Inhibitory effects of dietary calcium on the initial uptake and subsequent retention of heme and nonheme iron in humans: comparisons using an intestinal lavage method.

BACKGROUND: Calcium is the only reported dietary inhibitor of both heme- and nonheme-iron absorption. It has been proposed that the 2 forms of iron enter a common pool in the enterocyte and that calcium inhibits the serosal transfer of iron into blood. OBJECTIVES: We aimed to ascertain whether the inhibitory effect of calcium occurs during initial mucosal uptake or during serosal transfer and to compare the serosal transfer of heme and nonheme iron, which should not differ if the 2 forms have entered a common mucosal iron pool. DESIGN: Whole-gut lavage and whole-body counting were used to measure the initial uptake (8 h) and retention (2 wk) of heme and nonheme iron with and without a calcium supplement (450 mg). Two experiments tested basal meals with low iron bioavailability and 360 mg Ca (n = 15) or with high iron bioavailability and 60 mg Ca (n = 12). RESULTS: Added calcium reduced the initial uptake of heme iron by 20%, from 49% to approximately 40% from both meals (P = 0.02), and reduced the total iron absorbed from the low- and high-bioavailability meals by approximately 25% [from 0.033 to 0.025 mg (P = 0.06) and from 0.55 to 0.40 mg (P < 0.01), respectively]. Calcium did not affect the serosal transfer of either form of iron. CONCLUSIONS: Calcium supplementation reduced heme and total iron without significantly affecting nonheme-iron absorption, regardless of meal bioavailability. Calcium inhibited the initial mucosal uptake rather than the serosal transfer of heme iron. Differences in serosal transfer indicate that heme and nonheme iron did not enter a common absorptive pool within 8 h after a meal.

Increased contractility of cardiomyocytes from copper-deficient rats is associated with upregulation of cardiac IGF-I receptor.

Hearts from severely Cu-deficient rats show a variety of pathological defects, including hypertrophy and, in intact hearts, depression of contractile function. Paradoxically, isolated cardiomyocytes from these rats exhibit enhanced contractile properties. Because hypertrophy and enhanced contractility observed with other pathologies are associated with elevation of insulin-like growth factor-I (IGF)-I, this mechanism was examined for the case of dietary Cu deficiency. Male, weanling Sprague-Dawley rats were provided diets that were deficient (approximately 0.5 mg Cu/kg diet) or adequate (approximately 6 mg Cu/kg diet) in Cu for 5 wk. IGF-I was measured in serum and hearts by an ELISA method, cardiac IGF-I and IGF-II receptors and IGFBP-3 were measured by Western blotting analysis, and mRNAs for cardiac IGF-I and IGF-II were measured by RT-PCR. Contractility of isolated cardiomyocytes was assessed by a video-based edge-detection system. Cu deficiency depressed serum and heart IGF-I and heart IGFBP-3 protein levels and increased cardiac IGF-I receptor protein. Cardiac IGF-II protein and mRNA for cardiac IGF-I and IGF-II were unaffected by Cu deficiency. A Cu deficiency-induced increase in cardiomyocyte contractility, as indicated by increases in maximal velocities of shortening (-dL/dt) and relengthening (+dL/dt) and decrease in time to peak shortening (TPS), was confirmed. These changes were largely inhibited by use of H-1356, an IGF-I receptor blocker. We conclude that enhanced sensitivity to IGF-I, as indicated by an increase in IGF-I receptor protein, accounts for the increased contractility of Cu-deficient cardiomyocytes and may presage cardiac failure.

Controlled substitution of soy protein for meat protein: effects on calcium retention, bone, and cardiovascular health indices in postmenopausal women.

In a controlled feeding study, the effects of substituting 25 g soy protein for meat on calcium retention and bone biomarkers were determined. Postmenopausal women (n = 13) ate two diets that were similar, except that, in one diet, 25 g high-isoflavone soy protein (SOY) was substituted for an equivalent amount of meat protein (control diet), for 7 wk each in a randomized crossover design. After 3 wk of equilibration, calcium retention was measured by labeling the 2-d menu with (47)Ca, followed by whole-body counting for 28 d. Urinary calcium and renal acid excretion were measured at wk 3, 5, and 7. Biomarkers of bone and cardiovascular health were measured at the beginning and end of each diet. Calcium was similarly retained during the control and SOY diets (d 28, percent dose, mean +/- pooled sd: 14.1 and 14.0 +/- 1.6, respectively). Despite a 15-20% lower renal acid excretion during the SOY diet, urinary calcium loss was unaffected by diet. Diet also did not affect any of the indicators of bone or cardiovascular health. Substitution of 25 g high isoflavone soy protein for meat, in the presence of typical calcium intakes, did not improve or impair calcium retention or indicators of bone and cardiovascular health in postmenopausal women.

Controlled high meat diets do not affect calcium retention or indices of bone status in healthy postmenopausal women.

Calcium balance is decreased by an increased intake of purified proteins, although the effects of common dietary sources of protein (like meat) on calcium economy remain controversial. We compared the effects of several weeks of controlled high and low meat diets on body calcium retention, using sensitive radiotracer and whole body scintillation counting methodology. Healthy postmenopausal women (n = 15) consumed diets with similar calcium content (approximately 600 mg), but either low or high in meat (12 vs. 20% of energy as protein) for 8 wk each, in a randomized crossover design. After 4 wk of equilibration of each diet, calcium retention was measured by extrinsically labeling the 2-d menu with (47)Ca, followed by whole body scintillation counting for 28 d. Urinary and blood indicators of bone metabolism were also determined for each diet. Calcium retention was not different during the high and low meat dietary periods (d 28, mean +/- pooled SD: 17.1 and 15.6%, +/-0.6%, respectively; P = 0.09). An initially higher renal acid excretion in subjects consuming the high meat compared with the low meat diet decreased significantly with time. The diets did not affect urinary calcium loss or indicators of bone metabolism. In conclusion, under controlled conditions, a high meat compared with a low meat diet for 8 wk did not affect calcium retention or biomarkers of bone metabolism in healthy postmenopausal women. Calcium retention is not reduced when subjects consume a high protein diet from common dietary sources such as meat.

Initial uptake and absorption of nonheme iron and absorption of heme iron in humans are unaffected by the addition of calcium as cheese to a meal with high iron bioavailability.

BACKGROUND: Quantitative data on the mucosal uptake and serosal transfer of nonheme-iron absorption in humans and the effects of calcium on these components are limited. OBJECTIVE: Our objective was to measure the initial mucosal uptake and the subsequent serosal transfer of nonheme iron and to determine the effects of adding calcium to a meal on both heme- and nonheme-iron retention. DESIGN: Whole-gut lavage and whole-body scintillation counting methods were applied to determine the 8-h uptake of nonheme iron and the 2-wk retention (absorption) of heme and nonheme iron in healthy adults (n = 17) after the consumption of meals of radiolabeled food. RESULTS: The initial uptake and absorption of nonheme iron were 11% and 7%, respectively, and the absorption of heme iron was 15%. Two-thirds of the nonheme iron taken up by the mucosa within 8 h was retained by the body after 2 wk (serosal transfer index: 0.63). Serum ferritin correlated inversely with the initial uptake and absorption of nonheme iron, but not with the nonheme serosal transfer index or the absorption of heme iron. Adding calcium (127 mg in cheese) to the meal did not affect absorption. CONCLUSIONS: On the basis of its association with serum ferritin, the initial mucosal uptake was the primary control point for nonheme-iron absorption. An apparent reduction in heme-iron absorption associated with the lavage procedure suggested that uptake of heme iron may take longer and proceed further through the intestine than that of nonheme iron. The absorption of both forms of iron was unaffected by the addition of cheese to this meal with high iron bioavailability.