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The effect of calcium on iron absorption

  • Sean R Lynch (a1)
Abstract

The experimental and epidemiological evidence demonstrating that Ca inhibits Fe absorption was reviewed, with the objectives of estimating the potential impact of variations in Ca intake on dietary Fe bioavailability and of providing some guidelines for predicting the effects on Fe status of recent recommendations for higher dietary Ca intake. In animal models Ca salts reduced both haem- and non-haem-Fe absorption, the effect being dependent on the amount of Ca administered rather than the Ca:Fe molar ratio; dairy products had a variable effect; factors other than Ca may have been important. In single-meal human absorption studies, both haem- and non-haem-Fe absorption was inhibited by Ca supplements and by dairy products, the effect depending on the simultaneous presence of Ca and Fe in the lumen of the upper small intestine and also occurring when Ca and Fe were given in the fasting state. The quantitative effect, although dose dependent, was modified by the form in which Ca was administered and by other dietary constituents (such as phosphate, phytate and ascorbic acid) known to affect Fe bioavailability. The mechanism by which Ca influences Fe absorption has not been elucidated. The effects of factors that modulate Fe bioavailability are known to be exaggerated in single-meal studies, and measurements based on several meals are more likely to reflect the true nutritional impact. The results of most multiple-meal human studies suggest that Ca supplementation will have only a small effect on Fe absorption unless habitual Ca consumption is very low. Outcome analyses showed that Ca supplements had no effect on Fe status in infants fed Fe-fortified formula, lactating women, adolescent girls and adult men and women. However it should be noted that the subjects studied had adequate intakes of bioavailable Fe and, except in one study, had relatively high habitual Ca intakes. Although cross-sectional analyses in Europe have shown a significant inverse correlation between Ca intake (derived primarily from dairy foods) and Fe stores, the quantitative effect was relatively small. The general conclusion is that dietary Ca supplements are unlikely to have a biologically significant impact on Fe balance in Western societies unless Ca consumption is habitually very low; however, increased consumption of dairy products may have a small negative effect that could be functionally important in pregnancy if Fe supplements are not taken. It is uncertain whether the inverse relationship between consumption of dairy products and Fe status is due entirely to increased Ca intake; substitution of milk proteins for meat may also have negative effects on Fe balance.

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References
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Ames, SK, Gorham, BM & Abrams, SA (1999) Effects of high compared with low calcium intake on calcium absorption and incorporation of iron by red blood cells in small children. American Journal of Clinical Nutrition 70, 4448.
Amine, EK & Hegsted, DM (1971) Effect of diet on iron absorption in iron-deficient rats. Journal of Nutrition 101, 927936.
Anderson, HD, McDonough, KB & Elvehjem, CA (1940) Relation of the dietary calcium–phosphorus ratio to iron assimilation. Journal of Laboratory and Clinical Medicine 25, 464471.
Apte, SV & Venkatachalam, PS (1964) The influence of dietary calcium on absorption of iron. Indian Journal of Medical Research 52, 213218.
Barger-Lux, MJ (1991) Calcium supplementation and iron absorption. American Journal of Clinical Nutrition 54, 607.
Barrett, JFR, Whittaker, PG, Williams, JG & Lind, T (1994) Absorption of non-haem iron from food during normal pregnancy. British Medical Journal 309, 7982.
Barton, JC, Conrad, ME & Parmley, RT (1983) Calcium inhibition of inorganic iron absorption in rats. Gastroenterology 84, 90101.
Baynes, RD 1994 Iron deficiency. In Iron Metabolism in Heath and Disease, pp. 189225 [Brock, JH, Halliday, JW, Pippard, MJ and Powell, LW, editors]. London: WB Saunders Company Ltd..
Bothwell, TH, Charlton, RW, Cook, JD & Finch, CA 1979 Iron Metabolism in Man. Oxford: Blackwell Scientific Publications.
Bronner, F & Pansu, D (1999) Nutritional aspects of calcium absorption. Journal of Nutrition 129, 912.
Canonne-Hergaux, F, Gruenheid, S, Ponka, P & Gros, P (1999) Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. Blood 93, 44064417.
Carafoli, E (1994) Biogenesis: plasma membrane calcium ATPase: 15 years of work on the purified enzyme. FASEB Journal 8, 9931002.
Center for Nutrition Policy and Promotion, US Department of Agriculture (1996) Nutrient Content of the U.S. Food Supply, 1990–1994. Preliminary Data. Washington, DC: US Department of Agriculture.
Chapman, DG & Campbell, JA (1957) Effect of bone meal on the utilization of iron by anaemic rats. British Journal of Nutrition 11, 117126.
Chapman, DG & Campbell, JA (1957) Effect of calcium and phosphorus salts on the utilization of iron by anaemic rats. British Journal of Nutrition 11, 127133.
Cleveland, LE, Goldmann, JD and Borrud, LG 1996 Data Tables: Results from USDA's 1994 Continuing Survey of Food Intakes by Individuals and 1994 Diet and Health Knowledge Survey. Beltsville, MD: Agricultural Research Service, US Department of Agriculture.
Conrad, ME & Umbreit, JN (1993) A concise review: iron absorption — the mucin–mobilferrin–integrin pathway. A competitive pathway for metal absorption. American Journal of Hematology 42, 6773.
Cook, JD (1990) Adaptation in iron metabolism. American Journal of Clinical Nutrition 51, 301308.
Cook, JD, Dassenko, SA & Lynch, SR (1991) Assessment of the role of nonheme-iron availability in iron balance. American Journal of Clinical Nutrition 54, 717722.
Cook, JD, Dassenko, SA & Whittaker, P (1991) Calcium supplementation: effect on iron absorption. American Journal of Clinical Nutrition 53, 106111.
Cook, JD & Monsen, ER (1976) Food iron absorption in human subjects. III. Comparison of the effect of animal proteins on nonheme iron absorption. American Journal of Clinical Nutrition 29, 859867.
Crowther, RS, Marriott, C & James, SL (1984) Cation induced changes in the rheological properties of purified mucus glycoprotein gels. Biorheology 21, 253263.
Dallman, PR 1992 Changing iron needs from birth through adolescence. In Nutritional Anemias, Nestlé Nutrition Workshop Series 30 pp. 2938. [Fomon, SJ and Zlotkin, S, editors]. New York: Vevey/Raven Press Ltd.
Dalton, MA, Sargent, JD, O'Connor, GT, Olmstead, EM & Klein, RZ (1997) Calcium and phosphorus supplementation of iron-fortified infant formula: no effect on iron status of healthy full-term infants. American Journal of Clinical Nutrition 65, 921926.
Dawson-Hughes, B, Seligson, FH & Hughes, VA (1986) Effects of calcium carbonate and hydroxyapatite on zinc and iron retention in postmenopausal women. American Journal of Clinical Nutrition 44, 8388.
Deehr, MS, Dallal, GE, Smith, KT, Taulbee, JD and Dawson-Hughes, B (1990) Effect of different calcium sources on iron absorption in postmenopausal women. American Journal of Clinical Nutrition 51, 9599.
DeMaeyer, E and Adiels-Tegman, M (1985) The prevalence of anaemia in the world. World Health Statistics Quarterly 38, 302316.
Dorey, C, Cooper, C, Dickson, DPE, Gibson, JF, Simpson, RJ & Peters, TJ (1993) Iron speciation at physiological pH in media containing ascorbate and oxygen. British Journal of Nutrition 70, 157169.
Dunn, JA (1968) The effects of dietary calcium salts and fat on iron absorption in the rat. South African Journal of Medical Science 33, 6570.
Expert Scientific Working Group (1985) Summary of a report on assessment of the iron nutritional status of the United States population. American Journal of Clinical Nutrition 42, 13181330.
Feher, JJ, Fullmer, CS & Wasserman, RH (1992) Role of facilitated diffusion of calcium by calbindin in intestinal calcium absorption. American Journal of Physiology 262, C517–C526.
Fleming, DJ, Jacques, PF, Dallal, GE, Tucker, KL, Wilson, PWF & Wood, RJ (1998) Dietary determinants of iron stores in a free-living elderly population: the Framingham heart study. American Journal of Clinical Nutrition 67, 722733.
Freeman, S & Ivy, AC (1942) The influence of antacids upon iron retention by the anemic rat. American Journal of Physiology 137, 706709.
Fuhr, I & Steenbock, H (1943) The effect of dietary calcium, phosphorus, and vitamin D on the utilization of iron. III. The relation of rickets to anemia. Journal of Biological Chemistry 147, 7175.
Galan, P, Cherouvrier, F, Preziosi, P & Hercberg, S (1991) Effects of the increasing consumption of dairy products upon iron absorption. European Journal of Clinical Nutrition 45, 553559.
Galan, P, Hercberg, S, Soustre, Y, Dop, MC & Dupin, H (1985) Factors affecting iron stores in French female students. Human Nutrition: Clinical Nutrition 39C, 279287.
Galan, P, Yoon, H-C, Preziosi, P, Viteri, F, Valeix, P, Fieux, B, Briancon, S, Malvy, D, Roussel, A-M, Favier, A & Hercberg, S (1998) Determining factors in the iron status of adult women in the SU.VI.MAX study. European Journal of Clinical Nutrition 52, 383388.
Gleerup, A, Rossander-Hulthen, L, Gramatkovski, E & Hallberg, L (1995) Iron absorption from the whole diet: comparison of the effect of two distributions of daily calcium intake. American Journal of Clinical Nutrition 61, 97104.
Grasbeck, R, Kuovonen, I, Lundberg, M & Tehunen, R (1979) An intestinal receptor for heme. Scandinavian Journal of Haematology 23, 59.
Grasbeck, R, Majuri, R, Kuovonen, I & Tenhunen, R (1982) Spectral and other studies on the intestinal haem receptor of the pig. Biochimica et Biophysica Acta 700, 137142.
Green, R, Charlton, RW, Seftel, H, Bothwell, T, Mayet, F, Adams, B, Finch, C & Layrisse, M (1968) Body iron excretion in man. A collaborative study. American Journal of Medicine 45, 336353.
Greenberger, NJ, Balcerzak, SP & Ackerman, GA (1969) Iron uptake by isolated intestinal brush borders: changes induced by alterations in iron stores. Journal of Laboratory and Clinical Medicine 73, 711721.
Greig, WA (1952) The effects of additions of calcium carbonate to the diet of breeding mice. II. Hematology and histopathology. British Journal of Nutrition 6, 280294.
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 338, 482488.
Hallberg, L (1998) Does calcium interfere with iron absorption? American Journal of Clinical Nutrition 68, 34.
Hallberg, L, Bjorn-Rasmussen, E, Howard, L & Rossander, L (1979) Dietary heme iron absorption. A discussion of possible mechanisms for the absorption-promoting effect of meat and for the regulation of iron absorption. Scandinavian Journal of Gastroenterology 14, 769779.
Hallberg, L, Brune, M, Erlandsson, M, Sandberg, A-S and Rossander-Hulten, L (1991) Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans. American Journal of Clinical Nutrition 53, 112119.
Hallberg, L, Brune, M & Rossander, L (1989) Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate. American Journal of Clinical Nutrition 49, 140144.
Hallberg, L & Hulten, L (2000) Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. American Journal of Clinical Nutrition 71, 11471160.
Hallberg, L & Rossander, L (1982) Effect of different drinks on the absorption of non-heme iron from composite meals. Human Nutrition Applied Nutrition 36, 116123.
Hallberg, L and Rossander-Hulten, L (1991) Iron requirements in menstruating women. American Journal of Clinical Nutrition 54, 10471058.
Hallberg, L, Rossander-Hulten, L, Brune, M & Gleerup, A (1992) Calcium and iron absorption: mechanism of action and nutritional importance. European Journal of Clinical Nutrition 46, 317327.
Hallberg, L, Rossander-Hulten, L, Brune, M & Gleerup, A (1992) Bioavailability in man of iron in human milk and cows' milk in relation to their calcium contents. Pediatric Research 31, 524527.
Hallberg, L, Rossander-Hulten, L, Brune, M & Gleerup, A (1992) Inhibition of haem-iron absorption in man by calcium. British Journal of Nutrition 69, 533540.
Han, O, Failla, ML, Hill, AD, Morris, ER & Smith, JC (1995) Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells. Journal of Nutrition 125, 12911299.
Hazell, T (1985) Minerals in foods: dietary sources, chemical forms, interactions, bioavailability. World Review of Nutrition and Dietetics 46, 1123.
Heaney, RP, Smith, KT, Recker, RR & Hinders, SM (1989) Meal effects on calcium absorption. American Journal of Clinical Nutrition 49, 372376.
Hurrell, RF, Juillerat, MA, Reddy, MB, Lynch, SR, Dassenko, SA & Cook, JD (1992) Soy protein, phytate, and iron absorption in humans. American Journal of Clinical Nutrition 56, 573578.
Hurrell, RF, Lynch, SR, Trinidad, TP, Dassenko, SA & Cook, JD (1989) Iron absorption as influenced by bovine milk proteins. American Journal of Clinical Nutrition 49, 546552.
Ilich-Ernst, JZ, McKenna, AA, Badenhop, NE, Clairmont, AC, Andon, MB, Nahhas, RW, Goel, P & Matkovic, V (1998) Iron status, menarche, and calcium supplementation in adolescent girls. American Journal of Clinical Nutrition 68, 880887.
Jackson, LS & Lee, K (1992) The effect of dairy products on iron availability. Critical Reviews in Food Science and Nutrition 31, 259270.
Jordan, I & Kaplan, J (1994) The mammalian transferrin-independent iron transport system may involve a surface ferrireductase activity. Biochemical Journal 302, 875879.
Kalkwarf, HJ & Harrast, SD (1998) Effects of calcium supplementation and lactation on iron status. American Journal of Clinical Nutrition 67, 12441249.
Kletzein, SW (1935) The influence on iron assimilation of some of the elements in groups 1 and 2 of the periodic system. Journal of Nutrition 9, Suppl., 9.
Kletzein, SW (1938) The influence of calcium and phosphorus on iron assimilation. Journal of Nutrition 15, Suppl., 16.
Kletzein, SW (1940) I. The role of calcium in iron assimilation. Journal of Nutrition 19, 187197.
Layrisse, M, Martinez-Torres, C, Cook, JD, Walker, R & Finch, CA (1973) Iron fortification of food: its measurement by the extrinsic tag method. Blood 41, 3352.
Lonnerdal, B (1997) Effects of milk and milk components on calcium, magnesium and trace element absorption during infancy. Physiological Reviews 77, 643669.
Looker, AC, Dallman, PR, Carroll, MD, Gunter, EW & Johnson, CL (1997) Prevalence of iron deficiency in the United States. Journal of the American Medical Association 227, 973976.
McMillan, JA, Landaw, SA & Oski, FA (1976) Iron sufficiency in breast-fed infants and the availability of iron from human milk. Pediatrics 58, 686691.
McMillan, JA, Oski, FA, Lourie, G, Tomarelli, RM & Landaw, SA (1977) Iron absorption from human milk, simulated human milk, and proprietary formulas. Pediatrics 60, 896900.
Manis, JG & Schachter, D (1962) Active transport of iron by intestine; features of the two-step mechanism. American Journal of Physiology 203, 7380.
Manis, JG & Schachter, D (1962) Active transport of iron by intestine: effects of oral iron and pregnancy. American Journal of Physiology 203, 8186.
Mehansho, H, Kanerva, RL, Hudepohl, GR & Smith, KT (1989) Calcium bioavailability and iron–calcium interaction in orange juice. Journal of the American College of Nutrition 8, 6168.
Minihane, AM and Fairweather-Tait, SJ (1998) Effect of calcium supplementation on daily nonheme-iron absorption and long-term iron status. American Journal of Clinical Nutrition 68, 96102.
Monsen, ER & Cook, JD (1976) Food iron absorption in human subjects. IV. The effects of calcium and phosphate salts on absorption of nonheme iron. American Journal of Clinical Nutrition 29, 11421148.
Moss, AJ, Levy, AS, Kim, I and Park, YK. (1989) Use of Vitamin and Mineral Supplements in the United States: current Users, Types of Products, and Nutrients. Advance Data from Vital and Health Statistics no. 174. Hyattsville, MD: National Center for Health Statistics.
Muir, A & Hopfer, U (1985) Regional specificity of iron uptake by small intestinal brush-border membranes from normal and iron deficient mice. American Journal of Physiology 248, G376–G379.
Nathanson, MH & McLaren, GD (1987) Computer simulation of iron absorption: regulation of mucosal and systemic iron kinetics in dogs. Journal of Nutrition 117, 10671075.
NIH Consensus Development Panel on Optimal Calcium Intake (1994) NIH Consensus Conference. Optimal calcium intake. Journal of the American Medical Association 272, 19421948.
Parmley, RT, Barton, JC, Conrad, ME, Austin, RL & Holland, RM (1981) Ultrastructural cytochemistry and radioautography of hemoglobin-iron absorption. Experimental Molecular Pathology 34, 131144.
Pollack, S, George, JN, Reba, RC, Kaufman, RM & Crosby, WH (1965) The absorption of nonferrous metals in iron deficiency. Journal of Clinical Investigation 44, 14701473.
Prather, TA & Miller, DD (1992) Calcium carbonate depresses iron bioavailability in rats more than calcium sulfate or sodium carbonate. Journal of Nutrition 122, 327332.
Preziosi, P, Hercberg, S, Galan, P, Devanlay, M, Cherouvrier, F & Dupin, H (1994) Iron status of a healthy French population: factors determining biochemical markers. Annals of Nutrition and Metabolism 38, 192202.
Recker, RR (1985) Calcium absorption and achlorhydria. New England Journal of Medicine 313, 7073.
Reddy, MB & Cook, JD (1997) Effect of calcium on nonheme-iron absorption from a complete diet. American Journal of Clinical Nutrition 65, 18201825.
Robinson, S, Godfrey, K, Denne, J & Cox, V (1998) The determinants of iron status in early pregnancy. British Journal of Nutrition 79, 249255.
Root, MM, Hu, J, Stephenson, LS, Parker, RS & Campbell, TC (1999) Iron status of middle-aged women in five countries of rural China. European Journal of Clinical Nutrition 53, 199206.
Rossander, L, Hallberg, L and Bjorn-Rasmussen, E (1979) Absorption of iron from breakfast meals. American Journal of Clinical Nutrition 32, 24842589.
Saarinen, UM, Siimes, MA & Dalman, PR (1977) Iron absorption in infants: high bioavailability of breast milk iron as indicated by the extrinsic tag method of iron absorption and by the concentration of serum ferritin. Journal of Pediatrics 91, 3639.
Seligman, PA, Caskey, JH, Frazier, JL, Zucker, RM, Podell, ER & Allen, RH (1983) Measurements of iron absorption from prenatal multivitamin–mineral supplements. Obstetrics and Gynecology 61, 356362.
Sokoll, LJ and Dawson-Hughes, B (1992) Calcium supplementation and plasma ferritin concentrations in premenopausal women. American Journal of Clinical Nutrition 56, 10451048.
Soustre, Y, Dop, MC, Galan, P & Hercberg, S (1986) Dietary determinants of the iron status in menstruating women. International Journal for Vitamin and Nutrition Research 56, 281286.
Stein, WD (1992) Facilitated diffusion of calcium across the intestinal epithelial cell. Journal of Nutrition 122, Suppl. 3, 651656.
Stekel, A, Monckeberg, F and Beyda, V. (1986) Combating Iron Deficiency in Chile: A Case Study. Washington, DC: International Life Sciences Institute–Nutrition Foundation.
Takkunen, H (1976) Iron deficiency in the Finnish adult population. Scandinavian Journal of Haematology 25, 187.
Tidehag, P, Sandberg, A-S, Hallmans, G, Wing, K, Turk, M, Holm, S & Grahn, E (1995) Effect of milk and fermented milk on iron absorption in ileostomy subjects. American Journal of Clinical Nutrition 62, 12341238.
Turnland, JR, Smith, RG, Kretsch, MJ, Keyes, WR & Shah, AG (1990) Milk's effect on the bioavailability of iron from cereal-based diets in young women by use of in vitro and in vivo methods. American Journal of Clinical Nutrition 52, 373378.
van de Vijver, LPL, Kardinaal, AFM, Charzewska, J, Rotily, M, Charles, P, Maggiolini, M, Ando, S, Vaananen, K, Wajszczyk, B, Heikkinen, J, Deloraine, A & Schaafsma, G (1999) Calcium intake is weakly but consistently negatively associated with iron status in girls and women in six European countries. Journal of Nutrition 129, 963968.
Wauben, IP & Atkinson, SA (1999) Calcium does not inhibit iron absorption or alter iron status in infant piglets adapted to a high calcium diet. Journal of Nutrition 129, 707711.
Wheby, MS, Jones, LG & Crosby, WH (1964) Studies on iron absorption. Intestinal regulatory mechanisms. Journal of Clinical Investigation 43, 14331442.
Wheby, MS & Spyker, DA (1981) Hemoglobin iron absorption kinetics in the iron deficient dog. American Journal of Clinical Nutrition 34, 16861693.
Whiting, SJ (1995) The inhibitory effect of dietary calcium on iron bioavailability: a cause for concern? Nutrition Reviews 53, 7780.
Whiting, SJ & Wood, RJ (1997) Adverse effects of high-calcium diets in humans. Nutrition Reviews 55, 19.
Yan, L, Prentice, A, Dibba, B, Jarjou, LMA & Stirling, DM (1996) The effect of long-term calcium supplementation on indices of iron, zinc, and magnesium status in lactating Gambian women. British Journal of Nutrition 76, 821831.
Zhou, JR & Erdman, JW (1995) Phytic acid in health and disease. CRC Critical Reviews in Food Science and Nutrition 35, 495508.
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