VitaDA Randomized, Controlled Trial of Vitamin D Supplementation in Infants and Children: Effects of Vitamin D Dose and Genotype of the Binding Protein

Vitamin D has recently been the subject of much attention. Advantages to the prevention of vitamin D deficiency (VDD) in young children are obvious: acutely, hypocalcemic seizures may occur in VDD, and rickets can result in long-term skeletal deformities. Previous research has emphasized the importance of identifying optimal supplementation doses and appropriate target thresholds for circulating 25-hydroxyvitamin D (25-OHD), the best described marker of vitamin D status. The timely next step is to objectively establish effective doses for the prevention of VDD, without creating risk from overzealous supplementation, in a population representative of those most at risk for overt disease. Although the primary role of vitamin D is considered to be its effect on intestinal calcium absorption, enormous variability of fractional calcium absorption in relation to 25-OHD levels exists. We provide evidence that a significant component of this variability is genetic in nature and in particular, relates to vitamin D binding protein (DBP) genotype. The aggregate data suggest that the critical mechanism for the development of nutritional rickets is reduction in availability of calcium to the skeleton, which is largely determined by vitamin D status and intestinal calcium absorption. Our proposal focuses on the establishment of a workable definition of vitamin D deficiency in an underserved and highly vulnerable population and to assess the impact of genetic variance in VDR and DBP as factors to be considered in the recommendation of vitamin D status assessment, taking into account the outcome of 25-OHD level, and in additional studies, potential functional consequences of vitamin D related to both its classical and non-classical effects.