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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.

Numerous studies have shown that iron-loaded diets increase markers of lipid peroxidation in rats, but few have addressed the effects of oral iron supplements on these markers. We investigated the effects of daily and intermittent iron supplements on iron and vitamin E status, and lipid peroxidation. Iron supplements were administered in doses equivalent to those often given to pregnant women in the developing world. In Study 1, iron-deficient (D) and iron-normal (N) rats were fed either 0 or 8000 microgram of supplemental iron daily for 21 d. In Study 2, D rats were fed either the same supplements daily or once every 3 d (8 supplements total). Lipid peroxidation was assessed by breath ethane and pentane and by malondialdehyde (MDA) (using GC-MS). In Study 1, daily supplemented N and D rats had liver nonheme iron concentrations that were 1.8- and 2.7-fold higher, respectively, than those in unsupplemented N rats. Breath ethane levels were also higher in supplemented rats (P < 0.05), but MDA (in plasma, liver, kidney) and liver vitamin E did not differ. Unexpectedly, severely D, anemic rats had significant elevations in the levels of breath ethane, liver MDA and kidney MDA. In Study 2, liver iron and breath ethane decreased progressively (P < 0.05) from 1 d to 3 d after the last iron dose in intermittently supplemented rats. We conclude that iron deficiency results in lipid peroxidation, but that its correction with daily iron supplements results in abnormal iron accumulation and increased lipid peroxidation in rats. These effects are mitigated by intermittent iron supplementation.

Daily iron supplementation programs for pregnant women recommend amounts of iron that are considered by some to be excessive and either lower-dose or less frequent iron supplementation regimens have been proposed. A randomized placebo-controlled study was performed to assess and compare the relative effectiveness of a weekly (WS) or twice weekly (TW) iron supplementation schedule in maintaining or achieving hemoglobin (Hb) levels at term considered to carry minimal maternal and fetal risk (90–130 g/L). Pregnant women (n = 116) at wk 10–30 of gestation (63 WS and 53 TW) were enrolled in the study (52 in WS and 44 TW completed the study). Women were randomly allocated to receive a 120-mg oral dose of iron as ferrous sulfate and 0.5 mg of folic acid weekly (n = 52) or 60 mg iron and 0.25 mg folic acid and a placebo twice weekly (n = 44). Hb hematocrit serum ferritin and transferrin saturation were estimated at baseline and at 36–39 wk of gestation. Baseline dietary data and the presence and intensity of intestinal helminthic infections were assessed. The duration of supplementation was 14 ± 4 wk and the median level of adherence was 60.5%. Hb concentrations improved in women following the TW regimen and in women following WS who had low baseline Hb levels. About 89% of WS women and 95% of TW women maintained Hb levels at term (between 90 g/L and130 g/L) a range associated with optimal pregnancy outcomes. One woman in the TW group exhibited higher Hb levels that potentially carried perinatal risk (>130 g/L). Intermittent iron and folic acid supplementation may be a valid strategy when used as a preventive intervention in prenatal care settings. (authors)

Pregnancy, mostly because of the mitochondria-rich placenta, is a condition that favors oxidative stress. Transitional metals, especially iron, which is particularly abundant in the placenta, are important in the production of free radicals. Protective mechanisms against free radical generation and damage increase throughout pregnancy and protect the fetus, which, however, is subjected to a degree of oxidative stress. Oxidative stress peaks by the second trimester of pregnancy, ending what appears to be a vulnerable period for fetal health and gestational progress. Conditions restricted to pregnancy, such as gestational hypertension, insulin resistance and diabetes, exhibit exaggerated indications of free radical damage. Antioxidants as well as avoidance of iron excess ameliorate maternal and early fetal damage. In rats both iron deficiency and excess result in free radical mitochondrial damage. Estimates of gestational iron requirements and of the proportion of iron absorbed from different iron supplemental doses suggest that with present supplementation schemes the intestinal mucosal cells are constantly exposed to unabsorbed iron excess and oxidative stress. Unpublished work carried out in Mexico City with nonanemic women at midpregnancy indicates that 60 mg/d of iron increases the risk of hemoconcentration, low birth weight and premature birth and produces a progressive decline in plasma copper. These risks are not observed in women supplemented with 120 mg iron once or twice per week. Studies on the influence of iron supplementation schemes on oxidative stress are needed.

This 7-mo double-blind study compared the efficacy of two iron supplementation schemes in improving iron nutrition among 116 healthy fertile-age women. They were randomly distributed in three groups, receiving: Group 1, iron + folate (60 mg and 250 microg, respectively) daily for 3 mo (currently recommended scheme), and folate (250 microg) weekly the subsequent 4 mo. Group 2, folate daily, and 60 mg iron only once weekly for 3 mo, and then weekly iron + folate for 4 mo. Group 3, folate daily for 3 mo and then weekly for 4 mo. At baseline, 16% had depleted stores (plasma ferritin

The mechanisms of the previously described competitive zinc:iron interaction were explored in healthy human volunteers, using the increment in plasma zinc concentration after an oral dose of 25 mg of zinc as zinc sulfate as the index of zinc absorption. Ferric iron in a 2:1 Fe/Zn ratio reduced the plasma uptake of zinc, but to a significantly lesser degree than ferrous iron; addition of 1 g of ascorbic acid increased the magnitude of the inhibitory effect of ferric iron to that seen with ferrous iron. An inverse relationship between some indices of iron status in adult women, or of parenteral iron administration in a child, and the magnitude of zinc:iron interaction was observed. Saturation of the intestinal mucosa with consecutive-day doses of therapeutic iron did not influence the uptake of zinc administered alone or in the context of a 2:1 ferrous iron:zinc ratio in solution. The results are most consistent with a combination of an intraluminal competition of the two minerals and an intracellular competition at a site "distal" to the regulatory step by which iron nutriture modulates the entry of iron into the body, but "proximal" to the site at which the daily administration of therapeutic doses of iron blocked the passage of dietary iron.

By serial determination of the change in plasma nickel concentration following a standard dose of 22.4 mg of nickel sulfate hexahydrate containing 5 mg of elemental nickel, the bioavailability of nickel was estimated in human subjects. Plasma nickel concentration was stable in the fasting state and after an unlabeled test meal, but after the standard dose of nickel in water was elevated 48.8, 73.0, 80.0, and 53.3 microgram/1, respectively, at hours 1, 2, 3, and 4. Plasma nickel did not rise above fasting levels when 5 mg of nickel was added to two standard meals: a typical Guatemalan meal and a North American breakfast. When 5 mg of nickel was added to five beverages-whole cow milk, coffee, tea, orange juice, and Coca Cola-the rise in plasma nickel was significantly suppressed with all but Coca Cola. Response to nickel also was suppressed in the presence of 1 g of ascorbic acid. Phytic acid in a 2:1 molar ratio with nickel, however, did not affect the rise in plasma nickel. The chelate of iron and ethylenediaminetetraacetate, NaFeEDTA, an iron-fortifying agent suggested for application in Central America, slightly but not significantly depressed plasma nickel rise at 2 hours, whereas disodium EDTA depressed plasma nickel levels significantly below the fasting nickel curve at 3 and 4 hours postdose. These studies suggest that the differential responses of inorganic nickel to distinct foods, beverages, and chemically-defined dietary constituents could be important to human nutrition.