The Effect of Long-term Dietary Supplementation with Antioxidantsa

The impact of diet and specific food groups on aging and age-associated degenerative diseases has been widely recognized in recent years. The modern concept of the free radical theory of aging takes as its basis a shift in the antioxidant/prooxidant balance that leads to increased oxidative stress, dysregulation of cellular function, and aging. In the context of this theory, antioxidants can influence the primary \u27intrinsic\u27 aging process as well as several secondary age-associated pathological processes. For the latter, several epidemiological and clinical studies have revealed potential roles for dietary antioxidants in the age-associated decline of immune function and the reduction of risk of morbidity and mortality from cancer and heart disease. We reported that long-term supplementation with vitamin E enhances immune function in aged animals and elderly subjects. We have also found that the beneficial effect of vitamin E in the reduction of risk of atherosclerosis is, in part, associated with molecular modulation of the interaction of immune and endothelial cells. Even though the effects of dietary antioxidants on aging have been mostly observed in relation to age-associated diseases, the effects cannot be totally separated from those related to the intrinsic aging process. For modulation of the aging process by antioxidants, earlier reports have indicated that antioxidant feeding increased the median life span of mice to some extent. To further delineate the effect of dietary antioxidants on aging and longevity, middle-aged (18 mo) C57BL\6NIA male mice were fed ad libitum semisynthetic AIN-76 diets supplemented with different antioxidants (vitamin E, glutathione, melatonin, and strawberry extract). We found that dietary antioxidants had no effect on the pathological outcome or on mean and maximum life span of the mice, which was observed despite the reduced level of lipid peroxidation products, 4-hydroxynonenol, in the liver of animals supplemented with vitamin E and strawberry extract (1.34 ± 0.4 and 1.6 ± 0.5 nmol/g, respectively) compared to animals fed the control diet (2.35 ± 1.4 nmol/g). However, vitamin E-supplemented mice had significantly lower lung viral levels following influenza infection, a viral challenge associated with oxidative stress. These and other observations indicate that, at present, the effects of dietary antioxidants are mainly demonstrated in connection with age-associated diseases in which oxidative stress appears to be intimately involved. Further studies are needed to determine the effect of antioxidant supplementation on longevity in the context of moderate caloric restriction

Dietary lipids modify the cytokine response to bacteria lipopolysaccharide in mice

To investigate the effect of dietary lipids with different fatty acid compositions upon the in vivo cytokine response to bacterial lipopolysaccharide (LPS), mice were fed for 5 weeks on a low-fat diet or on one of four high-fat diets that contained 20%, by weight, of coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO). The mice were injected intraperitoneally with a non-lethal dose of Escherichia coli LPS (100 ?g/20 g body weight) and killed 90 or 180 min later. Plasma tumour necrosis factor-? (TNF-?), interleukin (IL)-1?, IL-6 and IL-10 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Plasma TNF-? and IL-10 concentrations were higher 90 min postinjection than after 180 min, whereas plasma IL-1? and IL-6 concentrations were higher 180 min postinjection than after 90 min. Peak plasma TNF-?, IL-1? and IL-6 concentrations were lower in the CO- and FO-fed mice than in those fed the SO diet. Peak plasma IL-10 concentrations were higher in CO-fed mice than in those fed some of the other diets. These observations suggest that, relative to the n-6 polyunsaturated fatty acid-rich SO diet, CO and FO diminish production of proinflammatory cytokines in vivo. This indicates that these fatty acids might be useful therapies in acute and chronic inflammatory diseases. The enhanced production of IL-10 following CO feeding appears to be an additional antiinflammatory effect of this oil, which could give added benefit in various clinical conditions.<br/