Calcium carbonate as a dietary supplement: its effects on soft tissues, with special reference to erythropoiesis

Abstract

This thesis describes some unexpected results obtained when a standard diet for breeding mice was supplemented with calcium carbonate at rates up to 2 per cent. The abnormalities observed included profound anaemia in both dams and their litters» and Impaired growth and reproductive efficiencyj in addition to the anaemia, young animals also exhibited thymus atrophy, hyperlipaemia, and fatty changes in the liver. The cause - or, at least, the major cause • of these disorders has proved to be an induced deficiency of iron, which can be largely overcome by feeding an iron supplement.The work is presented in three Parts, with, in addition, Technical, Bibliographical and Tabular Appendices. Part I is introductory, and contains a description of the abnormalities caused by dietary supplements of calcium carbonate, together with details of the experiment in which they were first recognised. The major portion of the experimental work and argument is included In Part II. This Part begins with an appraisal of the probable Importance of the observations, and proceeds to the formulation of a plan of research desired to elucidate the mechanism at work. The anaemia appears to be dyshaemopoietic in origin, and, after a survey of normal and abnormal erythropoiesis, its likely causes are listed. An experiment shows that a supplement of iron not only improves the blood haemoglobin concentration but also largely prevents the other abnormalities, and further evidence that calcium carbonate interferes with iron availability is adduced from later eaqperiments. It is also shown that restoration of the calcium : phosphorus ratio, effected by means of a supplement of inorganic phosphate, does not abolish the deleterious effects of calcium carbonate.Further work goes on to show that neither copper deficiency nor pyridoxin deficiency can have played any important part in causing the anaemia. However, supplements of cobalt or of dried thyroid (although not of iodine) increase the -iihaemoglobin level, and the effects of both are affected by the presence of calcium carbonate#Following discussion of the other abnormalities observed in soft tissues, it is shown that in every case they could arise secondarily to anaemia. Nevertheless, other possible causes - including deficiencies of manganese, pyridoxin, thyroid hormone, choline and inositol - are suggested and investigated, but it is shown that none of these plays any part.In Part III, the conclusion is reached that the effects on soft tissues which result from supplementing the diet with calcium carbonate can all be explained on the basis of an induced deficiency of iron, and that this is the major if not the sole cause of the entire syndrome. After reviewing the literature on caloium-phosphate-iron relationships, it is concluded that some important factor remains unrecognised, and suggestions are put forward to indicate the lines on which further investigations should proceed. Finally, the importance of the findings is discussed.