Fat soluble vitamins – Vitamin A
Vitamin A refers to any compound or mixture of compounds having vitamin A activity. In animals, vitamin A exists largely in the preformed state as retinol or as one of its related compounds: 3-dehydro-retinol, retinal, retinyl ester or retinoic acid. In plants, vitamin A occurs in the precursor or provitamin forms as carotenoids which may be converted into vitamin A. Vitamin A cannot be synthesized de novo by plants or animals and carotenoids are the only source of vitamin A for the entire animal kingdom.
Carotenoids are a class of closely related natural pigments synthesized by plants. Their main function is to absorb light during photosynthesis and provide protect5ion against photosensitization. Over 600 different carotenoids have been identified and approximately 40 of these occur in common food sources. Beta-carotene, alpha-carotene, lutein, alpha-cryptoxanthin and lycopene are the most common carotenoids found in human plasma. Some of these carotenoids, such as beta-carotene, alpha-carotene, and alpha-cryptoxanthin, are metabolized in the small intestine and function as precursors of vitamin A. However, other carotenoids, such as lycopene and lutein, are devoid of provitamin A activity. Carotenoids are also potent antioxidants and important physiological modulators. In recent studies, lycopene has been suggested to have potential anticarcinogenic properties.
Retinol is high molecular weight alcohol attached to a beta-ionone ring. The beta-ionone ring is essential for vitamin A activity. Retinol is a pale, viscous, fat soluble compound which is fairly heat stable but easily destroyed by oxidation and ultraviolet light. Beta-carotene is a symmetrical molecule consisting of two beta-ionone rings conjugated by a double bond in the center. Theoretically, hydrolysis of beta-carotene in the gut should yield two molecules of retinol. However, because of physiologic inefficiency in conversion of beta-carotene to retinol, the overall utilization of dietary beta-carotene as vitamin A from food is taken as one-sixth that of retinol. The efficiency of utilization of the other provitmain A carotenoids is about half that of beta-carotene.
The average North American diet provides about half of its vitamin A activity as carotenes from plant sources. Beta-carotene is the most significant carotenoid in the diet; gamma-and alpha-carotene and cryptoxanthine are also present in the diet. Sources of the provitmain A carotenoids include dark green leafy vegetables (chlorophyll masks the yellow carotene color), deep yellow vegetables, tomatoes and deep yellow fruit.
The remainder of dietary vitamin A is obtained from preformed vitamin A from animal sources. Sources of preformed vitamin A include liver, fish liver oil extracts, egg yolks, enriched milk products such as margarine and skim milk and evaporated milk. Some animal products contain both preformed vitamin A and provitamin A; the latter being obtained from the animal’s diet.
Absorption and Storage
Free retinol obtained from the diet or hydrolyzed from retinyl esters in the gut is absorbed into the intestinal mucosal cells, re-esterified and incorporated into chylomicrons, which ultimately enter the circulation. Chylomicron remnants containing retinyl esters are taken up by the liver. Conversion of the ingested carotene to vitamin A takes place primarily in the cells in the intestinal mucosa but also occurs in the liver and possibly the kidney.
Absorption of vitamin A and the carotenoids requires the presence of bile in the intestinal tract and other conditions favorable for fat absorption. Retinoic acid, however, is absorbed directly into the intestinal mucosa and released into the portal circulation complexed with albumin.
Storage of vitamin A occurs primarily in the liver as retinyl ester. When needed, retinol is mobilized from the liver and transported in the circulation to tissues complexed with retinol binding protein (RBP).
Vitamin A plays an important role in normal vision. The photoreceptors of the eye in the retina, which are sensitive to dim light, are the rods that contain 11-cis retinal that combines with the protein opsin to form rhodopsin in the dark. Rhodopsin when bleached by light is converted to all trans retinal and opsin. Conversion of the trans 11-cis retinal completes the cycle. However, when insufficient retinal is available to regenerate rhodopsin, the conversion is incomplete and night blindness (inability to see in dim light) results.
Retinal is also involved in daytime vision as a component of iodopsin. This pigment, contained in the cones of the retina, is sensitive to bright light.
Vitamin A is essential for the integrity and normal growth of epithelial cells. It is also involved in cell differentiation. In the presence of sufficient vitamin A, mucus secreting goblet cells are formed form epithelial basal cells. When there is a lack of vitamin A, the basal cells keratinize becoming hard, dry and irregular in shape.
Vitamin A is required for proper growth and development of bones and teeth. It is also necessary for normal reproduction in animals. Vitamin A is important for the maintenance of membrane integrity and functions of membranes such as those in the skin, respiratory and genitor-urinary tract.
Retinoic acid support normal growth but cannot replace retinol and retinal for night vision.
Vitamin A deficiency is one of the most prevalent forms of malnutrition in the world. Pregnant women, infants and young children are most susceptible.
Primary vitamin A deficiency is due to inadequate intakes of vitamin A or its precursors, the carotenoids. Causes of secondary vitamin A deficiency include malabsorption of fat and the fat-soluble vitamins, failure to convert dietary carotene to preformed vitamin A and depletion of body reserves. Parasitic infections associated with fever and systemic acute phase response also cause secondary vitamin A deficiency. This is probably induced by inflammatory cytokine-related mechanisms which include decrease in the hepatic secretion of retinol-RBP complex, the loss of the complex to the extravascular space or an increased loss in the urine.
The basic pathology of vitamin A deficiency is hyperkeratinization of skin and keratinizing metaplasia of the lining of the respiratory, gastrointestinal and genitourinary tracts and the endocrine, salivary, sebaceous and lacrimal glands. Vitamin A deficiency is associated with increased childhood morbidity and mortality. This is due to an increased risk of infectious diseases particularly in developing countries. Vitamin A supplements can help to achieve a rapid reduction in early childhood mortality and a lower level of childhood mortality can be sustained as long as adequate vitamin A supplementation in maintained.
The first symptoms of vitamin A deficiency are night blindness and drying of the conjunctiva of the eye. Bitot’s spots may be present in the cornea of the eye. With continued vitamin A deficiency, progressive damage to the eye results from drying of the cornea and irreversible corneal damage resulting in xerophthalmia, keratomalacia, and blindness. In children, retarded growth may occur as a result of vitamin A deficiency.
Excessive ingestion of carotenoids, while not toxic to man, results in carotenemia and yellow discoloration of the skin. In large doses preformed vitamin A is toxic to man. Chronic toxicity of vitamin A produces variable symptoms. These may include: anorexia, nausea, vomiting, abdominal pain, dry skin, rashes, headaches, loss of hair, abnormal skin pigmentation, increased fragility and pain in the long bones, menstrual irregularities and enlargement of the liver and spleen.
Due to the danger of chronic toxicity, regular consumption of supplemental doses of vitamin A above 3000 RE (10,000 IU) for children or 7500 RE (25,000 IU) for adults is contraindicated.
Low intakes of vitamin A and carotene are associated with an increased risk of developing certain cancers, such as breast cancer. However, the role of vitamin A in lung cancer is still unclear. The belief that vitamin A reduces cancer risk is based on the following observations: (1) the requirement of vitamin A for the maintenance of epithelial tissues, a common location where many cancers are located, (2) tumor surveillance by the immune system is dependent on adequate levels of vitamin A and (3) gene expression may be directly influenced by vitamin A and retinoids.
Biologically B-carotene acts as an antioxidant that may have a protective effect against free-radical damage of cellular membranes. For this reason there is much interest in increasing its intake. Ingestion of a large amount of carotenoids is nontoxic but may result in a benign condition characterized by yellow pigmentation of the skin.