This project will investigate four related questions concerning calcium absorption in humans: 1) What is the physiological basis for absorptive differences among apparently healthy adult women? 2) How long does it take to adapt to large changes in calcium intake? 3) What is the precise quantitative relationship between 1,25(OH)2D3 (calcitriol) dose and absorptive capacity (in women prepared with dietary suppression of endogenous calcitriol production)? and 4) What is the basis for the hyperabsorption of calcium citrate (and possibly other very soluble calcium salts) in patients with achlorhydria? The starting point of this investigation is the finding, by ourselves and others, that absorptive efficiency, measured under standard conditions, ranges from 10% to 60% in apparently healthy adult women, and that only 20-25% of this interindividual variation can be explained by such regulatory factors as usual dietary intake or endogenous calcitriol levels. The project consists of four related protocols. The first will measure fractional absorption in healthy adult women and will, at the same time, obtain such correlative data as levels of the principal hormones and co- factors known to influence absorption; the subjects will also undergo measurements of gastric emptying time and biopsies of duodenal mucosa, the latter for analysis of calcitriol receptor concentrations. Half of the subjects will be supplemented with 25(OH)vitamin D, to remove the factor of variability in vitamin D status. Our hypothesis is that much of the interindividual variation will be found to reside at the intestinal level, rather than in the various regulatory hormones and co-factors; but we will have to check to be certain, and regardless of where the variability resides, these protocols will develop useful information on relationships among the components of the system of absorptive regulation and adaptation. The second and third protocols will evaluate the process of adaptation to changing intake and the dose response relationship for calcitriol. The fourth will explore the hyperabsorption of citrate and other very soluble salts. Given the relatively low calcium intakes typical of American women, and the increasing recognition of the importance of maintaining an adequate calcium intake throughout life, it has become increasingly important to understand the reasons why some women absorb calcium efficiently and others do not.
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