While iron deficiency anemia is the most common type of the condition, anemia can have many causes, including genetic disorders, a shortage of vitamin B12 or folic acid, infection and cancer. According to the World Health Organization, iron deficiency anemia affects about a billion people across the planet.
How can iron deficiency, and even consequent anemia, protect us from infections? "With rare exception, bacteria need iron to grow," Zarychanski explains. "If you take away the iron, the bacteria can't multiply, which means your body can more easily overcome illness, especially infection."
This was most famously hinted at in 2003, in a large trial of iron supplementation for children in Tanzania. The study was halted early because the kids who had been given iron supplements developed a much higher risk of severe malaria than those given a placebo. As a result, the World Health Organization stopped recommending universal iron supplementation for children in malaria-endemic areas. According to Hal Drakesmith, a molecular immunologist at the University of Oxford who studies the role of iron in human immunity but was not connected to this study: "There is now pretty good evidence that iron deficiency could protect against severe malaria in children."
Studies have also suggested that iron can make tuberculosis worse. A lab experiment conducted in 2005 showed that giving mice iron-removing compounds limited the growth of the TB-causing bacteria. In other trials, people with tuberculosis fared worse when they received iron supplements.
Meanwhile, a 2007 investigation in Gambia demonstrated that elevated levels of iron were associated with a higher rate of death in people with HIV infection, while a 2013 study showed that children given iron to reduce anemia were more likely than others to develop diarrhea and respiratory conditions.
According to Zarychanski, iron deficiency is our "innate antimicrobial strategy." Once infected, humans appear to be programmed to reduce production of iron so that bacteria or viruses don't have enough of this nutrient to grow.
Scientists speculate that this may have helped our ancestors survive epidemics. Even in an era of antibiotics, such a strategy may still be useful, especially where pathogens are abundant and health care is poor. "There is evidence that low-iron states or even anemia could be beneficial in a setting where there is a big burden of infectious disease," Drakesmith says.
In addition, when too much iron enters a human body, the delicate balance of bacteria in the gut can be upset. As Drakesmith explains, lactobacilli, one of the "good" bugs that help digestion, don't require iron to grow, while the "bad" ones, such as salmonella and E.coli, do need it to grow.
In states of iron overload - which can be caused by diet, taking supplements or from genetic disorders - pathogenic bacteria can multiply and overwhelm the protective ones. A study of Kenyan infants published this year showed that iron fortification can result in considerably more diarrhea.
Beyond that, says Suzy Torti, a professor of molecular biology at the University of Connecticut, "in a local environment such as the gut that sees iron every day, excessive intake may increase cancer risk." She adds that "there is now a pretty convincing body of literature" connecting high intake of dietary iron with colon cancer. Not only does iron damage DNA by promoting oxidative stress - a disturbance in the balance between free radicals and antioxidants, which can cause cancer - it also stimulates the growth of tumors once they have begun, studies suggest.
Zarychanski suggests that anemia that commonly accompanies severe conditions such as cancer, heart disease and autoimmune disorders is an adaptive physiologic mechanism that helps us fight illness. In three separate studies, transfusing blood to treat anemia was found to cause more harm than good. Patients with myocardial infarction, for example, were more likely to have another heart attack within 30 days.
On the flip side, a 2008 clinical trial showed that bloodletting - which reduces iron stores - decreased cancer risk among otherwise healthy people with peripheral arterial disease.
Does that mean the medieval cure of bloodletting to combat illness wasn't completely misguided? "I've often thought there was something in there," admits Torti, adding that the potential utility of such a treatment depends on when, how and to whom it is administered.
Researchers say that future treatments for some diseases may involve using the iron hunger of pathogens and cancer cells against them. "Bacteria can become resistant to antibiotics, but what they can't do is avoid their need for iron to grow," Drakesmith says. "This is potentially another way of attacking them. Even if a minor iron deficiency develops, that wouldn't be too bad if it really helps to slow down the infection."
A 2008 study conducted on mice showed that iron chelators (compounds that remove iron from the body) limited the growth of bacteria. Similar treatment may be beneficial in cancer. "Targeted iron-depleting agents that could get to tumors and withdraw the iron from them could have a therapeutic potential," Torti says.
Does that all mean we should ditch iron-rich foods such as spinach when we get the flu? No, the scientists say.
"We do know that restoring iron deficiency with iron treatments does improve fatigue," Drakesmith says.
And while iron deficiency and mild anemia may sometimes be good, there's a fine line between benefits and costs, and that line is still being measured. "Just like a fever that gets too high, severe anemia can, after all, be a debilitating and detrimental condition," Zarychanski says.
