Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant ?-lipoic acid

Abstract

Anti-oxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes mellitus, thus providing a rationale of potential therapeutic value for diabetic patients. The effects of the anti-oxidant alpha-lipoic acid (thioctic acid) were studied in a 3-week multicentre, randomized, double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy; ALADIN) in 328 non-insulin-dependent diabetic patients with symptomatic peripheral neuropathy who were randomly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses (1200, 600, or 100 mg ALA) or placebo (PLAC). Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) were scored at baseline and at each visit (days 2-5, 8-12, and 15-19) prior to infusion. In addition, the Hamburg Pain Adjective List, a multidimensional specific pain questionnaire, and the Neuropathy Symptom and Disability Scores were assessed at baseline and day 19. According to the protocol 260 (65/63/66/66) patients completed the study. The total symptom score in the feet decreased from baseline to day 19 by -4.5 +/- 3.7 (-58.6%) points (mean +/- SD) in ALA 1200, -5.0 +/- 4.1 (-63.5%) points in ALA 600, -3.3 +/- 2.8 (-43.2%) points in ALA 100, and -2.6 +/- 3.2 (-38.4%) points in PLAC (ALA 1200 vs PLAC: p = 0.003; ALA 600 vs PLAC: p < 0.001). The response rates after 19 days, defined as an improvement in the total symptom score of at least 30%, were 70.8% in ALA 1200, 82.5% in ALA 600, 65.2% in ALA 100, and 57.6% in PLAC (ALA 600 vs PLAC; p = 0.002). The total scale of the Pain Adjective List was significantly reduced in ALA 1200 and ALA 600 as compared with PLAC after 19 days (both p < 0.01). The rates of adverse events were 32.6% in ALA 1200, 18.2% in ALA 600, 13.6% in ALA 100, and 20.7% in PLAC. These findings substantiate that intravenous treatment with alpha-lipoic acid using a dose of 600 mg/day over 3 weeks is superior to placebo in reducing symptoms of diabetic peripheral neuropathy, without causing significant adverse reactions.

Lipoic acid protects against oxidative stress induced impairment in insulin stimulation of protein kinase B and glucose transport in 3T3-L1 adipocytes

“…Shown is a blot representing five independent experiments Lipoic acid has been shown to exert beneficial effects in diabetes-related conditions in which oxidative stress was suggested to have a pathogenic role. The ALADIN study found a beneficial clinical effect of LA in the treatment of diabetic polyneuropathy [30]. In accordance with this, using animal models LA has been shown to prevent the diabetes-related reduction in peripheral nerve conduction velocity and endoneural blood flow [31,32].…”

The Effect of Alpha Lipoic Acid(Thioctacid HR®) on Endothelial Function in Diabetic and Hypertensive Patients

“…13) There are many reports demonstrating the improvement of endothelial dysfunction in diabetic patients in a dose-dependent manner. Lipoic acid supplementation has been reported to increase the unbound lipoic acid level, which can act as a potent antioxidant and reduce oxidative stress; 27) it is commonly marketed as an adjunct for the treatment of diabetic neuropathy.…”

“…[9][10][11][12] In many studies, ALA treatment has been shown to improve diabetic-induced endothelial dysfunction, probably due to the antioxidant effect of ALA. 13) 14) However, the effect of ALA treatment in patients with hypertension associated endothelial dysfunction is unknown.…”

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.…”