The free radical theory of ageing (FRTA), presented by Denham Harman in 1950s, proposed that aerobic organisms age due to reactive oxygen species (ROS)/free radical induced damage that accumulates in cells over time. Since antioxidants can neutralize free radicals by electron donation, the most logical approach was to use them as supplements in order to prevent ageing. In this chapter, we will discuss the inability of antioxidant supplementation to improve health and longevity.Although many antioxidants are efficient free radical quenchers in vitro, their in vivo effects are less clear. Recent evidence from human trials implies that antioxidant supplements do not increase lifespan and can even increase the incidence of diseases. Synthetic antioxidants were unable to consistently prevent ROS-induced damage in vivo, possibly as dietary antioxidants may not act only as ROS scavengers. Antioxidants can have dichotomous roles on ROS production. They are easily oxidized and can act as oxidants to induce damage when present in large concentrations. In appropriate amounts, they can modulate cellular metabolism by induction of cell stress responses and/or activate cell damage repair and maintenance systems. Therefore, the antioxidants' beneficial role may be reversed/prevented by excessive amounts of antioxidant supplements. On the other hand, ROS are also involved in many important physiological processes in humans, such as induction of stress responses, pathogen defence, and systemic signalling. Thus, both "anti-oxidative or reductive stress" (the excess of antioxidants) as well as oxidative stress (the excess of ROS) can be damaging and contribute to the ageing processes.
Keywords: Ageing; Antioxidants; Dietary supplements; Longevity; ROS.