TitleVitamins C and E: beneficial effects from a mechanistic perspective.
Publication TypeJournal Article
Year of Publication2011
AuthorsTraber MG, Stevens JF
JournalFree Radic Biol Med
Date Published2011 Sep 01
KeywordsAnimals, Antioxidants, Ascorbic Acid, Cytoprotection, Energy Metabolism, Free Radicals, Humans, Hypoxia-Inducible Factor 1, Inflammation, Neoplasms, Randomized Controlled Trials as Topic, Vitamin E

The mechanistic properties of two dietary antioxidants that are required by humans, vitamins C and E, are discussed relative to their biological effects. Vitamin C (ascorbic acid) is an essential cofactor for α-ketoglutarate-dependent dioxygenases. Examples are prolyl hydroxylases, which play a role in the biosynthesis of collagen and in down-regulation of hypoxia-inducible factor (HIF)-1, a transcription factor that regulates many genes responsible for tumor growth, energy metabolism, and neutrophil function and apoptosis. Vitamin C-dependent inhibition of the HIF pathway may provide alternative or additional approaches for controlling tumor progression, infections, and inflammation. Vitamin E (α-tocopherol) functions as an essential lipid-soluble antioxidant, scavenging hydroperoxyl radicals in a lipid milieu. Human symptoms of vitamin E deficiency suggest that its antioxidant properties play a major role in protecting erythrocyte membranes and nervous tissues. As an antioxidant, vitamin C provides protection against oxidative stress-induced cellular damage by scavenging of reactive oxygen species, by vitamin E-dependent neutralization of lipid hydroperoxyl radicals, and by protecting proteins from alkylation by electrophilic lipid peroxidation products. These bioactivities bear relevance to inflammatory disorders. Vitamin C also plays a role in the function of endothelial nitric oxide synthase (eNOS) by recycling the eNOS cofactor, tetrahydrobiopterin, which is relevant to arterial elasticity and blood pressure regulation. Evidence from plants supports a role for vitamin C in the formation of covalent adducts with electrophilic secondary metabolites. Mechanism-based effects of vitamin C and E supplementation on biomarkers and on clinical outcomes from randomized, placebo-controlled trials are emphasized in this review.

Alternate JournalFree Radic. Biol. Med.
PubMed ID21664268
PubMed Central IDPMC3156342
Grant ListR01 DK081761-01A1 / DK / NIDDK NIH HHS / United States
R01 DK067930 / DK / NIDDK NIH HHS / United States
HL081721 / HL / NHLBI NIH HHS / United States
DK067930 / DK / NIDDK NIH HHS / United States
R01 HL081721 / HL / NHLBI NIH HHS / United States
R01 DK067930-04 / DK / NIDDK NIH HHS / United States
DK081761 / DK / NIDDK NIH HHS / United States
R01 DK081761 / DK / NIDDK NIH HHS / United States
R01 HL081721-05 / HL / NHLBI NIH HHS / United States