February 1, 2014

Resveratrol in Diabetes Care

Study evaluates effects of resveratrol on several type 2 diabetes outcomes
Using a randomized double-blind placebo-controlled clinical trial, this study examined the effects of resveratrol in lowering blood glucose and other related outcomes (eg, insulin, metabolic markers, cardiovascular risk factors) in patients with type 2 diabetes.

Reference

Movahed A, Nabipour I, Lieben Louis X, et al. Antihyperglycemic effects of short term resveratrol supplementation in type 2 diabetic patients. Evid Based Complement Alternat Med. 2013;2013:851267.

Design

Using a randomized double-blind placebo-controlled clinical trial, this study examined the effects of resveratrol in lowering blood glucose and other related outcomes (eg, insulin, metabolic markers, cardiovascular risk factors) in patients with type 2 diabetes.

Participants

The participants were 66 subjects (33 females, 33 males) with type 2 diabetes (mean age=52.13 years). Two participants dropped out of the study. The subjects were randomly assigned to receive either 500 mg twice a day (a total of 1g/d) of resveratrol (n=33) or placebo tablets (n=31) for 45 days. Since the study was also intended to test the effectiveness of resveratrol when administered in conjunction with existing treatments against type 2 diabetes, all patients were allowed to continue with their antidiabetic medication.

Study Parameter Assessed

The assessments were taken at baseline and after 45 days of either resveratrol or placebo supplementation.

Primary Outcome Measures

The outcomes assessed were body weight, blood pressure, fasting blood glucose, haemoglobin A1c, insulin, homeostatic assessments for insulin resistance, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, and markers of liver and kidney damage.

Key Findings

Compared to baseline values, resveratrol treatment significantly decreased systolic blood pressure (129.03 ± 14.91 vs 121.45± 10.26; P<0.0001), fasting blood glucose (175.74 ± 49.63 vs 140.80 ± 39.74; P<-0.0001), hemoglobin A1c (8.6 ± 1.390 vs 7.60 ± 1.32; P<0.0001), insulin (10.20 ± 4.33 vs 5.37 ± 2.62; P<0.0001), and insulin resistance as measured by homeostasis model of assessment for insulin resistance, HOMA-IR (4.61 ± 2.77 vs. 1.91 ± 1.17; P<0.0001). In addition, HDL was significantly increased (41.40 ± 8.35 vs 46.15 ± 8.40; P=0.001), when compared to baseline levels. On the other hand, the placebo group had slightly increased fasting glucose (151.24 ± 51.52 vs 161.13 ± 53.16; P=0.002) and LDL (107.95 ± 31.67 vs 117.18 ± 29.88; P=0.003) when compared to baseline levels. Liver and kidney function markers were unchanged in the intervention group and placebo group.

No adverse effects were noted.

Practice Implications

Type 2 diabetes is one of the most prevalent chronic diseases in Western society, and consequently it has a major economic impact on healthcare. Numerous studies have demonstrated resveratrol can prevent, attenuate, or reverse diabetic dysfunction across multiple organ systems in animal models, including swine1 and nonhuman primates2–4 through targeting a complex array of signaling pathways. Despite its widespread use as a nutritional supplement and the fact that animal models have provided a strong case for resveratrol, well-designed human clinical trials examining the antidiabetic effects of resveratrol are limited.5

Indeed, a literature search identified 7 published human clinical trials, with 6 unique data sets, that have examined the effects of resveratrol treatment in diabetic adults.5–11 In general, these studies have found positive results for resveratrol on treating clinically relevant metabolic biomarkers in patients with type 2 diabetes.

Numerous studies have demonstrated resveratrol can prevent, attenuate, or reverse diabetic dysfunction across multiple organ systems.

For example, in the current randomized, double-blind, placebo-controlled clinical trial study, intake of 1 g/d of resveratrol for 45 days was found to significantly reduce systolic blood pressure, fasting blood glucose, hemoglobin A1c, insulin, and insulin resistance, while HDL was significantly increased, when compared to their baseline levels.11 The authors also found that resveratrol supplementation not only complemented standard antidiabetic medication but also provided added protection (over standard antidiabetic therapy).

These findings add to the results of recent clinical trials examining the effects of resveratrol supplementation in patients with type 2 diabetes. For example Bhatt et al6 and Brasnyo et al7 reported that treatment with resveratrol (250 g/day6 and 10mg/day7 respectively) resulted in an improvement in metabolic parameters in patients with type 2 diabetes.

In summary, even if resveratrol is effective in treating diabetic patients, it must be remembered that a number of other potential interventions exist, and therefore continued exploration of comparative efficacy and tolerability are essential.12 Future clinical trials should explore whether different dosages of resveratrol are at least equally effective as existing treatments, and also whether resveratrol can enhance the efficacy of existing pharmaceutical interventions. There is not yet sufficient long-term data to determine if clinical improvements in metabolic biomarkers are consistently accompanied by changes in the comorbidities associated with diabetes. Thus, there is reasonable incentive for continued exploration of the clinical efficacy of various resveratrol interventions as an adjunct to standard pharmaceutical management in type 2 diabetes through larger, long-duration clinical trials with additional outcome measures.

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References

1.  Burgess TA, Robich MP, Chu LM, Bianchi C, Sellke FW. Improving glucose metabolism with resveratrol in a swine model of metabolic syndrome through alteration of signaling pathways in the liver and skeletal muscle. Arch Surg. 2011;146(5):556-564.
2.  Marchal J, Blanc S, Epelbaum J, Aujard F, Pifferi F. Effects of chronic calorie restriction or dietary resveratrol supplementation on insulin sensitivity markers in a primate, Microcebus murinus. PLoS One. 2012;7(3):e34289.
3.  Fiori JL, Shin YK, Kim W, et al. Resveratrol Prevents beta-cell Dedifferentiation in Non-Human Primates Given a High Fat/ High Sugar Diet. Diabetes. 2013;62(10):3500-3513.
4.  Smoliga JM, Baur JA, Hausenblas HA. Resveratrol and health--a comprehensive review of human clinical trials. Mol Nutr Food Res. 2011;55(8):1129-1141.
5.  Tomé-Carneiro J, Larrosa M, Yáñez-Gascón MJ, et al. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res. 2013;72:69-82.
6.  Bhatt JK, Thomas S, Nanjan M J. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res. 2012;32(7):537-541.
7.  Brasnyo, P, Molnar GA, Mohas M, Marko L. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr. 2011;106(3):383-389.
8.  Elliott PJ, Walpole S, Morelli L, Lambert PD, Lunsmann W, Westphal CH, Lavu S. Resveratrol/SRT501 Sirtuin SIRT1 Activator Treatment of Type 2 Diabetes. Drugs Fut. 2009;34(4):291-295.
9.  Goh KP, Lee HY, Lau DP, Supaat W, Chan YH, Koh AFY. Effects of resveratrol in patients with type 2 diabetes mellitus on skeletal muscle SIRT1 expression and energy expenditure. Int J Sport Nutr Exerc Metab. 2013;[Epub ahead of print].
10. Kumar JB, Joghee NM. Resveratrol supplementation in patients with type 2 diabetes mellitus: A prospective, open label, randomized controlled trial. Inter Res J Pharmacy. 2013;4(8):245-249.
11. Movahed A, Nabipour I, Lieben LX, Thandapilly SJ, Yu L, et al. (2013). Antihyperglycemic effects of short term resveratrol supplementation in Type 2 Diabetic patients. Evid Based Complement Alternat Med. 2013;851267.
12. O'Connor AB. Building comparative efficacy and tolerability into the FDA approval process. JAMA. 2010;303(10):979-980.