The Nutrient Problem, As Seen through the Lens of Calcium

Nutrients are substances that an organism needs for optimal functioning but that it cannot make for itself from environmentally available raw materials. Thus, by definition, all nutrients are essential; if intakes of one or more of them are inadequate, health status and physiological functioning are suboptimal. The word “optimal” is used advisedly, inasmuch as departures from optimal function, however small, are precisely the forces that drive natural selection. The questions for nutrients, therefore, are not whether they are efficacious, but how much of each is needed to ensure optimal functioning—and of equal importance, how that quantity can be determined. In this issue of JCEM, Hill et al. (1) report estimates of that intake based upon the treasure trove of calcium balance studies in adolescents accumulated by Weaver and her colleagues at Purdue over the past 20 yr. They address not only the question of how much calcium is needed to ensure optimal status, but also whether body size affects the answer to that question. In interpreting these and similar studies, it is important to recall that nutrients, unlike most drugs and hormones, do not produce a monotonic response with respect to dose. Rather, response rises to some plateau value, above which further intake of the nutrient produces no further benefit. Thus, iron supplements increase hemoglobin concentration in patients with iron deficiency anemia, but only up to a normal hemoglobin level, above which further increases in iron intake produce no further changes in hemoglobin concentration. And in the case of calcium, retention rises up to a plateau level above which further increases in intake are without effect. Retention at that point is ultimately limited not by environmental availability, but by the genetic program for bone accumulation as modified by exercise. Thus, calcium intake is optimal when the skeletal demands are met, and correspondingly, measured calcium retention is maximized. Beyond that point, more calcium does not produce more bone, just as more iron does not produce more hemoglobin. Contrariwise, intakes below the threshold, because they limit bone accumulation, must be judged suboptimal. Logically, therefore, the required intake is the one that gets an individual up to that retention plateau. This plateau behavior for calcium is clearly evident in small animals (2), in which intake can be more readily manipulated than in humans. Several years ago, Matkovic and Heaney (3) reviewed studies reporting calcium balance during growth as a function of calcium intake and were able to find such plateau behavior in humans as well, with the plateau threshold for adolescents located at an intake of 1480 mg/d. Jackman et al. (4), from Weaver’s group, confirmed such behavior in an early subset of the studies employed in the analysis that is the subject of the current paper (1) and found a threshold of that same magnitude and with the low end of the uncertainty range for the threshold estimate at 1300 mg/d. That value, incidentally, was the basis for the estimated average requirement (EAR) for adolescents in the 1997 Dietary Reference Intakes (5). Figure 1 of the paper by Hill et al. (1) plots the results of the now nearly 300 balance studies accumulated by Weaver and her colleagues. It shows two key features of their data: 1) the threshold at which no further benefit is realized in adolescents is now a calcium intake of approximately 1600 mg/d; and 2) the retention rate itself rises as a function of body size. Neither of these findings is particularly surprising in itself, although the precise location of the plateau threshold could not have been predicted a priori. Nevertheless, available evidence concerning the di-