Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging
supplements, and even pet food. It is well-defined as a therapy for preventing diabetic
polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular
glutathione levels which otherwise decline with age. How do the biochemical properties
of LA relate to its biological effects? Herein, we review the molecular mechanisms
of LA discovered using cell and animal models, and the effects of LA on human subjects.
Though LA has long been touted as an antioxidant, it has also been shown to improve
glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification
via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through
repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their
chemical properties as a redox couple to alter protein conformations by forming mixed
disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting
that some of its therapeutic potential extends beyond the strict definition of an
antioxidant. Current trials are investigating whether these beneficial properties
of LA make it an appropriate treatment not just for diabetes, but also for the prevention
of vascular disease, hypertension, and inflammation.