Elsevier

Nutrition Research

Volume 24, Issue 11, November 2004, Pages 875-887
Nutrition Research

Twice the recommended daily allowance of iron is associated with an increase in plasma α-1 antichymotrypsin concentrations in Guatemalan school-aged children

https://doi.org/10.1016/j.nutres.2004.06.008Get rights and content

Abstract

The effects of iron on zinc status, oxidative stress, and inflammation were assessed in a randomized placebo-controlled trial; 66 children aged 8 to 11 years received iron (20 mg/d of elemental iron), zinc (42.5 mg/d of elemental zinc), or iron and zinc combined (20 and 42.5 mg/d, respectively) for 8 weeks. Hemoglobin, plasma ferritin (FT), and zinc concentrations were determined, and oxidative stress was based on plasma α-tocopherol, β-carotene, and thiobarbituric acid–reactive substance. Inflammation was based on increased α-1 acid glycoprotein, C-reactive protein, and α-1 antichymotrypsin (ACT) concentrations. At baseline, 19% of children were iron deficient (FT < 20 μg/L) and 69% had hypozincemia (zinc < 10.7 μmol/L) being distributed equally among the groups. Supplementation with iron or zinc alone improved, respectively, plasma FT or zinc concentrations (2-factor analysis of covariance, P ≤ .03), but no treatment interactions were found. Although none of the supplementation strategies was associated with oxidative stress or inflammation (2-factor analysis of covariance, P > .05), ACT concentrations increased with iron alone compared with the other supplementation strategies (median test, P < .01). The increase in ACT may represent a marker of peripheral activated oxidative stress; thus, twice the recommended daily allowance of iron alone warrants concern in augmenting reactive low-molecular-mass iron in nonanemic populations, although combination with zinc may mitigate this phenomenon.

Introduction

Iron supports oxidative metabolism. It is essential for gas exchange at tissue and cellular levels through oxygenation of hemoglobin in red cells and myoglobin in skeletal muscle [1]. Like many other transition elements, it possesses unfilled atomic orbitals that allow it to coordinate electron donors and participate in redox processes [2], [3] This advantage that makes iron an excellent catalyst also makes it a potentially hazardous agent because reactions involving oxygen can favor the formation of free radicals [2], [3].

Iron has been implicated in the pathology of several chronic degenerative diseases through its enhancement of free radical formation. Epidemiological studies have shown a positive association between ferritin concentrations and myocardial infarction in Finnish men [4], and a strong prediction of 5-year progression of carotid atherosclerosis by serum ferritin concentrations [5]. Excessive deposition of cerebral iron can also contribute to Parkinson's disease [6] and other neurodegenerative diseases such as Alzheimer's disease [7]. Finally, iron overload has been implicated in diabetes, hypertension, and cancer development in people with hemochromatosis [8]; even in those with no genetic predisposition, iron supplementation can enhance the risk for liver disease [9]. Because of its potential oxidative activity, iron concentrations are carefully controlled by iron-regulating proteins, maintaining a labile iron pool that is adequate for metabolic functions but reducing the levels of free iron that might generate free radical chain reactions or oxygen-reactive species [1], [10]. Thus, a concern of any iron intervention should be its possible contribution to altering iron's labile pool.

Iron is one of the most abundant elements in the earth's crust, whereas paradoxically, iron deficiency is the world's most common and widespread nutritional disorder [11]. It is estimated that 66% to 80% of the world's population may be iron deficient [11], [12]. In Guatemala, iron deficiency anemia (IDA) represents a moderate public health problem [12], [13]. Contributing factors include parasitic infections [14] and foods high in inhibitory dietary fiber and phytic acid such as corn tortillas [15], [16]. Hence, iron supplementation is an appropriate strategy to reduce iron deficiency and IDA [17].

Nonetheless, iron supplements can antagonize zinc absorption in adults [18]. Solomons [19] postulated that a total dose of >25 mg of iron may produce a measurable effect on zinc absorption. The present study was conducted to assess whether a dose of iron, equivalent to twice the recommended daily allowance (RDA) for school-aged children [20], would affect zinc status or induce oxidative stress and inflammation.

Section snippets

Methods and materials

We conducted a randomized placebo-controlled trial of iron or zinc alone or in combination. This efficacy study took place in Guatemala City, Guatemala, between February and April 2000. School children from low-income families, aged 8 to 11 years, were enrolled at a local public school with separate morning and afternoon sessions for girls and boys, respectively. Inclusion criteria included usual good health and the absence of chronic diseases. After screening, 77 schoolchildren (40 girls and

Results

Children were followed up for 54 days, during which 12.5% (5/40) of girls and 16% (6/37) of boys missed 5 or more days of classes and did not receive at least 90% of the supplementation dosage; they were excluded from this efficacy analysis. Micronutrient status of children at baseline did not differ among supplementation groups (Table 1). Hemoglobin concentrations ranged from 121 to 182 g/L at baseline; only one child had anemia based on a cutoff level of 121 g/L (anemia in 8- to 12-year old

Discussion

The 1995 Guatemalan National Micronutrient Survey determined that 26% of school-aged children suffered from IDA [13], making IDA a moderately serious public health problem in this population [12]. In this regard, iron supplementation with 30 to 60 mg/d of elemental iron is recommended in areas where IDA is a public health problem [12], [40]. In the present study, a daily dose of 20 mg of elemental iron was provided to compensate for high consumption of foods rich in chelating substances [14],

Acknowledgments

We are grateful for the collaboration of the children, parents, and authorities in the República de El Salvador and República de Colombia public schools in Guatemala City, Guatemala.

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