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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Systematic Review Article

The Effects of Resveratrol on Oxidative Stress Markers: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Author(s): Mahsa Omidian, Mina Abdolahi, Elnaz Daneshzad, Mohsen Sedighiyan, Mohadeseh Aghasi, Hamed Abdollahi, Parisa Omidian, Sasan Dabiri and Maryam Mahmoudi*

Volume 20, Issue 5, 2020

Page: [718 - 727] Pages: 10

DOI: 10.2174/1871530319666191116112950

Price: $65

Abstract

Objective: Recent trial studies have found that resveratrol supplementation beneficially reduces oxidative stress marker, but, there is no definitive consensus on this context. The present systematic review and meta-analysis aimed to investigate the effect of resveratrol supplementation on oxidative stress parameters.

Methods: We searched databases of Pubmed, Scopus and Cochrane Library up to December 2018 with no language restriction. Studies were reviewed according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Cochrane handbook. To compare the effects of resveratrol with placebo, weighted mean difference (WMD) with 95% confidence intervals (CI) were pooled based on the random-effects model.

Results: Among sixteen clinical trials, we found that resveratrol supplementation increased GPx serum levels significantly (WMD: 18.61; 95% CI: 8.70 to 28.52; P<0.001) but had no significant effect on SOD concentrations (WMD: 1.01; 95% CI: -0.72 to 2.74; P= 0.25), MDA serum levels (WMD: -1.43; 95% CI: -3.46 to 0.61; P = 0.17) and TAC (WMD: -0.09; 95% CI: -0.29 to 0.11; P = 0.36) compared to placebo. Finally, we observed that resveratrol supplementation may not have a clinically significant effect on oxidative stress.

Conclusion: However, the number of human trials is limited in this context, and further large prospective clinical trials are needed to confirm the effect of resveratrol supplement on oxidative stress markers.

Keywords: Resveratrol, Oxidative stress, Malondialdehyde, Glutathione peroxidase, Superoxide dismutase, Total anti-oxidant capacity.

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[1]
Murakami, A. Modulation of protein quality control systems by food phytochemicals. J. Clin. Biochem. Nutr., 2013, 52(3), 215-227.
[http://dx.doi.org/10.3164/jcbn.12-126] [PMID: 23704811]
[2]
Catalgol, B.; Batirel, S.; Taga, Y.; Ozer, N.K. Resveratrol: French paradox revisited. Front. Pharmacol., 2012, 3, 141.
[http://dx.doi.org/10.3389/fphar.2012.00141] [PMID: 22822401]
[3]
Young, I.S.; Woodside, J.V. Antioxidants in health and disease. J. Clin. Pathol., 2001, 54(3), 176-186.
[http://dx.doi.org/10.1136/jcp.54.3.176] [PMID: 11253127]
[4]
Moylan, J.S.; Reid, M.B. Oxidative stress, chronic disease, and muscle wasting. Muscle Nerve, 2007, 35(4), 411-429.
[http://dx.doi.org/10.1002/mus.20743] [PMID: 17266144]
[5]
Siti, H.N.; Kamisah, Y.; Kamsiah, J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul. Pharmacol., 2015, 71, 40-56.
[http://dx.doi.org/10.1016/j.vph.2015.03.005] [PMID: 25869516]
[6]
Sies, H. Total antioxidant capacity: appraisal of a concept. J. Nutr., 2007, 137(6), 1493-1495.
[http://dx.doi.org/10.1093/jn/137.6.1493] [PMID: 17513413]
[7]
Mittler, R. Oxidative stress, antioxidants and stress tolerance. Trends Plant Sci., 2002, 7(9), 405-410.
[http://dx.doi.org/10.1016/S1360-1385(02)02312-9] [PMID: 12234732]
[8]
Soveyd, N.; Abdolahi, M.; Djalali, M.; Hatami, M.; Tafakhori, A.; Sarraf, P.; Honarvar, N. M. The combined effects of ω-3 fatty acids and nano-curcumin supplementation on intercellular adhesion molecule- 1 (ICAM-1) gene expression and serum levels in migraine patients. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders).,, 2017, 16(10), 1120-1126.
[9]
Abdolahi, M.; Sarraf, P.; Javanbakht, M. H.; Honarvar, N. M.; Hatami, M.; Soveyd, N.; Tafakhori, A.; Sedighiyan, M.; Djalali, M.; Jafarieh, A. A novel combination of ω-3 fatty acids and nano-curcumin modulates interleukin-6 gene expression and high sensitivity C-reactive protein serum levels in patients with migraine: A randomized clinical trial study. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders).,, 2018, 17(6), 430-438.
[10]
Soveyd, N.; Abdolahi, M.; Bitarafan, S.; Tafakhori, A.; Sarraf, P.; Togha, M.; Okhovat, A.A.; Hatami, M.; Sedighiyan, M.; Djalali, M.; Mohammadzadeh Honarvar, N. Molecular mechanisms of omega-3 fatty acids in the migraine headache. Iran. J. Neurol., 2017, 16(4), 210-217.
[PMID: 29736227]
[11]
Abdolahi, M.; Jafarieh, A.; Sarraf, P.; Sedighiyan, M.; Yousefi, A.; Tafakhori, A.; Abdollahi, H.; Salehinia, F.; Djalali, M. The neuromodulatory effects of ω-3 fatty acids and nano-curcumin on the COX-2/ iNOS network in migraines: A clinical trial study from gene expression to clinical symptoms. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19(6), 874-884.
[http://dx.doi.org/10.2174/1871530319666190212170140] [PMID: 30760195]
[12]
Saedisomeolia, A.; Samadi, M.; Gholami, F.; Seyedi, M.; Effatpanah, M.; Hashemi, R.; Abdolahi, M.; Honarvar, N. M. Vitamin D's molecular action mechanism in attention-deficit/hyperactivity disorder: A reviewvof evidence. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders),, 2018, 17(4), 280-290.
[13]
Hatami, M.; Abdolahi, M.; Soveyd, N.; Djalali, M.; Togha, M.; Honarvar, N. M. Molecular mechanisms of curcumin in neuroinflammatory disorders: a mini review of current evidences. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders).,, 2019, 19(3), 247-258.
[http://dx.doi.org/10.2174/1871530319666181129103056]
[14]
Sedighiyan, M.; Abdolahi, M.; Taheri, E.; Qorbani, M.; Omidian, P.; Hosseini, S. The french maritime pine bark extract reduce metabolic syndrome risk and improve body composition in obesity: A new clinical approach. Acta Med. Iran., 2018, 56(3), 196-203.
[15]
Truong, V.L.; Jun, M.; Jeong, W.S. Role of resveratrol in regulation of cellular defense systems against oxidative stress. Biofactors, 2018, 44(1), 36-49.
[http://dx.doi.org/10.1002/biof.1399] [PMID: 29193412]
[16]
Quincozes-Santos, A.; Bobermin, L.D.; Latini, A.; Wajner, M.; Souza, D.O.; Gonçalves, C-A.; Gottfried, C. Resveratrol protects C6 astrocyte cell line against hydrogen peroxide-induced oxidative stress through heme oxygenase 1. PLoS One, 2013, 8(5)e64372
[http://dx.doi.org/10.1371/journal.pone.0064372] [PMID: 23691207]
[17]
Chen, C-Y.; Jang, J-H.; Li, M-H.; Surh, Y-J. Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells. Biochem. Biophys. Res. Commun., 2005, 331(4), 993-1000.
[http://dx.doi.org/10.1016/j.bbrc.2005.03.237] [PMID: 15882976]
[18]
Espinosa-Diez, C.; Miguel, V.; Mennerich, D.; Kietzmann, T.; Sánchez-Pérez, P.; Cadenas, S.; Lamas, S. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol., 2015, 6, 183-197.
[http://dx.doi.org/10.1016/j.redox.2015.07.008] [PMID: 26233704]
[19]
Kumar, A.; Singh, C.K.; Lavoie, H.A.; Dipette, D.J.; Singh, U.S. Resveratrol restores Nrf2 level and prevents ethanol-induced toxic effects in the cerebellum of a rodent model of fetal alcohol spectrum disorders. Molecular Pharmacology.,, 2011. 111, 071126.
[http://dx.doi.org/10.1124/mol.111.071126]
[20]
Soufi, F.G.; Mohammad-Nejad, D.; Ahmadieh, H. Resveratrol improves diabetic retinopathy possibly through oxidative stress - nuclear factor κB - apoptosis pathway. Pharmacol. Rep., 2012, 64(6), 1505-1514.
[http://dx.doi.org/10.1016/S1734-1140(12)70948-9] [PMID: 23406761]
[21]
Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann. Intern. Med., 2009, 151(4), 264-269, W64..
[http://dx.doi.org/10.7326/0003-4819-151-4-200908180-00135] [PMID: 19622511]
[22]
Higgins, J.P.; Altman, D.G.; Gøtzsche, P.C.; Jüni, P.; Moher, D.; Oxman, A.D.; Savović, J.; Schulz, K.F.; Weeks, L.; Sterne, J.A. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ, 2011, 343, d5928.
[http://dx.doi.org/10.1136/bmj.d5928] [PMID: 22008217]
[23]
Green, S.; Higgins, J. Cochrane handbook for systematic reviews of interventions; Version, 2005.
[24]
Borenstein, M.; Hedges, L.V.; Higgins, J.P.; Rothstein, H.R. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res. Synth. Methods, 2010, 1(2), 97-111.
[http://dx.doi.org/10.1002/jrsm.12] [PMID: 26061376]
[25]
Chachay, V.S.; Macdonald, G.A.; Martin, J.H.; Whitehead, J.P.; O'Moore-Sullivan, T.M.; Lee, P.; Franklin, M.; Klein, K.; Taylor, P.J.; Ferguson, M. Resveratrol does not benefit patients with nonalcoholic fatty liver disease. Clinical Gastroenterology and Hepatology.,, 2014, 12(12), 2092-2103.
[http://dx.doi.org/10.1016/j.cgh.2014.02.024]
[26]
Bhatt, J.K.; Nanjan, M.J. Resveratrol supplementation in patients with type 2 diabetes mellitus: A prospective, open label, randomized controlled trial. Nternational Research Journal of Pharmacy., 2013, 4(8), 245-249.
[http://dx.doi.org/10.7897/2230-8407.04849]
[27]
Samsami-Kor, M.; Daryani, N.E.; Asl, P.R.; Hekmatdoost, A. Anti-Inflammatory Effects of Resveratrol in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study. Arch. Med. Res., 2015, 46(4), 280-285.
[http://dx.doi.org/10.1016/j.arcmed.2015.05.005] [PMID: 26002728]
[28]
Sattarinezhad, A.; Roozbeh, J.; Shirazi Yeganeh, B.; Omrani, G.R.; Shams, M. Resveratrol reduces albuminuria in diabetic nephropathy: A randomized double-blind placebo-controlled clinical trial. Diabetes Metab., 2018.
[PMID: 29983230]
[29]
Seyyedebrahimi, S.; Khodabandehloo, H.; Nasli Esfahani, E.; Meshkani, R. The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial. Acta Diabetol., 2018, 55(4), 341-353.
[http://dx.doi.org/10.1007/s00592-017-1098-3] [PMID: 29357033]
[30]
Asghari, S.; Rafraf, M.; Farzin, L.; Asghari-Jafarabadi, M.; Ghavami, S.M.; Somi, M.H. Effects of Pharmacologic Dose of Resveratrol Supplementation on Oxidative/Antioxidative Status Biomarkers in Nonalcoholic Fatty Liver Disease Patients: A Randomized, Double-Blind, Placebo-Controlled Trial. Adv. Pharm. Bull., 2018, 8(2), 307-317.
[http://dx.doi.org/10.15171/apb.2018.036] [PMID: 30023333]
[31]
Samsamikor, M.; Daryani, N.E.; Asl, P.R.; Hekmatdoost, A. Resveratrol supplementation and oxidative/anti-oxidative status in patients with ulcerative colitis: a randomized, double-blind, placebo-controlled pilot study. Arch. Med. Res., 2016, 47(4), 304-309.
[http://dx.doi.org/10.1016/j.arcmed.2016.07.003] [PMID: 27664491]
[32]
Bhatt, J.K.; Thomas, S.; Nanjan, M.J. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr. Res., 2012, 32(7), 537-541.
[http://dx.doi.org/10.1016/j.nutres.2012.06.003] [PMID: 22901562]
[33]
Alberti, K.G.M.M.; Zimmet, P.Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet. Med., 1998, 15(7), 539-553.
[http://dx.doi.org/10.1002/(SICI)1096-9136(199807)15:7<539:AID-DIA668>3.0.CO;2-S] [PMID: 9686693]
[34]
Amirkhizi, F.; Siassi, F.; Minaie, S.; Djalali, M.; Rahimi, A.; Chamari, M. Is obesity associated with increased plasma lipid peroxidation and oxidative stress in women? ARYA Atheroscler., 2010, 2(4)
[35]
Ozata, M.; Mergen, M.; Oktenli, C.; Aydin, A.; Sanisoglu, S.Y.; Bolu, E.; Yilmaz, M.I.; Sayal, A.; Isimer, A.; Ozdemir, I.C. Increased oxidative stress and hypozincemia in male obesity. Clin. Biochem., 2002, 35(8), 627-631.
[http://dx.doi.org/10.1016/S0009-9120(02)00363-6] [PMID: 12498997]
[36]
Marseglia, L.; Manti, S.; D’Angelo, G.; Nicotera, A.; Parisi, E.; Di Rosa, G.; Gitto, E.; Arrigo, T. Oxidative stress in obesity: a critical component in human diseases. Int. J. Mol. Sci., 2014, 16(1), 378-400.
[http://dx.doi.org/10.3390/ijms16010378] [PMID: 25548896]
[37]
McAnulty, L.S.; Miller, L.E.; Hosick, P.A.; Utter, A.C.; Quindry, J.C.; McAnulty, S.R. Effect of resveratrol and quercetin supplementation on redox status and inflammation after exercise. Appl. Physiol. Nutr. Metab., 2013, 38(7), 760-765.
[http://dx.doi.org/10.1139/apnm-2012-0455] [PMID: 23980734]
[38]
Gliemann, L.; Schmidt, J.F.; Olesen, J.; Biensø, R.S.; Peronard, S.L.; Grandjean, S.U.; Mortensen, S.P.; Nyberg, M.; Bangsbo, J.; Pilegaard, H.; Hellsten, Y. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J. Physiol., 2013, 591(20), 5047-5059.
[http://dx.doi.org/10.1113/jphysiol.2013.258061] [PMID: 23878368]
[39]
Goldberg, D.M.; Yan, J.; Soleas, G.J. Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin. Biochem., 2003, 36(1), 79-87.
[http://dx.doi.org/10.1016/S0009-9120(02)00397-1] [PMID: 12554065]
[40]
Walle, T.; Hsieh, F.; DeLegge, M.H.; Oatis, J.E., Jr; Walle, U.K. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab. Dispos., 2004, 32(12), 1377-1382.
[http://dx.doi.org/10.1124/dmd.104.000885] [PMID: 15333514]
[41]
Liu, B.; Ghosh, S.; Yang, X.; Zheng, H.; Liu, X.; Wang, Z.; Jin, G.; Zheng, B.; Kennedy, B.K.; Suh, Y.; Kaeberlein, M.; Tryggvason, K.; Zhou, Z. Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metab., 2012, 16(6), 738-750.
[http://dx.doi.org/10.1016/j.cmet.2012.11.007] [PMID: 23217256]
[42]
Hsu, C-P.; Zhai, P.; Yamamoto, T.; Maejima, Y.; Matsushima, S.; Hariharan, N.; Shao, D.; Takagi, H.; Oka, S.; Sadoshima, J. Silent information regulator 1 protects the heart from ischemia/reperfusion. Circulation, 2010. 110, 958033.
[43]
Ungvari, Z.; Orosz, Z.; Rivera, A.; Labinskyy, N.; Xiangmin, Z.; Olson, S.; Podlutsky, A.; Csiszar, A. Resveratrol increases vascular oxidative stress resistance. Am. J. Physiol. Heart Circ. Physiol., 2007, 292(5), H2417-H2424.
[http://dx.doi.org/10.1152/ajpheart.01258.2006] [PMID: 17220179]
[44]
Tsai, S.H.; Lin-Shiau, S.Y.; Lin, J.K. Suppression of nitric oxide synthase and the down-regulation of the activation of NFkappaB in macrophages by resveratrol. Br. J. Pharmacol., 1999, 126(3), 673-680.
[http://dx.doi.org/10.1038/sj.bjp.0702357] [PMID: 10188978]
[45]
Xiao, B.H.; Shi, M.; Chen, H.; Cui, S.; Wu, Y.; Gao, X-H.; Chen, H-D. Glutathione peroxidase level in patients with vitiligo: a meta-analysis. BioMed research international.,, 2016.
[http://dx.doi.org/10.1155/2016/3029810]
[46]
Pastori, D.; Pignatelli, P.; Farcomeni, A.; Menichelli, D.; Nocella, C.; Carnevale, R.; Violi, F. Aging‐related decline of glutathione peroxidase 3 and risk of cardiovascular events in patients with atrial fibrillation. J. Am. Heart Assoc., 2016, 5(9)e003682
[http://dx.doi.org/10.1161/JAHA.116.003682] [PMID: 27609361]
[47]
González de Vega, R.; Fernández-Sánchez, M.L.; Fernández, J.C.; Álvarez Menéndez, F.V.; Sanz-Medel, A. Selenium levels and Glutathione peroxidase activity in the plasma of patients with type II diabetes mellitus. J. Trace Elem. Med. Biol., 2016, 37, 44-49.
[http://dx.doi.org/10.1016/j.jtemb.2016.06.007] [PMID: 27473831]
[48]
Tangvarasittichai, S. Serum levels of malondialdehyde in type 2 diabetes mellitus Thai subjects. Siriraj Medical Journal, 2017, 61(1), 20-23.
[49]
Lorente, L.; Rodriguez, S.T.; Sanz, P.; Abreu-González, P.; Díaz, D.; Moreno, A.M.; Borja, E.; Martín, M.M.; Jiménez, A.; Barrera, M.A. Association between pre-transplant serum malondialdehyde levels and survival one year after liver transplantation for hepatocellular carcinoma. Int. J. Mol. Sci., 2016, 17(4), 500.
[http://dx.doi.org/10.3390/ijms17040500] [PMID: 27058525]
[50]
Lorente, L.; Martín, M.M.; Abreu-González, P.; Ramos, L.; Argueso, M.; Cáceres, J.J.; Solé-Violán, J.; Lorenzo, J.M.; Molina, I.; Jiménez, A. Association between serum malondialdehyde levels and mortality in patients with severe brain trauma injury. J. Neurotrauma, 2015, 32(1), 1-6.
[http://dx.doi.org/10.1089/neu.2014.3456] [PMID: 25054973]
[51]
Amioka, N.; Miyoshi, T.; Otsuka, H.; Takaishi, A.; Ueeda, M.; Hirohata, S.; Ito, H. Impact of Serum Malondialdehyde-Modified Low-Density Lipoprotein Levels on Admission for Predicting Prognosis in Patients With Acute Coronary Syndrome Who Received Successful Percutaneous Coronary Intervention Circulation., 2018, 138(Suppl_1), A10661-A10661.
[52]
Gökçe Çokal, B.; Yurtdaş, M.; Keskin Güler, S.; Güneş, H.N.; Ataç Uçar, C.; Aytaç, B.; Durak, Z.E.; Yoldaş, T.K.; Durak, İ.; Çubukçu, H.C. Serum glutathione peroxidase, xanthine oxidase, and superoxide dismutase activities and malondialdehyde levels in patients with Parkinson’s disease. Neurol. Sci., 2017, 38(3), 425-431.
[http://dx.doi.org/10.1007/s10072-016-2782-8] [PMID: 27900485]
[53]
Gómez-Marcos, M.A.; Blázquez-Medela, A.M.; Gamella-Pozuelo, L.; Recio-Rodriguez, J.I.; García-Ortiz, L.; Martínez-Salgado, C. Serum superoxide dismutase is associated with vascular structure and function in hypertensive and diabetic patients. Oxidative medicine and cellular longevity.,, 2016.
[http://dx.doi.org/10.1155/2016/9124676]
[54]
Wang, L.; Jia, J.; Zhang, J.; Li, K. Serum levels of SOD and risk of autism spectrum disorder: A case-control study. Int. J. Dev. Neurosci., 2016, 51, 12-16.
[http://dx.doi.org/10.1016/j.ijdevneu.2016.04.004] [PMID: 27091401]
[55]
Mohseni, R.; Arab Sadeghabadi, Z.; Goodarzi, M.T.; Teimouri, M.; Nourbakhsh, M.; Razzaghy Azar, M. Evaluation of Mn-superoxide dismutase and catalase gene expression in childhood obesity: its association with insulin resistance. J. Pediatr. Endocrinol. Metab., 2018, 31(7), 727-732.
[http://dx.doi.org/10.1515/jpem-2017-0322] [PMID: 29953407]
[56]
Tabeshpour, J.; Mehri, S.; Shaebani Behbahani, F.; Hosseinzadeh, H. Protective effects of Vitis vinifera (grapes) and one of its biologically active constituents, resveratrol, against natural and chemical toxicities: A comprehensive review. Phytother. Res., 2018, 32(11), 2164-2190.
[http://dx.doi.org/10.1002/ptr.6168] [PMID: 30088293]
[57]
Nüesch, E.; Trelle, S.; Reichenbach, S.; Rutjes, A.W.; Tschannen, B.; Altman, D.G.; Egger, M.; Jüni, P. Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study. BMJ, 2010, 341, c3515.
[http://dx.doi.org/10.1136/bmj.c3515] [PMID: 20639294]

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