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Published in: Acta Diabetologica 4/2018

01-04-2018 | Original Article

The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial

Authors: ShadiSadat Seyyedebrahimi, Hadi Khodabandehloo, Ensieh Nasli Esfahani, Reza Meshkani

Published in: Acta Diabetologica | Issue 4/2018

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Abstract

Aims

Oxidative stress plays a pivotal role in the pathogenesis of type 2 diabetes (T2D). In vitro and animal studies have shown that resveratrol exerts an antioxidant effect, but clinical trials addressing this effect in patients with T2D are limited. The aim of this study was to determine whether resveratrol supplementation affects oxidative stress markers in a randomized, placebo-controlled, double-blind clinical trial.

Methods

A total of 48 patients with T2D randomly were assigned to receive 800 mg/day resveratrol or placebo for 2 months. Plasma total antioxidant capacity, malondialdehyde concentration, protein carbonyl and total thiol contents, intracellular superoxide anion (O2·) and hydrogen peroxide (H2O2) in PBMCs, the expression of genes involved in oxidative stress responses (Nrf2, SOD, Cat, HO-1, RAGE, NOS) in PBMCs, and metabolic and anthropometric parameters were measured at the baseline and at the trial end.

Results

Compared with the placebo group, resveratrol reduced plasma protein carbonyl content and PBMCs O2· level and significantly increased plasma total antioxidant capacity and total thiol content. Furthermore, the expression of Nrf2 and SOD was significantly increased after resveratrol consumption. Resveratrol had no significant effects on the metabolic and anthropometric parameters except for a significant reduction in weight, BMI, and blood pressure levels. Resveratrol was well tolerated, and no serious adverse event was occurred.

Conclusions

Our study demonstrated that 8 weeks of supplementation with 800 mg/day resveratrol has an antioxidant effect in the blood and PBMCs of patients with T2D.
Clinical Trial Registry number and website IRCT registration number: IRCT2015072523336N1 and http://​en.​search.​irct.​ir/​view/​24752.
Appendix
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Literature
1.
go back to reference Brasnyó P, Sümegi B, Winkler G, Wittmann I (2013) Resveratrol and oxidative stress in diabetes mellitus. In: Preedy V (ed) Diabetes: oxidative stress and dietary antioxidants. Elsevier Inc., Amsterdam Brasnyó P, Sümegi B, Winkler G, Wittmann I (2013) Resveratrol and oxidative stress in diabetes mellitus. In: Preedy V (ed) Diabetes: oxidative stress and dietary antioxidants. Elsevier Inc., Amsterdam
3.
go back to reference Ilechukwu C, Ebenebe U, Ubajaka C, Ilika A, Emelumadu O, Nwabueze S (2014) The role of oxidative stress in diabetes mellitus: a 24-year review. Afrimedic J 5(1):1–7 Ilechukwu C, Ebenebe U, Ubajaka C, Ilika A, Emelumadu O, Nwabueze S (2014) The role of oxidative stress in diabetes mellitus: a 24-year review. Afrimedic J 5(1):1–7
5.
go back to reference Folli F, Corradi D, Fanti P et al (2011) The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro-and macrovascular complications: avenues for a mechanistic-based therapeutic approach. Curr Diabetes Rev 7(5):313–324CrossRefPubMed Folli F, Corradi D, Fanti P et al (2011) The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro-and macrovascular complications: avenues for a mechanistic-based therapeutic approach. Curr Diabetes Rev 7(5):313–324CrossRefPubMed
6.
go back to reference Tiwari BK, Pandey KB, Abidi A, Rizvi SI (2013) Markers of oxidative stress during diabetes mellitus. J Biomark, Art id 378790 Tiwari BK, Pandey KB, Abidi A, Rizvi SI (2013) Markers of oxidative stress during diabetes mellitus. J Biomark, Art id 378790
8.
go back to reference Timmers S, de Ligt M, Phielix E et al (2016) Resveratrol as add-on therapy in subjects with well-controlled type 2 diabetes: a randomized controlled trial. Diabetes Care 39(12):2211–2217CrossRefPubMed Timmers S, de Ligt M, Phielix E et al (2016) Resveratrol as add-on therapy in subjects with well-controlled type 2 diabetes: a randomized controlled trial. Diabetes Care 39(12):2211–2217CrossRefPubMed
9.
go back to reference Gawlik K, Naskalski J, Fedak D et al. (2015) Markers of antioxidant defense in patients with type 2 diabetes. Oxid Med Cell Longev 2016:2352361 Gawlik K, Naskalski J, Fedak D et al. (2015) Markers of antioxidant defense in patients with type 2 diabetes. Oxid Med Cell Longev 2016:2352361
15.
go back to reference de la Lastra CA, Villegas I (2007) Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications. Portland Press Limited, London de la Lastra CA, Villegas I (2007) Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications. Portland Press Limited, London
16.
go back to reference Wood LG, Wark PA, Garg ML (2010) Antioxidant and anti-inflammatory effects of resveratrol in airway disease. Antioxid Redox Signal 13(10):1535–1548CrossRefPubMed Wood LG, Wark PA, Garg ML (2010) Antioxidant and anti-inflammatory effects of resveratrol in airway disease. Antioxid Redox Signal 13(10):1535–1548CrossRefPubMed
18.
go back to reference Thazhath SS, Wu T, Bound MJ et al (2016) Administration of resveratrol for 5 wk has no effect on glucagon-like peptide 1 secretion, gastric emptying, or glycemic control in type 2 diabetes: a randomized controlled trial. Am J Clin Nutr 103(1):66–70CrossRefPubMed Thazhath SS, Wu T, Bound MJ et al (2016) Administration of resveratrol for 5 wk has no effect on glucagon-like peptide 1 secretion, gastric emptying, or glycemic control in type 2 diabetes: a randomized controlled trial. Am J Clin Nutr 103(1):66–70CrossRefPubMed
19.
go back to reference Chakraborty A, Chowdhury S, Bhattacharyya M (2011) Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients. Diabetes Res Clin Pract 93(1):56–62CrossRefPubMed Chakraborty A, Chowdhury S, Bhattacharyya M (2011) Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients. Diabetes Res Clin Pract 93(1):56–62CrossRefPubMed
20.
go back to reference Ghorbani M, Vatannejad A, Khodadadi I, Amiri I, Tavilani H (2016) Protective effects of glutathione supplementation against oxidative stress during cryopreservation of human spermatozoa. Cryoletters 37(1):34–40PubMed Ghorbani M, Vatannejad A, Khodadadi I, Amiri I, Tavilani H (2016) Protective effects of glutathione supplementation against oxidative stress during cryopreservation of human spermatozoa. Cryoletters 37(1):34–40PubMed
21.
go back to reference Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R (2003) Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 329(1):23–38CrossRefPubMed Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R (2003) Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 329(1):23–38CrossRefPubMed
23.
go back to reference Soufi FG, Mohammad-nejad D, Ahmadieh H (2012) Resveratrol improves diabetic retinopathy possibly through oxidative stress–nuclear factor κB—apoptosis pathway. Pharmacol Rep 64(6):1505–1514CrossRefPubMed Soufi FG, Mohammad-nejad D, Ahmadieh H (2012) Resveratrol improves diabetic retinopathy possibly through oxidative stress–nuclear factor κB—apoptosis pathway. Pharmacol Rep 64(6):1505–1514CrossRefPubMed
26.
go back to reference Shradha B, Sisodia S (2010) Diabetes, dyslipidemia, antioxidant and status of oxidative stress. Intern J Res Ayurveda Pharm 1(1):33–42 Shradha B, Sisodia S (2010) Diabetes, dyslipidemia, antioxidant and status of oxidative stress. Intern J Res Ayurveda Pharm 1(1):33–42
28.
go back to reference Leonard SS, Xia C, Jiang B-H et al (2003) Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun 309(4):1017–1026CrossRefPubMed Leonard SS, Xia C, Jiang B-H et al (2003) Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun 309(4):1017–1026CrossRefPubMed
30.
go back to reference De Groote D, Van Belleghem K, Deviere J, Van Brussel W, Mukaneza A, Amininejad L (2012) Effect of the intake of resveratrol, resveratrol phosphate, and catechin-rich grape seed extract on markers of oxidative stress and gene expression in adult obese subjects. Ann Nutr Metab 61(1):15–24. https://doi.org/10.1159/000338634 CrossRefPubMed De Groote D, Van Belleghem K, Deviere J, Van Brussel W, Mukaneza A, Amininejad L (2012) Effect of the intake of resveratrol, resveratrol phosphate, and catechin-rich grape seed extract on markers of oxidative stress and gene expression in adult obese subjects. Ann Nutr Metab 61(1):15–24. https://​doi.​org/​10.​1159/​000338634 CrossRefPubMed
32.
go back to reference Losa G (2003) Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells. Eur J Clin Investig 33(9):818–823CrossRef Losa G (2003) Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells. Eur J Clin Investig 33(9):818–823CrossRef
33.
go back to reference Bo S, Ciccone G, Castiglione A et al (2013) Anti-inflammatory and antioxidant effects of resveratrol in healthy smokers a randomized, double-blind, placebo-controlled, cross-over trial. Curr Med Chem 20(10):1323–1331CrossRefPubMed Bo S, Ciccone G, Castiglione A et al (2013) Anti-inflammatory and antioxidant effects of resveratrol in healthy smokers a randomized, double-blind, placebo-controlled, cross-over trial. Curr Med Chem 20(10):1323–1331CrossRefPubMed
34.
go back to reference Imamura H, Yamaguchi T, Nagayama D, Saiki A, Shirai K, Tatsuno I (2017) Resveratrol ameliorates arterial stiffness assessed by cardio-ankle vascular index in patients with type 2 diabetes mellitus. Int Heart J 58(4):577–583CrossRefPubMed Imamura H, Yamaguchi T, Nagayama D, Saiki A, Shirai K, Tatsuno I (2017) Resveratrol ameliorates arterial stiffness assessed by cardio-ankle vascular index in patients with type 2 diabetes mellitus. Int Heart J 58(4):577–583CrossRefPubMed
35.
go back to reference Samsamikor M, Daryani NE, Asl PR, Hekmatdoost A (2016) Resveratrol supplementation and oxidative/anti-oxidative status in patients with ulcerative colitis: a randomized, double-blind, placebo-controlled pilot study. Arch Med Res 47(4):304–309CrossRefPubMed Samsamikor M, Daryani NE, Asl PR, Hekmatdoost A (2016) Resveratrol supplementation and oxidative/anti-oxidative status in patients with ulcerative colitis: a randomized, double-blind, placebo-controlled pilot study. Arch Med Res 47(4):304–309CrossRefPubMed
41.
go back to reference Méndez-del Villar M, González-Ortiz M, Martínez-Abundis E, Pérez-Rubio KG, Lizárraga-Valdez R (2014) Effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord 12(10):497–501CrossRefPubMed Méndez-del Villar M, González-Ortiz M, Martínez-Abundis E, Pérez-Rubio KG, Lizárraga-Valdez R (2014) Effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord 12(10):497–501CrossRefPubMed
43.
go back to reference Kim S, Jin Y, Choi Y, Park T (2011) Resveratrol exerts anti-obesity effects via mechanisms involving down-regulation of adipogenic and inflammatory processes in mice. Biochem Pharmacol 81(11):1343–1351CrossRefPubMed Kim S, Jin Y, Choi Y, Park T (2011) Resveratrol exerts anti-obesity effects via mechanisms involving down-regulation of adipogenic and inflammatory processes in mice. Biochem Pharmacol 81(11):1343–1351CrossRefPubMed
44.
go back to reference Lasa A, Churruca I, Eseberri I, Andrés-Lacueva C, Portillo MP (2012) Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes. Mol Nutr Food Res 56(10):1559–1568CrossRefPubMed Lasa A, Churruca I, Eseberri I, Andrés-Lacueva C, Portillo MP (2012) Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes. Mol Nutr Food Res 56(10):1559–1568CrossRefPubMed
45.
go back to reference Wang S, Liang X, Yang Q et al (2015) Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1. Int J Obes 39(6):967–976CrossRef Wang S, Liang X, Yang Q et al (2015) Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1. Int J Obes 39(6):967–976CrossRef
50.
go back to reference Tomé-Carneiro J, Larrosa M, González-Sarrías A, Tomas-Barberan FA, Teresa Garcia-Conesa M, Carlos Espin J (2013) Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Curr Pharm Des 19(34):6064–6093CrossRefPubMedPubMedCentral Tomé-Carneiro J, Larrosa M, González-Sarrías A, Tomas-Barberan FA, Teresa Garcia-Conesa M, Carlos Espin J (2013) Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Curr Pharm Des 19(34):6064–6093CrossRefPubMedPubMedCentral
52.
go back to reference Liu Z, Song Y, Zhang X et al (2005) Effects of trans-resveratrol on hypertension-induced cardiac hypertrophy using the partially nephrectomized rat model. Clin Exp Pharm Physiol 32(12):1049–1054CrossRef Liu Z, Song Y, Zhang X et al (2005) Effects of trans-resveratrol on hypertension-induced cardiac hypertrophy using the partially nephrectomized rat model. Clin Exp Pharm Physiol 32(12):1049–1054CrossRef
Metadata
Title
The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial
Authors
ShadiSadat Seyyedebrahimi
Hadi Khodabandehloo
Ensieh Nasli Esfahani
Reza Meshkani
Publication date
01-04-2018
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 4/2018
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-017-1098-3

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