Vitamin D and Citrate Metabolism: Studies on Rachitic Infants *

There are many reasons for considering the possibility that the metabolism of citrate is interrelated with the physiological effects of vitamin D and with the equilibrium of calcium and phosphorus in the body. Hamilton and Dewar10 and Shohl'7 demonstrated that the addition of citrate to rachitogenic diets resulted in prevention or cure of rickets in rats. Subsequently, Shohl and Butler1' showed that the feeding of mixtures of sodium citrate and citric acid to rachitic infants on a milk diet produced healing of the rickets although no vitamin D was given. Since the administration of dicarboxylic acids which do not form complex ions with calcium does not cause healing of rickets,' it is possible that the effect of oral citrate is related to its property of reducing the concentration of ionized calcium by virtue of the formation of an undissociated calcium citrate complex." Dickens' added further interest to the possible role of citrate in bone formation by his studies of the citrate content of bone. He noted that bone contained appreciable amounts of citrate which was bound to the bone salt so that it was not eluted by water. The citrate content of the bone of a rachitic animal was found to be less than that of normal bone. Nicolaysen1 extended this particular phase of the study and found that the bone citrate of rachitic rats was reduced to a greater extent than was the calcium so that the molar ratio of citrate to clcium in rachitic bone was less than that found in the bone of normal rats. The presence of citrate in bone could be merely another consequence of its reaction with calcium to form an undissociated complex and may not necessarily indicate any participation of citrate in the primary reactions leading to deposition of bone salt. The possibility that the metabolism of citrate might be altered in the vitamin D deficient subject developed from a study by Freudenberg,8 which was concerned with the effect of vitamin D on the urinary excretion of organic acids in rachitic infants. Freudenberg suggested that the total organic acid excretion was high in the rachitic infant and was reduced by vitamin D therapy but his results were inconclusive. He had also determined separately the citrate content of the urine, and although there was considerable variation from day to day there did seem to be a real increase of citrate excretion following vitamin