Implications of Reappraising the Iron-Deficiency Anemia Hypothesis

Abstract

In 2009, Walker and colleagues questioned the validity of the iron‐deficiency anemia hypothesis as an explanatory mechanism for the presence of porotic hyperostosis (PH) and cribra orbitalia. They presented evidence demonstrating that iron deficiency inhibits, rather than promotes, marrow hypertrophy and argued a link between both PH and hemolytic or megaloblasic anemias (including vitamin B12 deficiency). This paper suggests that dismissing the iron‐deficiency anemia hypothesis may be premature, but, if dismissed, may result in unforeseen consequences. Vitamin B12 deficiency and iron deficiency often result from similar proximate causes, i.e. lack of animal protein in the diet and sanitation problems that lead to parasitic or diarrheal diseases, thereby promoting nutrient losses. As a result, vitamin B12 deficiency and iron deficiency commonly co‐occur. In individuals with a co‐occurrence of iron deficiency and vitamin B12 deficiency, a possible inhibition of marrow hypertrophy caused by iron deficiency may prevent the development of PH, despite the presence of (vitamin B12) nutritional deficiency. The implications of dismissing the iron‐deficiency anemia hypothesis are that many skeletal populations may exhibit hidden heterogeneity, i.e. individuals who are the most nutritionally stressed, with multiple nutrient deficiencies, would mimic the non‐stressed individuals and neither would show evidence of PH. However, the inclusion of multiple stress indicators and greater understanding of biocultural context in bioarchaeological analyses may mitigate the potential impacts of hidden heterogeneity in the expression of PH. Copyright © 2013 John Wiley & Sons, Ltd.

The skeletal manifestation of malaria: An epidemiological approach using documented skeletal collections

“…Megaloblastic anemia arises in individuals with a nutritional deficiency in vitamin B 12 , and hemolytic anemia arises in individuals with genetic disorders conferring protection from malaria (thalassemia and sickle-cell anemia), as well as in individuals with a malarial infection (Walker et al, 2009). Although Walker et al's (2009) article is still being debated in the literature (Oxenham and Cavill, 2010;Rothschild, 2012;McIlvaine, 2013), a recent article by Gowland and Western (2012) found evidence to support the connection between malaria and skeletal lesions of anemia. They showed through a spatial epidemiological approach that the presence of cribra orbitalia lesions in skeletal remains across Great Britain matched with higher Anopheles mosquito vector presence, lower altitude and marshy environments, and higher incidences of historically recorded undulating fevers consistent with malarial infection.…”

Infant and childhood diet at the passage tomb of Alto de la Huesera (north‐central Iberia) from bone collagen and sequential dentine isotope composition

“…Nutritional deficiencies are seen in 11 cases of cribra orbitalia related to anaemia, though its cause is debated (e.g., vitamin B 12 or iron deficiency, malabsorption, high parasite loads, etc. ; McIlvaine, 2015;Oxenham & Cavill, 2010;Walker, Bathurst, Richman, Gjerdrum, & Andrushko, 2009) and three long bone deformities attributable to rickets (i.e., vitamin D and/or calcium deficiency; Mughal, Salama, Greenaway, Laing, & Mawer, 1999). There are several cases of degenerative disease, entheseal changes, and at least seven cranial depressions and eight postcranial fractures (Etxeberria, 1991;Fernández-Crespo, 2012).…”

Mother City and Colony: Bioarchaeological Evidence of Stress and Impacts of Corinthian Colonisation at Apollonia, Albania

“…CO and PH represent a vascular response to stress, resulting in a sponge-like lesion on the roof of the orbit or the cranial vault, respectively. Both CO and PH are considered nonspecific stress indicators, but they are most commonly linked with nutritional deficiencies, including especially iron or vitamin B 12 deficiency (Stuart-MacAdam, 1987;Walker et al, 2009;McIlvaine, 2013). Both conditions have also been linked with infection (e.g.…”