Physiology of Absorption, Metabolism, and Excretion

Calcium is absorbed by active transport and passive diffusion across the intestinal mucosa. Active transport of calcium into enterocytes and out on the serosal side is dependent on the action of 1,25-dihydroxyvitamin D (1,25(OH)2D), the active form of vitamin D, and its intestinal receptors. This mechanism accounts for most of the absorption of calcium at low and moderate intake levels. Passive diffusion involves the movement of calcium between mucosal cells and is dependent on the luminal:serosal calcium concentration gradient. Passive diffusion becomes more important at high calcium intakes (Ireland and Fordtran, 1973).

It has long been recognized that fractional calcium absorption varies inversely with dietary calcium intake (Ireland and Fordtran, 1973; Malm, 1958; Spencer et al., 1969). For example, when calcium intake was acutely lowered from 2,000 to 300 mg (50 to 7.5 mmol)/day, healthy women increased their fractional whole body retention of ingested calcium, an index of calcium absorption, from 27 percent to about 37 percent (Dawson-Hughes et al., 1993). This adaptation required 1 to 2 weeks and was accompanied by a decline in serum calcium and a rise in serum parathyroid hormone (PTH) and 1,25(OH)2D concentrations. In general, the adaptive rise in the fraction of calcium absorbed as intake is lowered is not sufficient to offset the loss in absorbed calcium that occurs with a decrease in calcium intake, however modest that decrease. This is clear from the demonstrations that absorbed calcium and calcium intake, throughout a wide intake range, are positively related (Gallagher et al., 1980; Heaney et al., 1975).

Fractional calcium absorption varies through the lifespan. It is highest (about 60 percent) in infancy (Abrams et al., 1997a; Fomon and Nelson, 1993) and rises again in early puberty. Abrams and Stuff (1994) found fractional absorption in Caucasian girls consuming a mean of about 925 mg (23.1 mmol)/day of calcium to average 28 percent in prepubertal children, 34 percent in early puberty (the age of the growth spurt), and 25 percent 2 years later. Fractional absorption remains at about this value (25 percent) in young adults, with the exception that it increases during the last two trimesters of pregnancy (Heaney et al., 1989). With aging, fractional absorption gradually declines. In postmenopausal women, fractional absorption declined by an average of 0.21 percent/year (Heaney et al., 1989). Bullamore and colleagues (1970) reported that men lose absorption efficiency with aging at about the same rate as women.

Renal calcium excretion is a function of the filtered load and the



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