Maret G. Traber

TOBACCO-RELATED DISEASES: Is There a Role for Antioxidant Micronutrient Supplementation?

It is clear that smoking causes an increase in free radicals, reactive nitrogen and oxygen species (RNS and ROS, respectively), and that cigarette smoking is associated with increases in the incidence and severity of several diseases including atherosclerosis, cancer, and chronic obstructive lung disease. Although there is still no unequivocal evidence that oxidative stress is a contributor to these diseases or that an increased intake of antioxidant nutrients is beneficial, the observation that smokers have lower circulating levels of some of these nutrients, raises concern. This article discusses the possible links between the observed oxidant-induced damage related to tobacco smoking, effects on cellular mechanisms, and their potential involvement in the causation and enhancement of disease processes.

Intestinal expression of human apolipoprotein A-IV in transgenic mice fails to influence dietary lipid absorption or feeding behavior.

Two transgenic mouse lines, expressing low or high amounts of human apo A-IV were created. In low and high expressor HuAIVTg mice on a chow diet, serum human apo A-IV levels were 6 and 25 times the normal human level and on a high fat diet, they were 12 and 77 times higher. Human apo A-IV was equally distributed between lipoprotein (mainly HDL) and lipid-free fractions. Intestinal absorption of radiolabeled cholesterol and triglycerides was unaffected in HuAIVTg mice. Vitamin A, carried exclusively in chylomicrons and their remnants, was catabolized normally. When an intragastric vitamin E bolus is given to the HuAIVTg mice, the initial absorption and appearance in triglyceride-rich lipoproteins was similar to that observed in normal mice. However, elevated amounts of vitamin E were subsequently observed in the VLDL of the HuAIVTg mice. Furthermore, in the fed state, serum VLDL triglycerides were markedly elevated in HuAIVTg mice. This effect was greater in high expressor mice. Serum total cholesterol was not elevated, but the distribution was altered in the HuAIVTg mice; VLDL-C was increased at the expense of VLDL-C. Kinetic studies suggested a delayed clearance of VLDL in HuAIVTg mice. Apo A-IV has been suggested to be a satiety factor, but no effect on feeding behavior or weight gain was observed in these HuAIVTg mice. In summary, our studies with HuAIVTg mice show that additional apo A-IV does not effect intestinal absorption of fat and fat-soluble vitamins, and at least chronic elevation of plasma apo A-IV does not effect feeding behavior in this model system.

Vitamin E kinetics in smokers and nonsmokers

Does cigarette smoking increase vitamin E utilization in vivo? A trial was carried out in 6 smokers and 5 nonsmokers of comparable ages and serum lipids. Subjects consumed 75 mg each d(3)-RRR and d(6)-all rac-alpha-tocopheryl acetates (natural and synthetic vitamin E, respectively) daily for 7 d with a standardized breakfast. Fasting blood samples were drawn on days -7, -6, -5, -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 6, 7, 9, 14, 21 (negative days indicate supplementation). In both groups, plasma d(3)-alpha-tocopherol concentrations were approximately double of d(6)-alpha-tocopherol. At day 0, the %d(3) alpha-tocopherols (d(3)-alpha-tocopherol/total-alpha-tocopherol x 100) were similar in both smokers and nonsmokers. Subsequently, there was a trend toward a faster exponential disappearance of the plasma %d(3) alpha-tocopherol in smokers compared with nonsmokers (0.30 +/- 0.04 compared with 0.24 +/- 0.05, p =.0565). The calculated %d(3) half-lives were 55.6 +/- 7.4 h in smokers and 72.1 +/- 17.3 h in nonsmokers (p =.0630). By day 21, the %d(3) in smokers had decreased to 1.4% +/- 0.3% while it was 2.2% +/- 0.7% (p =.0418) in the nonsmokers. These data suggest that smoking increases plasma vitamin E disappearance, but further studies are needed to confirm this finding and to assess its cause.

The new US Dietary Reference Intakes for vitamins C and E.

The Dietary Reference Intakes (DRIs) for nutrients are set by the Food and Nutrition Board of the Institute of Medicine (IOM), US National Academy of Sciences. New DRIs for vitamin C, vitamin E, selenium and carotenoids were published in April 2000 by the IOM Panel on Dietary Antioxidants and Related Compounds.1 These DRI values encompass the estimated average requirement (EAR), the recommended dietary allowance (RDA), the range of adequate intakes and the tolerable upper intake level (UL). The RDA is defined as ‘the average daily dietary intake level that is sufficient to meet the nutrient requirement of nearly all (97–98%) healthy individuals in a particular life stage and gender group’.1 Since the last publication of the RDAs in 1989,2 the Food and Nutrition Board has changed the criteria for establishing the RDA of a given nutrient from prevention of deficiency disease to evaluation of its potential for prevention of chronic disease.3 Nevertheless, the ‘health benefits’ of the antioxidant nutrients as described in the revised 2000 RDAs were primarily those related to the prevention of deficiency symptoms, not the prevention of chronic diseases.1 Not surprisingly, therefore, the new RDAs for dietary antioxidants differ little from the RDAs published in 1989.2 The new RDAs for adults (≥19 years) for vitamin C are 90 mg/day for men and 75 mg/day for women (1989 RDA: 60 mg/day for both men and women). The new RDA for vitamin E (natural or 2R-αtocopherol) is 15 mg/day for both men and women (1989 RDAs for men and women, respectively, 10 and 8 mg/day α-tocopherol equivalents). The new RDA for selenium is 55 μg/day for men and women (1989 RDAs for men and women, respectively, 70 and 55 μg/day). No DRIs were set for β-carotene and other carotenoids, other than to recommend the consumption of fruits and vegetables. The Panel considered the possibility that higher intakes than the RDAs might prevent chronic diseases, but concluded that there was insufficient data to prove that increased intakes of antioxidants exert beneficial health effects beyond the prevention of deficiency symptoms.1 Nonetheless, the Panel emphasized that the hypothesis that antioxidants are beneficial in thwarting chronic disease is promising. The Panel also established ULs for dietary antioxidants. The UL is defined as ‘the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects to almost all individuals in the general population’.1 The ULs for adult men and women are: 2 g/day for vitamin C; 1 g/day for vitamin E (any form of supplemental α-tocopherol); 400 μg/day for selenium; and no recommendations for β-carotene and other carotenoids. In this article, we present a critique of the recommendations for vitamins C and E, as well as a short summary of the current evidence for health benefits and recommendations for these two antioxidant vitamins.

Gene-Nutrient Interactions Exemplified by the α-Tocopherol Content of Tissues from α-Tocopherol Transfer Protein-Null Mice Fed Different Dietary Vitamin E Concentrations

YUNSOOK LIM,a BETTINA C. SCHOCK,a KISHORCHANDRA GOHIL,a SCOTT W. LEONARD,b LESTER PACKER,c CARROLL E. CROSS,a AND MARET G. TRABERa,b aCenter for Comparative Respiratory Biology and Medicine, Department of Internal Medicine, University of California, Davis, Davis, California, USA bDepartment of Nutrition and Food Management, Linus Pauling Institute, Corvallis, Oregon, USA cDepartment of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, California, USA