Vitamin A; sources, significance, toxicity


Vitamin A is a nutrient of global importance. Shortages in its consumption are estimated to affect an estimated 140 million children worldwide, some 90% of whom live in Southeast Asia and Africa. In recent years, substantial progress has been made in reducing the magnitude of this problem. In 1994, nearly 14 million preschool children (three-quarters from south Asia) were estimated to have clinical eye disease (xerophthalmia) due to vitamin A deficiency. By 2005, that prevalence had declined; yet some 5.2 million children remain affected by night blindness. If untreated, two-thirds of those children die within months of going blind owing to their increased susceptibility to infections enhanced by the deficiency. Vitamin A deficiency remains the single most important cause of childhood blindness in developing countries. At the same time the prevalence of subclinical deficiency (serum retinol levels 0.7 μmol/l) has increased. Of the world’s preschool children, 33% (estimates range from 75 to 254 million) appear to be growing up with insufficient vitamin A . More than 19 million pregnant women in developing countries are also vitamin A-deficient; a third are affected by night blindness. Subclinical vitamin A deficiency is also associated with increased child mortality, having public health significance in at least 122 countries in Africa, southern and Southeast Asia, and some parts of Latin America and the western Pacific. High rates of morbidity and mortality have long been associated with vitamin A deficiency; recent intervention trials have indicated that providing vitamin A can reduce child mortality by about 25%, and birth-related maternal mortality by 40%. Vitamin A deficiency in these areas does not necessarily imply insufficient national or regional supplies of food vitamin A, as vitamin A deficiency can also be caused by insufficient dietary intakes of protein, fats, and oils. Still, most studies show that children with histories of xerophthalmia consume fewer dark green leafy vegetables than their counterparts without such histories.

Vitamin A


Dietary Sources of Vitamin A

Vitamin A exists in natural products in many different forms. It exists as preformed retinoids, which are stored in animal tissues, and as provitamin A carotenoids, which are synthesized as pigments by many plants and are found in green, orange, and yellow plant tissues. In milk, meat, and eggs, vitamin A exists in several forms, mainly as long-chain fatty acid esters of retinol, the predominant one being retinyl palmitate. The carotenoids are present in both plant and animal food products; in animal products, their occurrence results from dietary exposure. Carotenoid pigments are widespread among diverse animal species, with more than 500 different compounds estimated. About 60 of these have provitamin A activity, i.e., those that can be cleaved by animals to yield at least one molecule of retinol. In practice, however, only five or six of these provitamins A are commonly encountered in foods.

Therefore, actual vitamin A intakes depend on the patterns of consumption of vitamin A-bearing animal food products and provitamin A-bearing fruits and vegetables, the relative contributions of which are influenced by food availability and personal food habits.

Foods Rich in Vitamin A

Several foods contain vitamin A activity; however, relatively few are rich dietary sources, those being green and yellow vegetables, liver, oily fishes, and vitamin A-fortified products such as margarine. It should be noted that, for vitamin A and other vitamins that are susceptible to breakdown during storage and cooking, values given in food composition tables are probably high estimates of amounts actually encountered in practical circumstances.



Feeding provitamin A carotenoids retinyl esters, retinol, and retinal can support the maintenance of healthy epithelial cell differentiation, normal reproductive performance, and visual function

Vitamin A in Vision

The best elucidated function of vitamin A is in the visual process, where, as 11-cis-retinal, it serves as the photosensitive chromophoric group of the visual pigments of rod and cone cells of the retina. Rod cells contain the pigment rhodopsin; cone cells contain one of three possible iodopsins. In each case, 11-cis-retinal is bound (via formation of a Schiff base) to a specific lysyl residue of the respective apo-protein (collectively referred to as opsins)

Vitamin A in Bone Metabolism

Vitamin A has an essential role in the normal metabolism of bone. This is indicated by results of animal studies that have shown both low and high vitamin A intakes to reduce bone mineral density. The results of observational studies in humans, however, have been inconsistent in this regard, with only some showing high intakes of vitamin A reducing bone mineral density or increasing fracture risk.

Vitamin A in Hematopoiesis

Because chronic deprivation of vitamin A leads to anemia, a role for the vitamin in hematopoiesis has been suggested. Cross-sectional studies have shown low hemoglobin levels to be associated with the prevalence of signs of xerophthalmia in children, and children with mildto- moderate vitamin A deficiency or mild xerophthalmia to have lower circulating hemoglobin levels than nondeficient children; serum retinol level has been shown to explain 4–10% of the variation in hemoglobin level among pre-adolescent children in developing countries.

Immune Function

Vitamin A-deficient animals and humans are typically more susceptible to infection than are individuals of adequate vitamin A nutriture. They show changes in lymphoid organ mass, cell distribution, histology, and lymphocyte characteristics. Vitamin A deficiency is typically associated with malnutrition, particularly protein-energy malnutrition. This may be due to the common origins of each condition, i.e., in grossly unbalanced diets and poor hygiene, resulting in the fact that malnourished children are likely to be deficient in vitamin A and other essential nutrients.

Skin Health

Vitamin A has a role in the normal health of the skin. Its vitamers, as well as carotenoids, are typically found in greater concentrations in the subcutis than in the plasma (significant amounts are also found in the dermis and epidermis), indicating the uptake of retinol from plasma RBP4. Epithelial cell phenotypes are regulated by hormonal cycles and vitamin A intake; vitamin A deficiency impairs the terminal differentiation of human keratinocytes and causes the skin to be thick, dry and scaly. It also results in obstruction and enlargement of the hair follicles.

Cardiovascular Health

Epidemiologic investigations have repeatedly found inverse relationships between the level of consumption of provitamin A-containing fruits and vegetables and risks of cardiovascular disease. Indeed, plasma retinol levels have been found to be related inversely to the risk of ischemic stroke, and low plasma β-carotene concentrations are associated with increased risk of myocardial infarction

Treatment of Vitamin A Deficiency

Because vitamin A is stored in appreciable amounts in the liver, it can be administered in relatively large, infrequent doses with efficacy. In cases of clear or suspected xerophthalmia, particularly in communities in which the deficiency is prevalent, vitamin A is administered orally in large doses, followed by an additional dose the next day and a third a few weeks later. Oral administration of water-miscible or oil solutions of the vitamin are as effective as water-miscible preparations administered parenterally. Water-miscible preparations are much more effective than oil solutions when administered parenterally, i.e., by intramuscular injection. Topical administration on the skin is ineffective.


The hepatic storage of vitamin A tends to mitigate against the development of intoxication due to intakes in excess of physiological needs. However, persistent large overdoses (more than 1,000 times the nutritionally required amount) can exceed the capacity of the liver to store and catabolize, and will thus produce intoxication.



The Vitamins

Fourth Edition

Gerald F. Combs, Jr

Professor Emeritus

Cornell University

Ithaca, NY

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