Lawrence J. Machlin

Free radical tissue damage: protective role of antioxidant nutrients.

Highly reactive molecules called free radicals can cause tissue damage by reacting with polyunsaturated fatty acids in cellular membranes, nucleotides in DNA, and critical sulfhydryl bonds in proteins. Free radicals can originate endogenously from normal metabolic reactions or exogenously as components of tobacco smoke and air pollutants and indirectly through the metabolism of certain solvents, drugs, and pesticides as well as through exposure to radiation. There is some evidence that free radical damage contributes to the etiology of many chronic health problems such as emphysema, cardiovascular and inflammatory diseases, cataracts, and cancer. Defenses against free radical damage include tocopherol (vitamin E), ascorbic acid (vitamin C), β‐carotene, glutathione, uric acid, bilirubin, and several metalloenzymes including glutathione peroxidase (selenium), catalase (iron), and superoxide dismutase (copper, zinc, manganese) and proteins such as ceruloplasmin (copper). The extent of tissue damage is the result of the balance between the free radicals generated and the antioxidant protective defense system. Several dietary micronutrients contribute greatly to the protective system. Based on the growing interest in free radical biology and the lack of effective therapies for many of the chronic diseases, the usefulness of essential, safe nutrients in protecting against the adverse effects of oxidative injury warrants further study.—Machlin, L. J.; Bendich, A. Free radical tissue damage: protective role of antioxidant nutrients. FASEB J. 1: 441‐445; 1987.

Vitamin E and human health: Rationale for determining recommended intake levels

The recent literature provides strong evidence that vitamin E intakes much higher than the current recommendations can contribute to and/or improve human health. In fact, the available data indicate that at higher-than-current recommended intake levels, vitamin E affects several functions related to human health. For example, Vitamin E is required to protect polyunsaturated fatty acids (PUFAs) against auto-oxidation. The amount of vitamin E needed to protect PUFAs against oxidative damage is at least 0.4-0.8 mg vitamin E per gram PUFAs and may be in excess of 1.5 mg/g when diets contain higher-than-average levels of long-chain PUFAs. Based upon studies of vitamin E kinetics and metabolism, a daily vitamin E intake of 135-150 IU is suggested. Important functions such as protection against oxidative damage, immune response, and the propensity of platelets to adhere to the vessel wall are related to vitamin E intakes. Vitamin E intake of 40 IU/d was the least amount demonstrated to inhibit low-density lipoprotein oxidation; a dose-dependent effect was seen up to 800 IU/d. Vitamin E intakes of at least 60 IU/d enhanced immune responses and intakes of 200 IU-400 IU/d decreased platelet adhesion to the vessel wall. Based upon the effects of modulating these functions, it is hypothesized that vitamin E plays a pivotal role in the prevention of cardiovascular diseases. Indeed, many observational studies have reported vitamin E to reduce the risk of cardiovascular disease. Recent intervention studies corroborate these findings. Of equal importance, there is a solid body of literature that demonstrates that these and much higher vitamin E intakes are safe.

Influence of vitamin E on platelet aggregation and thrombocythemia in the rat.

Summary Collagen-induced platelet aggregation was increased in 9-10 wk old vitamin E deficient rats although there was no difference in platelet count between deficient and control animals. With a more prolonged deficiency (at 15 wk) both platelet aggregation and platelet counts were elevated in the vitamin E deficient animals.

Biopsy method for human adipose with vitamin E and lipid measurements

An adaptation of the needle biopsy procedure of Beynen and Katan for human adipose tissue, which yields 2–10 mg adipose samples, is described and evaluated. Micromethods are presented for the analysis of α-tocopherol, cholesterol and fatty acids in each adipose specimen. The needle biopsy procedure, which uses a Vacutainer to create suction, is compared with a punch biopsy method. The needle biopsy is rapid (6 samples/hr), simple and unobjectionable to the subjects, and provides samples with reproducible ratios of cholesterol and α-tocopherol. Unlike the punch biopsy, the needle biopsy reliably obtains specimens with a lipid composition typical of adipocytes. The needle biopsy method is adaptable to nutritional studies of tocopherol and fatty acid metabolism in adipose, and to studies of hazardous compounds stored in adipose. The linoleic acid content of adipose from residents of the West Coast was found to be considerably higher than values reported earlier. The adipose fatty acid data indicate an increase in human adipose linoleate when compared with earlier reports and suggest a trend toward increasing linoleic acid in the American diet.

INTERACTIONS OF VITAMIN E WITH VITAMIN C, VITAMIN B12, AND ZINC

In the past, clarification of the interaction of vitamin E with selenium, polyunsaturated fatty acids, vitamin A, and iron has led to an understanding of many previously perplexing observations concerning vitamin E status in man and animals. The interactions of vitamin E with vitamin C, vitamin B,,, and zinc are less well explored. Greater knowledge of these interactions will, undoubtedly, lead to a better understanding of both the biochemical function of vitamin E and the clinical manifestations of a deficiency of this vitamin.

Drug metabolism and hepatic heme proteins in the vitamin E-deficient rat

Abstract Hepatic microsomes prepared from vitamin E deficient and supplemented rats were analyzed for cytochrome P-450 content and drug metabolizing activity. Reduced levels of benzo[α]pyrene hydroxylase and ethylmorphine N -demethylase activities were observed in microsomes derived from rats fed a diet deficient in vitamin E compared to those of control rats. NADPH-mediated destruction of P-450, and pentobarbital and zoxazolamine sleeping times were similar in the two groups. Induction with 3-methylcholanthrene raised the levels of benzo[α]pyrene hydroxylase activity of both supplemented and deficient rats to the same absolute levels. No differences were noted in cytochrome P-450 or P-448 content between control and tocopherol deficient rats, nor did the activity of liver catalase differ between the two dietary groups. Thus, these studies did not demonstrate any impairment of heme protein synthesis in vitamin E deficient rats.

Differences in Vitamin E Levels in Tissues of the Spontaneously Hypertensive and Wistar-Kyoto Rats

Abstract Tissue vitamin E levels were significantly lower in spontaneously hypertensive rats (SHR) than in the normotensive, genetically related Wistar/Kyoto (W/K). This difference was also observed when animals were given identical oral doses of vitamin E. The possible relationship of lower vitamin E tissue levels to lower immune responses in the SHR is discussed.

Strain Differences in Testes Degeneration, Myopathy, and the Lymphocyte Mitogen Response in Vitamin E-Deficient Rats

Abstract The differences in sensitivity to vitamin E deficiency were examined in two genetically related inbred strains of rat, the spontaneously hypertensive rat and its genetic ancestor, the Wistar-Kyoto rat, as well as in the outbred Sprague-Dawley strain. The three strains showed differences in growth rate, myopathy, testes degeneration, and immunological responses in response to vitamin E deficiency with the spontaneously hypertensive rat showing the greatest sensitivity to the deficiency.