The shifting perception on antioxidants: The case of vitamin E and β-carotene

• To date, the debate on the health benefit of antioxidants continues.
• The effect of vitamin E and β-carotene on BPDE-DNA adduct formation was evaluated.
• Both antioxidants promote DNA adduct formation by inhibition of GST π.
• Accurate benefit–risk analyses give a balanced view on the effects of antioxidants.

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.

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