title: The shifting perception on antioxidants: the case of vitamin E and β-carotene.
abstract: Antioxidants are vital for aerobic life, and for decades the expectations of antioxidants as health promoting agents were very high. However, relatively recent meta-analyses of clinical studies show that supplementation of antioxidants does not result in the presumed health benefit, but is associated with increased mortality. The dilemma that still needs to be solved is: what are antioxidants in the end, healthy or toxic? We have evaluated this dilemma by examining the presumed health effects of two individual antioxidants with opposite images i.e. the "poisonous" β-carotene and the "wholesome" vitamin E and focused on one aspect, namely their role in inducing BPDE-DNA adducts. It appears that both antioxidants promote DNA adduct formation indirectly by inhibition of the protective enzyme glutathione-S-transferase π (GST π). Despite their opposite image, both antioxidants display a similar type of toxicity. It is concluded that, in the appreciation of antioxidants, first their benefits should be identified and substantiated by elucidating their molecular mechanism. Subsequently, the risks should be identified including the molecular mechanism. The optimal benefit-risk ratio has to be determined for each antioxidant and each individual separately, also considering the dose.
authors.affiliation: Department of Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: m.vrolijk@maastrichtuniversity.nl.
authors.forename: Misha F
authors.initials: MF
authors.lastname: Vrolijk
authors.affiliation: Department of Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; Netherlands Food and Consumer Product Safety Authority (NVWA), 3540 AA Utrecht, The Netherlands.
authors.forename: Antoon
authors.initials: A
authors.lastname: Opperhuizen
authors.affiliation: National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands.
authors.forename: Eugène H J M
authors.initials: EH
authors.lastname: Jansen
authors.affiliation: Department of Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Godschalk
authors.affiliation: Department of Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: Van Schooten
authors.affiliation: Department of Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
authors.affiliation: Department of Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002460:Cell Line; D018736:DNA Adducts / Q000096:biosynthesis; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012307:Risk Factors; D014810:Vitamin E / Q000494:pharmacology*; D019207:beta Carotene / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D018736:DNA Adducts; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D019207:beta Carotene; D014810:Vitamin E; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D051549:Glutathione S-Transferase pi; D001205:Ascorbic Acid
keywords: DNA damage; Glutathione-S-transferase; Risk–benefit analysis; Vitamin E; β-Carotene