Resveratrol, a polyphenol found in the skins of red grapes, is a potent antioxidant that is being touted for its anti-inflammatory, anti-cancer, anti-aging, and cardioprotective effects. Some studies have shown that resveratrol intake improves insulin sensitivity in diabetic rats and patients with type 2 diabetes mellitus (T2DM).1-3 However, studies with resveratrol have been inconsistent with a few randomized control trials showing that it was not an effective glycemic control agent.4,5
A new review attempted to resolve these contradictions by examining the data from the randomized control trials carried out in the past. The results of this analysis were published recently in Nutrition and Metabolism.6 Nine randomized clinical trials involving a total of 283 participants with T2DM were included in the analysis. While all studies monitored fasting plasma glucose, some also monitored glycated hemoglobin (HbA1c) and insulin resistance. They also monitored systolic and diastolic blood pressure, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and insulin concentrations. The daily dose of resveratrol in these studies ranged from 8 milligrams to 3000 milligrams taken over a period that varied from four weeks to 12 months. The data from these studies were pooled together and statistically analyzed.
The results show that resveratrol significantly reduced fasting plasma glucose levels in patients with T2DM compared to the control group. Fasting plasma glucose levels were reduced significantly in patients who received high doses of resveratrol but did not decline in those who received low doses.
Glycated hemoglobin (HbA1c or hemoglobin that is bound to glucose) levels are a good indicator of the blood glucose levels during the six to eight weeks before the test and are not affected by the everyday spikes and dips in blood glucose levels. Of the nine studies used for analysis, six had data on HbA1c levels, which involved 228 patients. Analysis of this data shows that HbA1c levels did not decline with resveratrol intake: they remained unchanged.
Analysis of inulin resistance data, which was obtained from five trials and involved 153 patients, showed that insulin resistance was significantly reduced (or sensitivity to insulin significantly improved) with resveratrol intake. The data also revealed a decline in insulin levels and systolic and diastolic blood pressure with resveratrol intake. However, LDL-c and HDL-c levels were unaffected by resveratrol intake. A high dose (more than 100 milligrams/day) was effective in lowering glucose levels, whereas low doses (less than 100 milligrams/day) had no effect.
A notable limitation of the study was that different forms of resveratrol (extracts and powders) were used, and the dose and duration of dosage across different studies was variable. These differences can affect the inferences drawn, and therefore, further studies on a larger scale are required to understand the dose-dependent effects of resveratrol.
Overall, these results show that resveratrol intake improves glycemic control in individuals with type 2 diabetes mellitus. The various antidiabetic and glycemic control agents that are currently in use (insulin, biguanides, sulfonylureas, α-glucosidase inhibitors, and DPP-4 inhibitors) are limited because of contraindications or side effects such as hypoglycemia and weight gain. A few studies have shown that resveratrol at a dose of up to 1 gram/day has no toxic effects.5,7 While these results need to be validated in larger trials, resveratrol may represent a viable alternative for the management of type 2 diabetes mellitus.
Written by Usha B. Nair, Ph.D.
- Méndez-del Villar M, González-Ortiz M, Martínez-Abundis E, Pérez-Rubio KG, Lizárraga-Valdez R. Effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord. 2014 Dec;12(10):497-501. doi: 10.1089/met.2014.0082. Epub 2014 Aug 19. PubMed PMID: 25137036.
- González-Rodríguez Á, Santamaría B, Mas-Gutierrez JA, Rada P, Fernández-Millán E, Pardo V, Álvarez C, Cuadrado A, Ros M, Serrano M, Valverde ÁM. Resveratrol treatment restores peripheral insulin sensitivity in diabetic mice in a sirt1-independent manner. Mol Nutr Food Res. 2015 Aug;59(8):1431-42. doi: 10.1002/mnfr.201400933. Epub 2015 Apr 28. PubMed PMID: 25808216.
- Lee YE, Kim JW, Lee EM, Ahn YB, Song KH, Yoon KH, Kim HW, Park CW, Li G, Liu Z, Ko SH. Chronic resveratrol treatment protects pancreatic islets against oxidative stress in db/db mice. PLoS One. 2012;7(11):e50412. doi: 10.1371/journal.pone.0050412. Epub 2012 Nov 30. PubMed PMID: 23226280; PubMed Central PMCID: PMC3511555.
- Bo S, Ponzo V, Ciccone G, Evangelista A, Saba F, Goitre I, Procopio M, Pagano GF, Cassader M, Gambino R. Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. Pharmacol Res. 2016 Sep;111:896-905. doi: 10.1016/j.phrs.2016.08.010. Epub 2016 Aug 9. PubMed PMID: 27520400.
- Thazhath SS, Wu T, Bound MJ, Checklin HL, Standfield S, Jones KL, Horowitz M, Rayner CK. 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. 2016 Jan;103(1):66-70. doi: 10.3945/ajcn.115.117440. Epub 2015 Nov 25. PubMed PMID: 26607942.
- Zhu X, Wu C, Qiu S, Yuan X, Li L. Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: systematic review and meta-analysis. Nutr & Metab. 2017 Sept;14:60. doi: 10.1186/s12986-017-0217-z.
- Movahed A, Nabipour I, Lieben Louis X, Thandapilly SJ, Yu L, Kalantarhormozi M, Rekabpour SJ, Netticadan T. Antihyperglycemic effects of short term resveratrol supplementation in type 2 diabetic patients. Evid Based Complement Alternat Med. 2013;2013:851267. doi: 10.1155/2013/851267. Epub 2013 Sep 1. PubMed PMID: 24073011; PubMed Central PMCID: PMC3773903.