Effects of Alpha-lipoic Acid Supplementation on Human Diabetic Nephropathy: A Systematic Review and Meta-analysis

Background: Diabetic nephropathy (DN) is kidney dysfunction, which occurs due to elevated urine albumin excretion rate and reduced glomerular filtration rate. Studies on 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 search procedure included PubMed Central, Embase, Cochrane Library (trials), and Web of Science (protocol registration: INPLASY202060095). Results: We found that ALA supplementation decreased 24h urine albumin 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 results of studies examining only ALA did not differ from those examined ALA in combination with additional medicines (Chisquared= 0.19; p=0.66; I²=0%), while neither ALA nor ALA plus medication had an effect on 24h urine albumin 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 examining ALA plus medication were excluded, it was found that 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.