On the Nature of the Toxic Action of Vitamin D

Abstract

Early experience with incompletely purified preparations of vitamin D demonstrated a high degree of toxicity which was first ascribed to by-products such as toxisterol and tachysterol. Later calciferol also was found to be toxic in large doses. While hypercalcemia commonly occurs with intoxication from calciferol, viosterol, toxisterol or tachysterol, it has been amply demonstrated that hypercalcemia is not per se the cause of toxicity.

The fact that the symptom complex of intoxication is identical, qualitatively, when produced by any of these agents leads to a tentative assumption that intoxication in each case may not be due fundamentally, to hypervitaminosis D, but to the formation of toxic products either in the alimentary canal or in the process of intrinsic metabolism when an excess of the vitamin in the form of calciferol or viosterol has been administered.

Crystalline ergosterol dissolved in ether was irradiated with a quartz mercury vapor lamp, according to directions kindly supplied by Dr. F. G. McDonald. One lot assayed by the line test yielded 9,000,000 (±15%) units per gram of original ergosterol. A part of this was recovered from the ether without purification; consequently the material comprised a mixture of calciferol, ergosterol and other products in unknown proportions.

A portion of this material was then further irradiated and on recovery without purification yielded, on assay, 3,000,000 (± 15%) units of vitamin D per gram of original ergosterol, showing that there had been further decomposition so that there must have been still a larger proportion of other products and less unchanged ergosterol (Gp II).

Next, a solution of calciferol in oil, 1,000,000 units per gram of solution, was allowed to stand open in a warm room until it became cloudy and the quality of taste was markedly altered. On assay this was found to contain only 50,000 units per gram (Gp III). In Table I are shown the results of experiments on dogs with these preparations.