Alpha-Lipoic Acid (ALA)

Alpha-lipoic acid is a universal antioxidant active in both aqueous and lipid compartments that regenerates other antioxidants; it has strong evidence for reducing neuropathic symptoms in diabetic polyneuropathy and improving insulin sensitivity.

antioxidantmetabolicneuroprotectiveinsulin-sensitivityglucose

Dosing model

FLATFixed dose (no body-weight scaling).

Min dose

600 mg

Max dose

1200 mg

Rounding

100 mg

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Evidence

2 records

Neuropathic symptoms in diabetic sensorimotor polyneuropathy

Patients with type 1 or type 2 diabetes and symptomatic polyneuropathy • RCT

High

The SYDNEY 2 trial (n=181, 5 weeks) found all three oral ALA doses (600, 1200, 1800 mg/day) significantly reduced the Total Symptom Score versus placebo (~50% vs 32% reduction); 600 mg/day provided the optimal risk-to-benefit ratio with fewer side effects than higher doses.

Dose: 600 mg • Duration: 5 weeks

Citation: Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006;29(11):2365-70.

Neuropathic symptoms and deficits (intravenous ALA trials)

Diabetic patients with symptomatic polyneuropathy • meta-analysis of RCTs

High

Meta-analysis of 4 RCTs (ALADIN I, ALADIN III, SYDNEY, NATHAN II; n=1,258) found IV ALA 600 mg/day for 3 weeks significantly improved Total Symptom Scores (24.1% relative difference vs placebo) and neuropathic deficits; responder rate 52.7% vs 36.9% for placebo.

Dose: 600 mg • Duration: 3 weeks

Citation: Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabet Med. 2004;21(2):114-21.

Intravenous administration; oral bioavailability is lower. Oral 600 mg/day achieves similar clinical improvements over longer duration per SYDNEY 2.

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