Preformed vitamin A (retinol) is found only in animal foods, with the highest levels in mammalian, fowl, and fish livers, and in fish-liver oil, but with great seasonal variation. The next highest levels are in kidneys and fatty fish (e. g., salmon), whereas a third tier consists of milk, butter, and eggs, again with seasonal variation.
Carotenoids (beta-carotene and related compounds) are precursors of vitamin A that occur in green leaves and yellow and red vegetables and constitute the main source of vitamin A in the human diet. In decreasing order of beta-carotene content, these sources include parsley, sweet potato, broccoli, lettuce, tomato, and cabbage. Smaller, but significant, amounts are in legumes such as chickpeas and green and black grams. Yellow maize also contains beta-carotene. Fowl that eat grains and seeds absorb and accumulate carotenoids in their fat, so that their flesh can also be a source of this provitamin.
A special case as a source of beta-carotene is red palm oil, a vegetable oil used for cooking in several areas of Africa, Southeast Asia, and South America. It contains 0.6 to 1 RE per gram of oil and, in these areas, represents an important source of the provitamin (Underwood 1984: 290).The oil is extracted from the fleshy mesocarp of the palm nut and is prepared by boiling the fruit in water, cooling, and removing the oily layer. Unfortunately, substantial losses of beta-carotene can occur during cooking and storage.
Foods that lack vitamin A or carotenoids are wheat, oats, rice, potatoes, cassava, manioc, onions, nuts, sugar, olive oil, pork, and lard. In light of this lack, it is of interest to consider traditional diets of children in countries where vitamin A deficiency is a widespread public health problem. J. M. May and D. L. McLellan (1970), for example, have described the foods given to children in rural Ethiopia after weaning (at about 18 months of age).These included pancakes (injera - made from a local low-protein cereal grain called toff [tef], fermented and wet-cooked on a large griddle over an open fire) and a stew (wot - made of legumes, barley, onions, and garlic). The wot may contain some meat, although two-thirds of rural Ethiopians never eat meat. The children of a family are especially disadvantaged in terms of nutrition because the order of feeding is first the father, then guests, male persons, mother, and, last, children. Often, by the time the children eat, the wot, containing small amounts of carotenoids, is gone, and only injera is left.
Another example is drawn from Ghana, where the principal diet in rural areas consists of either fermented maize flour (keuke) made into a dough and cooked, or a soup or porridge of millet (tuwonsafe). In tropical forest regions, sun-dried cassava is ground to a flour (konkote) and boiled to a puree. Any oils in the diet are from groundnuts. Once again, fathers eat first, then other males, with women and children last. Moreover, there are taboos against women consuming eggs in some parts of Ghana. Clearly, with such a diet and such cultural habits, vitamin A deficiency is likely to be widespread.
A final example is found in India, where a public health problem exists with respect to vitamin A deficiency: The poor eat principally parboiled rice, or millet or wheat flours mixed with water and cooked as pancakes (chapattis). Cooking oil is from seeds; legumes are cooked with spices, and fat and vegetable intake is low (1 percent of the diet). Children are weaned at 2 years, then given boiled milk, diluted with water, along with rice or chapattis. No wonder that vitamin A deficiency diseases are prevalent among the poor.
Future Prospects Basic Biology
Since the discovery, in 1987, of the mechanism of gene activation by retinoic acid, establishing vitamin A as a hormone, progress in the understanding of its basic biology has been breathtakingly rapid. The pleiotropic action of vitamin A (i. e., the multiple physiological functions of this vitamin) in development, growth, and differentiation, and the legion of enzymes affected by it, has been a puzzle since the early work of Wolbach and Howe (1925). This puzzle is now in the process of being solved.
The regulation and control of growth factors, hormones, enzymes, and homeobox genes (i. e., genes controlling embryonic development) by retinoic acid can now be explained on a rational basis because of the discovery of nuclear retinoic acid receptors (RARs), proteins that bind metabolites of retinol (all-trans-retinoic acid and 9-cis-retinoic acid) and, in a variety of combinations, interact with the DNA in the promoter regions of a large number of genes. These genes are then activated to express specific mRNAs (messenger RNAs) and proteins that can regulate and control development, growth, and differentiation.
Researchers are sequencing the relevant genes and tracing their evolutionary development. They are also in the process of elucidating the genes’ interaction with RARs and the functions of the specific proteins expressed (enzymes, hormones, growth factors). Thus, the fields of biochemistry, endocrinology, genetics, embryology, evolution, and oncology will be greatly expanded, all on the basis of our recognition of the nuclear RARs. It has now become clear that the immune system is also influenced by vitamin A, and important advances in research on the action of vitamin A on the immune response can be expected.
Cancer and Other Diseases
Acute promyelocytic leukemia and skin cancer have been successfully treated with vitamin A derivatives. On the basis of experimental work, one can expect other forms of cancer to yield to efforts at treatment by retinoids. Chemoprevention treatment by retinoids of persons at high risk (e. g., recurrent squamous carcinoma of the head and neck) will certainly expand. Skin diseases (acne, psoriasis, and others) have been successfully treated with retinoids, and the possibility exists that rheumatoid arthritis and other inflammatory diseases may ultimately yield to retinoid treatment.
Public Health
Future prospects for the alleviation of the horrendous tragedy of preventable childhood blindness and children’s infectious diseases by vitamin A or beta-carotene now lie in the hands of governments, international organizations, and nongovernmental agencies. The problem is not one of science but of economics, education, and, ultimately, politics. The science is merely concerned with methods of determining in which population groups the children are at risk of vitamin A deficiency and the severity of the deficiency. This assessment can be done by blood tests, but simpler methods are being sought. Once the deficient population group has been ascertained, it is necessary to direct efforts for a cure in such a way that the vitamin reaches the children in need. This implementation involves improving the children’s overall diet and sanitation, removing parasites, educating the mothers, diversifying the food supply, fortifying foods, and supplementing with vitamins. Considering the millions of children and the multitude of countries affected (see Table IVA.1.2), each with its own government, bureaucracy, and dietary and cultural traditions, the elimination of vitamin A depletion and deficiency will be a daunting task.
George Wolf
The author thanks Dr. Barbara A. Underwood of the WHO Nutrition Unit, Geneva, Switzerland, for making available and giving permission to use material from unpublished documents from the World Health Organization.