Alpha-Lipoic Acid (Thioctic Acid · R-ALA · Racemic ALA)

Mechanism of action

• Mitochondrial cofactor for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes
• Direct radical scavenger in both aqueous and lipid compartments (dual-soluble antioxidant)
• Recycles other antioxidants (vitamin C / E / glutathione)
• NRF2 / endogenous antioxidant gene expression modulation

Molecular + tissue targets

• Mitochondrial oxidative phosphorylation
• Diabetic neuropathy symptom burden
• Hepatic and peripheral oxidative stress markers

Dosage range

600 mg/day intravenous for 3 weeks established the symptomatic improvement in diabetic polyneuropathy (Ziegler 2004 PMID 14984445 Diabetic Medicine meta-analysis of ALADIN I + ALADIN III + SYDNEY + NATHAN II · n=1,258 patients · responder rates 52.7% ALA vs 36.9% placebo · 24.1% relative difference). Oral 600-1,800 mg/day used in some trials but evidence base is strongest at the IV 600 mg/day protocol

Safety notes

Generally well tolerated; rare biotin metabolism interaction (high-dose ALA may reduce biotin status); insulin sensitisation effect requires monitoring in diabetic patients adjusting hypoglycaemic medications; the dietary supplement form is not equivalent to the IV protocol used in the strongest evidence base

Common use cases

• symptomatic diabetic sensorimotor polyneuropathy (positive evidence at 600 mg/day IV 3-week dosing)
• antioxidant adjunct in metabolic conditions
• general mitochondrial cofactor supplementation