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International Formula Council Critique of the Study, “Increased murine neonatal iron intake results in Parkinson-like neurodegeneration with age”
(published in Neurobiology of Aging)

The article by Julie Andersen from the Novato, California, Buck Institute for Age Research is an extension of prior work by this group to evaluate the hypothesis that brain iron may be involved in the development of Parkinson’s disease.  In this study the scientists used an animal model to study the part of the brain affected by human Parkinson’s disease.  Such work is important in the search for better ways to manage this debilitating condition.  However, it is inappropriate and misleading based on this study to infer clinical implications related to current infant feeding practices, both for parents faced with feeding decisions and persons afflicted by Parkinson’s disease.

The authors report finding that an extremely high intake of iron administered once daily for seven days by oral gavage in early life caused delayed damage to the part of the mouse brain that in humans is involved in Parkinson’s disease.  Half of the animals received a chemical known to damage the area of the brain involved in Parkinson’s disease.  For impact the authors state that the dose of iron given to the animals is like that used in iron-fortified infant formula.  It is not.  Also, the iron was administered as a single nutrient, not balanced by the other nutrients that modify its absorption, as is the case in infant formula.  It is also important to note that the authors misstated the iron content of mature human milk by a factor of 10 (0.03 mg/L vs. 0.3 mg/L).  In fact, the dose used in the study is more than 2,000 times the amount of iron consumed by breastfed infants and more than 60 times that consumed in iron-fortified infant formula on a weight-adjusted basis (see Table below).  It is more than ten times the dose of iron used to treat iron deficiency anemia in infants. 

It is important to note limitations of the animal model used in this study.  Mice are far more immature at birth than are human infants and mouse milk provides approximately 50 times the concentration of iron found in human milk.  Therefore it is not particularly surprising that providing an iron intake of equivalent to more than 40 times that already present in mouse milk could be detrimental to the health of the animal.  Acute and chronic toxic effects of high levels of iron intake and iron accumulation in the body are medically well known.  This toxic level of dietary iron could not only damage the developing brain, but other tissues in the body.  The authors did not report the iron accumulation in other tissues as a result of the iron dosing.  The form of iron used in this study is not one of the many forms of iron that have been confirmed by FDA as safe for use in infant formula.

This study also needs to be put in an appropriate context.  Iron is a mineral essential to human health.  In the absence of additional dietary iron by 4-6 months of age, exclusively breastfed infants begin to show evidence of iron deficiency.  Infants who are breastfed for an extended period of time need additional sources of iron in their diet.  Iron deficiency anemia is associated with slowed infant development, which may cause permanent brain damage.  Routine use of the well-accepted public health measure of providing non-breastfed infants with iron-fortified infant formula has reduced the incidence of iron deficiency anemia and its possible lifelong consequences from 20 % to 2 % in at-risk US populations.  To be eligible for use in the USDA Women, Infants and Children feeding program, infant formulas must be iron-fortified because of the extensively studied and proven benefit of providing iron in the diet of young infants. 

Conclusion:  It is inappropriate to put this important public health advance and the normal developmental status of infants at risk on the basis of a rodent study using extremely high doses of iron in a model with unproven relevance to infant feeding practices.  Parents should not make feeding decisions based on the results of this report. 

Table: Dietary iron concentration in milk, infant iron intake, and comparison with mouse iron intake as reported in Kaur et al. 2006

#Intake based on a 5 kg infant ingesting 750 mL per day.
*Value was calculated by dividing mouse iron intake per body weight by infant iron intake per body weight.

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