Life Extension Magazine March 2005
Effects of vitamin E supplementation on oxidative stress in streptozotocin induced diabetic rats: investigation of liver and plasma.
This experimental study was designed to investigate the effects of vitamin E supplementation, especially on lipid peroxidation and antioxidant status elements 3/4 namely, glutathione (GSH), CuZn superoxide dismutase (CuZn SOD), and glutathione peroxidase (GSH Px), both in blood and liver tissues of streptozotocin (STZ) diabetic rats. The extent to which blood can be used to reflect the oxidative stress of the liver is also investigated. In diabetic rats, plasma lipid peroxide values were not significantly different,from control,whereas erythrocyte CuZn SOD (p < 0.01), GSH Px (p < 0.001) activities and plasma vitamin E levels (p < 0.001), were significantly more elevated than controls. Vitamin E supplementation caused significant decreases of erythrocyte GSH level (p < 0.01) in control rats and of erythrocyte GSH Px activity (p < 0.05) in diabetic rats. Liver findings revealed significantly higher lipid peroxide (p < 0.001) and vitamin E (p < 0.01) levels and lower GSH (p < 0.001), CuZn SOD (p < 0.001) and GSH Px (p < 0.01) levels in diabetic rats. A decreased hepatic lipid peroxide level (p < 0.01) and increased vitamin E/lipid peroxide ratio (p < 0.001) were observed in vitamin E supplemented, diabetic rats. A vitamin E supplementation level which did not cause any increase in the concentration of the vitamin in the liver or blood, was sufficient to lower lipid peroxidation in the liver. Vitamin E/lipid peroxide ratio is suggested as an appropriate index to evaluate the efficiency of vitamin E activity,independent of tissue lipid values. Further, the antioxidant components GSH, GSH Px and CuZn SOD and the relationships among them, were affected differently in the liver and blood by diabetes or vitamin E supplementation.
Yonsei Med J. 2004 Aug 31;45(4):703-10
Lipid peroxidation in men after dietary supplementation with a mixture of antioxidant nutrients.
Antioxidants and antioxidant enzymes protect living organisms against the attack of reactive oxygen species. An adequate daily intake of the individual antioxidants is therefore important to prevent the cells against oxidative damage. We investigated the effect of a modest dietary supplementation with a mixture of antioxidant nutrients (100 mg vitamin E, 100 mg vitamin C,6 mg beta-carotene and 50 microg of selenium per day) for 3 months on the plasma antioxidant capacity and indices of oxidative stress. Two groups of middle-age men were selected: group 1 with survivors of myocardial infarction (MI), and group 2 with clinically normal controls. The values of total antioxidant capacity of plasma (FRAP) significantly increased after supplementation with antioxidants in the both groups. Markers of in vivo lipid peroxidation, plasma malondialdehyde (MDA) and conjugated diene (CD) levels significantly decreased in the both supplemented groups. MDA and CD values were significantly higher at baseline in the group of survivors of myocardial infarction when compared with the group of healthy men. The results demonstrate that short-term and modest supplementation with a mixture of antioxidant nutrients improves antioxidative capacity and reduces products of lipid peroxidation in plasma. Since a more pronounced effect was observed within the group of survivors of myocardial infarction, a recommendation of antioxidant supplements seems appropriate for patients with a history of cardiovascular disease.
Bratisl Lek Listy. 2004;105(7-8):277-80
The role of metabolism in the antioxidant function of vitamin E.
Vitamin E (alpha-tocopherol), the principal chain-breaking antioxidant in biological membranes, prevents toxicant- and carcinogen-induced oxidative damage by trapping reactive oxyradicals. Although alpha-tocopherol antioxidant reactions appear to be not under direct metabolic control, alpha-tocopherol may function through redox cycles, which deliver reducing equivalents for antioxidant reactions and link antioxidant function to cellular metabolism. This review describes the antioxidant chemistry of alpha-tocopherol and evaluates the experimental evidence for the linkage of alpha-tocopherol turnover to cellular metabolism through redox cycles. Numerous in vitro experiments demonstrate antioxidant synergism between alpha-tocopherol and ascorbate, reduced glutathione, NADPH, and cellular electron transport proteins. Nevertheless, evidence that a one-electron redox cycle regenerates alpha-tocopherol from the tocopheroxyl radical is inconclusive. The difficulty of separating tocopheroxyl recycling from direct antioxidant actions of other antioxidants has complicated interpretation of the available data. A two-electron redox cycle involving alpha-tocopherol oxidation to 8a-substituted tocopherones followed by tocopherone reduction to alpha-tocopherol may occur, but would require enzymatic catalysis in vivo. Metabolism of antioxidant-inactive alpha-tocopheryl esters releases alpha-tocopherol, whereas reductive metabolism of alpha-tocopherylquinone, an alpha-tocopherol oxidation product, yields alpha-tocopherylhydroquinone, which also may provide antioxidant protection.
Crit Rev Toxicol. 1993;23(2):147-69
Regulation of selenoprotein GPx4 expression and activity in human endothelial cells by fatty acids, cytokines and antioxidants.
Phospholipid hydroperoxide glutathione peroxidase (GPx4) is the only antioxidant enzyme known to directly reduce phospholipid hydroperoxides within membranes and lipoproteins, acting in conjunction with alpha-tocopherol to inhibit lipid peroxidation. Peroxidation of lipids has been implicated in a number of pathophysiological processes, including inflammation and atherogenesis. We investigated the relative positive and negative effects of specific polyunsaturated fatty acids (PUFAs) and inflammatory cytokines on the activity and gene expression of the selenium-dependant redox enzyme GPx4. In human umbilical vein endothelial cells (HUVEC), GPx4 mRNA levels and activity were increased optimally by 114 nM selenium (as sodium selenite). Docosahexaenoic acid (DHA) and conjugated linoleic acid (CLA) further increased mRNA levels whereas arachidonic acid (ARA) had no effect; enzyme activity was decreased by DHA, was unaffected by CLA or was increased by ARA. GPx4 protein levels increased with selenium, ARA and DHA addition but not with CLA. Interleukin-1beta (IL-1beta) increased GPx4 mRNA, protein and activity whereas TNFalpha at 1 ng/ml increased activity while at 3 ng/ml it reduced activity and mRNA. Conversely, alpha-tocopherol reduced mRNA levels without affecting activity. These results indicate that lipids, cytokines and antioxidants modulate GPx4 in a complex manner that in the presence of adequate selenium, may favour protection against potentially proatherogenic processes.
Atherosclerosis. 2003 Nov;171(1):57-65
Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans.
Despite promising evidence from in vitro experiments and observational studies, supplementation of diets with alpha-tocopherol has not reduced the risk of cardiovascular disease and cancer in most large-scale clinical trials. One plausible explanation is that the potential health benefits of alpha-tocopherol supplements are offset by deleterious changes in the bioavailability and/or bioactivity of other nutrients. We studied the effects of supplementing diets with RRR-alpha-tocopheryl acetate (400 IU/d) on serum concentrations of gamma- and delta-tocopherol in a randomized, placebo-controlled trial in 184 adult nonsmokers. Outcomes were changes in serum concentrations of gamma- and delta-tocopherol from baseline to the end of the 2-mo experimental period. Compared with placebo, supplementation with alpha-tocopherol reduced serum gamma-tocopherol concentrations by a median change of 58% [95% CI = (51%, 66%), P < 0.0001], and reduced the number of individuals with detectable delta-tocopherol concentrations (P < 0.0001). Consistent with trial results were the results from baseline cross-sectional analyses, in which prior vitamin E supplement users had significantly lower serum gamma-tocopherol than nonusers. In view of the potential benefits of gamma- and delta-tocopherol, the efficacy of alpha-tocopherol supplementation may be reduced due to decreases in serum gamma- and delta-tocopherol levels. Additional research is clearly warranted.
J Nutr. 2003 Oct;133(10):3137-4