The antioxidants dilemma: are they potentially immunosuppressants and carcinogens?

INTRODUCTION Antioxidants and a large number of natural supplements were introduced in recent decades (Lu et al., 2013). It has been hypothesized that antioxidant consumption might reverse oxidative stress which decreases the adverse effects elicited as outcomes of oxidative stress including inflammation, carcinogenesis, and atherosclerosis (Ghorbanihaghjo et al., 2012; Bjelakovic et al., 2014). A large number of studies have been conducted in order to convey evidence for beneficial effects of antioxidants in health and disease (Bjelakovic et al., 2012). However, most of these studies were conducted for a short time interval evaluating limited numbers of targeted biochemical markers both in animal and human studies. Only a small number of prolonged cohort studies have been performed to critically assess the effects of chronic consumption of antioxidants. Unexpectedly, in a recently published systematic review by Bjelakovic et al. on 78 randomized clinical trials on antioxidants supplementation including selenium, β-carotene, vitamin C, vitamin A, and vitamin E, not only have no favorable effects been observed, but additionally, mortality rates have risen (Bjelakovic and Gluud, 2007; Bjelakovic et al., 2012). Surprisingly, it has been shown that antioxidant supplementation may increase the risk of skin malignancy in women (Hercberg et al., 2007). There are also a number of reports, in which a history of longtime supplementation with carotenoids has increased risk of malignancy in smokers and patients with tuberculosis (Albanes et al., 1996; Omenn et al., 1996; Holick et al., 2002; Shiels et al., 2011). Natural and green products are assumed to be harmless in common belief. The general faith toward the health benefits of products containing antioxidants is partly because of misinformation conveyed by industries manufacturing these food products, which promoted putative overuse of these products as dietary supplements. However, the harmful effects of these products have remained obscured for unknown reasons (Lu et al., 2013). It is crucial to emphasize the harmful effects of the chronic consumption of antioxidants, including potential toxicity, in addition of potential benefits. According to Watson “the time has come to seriously ask whether antioxidant use much more likely causes than prevents cancer” (Watson, 2013). In this article we have tried to discuss probable mechanisms by which chronic antioxidant consumption provokes adverse effects. We have attempted to depict the role of antioxidants in a comprehensive model of inflammation, oxidative stress, and cancer.