The effect of oral alpha-lipoic acid supplement on nutritional status and serum levels of metabolic, oxidative, inflammatory indicators and serum cytokeratin-18 in patients with nonalcoholic fatty liver disease

Abstract

Background and Objectives: Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrom, is now considered a major public health challenge worldwide, which is closely associated with obesity, type 2 diabetes and insulin resistance (IR). Alpha lipoic acid (ALA) is a natural compound containing sulfhydryl groups which itsantioxidant, lipid-lowering and insulin sensitizing properties have been shown in different experimental and animal models.Accordingly, the present study aimed to investigate the effect of ALA supplementation on metabolic, oxidative stress, inflammatory indicators and serum levels of cytokeratin-18 (CK-18) in obese patient with NAFLD. Methods and Materials: In this double-blind, placebo-controlled clinical trial, 50 obese patients with NAFLD were randomly allocated into two groups, receiving either 1200 mg ALA (two 600 mg capsules of ALA) or placebo (two 600 mg capsules of placebo) for 12 weeks. The anthropometric indices, dietary intakes information, and physical activity of the participants were assessed before, at the middle and after of the intervention.Venus blood samples of participants were obtained after 12-14 hours fasting to determine the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX), serum levels of total antioxidant capacity (TAC), lipid profile, blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), liver enzymes, malondialdehyde (MDA) levels, interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β1), fetuin-A, sirtuin-1 (SIRT-1) and CK-18 at baseline and after 12 weeks of the intervention. Moreover, all participants underwent ultrasonography for confirming and grading of liver steatosis severity before and after the intervention. Results: Forty-five patients completed the trial (ALA group=23; placebo group=22). Energy and carbohydrate intakes significantly decreased in both groupsby the end of the study, while there were no significant changes in fat and protein intakes in both groups. However, there were no significant difference in the dietary intake of energy and macronutrients intakes between the groupsat the end of the study. There were no significant difference in physical activity level between and within the groups throughout the intervention.Although significant alleviations in the weight, body mass index (BMI) and waist circumference (WC) were observed in both groups, no significant differences in these variables were observed between the groups at the end of study. ALA supplementation caused a significant decrease in serum concentration of insulin (p=0.019), fetuin-A (p=0.042), HOMA-IR (p=0.024) and serum triglyceride (p=0.037), but did not affect blood glucose, serum SIRT-1 and otherlipid profile parameters. Moreover, ALA supplementation led to a significant increase in serum TAC (p=0.038) and significant decrease in serum levels of MDA (p=0.044), in comparison with the placebo group. Nonetheless, no significant differences were observed between the study groups for SOD and GPX activities. There were no significant differences in the serum levels of liver enzymes, IL-10, TNF-α, TGF-β1 and CK-18 between two groups. In the ALA group, 91.3% of the patients showed a clinically improvement in liver steatosis, whereas the liver steatosis of only 54.5% of those in the placebo group improved. We found the number needed to treat (NNT) values for at least one and two grade improvement in liver steatosis were 3 and 6, respectively. ALA supplementation was significantly more effective than placebo in at least one grade reduction in liver steatosis (p=0.005). Conclusion: Our results revealed that ALA supplementation (1200 mg/day) for 12 weeks had beneficial effects on lipid profile, insulin sensitivity, oxidative stress status and liver steatosis in NAFLD patients and could be a adjuvant therapeutic option for this disease.