Alpha-Lipoic Acid for Diabetic Peripheral Neuropathy

Study Population: Adults 18 years and older who have type 1 or type 2 diabetes with symptomatic diabetic peripheral neuropathy (DPN) diagnosed on the basis of clinical symptoms or electrophysiological studies

Efficacy End Points: Change in neuropathy symptoms, change in impairment

Harm End Points: Adverse events leading to cessation of treatment

Narrative: Patients with diabetes have insufficient insulin production (type 1) or insulin resistance (type 2). Diabetes is a leading public health concern; its prevalence is estimated to increase to approximately 10% of the world's population by 2030 and approximately 11% by 2045.¹ Around one-third of patients with diabetes experience DPN, the most common complication of diabetes.² The pathophysiology of DPN is not well understood and likely multifactorial, including direct effects of hyperglycemia, inflammation, and oxidative stress. DPN is a major risk factor for the loss or decrease of protective sensation and a significant risk factor for diabetic foot ulcerations and nontraumatic amputations.³

Alpha-lipoic acid, also known as thioctic acid, is a natural thiol supplement with potent antioxidant and metal-chelating effects. Alpha-lipoic acid is postulated to regenerate endogenous antioxidants, stimulate glucose uptake within cells, and reduce inflammation.⁴

The 2024 Cochrane review discussed here evaluated the effectiveness of alpha-lipoic acid compared with placebo on DPN symptoms in adults.⁵ The systematic review included three studies that were placebo-controlled, parallel-group randomized controlled trials, enrolling 816 adult participants (mean age 57.8 years) who received treatment for at least 6 months. The primary outcome was reduction in neuropathy symptoms 6 months after randomization (as measured by Total Symptom Score or other validated instruments). Secondary outcomes included change in neuropathy symptoms at 24 months, impairment at 6 and 24 months (measured using validated scores such as the Neuropathy Impairment Score-Lower Limbs subscale), and adverse events that led to discontinuing the intervention.⁵

Moderate-certainty evidence showed that alpha-lipoic acid had little or no effect compared with placebo on diabetic peripheral neuropathy symptoms after 6 months (standard mean difference [SMD] = −0.16; 95% CI, −0.83 to 0.51; one randomized controlled trial, 330 participants) and 24 months (SMD = −0.23 points; 95% CI, −0.67 to 0.21; one randomized control trial, 421 participants).

Low-certainty evidence showed that alpha-lipoic acid had little or no effect on impairment after 6 months (SMD = −1.02; 95% CI, −2.93 to 0.89; one randomized controlled trial, 245 participants) or after 24 months (SMD = −0.07; 95% CI, −0.24 to 0.11; two studies, 486 participants).

Moderate-certainty evidence showed that alpha-lipoic acid resulted in little or no difference in adverse events at 6 months compared with placebo (risk ratio = 1.48; 95% CI, 0.50 to 4.35; three randomized control trials, 1,090 participants). No studies evaluated quality of life or complications of DPN. All studies and data were downgraded due to the risk of attrition bias.⁵