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Vitamin E and stress

1. Dietary unsaturated fatty acid stress and the metabolism of α-tocopherol in the rat

Published online by Cambridge University Press:  09 March 2007

J. Green
Affiliation:
Walton Oaks Experimental Station, Vitamins Ltd, Tadworth, Surrey
A. T. Diplock
Affiliation:
Walton Oaks Experimental Station, Vitamins Ltd, Tadworth, Surrey
J. Bunyan
Affiliation:
Walton Oaks Experimental Station, Vitamins Ltd, Tadworth, Surrey
D. Mchale
Affiliation:
Walton Oaks Experimental Station, Vitamins Ltd, Tadworth, Surrey
I. R. Muthy
Affiliation:
Walton Oaks Experimental Station, Vitamins Ltd, Tadworth, Surrey
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Abstract

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1. A critical analysis of the biological antioxidant theory of vitamin E function has been made and the implications of the theory have been tested.

2. When small amounts of [5-Me-14C]α-tocopherol were present in lipid systems subject to autoxidation in vitro, it was found that, whether the tocopherol was the sole antioxidant or was in synergistic combination with a secondary antioxidant (ascorbic acid), peroxidation did not occur without concomitant destruction of the tocopherol. This was so, whether a simple fat substrate or a liver homogenate (subject to catalysis) was used. The decomposition of tocopherol took place even when the secondary antioxidant was in large excess, as would occur under physiological conditions in the vitamin E-deficient animal, and accelerated as the induction period neared its end.

3. When [5-Me-14C,3H]α-tocopherol and ascorbic acid were used as a synergistic antioxidant couple in vitro, tocopherol recovered from the peroxidizing system always had the same isotopic ratio as the starting material. This means that regeneration of tocopherol by the secondary antioxidant cannot involve, as an intermediate, a tocopherol carbon radical formed by loss of hydrogen from the 5-methyl group. Such radicals probably dimerize before they can be regenerated. The same result was found when doubly labelled α-tocopherol was given to the rat and recovered later from its tissues.

4. In a series of experiments, rats were rigorously depleted of vitamin E for periods up to 7 months and then given as little as 50 μg [14C]D-α-tocopherol. They were then given, either by stomach tube daily or by dietary addition, large amounts of methyl linoleate or vitamin E-free polyunsaturated fatty acid methyl esters prepared from cod-liver oil and compared with controls given methyl oleate for up to 31 days. When the possibility of interaction between the lipid and tocopherol in the gut was eliminated, analyses of liver, kidney, testis, adrenal, adipose tissue, whole carcass and faeces showed that there was no effect of the polyunsaturated fatty acids on either the metabolism or recovery of [14C]α-tocopherol in any of the animals.

5. When interaction between the administered fatty acid esters and tocopherol in the gut was allowed to take place, a marked destruction of [14C]α-tocopherol in the tissues was observed in animals given the polyunsaturated esters. The importance of oxidative destruction of tocopherol in the gut before absorption was demonstrated in a nutritional trial, in which cod-liver oil and lard were compared and the degrees of resistance of rats' erythrocytes to dialuric acid-induced haemolysis was used as an index of vitamin E depletion.

6. Similar experiments with [14Cα-tocopherol in weanling rats given large amounts of cod-liver oil methyl esters also showed little effect. Although there was a suggestion that prolonged feeding of partly peroxidized polyunsaturated esters could lead to a slight depression of tissue tocopherol concentrations, no significant differences were usually obtained.

7. Fourteen-day-old rats were given a vitamin E-deficient diet and received three weekly doses of 0.5 mg α-tocophcryl acetate. The dosage was stopped, the rats were then given a deficient diet containing 4% of either vitamin E-free linseed oil fatty acids or oleic acid, and the rate of their tocopherol depletion was measured by the erythrocyte haemolysis test. No effect of the polyunsaturated fatty acids was found. Nor was there any effect on the concentrations of ‘secondary antioxidants’ (glutathione and ascorbic acid) in liver, kidney, testis, muscle or adipose tissue.

8. The results of the experiments in vivo contrast strongly with those in vitro. They lead to the conclusion that lipid peroxidation, if it occurs in the living animal, is irrelevant to the problem of vitamin E function. This conclusion has been substantiated by a critical review of the literature on the quantitative aspects of the vitamin E-dietary fat relationship.

9. The effects of dietary fat stress in vitamin E-deficient animals are, we believe, due to two causes: (1) destruction of tocopherol in the diet or in the gastro-intestinal tract of the animal, and (2) the existence of an increased requirement for vitamin E for the metabolism of certain long-chain fatty acids. The specific effects of certain of these substances in producing or accelerating some vitamin E deficiency diseases may be related to the toxic states known to be induced in vitamin E-deficient animals by other stress factors.

Type
Research Article
Copyright
Copyright © The Nutrition Society 1967

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