The double burden of malnutrition: obesity and iron deficiency

Background: The world faces a “double burden” of malnutrition; this is true especially in transition countries like Mexico. The co-existence of obesity and iron deficiency (ID) within a person has been clearly demonstrated in several studies but the mechanisms linking them remain largely unknown. Objectives: To investigate possible mechanisms that link obesity and iron status through the following specific objectives: a) reviewing the existing literature; b) investigating the coexistence of obesity and iron deficiency at the national level in Mexico; c) assessing and comparing iron absorption and blood volume (BV) in healthy, non-anemic women from different body mass index (BMI) categories, and evaluating if ascorbic acid improves iron absorption in overweight (OW) and obese (OB) women; d) evaluating if differences in BV explains reduced iron status in OW/OB women; and e) evaluating whether fat loss in obese subjects decreases inflammation and serum hepcidin and thereby improves iron absorption. Methods: a) A literature review was conducted using Google Scholar and PubMed search engines; b) data from the 1999 Mexican Nutrition Survey, which included 1174 children (aged 5–12 y) and 621 nonpregnant women (aged 18–50 y), was used to assess the relationship between BMI, dietary iron, and dietary factors affecting iron bioavailability, iron status, and inflammation; c & d) healthy, non-anemic Swiss women (n=62) (BMI 18.5-39.9 kg/m2) consumed a stable-isotope labelled wheat-based test meal, without (-AA) and with (+AA) 31.4 mg ascorbic acid. We measured iron absorption, body composition by dual energy X-ray absorptiometry (DXA), blood volume by carbon monoxide (CO)-rebreathing method, iron status, inflammation and serum hepcidin; e) We performed a 6-month, prospective study in OB (BMI, ≥35<45 kg/m2) adults from Mexico (n=..), who had recently undergone laparoscopic sleeve-gastrectomy (LSG). At 2 months and 8 months post-LSG, subjects consumed a test drink with 6mg 57Fe as ferrous sulfate and were intravenously infused with 100 μg 58Fe as iron citrate and we measured body composition by DXA, iron status, hepcidin and inflammation. Results: a) Obesity-related subclinical inflammation and its effects on hepcidin levels seem to be the most plausible explanation for the link between ID and obesity; b) the risk of iron deficiency in OB women and children was 2-4 times that of normal-weight individuals at similar dietary iron intakes. In addition, we found that C-reactive protein but not iron intake was a strong negative predictor of iron status, independently of BMI (P < 0.05); c) dietary iron absorption was lower in OW/OB versus normal weight subjects (Geometric mean (95%CI): 12.9 (9.7, 16.9)%) vs 19.0 (15.2, 23.5)%, P=0.049). Moreover, the enhancing effect of ascorbic acid on iron absorption in overweight/obese (28%) was only half that in normal weight women (56%); d) OW/OB women presented higher absolute blood volume and lower serum iron compared to the normal weight group. BV (r2=0.22, β=-0.29, P=0.02) was a negative predictor for serum iron when adjusted for body iron stores. We developed an equation to calculate BV in OW and OB women considering weight, height and lean body mass; e) Fat loss lead to a reduction of inflammation (Interleukin-6) and hepcidin concentrations. In iron-deficient subjects (n=17), iron absorption significantly increased after fat loss (Geometric mean (95%CI): 9.7% (6.5-14.6) to 12.4% (7.7-20.1) (P=0.03), while in iron sufficient subjects (n=21), it did not change (Geometric mean (95%CI): 5.9% (4.0-8.6) and 5.6% (3.9-8.2)) (P=0.81)). Conclusion: Increased hepcidin concentrations, along with subclinical inflammation, limits dietary iron absorption in subjects with excessive body fat, especially in iron deficient individuals. Due to a dilutional effect of blood volume, ‘true’ hypoferremia might be overestimated in populations with a high prevalence of obesity when using serum iron as an indicator. OW/OB individuals may require: higher dietary iron intake combined with iron absorption enhancers to keep their iron status in balance; and a reduction of the obesity-related inflammatory process in order to ensure adequate iron absorption.