Abstract
It has been suggested that calcium inhibits the absorption of dietary iron by directly affecting enterocytes. However, it is not clear if this effect is due to a decreased uptake of iron or its efflux from enterocytes. We studied the effect of calcium on the uptake, efflux, and net absorption of non-heme iron using the intestinal-like epithelial cell line Caco-2 as an in vitro model. Caco-2 cells were incubated for 60 min in a buffer supplemented with non-heme iron (as sulfate) and calcium to achieve calcium to iron molar ratios ranging from 50:1 to 1,000:1. The uptake, efflux, and net absorption of non-heme iron were calculated by following a radioisotope tracer of 55Fe that had been added to the buffer. Administration of calcium and iron at molar ratios between 500 and 1,000:1 increased the uptake of non-heme iron and decreased efflux. Calcium did not have an effect on the net absorption of non-heme iron. At typical supplementary doses for calcium and non-heme iron, calcium may not have an effect on the absorption of non-heme iron. The effect of higher calcium to iron molar ratios on the efflux of non-heme iron may be large enough to explain results from human studies.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Sharp P, Srai SK (2007) Molecular mechanisms involved in intestinal iron absorption. World J Gastroenterol 13(35):4716–4724
Disler PB, Lynch SR, Charlton RW, Torrance JD, Bothwell TH, Walker RB, Mayet F (1975) The effect of tea on iron absorption. Gut 16(3):193–200
Hurrell RF, Juillerat MA, Reddy MB, Lynch SR, Dassenko SA, Cook JD (1992) Soy protein, phytate, and iron absorption in humans. Am J Clin Nutr 56(3):573–578
Layrisse M, Martinez-Torres C (1972) Model for measuring dietary absorption of heme iron: test with a complete meal. Am J Clin Nutr 25(4):401–411
Lynch SR, Dassenko SA, Cook JD, Juillerat MA, Hurrell RF (1994) Inhibitory effect of a soybean-protein–related moiety on iron absorption in humans. Am J Clin Nutr 60(4):567–572
Gibson RS, Yeudall F, Drost N, Mtitimuni BM, Cullinan TR (2003) Experiences of a community-based dietary intervention to enhance micronutrient adequacy of diets low in animal source foods and high in phytate: a case study in rural Malawian children. J Nutr 133(11 Suppl 2):3992S–3999S
Hallberg L, Brune M, Erlandsson M, Sandberg AS, Rossander-Hulten L (1991) Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans. Am J Clin Nutr 53(1):112–119
Shawki A, Mackenzie B (2010) Interaction of calcium with the human divalent metal-ion transporter-1. Biochem Biophys Res Commun 393(3):471–475
Thompson BA, Sharp PA, Elliott R, Fairweather-Tait SJ (2010) Inhibitory effect of calcium on non-heme iron absorption may be related to translocation of DMT-1 at the apical membrane of enterocytes. J Agric Food Chem 58(14):8414–8417. doi:10.1021/jf101388z
Hallberg L, Rossander-Hulthen L, Brune M, Gleerup A (1993) Inhibition of haemiron absorption in man by calcium. Br J Nutr 69(2):533–540
Rouault TA (2005) The intestinal heme transporter revealed. Cell 122(5):649–651. doi:10.1016/j.cell.2005.08.027
Looker A (2006) Dietary calcium. In: Weaver C, Heaney R (eds) Calcium in human health. Humana Press, Totawa, pp 105–127
Weaver CM (2009) Closing the gap between calcium intake and requirements. J Am Diet Assoc 109(5):812–813
Disler PB, Lynch SR, Torrance JD, Sayers MH, Bothwell TH, Charlton RW (1975) The mechanism of the inhibition of iron absorption by tea. S Afr J Med Sci 40(4):109–116
Lynch SR (1997) Interaction of iron with other nutrients. Nutr Rev 55(4):102–110
Lynch SR, Dassenko SA, Morck TA, Beard JL, Cook JD (1985) Soy protein products and heme iron absorption in humans. Am J Clin Nutr 41(1):13–20
Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388(6641):482–488
Cook JD, Morck TA, Lynch SR (1981) The inhibitory effect of soy products on nonheme iron absorption in man. Am J Clin Nutr 34(12):2622–2629
Fleming RE, Bacon BR (2005) Orchestration of iron homeostasis. N Engl J Med 352(17):1741–1744. doi:10.1056/NEJMp048363
McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, Barrow D, Miret S, Bomford A, Peters TJ, Farzaneh F, Hediger MA, Hentze MW, Simpson RJ (2000) A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 5(2):299–309. doi:S1097-2765(00)80425-6
Cook JD, Dassenko SA, Whittaker P (1991) Calcium supplementation: effect on iron absorption. Am J Clin Nutr 53(1):106–111
Cook JD, Layrisse M, Finch CA (1969) The measurement of iron absorption. Blood 33(3):421–429
Kalkwarf HJ, Harrast SD (1998) Effects of calcium supplementation and lactation on iron status. Am J Clin Nutr 67(6):1244–1249
Molgaard C, Kaestel P, Michaelsen KF (2005) Long-term calcium supplementation does not affect the iron status of 12–14-y-old girls. Am J Clin Nutr 82(1):98–102
Minihane AM, Fairweather-Tait SJ (1998) Effect of calcium supplementation on daily nonheme-iron absorption and long-term iron status. Am J Clin Nutr 68(1):96–102
INACG (1998) Guidelines for the use of iron supplements to prevent and treat iron deficiency anemia. 18–21
Acknowledgment
This work was supported by grants from Fondecyt 1095038 and Mecesup 313.
Author information
Authors and Affiliations
Corresponding author
Additional information
The corresponding author states that all other authors have read the manuscript and have agreed to submit it in its current form for consideration for publication in Biological Trace Element Research.
Rights and permissions
About this article
Cite this article
Gaitán, D.A., Flores, S., Pizarro, F. et al. The Effect of Calcium on Non-heme Iron Uptake, Efflux, and Transport in Intestinal-like Epithelial Cells (Caco-2 Cells). Biol Trace Elem Res 145, 300–303 (2012). https://doi.org/10.1007/s12011-011-9207-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-011-9207-6