Vitamin D. Previous to 1922 nearly all infants and young children in the north temperate zone suffered at least a mild attack of rickets. In this condition the bones do not calcify and, as a consequence, are subjected to deformity. The cause of the disease was long a mystery, although it had been recognized for more than one hundred years that cod liver oil was a specific for its prevention or cure. It was not until rickets had been produced experimentally in animals that much progress was made in understanding human rickets.

Rickets develops in young animals when they are fed a diet deficient in calcium, excessive in phosphorus, and deficient in vitamin D - a substance which is abundant in cod liver oil. Rickets also develops when the diet contains little phosphorus, an excessive amount of calcium, and a deficiency of vitamin D. In this disease the phosphorus content of the blood is markedly reduced, the inorganic phosphate being as low as one-fourth the normal eight milligram per hundred cubic centimeters of plasma. Feeding cod liver oil tends to raise the phosphorus content of the blood to the normal level.

When the diet is deficient in calcium and contains excessive phosphorus, the phosphorus is absorbed into the blood but cannot be deposited in the bones because there is no calcium to combine with it. This phosphorus is excreted as phosphate to a considerable extent into the intestine and carries with it some calcium irrespective of the needs of the body for this element. Rickets so produced tends to be complicated by tetany, a condition in which the blood calcium is reduced. In the reverse of this condition - that is, when a low phosphorus, high calcium diet is fed - an excess of calcium is absorbed in the blood but cannot be retained and is excreted into the intestine, taking with it a certain amount of phosphorus irrespective of the needs of the body for this element. This quickly reduces the content of phosphorus in the blood. The provision of vitamin D tends to regulate the calcium and phosphorus metabolism so as to keep the blood at a normal concentration as respects these elements.

While vitamin D occurs in abundance only in cod liver oil, and to a lesser extent in egg yolk, the mother substance of it, ergosterol, occurs widely distributed in plant products. It is most abundant in the fungi and was originally discovered in the oil of ergot. Ordinary yeast contains about 0.15 of 1 per cent on a dry basis, but may be cultivated under conditions where much higher yields are obtained. Ergosterol is chemically a sterol related to cholesterol, which is a component of every living cell and is especially abundant in nerves and brain. Ergosterol is a white crystalline substance which, when administered to a rachitic infant or rat, exerts no beneficial effects if the substance is kept in subdued light. If, however, the ergosterol has been exposed for a brief period to a source of ultra-violet rays, it is activated or changed into vitamin D. Only wave lengths between 265 and 313 microns are effective in activating ergosterol. This discovery constituted the first demonstration that a vitamin is a chemical substance. Activated ergosterol is now prepared in large amounts and is marketed dissolved in some vegetable oil which is palatable and does not easily grow rancid. The commercial product is known as Viosterol and is, to a considerable extent, now being prescribed by physicians instead of cod liver oil. It is recognized, however, that the diet of the child must provide a liberal amount of vitamin A in order to make Viosterol therapy equivalent to cod liver oil therapy, since cod liver oil is rich in both A and D.

The discovery of ergosterol and its activation by ultraviolet rays explains the relation of climate to rickets. Rickets has been rare in the Tropics because there people expose a considerable area of their skin to a sunlight rich in ultra-violet rays. These rays are sufficiently penetrating to activate the ergosterol in the skin and so to protect the development of the bones. Peoples in the Far North, who also escape rickets, do so because they take vitamin D in the oils of marine origin, eggs, etc.

Vitamin E. There is widely distributed in vegetable products a substance which has been shown to affect reproduction in the rat. Female rats deprived of this substance exhibit normal oestrus, ovulation, copulation, and implantation. In gestation where E is insufficient or absent, the embryos at first appear normal but show retardation in development by the eighth day or soon thereafter. There is no detectable abnormality of structure, but sometime between the twelfth and twentieth day foetal death occurs, usually on the twelfth or thirteenth. The maternal placenta is not altered structurally sufficiently to indicate that its function is impaired. In males kept on an E-free diet, sterility develops after about the seventieth day. Spermatogenesis ceases and spermatozoa are replaced by spermatids. Sterility in the male once developed is permanent. The testes of such rats undergo a slow progressive desquamation and degeneration of the germinal epithelium involving chromolysis, plasmolysis, pycnosis, giant-cell formation, karyolysis and karyorrhexis of the germ cells followed by lipoid degeneration, granular liquefaction, and final dissolution of the cells.

Vitamin E is soluble in fats and is most abundant in the oil of wheat germ. Apparently all cereals and leafy vegetables, and probably root vegetables as well, contain a considerable amount of this principle.

Vitamin G. Pellagra was not recognized in the United States until 1908. From that time it increased rapidly, especially in the southern states. Numerous efforts have been made to discover the etiology of the disease, which is characterized by stomatitis, diarrhea, dermatitis, and thickening and bronzing of the skin where exposed to light. Nervous symptoms also become prominent as the disease develops. A characteristic of pellagra is its tendency to develop in the spring, and it is much more common among people in low economic circumstances than among the well-to-do. The outstanding research on the subject was carried out by Goldberger between the years 1922 and 1926. He seems to have established that it is due to deficiency of one of the water-soluble vitamins, which is now designated by the letter G. Some British workers speak of it as the anti-dermatitis vitamin. It is much more stable toward high temperatures than is the anti-beri-beri vitamin B and survives heating under pressure at a temperature of about 118° for three or four hours. Goldberger found yeast to be the most potent source of vitamin G. He believes yeast, eggs, meat, and milk, in the order given, to be effective foods in the prevention or cure of pellagra. Yeast administration is widespread in areas where pellagra is endemic, and appears to be effective where taken in sufficient amounts.