A. Vitamin A
Vitamin A is necessary for support of growth, health and life of major animal species. In the absence of vitamin A, animals will cease to grow and eventually die. Although retinol is needed for normal vision and some aspects of reproduction, recent discoveries have revealed that most, if not all, actions of vitamin A in development, differentiation and metabolism are mediated by nuclear receptor proteins that bind retinoic-acid, the active form of vitamin A (Anonymous, 1993). A group of retinoic acid-binding proteins (receptors) function in the nucleus by attaching to promoter regions in a number of specific genes to stimulate their transcription and thus affect growth, development and differentiation. Retinoic acid receptors in cell nuclei are structurally homologous and functionally analogous to the known receptors for steroid hormones, thyroid hormone (triiodothyronine) and vitamin D [1,25-(OH)2D]. Thus, retinoic acid is now recognized to function as a hormone to regulate the transcription activity of a large number of genes (Ross, 1993; Shin and McGrane, 1997).
Retinoids have a wide spectrum of biological activities. Retinoic acid plays an important role in growth and differentiation of embryonic tissues. It also regulates the differentiation of epithelial, connective and hematopoietic tissues (Safonova et al., 1994). The nature of the growth and differentiation response elicited by retinoic acid depends upon cell type. Retinoic acid can be an inhibitor of many cell types with a potential to reduce adipose tissues in meat producing animals (Suryawan and Hu, 1997).
Vitamin A deficiency causes at least four different and probably physiologically distinct lesions: loss of vision due to a failure of rhodopsin formation in the retina; defects in bone growth; defects in reproduction (i.e., failure of spermatogenesis in the male and resorption of the fetus in the female); and defects in growth and differentiation of epithelial tissues, frequently resulting in keratinization. Keratinization of these tissues results in loss of function in the alimentary, genital, reproductive, respiratory and urinary tracts. Such altered characteristics increase the susceptibility of the affected tissue to infection. Thus, diarrhea and pneumonia are typical secondary effects of vitamin A deficiency.
More is known about the role of vitamin A in vision than any of its other functions. Retinol is utilized in the aldehyde form (trans form to 11-cis-retinal) in the retina of the eye as the prosthetic group in rhodopsin for dim light vision (rods) and as the prosthetic group in iodopsin for bright light and color vision (cones). Retinoic acid has been found to support growth and tissue differentiation but not vision or reproduction (Scott et al., 1982). Vitamin A-deficient rats fed retinoic acid were healthy in every respect, with normal estrus and conception, but failed to give birth and resorbed their fetuses. When retinol was given even at a late stage in pregnancy, fetuses were saved. Male rats on retinoic acid were healthy but produced no sperm, and without vitamin A both sexes were blind (Anonymous, 1977).
Disease resistance is a function of vitamin A, with the vitamin needed for maintenance of mucous membranes and normal function of the adrenal gland. Vitamin A deficiency can impair regeneration of normal mucosal epithelium damaged by infection or inflammation (Ahmed et al., 1990; Stephensen et al., 1993) and thus could increase the severity of an infectious episode and/or prolong recovery from that episode. Adequate dietary vitamin A is necessary to help maintain normal resistance to stress and disease.
An animal’s ability to resist infectious disease depends on a responsive immune system, with a vitamin A deficiency causing a reduced immune response. In many experiments with laboratory and domestic animals, the effects of both clinical and subclinical deficiencies of vitamin A on the production of antibodies and on the resistance of different tissues against microbial infection or parasitic infestation have frequently been demonstrated (Kelley and Easter, 1987). Supplemental vitamin A improved the health of animals infected with roundworms, of hens infected with the genus Capillaria and of rats with hookworms (Herrick, 1972). Vitamin A is a valuable nutritional aid in the management of ringworm (Trichophyton verrucosum) infection in cattle.
Vitamin A deficiency affects immune function, particularly the antibody response to T cell-dependent antigens (Ross, 1992). The RAR-alpha mRNA expression and antigen-specific proliferative responses to T lymphocytes are influenced by vitamin A status in vivo, and directly modulated by retinoic acid (Halevy et al., 1994). Vitamin A deficiency affects a number of cells of the immune system, and repletion with retinoic acid effectively reestablishes the number of circulating lymphocytes (Zhao and Ross, 1995).
A diminished primary antibody response could also increase the severity and/or duration of an episode of infection, whereas a diminished secondary response could increase the risk of developing a second episode of infection. Vitamin A deficiency causes decreased phagocytic activity in macrophages and neutrophils. The secretory immunoglobulin A (IgA) system is an important first line of defense against infections of mucosal surfaces (McGhee et al., 1992). Several studies in animal models have shown that the intestinal IgA response is impaired by vitamin A deficiency (Wiedermann et al., 1993; Stephensen et al., 1996).
B. Beta-Carotene Function Independent of Vitamin A
Recent animal studies indicate that certain carotenoids have antioxidant capacities, but without vitamin A activity, can enhance many aspects of immune functions, act directly as antimutagens and anticarcinogens, protect against radiation damage and block the damaging effects of photosensitizers.
Since 1978, several studies have indicated that beta-carotene has a function independent of vitamin A in cattle (Lotthammer, 1979; Bindas et al., 1984). Cows fed supplemental beta-carotene had a higher intensity of estrus, increased conception rates and reduced frequency of follicular cysts compared to animals receiving only vitamin A. The corpus luteum of the cow has higher beta-carotene concentrations than any other organ, and it has been suggested that beta-carotene has a specific effect on reproduction in addition to its role as a precursor of vitamin A.
Graves-Hoagland et al. (1988, 1989) reported a positive relationship between postpartum bovine progesterone production and plasma concentrations of beta-carotene. In contrast, a negative relationship exists between postpartum bovine luteal function and plasma vitamin A. Other researchers have found no effect (Folman et al., 1979; Wang et al., 1988) or adverse effects (Folman et al., 1987) of beta-carotene supplementation on fertility of cattle.
Aréchiga et al. (1998) reported that for cows fed beta-carotene, the pregnancy rate at 120 days postpartum was 14.3% higher and milk yield was 6% to 11% higher than controls. Injectable beta-carotene has increased conception rates in swine and improved live births and live weights in pigs (Chew, 1993). Beta-carotene supplementation had a positive effect on the pregnancy rate of mares in some studies (Ahlswede and Konermann, 1980; Peltier et al., 1997).
Vitamin A and beta-carotene have important roles in protecting animals against numerous infections, including mastitis. Potential pathogens are regularly present in the teat orifice, and under suitable circumstances can invade the mammary gland and initiate clinical mastitis. Any unhealthy state of the epithelium would increase susceptibility of the mammary gland to invasion by pathogens. There are reports of improved mammary health in dairy cows supplemented with beta-carotene and vitamin A during the dry (Dahlquist and Chew, 1985) and lactating (Chew and Johnston, 1985) periods.
Polymorphonuclear neutrophils (PMN) are the major line of defense against bacteria in the mammary gland. Beta-carotene supplementation seems to exert a stabilizing effect on PMN and lymphocyte function during the period around dry-off (Tjoelker et al., 1990). Daniel et al. (1991a, b) reported that beta-carotene enhanced the bactericidal activity of blood and milk PMN, against S. auereus but did not affect phagocytosis. Vitamin A either had no effect or supressed bactericidal activity and phagocytosis. Control of free radicals is important for bactericidal activity but not for phagocytosis. The antioxidant activity of vitamin A is not important; it does not quench or remove free radicals. Beta-carotene, on the other hand, does have significant antioxidant properties and effectively quenches singlet oxygen free radicals (Di Mascio et al., 1991; Zamora et al., 1991).
Currently, there are significantly new views on the health benefits of megavitamin doses, particularly the antioxidant vitamins (C, E, and beta-carotene). Because free radical-induced damage to mammalian tissues is believed to contribute to the aging process and to the development of some degenerative diseases (Canfield et al., 1992), it has been proposed that dietary carotenoids serve as antioxidants in tissues (Thurnham, 1994).