The Effect of Alpha-Lipoic Acid as an Anti-Hyperuricemic Agent: A Comprehensive Review

Hyperuricemia, characterized by elevated serum uric acid levels (>6.8 mg/dL), represents a significant metabolic disorder associated with gout, cardiovascular disease, chronic kidney disease, and metabolic syndrome. Current first-line therapies primarily target xanthine oxidase inhibition or uricosuric mechanisms but are limited by adverse effects and incomplete efficacy in certain patient populations. Alpha-lipoic acid (ALA), a naturally occurring organosulfur compound with potent antioxidant properties, has emerged as a potential adjunctive therapy for hyperuricemia through multiple mechanisms including xanthine oxidase inhibition, enhancement of renal uric acid excretion, and mitigation of oxidative stress-induced endothelial dysfunction. This review synthesizes preclinical and emerging clinical evidence from 2020–2024 demonstrating ALA's anti-hyperuricemic effects. Animal studies consistently show that ALA administration (50–100 mg/kg/day) significantly reduces serum uric acid levels by 25–40% in potassium oxonate-induced hyperuricemic models, with concomitant improvements in renal function markers and oxidative stress parameters. In vitro studies confirm direct xanthine oxidase inhibitory activity (IC₅₀ = 2.9 μg/mL), though less potent than allopurinol (IC₅₀ = 1.7 μg/mL). Combination therapy with conventional urate-lowering agents demonstrates synergistic effects, particularly with febuxostat, resulting in superior renal and vascular protection compared to monotherapy. While human clinical trials remain limited, existing evidence supports ALA's safety profile and potential as an adjunctive therapy. Further randomized controlled trials are warranted to establish optimal dosing regimens and confirm clinical efficacy in human hyperuricemia.