Effect of Resveratrol on Markers of Oxidative Stress and Sirtuin 1 in Elderly Adults with Type 2 Diabetes.

Type 2 diabetes (T2D) affects a large part of the adult population and impairs its quality of life. Because of this, natural compounds with antioxidant, anti-inflammatory and hypoglycemic properties have been used as adjuvants. Among these compounds, resveratrol (RV) stands out, a polyphenol that has been studied in several clinical trials, the results of which are controversial. We conducted a randomized clinical trial on 97 older adults with T2D to evaluate the effect of RV on oxidative stress markers and sirtuin 1, using doses of 1000 mg/day (EG1000, n = 37) and 500 mg/day (EG500, n = 32) compared with a placebo (PG, n = 28). Biochemical markers, oxidative stress and sirtuin 1 levels were measured at baseline and after six months. We observed a statistically significant increase (p < 0.05) in total antioxidant capacity, antioxidant gap, the percentage of subjects without oxidant stress and sirtuin 1 levels in EG1000. In the PG, we observed a significant increase (p < 0.05) in lipoperoxides, isoprostanes and C-reactive protein levels. An increase in the oxidative stress score and in the percentage of subjects with mild and moderate oxidative stress was observed too. Our findings suggest that 1000 mg/day of RV exerts a more efficient antioxidant effect than 500 mg/day.

Influence of Age and Dose on the Effect of Resveratrol for Glycemic Control in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis.

Background: Several clinical trials have suggested that resveratrol has hypoglycemic properties; however, there are other studies in which such an effect has not been observed. Methods: We carried out a systematic search in several databases; seventeen studies were selected for the systematic review and fifteen were included in the meta-analysis. Results: Resveratrol decreases glucose levels in subjects aged 45−59 years at doses <250 mg/day (−8.64 mg/dL, p < 0.00001), 250−500 mg/day (−22.24 mg/dL, p = 0.0003), and 500−1000 mg/day (−28.40 mg/dL, p = 0.0008), while in subjects older than 60 years, it only decreases with doses of 250−500 mg/day. Likewise, HbA1c improved in subjects aged 45−59 years with doses of 250−500 mg (−0.60%, p < 0.00001), but not in subjects older than 60 years. Insulin levels improved in subjects aged 45−59 years with doses < 250 mg/day (−0.80 mIU/L, p = 0.0003) and doses of 250−500 mg/day (−5.0 mIU/L, p = 0.0003), although in subjects older than 60 years, they only improved with doses of 250−500 mg/day (−1.79 mIU/L, p = 0.01). On the other hand, HOMA-IR only improved in subjects older than 60 years with doses of 250−500 mg/day (−0.40, p = 0.01). Conclusions: Resveratrol has a statistically significant dose−response effect on glucose concentrations, HbA1c, and insulin levels; however, there is not enough scientific evidence to propose a therapeutic dose.

Hypoglycemic Effect of Resveratrol: A Systematic Review and Meta-Analysis.

Resveratrol (RV) is a polyphenolic compound with antioxidant, anti-inflammatory, and hypoglycemic properties. Several in vitro and animal model studies have demonstrated the beneficial effects of RV; however, the results in humans are not conclusive. After a search of different databases, 32 studies were selected for this systematic review and 30 were included in the meta-analysis. Studies that evaluated the effect of RV on glucose, insulin, HbA1c, and insulin resistance (HOMA-IR) levels were included. A significant decrease of glucose (-5.24 mg/dL, p = 0.002) and insulin levels (-1.23 mIU/L, p = 0.0003) was observed. HbA1c and HOMA-IR did not show significant changes. Due to heterogeneity, sub-analyzes were performed. Sub-analysis by dose revealed that glucose levels improve significantly after the administration of 500-1000 mg/day of RV (-7.54 mg/dL, p = 0.002), while insulin improves with doses lower than 500 mg/day (-1.43 mIU/L, p = 0.01) and greater than 1000 mg/day (-2.12 mIU/L, p = 0.03). HbA1c and HOMA-IR remained unchanged after sub-analysis by dose. Our findings suggest that RV improves glucose and insulin levels in subjects with type 2 diabetes mellitus (T2DM) and aged 45-59 years, regardless of the duration of the intervention. HbA1c improves with interventions ≥3 months. HOMA-IR does not exhibit significant changes after RV administration.

The Effect of 600 mg Alpha-lipoic Acid Supplementation on Oxidative Stress, Inflammation, and RAGE in Older Adults with Type 2 Diabetes Mellitus.

Alpha-lipoic acid (ALA) has been used as a dietary supplement at different doses in patients with diabetes mellitus type 2 (T2DM) due to its antioxidant, anti-inflammatory, and hypoglycemic effects. However, the reports on the effects of ALA are controversial. For this reason, the purpose of the present study was to determine the effect of 600 mg/day of ALA on the markers of oxidative stress (OxS) and inflammation and RAGE in older adults with T2DM. A quasiexperimental study was carried out with a sample of 135 sedentary subjects (98 women and 37 men) with a mean age of 64 ± 1 years, who all had T2DM. The sample was divided into three groups: (i) experimental group (EG) with 50 subjects, (ii) placebo group (PG) with 50 subjects, and control group (CG) with 35 subjects. We obtained the following measurements in all subjects (pre- and posttreatment): glycosylated hemoglobin (HbA1c), receptor for advanced glycation end products (RAGE), 8-isoprostane, superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant status (TAS), and inflammatory (CRP, TNF-α, IL-6, IL-8, and IL-10) markers. Regarding the effect of ALA on HbA1c, a decrease was observed in the EG (baseline 8.9 ± 0.2 vs. posttreatment 8.6 ± 0.3) and the PG (baseline 8.8 ± 0.2 vs. posttreatment 8.4 ± 0.3) compared to the CG (baseline 8.8 ± 0.3 vs. six months 9.1 ± 0.3) although the difference was not statistically significant (p < 0.05). There was a statistically significant decrease (p < 0.05) in the blood concentration of 8-isoprostane in the EG and PG with respect to the CG (EG: baseline 100 ± 3 vs. posttreatment 57 ± 3, PG: baseline 106 ± 7 vs. posttreatment 77 ± 5, and CG: baseline 94 ± 10 vs. six months 107 ± 11 pg/mL). Likewise, a statistically significant decrease (p < 0.05) in the concentration of the RAGE was found in the EG (baseline 1636 ± 88 vs. posttreatment 1144 ± 68) and the PG (baseline 1506 ± 97 vs. posttreatment 1016 ± 82) compared to CG (baseline 1407 ± 112 vs. six months 1506 ± 128). A statistically significant decrease was also observed in all markers of inflammation and in the activity of SOD and GPx in the CG with respect to the EG and PG. Our findings suggest that the administration of ALA at a dose of 600 mg/day for six months has a similar effect to that of placebo on oxidative stress, inflammation, and RAGE in older adults with T2DM. Therefore, higher doses of ALA should be tried to have this effect. This trial is registered with trial registration number ISRCTN13159380.