dihydrolipoic

Dihydrolipoic acid (DHLA) is the reduced, dithiol form of α-lipoic acid. It is produced when the disulfide bond of the lipoamide moiety is reduced to two thiol groups. In cells, DHLA is generated during the catalytic cycles of lipoamide-containing enzyme complexes and is reoxidized back to lipoic acid by lipoamide dehydrogenase, with NAD+ serving as the electron acceptor.

DHLA is a redox-active molecule with important roles as an antioxidant and as a cofactor in mitochondrial metabolism. As the intracellular antioxidant form of lipoic acid, it scavenges reactive oxygen and nitrogen species and can help regenerate oxidized forms of other antioxidants, such as vitamin C, vitamin E, and glutathione. In mitochondria, the lipoamide cofactor cyclically shuttles electrons during the transfer of acyl groups in enzyme complexes, including pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, a process linked to the redox state of DHLA/LA.

DHLA occurs endogenously in cells and can be derived from dietary α-lipoic acid taken up by tissues, where it is reduced to the dihydrol form. α-Lipoic acid is widely used as a dietary supplement for antioxidant support, but DHLA itself is not commonly marketed as a separate supplement. The DHLA/LA redox couple contributes to cellular redox balance, and its activity is interconnected with the broader cellular antioxidant network.