| Based on the FRTA, it seems reasonable to speculate that antioxidant supplementation should have an effect on longevity. In fact, however, there is no rigorous, reproducible experimental evidence that antioxidant supplements have any effect on maximum lifespan of humans or other vertebrates. At the same time, antioxidant supplements, most of which include vitamins, may improve health, particularly in those subjects with vitamin deficiencies. Thus, effects of antioxidant therapy on mean (and healthy) lifespan are not unexpected. Failure to affect maximum lifespan may result from the fact that there are so many mechanisms for production and control of free radicals and inhibiting or reversing damage to biomolecules. Many of these processes depend on the activity of enzymes that detoxify ROS or regenerate endogenous antioxidants. These enzymes, such as superoxide dismutase and glutathione peroxidase (Chapter 37), are induced in response to oxidative stress, and may also be repressed during times of low oxidative stress. Thus, the body may respond to maintain a homeostatic balance between pro-oxidant and antioxidant forces (see Fig. 37.1), countering efforts to enhance antioxidant defenses. This response may be essential, for example, to maintain effective bactericidal activity during the respiratory burst accompanying phagocytosis.
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