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Alpha lipoic acid improves measures of neuropathy in people with diabetes, study shows


  • Multi-center, randomized, double-blind, placebo-controlled trial
  • Participants include 460 patients with diabetes and mild-to-moderate polyneuropathy
  • Supplementation consists of ALA (600 mg/day) for 4 years
  • ALA has no effect on a composite neuropathy score, but significantly improves individual scores.
  • No between-group difference in treatment tolerability


This multi-center, randomized, double-blind, placebo-controlled trial was designed to evaluate the efficacy and safety of alpha lipoic acid (ALA) over 4 years in patients with mild-to-moderate diabetic distal symmetric sensorimotor polyneuropathy (DSPN). It is the NATHAN (Neurological Assessment of Thioctic Acid in Diabetic Neuropathy) 1 Trial conducted in 36 centers in the United States, Europe and Canada.

For this study, researchers randomly assigned 460 men and women, mean age 53-54 years, with type 1 or type 2 diabetes and mild-to-moderate DSPN to one of two oral treatments for 4 years: ALA (600 mg, once daily) or placebo. The primary end point was a composite score (NIS-LL+7) consisting of the Neuropathy Impairment Score (NIS)-Lower Limbs (NIS-LL) and seven neurophysiologic tests. Secondary outcome measures included NIS, NIS-LL, nerve conduction, and quantitative sensory tests (QSTs).

Data analysis (based on intention to treat) included 454 participants. Treatment tolerability showed no between-group differences. The rates of serious adverse events were higher with ALA (38%) than placebo (28%).

No significant (P<.05) between-group difference was reported for the primary end point (NIS-LL+7 composite neuropathy score). The authors note that the lack of improvement was likely due to the fact that nerve conduction and QST results did not significantly worsen with placebo.

ALA treatment, however, significantly improved the NIS score and the NIS-LL muscular weakness subscore (P<.05) and showed a trend toward an improved NIS-LL score (P=.05) compared to placebo. More patients showed a clinically meaningful improvement and fewer showed progression of NIS and NIS-LL with ALA than with placebo (P<.05).

These findings indicate that ALA supplementation (600 mg, once daily) for 4 years may offer clinically meaningful benefits for the treatment of diabetic neuropathy.


Ziegler D, Low PA, Litchy WJ, et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011;34(9):2054-60.

PMID: 21775755