Vitamin A

Vitamin A or retinol [3, 7-dimethyl-9-(2,6,6, trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol] is also found in foods and biological tissues as retinyl esters such as retinyl acetate (used in food supplements) and retinyl palmitate. Retinyl palmitate is a major storage form of vitamin A in the body, and liver is a major storage site. The best known function of vitamin A is in vision, where it participates (as the metabolite retinal) in the visual cycle. However, in the chemical form retinoic acid (both as all-trans retinoic acid and as 9-cis retinoic acid, both of which can be formed from retinol in the in the body), vitamin A plays an important role in control of gene expression. Retinoic acid maintains differentiation of epithelial cells such as skin, lung, and intestinal tissue, but this form of vitamin A cannot be used in vision.

Deficiencies:
Night blindness is one of the early signs of vitamin A deficiency because of the role of vitamin A in vision. Bacterial invasion and permanent scarring of the cornea of the eye (xerophthalmia) is a symptom of a more profound deficiency. However, this is due to a different mechanism, the lack of vitamin A for control of gene expression. Profound vitamin A deficiency also results in altered appearance and function of skin, lung, and intestinal tissues. Children are most at risk of vitamin A deficiency because they have not yet developed adequate vitamin A stores. It has been estimated that 0.5 million children in the world become blind each year; 70% of these are due to vitamin A deficiency. Over half of these blind children die from malnutrition and associated illnesses.

Clinical uses:
Synthetic retinoids such as 13-cis retinoic acid (trade name Accutane, also known as isotretinoin) are used to treat acne and skin wrinkling. Other derivatives, such as 4-hydroxyphenylretinamide (4-HPR, Fenretinide), are used to treat breast cancer. No one should consume vitamin A in quantities exceeding the Recommended Dietary Allowance (RDA) without a doctor's advice because of the dangers of toxicity.

Diet recommendations: The RDAs are 1000 µg Retinol Equivalents (RE)/day for adult human males, 800 µg RE for adult females, and 1300 µg RE and 1200 µg RE for adult females during the 1st and 2nd six months of lactation. In infants the RDA is 375 µg RE. In children ages 1-3, 4-6 and 7-10 years, the RDAs are 400, 500 and 700 µg RE, respectively.

Food sources:
The RDA can be met by consuming dietary preformed vitamin A (retinyl esters) from liver, eggs and fortified foods, and provitamin A carotenoids such as beta-carotene, which are found in green leafy vegetables as well as in orange and red fruits and vegetables.

Toxicity: Acute intake of extremely high doses of vitamin A (>200,000 mg RE in adult humans) can cause nausea, vomiting, headache, and increased cerebrospinal pressure. Symptoms are generally transient. Chronic high intakes (e.g., >10x RDA) can cause hair loss, bone and muscle pain, headache, liver damage, and increased blood lipid concentrations. A particular danger in pregnant women is teratogenesis (birth defects). On the other hand, carotenoids as a source of vitamin A are not toxic, even with very high intakes.

Recent research: Studies focusing on the role of retinoic acid isomers in the control of gene expression are explaining effects of vitamin A in hitherto unexpected metabolic pathways, as well as in established functions. This role of vitamin A in gene expression undoubtedly explains the anticancer and antiacne effects of vitamin A, for example. The presence of several nuclear binding proteins for retinoic acid as well as numerous controls on the metabolism and plasma transport of vitamin A provide an exquisite system for controlling the effects of vitamin A.

For further information:

Olson, J.A. (1994) Vitamin A, retinoids, and carotenoids. In: Modern Nutrition in Health and Disease (Shils, M.E., Olson, J.A. & Shike, M., eds), 8th ed., pp. 287-307, Lea & Febiger, Philadelphia, PA

Sporn, M.B., Roberts, A.B. & Goodman, D.S. (eds.) (1994) The Retinoids, 2nd ed. Raven Press, New York, NY.

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