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Micronutrient Interactions: Impact on Child Health and ... - Idpas.org

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Ir<strong>on</strong>–ascerbic Acid <strong>and</strong> Ir<strong>on</strong>–calcium <str<strong>on</strong>g>Interacti<strong>on</strong>s</str<strong>on</strong>g> <strong>and</strong> Their Relevance in Complementary Feeding<br />

Ir<strong>on</strong>-calcium <str<strong>on</strong>g>Interacti<strong>on</strong>s</str<strong>on</strong>g><br />

An inhibitory effect of calcium <strong>on</strong> ir<strong>on</strong> absorpti<strong>on</strong><br />

was recognized nearly 60 years ago.<br />

In the past 10–15 years many investigators<br />

have focused <strong>on</strong> this issue, trying to define<br />

the practical importance of the interacti<strong>on</strong><br />

<strong>and</strong> the mechanism by which it occurs. The<br />

results of these studies are often c<strong>on</strong>flicting<br />

because several factors influence the interacti<strong>on</strong><br />

between calcium <strong>and</strong> ir<strong>on</strong> absorpti<strong>on</strong>,<br />

including the molar ratio of calcium<br />

to ir<strong>on</strong>, the forms of calcium <strong>and</strong> ir<strong>on</strong>,<br />

whether these minerals are c<strong>on</strong>sumed in the<br />

presence of food, <strong>and</strong> the ir<strong>on</strong> status of the<br />

subjects.<br />

The mechanism by which calcium impairs<br />

ir<strong>on</strong> absorpti<strong>on</strong> remains c<strong>on</strong>troversial<br />

(Hallberg et al. 1992a). It probably does<br />

not involve reducti<strong>on</strong> of intestinal pH or<br />

the formati<strong>on</strong> of insoluble ir<strong>on</strong> salts such as<br />

carb<strong>on</strong>ates. It is not clear whether calcium<br />

competes for low-molecular-weight lig<strong>and</strong>s<br />

that enhance ir<strong>on</strong> absorpti<strong>on</strong>. Calcium<br />

equally inhibits the absorpti<strong>on</strong> of n<strong>on</strong>heme<br />

<strong>and</strong> heme ir<strong>on</strong> (Hallberg et al. 1991), which<br />

enter the mucosal cell by different pathways<br />

<strong>and</strong> leave in the same form, suggesting that<br />

calcium inhibits the intracellular transport<br />

of ir<strong>on</strong> (Hallberg et al. 1992b). Calcium may<br />

compete for ir<strong>on</strong>-binding sites in<br />

mobilferrin, a protein in the duodenal mucosa<br />

that may assist ir<strong>on</strong> transport through<br />

the cell (C<strong>on</strong>rad <strong>and</strong> Umbreit 1993).<br />

Mobilferrin can bind calcium although it<br />

has a greater affinity for ir<strong>on</strong>. Calcium may<br />

also inhibit the release of ir<strong>on</strong> from mucosal<br />

cells into the circulati<strong>on</strong> (Wienk et al. 1996).<br />

The inhibitory effect of calcium <strong>on</strong> ir<strong>on</strong><br />

absorpti<strong>on</strong> is independent of the amount of<br />

phytate in a meal (Hallberg et al. 1992b)<br />

<strong>and</strong> does not interfere with the enhancing<br />

effect of meat (Hallberg et al. 1992b) or<br />

ascorbic acid (Hallberg et al. 1992a). It is<br />

important to recognize that adding calcium<br />

to wheat flour before leavening causes a further<br />

substantial decrease in ir<strong>on</strong> absorpti<strong>on</strong><br />

because calcium inhibits phytase activity in<br />

yeast (Hallberg et al. 1991). As little as 40<br />

mg calcium added to 80 g flour inhibited<br />

phytate degradati<strong>on</strong> during leavening by<br />

50%. This means that calcium fortificati<strong>on</strong><br />

of wheat flour may reduce the beneficial effects<br />

of fermentati<strong>on</strong> <strong>on</strong> the bioavailability<br />

of ir<strong>on</strong> <strong>and</strong> other minerals bound to phytate.<br />

Amount of Calcium<br />

Hallberg et al. (1991) added between 40 <strong>and</strong><br />

600 mg of calcium, as calcium chloride or<br />

dairy products, to wheat rolls c<strong>on</strong>taining<br />

3.8 mg ir<strong>on</strong>. Ir<strong>on</strong> absorpti<strong>on</strong> fell relatively<br />

linearly to about 40% at 300–600 mg calcium.<br />

There was no effect of adding 40 mg<br />

calcium (calcium-ir<strong>on</strong> molar ratio 14:1),<br />

<strong>and</strong> at the upper end adding 600 mg rather<br />

than 300 mg had relatively little additi<strong>on</strong>al<br />

inhibitory effect. However, it is not <strong>on</strong>ly the<br />

calcium-ir<strong>on</strong> molar ratio that is important,<br />

because there was no effect of adding 3 mg<br />

calcium <strong>on</strong> the absorpti<strong>on</strong> of a trace amount<br />

(0.01 mg) of ir<strong>on</strong>, a calcium-ir<strong>on</strong> molar ratio<br />

of 420:1 (Hallberg et al. 1992a).<br />

Form of Calcium<br />

The form of calcium also influences its inhibitory<br />

effect <strong>on</strong> ir<strong>on</strong> absorpti<strong>on</strong>. A review<br />

by Whiting (1995) revealed that 500–600 mg<br />

calcium added to meals typically reduced<br />

ir<strong>on</strong> absorpti<strong>on</strong> by about 40% when added<br />

as cheese <strong>and</strong> milk; 40–50% when added as<br />

calcium phosphate, carb<strong>on</strong>ate, or hydroxyapatite;<br />

<strong>and</strong> 60–70% when added as<br />

more soluble calcium citrate <strong>and</strong> calcium<br />

citrate malate supplements (Hallberg et al.<br />

1992b, Cook et al. 1991b, Deehr et al. 1990,<br />

Daws<strong>on</strong>-Hughes et al. 1986). Calcium carb<strong>on</strong>ate<br />

had no effect <strong>on</strong> ir<strong>on</strong> absorpti<strong>on</strong> in<br />

at least <strong>on</strong>e report (Seligman et al. 1983).<br />

Although these observati<strong>on</strong>s may indicate<br />

that more soluble forms of calcium have a<br />

greater effect <strong>on</strong> ir<strong>on</strong> absorpti<strong>on</strong> because the<br />

inhibiti<strong>on</strong> occurs within the mucosal cell,<br />

15

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