The Centennial of Vitamin A: A Century of Research in Retinoids and Carotenoids

Abstract

Although the birth of vitamin A is often dated to 1913, when 2 landmark studies demonstrated the growth-promoting activities of fat-soluble accessory factors (1, 2), earlier studies that are often overlooked provided intriguing glimpses of what was soon to come. For example, a cocktail prepared from minced carrots was offered as a cure for helminth infections by the German pharmacist Heinrich Wackenroder (1798–1854) (reviewed in ref. 3). Later, he was the first to isolate carotene. In apparently unrelated studies, chemists were analyzing the nature of plant and animal pigments (3): William Zeise (1789–1847) showed that the carrot pigment is a hydrocarbon, Jons Berzelius (1779–1848) demonstrated that xanthophyll is an oxygencontaining hydrocarbon, and Adolph Lieben (1836–1914) isolated carotenoid from the bovine corpus luteum. Unaware of the close relationships between these different pigments, Johann Ludwig Wilhelm Thudichum (1829– 1901) (3), using newly developed spectroscopic methods, demonstrated that all shared important structural features. Richard Willstaetter, (1872–1942) (3, 4), who invariably encountered and analyzed these pigments in chlorophyll preparations, assigned the chemical formula C40H56 to carotene and C40H56O2 to xanthophyll, thus capping the issue. Meanwhile, the Polish biochemist Casimir Funk (1884– 1967) and his British rival, Sir Frederick Hopkins (1861– 1947), proposed the concept of “vitamins” in reference to a group of essential but minor components in ordinary food stuffs such as brown rice and milk (5). These substances had no intrinsic caloric value, but were essential for healthy mammalian development. In 1913, the stage was set for Elmer McCollum (1879–1967), Marguerite Davis (1887– 1967), Thomas Osborne (1859–1929), and Lafayette Mendel (1872–1935) to obtain proof of principle by showing that tiny amounts of an accessory factor found in milk and egg yolk, later known as “fat-soluble A” (thereafter, vitamin A), is indispensible for rearing newborn rats. It took another 20 yr for Paul Karrer (1889–1971) to solve the structure of vitamin A (6), establish its chemical kinship with carotenoids, and set the stage for an ever-expanding interest in its functions (Table 1).