It can be stated that the discovery of vitamin A (of course the first vitamin) opened the large field of the fat-soluble vitamins. Experiments by Stepp (Biochem Zeitschr, 1909, 22, 452) showed that mice fed diets extracted with ether and alcohol ("lipoid-free" diets) died. Survival was obtained when a fraction extracted from egg yolk by cold ethyl alcohol was added to the lipid-free food. Additions of lard or olive oil were ineffective so that the "new" nutrient was a specific lipid, not a simple glyceride (McCollum et al., J Biol Chem, 1913, 15, 167). The same authors proved that the new substance was present in the unsaponifiable fraction of butter fat. The active principle, first designated fat-soluble A, was later called vitamin A (Funk, J State Med 1912, 20, 341).
It was later demonstrated that carotene had vitamin A value and in 1929, Moore (Lancet, ii. 217) proved the in vivo conversion of carotene to vitamin A. Thus, certain carotenoids act as provitamin A, they come from plants but vitamin A is only of animal origin. The conversion is made mainly in the gut but vitamin A is often present esterified with higher fatty acids.
Epidemiological studies indicated very early
that there was a relationship between the protection against rickets and exposure to
sunlight. This led to the discovery of provitamins D. It was observed first that exposure
of the body to ultraviolet rays prevented or cured rickets but later it was discovered
that irradiation of food was as efficient. At the same time (1923), it was observed that
the antirachitic product of irradiation was stored in the liver. Steebock (J Biol Chem,
1924, 61, 405) observed that the active substance was present in the unsaponifiable
fraction of the food and accompanied cholesterol. Cod liver oil was by far the richest in
this substance and owed its reputation and its therapeutic properties to the fact that it
prevented efficiently rickets. By 1921 Mellanby was already confident that an antirachitic
substance existed, but he could not exclude the possibility that it was identical with
vitamin A. Later, McCollum (J Biol Chem, 53, 293) was able to make the distinction between
the two vitamins. Before the isolation by Brockmann and others of the active compound (now
called Vitamin D3 or cholecalciferol, produced by irradiation of 7-dehydrocholesterol), it
was shown that vitamin D2, calciferol or ergocalciferol could be produced by irradiation
of ergosterol. The term vitamin D1 was discarded since the material to which it was first
applied has been found a mixture of sterols and calciferol.
The presence in vegetable oils of material essential for normal reproduction in rats was demonstrated in the early 1920's (Evans, J Metab Res, 1922, 1, 319; Mattill, Proc Soc Exp Biol, 1923, 20, 420). The term vitamin E (or antisterility factor) was proposed by Sure (1924). Muscular dystrophy, neurological and vascular degeneration were also described after vitamin E deficiency. In 1936 (Evans, J Biol Chem,113, 319), two compounds with vitamin E activity were isolated from wheat germ oil after saponification and precipitation with cyanic acid, they were named a- and b-tocopherol (Greek tokos, birth; phero, to bear). Their synthesis was realized in 1938 (Karrer, Helv Chim Acta,21, 520). More recent works had enlarged the field of the vitamin E group when parent compounds, tocotrienols, were discovered in rice lipids, rubber latex and palm oil (McHale, J Chem Soc, 1963, 784; Dunphy, Nature, 1965, 207, 521). The first report by Olcott (J Biol Chem, 1931, 93, 65) of antioxidant properties of a fraction isolated from lettuce lipids and having high vitamin E activity and later the observation by Dam (Acta Physiol Scand, 1945, 10, 162) of peroxides in adipose tissues of animals fed diets deficient in vitamin E initiate several investigations in this field. An important school of thought appeared holding the view that the biological properties of vitamin E are all due to its antioxidant power.