Biomarkers and the Complexities of Iron Deficiency

According to the World Health Organization, anemia affects at least 50% of women of reproductive age, most prevalently in South Asia and West Africa, and about half of these cases are attributable to iron deficiency (Stevens et al. 2013). Within these developing regions, plant-based energy sources dominate dietary patterns (FAO 2016), with pulses, roots and tubers, cereals, wheat, and rice among the primary commodities.

For the past decade it has been evident that biomarkers, including iron, transferrin, transferrin saturation, soluble transferrin receptor, the ratio of these transferrin assessments, and cytokines, may differentiate anemias associated with chronic disease and iron-deficiency anemia. Potential chronic disease indicators include key factors such as interleukin-1, interferon-γ, alpha₁-antitrypsin, and erythropoietin.

Decades of food composition research have established that the previously mentioned plant-based commodities contain a variety of innate substances that bind cations such as iron, thus reducing their biological availability. For example, iron bioavailability from pulses is only 2–5%, whereas that of ferrous sulfate is approximately 20% (DellaValle et al. 2015). It appears that iron uptake may be upregulated among anemic women. Cereals, legumes, and seeds typically contain substances such as oxalates and phytates that bind minerals, thereby reducing their absorption among humans.

With respect to heme iron, the consensus is that animal protein actually improves its absorption. On the other hand, soy protein appears to decrease the absorption of heme and non-heme iron in humans (Etcheverry et al. 2006). These data illustrate the importance of a food matrix and model systems when evaluating the potential bioavailability of iron and other minerals.

A recent publication acknowledged the global public health significance of iron-deficiency anemia and suggested that iron from insects may contribute to resolving this issue (Latunde-Dada et al. 2016). The publication presented in vitro data signifying that insect iron may be a biologically bioavailable equivalent to meat sources of this nutrient. However, the paper did not adequately assess the chemistry of insect iron (other than possible solubility) while advocating cell culture responses are equivalent to validated in vivo methods, particularly those that invoke iron-depleted animal models or hemoglobin-repletion clinical evaluations among humans.

The complexities of addressing iron-deficiency anemia also involve emerging consensus on appropriate biomarker(s) for this condition (Raiten et al. 2011). For example, instead of hemoglobin or hematocrit for international biological cutoffs for iron-deficiency anemia, iron status could be assessed by serum ferritin, a combination of ferritin and soluble transferrin receptor, or possibly hepcidin. While hepcidin and its relation to anemia is interesting, perhaps of greater clinical significance is its potential role in kidney function, inflammatory processes, fundamental erythropoiesis, and possibly iron accumulation during pregnancy when there may be low hepcidin levels in women and newborns. One of many questions when determining the next generation of biomarkers for iron status involves, in general, the age, gender, genetics, and health status of individuals (Kulik-Rechberger et al. 2016).

The next generation of biomarkers for iron status requires a greater understanding of the functional properties and biological implications of this mineral (Drakesmith 2016). There are several global initiatives evaluating the health implications of next-generation biomarkers (Prentice 2016, van Ommen and Wopereis 2016). For example, BOND (Biomarkers of Nutrition for Development) focuses on harmonizing the processes for making decisions about what biomarkers are best for use in support of research, program development and evaluation, and generation of evidence-based policy.

The other major biomarker initiative is INSPIRE (Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence), which identified five working groups charged to provide guidance within the global food and nutrition enterprise. The public health issues surrounding dietary iron and individual iron status were heightened following an apparent increase in mortality and morbidity among children who were not anemic yet presented infections from malaria and other diseases when provided supplementary iron (Sazawal et al. 2006).

According to the 2016 National Nutrition Research Roadmap, only a few biomarkers appear to be valid for assessing the risk or probability of developing certain chronic diseases or conditions. The food industry, nutrition-based organizations, and pharmaceutical firms should collaborate in the development of noninvasive tests of biological materials, fluid-based biomarkers of food and nutrient intake, new predictive approaches that assess nutritive status, and research tool kits that leverage biomarker profiles. Ultimately, these movements could translate to unique and possibly individual dietary patterns and practical nutrition policies and practices across populations.

Roger Clemens, DrPH, CFS,
Contributing Editor
Adjunct Professor,
Univ. of Southern California School of Pharmacy,
Los Angeles, Calif.
[email protected]