Vitamin Imbalance in Metabolic Disease

Abstract

Abstract Like other constituents of blood or serum, the deviation of a vitamin titer from the normal range may mean a number of things: reduced intake or absorption, increased utilization, increased demand, increased excretion will all cause a decrease of titer; their opposites, an increase. A vitamin is often the etiological center of a disease, as vitamin B12 and folic acid in macrocytic anemias. Here, because of the obvious implications for diagnosis and therapy, the determination of the "nucleogenic" vitamins, B12 and folic acid, is imperative in the routine of clinical hematology. Where the connection between a vitamin and a disease is less transparent a wide field remains open for the discovery of meaningful correlations between vitamin content of body fluids and tissues to physiologic or pathologic events. To single out the case of a physiological state of general importance, the vitamin equilibrium between mother and newborn offers now possibilities for the management of pregnancy, especially in regions where preventive "shot-in-the-dark" polyvitamin therapy is financially impossible. In the field of pathology, the significance of vitamin B12 in toxemia of pregnancy deserves further study. The so-called normal range of blood and serum vitamin levels is always derived from observations on healthy young subjects. Why not a comparison with healthy old subjects, whose percentage in the population is steadily increasing? Much may be learned about the cause of the decrease of physiological function and of the increased susceptibility to organic disease in old age, if the role of vitamins as parameter of these alterations were investigated with a view to preventive therapy. A glance at vitamins in clinical medicine opens a wide panorama with challenging aspects in hepatic conditions, in oxalosis and calculus disease, in obscure but widely spread neurological diseases, and in many others. Astute clinical observations, combined with knowledge of the function and mechanism of vitamin action, will bring vitamin analysis into the picture as a useful tool. Special mention must be accorded to iatrogenic effects, where the usefulness of novel synthetic drugs is impaired by untoward side effects of obscure etiology. Some of these side effects may find their explanation in the inhibitory action of the drug upon a vitamin, as in the case of Primidone vs. folic acid (15). The mode of the toxic action of Thalidomide has not yet been determined. Because of our previous experience with the use of protozoa in the detection of metabolic lesions induced by drugs, as exemplified already in the case of Primidone, Frank and Baker have studied the antimetabolic nature of thalidomide, using Ochromonas danica, Ochromonas malhamensis, and Euglena gracilis; they found inhibition of growth which was overcome by nicotinic acid or amide, by nicotinamide adenine dinucleotide (NAD, formerly DPN), or by vitamin K. This points to interference by thalidomide with the pathway of cellular oxidative phosphorylation. While thalidomide is remarkably nontoxic to the nonpregnant animal, the blocking of normal morphogenesis in the fetus must be ascribed to this metabolic interference. In general, such relationships appear to be fortuitous until the structural chemical kinship of drug and vitamin is recognized.