What does it mean to target specific serum 25-hydroxyvitamin D concentrations in children and adolescents?

The task of determining dietary requirements for vitamin D intake is one of the key unresolved issues in vitaminand mineralrelated nutrition. The complexities of issues, including determining intake sources of vitamin D, seasonal changes in sun exposure at different latitudes, and population-related differences in the storage and metabolism of vitamin D, make the process of setting dietary guidelines difficult. In determining dietary requirements, most have chosen to use the serum 25-hydroxyvitamin D [25(OH)D] concentration as the primary biomarker of vitamin D, especially in healthy populations. This is despite the fact that the serum 25(OH)D concentration is not clearly a functional biomarker and is inconsistently related to identified health outcomes in otherwise healthy pediatric populations except at the extremes of usual population values (1, 2). Nonetheless, there remains considerable interest in defining the relation between dietary vitamin D intake and serum 25(OH)D concentrations in children in whom relatively few such data exist (3). In infants, an intake of 400 IU/d will allow the vast majority if not nearly all infants who receive an appropriate diet to maintain a 25(OH)D concentration . 30 nmol/L, which appears to be adequate to prevent rickets (3, 4), but comparable data in older children are minimal. Two recent studies published in this issue of the Journal (5, 6) directly address this data limitation by using studies in young children and adolescents given vitamin D3 supplements of 0, 400, or 800 IU/d (0, 10, or 20 lg/d). The populations studied in each report were white children in Denmark and consisted of 20 wk of wintertime supplementation in randomized, placebo-controlled, doseresponse trials. Results in children 4–8 y of age (5) showed that average total vitamin D daily intakes of 4.4 lg (175 IU) achieved a 50% population response of serum 25(OH)D concentration to.40 nmol/L and that total daily intakes of 19.5 lg (;800 IU/d) achieved a 97.5% response of serum 25(OH)D concentration to.50 nmol/L. In adolescents (6), a daily total intake of 6.6 lg (265 IU) met the 50% population response of serum 25(OH)D concentration to . 40 nmol/L, and an intake . 30 lg (1200 IU) would be needed to achieve a 97.5% response of serum 25(OH)D concentration to . 50 nmol/L. Of importance is that these conclusions were based on modeling responses of the individual subject data. In the provided data set, a daily intake of;1000 IU/d (25 lg) led to a 25(OH)D value . 50 nmol/L in nearly all of the adolescent study subjects (6). It is also important to note that the populations in these studies do not reflect fully a more racially diverse population or populations with greater sun exposure. Thus, caution should be used in interpreting these results on a global basis. These results are very consistent with the Institute of Medicine’s (IOM) 2011 report that establishes the Estimated Average Requirement at a daily vitamin D intake of 400 IU (10 lg). This intake would achieve the targeted adequate serum 25(OH)D concentration of 40 nmol/L in 50% of the population (3). The IOM’s conclusion was based, however, on limited data, and it is important that the current (5, 6) studies support these results. These results should lead to further discussion about the real meaning of values of serum 25(OH)D concentrations in children. Despite much fanfare, there are few data, either available to the IOM committee or available at the present time, that indicate a specific health benefit to achieving any given value of serum 25(OH)D, although there is reasonable support for the idea that values ,30 nmol/L increase the risk of rickets in young children (3). It has been shown that serum 25(OH)D values of 40 nmol/L, consistent with the average values in the US population of children, lead to rates of calcium absorption consistent with those of children with values of 50–80 nmol/L (7). Although there continue to be numerous reports relating very low vitamin D status to a range of health problems, these have overwhelmingly been association studies. There have been only a few small controlled trials that evaluated these relations, and results have been conflicting in children, especially when only considering outcomes in children who are not clearly deficient in vitamin D intake or serum 25(OH)D values. One important area of persistent confusion is the interpretation of the Recommended Dietary Allowance (RDA) for vita-