Res 42, 725734.
36.Pal, S, Ho, N, Santos, C, etal. (2003) Red wine polyphenolics increase LDL receptor expression and activity and suppress the secretion of ApoB100 from human HepG2 cells. J Nutr 133, 700706.
37.Del Rio, D, Costa, LG, Lean, ME, etal. (2010) Polyphenols and health: what compounds are involved? Nutr Metab Cardiovasc Dis 20, 16.
38.Galvano, F, La Fauci, L, Vitaglione, P, etal. (2007) Bioavailability, antioxidant and biological properties of the natural free-radical scavengers cyanidin and related glycosides. Ann Ist Super Sanita 43, 382393.
39.Grassi, D, Necozione, S, Lippi, C, etal. (2005) Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension 46, 398405.
40.Engler, MB, Engler, MM, Chen, CY, etal. (2004) Mietus-Snyder. Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in Healthy adults. Am Coll Nutr 23, 197204.
41.Tokede, OA, Gaziano, JM & Djousse, L (2011) Effects of cocoa products/dark chocolate on serum lipids: a meta-analysis. Eur J Clin Nutrn 65, 879886.
42.Jia, L, Liu, X, Bai, YY, etal. (2010) Short-term effect of cocoa product consumption on lipid profile: a meta-analysis of randomized controlled trials. Am J Clin Nutr 92, 218225.
43.Kondo, K, Hirano, R, Matsumoto, A, etal. (1996) Inhibition of LDL oxidation by cocoa. Lancet 348, 1514.
44.Yamashita, Y, Okabe, M, Natsume, M, etal. (2012) Prevention mechanisms of glucose intolerance and obesity by cacao liquor procyanidin extract in high-fat diet-fed C57BL/6 mice. Arch Biochem Biophys 527, 95104.
45.Ramos-Romero, S, Perez-Cano, FJ, Ramiro-Puig, E, etal. (2012) Cocoa intake attenuates oxidative stress associated with rat adjuvant arthritis. Pharmacol Res 66, 207–12.
46.Sung, JH, Lee, SJ, Park, KH, etal. (2004) Isoflavones inhibit 3-hydroxy-3-methylglutaryl coenzyme a reductase in vitro. Biosci. Biotechnol. Biochem 68, 428432.
47.Vinson, JA, Mandarano, MA, Shuta, DL, etal. (2002) Beneficial effects of a novel IH636 grape seed proanthocyanidin extract and a niacin-bound chromium in a hamster atherosclerosis model. Mol Cell Biochem 240, 99103.
48.Giribabu, N, Eswar Kumar, K, Swapna Rekha, S, etal. (2015) Vitis vinifera (Muscat variety) seed ethanolic extract preserves activity levels of enzymes and histology of the liver in adult male rats with diabetes. Evid Based Complement Alternat Med 542026.
49.Tebib, K, Besançon, P & Rouanet, JM (1994) Dietary grape seed tannins affect lipoproteins, lipoprotein lipases and tissue lipids in rats fed hypercholesterolemic diets. J Nutr 124, 24512457.
50.Leifert, WR & Abeywardena, MY (2008) Cardioprotective actions of grape poly-phenols. Nutr Res 28, 729737.
51.Espín, JC, González-Sarrías, A & Tomás-Barberán, FA (2017) The gut microbiota: a key factor in the therapeutic effects of (poly) phenols. Biochem Pharmacol 139, 8293.
52.Feliciano, RP, Mills, CE, Istas, G, etal. (2017) Absorption, metabolism and excretion of cranberry (poly) phenols in humans: a dose response study and assessment of inter-individual variability. Nutrients 9, 268.
53.Brewer, MS (2011) Natural antioxidants: sources, compounds, mechanisms of action, and potential applications. Comprehen Rev Food Sci Food Safety 10 221247.
54.Leifert, WR & Abeywardena, MY (2008) Grape seed and red wine polyphenol extracts inhibit cellular cholesterol uptake, cell proliferation, and 5-lipoxygenase activity. Nutr Res 28, 842850.


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Effects of grape seed extract on dyslipidaemia: a systematic review and dose–response meta-analysis of randomised controlled trials

  • Javad Anjom-Shoae (a1) (a2), Alireza Milajerdi (a1) (a2), Bagher Larijani (a3) and Ahmad Esmaillzadeh (a2) (a4) (a5)


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