Vitamin A itself does not occur in plant products, but its precursors, carotenes, do occur in several forms. These compounds (carotenoids) are commonly referred to as provitamin A because the body can transform them into active vitamin A. The combined potency in a feed, represented by its vitamin A and carotene content, is referred to as its vitamin A value. Vitamin A occurs in three forms: retinol, retinal, and retinoic acid. Retinol is the alcohol form of vitamin A. Replacement of the alcohol group (-OH) by an aldehyde group (-CHO) yields retinal, and replacement by an acid group (-COOH) gives retinoic acid. Vitamin A products for feed use include the acetate, propionate and palmitate esters. Vitamin A alcohol (retinol) is a nearly colorless, fat-soluble, long-chain, unsaturated compound with five bonds (Illus. 2-1). Since it contains double bonds, vitamin A can exist in different isomeric forms. Vitamin A and its precursors, carotenoids, are rapidly destroyed by oxygen, heat, light and acids. Presence of moisture and trace minerals reduces vitamin A activity in feeds (Olson, 1984).
1. Precursors of vitamin A, the carotenes, occur as orange-yellow pigments, mainly in green leaves and to a lesser extent in corn. Four of these carotenoids, alpha-carotene, beta-carotene, gamma-carotene, and cryptoxanthin (the main carotenoid of corn), are of particular importance because of their provitamin A activity. Vitamin A activity of beta-carotene is substantially greater than that of other carotenoids. As an example, both alpha-carotene and cryptoxanthin have about one-half the conversion rate of beta-carotene (Tanumihardjo and Howe, 2005). However, biological tests have consistently shown that pure vitamin A has twice the potency of beta-carotene on a weight-to-weight basis. Only one molecule of vitamin A is formed from one molecule of beta-carotene. Lycopene is an important carotenoid for its antioxidant function but does not possess the beta-ionone ring structure (required for vitamin A activity) and, therefore, is not a precursor of vitamin A. In humans, beta-carotene and lycopene are the predominant carotenoids in tissue (Ribaya-Mercado et al., 1995).
A number of factors influence digestibility of carotene and vitamin A. Working with lambs, Donoghue et al. (1983) reported that dietary levels of vitamin A, ranging from mildly deficient to toxic, affect digestion and uptake. Percentage transfer from the digestive tract from supplemental dietary levels of 0, 100 and 12,000 µg retinol per kg were 91%, (Note: I am confused how 0 was 91%) 58% and 14%, respectively. Wing (1969) reported that the apparent digestibility of carotene in various forages fed to dairy cattle averaged about 78%. Variables that influenced carotene digestibility included month of forage harvest, type of forage (hay, silage, greenchop or pasture), species of plant and plant dry matter. In general, carotene digestibility was higher during warmer months than during winter.
Several papers indicate that appreciable amounts of carotene or vitamin A may be degraded in the rumen. Various studies with different diets have indicated preintestinal vitamin A disappearance values ranging from 40% to 70% (Ullrey, 1972). Rode et al. (1990) compared microbial degradation of vitamin A (retinol acetate) from steers fed concentrate, hay or straw diets. Estimated effective rumen degradation of biologically active vitamin A was 67% for cattle fed concentrates compared to 16% and 19% for animals fed hay and straw diets, respectively.
In most mammals the product ultimately absorbed from the intestinal tract as a result of feeding carotenoids is mainly vitamin A. There is considerable species specificity regarding the ability to absorb dietary carotenoids. In some species, such as the rat, pig, goat, sheep, rabbit, buffalo and dog, almost all the carotene is cleaved in the intestine. In humans, some breeds of cattle, horses and carp, significant amounts of carotene can be absorbed. Absorbed carotene can be stored in the liver and fatty tissues. Hence, these latter animals have yellow body and milk fat, whereas animals that do not absorb carotene have white fat. In the case of cattle, there is a strong breed difference in absorption of carotene. The Holstein is an efficient converter, having white adipose tissue and milk fat. The Guernsey and Jersey breeds, however, readily absorb carotene, resulting in yellow adipose fat and also butterfat.
The chick on the other hand absorbs only hydroxy carotenoids (e.g. lutein and zeaxanthin) in the uncharged form and stores them in tissues. These carotenes provide no vitamin A but result in the yellow color of the carcass and eggs. Like other species the hydrocarbon carotenoids which provide vitamin A activity are converted in the chick intestine and absorbed as vitamin A.
Beta-carotene present in feed is converted to retinal in the intestinal mucosa by an enzyme. The retinal is then reduced to retinol (vitamin A). However, extensive evidence exists also for random (excentric) cleavage, resulting in retinoic acid and retinal, with a preponderance of apocarotenals formed as intermediates (Wolf, 1995). The cleavage enzyme has been found in many vertebrates but is not present in the cat or mink. Therefore, these species cannot utilize carotene as a source of vitamin A. The main site of vitamin A and carotenoid absorption is the mucosa of the proximal jejunum. Although carotenoids are normally converted to retinol in the intestinal mucosa, they may also be converted in the liver and other organs, especially in yellow fat species such as poultry and Guernsey and Jersey breeds of cattle (McGinnis, 1988). Either dietary retinol or retinol resulting from conversion of carotenoids is then esterified with a long-chain fatty acid, usually palmitate.
A number of factors affect absorption of carotenoids. Cis-trans isomerism of the carotenoids is important in determining their absorbability, with the trans forms being more efficiently absorbed (Stahl et al., 1995). Among carotenoids, there is a differential uptake and clearance of specific carotenoids (Bierer et al., 1995; Johnson et al., 1997). Dietary fat is important on the absorption process (Roels et al., 1958; Fichter and Mitchell, 1977). Dietary antioxidants (e.g., vitamin E) also appear to have an important effect on the utilization and perhaps absorption of carotenoids. It is uncertain whether the antioxidants contribute directly to the efficient absorption or whether they protect both carotene and vitamin A from oxidative breakdown. Protein deficiency reduces absorption of carotene from the intestine.
Different species of animals convert beta-carotene and vitamin A with varying degrees of efficiency. Some factors that influence the rate at which carotenoids are converted to vitamin A are type of carotenoid, class and production level of animal, individual genetic differences in animals and level of carotene intake (NRC, 1996). Efficiency of vitamin A conversion from beta-carotene is decreased with higher levels of intake (Van Vliet et al., 1996). The conversion rate of the rat has been used as the standard value, with 1 mg of beta-carotene equal to 1,667 IU of vitamin A. Based on this standard, the comparative efficiencies of various species are shown in Table 2-1. Of the species studied, only poultry are equal to the rat in vitamin conversion, with cattle being only 24% as efficient. For the chicken, as beta-carotene level is increased, conversion efficiency drops from a ratio of 2:1 to 5:1; for calves the conversion efficiency drops from 8:1 to 16:1 (Bauernfeind, 1972).
Stress conditions, such as extremely hot weather, viral infections and altered thyroid function, have also been suggested as causes for reduced carotene to vitamin A conversion. Vitamin A requirements are higher under stressful conditions such as abnormal temperatures or exposure to disease conditions. As an example with poultry, coccidiosis not only causes destruction of vitamin A in the gut but also injures the microvilli of the intestinal wall. Mycotoxins are known to cause digestive disturbances such as vomiting and diarrhea as well as internal bleeding. They can also interfere with absorption of dietary vitamins A, D3, E and K (McDowell and Ward, 2008). Vitamin A deficiency in poultry may not only act directly on the growth plate for bone development, but may also indirectly affect growth by systemic mechanisms. For example, vitamin A appears to be required for growth hormone secretion, and for thyroid hormone secretion and action (DeLuca et al., 2000). The efficiency of beta-carotene in meeting the vitamin A requirements of trout and salmon apparently is dependent on water temperature. Cold-water fish utilize precursors of vitamin A at 12.4° to 14°C, but do not at 9°C (Poston et al., 1977). Activity of beta-carotene-15, 15′-dioxygenase, which oxidizes beta-carotene to retinal in the intestinal mucosa, may be restricted at cold temperatures. Dietary retinyl esters are hydrolyzed to retinol in the intestine. They are absorbed as the free alcohol and then re-esterified in the mucosa. The retinyl esters are transported mainly in association with lymph chylomicrons to the liver where they are hydrolyzed to retinol and re-esterified for storage. The primary storage form is retinyl palmitate. Hydrolysis of the ester storage form mobilizes vitamin A from the liver as free retinol. Retinol is released from the hepatocyte as a complex with retinol-binding protein (RBP). Retinol in association with RBP circulates to peripheral tissues complexed to a thyroxine-binding protein, transthyretin (Blomhoff et al., 1991; Ross, 1993). The retinol-transthyretin complex is transported to target tissues, where the complex binds to a cell-surface receptor. The receptor was found to be located in all tissues known to require retinol for their function, particularly the pigment epithelium of the eye (Wolf, 2007). Once the retinoids are transferred into the cell they are quickly bound by specific binding proteins in the cell cytosol. The intracellular retinoid-binding proteins bind retinol, retinal and retinoic acid for purposes of protection against decomposition, solubilize them in aqueous medium, render them nontoxic and transport them within cells to their site of action. These binding proteins also function by presenting the retinoids to the appropriate enzymes for metabolism (Wolf, 1991). Some of the principal forms of intracellular (cytoplasmic) retinoid-binding proteins are cellular retinol-binding proteins (CRBP, I and II), cellular retinoic acid-binding proteins (CRABP, I and II), cellular retinaldehyde binding protein (CRALBP) and six nuclear retinoic acid receptors (RAR and RXR, with alpha, beta and gamma forms). There are two classes of nuclear receptors with all-trans retinoic acid the ligand for RAR; 9-cis-retinoic acid is the ligand for RXR (Kasner et al., 1994; Kliewer et al., 1994). Retinol is readily transferred to the egg in birds, but the transfer of retinol across the placenta is marginal and mammals are born with very low liver stores of vitamin A. In the pig, uterine RBP has been identified in the uterus, with the function of delivering retinol to the fetus (Clawitter et al., 1990). The main excretory pathway for vitamin A is by elimination as glucuronide conjugates in the bile prior to fecal excretion.
The liver normally contains about 90% of the total body vitamin A. The remainder is stored in the kidneys, lungs, adrenals and blood, with small amounts also found in other organs and tissues. Several studies have shown that the liver can store enough vitamin A to protect the animal from long periods of dietary scarcity. This large storage capacity must be considered in studies of vitamin A requirements to ensure that intakes that appear adequate for a given function are not being supplemented by reserves stored prior to the period of observation. Measurement of the liver store of vitamin A at slaughter or a biopsy (Illus. 2-2) is a useful technique in studies of vitamin A status and requirements.
During periods of low dietary carotene, stored vitamin A can be mobilized and utilized without signs of vitamin A deficiency. At birth, the mammal usually does not have sufficient vitamin A reserves to provide for its needs for any substantial time. Accordingly, it is important that young animals receive colostrum, which generally is high in vitamin A, within a few hours after birth. If the dam has received a diet low in vitamin A activity, the newborn animal is likely to be susceptible to a vitamin A deficiency because body reserves are low and colostrum will have a subnormal content (Miller et al., 1969). Grazing livestock with access to green, high-quality pastures can store sufficient vitamin A in the liver to be adequate for periods of low intake during the winter or dry season, perhaps as long as 4 to 6 months. Cattle grazing good pasture will have 30 to 80 mg per kg (13.6 to 36.4 mg per lb) of liver vitamin A (Rumsey, 1975), and cattle entering the feedlot with 20 to 40 mg per kg (9.1 to 18.2 mg per lb) will have adequate liver stores for 3 to 4 months (Perry et al., 1967). Intramuscular injection of 1 million IU of emulsified vitamin A apparently provides sufficient vitamin A to prevent deficiency signs for 2 to 4 months in growing or breeding beef cattle (NRC, 1996). Because of vitamin A storage, sheep that graze on green forage during the normal growing season may be able to do reasonably well on a low-carotene diet of dry feed for periods of 4 to 6 months (NRC, 1985). Goats that have had access to good quality green feed can probably depend on vitamin A stores for a minimum of 3 months without detrimental effects (NRC, 1981). The tendency of the goat to search out palatable green plant parts ensures it an advantage over other ruminant species. However, goats that are forced to consume more conventional cattle or sheep diets because of the unavailability of browse would not have such an advantage (NRC, 1981). Liver vitamin A concentrations in swine are substantial and are useful to evaluate status of the vitamin (Hoffmann-LaRoche, 1991).
Vitamin A is necessary for support of growth, health and life of all major animal species. In the absence of vitamin A, animals will cease to grow and eventually die. Vitamin A and its derivatives, the retinoids, have a profound influence on organ development, cell proliferation, and cell differentiation and their deficiency originates or predisposes a number of disabilities (McDowell, 2000; Esteban-Pretel et al., 2010). Even with a mild vitamin A deficiency in pregnant rats, there was reduction of nephrons in the fetuses resulting in kidney malfunction (Marín et al., 2005; Bhat and Manolescu, 2008). Vitamin A deficiency in rats induced anatomic and metabolic changes comparable to those associated with neurodegenerative disorders; slowing of cerebral growth was correlated with retinol level (Rahab et al., 2009). During embryogenesis, retinoic acid has been shown to influence processes governing the patterning of neural tissue and cranio-facial, eye and olfactory system development; retinoic acid continues to influence the development, regeneration, and well-being of neurons (Asson-Batres et. al., 2009). Retinoic acid also regulates the differentiation of epithelial, connective and hematopoietic tissues (Safonova et al., 1994). It has been suggested that retinoic acid is an effective antidiabetic agent that could be considered in the treatment of type 2 diabetes (Wolf, 2009; Manolescu et al., 2010). 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). Proliferation and cellular aggregation are both critical features for survival and self-renewal of primordial germ cells (PGCs). With growing chicks, retinoic acid promoted PGC proliferation and increased intercellular aggregation of PGCs (Yu et al., 2011). 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). 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 (McDowell, 2000; Solomons, 2006). 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; Lessard et al., 1997). 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 re-establishes 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). Recent animal studies indicate that certain carotenoids without vitamin A activity have antioxidant capacities, and can enhance many aspects of immune functions, act directly as antimutagens and anticarcinogens, protect against radiation damage and block the damaging effects of photosensitizers (Chew, 1995; Koutsos, 2006; Lindshield and Erdman, Jr., 2006).
Beta-carotene can function as a chain-breaking antioxidant, it deactivates reactive chemical species such as singlet oxygen, triplet photochemical sensitizers and free radicals which would otherwise induce potentially harmful processes (e.g., lipid peroxidation) (McDowell, 2004).
In humans, carotenoids had a preventive role in bladder cancer and implications for prevention of other types of cancer (Schabath et al., 2004).
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. 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; Lindshield and Erdman Jr., 2006).
Currently, there are significant 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).
In poultry carotenoids can directly affect gene expression and this mechanism may enable carotenoids to modulate the interaction between B cells and T cells, thus regulating humeral and cell-mediated immunity (Koutsos, 2003). Lack of carotenoids was reported to increase parameters of systemic inflammation in growing chicks (Koutsos et al., 2006).
In the lipid environment of biological membranes a combination of carotenoids and other antioxidants, especially tocopherols, may provide better antioxidant protection than tocopherols alone. Antioxidant properties of carotenoids include scavenging singlet oxygen and peroxyl radicals, sulfur, sulfonyl and NO2 radicals and providing protection of lipids from superoxide and hydroxyl radical attack (Surai, 2002). Therefore, carotenoids can actively quench singlet oxygen (O2) and prevent lipid peroxidation. One molecule of beta-carotene is able to quench 1,000 molecules of O2before it reacts chemically and forms products. Although the principal antioxidant carotenoid is beta-carotene, other carotenoids (e.g., lutein, lycopene and zeaxanthin) have strong antioxidant activities (McDowell, 2006).
The requirement for vitamin A is listed in NRC (1994) as 1,500 IU per kg of diet (681 IU per lb) for broilers, growing geese and growing layer replacement birds. The requirement for laying and breeding chickens, assuming a feed intake of 100 g per day, is higher at 3,000 IU per kg (1,364 IU per lb) of diet. The requirement for all classes of turkeys is 5,000 IU per kg (2,273 IU per lb). The requirement for ducks is listed as 2,500 IU per kg (1.136 IU per lb) of diet for the growing phases and 4,000 IU per kg (1,181 IU per lb) of diet for breeders. The requirement for starting and growing Japanese quail is 1,650 IU per kg (750 IU per lb) of diet and 3,300 IU per kg (1,500 IU per lb) for breeders. Shrivastav and Panda (1999) reviewed the quail nutrition research in India. Under tropical and subtropical conditions, Shim and Vohra (1984) suggested a dietary vitamin A requirement of 4,000 IU per kg (1,181 IU per lb) for growing and laying quail. For most animals, vitamin A has been considered to be required at 100 to 200 IU per kg (45 to 90 IU per lb) of body weight per day (Olson, 1984). The most common carotenoids that have vitamin A activity in poultry are beta-carotene, alpha-carotene and cryptoxanthin. The provitamin A value of alpha-carotene and cryptoxanthin is about half of beta-carotene (Tanumihardjo and Howe, 2005). Different species of animals convert beta-carotene to vitamin A with varying degrees of efficiency. Some factors that influence the rate at which carotenoids are converted to vitamin A are type of carotenoid, class and production intake of animal, individual genetic differences in animals, and level of carotenoid intake. Compared to other species, poultry are very efficient in conversion of beta-carotene to vitamin A. Efficiency of vitamin A conversion from beta-carotene is decreased with higher levels of intake (Van Vliet et al., 1996). For the chicken, as beta-carotene intake level is increased, conversion efficiency drops from a ratio of 2:1 to 5:1.Stress conditions, such as extremely hot weather, viral infections, and altered thyroid function, have also been suggested as causes for reduced carotene to vitamin A conversion. Vitamin A requirements are higher under stressful conditions such as abnormal temperatures or exposure to disease conditions. As an example with poultry, coccidiosis not only causes destruction of vitamin A in the gut but also injures the microvilli of the intestinal wall, thereby decreasing absorption of vitamin A and at the same time causing anorexia for several days (Scott et al., 1982). Vitamin A deficiency is often seen in heavily parasitized animals that supposedly were receiving an adequate amount of the vitamin (McDowell, 2004). Vitamin A requirements should be sufficient to provide for satisfactory growth, reproduction and hatchability, egg production and prevention of deficiency signs under laboratory conditions. Present requirements should be designed to be adequate for these purposes under practical conditions of feeding and management as well as allow for a certain amount of feed storage. The decision as to the minimum vitamin A requirements of young poults and chicks depends upon whether the criterion of optimum requirement is based upon growth and feed utilization or also considers liver storage. Storage of vitamin A in the liver certainly appears to be desirable since under conditions of little or no liver storage, stresses and diseases may precipitate vitamin A deficiency. The amount of vitamin A added to poultry diets is usually in excess of the requirements contained in the NRC publication because no safety factors are built into the NRC figures (NRC, 1994). Additional vitamin A is added to allow for loss of activity due to oxidative destruction of the vitamin A ester during feed processing and storage, variability of carotenes in feedstuffs, changes in feed consumption, genetic differences in animals and stress due to disease and other environmental factors. The minimum vitamin A requirement for normal growth may be lower than those required for higher rates of gain, resistance to various diseases, and normal bone development. Sklan et al. (1995) suggest that maximal immune response in the poult may be achieved at dietary intakes of vitamin A at or higher than those recommended by NRC. In chicks with no added dietary vitamin A, antibody production and proliferative response were depressed in comparison with chicks receiving vitamin A. Supplementation of small amounts of vitamin A enhanced the responses; both antibody production and proliferative responses increased with dietary vitamin A until the diet contained 6,660 IU per kg (3,027 IU per lb). Above this level the responses decreased (Sklan et al., 1994). This suggests that maximal immune responses in the chick may be achieved at dietary intakes of vitamin A considerably higher than NRC recommendations. In humans, vitamin A stores were positively associated with several measures of innate immune activity across a broad range of stores, suggesting that vitamin A enhances protection against diverse pathogens even at concentrations above those needed to maintain normal vision (Ahmed et al., 2009). High stress affects the immune system and, therefore, increases nutrient requirements including vitamin A (Friedman and Sklan, 1989; Panda and Combs, 1963). Friedman and Sklan (1997) report that optimum immune responses in growing chicks and turkeys were obtained with vitamin A intakes that were three- to ten-fold higher than NRC recommended levels. A combination of vitamin A (15,000 IU per kg or 6,818 IU per lb diet) and vitamin E (250 ppm) was more effective than either vitamin alone in reducing heat stress (32°C)-related decreases in broiler performance (Sahin et al., 2001a). High environmental temperature not only has an adverse effect on laying performance but also can impede disease resistance (Lin et al., 2006). Vitamin A supplementation at high levels (2-3 times the NRC requirement) to commercial layer hens under heat stress was beneficial to laying performance and immune function (Lin et al., 2002). Hens suffering heat stress immediately after Newcastle disease vaccination need higher dietary vitamin A intake to obtain the maximal level of antibody production (Davis and Sell, 1989). Vitamin A could alleviate the oxidative injuries induced by heat exposure and immune challenge (Wang et al. 2002). In broiler chickens, vitamin A supplementation (15,000 IU per kg or 6,818 IU per lb) resulted in an improved liveweight gain, feed efficiency, and carcass traits, as well as a decrease in serum malonyldialdehyde (MDA) concentrations, which serve as an indicator of lipid peroxidation (Kucuk et al., 2003).
Concentrations of vitamin A in feedstuffs are highly variable. The naturally occurring sources with the highest vitamin A activity are fish oils and liver. Among the common foods of animal origin, milk fat, egg yolk and liver are excellent sources of vitamin A activity, provided the animal from which they were obtained received adequate vitamin A for an extended period.
Sources of supplemental vitamin A are derived primarily from fish liver oils, in which the vitamin occurs largely in esterified form, and from industrial chemical synthesis. Before the era of the chemical production of vitamin A, the principal source of vitamin A concentrates was the liver and/or body oils of marine fish. Since industrial synthesis was developed in 1949, the synthetic form has become the major source of the vitamin to meet the requirements for domestic animals and humans. The synthetic vitamin usually is produced as the all-trans retinyl palmitate or acetate.
Provitamin A carotenoids, mainly beta-carotene in green feeds, are the principal source of vitamin A for grazing livestock. Although the yellow color of carotenoids is masked by chlorophyll, all green parts of growing plants have high carotene content, and thus have high vitamin A value. In fact, the degree of green color in a roughage is good index of its carotene content. Good pasture always provides a liberal supply, and type of pasture plant, whether grass or legume, appears to have minor importance. At maturity, however, leaves contain much more carotene than stems, and, therefore, legume hay is higher in vitamin content than grass hay (Maynard et al., 1979). In all hays and other forage, vitamin A value decreases after the bloom stage. Plants at maturity can have 50% or less of the maximum carotenoid value of immature plants.
Wing (1969) reported carotene digestibility in plants to be greater during the warmer months. Variations were found in the digestibility of carotenes in plants according to year, species of plant, dry matter content and form of forage. Carotene digestibility was somewhat lower in silages than in pastures or hay. Average published values of carotene content can serve only as approximate guides in feeding practice because many factors affect actual potency of individual samples as fed (NRC, 1982).
Cooking processes commonly used in human food preparation do not cause much destruction to the vitamin potency. The blanching and freezing process generally causes little loss of carotenoid content in vegetables and fruits. Heat, however, does isomerize the all-trans-carotenoids to cis-forms. In a report from Indonesia, isomerication during traditional cooking caused a loss of up to 9% of vitamin A potency (Van Der Pol et al., 1988). Hydrogenation of fats lessens their vitamin A value, while saponification does not destroy the vitamin if oxidation is avoided.
Both carotene and vitamin A are destroyed by oxidation, which is the most common cause of any depreciation that may occur in the activity of sources. The process is accelerated at high temperatures, but heat without oxygen has a minor effect. Butter exposed in thin layers in air at 50°C loses all its vitamin A potency in 6 hours, but in the absence of air there is little destruction at 120°C over the same period. Cod liver oil in a tightly corked battle had shown activity after 31 years, but it may lose all of it potency in a few weeks when incorporated in a feed mixture stored under usual conditions (Maynard et al., 1979).
Much of the carotene content is destroyed by oxidation in the process of field curing. Russell (1929) found that there may be a loss of more than 80% of the carotene of alfalfa during the first 24 hours of the curing process. It occurs chiefly during the hours of daylight, due in part to photochemical activation of the destructive process. In alfalfa leaves, sunlight-sensitized destruction is 7% to 8% of the total pigment present, while enzymatic destruction amounts to 27% to 28% (Bauernfeind, 1972). Enzymatic destruction requires oxygen, is greatest at high temperatures and ceases after complete dehydration.
All-trans beta-carotene is the predominant isomer in feeds, thermal processing can substantially increase the proportions of cis isomers (9-c and 13-c); beta-carotene is the more bioavailable isomer (Deming et al., 2002). It would seem likely that the isomers of beta-carotene would increase in the fermentation process of silage, resulting in a lower bioavailable beta-carotene.
Hay crops cut in the bloom stage or earlier and cured without exposure to rain or too much sun retain a considerable proportion of their carotene content, while those cut in the seed stage and exposed to rain and sun for extended periods lose most of it. Green hay curing in the swath may lose one-half of its vitamin A activity in one day’s exposure to sunlight. Thus, hay usually has only a small proportion of the carotene content of fresh grass. Under similar conditions of curing, alfalfa and other legume hays are much higher in carotene content than grass hays because of their leafy nature, but a poor grade of alfalfa may have less than a good grade of hay (Maynard et al., 1979).
The carotene content of dried or sun-cured forages decreases on storage, and the rate of destruction depends on factors such as temperature, exposure to air and sunlight, and length of storage. Under average conditions, carotene content of hay can be expected to decreases about 6% to 7% per month. In artifical curing of hays using a “hay drier,” carotene loss is slight because of the rapidity of the process and protection against exposure to oxygen; the final product has two to ten times the value of field-cured hay. Severe heating of hay in the mow or stack reduces the vitamin A content, and there is a gradual loss in storage, so that old hay is lower in carotene content than new hay. Aside from yellow corn and it’s by-products, practically all concentrates used in feeding animals are devoid of vitamin A value, or nearly so. In addition, yellow corn contains a high proportion of non-beta-carotenoids (i.e., cryptoxanthin, lutein and zeacarotene) that have much less vitamin A value than beta-carotene.
The potency of yellow corn is only about one-eighth that of good roughage. There is evidence that yellow corn may lose carotene rapidly during storage. For example, a hybrid corn high in carotene lost about 50% if its carotene content after 8 months of storage at 25°C. Less carotene was lost during storage at 7°C (Quackenbush, 1963). Bioavailability of natural beta-carotene was less than chemically synthesized forms (White et al., 1993). In ferrets, all trans-beta-carotene was less bioavailable from carrot juice than beta-carotene beadlet-fortified beverages (White et al., 1993). For calves, a small enhancing effect of mild heat treatment of carrots on serum and tissue accumulation of carotenoids has been reported (Poor et al,. 1993).
In forages, the carotene in alfalfa hay may be more bioavailable than that in grass hay (NRC, 1989b). A marked discrepancy exists between the carotene content of corn silage and the vitamin A status of ruminants fed corn silage. On the average, corn silage carotenes were found to be about two-thirds as effective as beta-carotene for maintaining liver stores in rats (Miller et al., 1969; Rumsey, 1975). Martin et al. (1971) reported five-fold less carotene in October and November corn silage than in September corn silage. More mature silages were not able to sustain liver vitamin A stores in beef steers, particularly if the ensiled corn plant was finely chopped. Diets high in corn silage harvested after a killing frost and fed to cattle would be marginal in their supply of both carotene and alpha-tocopherol. Likewise, after a killing frost for four grasses in Florida, both beta-carotene and alpha-tocopheral concentrations were dramatically reduced (Arizmendi-Maldonado et al., 2003). Miller et al, (1969) reported that ethanol, sometimes found in corn silage as a product of fermentation, may reduce liver vitamin A stores as much as 26% by increasing mobilization of vitamin A from the liver. Since vitamin A supports the differentiation of epithelial cells, there would seem to be an effect on the immune functions of birds.
The major source of supplemental vitamin A used in animal diets is trans-retinyl acetate (McGinnis, 1988). The acetate, propionate and palmitate esters are chemically synthesized by vitamin A manufacturers. These are available in gelatin beadlet product forms for protection against oxidative destruction in premixes, mash, and cubed and pelleted feeds. Carbohydrates, gelatin and antioxidants also are generally included inside the beadlets to stabilize the vitamin A. These provide physical and chemical protection against factors normally present in feed that are destructive to vitamin A. The vitamin A acetate products most frequently used in ruminant feeds contains 650,000 IU of United States Pharmacopia Units (USP) per gram of product. (Note: the IU and USP units are equal in value and one unit equals the activity of the 0.3 µg of all-trans retinol or 0.344 µg of all-trans retinyl acetate.)
Clinical signs of vitamin A deficiency are similar among chickens, turkeys and other poultry species. On the same low-vitamin A diet, turkeys and Japanese quail would exhibit clinical signs earlier than chickens due to their higher requirement for the vitamin. In poultry, vitamin A deficiency causes reduced growth (Illus. 2-3), lowered resistance to disease, eye lesions, muscular incoordination (Illus. 2-4), lowered egg production and blood spots in eggs (Scott et al., 1982; Squires and Naber, 1993b).
Courtesy of L.M. Potter, Virginia Polytechnic Institute
Courtesy of M.L. Scott, R.H. Cornell University, L.R. McDowell, University of Florida
Squires and Naber (1993b) report a large incidence of blood spots in eggs from a vitamin A-deficient dietary treatment, which agrees with the results reported by Bearse et al. (1960). Gross and histologic examination of the reproductive tract of deficient hens verifies that the ovary is structurally changed by vitamin A-deficiency (Bermudez et al., 1993). Hens fed a vitamin A-deficient diet had increased numbers of atretic follicles on the ovary and these follicles had moderate to severe hemorrhage (Bermudez et al., 1993). In contrast, hens with low rates of egg production fed a vitamin A-supplemented diet did not have hemorrhaged ovarian follicles. Conversely, Squires and Naber (1993b) reported that hens fed vitamin A-deficient diets continued to produce eggs through 12 weeks of lay, presumably due to mobilization of liver stores of the vitamin. After this, the vitamin A content of yolks of the few eggs produced was similar to the yolk vitamin A content of supplemented hens. Yolk vitamin A content is thus a poor indicator of flock vitamin A status. Average survival times of the progeny fed a vitamin A-free diet increased in a linear fashion with increasing levels of vitamin A in the maternal turkey diet (Jensen, 1965). Vitamin A level of the hen’s diet is positively correlated with the growth of chicks and poults from that hen, and the level of vitamin A in the chick’s and poult’s diet is positively correlated with growth. Clearly a deficiency of vitamin A will produce a loss of appetite and a reduction in growth. A severe deficiency will produce ataxia and death if not corrected (Hill et al., 1961). As vitamin A deficiency progresses in adult poultry, they become emaciated and weak and their feathers are ruffled. A marked decrease in egg production occurs and the length of time between clutches increases greatly. Hatchability is decreased and there is an increase in embryonic mortality in eggs from affected birds. A watery discharge from the nostrils and eyes is noted and eyelids are often stuck together. When day-old chicks are given a vitamin A-free diet, clinical signs may appear at the end of the first week if the chicks are progeny of hens receiving a diet low in vitamin A. If chicks are progeny of hens receiving high levels of vitamin A, signs of deficiency may not appear until chicks are six or seven weeks of age, even though they are receiving a diet completely devoid of vitamin A (Scott et al., 1982; West et al., 1992). Gross signs of vitamin A deficiency in chicks are characterized by anorexia, cessation of growth, drowsiness, weakness, incoordination, emaciation and ruffled plumage. The mucous epithelium is replaced by a stratified squamous, keratinizing epithelium. The mucous membranes of the nasal passage, mouth, esophagus and pharynx of poultry are affected and develop white pustules (Scott et al., 1982). The kidneys may be distended with uric acid deposits and the epithelium of the eye is affected, which produces exudates and eventually xerophthalmia. Severe vitamin A deficiency causes increased intestinal mucosal cell numbers (hyperplasia), reduced intestinal mucosal cell size, the loss of mucosal protein, reduced villus height and crypt depth, and diminished activities of gut disaccharidases, transpeptidase and alkaline phosphatase (Uni et al., 1998). It is clear that there is a breakdown of the epithelium of many systems in the body due to a vitamin A deficiency. Loss of membrane integrity, in turn, alters water retention (Lopez et al., 1973) and impairs the ability to withstand infection (Sijtsma et al., 1989a). Bacteria and other pathogenic microorganisms may invade tissues and enter the body, thereby producing infections that are secondary to original vitamin A deficiency signs. There have been many studies on the effect of supplemental vitamins especially vitamins A, D3, E and C on the immune response of broilers and layers. In general, the response to vitamin supplementation occurred at dietary concentrations at least 10 x those suggested by NRC (1994) and often at levels of 2-3x of those used commercially (Leeson, 2008). Inadequate vitamin A also reduces the immune system’s response to challenge and further contributes to disease susceptibility (Davis and Sell, 1989). Many experiments have revealed that increased morbidity is observed in chickens experimentally infected with Newcastle disease virus and fed a diet marginally deficient in vitamin A (Sijtsma et al., 1989a, b; Lin et al., 2002). Low dietary vitamin A has been shown to cause reduced antibody production, depressed T-cell responses, distributed immunoglobulin metabolism, reduced phagocytosis and decreased resistance to infection by bacterial and viral pathogens and protozoan enteropathogens (Davis and Sell, 1989; Friedman and Sklan, 1997; Lessard et al., 1997; Coskun et al., 1998). Viral infections have been found to impair the vitamin A status of chickens (West et al., 1992). Vitamin A deficiency can cause alterations in bone growth, which creates several areas of compression on the central nervous system that cause a loss in mobility (Howell and Thompson, 1967). Nockels (1988) reported that hypothyroidism is an early indication of vitamin A deficiency in chicks. Reductions in testis size, circulating testosterone and fertility have been reported during vitamin A deficiency in cockerels (Damjanou et al., 1980). The level of carotenoids to which a developing embryo is exposed affects subsequent deposition of dietary carotenoids in tissue of the posthatch chick. Chicks hatched from carotenoid-depleted eggs will have a compromised immune function. Koutsos et al. (2006) reported that chicks from carotenoid-depleted eggs that lacked carotenoid exposure posthatch had increased parameters of systemic inflammation.
The vitamin A activity contained in ingredients of typical poultry diets is very unpredictable. Therefore, the total requirement is usually added to the ration as a commercially synthesized and stabilized vitamin A product. Vitamin A can be supplemented as part of a concentrate, as a liquid supplement or in drinking water preparations. The most convenient and often most effective means of providing vitamin A to poultry is inclusion in premixes that are added to feed. This allows for consumption of the vitamin. The major source of supplemental vitamin A used in diets is trans-retinyl acetate (McGinnis, 1986). The vitamin A acetate products most frequently used in feeds contain 1,000,000 IU or United States Pharmacopeia Units (USP) per gm of product. The acetate, propionate and palmitate esters are chemically synthesized by vitamin A manufacturers. Because of the lack of stability of vitamin A, particularly regarding exposure to oxygen, trace minerals, pelleting, feed storage and other factors, the feed industry has readily accepted the dry stabilized forms of the vitamin. Stabilized and protectively coated (or beadlet) forms of vitamin A slow destruction of the vitamin, but for highest potency, fresh supplies of the mixture should be available on a regular basis. Practical considerations that affect vitamin A stability are listed in Table 2-2. The gelatin beadlet, in which the vitamin A ester is emulsified into a gelatin-plasticizer-antioxidant viscous liquid formulation and spray dried into discrete dry particles, results in products with good chemical stability, physical stability and excellent biologic availability.
Table 2-2: Practical Factors that Affect Vitamin A Stability
Adapted from Hoffmann-La Roche (1989)
New technology has further improved vitamin A stability by a cross-linking process, such as the reaction between gelatin and sugar, that makes the beadlet insoluble in water, giving it a more resistant coating that can sustain higher pressure, friction, temperature and humidity (Frye, 1994). Several factors can influence the loss of vitamin A from feedstuffs during storage. The trace minerals in feeds and supplements, particularly copper, are detrimental to vitamin A stability. Dash and Mitchell (1976) reported the vitamin A content of 1,293 commercial feeds over a three-year period. The loss of vitamin A was over 50% in one year’s time. Vitamin A loss in commercial feeds was evident even if the commercial feeds contained stabilized vitamin A supplements. There is evidence that yellow corn may lose carotene rapidly during storage. For instance, a hybrid corn high in carotene lost one-half of its carotene in eight months of storage at 25°C (77°F) and about three-quarters in three years. Less carotene was lost during storage at 7°C (45°F) (Quackenbush, 1963). Adams and Zimmerman (1984) showed that samples of moldy corn averaged 98% less carotene than sound corn. Because of vitamin A variability in feeds and losses during processing and storage, most animal nutritionists tend to ignore vitamin A activity in feedstuffs and rely exclusively on dietary fortification to arrive at vitamin allowances for poultry. The stability of vitamin A in feeds and premixes has been improved tremendously in recent years by chemical stabilization as an ester, by the use of antioxidants and by physical protection using coatings (Shields et al., 1982). Nevertheless, vitamin A supplements should not be stored for prolonged periods prior to feedings. Chen (1990) measured the stability of three commercial cross-linked vitamin A beadlets on the market in trace mineral premixes and feeds. After three months of storage at high temperature and humidity, vitamin A retention varied from 30% to 80%, depending on the antioxidant present in the beadlet. In a 30% concentrate pelleted at 93°C (199°F), after three months of storage at high temperature and humidity, retention varied from 57% to 62%. During the last decade, improvements in vitamin A stability through extrusion increased by 35%, mainly because of the use of cross-linking processes (Frye, 1994). Vitamin A and carotene destruction also occurs from processing feeds with steam and pressure. Pelleting effects of vitamin A in feed are determined by die thickness and hole size, which produce frictional heat and a shearing effect that can break supplemental vitamin A beadlets and expose the vitamin. In addition, steam application exposes feed to heat and moisture. Running fines back through the pellet mill exposes vitamin A to the same factors a second time. Between 5% and 40% of vitamin A present at mixing may be destroyed during pelleting of poultry feed. Diseases and mycotoxins increase the need for supplemental vitamin A. It should be noted that diseases (i.e., enteric diseases such as malabsorption syndrome, coccidiosis and diarrhea, and mycotoxins) can interfere with the absorption and utilization of vitamin A. The effect of mycotoxins in the feed should be considered since aflatoxin is known to interfere with protein synthesis (Doerr, 1987). Thus, it can be seen how mycotoxins might interfere with retinol-binding protein (RBP) synthesis and the transport of vitamin A. Aflatoxin can also cause poor pigmentation in birds by interfering with the absorption, transport and deposition of carotenoids (Tyczkowski and Hamilton, 1987). Poultry nutritionists increasingly recognize that carotenoids play an important role beyond that of a precursor for vitamin A or as a pigment. In avian species, the primary carotenoids of economical and ecological interest are the oxygenated carotenoids, including lutein, its isomer zeaxanthin, and canthaxanthin. Lutein, the second most abundant carotenoid in nature, is consumed by wild birds and is routinely fed to commercial poultry flocks (often in combination with canthaxanthin) to pigment skin and eggs in order to optimize consumer product acceptance (Hernandez et al., 2001). Lutein is also consumed and absorbed by animals. In addition to pigmentation properties, there is considerable interest in the role of this carotenoid in avian and mammalian immune responses. Dietary lutein affects antibody production, B-cell proliferation and differentiation, the delayed-type hypersensitivity response, and T-cell subset proportions. In addition to acquired immune responses, the proposed antioxidant function of carotenoids suggests a role for carotenoid-based modulation of innate immune responses, as shown for other antioxidant nutrients (Leshchinsky and Klasing, 2001). The carotenoid commonly used in laying hen diets, canthaxanthin, is deposited in the yolk at a level that is linearly related to the level in the diet (Grashorn and Steinberg, 2002). Other carotenoids that have been considered for inclusion in eggs include lycopene (Kang et al., 2003). Kang et al.(2003) reported that inclusion rates of lycopene of >4 mg per kg (>1.8 mg per lb) feed resulted in a significant effect on yolk color, however when considering the potential nutritional benefits of lycopene inclusion, it should be noted that the deposition rate into the yolk was~ 2%.Maximal immune responses in poultry may be achieved at higher dietary intakes of vitamin A and carotene than those needed for other functions (Sklan et al.,1994, 1995; Haq et al., 1996; Friedman and Sklan, 1997). Sklan et al. (1995) reported that vitamin A intakes between 2 and 6 µg per g improve lymphocyte proliferation in poults as well as antibody titers to Newcastle disease virus. Cockerels fed beta-carotene and canthaxanthin were reported to produce significantly higher antibody titers in response to Newcastle disease virus vaccination than control birds (McWhinney et al., 1989). Tengerdy et al. (1990) reported that beta-carotene in combination with vitamin E provided increased protection against Escherichia coliinfection in chickens. The loss of carotenoids in poultry infected with coccidiosis was until recently believed to be the consequence of intestinal mucosal hyperplasia leading to malabsorption (Allen, 1988). Recent evidence indicates that the carotenoid losses are instead the result of oxidation resulting from the birds’ cell-mediated immune response to the coccidial challenge (Allen, 1997). Oxidative bursts from the cell-mediated immune response have been documented to cause losses in vitamin E (Allen et al., 1996) and are presumed to have the same effect on vitamin A. To illustrate, Augustine and Ruff (1983) reported a 48% loss of plasma retinol levels in poults infected by Eimeria meleagrimitis. Components of plants in the diets of poultry can impact the availability and metabolism of vitamin A. Saponins have been shown to interfere with vitamin A absorption (Jenkins and Atwal, 1994). Dietary exposure to pyrrolizidine alkaloids apparently impairs the mobilization of vitamin A stored in the liver (Huan et al., 1992).
Short-term administration of vitamin A in drinking water or by injection is recommended to support any specific measures used in treatment of diseased and convalescent animals. This is particularly true for poultry in which vitamin A stores may have been depleted due to fever or in animals suffering from intestinal disorders where vitamin A absorption is seriously impaired.
The decision for vitamin A supplementation should be based mainly on whether or not a deficiency could be a practical problem. As with most nutrients, a borderline deficiency is much more likely to occur than is a severe deficiency. Likewise, a marginal deficiency adversely affecting performance by a few percentage points is not easily detected (McDowell, 2000). Based on the positive results that may be derived and taking into account that vitamin A supplementation is inexpensive and no toxicity problems have been reported when given at recommended levels, it seems beneficial to supplement vitamin A at all times for poultry and to increase the levels of supplementation fortification substantially for poultry that are subjected to disease or stress.
Increased levels of vitamin A are also important under intensive housing conditions where there are increased requirements in early life or under conditions of stress (McDowell and Ward, 2008). The practice has been found particularly valuable under the following circumstances: for day-old chicks before transport and for laying hens when, for reasons unknown, laying performance suddenly drops (Hoffmann-La Roche, 1967). In laying hens, Squires and Naber (1993b) noted optimized egg production when hens were fed a vitamin A level of 8,000 IU per kg (3,636 IU per lb). However, hatchability of fertile eggs was optimized with a vitamin A level of 16,000 IU per kg (7,273 IU per lb).
Most modern poultry operations provide higher vitamin A concentrations as part of optimum vitamin nutrition programs than recommended by the current NRC. The current NRC (1994) recommendations are minimum requirements established decades ago and do not reflect the genetic selection which has dramatically increased production rates and improved feed efficiency (McDowell and Ward, 2008). Earlier vitamin A requirements were also established under management systems that do not take into account divergent management systems of today. These systems can require more vitamin A due to fluctuations in environmental temperatures and influencing factors, including infectious diseases, stress, parasites, biological variations, diet composition, bioavailability and nutrient interrelations. Diets with optimal vitamin A insure optimum performance with a highly favorable cost-to-benefit relationship.
In general, the possibility of vitamin A toxicity for poultry is remote. However, of all vitamins, vitamins A and D3 have the greatest chance of being provided in toxic concentrations to poultry. Excess vitamin A has been demonstrated to have toxic effects in most species studied. Presumed upper safe levels are four to 10 times the nutritional requirements for non-ruminant animals, including poultry (NRC, 1987). Most of the harmful effects have been obtained by feeding over 100 times the daily requirements for a period of time. Thus, small excesses of vitamin A for short periods of time should not exert any harmful effects. Recommended upper safe levels of vitamin A for poultry are presented in Table 2-3 (NRC, 1987).
The clinical signs of vitamin A toxicity in poultry include weight loss; decreased feed intake; swelling and crusting of the eyelids to the extent that they become sealed closed; inflammation of the mouth, adjacent skin and skin of the feet; decreased bone strength; bone abnormalities; and mortality (Scott et al., 1982). Skin lesions at the commissure of the beak, nose and eyes attributable to mucous membrane hyperplastic activity have been shown to occur in chicks within 72 hours after oral dosing with 60,000 IU vitamin A (Kriz and Holman, 1969). Excessive doses of vitamin A to the laying hen results in an adverse effect on vitamin E, carotenoids and ascorbic acid in the embryonic/neonatal liver and can compromise the antioxidant status of the progeny (Surai et al., 1998; Grobas et al., 2002). Excess vitamin A (10 and 20 g/ml) in a culture medium from broiler chickens showed a down-regulation of alkaline phosphate activity, as well as calcium-binding protein mRNA expression of osteoblasts (Guo et al., 2011). High dietary vitamin A (4,000 IU per kg or 1,818 IU per lb) in hen diets significantly lowered egg yolk vitamin E (Grobas et al., 2002). Excess vitamin A given to chicks during early postnatal development was associated with inhibition of vitamin E and carotenoid utilization (Surai and Kuklenko, 2000). It was concluded that the effect of vitamin A on development of the antioxidant system in the neonatal chick is dose-dependent and an excess of vitamin A can compromise the antioxidant defense system. It is believed that release of lysosomal enzymes is responsible for degradative changes observed in tissues and intact animals suffering from hypervitaminosis A (Fell and Thomas, 1960). In hypervitaminosis A, retinol penetrates the lipid of the membrane and causes it to expand. Because the protein of the membrane is relatively inelastic, the membrane is weakened. Thus, many phenomena in hypervitaminosis can be explained in terms of damage to membranes, either in cells or of organelles within cells. Excess vitamin A affects metabolism of other fat-soluble vitamins via competition for absorption and transport. Therefore, in diets containing barely adequate levels of vitamins D3, E and K, a marked increase in dietary vitamin A may cause decreases in growth or egg production due to a deficiency of one or more of the other fat-soluble vitamins rather than a toxic effect of vitamin A. Retinoid-induced hemorrhaging in rats fed diets deficient in vitamin K has been reported (McCarthy et al., 1989). The mechanisms of absorption and transport are similar for the carotenoid pigments and the fat-soluble vitamins. A marked increase in dietary vitamin A has been shown to interfere with absorption of carotenoids, thereby resulting in decreased pigmentation for poultry. While the absolute level of vitamin A supplementation is important, the ratio of vitamin A to the other fat-soluble vitamins is also of significance. High dietary levels of vitamin A impede the utilization of vitamin D3in broilers fed low levels (500 IU per kg or 227 IU per lb) of supplemental vitamin D3 (Aburto and Britton, 1998b). In the presence of low levels of vitamin D3, the addition of vitamin A reduced body weight and bone ash and resulted in rickets. It is not uncommon to encounter field rickets when these levels of vitamin A are fed, even though the level of vitamin D3 would normally be considered more than adequate. Conversely, high dietary levels of vitamin E or vitamin D3have been shown to protect the chick from vitamin A toxicosis. Route of administration of vitamin A has an influence on the toxicity of the vitamin. In chicks and poults, levels of vitamin A that caused adverse changes in body weight, packed cell volume, serum calcium or phosphorus, or bone ash were 100 times the NRC requirement when birds were fed ad libitum, but only 10 times the NRC level when birds were fed via force feeding.
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