Alpha Lipoic Acid (ALA / R-ALA)

Ziegler et al. (Diabetes Care, 2006; PMID 17065669): the SYDNEY 2 trial: randomized, placebo-controlled, 181 adults with diabetic polyneuropathy, oral alpha-lipoic acid at 600, 1,200 or 1,800 mg/day for 5 weeks. Symptoms improved at all three doses, and the authors concluded that 600 mg once daily gave the best risk-to-benefit ratio. This is not the ALADIN trial; ALADIN I, II and III are separate, mostly intravenous studies, and ALADIN III did not improve symptoms. Ansar et al. (Saudi Med J, 2011; PMID 21666939): randomized trial of oral alpha-lipoic acid on blood glucose and insulin resistance in type 2 diabetes. Han et al. (Eur J Endocrinol, 2012; PMID 22837391): systematic review and meta-analysis of alpha-lipoic acid in diabetic peripheral neuropathy. Ziegler et al. (Diabetes Care, 2011; PMID 21775755): the NATHAN 1 trial: randomized, placebo-controlled, 460 adults with mild to moderate diabetic polyneuropathy, oral racemic alpha-lipoic acid 600 mg once daily for 4 years; the primary composite endpoint did not differ (P=0.105), some secondary impairment scores favored treatment, and serious adverse events were more frequent on alpha-lipoic acid (38.1 versus 28.0 percent). Both oral trials used racemic ALA, not R-ALA. Grade C: on oral trials the evidence is one positive 5-week trial (SYDNEY 2) and one 4-year trial whose primary endpoint was null with more serious adverse events on treatment (NATHAN 1); the pooled neuropathy analysis (Han 2012) is mostly intravenous and its authors rate the trials poorly. A single positive short trial without an independent oral replication is C.