Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (α-lipoic acid): A two year multicenter randomized double-blind placebo-controlled trial (ALADIN II)

Abstract

Short-term trials with the antioxidant thioctic acid (TA) appear to improve neuropathic symptoms in diabetic patients, but the long-term response remains to be established. Therefore, Type 1 and Type 2 diabetic patients with symptomatic polyneuropathy were randomly assigned to three treatment regimens: (1) 2 x 600(mg of TA (TA 1200), (2) 600)mg of TA plus placebo (PLA) (TA 600) or (3) placebo and placebo (PLA). A trometamol salt solution of TA of 1200 or 600 mg or PLA was intravenously administered once daily for five consecutive days before enrolling the patients in the oral treatment phase. The study was prospective, PLA-controlled, randomized, double-blind and conducted for two years. Severity of diabetic neuropathy was assessed by the Neuropathy Disability Score (NDS) and electrophysiological attributes of the sural (sensory nerve conduction velocity (SNCV), sensory nerve action potential (SNAP)) and the tibial (motor nerve conduction velocity (MNCV), motor nerve distal latency (MNDL)) nerve. Statistical analysis was performed after independent reviewers excluded all patients with highly variable data allowing a final analysis of 65 patients (TA 1200: n = 18, TA 600: n = 27; PLA: n = 20). At baseline no significant differences were noted between the groups regarding the demographic variables and peripheral nerve function parameters for these 65 patients. Statistically significant changes after 24 months between TA and PLA were observed (mean +/- SD) for sural SNCV: +3.8 +/- 4.2 m/s in TA 1200, +3.0+/-3.0m/s in TA 600, -0.1+/-4.8m/s in PLA (p < 0.05 for TA 1200 and TA 600 vs. PLA); sural SNAP: +0.6+/-2.5 microV in TA 1200, +0.3+/-1.4 microV in TA 600, -0.7 +/- 1.5 microV in PLA (p = 0.076 for TA 1200 vs. PLA and p < 0.05 for TA 600 vs. PLA), and in tibial MNCV: +/- 1.2 +/- 3.8 m/s in TA 1200, -0.3 +/- 5.2 m/s in TA 600, 1.5 +/- 2.9 m/s in PLA (p < 0.05 for TA 1200 vs. PLA). No significant differences between the groups after 24 months were noted regarding the tibial MNDL and the NDS. We conclude that in a subgroup of patients after exclusion of patients with excessive test variability throughout the trial, TA appeared to have a beneficial effect on several attributes of nerve conduction.

Nutritional therapy improves function and complements corticosteroid intervention in mdx mice

“…The safety of each of the four compounds used in this study has been previously assessed in humans. 1,5,12,13,29,32,38,47,49 Consequently, we did not make extensive measurements of safety. However, we did monitor animal body weight, body condition, and eating behavior daily throughout the intervention, and organs were inspected by a pathologist for gross morphological abnormalities at the time of sacrifice.…”

“…17,44 In humans, ␣-LA supplementation reduced low-density lipoprotein oxidative damage 27 and improved nerve function in diabetic neuropathy. 38 Additionally, ␣-LA enhances CrM uptake in young healthy males, 5 an effect that may be relevant in DMD where oxidative stress is increased. 39 Interestingly, a weaker antioxidant, green tea extract, reduced muscle necrosis and regeneration in the fast-twitch muscle of mdx mice.…”

Is α‐lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity

“…The ALADIN and SID-NEY clinical trials of LA showed that its oral or intravenous administration improves nerve conduction velocity and neuropathic symptoms, such as pain, burning, paresthesia, and numbness (42)(43)(44)(45). To date, the therapeutic use of LA in the treatment of diabetic polyneuropathies remains the best documented and the most significant benefit of LA to human health.…”

THERAPY OF ENDOCRINE DISEASE: A systematic review and meta-analysis of α-lipoic acid in the treatment of diabetic peripheral neuropathy

“…Though another study measured nerve conduction velocities, its outcomes of sural SNCV and tibial MNCV were based on given ALA i.v. for 5 days followed by long-term oral supplement (12). All these above studies were excluded.…”