Vitamins C and E: Beneficial effects from a mechanistic perspective

• Published in: Free radical biology & medicine 2011-09, Vol.51 (5), p.1000-1013
• Main Authors: Traber, Maret G., Stevens, Jan F.
• Format: Article
• Language: English
• Subjects: alkylation; alpha-tocopherol; Animals; Antioxidant; antioxidant activity; antioxidants; Antioxidants - metabolism; Antioxidants - therapeutic use; apoptosis; Ascorbic acid; Ascorbic Acid - metabolism; Ascorbic Acid - therapeutic use; Biomarkers; biosynthesis; blood pressure; Collagen; Cytoprotection - drug effects; endothelial nitric oxide synthase; energy metabolism; Energy Metabolism - drug effects; erythrocytes; Free Radicals - metabolism; gene expression regulation; genes; Humans; Hypoxia-Inducible Factor 1 - metabolism; inflammation; Inflammation - drug therapy; Inflammation - metabolism; Lipid peroxidation; Neoplasms - drug therapy; Neoplasms - metabolism; neutralization; neutrophils; Oxidative stress; procollagen-proline dioxygenase; Randomized Controlled Trials as Topic; reactive oxygen species; secondary metabolites; signs and symptoms (animals and humans); transcription factors; Vitamin E - metabolism; Vitamin E - therapeutic use; vitamin E deficiency; α-Tocopherol
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2011.05.017

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.