Alpha-lipoic acid (ALA) is a sulfur-containing antioxidant compound synthesized in mitochondria that functions as a cofactor for several key mitochondrial enzymes. It is both water- and fat-soluble, allowing it to work throughout the body, and can regenerate other antioxidants including vitamin C, vitamin E, and glutathione.
Alpha-lipoic acid functions as a cofactor for pyruvate dehydrogenase and Ξ±-ketoglutarate dehydrogenase in the TCA cycle. As an antioxidant, ALA directly scavenges reactive oxygen species (ROS) and reactive nitrogen species. Its reduced form (dihydrolipoic acid) can regenerate vitamin C from dehydroascorbate, vitamin E from tocopheryl radical, and glutathione from GSSG. ALA also chelates metal ions (copper, iron) that catalyze oxidative reactions. In neurons, ALA improves mitochondrial function, reduces oxidative damage, and enhances glucose uptake via GLUT transporters. ALA activates AMPK improving insulin sensitivity and glucose metabolism.
Alpha-lipoic acid is used therapeutically for diabetic neuropathy (600 mg/day), where it reduces oxidative stress, improves nerve conduction, and relieves neuropathic pain symptoms. It supports mitochondrial function and energy production, making it beneficial for fatigue, metabolic syndrome, and neurodegenerative conditions. ALA helps prevent oxidation of dopamine (reducing neurotoxic quinones) and 4-hydroxyestrogens (preventing DNA damage), making it important in conditions with high dopamine or estrogen. It is generally well-tolerated with doses of 300-600 mg daily.
- Both water- and fat-soluble antioxidant
- Cofactor for TCA cycle enzymes (pyruvate dehydrogenase, Ξ±-ketoglutarate dehydrogenase)
- Regenerates vitamin C, vitamin E, NAC, and glutathione
- 600 mg/day used for diabetic neuropathy
- Chelates metal ions (copper, iron) preventing oxidative reactions
- Activates AMPK improving insulin sensitivity
- Prevents dopamine oxidation to neurotoxic quinones
- Prevents 4-hydroxyestrogen oxidation and DNA damage
- antioxidants β master antioxidant that regenerates other antioxidants
- Vitamin C β ALA regenerates vitamin C from its oxidized form
- Vitamin E β ALA regenerates vitamin E from tocopheryl radical
- NAC β works synergistically with NAC in antioxidant defense
- glutathione β ALA helps regenerate glutathione from GSSG
- diabetic neuropathy β 600 mg/day ALA reduces symptoms and improves nerve function
- mitochondrial function β cofactor for mitochondrial enzymes; improves mitochondrial health
- TCA cycle β cofactor for pyruvate dehydrogenase and Ξ±-ketoglutarate dehydrogenase
- oxidative stress β reduces oxidative stress through direct ROS scavenging
- insulin sensitivity β improves insulin sensitivity via AMPK activation
- dopamine β prevents dopamine auto-oxidation to neurotoxic quinones
- estrogen β prevents oxidation of 4-hydroxyestrogens preventing DNA damage
- copper β chelates copper preventing copper-catalyzed oxidative reactions
- iron β chelates iron preventing Fenton reactions
- AMPK β activates AMPK improving metabolic health
- neuroprotection β protects neurons from oxidative damage
- glucose metabolism β enhances glucose uptake via GLUT transporters
- metabolic syndrome β beneficial in metabolic syndrome for improving insulin sensitivity
- fatigue β reduces fatigue by improving mitochondrial energy production
- heavy metals β chelates heavy metals reducing their toxic effects