Is it Time to Reexamine Iron Content in Infant Formula?

A Buck Institute study suggests a need to reexamine iron supplementation in human infant formula, most of which results in the absorption of twelve times the amount of iron versus that absorbed from human breast milk. The suggestion is based on research that shows neonatal mice fed the human equivalent of iron supplementation in human formula developed neurodegeneration akin to that observed in Parkinson’s disease (PD) as they aged. Age is the largest risk factor for PD in humans. The study appears in the June 15 on-line edition of the journal Neurobiology of Aging.

Patients with PD have long been shown to have elevated levels of iron in the brain, compared to those without the incurable, progressive neurodegenerative disorder which affects 1.5 million people in this country. The symptoms of PD include tremor, slowness of movement, rigidity and problems with balance. Epidemiologic studies suggest that there is not a clear correlation between dietary iron intake in adults and the incidence of PD. The question remains, how does the iron get into the brain? Research led by Buck Institute faculty member Julie Andersen, PhD, suggests that the iron can collect in the brain during the first two years of life, before the human blood/brain barrier is fully closed.

The research involved delivering iron orally to mouse pups on a daily basis starting at ten days of age for one week. That time period is equivalent to the first year of human life; the dosage was equivalent to the amount of iron in fortified infant formula. The mice were then allowed to age normally to two, 12, 16 and 24 months of age. Iron levels were measured in the substantia nigra (SN), an area of the brain where dopamine, the neurotransmitter associated with Parkinson’s disease, is made. Excess iron is believed to cause oxidative stress which eventually destroys the neurons which produce dopamine.

Iron levels in the iron-fed pups were found to be significantly increased in the SN by two months of age; by 12 months of age (the human equivalent of middle-age) the mice began to show signs of SN neurodegeneration. Within 16 -24 months (60 to 80 years of age in humans) the mice showed an actual loss of dopamine-producing neurons. All of the mice, bred from the same genetic strain, showed signs of damage.

“We recognize that this work is in mice, not humans,” said Andersen, “We’re not saying not to supplement infant formula with iron, but perhaps the levels need to be adjusted.” Human infant formula, which is regulated by the FDA, is supplemented with iron to prevent iron-deficiency anemia, which can lead to mental retardation. Although iron supplementation in humans shows no discernable adverse effects up to six years of age, its affects later in life have yet to be assessed, according to the American Academy of Pediatrics.

“We really have very few models to study early exposure to toxins as a risk factor for a late-life disease such as PD,” said J. William Langston, MD, CEO and Scientific Director of the Parkinson’s Institute. “We haven’t had good proof of principle; Julie’s work really is one of the few examples where that seems to be the case in an experimental model. Early life exposure to iron does seem to set up a sequence of processes that leads to cell damage in the substania nigra later in life.” Langston added, “That’s a really important principle known as ‘long-latency neurotoxicity’ that scientists have been trying to prove for many, many years. Her work could be groundbreaking, moving this field forward. And of course this research has obvious public health implications.”

Studies involving the mice continue in the Andersen lab; efforts are aimed at determining whether the oxidative damage is reversible, and at what point that could be accomplished. Once the blood/brain barrier is closed, the iron cannot be removed from the brain. An earlier study by Andersen showed that “tying up” excess iron in mice by using a metal chelator (derived from the Greek word for claw) prevented damage to the dopamine-producing neurons of the SN.

“Extensive elimination of iron from the brain is not desirable,” said Andersen. “It is an essential trace metal needed for many biological reactions including the synthesis and release of neurotransmitters. However, we think the results of this study warrant further epidemiological studies in humans, especially as it impacts on neurological function in older individuals.”  Andersen added, “It would also be interesting to assess the value of iron chelation as a possible therapeutic in regards to the progression of age-related neurodegeneration as a consequence of high iron intake in infants.”

Joining Andersen in the study include Deepinder Kaur, lead author on the publication as well as Subramanian Ragajolan and Shankar Chinta from the Buck Institute and Dino Dimonte at the Parkinson’s Institute in Sunnyvale, California. This work was funded as part of a collaborative center grant on the role of the environment in Parkinson’s disease funded by the National Institute of Environmental Health (NIEH).

The Buck Institute is the only freestanding institute in the United States that is devoted solely to basic research on aging and age-associated disease. The Institute is an independent nonprofit organization dedicated to extending the healthspan, the healthy years of each individual’s life.  The National Institute of Aging designated the Buck a “Nathan Shock Center of Excellence in the Biology of Aging,” one of just five centers in the country.  Buck Institute scientists work in an innovative, interdisciplinary setting to understand the mechanisms of aging and to discover new ways of detecting, preventing and treating conditions such as Alzheimer’s and Parkinson’s disease, cancer and stroke.  Collaborative research at the Institute is supported by new developments in genomics, proteomics and bioinformatics technology.