Review articleCalcium supplementation and iron status of females
Introduction
Iron is essential for several crucial physiologic functions including transporting and storing oxygen, carrying electrons, and catalyzing various reactions ranging from oxidative metabolism to cellular proliferation. The metabolism of iron is highly conserved in healthy people as the body has limited capacity to excrete excess iron. Iron balance is regulated by the control of absorption, which is influenced by the amount of iron in body stores and the level of erythropoietic activity.1 Loss of iron occurs with certain conditions such as menses, pregnancy and consequent iron transfer to the fetus, and bleeding due to injury, infection, or other causes. Women with child-bearing potential represent a risk group for lower-than-recommended iron status and anemia (due to frank iron deficiency).
Calcium is the major structural component in bone and teeth. Calcium is also required for many important physiologic functions such as cell proliferation, responses to hormones, and release of neurotransmitters.2 The metabolism of calcium is tightly regulated by parathyroid hormone, calcitonin, and vitamin D to maintain serum calcium concentration and prevent deleterious neurologic, gastrointestinal, and renal effects.2, 3 Low-calcium intake causes a release of calcium from bone and increases the risk of osteoporosis. The most critical time for increasing bone-mineral density for women is before age 30 y, although consumption of recommended levels of calcium during adulthood is also necessary for bone health.
Several short-term studies have recently shown that concurrent ingestion of calcium and iron from the same meal inhibits iron absorption. Some of these studies have used food sources of calcium and others have used supplemental calcium; both sources reduced iron intakes from single meals. Long-term studies of calcium supplementation, however, do not indicate that iron status in women was decreased.
A major randomized, double-blind, placebo-controlled clinical trial demonstrated that 1200 mg of supplemental calcium carbonate (CaCO3) per day significantly reduced the symptoms of premenstrual syndrome in women of child-bearing age.4 Because this particular female population is often also at risk for low iron status as a consequence of menstruation and low iron intake, it is important to examine the effects of calcium supplementation on the iron status of menstruating women.
Thus, this article reviews the data from studies that have examined the short- and long-term consequences of calcium intakes (at or above recommended levels, mainly from supplements) in women who may be at risk for low iron status.
Section snippets
Regulation of iron metabolism
The main function of iron metabolism is to recycle iron released from destroyed erythrocytes and incorporate this iron into the hemoglobin in newly formed erythrocytes (erythropoesis). Iron is tightly conserved as it moves from circulating red blood cells (e.g., hemoglobin) to iron stores (e.g., ferritin); there are also separate tissue iron pools (e.g., myoglobin and enzymes), labile iron pools, and iron-transport proteins, such as transferrin. The predominant iron carrier in blood is
Absorption, uptake, and transport
In healthy individuals who have minimal iron loss, normal iron balance is regulated by the control of iron absorption occurring in the small intestine. Iron is taken up by mucosal cells lining the intestinal lumen, exits these cells, and enters the capillaries, where it is bound to transferrin. Transferrin transports iron in the blood and delivers iron to cells via the transferrin receptor. Newly absorbed iron can remain bound to transferrin in the plasma, it can remain within cells as
The basis of an individual’s iron status
There is no single sensitive and specific indicator of overall iron status. Thus, investigators use a variety of indirect methods to estimate iron status (Table I). Indices such as red-blood-cell count, hemoglobin concentration, hematocrit (Hct), mean corpuscular volume (MCV) of the red blood cell, and erythrocyte zinc protoporphyrin (ZPP) are used to evaluate erythropoesis and heme synthesis, which are processes that are highly dependent on iron status. Serum iron concentration, total
Studies examining the effects of calcium supplementation on acute iron absorption
Single- and multimeal absorption studies are common methods to identify the potential for mineral-to-mineral interactions. Hallberg et al.5 initiated a study to 1) examine the effect of calcium on heme-iron absorption from a meal containing meat versus heme-iron absorption from a meatless meal and 2) compare the effect of calcium on non-heme and heme absorption from a meal containing meat. During the first phase of the iron-absorption study, hamburger containing hemoglobin (source of heme iron)
Studies examining calcium and iron dosing schedules
Because the results of short-term mineral-to-mineral interaction studies have suggested a potential for similar long-term effects of calcium on iron absorption, several studies examined the potential for an optimal dosing schedule for calcium and iron. In a single-meal study, Gleerup et al.12 investigated the duration of the inhibitory effect of calcium on iron absorption by giving volunteers natural sources of dietary calcium at various times before giving an iron-containing meal. Twenty-one
Relevance of single-meal studies
The body of evidence suggests an acute inhibitory effect of calcium on iron absorption. However, the results of controlled single-meal studies may exaggerate the effect on iron absorption and may not predict the long-term effects of calcium on iron status. Some studies have shown that conventional meals reduce this calcium effect less than the meals provided in single-meal studies.11, 13 Cook et al.14 examined the effect of a self-selected diet versus diets designed to maximally enhance or
Form of calcium
In addition to meal composition, the type of calcium salt used may be a factor in the extent of the interference in iron absorption. Two studies used whole-body retention of 59Fe to measure the effect of various calcium sources in postmenopausal women.18, 19 In one study, 500 mg of elemental calcium as calcium carbonate or hydroxyapatite significantly reduced iron absorption when administered with test meals.18 The effects of several other sources of calcium were examined by Deehr et al.19
Calcium supplementation and studies of long-term effects on iron status
Several studies have explored whether long-term calcium supplementation compromises iron status. Snedeker et al.20 examined iron utilization for 39 d in nine adult males fed diets supplemented with different levels of calcium as calcium gluconate and phosphorus as glycerol phosphate. Dietary-supplementation levels included 1) 780 mg of calcium plus 843 mg of phosphate, 2) 780 mg of calcium plus 2442 mg of phosphate, and 3) 2382 mg of calcium plus 2442 mg of phosphate. Although subjects in group
Conclusions
The totality of the evidence from the studies reviewed indicates that supplementation with calcium, at the levels found to reduce symptoms of prementrual syndrome4 and enhance bone-mineral density2 (1200 mg/d), does not affect normal iron status in healthy menstruating females. There are also studies suggesting that, in healthy premenarchial girls, toddlers, and infants with normal iron status, calcium supplementation does not reduce iron status.27, 29, 31
Acknowledgements
The author acknowledges the technical assistance of Zina Manji, PharmD. The author is appreciative of the constructive comments from Dr. R. Heaney, Dr. V. Matkovic, and Dr. B. Daggy.
References (31)
- et al.
Calcium
Lancet
(1998) - et al.
Calcium carbonate and the premenstrual syndromeeffects on premenstrual and menstrual symptoms
Am J Obstet Gynecol
(1998) - et al.
Calciumeffect of different amounts on nonheme- and heme-iron absorption in humans
Am J Clin Nutr
(1991) - et al.
Iron absorption from the whole dietcomparison of the effect of two different distributions of daily calcium intake
Am J Clin Nutr
(1995) Does calcium interfere with iron absorption?
Am J Clin Nutr
(1998)- et al.
Calcium inhibition of inorganic iron absorption in rats
Gastroenterology
(1983) - et al.
Effect of calcium supplementation on daily nonheme-iron absorption and long-term iron status
Am J Clin Nutr
(1998) - et al.
Assessment of the role of nonheme-iron availability in iron balance
Am J Clin Nutr
(1991) - et al.
Effect of calcium intake on nonheme-iron absorption from a complete diet
Am J Clin Nutr
(1997) - et al.
Estimation of nonheme-iron bioavailability from meal composition
Am J Clin Nutr
(2000)
Effect of milk and fermented milk on iron absorption in ileostomy subjects
Am J Clin Nutr
Effects of calcium carbonate and hydroxyapatite on zinc and iron retention in postmenopausal women
Am J Clin Nutr
Effects of difference calcium sources on iron absorption in postmenopausal women
Am J Clin Nutr
Effect of dietary calcium and phosphorus levels on the utilization of iron, copper, and zinc by adult males
J Nutr
Calcium supplementation and plasma ferritin concentrations in premenopausal women
Am J Clin Nutr
Cited by (36)
Dairy Product (Calcium) Consumption and Iron Nutrition
2017, Nutrients in Dairy and their Implications for Health and DiseaseFood protein-derived chelating peptides: Biofunctional ingredients for dietary mineral bioavailability enhancement
2014, Trends in Food Science and TechnologyCitation Excerpt :In addition, calcium is important for intracellular metabolism, bone growth, blood clotting, nerve conduction, muscle contraction and cardiac function (Bass & Chan, 2006). Calcium is also responsible for many important physiological functions such as cell proliferation, responses to hormones and the release of neurotransmitters (Bendich, 2001). Zinc is a catalytic component of a large number of enzymes and has a structural and biological role in many proteins, peptides, hormones, transcriptional and growth factors and cytokines (Bozalioğlu, Özkan, Turan, & Şimşek, 2005).
Bioavailability of Calcium, Iron, and Zinc in Whole Wheat Flour
2014, Wheat and Rice in Disease Prevention and HealthOne-month of calcium supplementation does not affect iron bioavailability: Arandomized controlled trial
2014, NutritionCitation Excerpt :One of the limitations of the present study was a lack of assessment into the molecular mechanisms involved in the effect of Ca supplementation on Fe bioavailability. Nevertheless, our results suggest that the body is able to regulate the response of Fe absorption despite a prolonged exposure to Ca; probably through an adaptive response of the enterocyte [20,38]. We suggest that the acute effect of Ca supplementation on Fe bioavailability can be an important modulator of a subsequent response in the development of the intestinal crypt-villus unit, thus promoting Fe absorption efficiency; however this process is poorly understood.
Chapter 16 Minerals: functions, requirements, excessive intake and toxicity
2006, Biology of Growing Animals