Too much of a good thing: Evolutionary perspectives on infant formula fortification in the United States and its effects on infant health

Abstract

Recently, there has been considerable debate regarding the appropriate amount of iron fortification for commercial infant formula. Globally, there is considerable variation in formula iron content, from 4 to 12 mg iron/L. However, how much fortification is necessary is unclear. Human milk is low in iron (0.2-0.5 mg/L), with the majority of infant iron stores accumulated during gestation. Over the first few months of life, these stores are depleted in breastfeeding infants. This decline has been previously largely perceived as pathological; it may be instead an adaptive mechanism to minimize iron availability to pathogens coinciding with complementary feeding. Many of the pathogens involved in infantile illnesses require iron for growth and replication. By reducing infant iron stores at the onset of complementary feeding, infant physiology may limit its availability to these pathogens, decreasing frequency and severity of infection. This adaptive strategy for iron regulation during development is undermined by the excess dietary iron commonly found in infant formula, both the iron that can be incorporated into the body and the excess iron that will be excreted in feces. Some of this excess iron may promote the growth of pathogenic, iron requiring bacteria disrupting synergistic microflora commonly found in breastfed infants. Evolutionarily, mothers who produced milk with less iron and infants who had decreased iron stores at the time of weaning may have been more likely to survive the transition to solid foods by having limited iron available for pathogens. Contemporary fortification practices may undermine these adaptive mechanisms and increase infant illness risk.

Is early-life iron exposure critical in neurodegeneration?

“…A review of the possible impact of iron fortification on the establishment of intestinal flora and early infant health posits that the depletion of iron stores in infants that is normally interpreted as low-level anaemia might, in fact, be a mechanism that evolved to restrict access to iron for potential pathogens, and that iron supplementation in early life disrupts this long-standing defence mechanism. 129 Vulnerability to toxins is high during intrauterine life and childhood, when critical windows of susceptibility might exist owing to immature physiological mechanisms for adequate processing of chemicals. Such vulnerability might also manifest when essential nutrients such as iron are introduced in excess.…”

Scientific Opinion on the essential composition of infant and follow-on formulae

“…The absorption of iron from human milk is high. Absorption efficiencies up to 50 % have been reported but have been observed to vary down to 25 % with infant age and total dietary iron intake Domellöf, 2007;Quinn, 2014).…”

“…Assuming that, on average, 0.15 mg/day of iron has to be absorbed from formula in the first four to six months of life and that under a conservative assumption the absorption efficiency is around 10 % (range 7-14 %) (Quinn, 2014), an iron intake from formula of 1.5 mg/day in the first four to six months of life would ensure a sufficient iron supply to the infant.…”

Infant food applications of complex carbohydrates: Structure, synthesis, and function

“…Most infant foods are milk-based products fortified with ingredients such as vegetable oils, starches, and vitamins to mirror the molecular composition of human milk. [17–19] Molecular composition is critical as infant formula is the sole source of nutrition for a vulnerable population. The first four to six months of life represent a period of rapid growth and development.…”