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

Abstract

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.

Impact of Alpha-Lipoic Acid Chronic Discontinuous Treatment in Cardiometabolic Disorders and Oxidative Stress Induced by Fructose Intake in Rats

“…Due to its ability to reduce OS and serum uric acid level, to improve general antioxidant capacity by increasing GSH level and GPx activity or to down-regulate NF-kB [42,63] and upregulate heme-oxygenase-1 expressions [41], the AL discontinuous treatment ameliorates the elevation of serum CRP, thus preventing the systemic inflammatory process induced by chronic fructose consumption. Even if there are studies that support a decrease in inflammatory markers under a treatment with AL in humans, the available data in this context of inflammation are quite controversial, probably due to the different characteristics of population and the variety of studies design [64,65].…”

Alpha‐lipoic acid supplementation significantly reduces the risk of obesity in an updated systematic review and dose response meta‐analysis of randomised placebo‐controlled clinical trials

“…Additionally, study by Masharani et al and Konrad et al because of low sample size were not included in this study. As a result, totally, 24 studies were included in the current systematic review and meta‐analysis, whereas 21, 18 and 11 studies were included in the meta‐analysis of the effects of ALA on BMI, weight and WC, respectively.…”

“…Four studies employed a parallel design. Eighteen studies included both genders, and six studies included only female or male subjects. Most studies were conducted in China and Iran .…”

The Beneficial Effects of Alpha Lipoic Acid Supplementation on Lp-PLA2 Mass and Its Distribution between HDL and apoB-Containing Lipoproteins in Type 2 Diabetic Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

“…Zhang et al reported a significant reduction in serum levels of TC, LDL, and TG and a significant increase in HDL levels after intravenous administration of 600 mg ALA once daily for two weeks in obese-IGT patients [37]. In a study by Mendoza et al, after treatment with 600 mg ALA for six months in type 2 diabetic patients, a significant reduction in TC and an increase in HDL levels were reported; however, any significant change in TG levels was not observed [73]. In another study, supplementation with 600 mg ALA for 20 weeks in diabetic patients led to a nonsignificant effect on serum levels of TC, LDL, HDL, and TG [72].…”

“…* according to paired t-test; * * time to group interaction according to two-way repeated measure ANOVA. 8 Oxidative Medicine and Cellular Longevity glucose after supplementation with 600 mg ALA for six months [73]. In contrast, in one clinical study, after eight weeks of supplementation with 300 mg ALA in type 2 diabetic patients, an improvement in serum levels of glucose and HOMA-IR was reported [74].…”