The Sensory Symptoms of Diabetic Polyneuropathy Are Improved With α-Lipoic Acid

Abstract

OBJECTIVE -Because ␣-lipoic acid (ALA), a potent antioxidant, prevents or improves nerve conduction attributes, endoneurial blood flow, and nerve (Na(ϩ) K(ϩ) ATPase activity in experimental diabetes and in humans and may improve positive neuropathic sensory symptoms, in this report we further assess the safety and efficacy of ALA on the Total Symptom Score (TSS), a measure of positive neuropathic sensory symptoms.RESEARCH DESIGN AND METHODS -Metabolically stable diabetic patients with symptomatic (stage 2) diabetic sensorimotor polyneuropathy (DSPN) were randomized to a parallel, double-blind study of ALA (600 mg) (n ϭ 60) or placebo (n ϭ 60) infused daily intravenously for 5 days/week for 14 treatments. The primary end point was change of the sum score of daily assessments of severity and duration of TSS. Secondary end points were sum scores of neuropathy signs (NIS), symptoms (NSC), attributes of nerve conduction, quantitative sensation tests (QSTs), and an autonomic test.RESULTS -At randomization, the groups were not significantly different by the criteria of metabolic control or neuropathic end points. After 14 treatments, the TSS of the ALA group had improved from baseline by an average of 5.7 points and the placebo group by an average of 1.8 points (P Ͻ 0.001). Statistically significant improvement from baseline of the ALA, as compared with the placebo group, was also found for each item of the TSS (lancinating and burning pain, asleep numbness and prickling), NIS, one attribute of nerve conduction, and global assessment of efficacy.CONCLUSIONS -Intravenous racemic ALA, a potent antioxidant, rapidly and to a significant and meaningful degree, improved such positive neuropathic sensory symptoms as pain and several other neuropathic end points. This improvement of symptoms was attributed to improved nerve pathophysiology, not to increased nerve fiber degeneration. Because of its safety profile and its effect on positive neuropathic sensory symptoms and other neuropathic end points, this drug appears to be a useful ancillary treatment for the symptoms of diabetic polyneuropathy. Diabetes Care 26:770 -776, 2003T he neuropathies associated with diabetes are heterogeneous (1). Perhaps the most common variety is diabetic sensorimotor polyneuropathy (DSPN), the disorder studied here. This variety appears to be caused by chronic hyperglycemia and associated metabolic derangements, damaging neurons (axons) or Schwann cells (or myelin) directly or indirectly by functional and structural alterations of microvessels or the blood nerve barrier. Inflammation, perhaps from immune mechanisms, may also be implicated in some cases (2).Recognizing that total hyperglycemic exposure may be the most important modifiable risk covariate for diabetic complications such as DSPN (3-8), why search for ancillary treatments in addition to rigorous glucose control? First, despite considerable effort to achieve near euglycemia (by frequent monitoring of plasma glucose, use of multiple injections of insulin, or use of insulin pumps), many ...

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

“…So ALA should be considered as a good choice among pathogenetically oriented treatments of diabetic neuropathy. As ALA was first used therapeutically in Germany to treat diabetic neuropathy, there have been various controlled clinical trials assessing the efficacy of ALA in treating diabetic neuropathy (12,33,34,35,36,37). The findings of ALADIN study substantiated that i.v.…”

“…It appears to show an unequivocal and large beneficial effect of i.v. racemic ALA on the frequency and severity of the positive neuropathic sensory symptoms due to diabetic polyneuropathy (36). It was of particular interest that no significant adverse reactions in association with ALA were observed in the treatment of the above studies.…”

Erythropoietin both protects from and reverses experimental diabetic neuropathy

“…In one successful experiment using a probucol derivative, coadministration of a NO synthase inhibitor abolishes the effects of antioxidants, suggesting that the benefits arise from effects on the neurovasculum (61). Finally, lipoic acid has been shown in diabetic patients to improve function and reduce symptoms in patients with established diabetic polyneuropathy (62).…”

Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis

“…Response in these patients is best evaluated by using the hematologic criteria described below. Techniques used to assess diabetic neuropathy are not in widespread use but have been shown to reproducibly gauge neuropathic changes [86,87].…”