Alpha-Lipoic Acid — The Universal Antioxidant
Alpha-lipoic acid (ALA) is a naturally occurring dithiol compound synthesised in mitochondria that functions as a cofactor for key metabolic enzymes (pyruvate dehydrogenase, α-ketoglutarate dehydrogenase). It is unique among antioxidants in being both fat- and water-soluble, and in recycling other antioxidants (vitamins C and E, glutathione, CoQ10). ALA levels decline with age.
Mechanism of Action
ALA and its reduced form DHLA (dihydrolipoic acid) directly scavenge free radicals and chelate heavy metals. DHLA regenerates oxidised glutathione, vitamin C, and vitamin E. ALA activates Nrf2 (antioxidant response element), AMPK, and inhibits NF-κB. R-ALA (the natural isomer) is more bioactive than the synthetic racemic mixture.
Human Trial Evidence
Multiple RCTs confirm ALA reduces neuropathic pain in diabetic peripheral neuropathy (600 mg/day IV or oral). A 2010 Diabetes Care meta-analysis showed ALA significantly improved insulin sensitivity. A 2019 Nutrients RCT showed 600 mg/day ALA improved cognitive function in Alzheimer's patients over 12 months.
Dosing Protocol
300–600 mg/day of R-ALA (or 600–1,200 mg/day of racemic ALA). Best taken on an empty stomach (food reduces absorption by 30%). R-ALA is more potent and better tolerated than racemic ALA. Sodium R-ALA salt is more stable and bioavailable than free R-ALA.
Safety & Contraindications
Well-tolerated. May cause mild GI effects (nausea, heartburn) — take on empty stomach. At high doses, may lower blood glucose — caution in diabetics on medication. Chelates heavy metals — take away from mineral supplements. May reduce thyroid hormone levels at high doses.