Human calcium absorption

The steroid hormone 1,25-dihydroxy vitamin D3 (calcitriol) slowly increases both intestinal calcium absorption and bone resorption, and is also stimulated through low calcium levels. In contrast, calcitonin rapidly inhibits osteoclast activity and thus decreases serum calcium levels. Calcitonin is secreted by the clear cells of the thyroid and inhibits osteoclast activity by increasing the intracellular cyclic AMP content via binding to a specific cell surface receptor, thus causing a contraction of the resorbing cell membrane. The biological relevance of calcitonin in human calcium homeostasis is not well established. 

Calcium absorption data are needed from animal and human subjects having similar nutritional and physiological characteristics and which have consumed identical calcium sources. 

An attempt was made to collate data on human and rat apparent calcium absorption values for several calcium sources. Absorption values were so variable within species and calcium sources that a correlation could not be justified. Much of this variability may be due to methodological differences between the design of the rat and the human experiments. Most of the animal experiments were conducted using rapidly growing rats which were fed modest amounts of calcium but which have high calcium requirements. 

Some degree of standardization of methodologies for rats and human experimentation must be done before a reasonable comparison can be made on the correlation between the calcium absorption responses of these two species. 

Table I. Comparison of Various Dietary and Physiological Factors on Apparent Calcium Absorption by Rats and Humans...

Isotopic methods for estimating calcium absorption have been evaluated by several researchers (49,55-58). From the human data of Harrison et al. (55), the relationship between percent calcium absorption determined by isotope dilution (Y) and excreta counting... 

Since the early 1970 s, research has been directed at identifying the mechanism by which the calciuria is induced. Attention was given first to the question of whether the elevated urinary calcium excretion was caused by an increase in the intestinal absorption of calcium. Results of calcium balance studies in human subjects showed that protein ingestion either had no effect on calcium absorption (4) or that the effect was insufficient to account for the calciuria (5j. Consequently, negative calcium balance is a frequent observation in human studies when high protein diets are fed, and this situation is not improved by high calcium intakes (4 ). 

More than 40 years ago, calcium absorption from brown (whole wheat) bread which was fed to human subjects was found to be poorer than was that when white (extracted wheat flour) was fed 04,5). Since then, many studies have sought to define the extent of inhibition of calcium intestinal bioavailability by various forms of dietary fiber with mixed results and conclusions (6-18). 

Most of the forementioned studies which examined the influence of various dietary fiber on the bioavailability of calcium by human subjects have depended upon the comparative measurements of calcium content of diets and calcium contents of stools and urine. As reviewed by Allen (3), calcium balance studies have distinct limitations relative to accuracy and precision. However, their ease of application and cost, laboratory equipment requirements, and real (or perceived) safety in comparison to available radioactive or stable isotope methods continue to make their use popular. In calcium balance studies, calcium absorption is assumed to be the difference between calcium excretion in the feces and calcium intake. Usually this is expressed as a percent of the calcium intake. This method assumes that all fecal calcium loss is unabsorbed dietary calcium which is, of course, untrue since appreciable amounts of calcium from the body are lost via the intestinal route through the biliary tract. Hence, calcium absorption by this method may underestimate absorption of dietary calcium but is useful for comparative purposes. It has been estimated that bile salts may contribute about 100 g calcium/day to the intestinal calcium contents. Bile salt calcium has been found to be more efficiently absorbed through the intestinal mucosa than is dietary calcium (20) but less so by other investigators (21). 

Interest in the possible connection between intake of fat and absorption of calcium was generated by the concurrent massive losses of calcium in patients with steatorrhea, fatty diarrhea (46, 47). Ordinarily, however, fat is very efficiently absorbed from the gastrointestinal tract. Results of several studies in human adults and children indicate little or no effect of level of dietary fat on absorption of calcium (48-54). However, influence of level of dietary fat on calcium absorption in rat studies has produced conflicting results (55-57). 

Several studies have been conducted on calcium-fat interactions in human infants (64-70). Low synthesis of bile salts and low pancreatic lipase activity may be responsible for poorer fat utilization in infants than in adults (63,71). Fat from infant formulas may be lower than that from human milk because of the lack of a bile-stimulated lipase in the former (72). In infants, fat absorption tends to decrease with increase in fatty acid length, with lower degree of saturation, and with increase of total fat (3). Triglyceride structure may also influence fat absorption in the infant and, thus, indirectly, might also affect calcium absorption in the infant. 

As shown in Table III, mean fecal calcium losses tended to be higher when the higher fat diet was fed in comparison to results when the lower fat diet was fed. Therefore, apparent calcium absorption was higher when the low fat diet was fed. These differences were significant at only the P< 0.075 level hence, only a trend was illustrated. In this study no attempt was made to equalize fatty acid proportionality patterns or cholesterol intake. These or other dietary or non-dietary factors may have influenced the observed apparent trends. Other studies with human adults have not demonstrated any apparent influence on level of dietary fat on calcium absorption. 

Hicks, P. D., and Abrams, S. A. (2006). Formula-fed full term infants have lower fractional absorption but greater total calcium absorption than human milk-fed infants. FASEB ]. 20, A991. 

Ireland, P., and Fordtran, J. S. (1973). Effect of dietary calcium and age on jejunal calcium absorption in humans studied by intestinal perfusion. /. Clin. Invest. 52, 2672-2681. 

HV167 Fredlund K., E. L. Bergman, L. Rossander-Hulthen, M. Isaksson, A. Almgren, and A. S. Sandberg. Hydro-thermal treatment and malting of barley improved zinc absorption but not calcium absorption in humans. Eur J Clin Nutr 2003 57(12) 1507-1513. 

There is some evidence, mostly from animal studies, to suggest that high dietary levels of phosphorus, especially if dietary levels of calcium are low, may adversely affect bone mass and calcium metabolism (Greger and Krystofiak 1982). However, in humans there is little direct evidence to indicate that large variations in dietary phosphorus or in the Ca P ratio have any significant influence on calcium utilization or balance (Heaney et al. 1982). Some preliminary findings, however, suggest that the form of phosphorus may influence calcium absorption (Zemel et al. 1982). Hexametaphosphate, as compared with orthophos-... 

The rate of calcium absorption by the intestines was measuied in human subjects by releasing calciurn into the gut using long tubes and measuring the rate of disappearance (absorption) of the calcium by withdrawing small samples of the fluids of the gut lumen and analyzing the fluids. State evidence that the body s response m a low-calcium diet includes a change in the efficiency of absorption by the gut (see Table 9.6). 

Calcium absorption may be influenced by the solubility of the specific calcium salt. Rates of absorption of calcium from calcium salts, such as Ca acetate, Ca lactate, Ca gluconate, Ca citrate, and Ca carbonate, seem to be similar and to fall in the range 25 to 40%. These values were determined in studies with humans in the absence of a concurrent meal (Sheikh el al., 1987). The test dose contained 5CX) mg of Ca. The absorbability of the calcium in whole milk falls in this range and is about 30%. 

Postprandial glucose-dependent insulinotropic polypeptide (GIP) levels were lowered in a guar-gum-supplemented meal (Morgan et al., 1990) and may contribute to lower insulin levels. Guar delays intestinal calcium absorption in humans (Gulliford et al., 1988b). The decrease in pancreatic amylase release may simply be a result of diminished insular-exocrine axis. 

It is a well-known fact that fractional absorption of calcium in man ranges from 20 to 70% (Heaney etal. 1990). A number of studies have also shown there to be a decrease in the rate of fractional absorption of calcium with increasing age (for a review, see Armbrecht 1990). Adaptation of intestinal calcium absorption to changes in calcium intake via the vitamin D endocrine system has also been demonstrated in human subjects (Sheikh etal. 1990). A low serum Ca level stimulates the renal synthesis of 1,25(OH)2Dj (Fraser 1980), which in turn leads to increased absorption of calcium from the intestinal lumen. It is through this mechanism that the fractional absorption of calcium from the intestine... 

Bargee-Lux MJ, Heaney RP and Recker RR (1989) Time course of calcium absorption in humans evidence for a colonic component. Calcif Tissue Int 44 308-311. 

Norman (152) in 1977 reported that la,24(i ),25-trihydroxyvitamin D3 is less potent than la,25-dihydroxyvitamin D3 in the rachitic chick in terms of its ability to stimulate intestinal calcium absorption, mobilize bone calcium, and induce intestinal calcium binding protein. DeLuca (27) had shown earlier that 24,25-dihydroxyvitamin D3 must be converted to la,24,25-trihydroxyvitamin D3 in the kidney in order to have biological activity. Gray (62) in 1974 had demonstrated presence of a peak in the analysis of the plasma of normal and nephrectomized humans given H-labeled 25-hydroxyvitamin D3, which was chromatographically similar to authentic la,24,25-trihydroxyvitamin D3. DeLuca 182) has recently shown that the renal 24-hydroxylase enzyme requires presence of a hydroxyl group be on the 25-carbon of the vitamin D3 molecule before further hydroxylation can take place. The 24(i )-hydroxylase is, however, not totally isolated in the kidney as the la-hydroxylase appears to be. DeLuca 182) finds that nephrectomized animals also metabolize la,25-dihydroxyvitamin D3 to la,24(i ),25-trihydroxyvitamin D3. 

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