Antioxidant vitamins and their functions in immune responses.
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Animals↗
Biomedical subjects
A Bendich
Publications and source records attributed to A Bendich.
Characterization of immunomodulatory activity of retinoids.
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Adjuvants, Immunologic↗
Ascorbic acid safety: analysis of factors affecting iron absorption.
The potential for excessive iron absorption by subjects ingesting ascorbic acid doses above the recommended dietary allowance (60 mg) was evaluated by examining published literature (24 studies, 1412 subjects) in which ascorbic acid was part of a test meal given to determine effects on iron absorption. Three parameters associated with iron absorption were identified: (1) a relatively shallow slope for the dose-response curve relating ascorbic acid dosage (1-1000 mg) and percent iron absorption; (2) no significant effect of ascorbic acid on the absorption of high (60 mg) iron doses; and (3) an inverse relationship between iron absorption and plasma transferrin saturation. Ascorbic acid did not increase the incidence of 'high' iron absorbers (greater than 2 SD from population mean) above control levels; limited data for ascorbic acid doses greater than 100 mg/d indicated no change in the distribution of iron absorption values.
Adult↗
Antioxidant micronutrients and immune responses.
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Animals↗
Vitamin B6 safety issues.
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Abnormalities, Drug-Induced↗
Effect of dietary lipids on hepatic and plasma beta-carotene and vitamin A levels in rats fed beta-carotene.
Diets low in carotenoids have been associated with greater risks of developing certain cancers. Diets high in fats, especially unsaturated fats, have also been associated with increased risks of developing cancer. This study was undertaken to evaluate the effect of fat type on the beta-carotene status in a rat model. Rats were fed diets containing 2 g/kg beta-carotene or placebo and either 10% lard or corn oil for 13-16 weeks. Plasma vitamin A was unaffected by the dietary regimes. Liver vitamin A levels were significantly increased in the beta-carotene groups and were greater in the lard-fed animals. No detectable level of plasma beta-carotene was found in the rats fed placebo diets. In animals given dietary beta-carotene, plasma beta-carotene levels were significantly reduced in the group fed corn oil compared to the group fed lard. Liver beta-carotene levels were higher in the groups fed corn oil. The results suggest that the type of dietary fat can significantly affect the circulating and tissue levels of beta-carotene.
Animals↗
Safety of vitamin A.
Vitamin A adequacy is discussed in terms of the recommended allowances appropriate for the needs of the majority of individuals. Deficiency can result in xerophthalmia and permanent blindness and in increased mortality rates among children. Toxicity has been associated with the overconsumption of vitamin A supplements. Acute hypervitaminosis A may occur after ingestion of greater than or equal to 500,000 IU (over 100 times the RDA) by adults or proportionately less by children. Symptoms are usually reversible on cessation of overdosing. Factors influencing chronic hypervitaminosis A include dosing regimen, physical form of the vitamin, general health status, dietary factors such as ethanol and protein intake, and interactions with vitamins C, D, E, and K. Both excess and deficiency of vitamin A in pregnant animals was shown to be teratogenic. In humans, congenital malformations associated with maternal over-use of high doses of vitamin A were reported but no cause-and-effect relationship has been established. Deficiency of the vitamin during pregnancy has also been associated with congenital abnormalities. Reported incidences of vitamin A toxicity are rare and have averaged fewer than 10 cases per year from 1976 to 1987.
Adolescent↗
Carotenoids and the immune response.
There is growing evidence from in vitro and in vivo laboratory animal studies that beta-carotene can protect phagocytic cells from autooxidative damage, enhance T and B lymphocyte proliferative responses, stimulate effector T cell functions, and enhance macrophage, cytotoxic T cell and natural killer cell tumoricidal capacities, as well as increase the production of certain interleukins. Many of these effects have also been seen with carotenoids lacking provitamin A activity but having the antioxidant and singlet oxygen quenching capacities of beta-carotene. The association of immunoenhancement with decreased tumor burden in animals given carotenoids suggests a potential explanation for the epidemiological data linking lower carotenoid status with higher incidences of certain cancers. Since vitamin A is a relatively poor antioxidant and cannot quench singlet oxygen, beta-carotene may have more importance as a nutrient than simply serving as a precursor of vitamin A.
Animals↗
Symposium conclusions: biological actions of carotenoids.
The symposium on the biological action of carotenoids highlighted the antioxidant and singlet oxygen quenching properties of beta-carotene and other carotenoids of similar structure but lacking provitamin A activity. The provitamin A functions of beta-carotene were also discussed. The immuno-enhancing and anticarcinogenic actions of the carotenoids could be associated with functions unrelated to their ability to form vitamin A. Thus, the symposium emphasized the expansion of the role of beta-carotene beyond its classic nutritional function and has examined the importance of other dietary carotenoids.
Animals↗
Biological actions of carotenoids.
Of 600 carotenoids from natural sources that have been characterized, fewer than 10% serve as precursors of vitamin A. Many dietary carotenoids, both with and without provitamin A activity, are found in the blood and tissues of humans. beta-Carotene, the most nutritionally active carotenoid, comprises 15-30% of total serum carotenoids. Vitamin A is formed primarily by the oxygen-dependent central cleavage of beta-carotene and other provitamin A carotenoids. Several carotenoids show enhancement of the immune response, inhibition of mutagenesis, reduction of induced nuclear damage, and protection from various neoplastic events in cells, tissues, and whole animals. Carotenoids also protect against photo-induced tissue damage. Some carotenoids, including beta-carotene, quench highly reactive singlet oxygen under certain conditions and can block free radical-mediated reactions. In epidemiological studies, the intake of carotenoid-rich fruits and vegetables has been correlated with protection from some forms of cancer, particularly lung cancer. Similarly, serum beta-carotene levels have been associated with a decreased chance of developing lung cancer. It must be stressed, however, that these epidemiological associations do not show cause and effect. In this regard, long-term intervention trials with beta-carotene supplements are in progress. Whatever the results of these trials, carotenoids clearly show biological actions in animals distinct from their function as precursors of vitamin A.
Animals↗
Vitamin E and immune functions.
Vitamin E, the major lipid-soluble antioxidant present in all cellular membranes, is an important nutrient for optimal immune function. When animals are fed nutritionally complete diets lacking vitamin E, immune responses are adversely affected. Supplementation of these diets with higher than nutritionally adequate levels of vitamin E enhances immune responses. High levels of PUFA are immunosuppressive, and vitamin E can partially overcome this immunosuppression. High levels of vitamin C can protect tissue levels of vitamin E and may indirectly contribute to the immunoenhancement by vitamin E. Severe selenium deficiency is immunosuppressive. Vitamin E can protect some aspects of immune responses from the adverse effects of selenium deficiency. These data clearly indicate that nutrients that affect the overall antioxidant status have important effects on immune functions. In addition, antioxidant nutrient interactions can synergize to overcome the adverse effects of polyunsaturated fatty acids on immune functions (Fig 2).
Animals↗
The safety of beta-carotene.
Epidemiological studies have associated low dietary and/or plasma level of carotenoids with higher incidences of certain cancers. This evidence has led the National Cancer Institute to initiate more than a dozen prospective clinical trials in which supplements of beta-carotene alone, or in combination with other micronutrients, are being taken. In these trials, the beta-carotene supplements are given in the range of 15-50 mg/day. The safety of this level of intake is well documented. beta-Carotene has been successfully used to treat inherited photosensitivity diseases for more than 15 years at dosages of 180 mg/day or more, without any adverse effects other than hypercarotenemia. Toxicity studies in animals have shown that beta-carotene is not carcinogenic, mutagenic, embryotoxic, or teratogenic and does not cause hypervitaminosis A. In the few isolated reports of carotenoid-related toxicity, the findings are associated with very large intakes of foods containing beta-carotene, among other constituents, and have not been substantiated in individuals who have taken high doses of beta-carotene for several years.
Animals↗
Safety of oral intake of vitamin E.
A review of the literature concerning the safety of oral intake of vitamin E indicated that the toxicity of vitamin E is low. Vitamin E supplementation has resulted in inconsistent effects in serum lipid and lipoprotein levels. Animal studies showed that vitamin E is not mutagenic, carcinogenic, or teratogenic. In human studies with double-blind protocols and in large population studies, oral vitamin E supplementation resulted in few side effects even at doses as high as 3200 mg/d (3200 IU/d).
Animals↗
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), beta-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.
Animals↗
Safety of pyridoxine--a review of human and animal studies.
A literature review was conducted on adverse effects associated with administration of high oral doses of pyridoxine (vitamin B6) to animals and man. The human data suggest that doses of pyridoxine greater than 500 mg/day for prolonged periods of time can result in sensory nerve damage. Doses less than 500 mg/day appear to be safe on the basis of literature reports where the compound was administered for periods ranging from 6 months to 6 years.
Abnormalities, Drug-Induced↗
Oxidation as a possible mechanism of cellular aging: vitamin E deficiency causes premature aging and IgG binding to erythrocytes.
Senescent-cell antigen is a "neo-antigen" that appears on the surface of senescent cells and initiates IgG binding and cellular removal. As an approach to evaluating oxidation as a possible mechanism for generation of senescent-cell antigen, we studied erythrocytes from vitamin E-deficient rats. Vitamin E is localized primarily in cellular membranes. Its major role is the termination of free-radical chain reactions propagated by the polyunsaturated fatty acids of membrane propagated by the polyunsaturated fatty acids of membrane phospholipids. Results of our studies indicate that erythrocytes of all ages from vitamin E-deficient rats behave like old erythrocytes from normal rats, as determined by their susceptibility to phagocytosis, IgG binding, anion transport ability, and glyceraldehyde-3-phosphate dehydrogenase activity. Increased breakdown products of band 3 were observed with immunoblotting in membranes of erythrocytes from vitamin E-deficient rats. Breakdown products of band 3 are known to increase as cells age in normal individuals. The data suggest that oxidation may be a possible mechanism for erythrocyte aging and generation of senescent-cell antigen in vivo.
Anemia, Hemolytic↗
Effect of beta-carotene and canthaxanthin on the immune responses of the rat.
Male Wistar Kyoto rats were fed diets containing either 2 g/kg (0.2%) beta-carotene, canthaxanthin or basal diet for up to 66 wk. Plasma and tissues were analyzed for vitamin A, vitamin E, beta-carotene or canthaxanthin levels. In vitro immune responses of splenocytes to T- and B-lymphocyte mitogens were determined. T- and B-lymphocyte responses were consistently enhanced in the groups fed beta-carotene or canthaxanthin. Since canthaxanthin cannot be converted to vitamin A, the immunoenhancement seen in these experiments is attributed to a carotenoid effect.
Animals↗
Dietary vitamin E requirement for optimum immune responses in the rat.
Supplementation of diets with vitamin E has been shown to enhance immune responses in numerous animal models. However, these experiments have not investigated the dietary requirement of vitamin E for optimal T- and B-lymphocyte mitogen responses and compared this directly with the requirement for growth, maintenance of spleen-body weight ratios, platelet count as well as prevention of myopathy and red blood cell lysis. We have found that male weanling rats maintain normal rate of growth and spleen-body weight ratio when fed purified diets containing 7.5 mg/kg vitamin E. A level of 15 mg/kg was adequate to prevent myopathy, and 50 mg/kg was necessary for the prevention of red blood cell hemolysis. The dietary requirement for optimum T- and B-lymphocyte responses to mitogens was greater than 50 mg/kg and was significantly correlated with plasma vitamin E levels over a range of 0.04-18 micrograms/ml. Thus, the requirement for this index of immune system activity was higher than for the other functional parameters of vitamin E adequacy measured. Therefore, the immune system responds to changes in dietary vitamin E well before there are signs of frank vitamin deficiency.
Animals↗