Developmental Physiology of Iron Absorption, Homeostasis, and Metabolism in the Healthy Term Infant

Lönnerdal, Bo; Georgieff, Michael; Hernell, Olle

doi:10.1016/j.jpeds.2015.07.014

Cited by 59 publications

(78 citation statements)

References 63 publications

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“…37 As noted above, human milk contains several prebiotic factors, including a range of oligosaccharides. Lactoferrin, which binds and facilitates the uptake of iron by the enterocyte, 38 is also a prebiotic with important functional characteristics that foster a healthy intestinal microbiome. Lactoferrin binds iron avidly and contributes to the low iron environment in the gut lumen of breastfed infants.…”

Section: Mineral-mineral Interactionsmentioning

confidence: 99%

Balancing Benefits and Risks of Iron Fortification in Resource-Rich Countries

Krebs

Domellöf

Ziegler

2015

The Journal of Pediatrics

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or the last 25 years, the American Academy of Pediatrics (AAP) has endorsed the use of iron-fortified infant formulas, noting "no role for the use of low-iron formulas." The rationale for these policies was the recognition that the increase in the use of iron-fortified formulas, accounting for 80% of all formula sold in 1985, was responsible for the declining prevalence of iron-deficiency anemia in US infants. 1 These recommendations were also based on the absence of evidence of discernible adverse effects. Controlled trials had reported no differences in gastrointestinal symptoms, such as colic, constipation, diarrhea, regurgitation, and fussiness, among infants receiving low-iron vs iron-fortified formulas. 2,3 Likewise, evidence was lacking to support another theoretical concern of clinically significant interactions with other micronutrients, specifically zinc and copper. In 1999, the AAP took an even stronger stand and recommended that low iron formulas be removed from the market entirely, 4 for reasons similar to those of the 1989 policy. Further, it was recommended that the minimum iron content for all term infant formulas be at least 4 mg/L. 4 Currently, standard, term infant formulas on the market are all ironfortified and contain 4-12 mg/L of iron, even though there are some regional differences. In the US, the AAP recommends that infant formulas have an iron content of 10-12 mg/L 5 ; in Europe, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends 4-8 mg/L. 6 In the recommendations, the contrast in the iron exposure of formula-fed infants vs breastfed infants has primarily focused on the better bioavailability of the iron in breast milk. Although an absorption efficiency of approximately 50% is often quoted, some studies have actually reported absorption in the range of 12%-16%, 7,8 making that bioavailability distinction much less potent. This also suggests that absorption of substantial amounts of dietary iron simply is not critical during the early months of life in healthy infants of normal birth weight. Among all the compositional differences between human milk and formula, the differences in iron content are the most extreme. Virtually all mammalian milks are low in iron, with the exception of rodents, in which postnatal growth is extremely rapid. It seems implausible that this conserved biological pattern is without purpose. It is also clear that iron deficiency occurs in breastfed infants only after the very early months of life. The practical challenge is to identify when the birth iron endowment is exhausted, at which point the infant needs a source of iron from the diet. This article will discuss the potential advantages of a low iron intake for the infant and the potential adverse effects of drastically altering this, especially in the first 6 months of life. From the outset, two realities must be acknowledged. First, iron deficiency (especially without anemia) in infants remains common, particularly in high-risk groups, including older normal breastfed i...

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Section: Mineral-mineral Interactionsmentioning

confidence: 99%

Balancing Benefits and Risks of Iron Fortification in Resource-Rich Countries

Krebs

Domellöf

Ziegler

2015

The Journal of Pediatrics

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“…Unfortunately, using baking soda instead of baking yeast has been very common in traditional bakeries in Iran to expedite the process. Consequently, bread phytate content remains high and its pH becomes alkaline, both of which are not favorable for intestinal iron absorption from either fortified or unfortified foods …”

Section: Discussionmentioning

confidence: 99%

“…Consequently, bread phytate content remains high and its pH becomes alkaline, both of which are not favorable for intestinal iron absorption from either fortified or unfortified foods. 26,27 There are several enhancers of iron absorption from both unfortified and fortified breads. 28,29 Although the effect of these enhancers can be evaluated by in vitro experiments, the resulting data must be confirmed by human efficacy studies before implementation of a fortification program at the community level.…”

Section: Discussionmentioning

confidence: 99%

Higher bioavailability of iron from whole wheat bread compared with iron‐fortified white breads in caco‐2 cell model: an experimental study

Nikooyeh

2016

J Sci Food Agric

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“…Because the provision of iron by the supplementation or fortification of foods has been shown to be effective in preventing and treating ID and IDA, there are many such programs in both resource-rich and -constrained settings worldwide (5). The benefits of such programs are indisputable; however, reports are accumulating on various adverse effects of iron that is given to iron-replete infants and young children (6,7). These effects include decreased growth, increased morbidity, interactions with other trace elements (copper and zinc), impaired development, and changed gut microflora.…”

Section: Introductionmentioning

confidence: 99%

Excess iron intake as a factor in growth, infections, and development of infants and young children

Lönnerdal

2017

The American Journal of Clinical Nutrition

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122

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The provision of iron via supplementation or the fortification of foods has been shown to be effective in preventing and treating iron deficiency and iron deficiency anemia in infants and young children. However, iron is a pro-oxidative element and can have negative effects on biological systems even at moderate amounts. An increasing number of studies have reported adverse effects of iron that was given to infants and young-children populations who initially were iron replete. These effects include decreased growth (both linear growth and weight), increased illness (usually diarrhea), interactions with other trace elements such as copper and zinc, altered gut microbiota to more pathogenic bacteria, increased inflammatory markers, and impaired cognitive and motor development. If these results can be confirmed by larger and well-controlled studies, it may have considerable programmatic implications (e.g., the necessity to screen for iron status before interventions to exclude iron-replete individuals). A lack of understanding of the mechanisms underlying these adverse outcomes limits our ability to modify present supplementation and fortification strategies. This review summarizes studies on the adverse effects of iron on various outcomes; suggests possible mechanisms that may explain these observations, which are usually made in clinical studies and intervention trials; and gives examples from animal models and in vitro studies. With a better understanding of these mechanisms, it may be possible to find novel ways of providing iron in a form that causes fewer or no adverse effects even when subjects are iron replete. However, it is apparent that our understanding is limited, and research in this area is urgently needed.Am J Clin Nutr 2017;106(Suppl):1681S-7S.

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Developmental Physiology of Iron Absorption, Homeostasis, and Metabolism in the Healthy Term Infant

Cited by 59 publications

References 63 publications

Balancing Benefits and Risks of Iron Fortification in Resource-Rich Countries

Balancing Benefits and Risks of Iron Fortification in Resource-Rich Countries

Higher bioavailability of iron from whole wheat bread compared with iron‐fortified white breads in caco‐2 cell model: an experimental study

Excess iron intake as a factor in growth, infections, and development of infants and young children

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