Calcium is absorbed by active transport (transcellularly) and by passive diffusion (paracellularly) across the intestinal mucosa. Active transport of calcium is dependent on the action of calcitriol and the intestinal vitamin D receptor (VDR). This transcellular mechanism is activated by calcitriol and accounts for most of the absorption of calcium at low and moderate intake levels. Transcellular transport occurs primarily in the duodenum where the VDR is expressed in the highest concentration, and is dependent on up-regulation of the responsive genes including the calcium transport protein called transient receptor potential cation channel, vanilloid family member 6 or TRPV6 (Li et al., 1993; Xue and Fleet, 2009). These features—up-regulation of VDR and TRPV6—are most obvious during states in which a high efficiency of calcium absorption is required.
Passive diffusion or paracellular uptake involves the movement of calcium between mucosal cells and is dependent on luminal:serosal electrochemical gradients. Passive diffusion occurs more readily during higher calcium intakes (i.e., when luminal concentrations are high) and can occur throughout the length of the intestine (Ireland and Fordtran, 1973). However, the permeability of each intestinal segment determines passive diffusion rates. The highest diffusion of calcium occurs in the duodenum, jejunum, and ileum (Weaver and Heaney, 2006b).
From a recent series of controlled metabolic studies undertaken by the USDA, mean calcium absorption (also referred to as “fractional calcium absorption,” which is the percentage of a given dose of calcium that is absorbed) in men and non-pregnant women—across a wide age range—has been demonstrated to be approximately 25 percent of calcium intake (Hunt and Johnson, 2007). Mean urinary loss averages 22 percent and fecal loss 75 percent of total calcium intake, with minor losses from sweat, skin, hair, etc. In general, mean calcium absorption and calcium intake are directly related (Heaney et al., 1975; Gallagher et al., 1980; Hunt and Johnson, 2007). However, fractional calcium absorption varies inversely with calcium intake when the intake is very low (Malm, 1958; Spencer et al., 1969; Ireland and Fordtran, 1973). For example, when calcium intake was lowered from 2,000 to 300 mg, 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 type of adaptation occurs within 1 to 2 weeks and is accompanied by a decline in serum calcium concentration and a rise in serum PTH and calcitriol concentrations (see section below titled “Homeostatic Regulation of Calcium”). The fraction of calcium absorbed rises adaptively as intake