Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/8/2005
Publication Date: 9/1/2005
Citation: Roughead, Z.K., Zito, C.A., Hunt, J.R. 2005. 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. American Journal of Clinical Nutrition. 82:589-97. Interpretive Summary: We designed this study to determine how consuming a typical calcium supplement with a meal affects how the intestinal cell handles the two different forms of iron found in food (heme and nonheme). In two different experiments, healthy men and women ate either a hamburger with French fries and apple juice or a wheat muffin with eggs, Canadian bacon, shredded wheat with milk and tea, in random order. The hamburger test meal was designed to include enhancers of iron absorption (high iron bioavailability), while the wheat muffin meal was designed to include inhibitor of iron absorption (low iron bioavailability). Each time, we allowed 8 hours for the intestinal cells to take up the two forms of iron and then the volunteers drank a special solution called GoLytely which completely cleansed the intestinal tract of its contents. We compared the amount of heme and nonheme iron which remained in the body after 8 hours to the amounts remaining in the body 2 weeks later. We found that healthy individuals absorbed about 16x more iron from the hamburger meal than the wheat muffin meal (0.55 vs. 0.03 mg). We also found that adding a typical calcium supplement to either meal reduced the total amount of iron and heme iron absorbed from the meal. This effect seemed to occur at the initial entry of iron into the mucosal cell rather than later in the absorption process. Also, we concluded that heme iron is more bioavailable than nonheme iron at least partially because of its much higher initial uptake by the intestinal cell and that the initial uptake into the intestinal cell is an important step in the regulation of iron absorption. Although adding a calcium supplement to either meal reduced the total iron absorption by about 25%, long term studies are needed to test if the body adapts to compensate for the inhibitory effects of the additional calcium (from supplements or fortified foods) over time.
Technical Abstract: Background: Calcium is the only known dietary inhibitor of both heme and nonheme iron absorption. It is proposed that the two forms of iron enter a common pool in the enterocyte and that calcium inhibits the serosal transfer of iron into blood. Objective: To determine whether the inhibitory effect of calcium occurs during initial mucosal uptake or during serosal transfer, and whether the serosal transfer of heme and nonheme iron is similar, consistent with a common mucosal iron pool. Design: Whole gut lavage and whole body counting were used to measure the initial uptake (8 h) and subsequent retention (2 wk) of heme and nonheme iron with and without a calcium supplement (450 mg) from meals either low (Experiment A, n=15) or high in iron bioavailability (Experiment B, n=12). Results: Added calcium reduced the initial uptake of heme iron by 20%, from 49% to 40% from both meals (P = 0.02) and the total iron absorbed from the low and high bioavailability meals by ~25% (from 0.033 to 0.025 mg, P = 0.06; and 0.55 to 0.40 mg, P < 0.01, respectively). Calcium did not affect the serosal transfer of either form of iron. Conclusions: A typical calcium supplement reduced heme and total iron absorption, regardless of the meal bioavailability. Calcium inhibited the initial mucosal uptake rather than the serosal transfer of iron. Based on differences in the serosal transfer index, heme and nonheme iron did not enter a common absorptive pool within 8 h after consumption of a meal.