Vitamin A is an essential micronutrient that is required for the maintenance of normal functioning of the human body. It was the first fat soluble vitamin to be discovered and has been known to be an important dietary constituent for nearly a century (Hopkins 1912; McCollum 1915). Vitamin A is part of a family of compounds called retinoids; the naturally occurring ones are alcohol (retinol), aldehyde (retinal), and acid (retinoic acid). For human physiology, retinol is the predominant form and 11-cis-retinol is the active form. The inactive retinoids, also known as provitamin A, are produced as plant pigments and are called carotenoids. Although many carotenoids occur in foods, approximately only 50% can be metabolized into the active retinoid forms. Beta-carotene, a retinol dimer, has the most significant provitamin A activity. Vitamin A is stored in the liver as retinyl esters and, when needed, transported into blood where it is carried by retinol binding protein (RBP) for delivery to other tissues (Shenai 1993).
Vitamin A is important for the normal functioning of the visual system, immune response, gene expression, reproduction, embryogenesis and haematopoiesis (Sommer 1996). It is essential for the maintenance of normal epithelial tissues throughout the body (Wolbach 1925). Preformed vitamin A is found only in animal foods such as liver, fish and dairy products (such as milk, cheese and butter), which constitutes 65% -75% of the dietary vitamin A intake. The remaining dietary vitamin A comes from carotenoids present in plant sources such as carrots, dark green leafy vegetables, red and orange fruits and red palm oil. The Recommended Dietary Allowances (RDAs) for vitamin A varies with age; for healthy breastfed infants up to six months of age, the average RDA is 400 mcg/d and for infants seven to 12 months of age, the RDA is 500 mcg/d. For children one to three years and four to eight years old, the RDA is 300 mcg/d and 400 mcg/d, respectively (DRI 2001).
Routine consumption of large amounts of vitamin A over a period of time can result in toxic symptoms which include liver damage, headaches, vomiting, skin desquamation, bone abnormalities, joint pain and alopecia. Hypervitaminosis A appears to be due to abnormal transport and distribution of vitamin A and retinoids caused by overloading of the plasma transport mechanisms (Smith 1976). A very high single dose can also cause transient acute toxic symptoms that may include a bulging fontanelle in infants; headaches in older children and adults; and vomiting, diarrhoea, loss of appetite, and irritability in all age groups. Toxicity from ingestion of food sources of preformed vitamin A is rare (Hathcock 1997).
Vitamin A deficiency is considered to be a major public health problem in 118 countries (WHO 2000). More than 7.2 million pregnant women in the developing world are vitamin A-deficient (serum or breast-milk vitamin A concentrations < 0.70 µmol/L) and another 13.6 million have low vitamin A status (0.70 - 1.05 µmol/L). Vitamin A deficiency affects nearly 140 million children worldwide (UNICEF 2005). Roughly 45% of vitamin A-deficient and xerophthalmic children and pregnant women with low-to-deficient vitamin A status live in South and South-East Asia. Africa accounts for 25 - 35% of the global cases of child and maternal vitamin A deficiency; about 10% of all deficient persons live in the Eastern Mediterranean region, 5 - 15% live in the Western Pacific and ˜5% live in the Region of the Americas (West 2002). Vitamin A deficiency may be secondary to decreased ingestion, defective absorption and altered metabolism, or increased requirements. Factors such as low dietary fat intake or intestinal infections may also interfere with the absorption of vitamin A. Vitamin A deficiency is the most important cause of childhood blindness and contributes significantly to morbidity and mortality from common childhood infections. It is a significant contributing factor in the 2.2 million diarrhea deaths each year among children under five, and in nearly one million measles deaths (SOWC 1998).
During pregnancy, women need additional vitamin A (an additional increment of 100 µg/day during the full gestation period above basal requirement) to sustain the growth of the fetus and to provide a limited reserve in the fetal liver as well as to maintain their own tissue growth. Because therapeutic levels of vitamin A are generally higher than preventive levels, the safe intake level recommended during pregnancy is 800 mcg retinol equivalents(RE)/day. Women who are or who might become pregnant should carefully limit their total daily vitamin A intake to a maximum of 3000 mcg RE (10000 IU) to minimize risk of fetal toxicity (WHO/NUT 1998). Infants have very low levels of vitamin A stores in the liver at birth, levels of and are dependent on breast milk as a source of vitamin A in the first few months of life. Thus, maternal vitamin A deficiency during lactation, artificial feeding or early weaning may result in vitamin A deficiency in infants (Underwood 1994). The physiologic needs for vitamin A of infants born to vitamin A-adequate mothers and fed breast milk with adequate vitamin A (in excess of 30 µg/dL or 1.05 µmol/L) are met for at least the first six months of life (Underwood 1994). Because of the need for vitamin A to support growth rate in infancy, which can vary considerably, a requirement estimate of 180 mcg RE/day seems appropriate. Average consumption of human milk by such infants is about 750 ml/day during the first six months (WHO/NUT/98.1 1998). Assuming an average concentration of vitamin A in human milk of about 1.75 mmol/l, the mean daily intake would have to be about 375 mcg RE, which is therefore the recommended safe level.
The role of vitamin A supplementation in children greater than six months of age is well established. Beaton and colleagues in their meta-analysis showed that vitamin A supplementation in children six months to five years of age significantly reduced mortality by 23% (Beaton 1993). A recent Cochrane Review concluded that two oral doses of 200,000 IU of vitamin A on consecutive days in children less than two years of age with measles was associated with a reduced risk of overall mortality (RR 0.18; 95% CI 0.03 to 0.61) and of pneumonia specific mortality (RR 0.33; 95% CI 0.08 to 0.92) (Huiming 2005). The World Health Organization (WHO) recommends administration of vitamin A at vaccination contacts in order to prevent vitamin A deficiency (WHO 1998). The policy has been to supplement 100,000 IU of vitamin A at the earliest possible opportunity after six months of age. However, it has now been recommended that an additional 50,000 IU of vitamin A be administered with each of the diphtheria-tetanus pertussis (DTP)/polio vaccinations, which are usually given at six, 10, and 14 weeks of age (Sommer 2002). National and regional programmes of vitamin A supplementation are in place in over 60 countries worldwide and target children greater than six months of age. These programs are not only highly effective in reducing mortality and morbidity, but in countries in which vitamin A deficiency constitutes a public health problem, these programmes appear to be among the most cost-effective public health interventions available. Such programs address child survival in children greater than six months of age, which accounts for a quarter of under five child deaths. In order to address the major proportion of deaths in children under five, children less than six months of age should be targeted. Supplementation with vitamin A between one and five months of age has not been found to have a beneficial effect (Daulaire 1992; Rahman 1995; West 1995; WHO/CHD 1998). Supplementation of neonates has been suggested as a feasible approach to bolstering body stores of vitamin A in early infancy and, therefore, have an impact on mortality and morbidity (Sugana 1978; Sommer 1995).