Supplementing iron and zinc: double blind, randomized evaluation of separate or combined delivery

Chang, Stephanie; Arifeen, Shams El; Bari, Sanwarul; Wahed, M. A.; Rahman, Kazi Mizanur; Rahman, Mahbubur; Mahmud, A; Begum, Nazma; Zaman, K.; Baqui, Abdullah H; Black, Robert E.

doi:10.1038/ejcn.2009.127

Cited by 49 publications

(47 citation statements)

References 20 publications

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“…However, a controlled trial in Swedish and Honduran infants providing iron supplements from 6 months to 9 months, among infants with Hb ≥110 g/L, iron treatment increased risk for diarrhoea 70. Recent controlled iron supplementation trials (12.5–15 mg Fe/day) in Peru71 and Bangladesh72 reported a significant increase in diarrhoea. Two large trials of iron and folic acid supplementation in infants and children (subjects aged 12–35 months received 12.5 mg Fe/day, younger children received half the dose) in Nepal73 and Tanzania3 reported no difference in diarrhoea incidence.…”

Section: Discussionmentioning

confidence: 99%

Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants

Jaeggi

Kortman

Moretti

et al. 2014

Gut

510

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Section: Discussionmentioning

confidence: 99%

Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants

Jaeggi

Kortman

Moretti

et al. 2014

Gut

510

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show abstract

“…In a controlled trial in infants given iron supplements from six to nine months, iron increased the risk of diarrhea in those infants with Hb ≥ 110 g/L [30]. Controlled iron supplementation trials (12.5–15 mg Fe/day) in Peru [31] and Bangladesh [32] reported a significant increase in diarrhea. Two very large trials of iron (with folic acid) supplementation in Nepal [33] and Tanzania [19], in which children aged 12 to 35 months received 12.5 mg Fe/day and infants aged 1 to 11 months received 6.25 mg Fe/day, reported cause-specific mortality and diarrhea incidence as secondary outcomes.…”

Section: Iron Intake and Diarrheamentioning

confidence: 99%

Iron Fortification of Foods for Infants and Children in Low-Income Countries: Effects on the Gut Microbiome, Gut Inflammation, and Diarrhea

2016

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Iron deficiency anemia (IDA) is common among infants and children in Sub-Saharan Africa and is a leading contributor to the global burden of disease, as well as a hindrance to national development. In-home iron fortification of complementary foods using micronutrient powders (MNPs) effectively reduces the risk for IDA by ensuring that the iron needs of infants and young children are met without changing their traditional diet. However, the iron dose delivered by MNPs is high, and comparable on a mg iron per kg body weight to the supplemental doses (2 mg/kg) typically given to older children, which increases diarrhea risk. In controlled studies, iron-containing MNPs modestly increase risk for diarrhea in infants; in some cases, the diarrhea is severe and may require hospitalization. Recent in vitro and in vivo studies provide insights into the mechanism of this effect. Provision of iron fortificants to school-age children and iron-containing MNPs to weaning infants decreases the number of beneficial ‘barrier’ commensal gut bacteria (e.g., bifidobacteria), increases the enterobacteria to bifidobacteria ratio and abundances of opportunistic pathogens (e.g., pathogenic Escherichia coli), and induces gut inflammation. Thus, although iron-containing MNPs are highly effective in reducing IDA, they may increase gastrointestinal morbidity in infants, and safer formulations are needed.

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“…In 6-to 9-mo-old Honduran and Swedish infants who were given iron supplements, iron increased risk of diarrhea in the nonanemic infants (49). There was a significant increase in diarrhea in 2 controlled iron-supplementation trials that gave 12.5-15 mg Fe/d in Peru (50) and Bangladesh (51). In Nepal (52) and Tanzania (14), large controlled intervention trials of folic acid and iron supplementation (12-to 35-mo-old children received 12.5 mg Fe/d; 1-to 11-mo-old infants received 6.25 mg Fe/d) reported on cause-specific mortality and diarrhea incidence as secondary outcomes.…”

Section: Increasing Iron Intakes and Risk Of Diarrheamentioning

confidence: 99%

The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review

Paganini

Zimmermann

2017

The American Journal of Clinical Nutrition

204

160

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In infants and young children in Sub-Saharan Africa, iron-deficiency anemia (IDA) is common, and many complementary foods are low in bioavailable iron. In-home fortification of complementary foods using iron-containing micronutrient powders (MNPs) and oral iron supplementation are both effective strategies to increase iron intakes and reduce IDA at this age. However, these interventions produce large increases in colonic iron because the absorption of their high iron dose ($12.5 mg) is typically ,20%. We reviewed studies in infants and young children on the effects of iron supplements and iron fortification with MNPs on the gut microbiome and diarrhea. Iron-containing MNPs and iron supplements can modestly increase diarrhea risk, and in vitro and in vivo studies have suggested that this occurs because increases in colonic iron adversely affect the gut microbiome in that they decrease abundances of beneficial barrier commensal gut bacteria (e.g., bifidobacteria and lactobacilli) and increase the abundance of enterobacteria including entropathogenic Escherichia coli. These changes are associated with increased gut inflammation. Therefore, safer formulations of iron-containing supplements and MNPs are needed. To improve MNP safety, the iron dose of these formulations should be reduced while maximizing absorption to retain efficacy. Also, the addition of prebiotics to MNPs is a promising approach to mitigate the adverse effects of iron on the infant gut. Am J Clin Nutr 2017;106(Suppl):1688S-93S.

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Supplementing iron and zinc: double blind, randomized evaluation of separate or combined delivery

Cited by 49 publications

References 20 publications

Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants

Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants

Iron Fortification of Foods for Infants and Children in Low-Income Countries: Effects on the Gut Microbiome, Gut Inflammation, and Diarrhea

The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review

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