Crystalline vitamin D

Abstract

In two earlier papers in these ‘Proceedings’ (Askew et al ., 1930, a ; Angus et al ., 1931) a crystalline antirachitic substance was described, obtained by vacuum distillation of the products of irradiation of ergosterol. In the second paper, the physical properties and antirachitic activities of a number of successive preparations of this product were recorded, and it was shown that these were sufficiently constant to suggest that it consisted mainly of one substance. We avoided the conclusions that it was yet pure, the properties showing distinct variations which suggested that other, and presumably inactive, substances were present to a variable extent. For convenience, and with reference to its conspicuous biochemical activity, we provisionally applied the name “calciferol” to this crystalline product of distillation. We realised, however, that the substance to which that name could be properly and definitely applied, as being the pure antirachitic vitamin, might differ to some extent from the product then described. Among other indications in that direction was the fact biological activity of this product was not greatly in excess of that shown by many samples of the crude irradiation product. It was indeed suggested that the irradiation mixture might contain more than one active substance ( cp . Bills et al. , 1931). Since that second publication, progress has been rapid in more than one laboratory. A few weeks later Windaus (1931) gave, at a discussion meeting of the Royal Society, a preliminary description of a crystalline product which he had separated after partial condensation of the mixed products of irradiation with maleic or citraconic anhydride (Diels’ reaction). Its melting-point, absorption and antirachitic activity were practically identical with those of our product, but its optical dextrorotation was so much lower that the two preparations could not be identical.

Old wine in new bottles: vitamin D in the treatment and prevention of tuberculosis

“…In 1903, Niels Finsen was awarded the Nobel Prize in Physiology or Medicine for his discovery that shortwave UV light was effective in the treatment of cutaneous TB (28) . Vitamin D 2 was purified and crystallised in 1931 (29) and Charpy subsequently pioneered the use of pharmacologic doses ( ‡1 . 25 mg daily) of vitamin D 2 to treat cutaneous TB (30) .…”

Tuberculosis

“…They subsequently reported that heated oxidised cod-liver oil could not prevent xerophthalmia but could cure rickets in rats, and concluded that "fatsoluble factor A" consisted of two entities, one which could prevent xerophthalmia (subsequently called vitamin A) and one which cured rickets (subsequently called vitamin D, as the terms vitamin B and vitamin C had already been coined) [ 59 ] . Vitamin D 2 was puri fi ed and crystallised in 1931 [ 60 ] , and Charpy subsequently pioneered the use of pharmacological doses ( ³ 1.25 mg or 50,000 IU daily) of vitamin D 2 to treat cutaneous TB [ 61 ] . Vitamin D 2 was also used to treat pulmonary TB, both as a single agent and, following the introduction of effective anti-tuberculous chemotherapy, as an adjunct to antibiotic treatment.…”

On the Actions of Crystalline Vitamin D2 (Calciferol) in Chronic Parathyroid Tetany1

“…That vitamin D itself, however, is toxic when given in large enough amounts, is borne out by the fact that the pure crystalline vitamin D2 (calciferol) has been shown to be toxic for experimental animals (17) and man (20).…”

“…In 1932 Askew and his associates succeeded in isolating pure vitamin D from crude irradiated ergosterol and named it " calciferol " (17). Their product was crystalline and had a potency of 40,000 international vitamin D units per milligram.…”

“…The patient was discharged from the hospital on December 17,1935, and has since been followed in the Outpatient Department. There have been several brief readmissions to the hospital for injections of parathormone, trial of special diets, and parathyroid gland transplantation.…”