A randomized, double-blind, placebo controlled study to evaluate the effect of alpha-lipoic acid on inhibition of ADP-and collagen-induced platelet aggregation ex vivo in diabetic neuropathy patients on gabapentin or pregabalin

ABSTRACT Background: Diabetic peripheral neuropathy (DPN) is a chronic microvascular complication in diabetic mellitus patients due to chronic hyperglycemia, resulting in platelet hyperactivity and dyslipidemia. Alpha-lipoic acid (ALA) is a potent antioxidant which has antiplatelet activity and lipid-modulating characteristics and plays a major role in the prevention of disease progression. Aim: To evaluate the effect of ALA on inhibition of platelet aggregation and lipid profile. Settings and Design: This was a prospective, randomized, double-blind, placebo-controlled study conducted at the Department of Clinical Pharmacology and Therapeutics at a tertiary care hospital. Materials and Methods: We recorded efficacy parameters including changes in inhibition of platelet aggregation, lipid profile, blood sugars, and glycated hemoglobin over 12 weeks of ALA (600 mg once daily orally) supplementation in DPN patients on gabapentin (300 mg twice daily [BD]) or pregabalin (75 mg BD) compared to placebo. We used Student’s t-test paired and unpaired for within-group and between-group comparisons, respectively. Results: A total of 52 study participants (males = 22, females = 30) with a mean age 55.63 ± 7.5 years were randomized to receive either ALA or placebo. Between-group analysis at 12 weeks showed that ALA significantly inhibited both collagen-induced platelet aggregation (from 32.61 ± 8.00 to 24.88 ± 5.30; P < 0.001) and adenosine diphosphate-induced platelet aggregation (from 34.00 ± 6.97 to 25.96 ± 6.45; P < 0.001) compared to placebo. Significant reduction in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides was found in the ALA group at 12 weeks compared to baseline. No serious adverse events were reported. Conclusion: ALA, an antioxidant, demonstrated a protective effect against DPN by the virtue of its inhibitory effect on platelet aggregation and lipid-modulating effects and was found to have good safety.