Vitamin D
The disease rachitis, now commonly called rickets, has apparently plagued mankind since ancient times. In 1650 infant rickets was described by Glisson in England. The disease was rampant especially among the children of the lower classes of people in England (and other sections of the world) for centuries. Infection was early postulated as a cause of the disease. Around London the abundance of fog was held by some to be a contributing factor. It is now known that the latter assumption was correct, although at that time it may have been predicated on erroneous beliefs.
In other words, the lack of sunshine due to the fog was a predisposing factor. The curative value ofliver, especially cod liver oil, was known centuries ago. Late in the eighteenth century it was used in parts of England as a therapeutic agent, although its specific value in preventing or curing rickets was apparently unknown until many years later. As late as 1920 Hess and Unger indicated that rickets was a very common disorder of infants living in the temperate zone. After World War I infant rickets in various parts of Europe was widespread. Our presentday knowledge of rickets and the chemical nature of the vitamers D is based primarily on a series of seemingly unrelated findings. Important among these are the following:
1. In 1918 Mellanby produced the first clear-cut experimental rickets in animals. Dogs were fed various diets of milk and porridge or bread and milk. Rickets developed regularly on such diets. He was able to demonstrate the presence of the antirachitic factor in cod liver oil and showed that this substance was far superior to butter fat and peanut, olive, or linseed oils in curing or protecting against rickets in his dogs.
2. Huldschinsky in 1919 demonstrated marked clinical improvement in severely rachitic children by, playing ultraviolet light on their bodies. This finding was important not only from the clinical standpoint but also afforded impetus to the theory, doubted by many, that sunlight is beneficial in the treatment of rickets.
3. In 1922 McCollum and co-workers demonstrated that cod liver oil contains a specific substance (vitamin) concerned with calcium deposition in rachitic rats. The presence of "fatsoluble A" in cod liver oil had been known for some time. By running air through the oil at lOO°C the destroyed the xeropbthalmia-curing principle, but the oil maintained a high activity in respect to calcium metabolism. Thus the dual vitamin nature of cod liver oil was established.
4. Two groups of investigators reported in 1924 that the irradiation of certain foods with ultraviolet light endowed them with antirachitic (vitamin D) activity. Steenbock and co-workers and Hess reported this remarkable finding at about the same time. Shortly after this it was demonstrated that the sterol fraction of foods actually contained the material that became antirachitic on irradiation and specifically that ergosterol was capable of a high degree of activation.
5. Angus and co-workers isolated crystalline vitamin D in 1931. They accomplished this by high vacuum distillation of the products obtained upon ultraviolet irradiation or ergosterol. This was named calciferol and is referred to as vitamin D2.
6. Vitamin Ps' activated 7-dehydrocholesterol, was isolated by Wiridaus and co-workers in 1936. They irradiated 7 -dehydrocholesterol in benzene and were able to separate crystalline derivatives-of the vitamin. The name vitamin D3 was proposed for the substance at that time is established now that small amounts of7-dehydrocholesterol accompany animal cholesterol.
The skin contains this precursor, and thus ultraviolet light, from the sun or from artificial sources, is able to activate and yield vitamin Ds to the body. As a result of the preceding 5ndings and, of course, many other outstanding observations, the value of sunlight and many artificially produced vitamin D products in the treatment of rickets was realized.
In the early 1930's vitamin D milk (ultraviolet irradiated) was widely available in the larger
enters of population, and a number of highly concentrated vitamin D preparations were marketed previous to that time. Likewise, the elucidation of the chemistry of the various ntamers D arid the photochemical changes proceeding during the ultraviolet irradiation of me precursors were markedly hastened. It became evident that two forms of vitamin Dare of importance in human nutrition: calciferol (vitamin D2), produced from irradiation of the plant sterol ergosterol, and vitamin Ds, the activation product of the animal sterol 7dehydrocholesterol. Many other vitamers are known, but they are at present of academic interest only.
Dihydrotachysterol, or AT 10, is a reduction product of tachysterol; the latter is one of the products of irradiation of ergosterol (see further). The parent substances which can be activated are also known as provitamins.
