Nutritional Aspects of Vitamin A and Carotenoids Historical
Vitamin A was discovered in the early 1900s by McCollum and colleagues at the University of Wisconsin and independently by Osborne and Mendel at Yale. Both groups were studying the effects of diets made from purified protein and carbohydrate sources, such as casein and rice flour, on the growth and survival of young rats. They observed that growth ceased and the animals died unless the diet was supplemented with butter, fish oils, or a quantitatively minor ether soluble fraction extracted from these substances, from milk, or from meats. The unknown substance was then called ‘‘fat-soluble A.’’ Not long thereafter, it was recognized that the yellow carotenes present in plant extracts had similar nutritional properties, and it was postulated that this carotenoid fraction could give rise through metabolism to the bioactive form of fat-soluble A, now called vitamin A, in animal tissues.
This was shown to be correct after b-carotene and retinol were isolated and characterized, and it was shown that dietary b-carotene gives rise to retinol in animal tissues. Within the first few decades of vitamin A research, vitamin A deficiency was shown to cause several specific disease conditions, including xerophthalmia; squamous metaplasia of epithelial and mucosal tissues increased susceptibility to infections; and abnormalities of reproduction. Each of these seminal discoveries paved the way for many subsequent investigations that have greatly expanded our knowledge about vitamin A. Although the discoveries made in the early 1900s may now seem long ago, it is interesting to note, as reviewed by Wolf [2], that physicians in ancient Egypt, around 1500 BC, were already using the liver of ox, a very rich source of vitamin A, to cure what is now referred to as night blindness.
Definition of Vitamin A , Retinoids, and Carotenoids Vitamin A is a generic term that refers to compounds with the iological activity of retinol. These include the provitamin A carotenoids, principally b-carotene, a-carotene, and b-cryptoxanthin, which are provided in the diet by green and yellow or orange vegetables and some fruits and preformed vitamin A, namely retinyl esters and retinol itself, present in foods of animal origin, mainly in organ meats such as liver, other meats, eggs, and dairy products.
The term retinoid was coined to describe synthetically produced structural analogs of the naturally occurring vitamin A family, but the term is now used for natural as well as synthetic compounds [3]. Retinoids and carotenoids are defined based on molecular structure. According to the Joint Commission on Biochemical Nomenclature of the International Union of Pure and Applied Chemistry and International Union of Biochemistry and Molecular Biology (IUPAC–IUB), retinoids are ‘‘a class of compounds consisting of four isoprenoid units joined in a head-to-tail manner’’ [4]. All-trans-retinol is the parent molecule of this family.
The retinoid molecule can be divided into three parts: a trimethylated cyclohexene ring, a conjugated tetraene side chain, and a polar carbon–oxygen functional group. Additional examples of key retinoids and structural subgroups, a history of the naming of these compounds, and current nomenclature of retinoids are available online [4]. The IUPAC–IUB defines carotenoids [5] as ‘‘a class of hydrocarbons (carotenes) and their oxygenated derivatives (xanthophylls) consisting of eight isoprenoid units joined in such a manner that the arrangement of isoprenoid units is reversed at the center of the molecule.’’ All carotenoids may be formally derived from the acyclic C40H56 structure that has a long central chain of conjugated double bonds, by (i) hydrogenation, (ii) dehydrogenation, (iii) cyclization, or (iv) oxidation, or any combination of these processes.
