Efeitos da suplementação com polifenol resveratrol em pacientes com diabetes mellitus tipo 2: uma revisão sistemática
DOI:
https://doi.org/10.33448/rsd-v9i10.8659Palavras-chave:
Resveratrol; Diabetes mellitus; Glicemia; Estresse oxidativo.Resumo
O presente estudo objetivou revisar sobre os efeitos da suplementação com resveratrol em pacientes diagnosticados com DM2. Trata-se de uma revisão sistemática, realizada mediante pesquisas nas bases de dados eletrônicos PubMed, Lilacs e Medline, publicados na língua inglesa, no período de 2011 a 2019, com os descritores “Resveratrol” and “Diabetes Mellitus”. Os critérios de inclusão utilizados foram: ensaio clínicos randomizados realizados com indivíduos com DM tipo 2. Foram excluídos estudos com animais, gestantes, lactantes, além de indivíduos com idade inferior a 18 anos. Observou-se que os efeitos da suplementação do resveratrol mais predominantes nesses pacientes foram relacionados a melhora na sensibilidade a insulina, ao controle glicêmico e uma possível redução do estresse oxidativo. Ainda existem controvérsias na literatura quanto a sua real eficácia nos pacientes diabéticos. Contudo não é descartada a utilização do resveratrol como adjuvante a terapia hipoglicemiante.
Referências
American Diabetes Association-ADA. (2019). Classification and Diagnosis of diabetes mellitus. Diabetes Care. 42 (Supl1), 513-528. https://www.diabetes.org.br /profissionais/images/pdf/Diretriz-2019-ADA.pdf
Avogaro, A., Kreutzenberg, S. V., & Fadini, G. (2008). Endothelial dysfunction: Causes and consequences in patients with diabetes mellitus. Diabetes Research and Clinical Practice, 82:S94–S101. https://doi.org/10.1016/j.diabres.2008.09.021
Bashmakov, Y. K., Assaad-Khalil, S., & Petyaev, I. M. (2011). Resveratrol may be beneficial in treatment of diabetic foot syndrome. Medical Hypotheses, 77(3), 364–367. https://doi.org/10.1016/j.mehy.2011.05.016
Bashmakov, Y. K., Assaad-khalil, S. H., Abou seif, M., Udumyan, R., Megallaa, M., Rohoma, K. H., et al. (2014). Resveratrol Promotes Foot Ulcer Size Reduction in Type 2 Diabetes Patients. ISRN Endocrinology, 2014:1–8. https://doi.org/10.1155/2014/816307
Bhatt, J. K., Thomas, S., & Nanjan, M. J. (2012). Resveratrol supplementation improves glycemic control in type2 diabetes mellitus. Nutrition Research. 32(7), 537–541. https://doi.org/10.1016/j.nutres.2012.06.003
Bo, S., Ponzo, V., Ciccone, G., Evangelhista, A., Saba, F., Goitre, I., et al. (2016). Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. Pharmacological Research, 111:896–905. https://doi.org/10.1016/j.phrs.2016.08.010
Bo, S., Ponzo, V., Evangelista, A., Ciccone, G., Goitre, I., Saba, F., et al. (2017). Effects of 6 months of resveratrol versus placebo on pentraxin 3 in patients with type 2 diabetes mellitus: a double-blind randomized controlled trial. Acta Diabetologica. 54(5),499–507. https://doi.org/10.1007/s00592-017-0977-y
Bode, L.M., Bunzel, D., Huch, M., Cho, G.S., Ruhland, D., Bunzel, M., et al. (2013). In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. Am J Clin Nutr, 97(2), 295–309. https://doi.org/10.3945/ajcn.112.049379
Brasnyo, P., Molnar, G.A., Mohás, M., Marko, L., Laczy, B., Cseh, J., et al. (2011). Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr. 106(3), 383-389. https://doi.org/10.1017/S0007114511000316
Chen, W.P., Chi, T.C., Chuang, L.M., & Su, M. (2007). Resveratrol enhances insulin secretion by blocking KATP and KV channels of beta cells. Eur J Pharmacol, 568(1-3), 269–77. https://doi.org/10.1016/j.ejphar.2007.04.062
Christenson, J., Whitby, S. J., Mellor, D., Thomas, J., McKune, A., Roach, P. D, et al. (2016). The efects of resveratrol supplementation in overweight and obese humans: a systematic review of randomized trials. Metab Syndr Relat Disord, 14(7), 323–333. https://doi.org/10.1089/met.2016.0035
Dalle-donne, I., Rossi, R., Giustarini, D., Milzani, A., & Colombo, R. (2003). Protein carbonyl groups as biomarkers of oxidative stress. Rev.Clin Chim Acta. 329(1-2), 23–38. https://doi.org/10.1016/S0009-8981(03)00003-2.
Daniel. R., Gokulanathan, S., Shanmugasundaram, N., Lakshmigandhan, M., & Kavin, T. (2012). Diabetes and periodontal disease. J Pharm Bioallied Sci, 4(2), 280–282. https://doi.org/10.4103/0975-7406.100251
Do, G. M., Jung, U. J., Park, H. J., Kwon, E. Y., Jeon, S. M, McGregor, R. A., et al. (2012). Resveratrol ameliorates diabetes-related metabolic changes via activation of AMPactivated protein kinase and its downstream targets in db/db Mice. Molecular Nutrition & Food Research.56(8),1282–1291. https://doi.org/10.1002/mnfr.201200067
Elgebaly, A., Radwan, I. A., Aboelnas, M. M., Ibrahim, H. H., Eltoomy, M. F. M, Atta, A. A, et al. (2017). Resveratrol supplementation in patients with non-alcoholic fatty liver disease: systematic review and meta-analysis. J Gastrointest Liver Dis, 26(1),59–67. https://doi.org/10.15403/jgld.2014.1121.261.ely.
Evans, J. L., Maddux, Ba., & Goldfine, I. D. (2005). The molecular basis for oxidative stress induced insulin resistance. Antioxid Redox Signal, 7(7), 1040–1052. https://doi.org/10.1089/ars.2005.7.1040
Faghihzadeh, F., Adibi, P., Rafei, R., & Hekmatdoost, A. (2014). Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease. Nutr Res, 34(10):837–843. https://doi.org/10.1016/j.nutres.2014.09.005
Ghanim, H., Sai, C. L., Abuaysheh, S., Korzeniewski, K., Patnaik, P., Marumganti, A., et al. (2010). An Antiinflammatory and Reactive Oxygen Species Suppressive Effects of an Extract ofPolygonum CuspidatumContaining Resveratrol. The Journal of Clinical Endocrinology & Metabolism. 95(9),1–8. https://doi.org/10.1210/jc.2010-482
Glodzik, L., Randall, C., Rusinek, H., & de Leon, M. J. (2013). Cerebrovascular reactivity to carbon dioxide in Alzheimer’s disease. A review. Journal of Alzheimer's disease. 35(3),427-40. https://doi.org/10.3233/JAD-122011
Gregg, E. W., Sattar N., & Ali, M. K. (2016). The changing face of diabetes complications. Lancet Diabetes Endocrinol. 4(6), 537-47. https://doi.org/10.1016/S2213-8587(16)30010-9
Groote, D., Van belleghem, K., Deviere, J., Van Brussel, W., Mukaneza, A., Amininejad, L., et al. (2012). Efect 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. Rev. Ann Nutr Metab. 61(1),15–24. https://doi.org/10.1159/000338634
Grover, H. S., & Luthra, S. (2013). Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease. J Indian Soc Periodontol, 17(3), 292–301. https://doi.org/10.4103/0972-124X.115642
Hahn, G. F., Oliveira, J. R., & Bock, P. M. (2017). The role of factor 2 erythroid nuclear factor 2 (Nrf2) in diabetes mellitus. Clin Biomed Res. 37(3), 203-213.
Hu, P., Zhao, L., & Chen, J. (2014). Physiologically achievable doses of resveratrol enhance 3T3-L1 adipocyte diferentiation. Eur J Nutr, 54(4), 569–579. https://doi.org/10.1007/s00394-014-0738-4
Imamura, H., Yamaguchi, T., Nagayama, D., Saik, A., Shirai, K., & Tatsuno, I. (2017). Resveratrol ameliorates arterial stifness assessed by cardio-ankle vascular index in patients with type 2 diabetes mellitus. Int Heart J. 58(4):577–583. https://doi.org/10.1536/ihj.16-373
International Diabetes Federation. IDF Atlas. 8. ed. Bruxelas: International Diabetes Federation; 2017. Recuperado de https://www.diabetesatlas.org/em /resources/?gclid=CjwKCAjw19z6BRAYEiwAmo64LS_2q5VvWM1E-J
Javid, Z. A., Hormoznejad, R., Yousefimanesh, H., Zakerkish, M., Haghighi‐zadeh, M. H., Dehghan, P., et al. (2016). The Impact of Resveratrol Supplementation on Blood Glucose, Insulin, Insulin Resistance, Triglyceride, and Periodontal Markers in Type 2 Diabetic Patients with Chronic Periodontitis. Phytotherapy Research, 31(1),108–114. https://doi.org/10.1002/ptr.5737
Jiang, W.J. (2008). Sirtuins: novel targets for metabolic disease in drug development. Biochem Biophys Res Commun, 373(3), 341–344. https://doi.org/10.1016/j.bbrc.2008.06.048
Juhasz, B., Varga, B., Gesztelyi, K. A., Zsuga, J., & Tosaki, A. (2010). Resveratrol: a multifunctional cytoprotective molecule. Current Pharmaceutical Biotechnology. 11(8), 810–818. https://doi.org 10.2174/138920110793262079
Kennedy, D. O., Wightman, E. L., Reay, J. L., Lietz, G., Okello, E. J., Wilde. A., et al. (2010). Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr, 91(6),1590-7. https://doi.org/10.3233/JAD-122011
Kim, S., Jin, Y., Choi, Y., & Park, T. (2011). Resveratrol exerts anti-obesity efects via mechanisms involving down-regulation of adipogenic and infammatory processes in mice. Biochem Pharmacol, 81(11),1343–135. https://doi.org/10.1016/j.bcp.2011.03.012
Lagouge, M., Argmann, C., Gerhart-hines, Z., Meziane, H., Lerin, C., Daussin, F., et al. (2006). Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell, 127(6):1109–22. https://doi.org/10.1016/j.cell.2006.11.013
Lasa, A., Churruca, I., Eseberri, I., Andres-Lacueva, C., & Portillo, M. P. (2012) Delipidating efect of resveratrol metabolites in 3T3-L1 adipocytes. Mol Nutr Food Res, 56(10):1559–68. https://doi.org/10.1002/mnfr.201100772
Lee, H., & Ko, G. (2014). Effect of metformin on metabolic improvement and gut microbiota. Appl Environ Microbiol, 80(19), 5935–43. https://doi.org/10.1128/AEM.01357-14
Lontchi-yimagou, E., Sobngwi, E., Matsha, T. E., & Kengne, A. P. (2013) Diabetes mellitus and inflammation. Curr Diabetes Rep. 13:435–444. https://doi.org/10.1007/s11892-013-0375-y
Louis, X. L., Thandapilly, S. J., Mohankumar, S. K., Yu, L.,Taylor, C. G., Zahradka, P., et al. (2012). Treatment with low- dose resveratrol reverses cardiac impairment in obese prone but not in obese resistant rats. Journal of Nutritional Biochemistry. 23(9), 1163–9. https://doi.org/10.1016/j.jnutbio.2011.06.010
Maratos-flier, E. (2013) Metabolic disease puts up a fight: microbes, metabolism and medications. Nature Medicine, 19:1218–19. https://doi.org/10.1038/nm.3373
Méndez-del villar, M., González-ortiz, M., Martínez-abundis, E., Karina, G., Perez, R., & Valdez, R .L. (2014). Efect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord, 12(10):497–501. https://doi.org/10.1089/met.2014.0082
Movahed, A., Nabipour, I., Lieben, L. X., Thandapilly, S. J., Yu, L., Kalantarhormozi, M., et al. (2013). Antihyperglycemic effects of short termresveratrol supplementation in type 2 diabetic patients. Evid Based Complement Alternat Med, 2013,1-11. https://doi.org/10.1155/2013/851267
Pereira, A. S., Shitsuka, D. M., Parreira, F. J., & Shitsuka, R. (2018). Metodologia da pesquisa científica. [e-book]. Santa Maria. Ed. UAB/NTE/UFSM. Recuperado de https://repositorio.ufsm.br/bitstream/handle/1/15824/Lic_Computacao_MetodologiaPesquisa-Cientifica.pdf?sequence=1.
Rivera, L., Moro, N. R., Zarzuelo, A., & Galisteo, M. (2009). Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol, 77(6),1053–63. https://doi.org/10.1016/j.bcp.2008.11.027
Schmatz, R., Perreira, L.B., Stefanello, N., Mazzanti, C., Spanevello, R., Gutierres, J., et al. (2012). Efects of resveratrol on biomarkers of oxidative stress and on the activity of delta aminolevulinic acid dehydratase in liver and kidney of streptozotocin-induced diabetic rats. Rev. Biochimie. 94(2), 374–383. https://doi.org/10.1016/j.biochi.2011.08.005
Seyyedebrahimi, S., Khodabandehloo, H., Nasliesfahani, 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. (2018). Rev.Acta Diabetol. 55(4),341-353. https://doi.org/10.1007/s00592-017-1098-3
Sharma, S., Misra, C. S., Arumugam, S., Roy, S., Shah, V., Davis, J. A, et al. (2011). Antidiabetic activity of resveratrol, a known SIRT1 activator in a genetic model for type-2 diabetes. Phytotherapy Research. 25(1),67–73. https://doi.org/10.1002/ptr.3221
Souf, F. G., Mohammad-nejad, D., & Ahmadieh H. (2012). Resveratrol improves diabetic retinopathy possibly through oxidative stress-nuclear fator-κB apoptosis pathway. Rev. Pharmacol. 64(6), 1505–14. https://doi.org/10.1016/S1734-1140(12)70948-9
Stanko, P., & Izakovicova Holla, L. (2014). Bidirectional association between diabetes mellitus and inflammatory periodontal disease. A review. Biomedical Papers of the Medical Faculty of the University Palacky Olomouc Czech Repub, 158(1), 35–38. https://doi.org/10.5507/bp.2014.005
Tamaki, N., Campos, R. C. O., Inagaki, Y., Fukui, M., Nagata, T., & Ito, H. O. (2014). Resveratrol improves oxidative stress and prevents the progression of periodontitis via the activation of the Sirt1/AMPK and the Nrf2/antioxidant defense pathways in a rat periodontitis model. Free Radic Biol Med, 75,222–229. https://doi.org/10.1016/j.freeradbiomed.2014.07.034
Thadapilly, S. J., Wojciechowski, P., Behbahani, J., Louis, X. L., Yu, L., Juric, D., et al. (2010). Resveratrol prevents the development of pathological cardiac hypertrophy and cantractile dysfunction in the SHR without lowering blood pressure. American Journal of Hypertension. 23(2), 192–196. https://doi.org/10.1038/ajh.2009.228
Thandapilly, S. J., Louis, X. L., Yang, T., Stringer, D. M., Yu, L., Zhang, S., et al. (2011). Resveratrol prevents norepinephrine induced hypertrophy in adult rat cardiomyocytes, by activating NO-AMPK pathway. European Journal of Pharmacology. 668(1-2), 217–224.
Thirunavukkarasu, M., Penumathsa, S. V., Koneru, S., Juhasz, B., Zhan, L., Otani H, et al. (2007). Resveratrol alleviates cardiac dysfunction in streptozotocininduced diabetes: role of nitric oxide, thioredoxin, and heme oxygenase. Free Radic Biol Med, 43(5),720–729. https://doi.org/10.1016/j.freeradbiomed.2007.05.004
Timmers, S., De ligt, M., Phielix, E., Weijer, T. V., Hansen, J., Kornips, E M., et al. (2016). Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial. Diabetes Care, 39(12),2211–17. https://doi.org/10.2337/dc16-0499
Timmers, S., Hesselink, M. K., & Schrauwen, P. (2013). Therapeutic potential of resveratrol in obesity and type 2 diabetes: new avenues for health benefits? Ann N Y Acad Sci, 1290(1),83–89. https://doi.org/10.1111/nyas.12185
Tomé-carneiro, J., Larrosa, M., González-sarrías, A., Barberan, A. T., Garcia, T., & Juan, C. (2013). Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Curr Pharm Des, 19(34),6064–93. https://doi.org/10.2174/13816128113199990407
Wang, S., Liang, X., Yang, Q., Fu, X., Rogers, C. J., Zhu, M., et al. (2015) Resveratrol induces brownlike adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1. Int J Obes, 39(6), 967–976. https://doi.org/10.1038/ijo.2015.23
Witte, A. V., Kerti, L., Margulies, D. S., & Floel, A. (2014). Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. The Journal of Neuroscience. 34(23),7862-70. https://doi.org/10.1523/JNEUROSCI.0385-14.2014
Yang, J. Y., Della-fera, M. A., Rayalam, S., Ambati, S., Hartzell, D. L., Park, H. J, et al. (2008). Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin. Life Sci, 82(20),1032–1039. https://doi.org/10.1016/j.lfs.2008.03.003
Yu, W., Fu, Y., & Wang, W. (2012). Cellular and molecular effects of resveratrol in health and disease. Journal of Cellular Biochemistry. 113(3), 752–759. https://doi.org/10.1002/jcb.23431.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2020 Valéria Silva de Lima; Alane Nogueira Bezerra; Natasha Vasconcelos Albuquerque; Camila Pinheiro Pereira ; Camila Moreira da Costa Alencar; Ana Thaís Alves Lima; Kelly Christine de Assis Ferreira

Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Autores que publicam nesta revista concordam com os seguintes termos:
1) Autores mantém os direitos autorais e concedem à revista o direito de primeira publicação, com o trabalho simultaneamente licenciado sob a Licença Creative Commons Attribution que permite o compartilhamento do trabalho com reconhecimento da autoria e publicação inicial nesta revista.
2) Autores têm autorização para assumir contratos adicionais separadamente, para distribuição não-exclusiva da versão do trabalho publicada nesta revista (ex.: publicar em repositório institucional ou como capítulo de livro), com reconhecimento de autoria e publicação inicial nesta revista.
3) Autores têm permissão e são estimulados a publicar e distribuir seu trabalho online (ex.: em repositórios institucionais ou na sua página pessoal) a qualquer ponto antes ou durante o processo editorial, já que isso pode gerar alterações produtivas, bem como aumentar o impacto e a citação do trabalho publicado.