Effects of alpha-lipoic acid supplementation on human diabetic nephropathy: A systematic review and meta-analysis

Abstract

Background: Diabetic nephropathy (DN) is a kidney dysfunction, which occurs due to elevated urine albumin excretion rate and reduced glomerular filtration rate. Studies in animals have shown that alpha-lipoic acid (ALA) supplementation can reduce the development of DN. Objectives: We performed a systematic review and meta-analysis to examine the effects of ALA supplementation on biological indices (albumin, creatinine etc.) indicative of human DN. Methods: The searching procedure included the databases PubMed Central, Embase, Cochrane Library (trials) and Web of Science, (protocol registration: INPLASY 202060095). Results: We found that ALA supplementation decreased urine albumin 24h excretion rate in patients with diabetes [standardized mean difference=-2.27; confidence interval (CI)=(-4.09)–(-0.45); I2=98%; Z=2.44; p=0.01]. A subgroup analysis revealed that the studies examining only ALA, did not differ from those examined ALA in combination with additional medicines (Chi-squared=0.19; p=0.66; I2=0%), while neither ALA nor ALA plus medication had an effect on urine albumin 24h excretion rate (p>0.05). Also, ALA supplementation decreased urine albumin mg/l [mean difference (MD)=-12.95; CI=(-23.88)–(-2.02); I2=44%; Z=2.32; p=0.02] and urine albumin to creatinine ratio [MD=-26.96; CI=(-35.25)–(-18.67); I2=0%; Z=6.37; p<0.01] in patients with diabetes. When the studies that examined ALA plus medication were removed, ALA supplementation had no effect on urine albumin mg/l (p>0.05), but did significantly decrease urine albumin to creatinine ratio [MD=-25.88, CI=(34.40–(-17.36), I2=0%, Z=5.95, p<0.00001]. Conclusion: The available evidence suggests that ALA supplementation does not improve biological indices that reflect DN in humans. Overall, we identified limited evidence and therefore, the outcomes should be considered with caution.