Dihydrolipoic acid
Dihydrolipoic acid (DHLA) is the reduced, active form of alpha-lipoic acid, with two free thiol groups that can give up electrons. Cells make it from alpha-lipoic acid.
Also called DHLA, reduced lipoic acid.
Lipoic acid's effect on glutathione depended on this conversion. Cells released DHLA, which reduced cystine to cysteine, and the cysteine was taken up and used to make glutathione (Han 1997). By this route cystine bypassed the xc- transporter, which is weakly present in lymphocytes and inhibited by glutamate (Han 1997).
In mouse cartilage cells exposed to the inflammatory signal IL-1 beta, DHLA lowered reactive oxygen species, ferrous iron and lipid peroxidation, lessened the fall in glutathione and GPX4, and protected collagen II, aggrecan and SOX9 while holding back MMP13 (Chen 2026). In mice, it slowed cartilage degeneration after surgery that destabilises the knee (Chen 2026).
Sources
- Han D, Handelman G, Marcocci L et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 1997.
- Chen Y, Fang J, Zhou Z et al. Dihydrolipoic acid suppresses ferroptosis in chondrocytes to ameliorate the progression of osteoarthritis by modulating the FOXO1/TXNIP signaling pathway. Free Radic Biol Med 2026.
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