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A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: interactions between iron and zinc
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
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2003 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 77, no 4, 883-890 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2003. Vol. 77, no 4, 883-890 p.
Keyword [en]
Iron, zinc, infants, randomized controlled trial, anemia, Indonesia, micronutrient supplementation
National Category
Medical and Health Sciences
URN: urn:nbn:se:umu:diva-3994PubMedID: 12663287OAI: diva2:142924
Available from: 2004-05-12 Created: 2004-05-12 Last updated: 2010-08-04Bibliographically approved
In thesis
1. Iron and zinc in infancy: results from experimental trials in Sweden and Indonesiaa
Open this publication in new window or tab >>Iron and zinc in infancy: results from experimental trials in Sweden and Indonesiaa
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Iron and zinc are difficult to provide in sufficient amounts in complementary foods to infants world-wide, resulting in high prevalence of both iron and zinc deficiency. These deficiency states cause anemia, delayed neurodevelopment, impaired growth, and increased susceptibility to infections such as diarrhea and respiratory infections.

Design: Two different intervention strategies; reduction of a possible inhibitor of iron and zinc absorption, i.e. phytate, or supplementation with iron and zinc, were applied to two different populations in order to improve iron and zinc nutrition:

In a high-income population (Umeå, Sweden), the amount of phytate in commonly consumed infant cereals was reduced. Healthy, term infants (n=300) were at 6 mo of age randomized to phytate-reduced infant cereals, conventional infant cereals, or infant formula and porridge.

In a low income population (Purworejo, Indonesia), daily iron and zinc supplementation was given. Healthy, term infants (n=680) were at 6 mo randomized to supplementation with iron, zinc, a combination of iron and zinc, or placebo.

Blood samples, anthropometrical measurements, and data on infant neurodevelopment and morbidity were collected. Also, in the Swedish study, detailed information on the dietary intake was recorded.

Results: In the Swedish study, the reduction of phytate had little effect on iron and zinc status, growth, development or incidence of diarrhea or respiratory infections, possibly due to the presence of high contents of ascorbic acid, which may counteract the negative effects of phytate. In the Indonesian study, significant negative interaction between iron and zinc was evident for several of the outcomes; Hb and serum ferritin improved more in the iron only group compared to placebo or the combined iron and zinc group. Further, supplementation with iron alone improved infant psychomotor development and knee-heel length, whereas supplementation with zinc alone improved weight and knee-heel length compared to placebo. Combined iron and zinc supplementation did decrease the prevalence of iron deficiency anemia and low serum zinc, but had no other positive effects. Vomiting was more common in the combined group.

Analyses of dietary intake from the Swedish study showed that dietary iron intake in the 6-11 mo period was significantly associated with Hb, but not serum ferritin at 9 and 12 mo, whereas the opposite was true in the 12-17 mo period, i.e. dietary iron intake was significantly associated with serum ferritin, but not Hb at 18 mo.

Conclusions: The phytate content of commercial infant cereals does not seem to contribute to poor iron and zinc status of Swedish infants as feared. However, the current definitions of iron and zinc deficiency in infancy may overestimate the problem, and a change in the recommended cutoffs is suggested. These studies also indicate that dietary iron is preferably channeled towards erythropoiesis during infancy, but to an increasing amount channeled towards storage in early childhood. This suggests that in evaluating dietary programs, Hb may be superior in monitoring response to dietary iron in infancy, whereas S-Ft may respond better later in childhood. However, as shown in this study, increasing Hb may not necessarily be an indicator of iron deficiency, as more dietary iron increased Hb regardless of iron status.

In the low-income setting combined supplementation with iron and zinc resulted in significant negative interaction. Thus, it is not possible to recommend routine iron-zinc supplementation at the molar concentration and mode used in this study. It is imperative that further research efforts are focused at finding cost-effective strategies to prevent iron and zinc deficiency in low-income populations.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2004. 105 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 887
Public health, Folkhälsomedicin
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
urn:nbn:se:umu:diva-277 (URN)91-7305-631-6 (ISBN)
Public defence
2004-05-28, Sal B, by 1D, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Available from: 2004-05-12 Created: 2004-05-12 Last updated: 2011-04-08Bibliographically approved

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