TitleAlpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential.
Publication TypeJournal Article
Year of Publication2009
AuthorsShay KPetersen, Moreau RF, Smith EJ, Smith AR, Hagen TM
JournalBiochim Biophys Acta
Volume1790
Issue10
Pagination1149-60
Date Published2009 Oct
ISSN0006-3002
KeywordsAnimals, Diabetic Neuropathies, Dietary Supplements, Humans, Hypertension, Inflammation, Models, Biological, Molecular Structure, Thioctic Acid, Vascular Diseases
Abstract

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.

DOI10.1016/j.bbagen.2009.07.026
Alternate JournalBiochim. Biophys. Acta
PubMed ID19664690
PubMed Central IDPMC2756298
Grant ListP01 AT002034 / AT / NCCIH NIH HHS / United States
P01 AT002034-077041 / AT / NCCIH NIH HHS / United States