Definition: Vitamin A is a generic term that refers to fat-soluble compounds found as preformed vitamin A (retinol) in animal products and as provitamin A carotenoids in fruits and vegetables. The three active forms of vitamin A in the body are retinol, retinal, and retinoic acid.

• Uses: Vitamin A is involved in regulating the growth and specialization of virtually all cells in the human body. Vitamin A has important roles in embryonic development, organ formation during fetal development, normal immune functions, and eye development and vision
• Deficiency: Vitamin A deficiency is a major cause of preventable blindness in the world. It is most prevalent among children and women of childbearing age. Vitamin A deficiency is associated with an increased susceptibility to infections, as well as to thyroid and skin disorders.
• Dietary allowance: The recommended dietary allowance (RDA) is 700 micrograms of retinol activity equivalents (μg RAE)/day for women and 900 μg RAE/day for men.
• Animal food sources rich in preformed vitamin A include dairy products, liver, and fish oils; fortified cereals may also contain preformed vitamin A. Rich sources of provitamin A carotenoids include orange and green vegetables, such as sweet potato and spinach.
• Supplement: Retinoic acid and analogs are used at pharmacological doses in the treatment of acute promyelocytic leukemia and various skin diseases.

Drug interactions

• Supplementation of rats with vitamin A prevented aspirin-induced mortality and reduced the incidence of peptic ulcers. The dose of vitamin A used in this study would be equivalent to 750 IU for each 325-mg aspirin tablet.
• Bile salt sequestrants: Treatment with bile salt sequestrants such as cholestyramine and colestipol may decrease intestinal absorption of fat-soluble vitamins, including vitamin A.
• Contraceptives, oral: Blood levels of vitamin A are frequently elevated in oral contraceptive users. This effect appears to result from an increase in the level of retinol-binding protein and is not thought to be of clinical significance.
• Administration of various doses of vitamin A reversed some of the adverse effects of glucocorticoid therapy in animals, including impairment of wound healing and immune function. In humans, topical application of vitamin A (Aquasol A; 200,000 IU per ounce) 3 times per day improved non-healing wounds in patients receiving glucocorticoids.
• Isotretinoin (13-cis retinoic acid): Isotretinoin (13-cis retinoic acid) may interfere with the processing of vitamin A in the retina. In a case-report, a teenager with cystic fibrosis who had been receiving long-term oral vitamin A supplementation developed night blindness after starting isotretinoin for cystic acne. The night blindness resolved after the dosage of vitamin A was increased.
• In a randomized trial, a single dose of vitamin A (180,000 IU) given 1 day before methotrexate prevented methotrexate-induced gastrointestinal mucosal damage (as measured by the D-xylose absorption test) in children with cancer. In mice, vitamin A supplementation (1,000 IU/kg of body weight per day) did not inhibit the antitumor effect of methotrexate.

Nutrient interactions

• Vitamin E: Vitamin E appears to enhance intestinal absorption and tissue uptake of vitamin A. Based on this effect of vitamin E, one group of investigators used the combination of vitamins A and E with a high degree of success to treat certain skin conditions (i.e., acne vulgaris, Darier’s disease, and pityriasis rubra pilaris) that had failed to respond to vitamin A alone. The addition of vitamin E improved clinical outcomes while allowing for the use of lower (and safer) vitamin A doses. The usual dose of vitamin E was 800 IU/day, although as much as 1,600 IU/day was used temporarily in patients with severely inflamed lesions.
• Zinc plays a role in vitamin A transport. Zinc deficiency is associated with decreased circulating and hepatic levels of vitamin A. In studies conducted in Bangladesh, combined supplementation with zinc and vitamin A was more effective than vitamin A alone in improving the vitamin A status of vitamin A-deficient children (see Chapter 31 for references).
• Vitamin K: Vitamin A toxicity has been associated with hypoprothrombinemia. This effect appears to be due to the inhibition of vitamin K2 synthesis by intestinal bacteria and to a direct interference with the hepatic actions of vitamin K.
• Administration of 50,000 IU/day of vitamin A to patients with various types of cancer was associated with a reduction of iodine uptake by the thyroid gland. In rats, supplementation with high doses of vitamin A decreased basal metabolism and thyroid gland weight.

Dosage and administration

• Frequently used doses of vitamin A to treat certain medical conditions have ranged from 25,000 IU/day to 300,000 IU/day or more for varying periods of time. Lower doses, such as 5,000–10,000 IU/day, are present in some multivitamin preparations. The choice of an appropriate vitamin A dosage in the clinical setting can be challenging, because of marked differences in the bioavailability and toxicity of different preparations (as noted above). Unfortunately, many reports in which vitamin A was used therapeutically did not specify what type of preparation was administered.
• When duplicating the dosages of vitamin A in published reports that did not specify the type of preparation used, it would be prudent to administer oil-based vitamin A, in order to decrease the probability of causing adverse effects. Patients taking potentially toxic doses of vitamin A should be advised to watch for early warning signs of toxicity, which include fatigue, headaches, joint pain, muscle aches, bone pain, and dry skin. Discontinuing treatment or decreasing the dosage when these early warning signs appear greatly reduces the risk that more serious adverse effects will occur. Patients receiving high doses of vitamin A should have periodic measurements of serum calcium and aminotransferases (liver enzymes). In most cases, the lowest effective dose of vitamin A should be used, and the treatment should be tapered as improvement occurs.