Supplemental zinc lowers measures of iron status in young women with low iron reserves

Zinc and iron compete during intestinal absorption, but postabsorptive interactions between these nutrients are less clear. Understanding these interactions is important to determine when supplementation with iron or zinc is proposed. The effect of zinc supplementation (22 mg Zn/d as zinc gluconate) or of iron supplementation (100 mg Fe/d as ferrous sulfate) for 6 wk on iron and zinc metabolism and absorption was evaluated in young women with low iron reserves. Young adult women (ages 20-28 y), nonanemic but with low iron stores (plasma ferritin< 20 microg/L), participated in the 70-d study. The women were divided in two groups (zinc-supplemented, n = 11; iron-supplemented, n = 12). The supplements were taken at bedtime. Iron and zinc biochemical indices and intestinal absorption were measured on d 1 and 56. Radioiron and stable isotopes of zinc were used to measure iron and zinc absorption from a test meal. In the iron-supplemented group, blood hemoglobin, plasma ferritin and the percentage of transferrin saturation increased (P < 0.01). Zinc indices did not change. In the zinc-supplemented group, plasma ferritin and the percentage of transferrin saturation decreased (P < 0.05), whereas the plasma transferrin receptor and erythrocyte zinc protoprophyrin levels increased (P < 0.05). Plasma and urinary zinc also increased (P < 0.01). Iron absorption (%) from the test meal increased (P < 0.01), whereas zinc absorption (%) decreased (P < 0.01) compared with baseline in the Zn-supplemented women. Our results indicate that the use of iron supplements in women with marginal iron status improves iron indices with no effect on zinc status. However, use of a modest zinc supplement improves zinc indices, but also appears to induce a cellular iron deficiency and, possibly, further reduce iron status.     

Women with low iron stores absorb iron from soybeans

BACKGROUND: Worldwide, 30% of the population, a greater proportion of whom are women and children, is iron deficient. Soybeans are a major source of nonheme iron in many human diets, but information on iron bioavailability is still conflicting. Because much of soybean iron is in ferritin [distinct from the poorly bioavailable iron in cereals resulting from interactions between calcium, Fe(III), phytate, and proteins in the meal], soybeans provide a target for manipulating seed iron composition to achieve increased iron bioavailability. OBJECTIVE: The aim was to reevaluate soybean iron bioavailability. DESIGN: Eighteen women, most with marginal iron deficiency, consumed meals with intrinsically labeled ((55)Fe) soybeans (hydroponically grown and nonnodulating) as soup (n = 11) or muffins (n = 7) and a reference dose of (59)Fe as ferrous sulfate in ascorbate solution. The radioactivity in red cells was measured 14 and 28 d later. RESULTS: The mean (55)Fe absorption from either soup or muffins was 27% and that from the reference dose was 61%. (55)Fe was distributed approximately equally between protein (49.3 +/- 3.0%) and phytate, a contrast with nodulating soybeans likely caused by a high phosphate content in the growth medium. There was an expected inverse correlation (r = -0.793, P < 0.001) between red cell radioactivity and serum ferritin concentration. CONCLUSIONS: These results show that soybeans appear to be a good source of nutritional iron in marginally iron-deficient individuals. More study is needed on the effect of plant nodulation on the form of soybean iron, aimed at enhancing bioavailability to combat iron deficiency in at-risk populations.     

Influence of prenatal iron and zinc supplements on supplemental iron absorption, red blood cell iron incorporation, and iron status in pregnant Peruvian women

BACKGROUND: It is estimated that 60% of pregnant women worldwide are anemic. OBJECTIVE: We aimed to examine the influence of iron status on iron absorption during pregnancy by measuring supplemental iron absorption, red blood cell iron incorporation, and iron status in pregnant women. DESIGN: Subjects were 45 pregnant Peruvian women (33+/-1 wk gestation), of whom 28 received daily prenatal supplements containing 60 mg Fe and 250 microg folate without (Fe group, n = 14) or with (Fe+Zn group, n = 14) 15 mg Zn, which were were consumed from week 10 to 24 of gestation until delivery. The remaining 17 women (control) received no prenatal supplementation. Iron status indicators and isotopes were measured in maternal blood collected 2 wk postdosing with oral (57Fe) and intravenous (58Fe) stable iron isotopes. RESULTS: Maternal serum ferritin and folate concentrations were significantly influenced by supplementation (P < 0.05). Serum iron was also significantly higher in the Fe than in the Fe+Zn (P < 0.03) or control (P < 0.001) groups. However, the supplemented groups had significantly lower serum zinc concentrations than the control group (8.4+/-2.3 and 10.9+/-1.8 micromol/L, respectively, P < 0.01). Although percentage iron absorption was inversely related to maternal serum ferritin concentrations (P = 0.036), this effect was limited and percentage iron absorption did not differ significantly between groups. CONCLUSIONS: Because absorption of nonheme iron was not substantially greater in pregnant women with depleted iron reserves, prenatal iron supplementation is important for meeting iron requirements during pregnancy.     

Iron deficiency, but not anemia, upregulates iron absorption in breast-fed peruvian infants

Iron absorption in adults is regulated by homeostatic mechanisms that decrease absorption when iron status is high. There are few data, however, regarding the existence of a similar homeostatic regulation in infants. We studied 2 groups of human milk-fed infants using (57)Fe (given as ferrous sulfate without any milk) and (58)Fe (given at the time of a breast-milk feeding) stable isotopes to determine whether healthy infants at risk for iron deficiency would regulate their iron absorption based on their iron status. We studied 20 Peruvian infants at 5-6 mo of age and 18 infants at 9-10 mo of age. We found no effect of infant hemoglobin concentration on iron absorption with 5-6 mo-old infants absorbing 19.2 +/- 2.1% and 9- to 10-mo-old infants absorbing 25.8 +/- 2.6% of the (57)Fe dose. For (58)Fe, 5- to 6-mo-old infants absorbed 42.6 +/- 5.0% and 9 to 10-mo-old infants absorbed 51.9 +/- 10.3%. Following log transformation, iron absorption from (57)Fe (r = -0.61, P = < 0.001) and (58)Fe (r = -0.61, P = < 0.001) were inversely correlated to serum ferritin (S-Ft). For both the (57)Fe and (58)Fe doses, infants with S-Ft <12 mg/L (n = 11) had significantly higher iron absorption than those with S-Ft >12 mg/L. We concluded that iron absorption in infants is related to iron status as assessed by serum ferritin but not hemoglobin concentration. Infants with low iron status upregulate iron absorption from breast milk at both 5-6 and 9-10 mo of age.     

Relationships among iron absorption, percent saturation of plasma transferrin and serum ferritin concentration in humans

The percent absorption of iron from four dietary sources was compared in 2018 human subjects with three indicators of iron status, serum ferritin concentration, percent saturation of plasma transferrin and iron absorption from a reference dose of ferrous sulfate. Higher correlation coefficients (r) were obtained by comparing dietary iron absorption with the reference dose absorption rather than with serum ferritin; for example, r = +0.61 and r = -0.38, respectively, for a meat and vegetable meal. However, in practice serum ferritin is almost as efficient as the reference dose absorption in estimating dietary iron absorption, because the 95% confidence limits calculated from the regression equations were very similar. The values of r calculated for iron absorption versus transferrin saturation were comparable to those obtained with the other indicators only in the range of transferrin saturation values below 25%, whereas in more iron-replete subjects (transferrin saturation greater than 25%), this correlation virtually disappeared. This indicates that, although both serum ferritin and transferrin saturation reflect iron status in iron-depleted subjects, the control of iron absorption in iron-replete subjects is more dependent on iron stores as reflected in the serum ferritin concentration than the percent saturation of transferrin.     

α-Lactalbumin and casein-glycomacropeptide do not affect iron absorption from formula in healthy term infants

Iron absorption from infant formula is relatively low. α-Lactalbumin and casein-glycomacropeptide have been suggested to enhance mineral absorption. We therefore assessed the effect of α-lactalbumin and casein-glycomacropeptide on iron absorption from infant formula in healthy term infants. Thirty-one infants were randomly assigned to receive 1 of 3 formulas (4 mg iron/L, 13.1 g protein/L) from 4-8 wk to 6 mo of age: commercially available whey-predominant standard infant formula (standard formula), α-lactalbumin-enriched infant formula (α-LAC), or α-lactalbumin-enriched/casein-glycomacropeptide-reduced infant formula (α-LAC/RGMP). Nine breast-fed infants served as a reference. At 5.5 mo of age, (58)Fe was administered to all infants in a meal. Blood samples were collected 14 d later for iron absorption and iron status indices. Iron deficiency was defined as depleted iron stores, iron-deficient erythropoiesis, or iron deficiency anemia. Iron absorption (mean ± SD) was 10.3 ± 7.0% from standard formula, 8.6 ± 3.8% from α-LAC, 9.2 ± 6.5% from α-LAC/RGMP, and 12.9 ± 6.5% from breast milk, with no difference between the formula groups (P = 0.79) or all groups (P = 0.44). In the formula-fed infants only, iron absorption was negatively correlated with serum ferritin (r = -0.49; P = 0.005) and was higher (P = 0.023) in iron-deficient infants (16.4 ± 12.4%) compared with those with adequate iron status (8.6 ± 4.4%). Our findings indicate that α-lactalbumin and casein-glycomacropeptide do not affect iron absorption from infant formula in infants. Low serum ferritin concentrations are correlated with increased iron absorption from infant formula.     

Ferrous sulfate is more bioavailable among preschoolers than other forms of iron in a milk-based weaning food distributed by PROGRESA, a national program in Mexico

After 1 y of distributing a milk-based fortified weaning food provided by the Mexican social program PROGRESA, positive effects on physical growth, prevalence of anemia, and several vitamin deficiencies were observed. There was no effect on iron status, which we hypothesized was related to the poor bioavailability of the reduced iron used as a fortificant in PROGRESA. The objective of this study was to compare the iron bioavailability from different iron sources added as fortificants to the weaning food. Children (n = 54) aged 2-4 y were randomly assigned to receive 44 g of the weaning food fortified with ferrous sulfate, ferrous fumarate, or reduced iron + Na(2)EDTA. Iron absorption was measured using an established double-tracer isotopic methodology. Iron absorption from ferrous sulfate (7.9 +/- 9.8%) was greater than from either ferrous fumarate (2.43 +/- 2.3%) or reduced iron + Na(2)EDTA (1.4 +/- 1.3%) (P < 0.01). The absorption of log-(58)Fe sulfate given with the iron source correlated with serum ferritin (s-ferritin) concentration (n = 13, r = 0.63, P = 0.01) and log-(57)Fe absorption (reference dose) (n = 14, r = -0.52, P = 0.02). Absorption from ferrous fumarate and reduced iron + Na2EDTA did not correlate with s-ferritin or absorption of (57)Fe. The recommended daily portion of the fortified complementary food provides an average of 0.256, 0.096, 0.046 mmol (1.44, 0.54, and 0.26 mg) of absorbed iron, if fortified with sulfate, fumarate and reduced iron + Na(2)EDTA, respectively. Ferrous sulfate was more bioavailable than either ferrous fumarate or reduced iron + Na(2)EDTA when added to the milk-based fortified food and more readily met the average daily iron requirements for children 2-3 y of age.     

A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: interactions between iron and zinc

BACKGROUND: Combined supplementation with iron and zinc during infancy may be effective in preventing deficiencies of these micronutrients, but knowledge of their potential interactions when given together is insufficient. OBJECTIVE: The goal was to compare the effect in infants of combined supplementation with iron and zinc and of supplementation with single micronutrients on iron and zinc status. DESIGN: Indonesian infants (n = 680) were randomly assigned to daily supplementation with 10 mg Fe (Fe group), 10 mg Zn (Zn group), 10 mg Fe + 10 mg Zn (Fe+Zn group), or placebo from 6 to 12 mo of age. Venous blood samples were collected at the start and end of the study. Five hundred forty-nine infants completed the supplementation and had both baseline and follow-up blood samples available for analysis. RESULTS: Baseline prevalences of anemia, iron deficiency anemia (anemia and low serum ferritin), and low serum zinc (< 10.7 micromol/L) were 41%, 8%, and 78%, respectively. After supplementation, the Fe group had higher hemoglobin (119.4 compared with 115.3 g/L; P < 0.05) and serum ferritin (46.5 compared with 32.3 microg/L; P < 0.05) values than did the Fe+Zn group, indicating an effect of zinc on iron absorption. The Zn group had higher serum zinc (11.58 compared with 9.06 micromol/L; P < 0.05) than did the placebo group. There was a dose effect on serum ferritin in the Fe and Fe+Zn groups, but at different levels. There was a significant dose effect on serum zinc in the Zn group, whereas no dose effect was found in the Fe+Zn group beyond 7 mg Zn/d. CONCLUSION: Supplementation with iron and zinc was less efficacious than were single supplements in improving iron and zinc status, with evidence of an interaction between iron and zinc when the combined supplement was given.     

Zinc and iron nutrition in Chilean children fed fortified milk provided by the Complementary National Food Program

OBJECTIVE: Chilean infants are at risk for isolated zinc and iron deficiencies because of a low consumption of animal products in low socioeconomic sectors. In 1999, the National Complementary Food Program of Chile manufactured a new milk (2 kg of powdered milk/mo) fortified with iron (Fe; 10 mg/L), zinc (Zn; 5 mg/L), and copper (0.5 mg/L) to be provided to infants until age 18 mo and to pregnant women. We analyzed the nutrition status of zinc and iron at age 18 mo in infants who consumed the fortified cow's milk. METHODS: Forty-two healthy male children with normal growth and from lower socioeconomic groups were studied. A nutrition survey was conducted; blood and hair samples for Zn in plasma and hair, hemoglobin, hematocrit, and serum ferritin were obtained. RESULTS: Mean intakes were: energy, 106 +/- 27 kcal. kg(-1). d(-1); protein, 3.8 +/- 1.1 g. kg(-1). d(-1); Zn, 5.2 +/- 1.9 g/d (0.98 mg Zn/MJ; 68% of World Health Organization recommendations); Fe, 11.2 +/- 5.5 mg/d; and dietary fiber, 9.8 +/- 3.9 g/d. Plasma Zn in 54.8% of children was no greater than 12.3 microM/L; 36% had hair Zn level no greater than 1.23 microM/g and 39% had serum ferritin levels no greater than 10 microg/dL (12% were anemic). Hair Zn was correlated to socioeconomic level (Spearman's rank correlation, r = -0.53; P < 0.001) and plasma Zn was correlated to the z weight/length (r = 0.47; P < 0.05), subscapular skinfold (r = 0.46; P < 0.05), and Zn intake (r = 0.46; P < 0.05). CONCLUSIONS: The fortified powdered cow's milk provided to infants until age 18 mo by the Complementary Food Program in Chile favorably affects the Fe status of these children, but possibly not the Zn nutrition; we suggest re-evaluation of the levels of Zn fortification.     

Inappropriate iron intake in children on long-term parenteral nutrition: outcome after iron withdrawal

Inappropriate parenteral iron intake in children on long-term parenteral nutrition can be responsible for iron overload. This study was carried out to monitor iron status changes when iron parenteral intake was stopped in case of iron overload. Seven children with serum ferritin concentrations above 800 ng/ml (6 with documented liver iron overload) were prospectively studied after total discontinuation of parenteral iron intake and without chelation therapy. Iron status was assessed, by means of ferritin and iron plasma concentrations, 8-15 months (T(1)) and 24-30 months (T(2)) after withdrawal of parenteral iron. Ferritin and iron concentrations declined at T(1), or T(2) in all but two children. At T(2) ferritin and iron concentrations were significantly lower (P < 0.05) than before iron parenteral discontinuation with a yearly reduction of 22 +/- 15% and 15 +/- 16%, respectively, for ferritin concentration and iron concentration. This fall in serum ferritin concentration is comparable to thalassemic subjects after bone marrow transplantation. The total withdrawal of parenteral iron intake improves iron status in children with iron overload. Nevertheless, iron overload related parenteral nutrition should be avoided by lowering iron intake in case of long-term total parenteral nutrition and by careful monitoring.     

Iron, zinc, and copper concentrations in breast milk are independent of maternal mineral status

BACKGROUND: Little is known about the regulation of iron, zinc, and copper in breast milk and the transport of these minerals across the mammary gland epithelium. OBJECTIVE: The objective was to study associations between breast-milk concentrations of iron, zinc, and copper and maternal mineral status. DESIGN: Milk samples from 191 Swedish and Honduran mothers were collected at 9 mo postpartum. Iron, zinc, and copper concentrations were measured by atomic absorption spectrometry. Blood samples from mothers were analyzed for plasma zinc and copper and 4 indexes of iron status: hemoglobin, plasma ferritin, soluble transferrin receptors, and zinc protoporphyrin. Complementary food energy (CFE) intake was used as an inverse proxy for breast-milk intake. RESULTS: Mean (+/-SD) breast-milk concentrations of iron were lower in the Honduran than in the Swedish mothers (0.21 +/- 0.25 compared with 0.29 +/- 0.21 mg/L; P < 0.001), and mean breast-milk concentrations of zinc and copper were higher in the Honduran than in the Swedish mothers [0.70 +/- 0.18 compared with 0.46 +/- 0.26 mg/L (P < 0.001) and 0.16 +/- 0.21 compared with 0.12 +/- 0.22 mg/L (P = 0.001), respectively]. Milk iron was positively correlated with CFE intake (r = 0.24, P = 0.001) but was not significantly correlated with any iron-status variable. Milk zinc was negatively correlated with CFE intake (r = -0.24, P = 0.001) but was not significantly correlated with maternal plasma zinc. Milk copper was not significantly correlated with CFE intake or maternal plasma copper. CONCLUSIONS: Milk iron, zinc, and copper concentrations at 9 mo postpartum are not associated with maternal mineral status, which suggests active transport mechanisms in the mammary gland for all 3 minerals. Milk iron concentrations increase and milk zinc concentrations decrease during weaning [corrected]     

Iron absorption from soybean ferritin in nonanemic women

BACKGROUND: Dietary ferritin, a protein cage around an iron mineral, is an underestimated source of bioavailable iron. Plant ferritin, the most common dietary ferritin, has not been studied. Iron from animal ferritin is absorbed as well as is iron from FeSO4 in women. OBJECTIVE: The objective was to examine iron absorption from purified soybean ferritin. DESIGN: Healthy, nonanemic women (n = 16) were fed a standardized meal (bagel, cream cheese, and apple juice) containing 1 microCi 59Fe/meal as FeSO4 or (extrinsically labeled) as iron-free soybean ferritin reconstituted with the high phosphate characteristic of plant ferritin (iron:phosphorus = 4:1). Iron-free, apo-soybean ferritin was prepared (with the use of thioglycolic acid and extensive dialysis) from purified ferritin. In a randomized crossover design, the other labeled meal, which contained FeSO4 or ferritin, was given after 4 wk. The subjects received 140 microg Fe as ferritin (2.5 mg) or as FeSO4. After 28 d, whole-body 59Fe and 59Fe in red blood cells were measured before and after dosing. RESULTS: There was no significant difference in whole-body iron absorption from soybean ferritin (29.9 +/- 19.8%) and that from FeSO4 (34.3 +/- 23.6%) or in iron absorption calculated from red blood cell incorporation (33.0 +/- 20.1% for soybean ferritin and 35.3 +/- 23.4% for FeSO4), which confirmed previous results with animal ferritin that was mineralized and labeled similarly. An inverse relation was observed between serum ferritin and iron absorption from both ferritin and FeSO4, which suggested that sensors regulating iron absorption respond similarly to iron provided as ferrous salts or as ferritin mineral. CONCLUSION: Iron from soybean ferritin is well absorbed and may provide a model for novel, utilizable, plant-based forms of iron for populations with a low iron status.     

Prenatal iron supplements impair zinc absorption in pregnant Peruvian women

Prenatal iron supplements may adversely influence zinc absorption during pregnancy. To examine the impact of prenatal iron supplements on supplemental zinc absorption, fractional zinc absorption was measured in 47 pregnant Peruvian women during the third trimester of pregnancy (33 +/- 1 wk gestation). Of these 47 women, 30 received daily prenatal supplements from wk 10-24 of pregnancy until delivery. Supplements contained 60 mg of Fe and 250 microg of folate without [iron group (Fe), n = 16] or with [iron and zinc supplemented group (Fe + Zn), n = 14] 15 mg of Zn. The remaining 17 women [unsupplemented control group (C)] received no prenatal supplementation. Zinc concentrations were measured in plasma, urine and cord blood and percentage zinc absorption was determined following dosing with oral ((67)Zn) and intravenous ((70)Zn) stable zinc isotopes. Percentage zinc absorption was significantly lower than controls in fasting women receiving iron- containing prenatal supplements (20.5 +/- 6.4 vs. 20.2 +/- 4.6 vs. 47.0 +/- 12.6%, Fe, Fe + Zn and C groups, respectively, P: < 0.0001, n = 40). Plasma zinc concentrations were also significantly lower in the Fe group compared to the C group (8.2 +/- 2.2 vs. 9.2 +/- 2.2 vs. 10.9 +/- 1. 8 micromol/L, Fe, Fe + Zn and C groups, respectively, P: = 0.002), and cord zinc concentrations were significantly related to maternal plasma Zn levels (y = 6.383 + 0.555x, r = 0.486, P: = 0.002). The inclusion of zinc in prenatal supplements may reduce the potential for iron supplements to adversely influence zinc status in populations at risk for deficiency of both these nutrients.     

Effect of beef and soy proteins on the absorption of non-heme iron and inorganic zinc in children

BACKGROUND: Iron and zinc deficiency remain substantial problems in small children in both developed and developing nations. Optimizing mineral absorption is an important strategy in minimizing this problem. OBJECTIVES: To assess the effects of beef and soy proteins on the bioavailability of non-heme iron and zinc in children. METHODS: We measured iron (n = 26) and zinc (n = 36) absorption in 4-8 y old children from meals differing only in protein source (beef or a low-phytate soy protein concentrate). Iron and zinc absorption were measured using multi-tracer stable isotope techniques. Iron absorption was calculated from the red blood cell iron incorporation measured after 14 days and zinc absorption from the ratio of the oral and intravenous excretion of the zinc tracers 48 hours after dosing. RESULTS: Iron absorption from the beef meal was significantly greater (geometric mean, 7.6%) than from the soy meal (3.5%, p = 0.0015). Zinc absorption from the beef meal was greater (mean +/- SD, 13.7 +/- 6.0%) than from the soy meal (10.1 +/- 4.1%, p = 0.047). CONCLUSION: These findings indicate that beef protein increases both non-heme iron and zinc absorption compared to soy protein. The effect of protein source on non-heme iron and inorganic zinc absorption should be one of the factors taken into account when designing diets for children. The inhibitory effect of the soy based meal on iron and zinc absorption could be overcome by fortifying the soy protein with these minerals during the production process.     

Maternal iron status influences iron transfer to the fetus during the third trimester of pregnancy

BACKGROUND: The effect of maternal iron status on fetal iron deposition is uncertain. OBJECTIVE: We used a unique stable-isotope technique to assess iron transfer to the fetus in relation to maternal iron status. DESIGN: The study group comprised 41 Peruvian women. Of these women, 26 received daily prenatal supplements containing iron and folate (n = 11; Fe group) or iron, folate, and zinc (n = 15; Fe+Zn group) from week 10-24 of pregnancy to 1 mo postpartum. The remaining 15 women (control group) received iron supplementation only during the final month of pregnancy. During the third trimester of pregnancy (+/- SD: 32.9 +/- 1.4 wk gestation) oral 57Fe (10 mg) and intravenous 58Fe (0.6 mg) stable iron isotopes were administered to the women, and isotope enrichment and iron-status indicators were measured in cord blood at delivery. RESULTS: The net amount of 57Fe in the neonates' circulation (from maternal oral dosing) was significantly related to maternal iron absorption (P < 0.005) and inversely related to maternal iron status during the third trimester of pregnancy: serum ferritin (P < 0.0001), serum folate (P < 0.005), and serum transferrin receptors (P < 0.02). Significantly more 57Fe was transferred to the neonates in non-iron-supplemented women: 0.112 +/- 0.031 compared with 0.078 +/- 0.042 mg in the control group (n = 15) and the Fe and Fe+Zn groups (n = 24), respectively (P < 0.01). In contrast, 58Fe tracer in the neonates' circulation was not significantly related to maternal iron status. CONCLUSION: The transfer of dietary iron to the fetus is regulated in response to maternal iron status at the level of the gut.     

Production of stable-isotope-labeled bovine heme and its use to measure heme-iron absorption in children

BACKGROUND: The use of stable isotopes has provided valuable insights into iron absorption in humans, but the data have been limited to nonheme iron. OBJECTIVE: Our objectives were to produce heme iron enriched in (58)Fe and to use it to study the absorption of heme iron and the effect of iron and zinc intakes on heme-iron absorption in children. DESIGN: Labeled bovine heme was produced in a bovine model. Forty-eight children were randomly assigned to consume identical meals containing 1 of 3 doses of labeled heme iron (2, 4, or 8 mg as hemoglobin) and 1 of 2 doses of inorganic zinc (1 or 9 mg); successful measurements of iron absorption, zinc absorption, or both were made in 40 of these subjects. We hypothesized that fractional heme-iron absorption would decrease as heme-iron intake increased and that higher zinc intakes would decrease heme-iron absorption. RESULTS: (58)Fe heme was produced with an enrichment (mass/mass) of 9.5%. Fractional iron absorption in children was significantly affected by the intake of heme iron (P = 0.0013) and of zinc (P = 0.0375), but, contrary to expectations, heme-iron absorption was higher at higher zinc intakes. Absolute heme-iron absorption was higher in the group with higher zinc intakes, but only for those with the lowest heme-iron intake (2 mg; P = 0.0147). Although fractional zinc absorption decreased as zinc intake increased (P = 0.031), absolute zinc absorption continued to increase across the intake range studied (P = 0.018). CONCLUSIONS: Heme iron intrinsically labeled with (58)Fe can be produced at sufficient enrichments for use in human studies. In children, heme iron and zinc absorption decrease as the dose of each mineral increases. Heme iron did not inhibit zinc absorption. At lower heme intakes, zinc intakes may increase heme-iron absorption.     

Adaptation in iron absorption: iron supplementation reduces nonheme-iron but not heme-iron absorption from food

BACKGROUND: Results of cross-sectional studies suggest that in healthy people, iron absorption adapts to meet physiologic needs and stabilize iron stores, but this has not been adequately tested in longitudinal studies. OBJECTIVE: We tested whether heme- and nonheme-iron absorption decrease in response to increased iron intake and whether iron stores reach a steady state. DESIGN: In a randomized, placebo-controlled trial, heme- and nonheme-iron absorption by healthy men and women (n = 57) were measured before and after 12 wk of supplementation with 50 mg Fe/d as ferrous sulfate. Serum and fecal ferritin were measured during supplementation and for 6 mo thereafter. RESULTS: Initially, both heme- and nonheme-iron absorption were inversely associated with serum ferritin concentration. Volunteers who took iron supplements, even those with serum ferritin <21 microg/L (n = 5), adapted to absorb less nonheme iron (3.2% at week 12 compared with 5.0% at week 0, P: < 0.001) but not less heme iron from a beef-based meal. Serum ferritin concentration was slightly but significantly higher after iron supplementation than after placebo (difference = 13 microg/L). This higher ferritin concentration persisted for >/=6 mo after supplementation, except in subjects with low iron stores, whose serum ferritin returned to baseline within 3 mo. Fecal ferritin excretion increased 2.5-fold (P: < 0.05) during supplementation. CONCLUSIONS: Healthy individuals, even those with low iron stores, had reduced nonheme-iron absorption from food in response to iron supplementation. Despite this partial adaptation, iron stores were greater after iron supplementation than after placebo and this difference was sustained, except in individuals with the lowest iron stores.     

Meat consumption in a varied diet marginally influences nonheme iron absorption in normal individuals

It is widely recognized that the intake of animal foods is the most important dietary determinant of the iron status of a population. The primary reason is the high bioavailability of heme iron, but it is also known from radiolabeled single-meal feeding studies in humans that muscle tissue facilitates absorption of nonheme iron. In the present study, we examined the effect of meat intake on nonheme iron absorption from a whole diet. Iron absorption was measured during 3 separate dietary periods in 14 volunteers (7 men and 7 women) by having them ingest a radioiron-labeled wheat roll with every meal for 5 d. The diet was freely chosen for the first dietary period and altered to eliminate or maximally increase the intake of muscle foods during the second and third periods. Nonheme iron absorption did not differ for the 3 dietary periods although the geometric mean of 4.81% when subjects consumed a freely chosen diet increased by 35% to 6.47% with maximum meat consumption (P = 0.075). When nonheme absorption was adjusted to normalize for differences in iron status using serum ferritin correction and the 3 absorption periods were pooled, multiple regression analysis indicated no significant relation with heme or nonheme iron, vitamin C, calcium, phosphorus, fiber, or tea content of the diet with the exception of animal tissue (P = 0.013). We conclude that the higher iron status associated with the consumption of an omnivorous diet is due more to the intake of heme iron than to the enhancing effect on nonheme iron absorption.     

Evaluation of an iron specific checklist for the assessment of dietary iron intake in pregnant and postpartum women

OBJECTIVE: This study developed and validated an iron checklist for assessing dietary iron intake of pregnant and postpartum women. METHODS: The checklist included 65 food and drink items. Iron intake measured by the checklist was compared with a diet history interview by paired t test and by the Bland-Altman method in 54 pregnant women. We then used the checklist to prospectively assess iron intake in a separate group of women in late pregnancy (n = 179) and at 6 mo postpartum (n = 177). The ability of the checklist to predict iron status was evaluated. RESULTS: There was no difference in reported mean iron intakes between the checklist and the diet history and there were good correlations between iron intake estimated from both methods (r = 0.69, P < 0.001 for food alone, r = 0.99, P < 0.001 for food plus supplements). However, the agreement between the two methods at an individual level was low. Pregnant women with low iron intake (lower than the recommended dietary intake) had lower serum ferritin levels (9.7 versus 14.5 microg/L, P < 0.001) and higher risk of iron deficiency (67.5% versus 34.9%, P < 0.0001) compared with women with adequate iron intake (at least the minimum recommended dietary intake), but these differences disappeared when women taking iron supplements were excluded. There was no association between iron intake and serum ferritin at 6 mo postpartum or between iron intake and hemoglobin levels at the end of pregnancy or at 6 mo postpartum. CONCLUSION: This simple iron checklist is a useful tool in describing iron intake of population samples of pregnant women but has limited ability to predict iron status.     

Serum iron curves can be used to estimate dietary iron bioavailability in humans

Erythrocyte incorporation of isotopic iron (Fe) is the standard method for assessing iron bioavailability, but the process is expensive, technically difficult, and gives no information on the kinetics of absorption. The main objective of this study was to validate serum Fe curves as measures of dietary iron absorption because previous work demonstrated that serum iron curves can be generated with iron doses as low as 5-20 mg and that up to 20 mg iron can be added to meals without affecting relative absorption. In 3 studies, groups (n = 10, 10, 21) of Fe-deficient, mildly anemic women consumed meals of varying calculated Fe bioavailability, with and without added ferric chloride (10 mg Fe). Blood samples were collected at baseline and every 30 min for 4 h after the meal. Serum Fe concentrations were measured. Areas under the serum Fe curves and peak concentrations were used in different models to estimate Fe absorption and uptake. In 21 subjects, (58)Fe-enriched ferric chloride was added to the meals, and blood was taken 2 wk later to calculate red cell isotope incorporation. The addition of 10 mg Fe to test meals produced measurable serum iron curves even when the meal Fe bioavailability was low. Serum Fe curves were highly reproducible and were affected as expected by food composition. Even the single measurement at the estimated time of peak iron concentration was correlated significantly with erythrocyte incorporation of (58)Fe (r = 0.72, P < 0.0001). Hence the extent and rate of absorption of nonheme iron from meals, rather than in individuals, can be investigated with such subjects without the need for isotopes.