Vitamin E, oxidative stress and ‘healthy ageing’

P. Borel and nine other investigators report in this issue their studies on ‘Postprandial chylomicron and plasma vitamin E responses in healthy older subjects compared with younger ones’ [1]. It is my opinion that the authors have demonstrated not differences between young and elderly adults, but differences in the lipoprotein metabolism of subjects who do and do not have elevated fasting plasma cholesterol and triglycerides. A further study should be carried out with elderly and young adults with similar lipid levels to investigate the effects of ageing on vitamin E transport independent of changed lipoprotein metabolism. This is an important area of investigation because vitamin E is the most potent chain-breaking, lipid-soluble antioxidant in plasma [2]. Oxidative stress is increasingly recognized as an adverse factor in a large number of chronic diseases, such as heart disease [3,4], cancer [5], diabetes [6] and Alzheimer’s disease [7]. Oxidative stress is a shift in the balance between cellular oxidants and antioxidants towards the former [8]. The major source of these reactive oxygen species and radicals in the body is the ‘leakage of electrons’ during oxidative metabolism for conversion of foodstuffs to energy [9,10]. Organisms have evolved a variety of mechanisms for guarding against an excess of oxygen free radicals. Indeed, reactive oxygen species ‘turn on’ various signal transduction pathways, eliciting cellular responses, especially defence mechanisms [11–13]. The interplay of antioxidants, antioxidant enzyme systems and the ability to generate reducing equivalents serve to protect and the defend the organism [14]. The dependence of this defensive mechanism on low molecular weight antioxidants raises the question ‘Are supplemental antioxidants beneficial in protecting against oxidative stress? ’. And this brings us to the idea of ‘healthy ageing’. If ageing is the accumulation of cellular damage caused by radicals, could ‘extra’ antioxidants prevent the damage that causes chronic disease or at least ameliorate or slow further damage? In contrast, does an inadequate supply of antioxidants promote chronic disease? Perhaps the most convincing evidence for the role of oxidative stress and protection by antioxidants in the disease process is that for heart disease. Here, it has been proposed that atherosclerosis results from damage to the endothelium caused by the oxidation of low-density lipoproteins (LDLs) and their sequelae [3]. Thus, LDLs enter the endothelial lining, where they become oxidized, leading to invasion of monocytes and their transformation into foam cells and ultimately atheroma. If this process is dependent upon LDL oxidation, then prevention of LDL oxidation should prevent, or at least limit, atheroma formation. Indeed, in the test tube LDLs isolated from subjects consuming supplemental vitamin E are less oxidizable [15]. More remarkably, vitamin E supplementation given to heart attack victims has resulted in a significant reduction in subsequent heart attacks [16]. This concept is also supported by epidemiological studies showing that vitamin E supplementation is associated with a decreased risk of chronic heart disease [17,18]. As chronic diseases occur, of necessity, with a higher incidence in elderly than in younger subjects, are vitamin E intakes in the elderly sufficient? Heseker & Schneider [19] surveyed 2006 healthy German men and women aged 18–88 years and estimated using 7-day food records that vitamin E intakes were not different between adult and older subjects. Furthermore, after adjusting for blood lipids and vitamin E intakes, the a-tocopherol plasma levels were not associated with age [19]. It is known that plasmaa-tocopherol levels are associated with plasma lipid levels [20]. A recent study by Cuchel et al. [21] demonstrated that consumption of a margarineenriched diet (containing hydrogenated fat) compared with a corn oil-enriched diet resulted in significantly higher a-tocopherol concentrations in both plasma and LDL, a result of higher plasma cholesterol concentrations during the period when subjects consumed the margarine-enriched diet. Raising plasma lipid levels clearly raises plasma vitamin E levels in the same subjects. Do elevated plasma lipids, especially cholesterol, have detrimental effects? Recent studies by Frost et al. [22] demonstrate that high plasma cholesterol levels are correlated with a greater incidence of coronary heart European Journal of Clinical Investigation (1997)27, 822–824