title: New perspectives on vitamin E: gamma-tocopherol and carboxyelthylhydroxychroman metabolites in biology and medicine.
abstract: Vitamin E (alpha-tocopherol or alphaT) has long been recognized as a classic free radical scavenging antioxidant whose deficiency impairs mammalian fertility. In actuality, alpha-tocopherol is one member of a class of phytochemicals that are distinguished by varying methylation of a chroman head group. Early studies conducted between 1922 and 1950 indicated that alpha-tocopherol was specific among the tocopherols in allowing fertility of laboratory animals. The unique vitamin action of alphaT, combined with its prevalence in the human body and the similar efficiency of tocopherols as chain-breaking antioxidants, led biologists to almost completely discount the "minor" tocopherols as topics for basic and clinical research. Recent discoveries have forced a serious reconsideration of this conventional wisdom. New and unexpected biological activities have been reported for the desmethyl tocopherols, such as gamma-tocopherol, and for specific tocopherol metabolites, most notably the carboxyethyl-hydroxychroman (CEHC) products. The activities of these other tocopherols do not map directly to their chemical antioxidant behavior but rather reflect anti-inflammatory, antineoplastic, and natriuretic functions possibly mediated through specific binding interactions. Moreover, a nascent body of epidemiological data suggests that gamma-tocopherol is a better negative risk factor for certain types of cancer and myocardial infarction than is a alpha-tocopherol. The potential public health implications are immense, given the extreme popularity of alphaT supplementation which can unintentionally deplete the body of gamma-tocopherol. These findings may or may not signal a major paradigm shift in free radical biology and medicine. The data argue for thorough experimental and epidemiological reappraisal of desmethyl tocopherols, especially within the contexts of cardiovascular disease and cancer biology.
authors.affiliation: Free Radical Biology and Aging Research Program, Oklahoma Medical Reserach Foundation, Oklahoma City, OK 73104, USA. Kenneth-Hensley@omrf.ouhsc.edu
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hensley
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Benaksas
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
authors.forename: Philip
authors.initials: P
authors.lastname: Comp
authors.forename: Paula
authors.initials: P
authors.lastname: Grammas
authors.forename: Ladan
authors.initials: L
authors.lastname: Hamdheydari
authors.forename: Shenyun
authors.initials: S
authors.lastname: Mou
authors.forename: Quentin N
authors.initials: QN
authors.lastname: Pye
authors.forename: Marcus F
authors.initials: MF
authors.lastname: Stoddard
authors.forename: Gemma
authors.initials: G
authors.lastname: Wallis
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Williamson
authors.forename: Melinda
authors.initials: M
authors.lastname: West
authors.forename: William J
authors.initials: WJ
authors.lastname: Wechter
authors.forename: Robert A
authors.initials: RA
authors.lastname: Floyd
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D001342:Autonomic Nervous System Diseases / Q000378:metabolism / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000517:prevention & control; D002839:Chromans / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D024504:gamma-Tocopherol / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D002839:Chromans; C483420:carboxyethyl-hydroxychroman; D024504:gamma-Tocopherol