Iron helps growing bodies, but could too much do harm?

One of the most basic responsibilities parents have is to feed their babies. Compared with the smorgasbord of possibilities later in life, food options for early babyhood are thankfully quite limited: The entire menu is either breast milk or formula (or often, both).

While the benefits of breast milk are clear, infant formula has come a long way since the days of concoctions brewed up in the kitchen with raw cow milk. (Side note: Please don’t do that.) In the United States, the Food and Drug Administration keeps an eagle eye on formula recipes and their safe preparation. And one important ingredient in the recipe is iron.

Overall, iron has been a clutch addition, drastically dropping the rates of anemia caused by iron deficiency. But that success story may not be so straightforward. Some nutrition experts say that formula makers are adding more iron than necessary, and that this extra iron may not be harmless. A provocative opinion article published in October suggests that excess iron during infancy might actually be dangerous.

In the article, scientists raise the possibility that too much iron early in life can kick off a chain of events that leaves the brain vulnerable decades later to neurodegenerative diseases such as Parkinson’s. The idea, proposed in the September Nature Reviews Neurology, is speculative — no human data exist to make that claim. But just as low iron levels are dangerous, it’s not hard to imagine that high levels are too, says article coauthor Dominic Hare, an analytical neurochemist of the University of Technology Sydney and the Florey Institute of Neuroscience and Mental Health in Melbourne. “My concern is that it’s entirely possible that this may be a case of too much of a good thing,” he says.

Before you swear off iron for you and your baby, please consider this: Iron is absolutely essential for growing bodies. The element isn’t just crucial for keeping the body humming along, iron is also needed to build it. Nowhere is this more obvious than in the developing brain. If babies don’t get enough iron, their brain cells have trouble forming connections and insulating the ones they have. Severe iron deficiency during infancy can lead to permanent mental and physical impairments. “I’ve spent a lifetime of research on the brain and behavior effects of insufficient iron,” says pediatrician Betsy Lozoff of the University of Michigan in Ann Arbor. “There are dozens and dozens of studies that show that’s problematic.”

Doctors have been aware of these consequences for decades. In the 1930s, anemia caused by iron deficiency was rampant among infants. Thirty years later, public health officials took action, and by the mid-1960s, several iron-supplemented formulas appeared on the market.  In 1969, the American Academy of Pediatrics issued guidelines stating that formula ought to be fortified with iron. This intervention worked, and in many cases, spectacularly well. In the ’70s and ’80s, rates of iron-deficiency anemia started dropping. “Iron fortification of infant foods is one of the big public health successes,” Lozoff says.

Yet this victory may be carrying along some extra baggage, Hare and his colleagues write. In young babies, the blood-brain barrier may not be fully sealed. Excess iron in the body could slip through this leaky barrier and reach the brain, Hare and colleagues propose. Studies from animals have shown that lots of iron early in life leads to higher iron levels in the brain later.

And that may be concerning, Hare says: Some studies have found troublesome links between high iron levels in the brain and certain brain diseases. Iron piles up in nerve cells found in the substantia nigra, the brain area that’s decimated in Parkinson’s disease. Alzheimer’s plaques made of the sticky amyloid-beta protein are lined with iron. And iron accumulation in the brain has been linked to flare-ups of multiple sclerosis. It’s not clear whether iron problems actually contribute to these disorders or whether iron is just a marker of them, but the link is definitely worth exploring.

So far, we don’t know whether an iron overload early in life might influence disorders that strike in old age. But there is a small hint about iron’s effects during childhood, and it comes from one of Lozoff’s studies. She and her colleagues followed 473 Chilean infantswho received formula with either low levels of iron (about 2.3 milligrams of iron per liter) or regular levels (about 12.7 milligrams per liter). (Most formula in the United States has 10 to 12 milligrams of iron per liter.)

Ten years later, children who received the higher-iron formula scored worse on spatial memory tests and visual-motor integration than the children who received the low-iron formula, Lozoff and colleagues reported in JAMA Pediatrics in 2012. The lower scores came mainly from a small number of children who had the highest levels of hemoglobin (a proxy for iron). So the idea is that for babies who already get plenty of iron, adding even more may be harmful. Because the results seem to be driven by just a handful of children — about 13 kids in each group — the study gives only a preliminary look at the issue. “That is a call for more research rather than the basis for any change in policy, because it’s only a few kids,” Lozoff says.

What’s more, bodies have evolved precise ways of regulating their iron stores. “If extra iron is given, iron absorption will decrease,” says pediatric gastroenterologist Robert Baker of the University at Buffalo. Given this tight bodily oversight, it’s not clear how much iron actually gets into the brain.

Yet the fact remains that the standard levels of iron in U.S. formulas are probably higher than necessary. European countries use formula with about half the iron (between 4 and 7 milligrams per liter) and have similar rates of iron-deficiency anemia, Hare says.

A recent panel of iron nutrition experts agreed that “current levels of iron fortification of infant formulas in the U.S. are not optimal and do not reflect current evidence for iron requirements in this age group.” Their new recommendations, published in October in a supplement to the Journal of Pediatrics, suggest dropping iron intake at birth and then gradually increasing it as the baby grows. For the first three months of life, babies would get by with the iron accumulated during gestation — no fortification needed, the panel wrote. After three months of age, infants ought to start taking formula that has between 2 and 4 milligrams of iron per liter, the recommendations suggest. Then from six to 12 months of age, infants should get between 4 and 8 milligrams of iron per liter.

Those recommendations are for healthy, full-term babies. Babies born prematurely or at low birth weights may have different needs, the committee wrote.

Clearly, iron deficiency can be disastrous, particularly for developing babies. And there’s no doubt that decades of fortification has reduced anemia. But Hare and colleagues raise a provocative issue: Just because some iron is good doesn’t mean more is better.  Perhaps iron overload comes with its own risks that remain to be seen. The first wave of infants who got iron-fortified formula are still relatively young and won’t hit their 60s until the 2030s.

So for now, Hare’s idea about the dangers of iron overload remains just that — an idea. It’s an idea that I find compelling, but the data aren’t there yet. “We are working on this as fast as we can,” Hare says. But following the bread crumbs from infant feeding to elderly brain changes is tough. And in the end, the trail may disappear.

It’s hard to sit with uncertainty, even more so when that uncertainty relates to what to feed your baby. The best we can do is to keep asking questions — and encouraging scientists, policy people and formula-makers to do the same.