Diabetic neuropathy involves oxidative stress as part of its pathogenesis, and the antioxidant alpha-lipoic acid (ALA) has been evaluated as a potential therapy. ALA has potent antioxidant activity—interacting with superoxide radicals, hydroxide radicals, and other reactive oxygen species. ALA also serves as a cofactor for mitochondrial respiratory enzymes, supporting healthy mitochondrial function. Two previous meta-analyses reported beneficial effects of intravenous ALA for diabetic neuropathy.

This clinical trial of oral ALA in patients with diabetic neuropathy was published by Agathos and colleagues in 2018. The study design was open-label and prospective, without a placebo control. Seventy-two patients with diabetic peripheral neuropathy were given oral ALA (Nevralip Retard®) in a dosage of 600 mg per day for 40 days. Patients were assessed at baseline and the end of the trial.

Symptom scores of neuropathy improved significantly from baseline to the end of the trial, based on 3 questionnaires: Neuropathy Symptoms Score (NSS), Subjective Peripheral Neuropathy Screen Questionnaire (SPNSQ), and Douleur Neuropathique Questionnaire (DN-4). Mean NSS score decreased from 7.9 to 5.3 (p<.001), SPNSQ showed significant improvements on 14 out of 15 questions, and DN-4 showed significant improvements on all 10 questions regarding pain.

Patients additionally reported an overall improvement in quality of life, based on the Brief Pain Inventory (BPI), Neuropathic Pain Symptom Inventory (NPSI), and Sheehan Disability Scale (SDS). Scores showed improvements in superficial burning, spontaneous pain, pressing pain, paroxysmal pain, evoked pain, and paraesthesia. Patients also experienced significant reductions in work disability, social life disability, and family life disability. Half of the participants rated their health condition as “very much better” or “much better” at the end of the intervention period. None reported worsening of symptoms.

Blood tests revealed a statistically significant reduction in triglycerides (from 147 mg/dL to 136 mg/dL). There were no significant changes in fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, hemoglobin A1C, or blood pressure. No adverse events were reported for the duration of the trial. This was a small clinical trial without placebo control, but the results show promise for the safe and effective use of oral ALA in patients with diabetic neuropathy.

Agathos E, Tentolouris A, Eleftheriadou I et al. Effect of α-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy. J Int Med Res. 2018; 46: 1779-1790.