Does moderate iron deficiency protect against childhood illness? A test of the optimal iron hypothesis in Tanzania

Abstract

Our results do not support the optimal iron hypothesis as conventionally formulated. The fact that we did not find an effect where some other studies have may be due to differences in study design, sample (e.g., age), or the baseline pathogenic ecology. Alternatively, it may be more fruitful to investigate iron regulation as an allostatic system that responds to infections adaptively, rather than to expect an optimal pre-infection value.

Lower incidence of respiratory infections among iron-deficient children in Kilimanjaro, Tanzania

“…Consistent with the pattern reported from Tanzanian [19] and in contrast to northern Kenya [6], elevated biomarkers of inflammation and diagnosed infectious diseases were more common, in cross-section, among children with severe iron deficiency (IDA) than iron replete children in Kilimanjaro. However, the incidence of diagnosed infectious disease was lowest among children with mild-to-moderate IDE; this pattern was restricted to respiratory infectious disease, such that risk for respiratory infection among children with IDE was 76% lower than that of iron replete children.…”

“…Among 5–10-year-old children in northern Kenya, the prevalence of infectious disease was highest among iron replete children (adjusted odds ratio, aOR: 2.9; P = 0.01) and no evidence of increased infectious disease prevalence among children with IDA due to compromised immune protection was apparent [6]. However, among a nationally representative sample of 6–59-month-old children in Tanzania, the prevalence of infectious disease was highest among children with IDA (aOR: 2.6; 95% CI: 1.76, 3.70) [19]. The disparity between these two studies, which employed very similar biomarkers and analyses, may be attributable to differences in the infectious disease ecologies of northern Kenya and Tanzania.…”

Anaemia, iron deficiency and susceptibility to infection in children in sub‐Saharan Africa, guideline dilemmas

“…As iron may be needed for pathogen functioning, a way for the host to protect itself from worsening infections is to create a state of functional iron deficiency in the presence of an infection (Hadley & DeCaro, ). This iron withholding response to microbial invasion – hypoferraemia of infection or functional iron deficiency – is mainly induced by hepcidin, a small amino acid primarily synthesized by hepatocytes (Nicolas et al , ; Park et al , ; Pigeon et al , ), as well as by several other cells, although in much lower quantities (Kroot et al , ).…”

The reproductive ecology of iron in women

“…However, iron withholding is an effective part of the human immune system, in what researchers call “nutritional immunity,” or the withholding of important nutrients from pathogens to reduce their reproductive rates (Oppenheimer, ; Weinberg, ). A study among Kenyan children found iron‐deficient children had lower rates of severe infection than the iron‐replete children, who had much higher odds of infection than any other group (Wander et al, ), although this relationship is not always consistent (Hadley and DeCaro, ). It has been hypothesized that mild IDA may be an adaptation that helps protect against infectious disease mortality (Denic and Agarwal, ).…”