Iron deficiency anemia (IDA) is a condition where the body has a low supply of iron or an insufficient number of red blood cells. IDA first became prevalent during the Neolithic revolution dating back 10,000 years. During this time, humans learned to domesticate animals, grow crops and thus, agriculture was born. Human lifestyle and diet changed from carnivorous hunter-gatherers to sedentary farmers with a cereal-based diet. Although humans were raising livestock, consumption of meat declined and consumption of cereal groups, dairy products and eggs, all poor sources of iron, increased. These factors put together led to an increase in IDA. Luckily, there is a simple treatment to IDA — iron supplements. Still, IDA persists and is in fact the most common nutritional disorder in the world! From an evolutionary perspective, being iron deficient actually has some advantages. It’s really a trade-off; although IDA causes fatigue, a lack of appetite, impaired child development and low birth weight in newborns, it can also prevent infection from diseases such as malaria, tuberculosis (TB), and the bubonic plague.
A clinical trial conducted in Nepal and Zanzibar provides some insight to the advantages of IDA. In Nepal, scientists provided iron supplements to children with IDA. Researchers found that it had no effect on child mortality but could potentially protect against diarrhea and acute respiratory illnesses. In contrast, a similar study was conducted in Zanzibar, an island off the coast of Tanzania. Researchers found iron supplements increased hospitalizations by 11% and mortality by 15%. The study in Zanzibar had to be stopped early because of the shocking results.
Global Iron Deficiency Anemia Prevalence in Pre-School Aged Children, 2008 (Source: WHO)
Why did iron supplementation work in Nepal but not in Zanzibar? The answer is: the difference in malaria prevalence. Cases of malaria in Nepal are relatively low but are extremely high in Zanzibar. Tanzania was one of the only countries to have an increasing malaria incidence in 2016. Once the malaria parasite, p. falciparum, has infected a human through a mosquito bite, it requires iron to replicate. Giving iron supplements in high transmission malaria regions is essentially feeding the malaria parasite.
Iron is also critical for the bacteria, mycobacterium tuberculosis, which causes tuberculosis (TB). It requires iron for growth inside the human body and providing iron supplements to recovering TB patients can cause relapse. The bacteria Yersinia pestis causes Bubonic plague, better known as black death or black plague. An overload of iron in the body, otherwise known as hemochromatosis, can increase susceptibility to the Bubonic plague. Experiments in mice have shown that injection with the yersiniabactin iron binding compound, which increases iron binding in the body, also increases the incidence and virulence of Yersinia pestis. Caucasians of European descent are more likely to have hemochromatosis, where black plague was widespread in the Middle Ages.
Compounding upon these discoveries, another study found that over-consumption of tea and coffee can actually decrease iron absorption by as much as 62%. And, as you could have guessed, tea and coffee are primarily grown in Africa and South Asia. Perhaps it is no longer a coincidence that areas of high TB and malaria also have high rates of IDA. We can also speculate that IDA accounted for the low prevalence of the Bubonic plague in Africa. Co-evolution of humans and pathogens has led to the prevalence of IDA in high malaria and TB regions.
Coffee exports by country, 2012 (Source: GeoCurrents)
Although evolution is often thought of as something of the past, it is becoming increasingly significant given the evolution of antibiotic resistant pathogens. It is more crucial now than ever to fully understand how and why IDA evolved, and why it continues to persist in the population. Understanding our evolutionary history may spark innovation for future scientific endeavours and perhaps provide a new perspective on combatting the malaria endemic.