Iron metabolism defined using stable isotopes in obesity

Introduction Iron deficiency is common in overweight (OW) and obese (OB) individuals and was shown to be at least partially mediated by adiposity-related inflammation. The proinflammatory cytokine interleukin 6 (IL6) induces hepcidin expression which may lead to decreased intestinal iron absorption. On the other hand, greater blood volume in OW/OB individuals may increase hemoglobin mass and iron requirements and confound iron biomarkers by hemodilution. Using stable iron isotopes, we have systematically studied iron metabolism in obesity. We have answered the following questions: 1) to what extent is hemodilution responsible for low iron status in OW/OB individuals; 2) what is the difference in iron absorption in OW/OB compared to normal weight (NW) participants and to what extent can ascorbic acid enhance iron absorption; 3) is the effect of obesity on iron absorption reversible by weight/fat loss. Methods In studies 1 and 2 we studied 62 healthy, non-anemic women in Switzerland. We determined blood volume using the carbon monoxide (CO) rebreathing method, body composition by dual energy X-ray absorptiometry (DXA), iron and inflammatory status. Furthermore, we determined iron absorption from two test meals in each person using stable iron isotopes. The test meals consisted of bread with butter and honey, with or without ascorbic acid (+AA/-AA). In study 3 we studied a group of 38 obese participants during weight loss induced by sleeve gastrectomy in Mexico. Iron absorption using stable isotopes was determined 2 and 8 months after sleeve gastrectomy to investigate the effect of weight/fat loss. We further measured iron status, hepcidin, inflammatory markers and anthropometrics including body fat by DXA at both time points. Results In study 1, OW/OB participants had significantly higher blood and plasma volume compared to NW. Furthermore, circulating masses of hepcidin, IL6, Hb and soluble transferrin receptor (sTfR) were higher while total mass of serum iron was lower (all p<0.05). In study 2, we showed that in OW/OB participants iron absorption was only two-thirds that in NW participants (p=0.049) and the increase in absorption with ascorbic acid was 56% in NW and only 28% in OW/OB (p<0.05 compared to –AA). In study 3, total body fat, IL6 and hepcidin were significantly reduced 8 months after surgery compared to 2 months. In subjects who were iron deficient at 2 months post surgery (n=17), iron absorption increased by 28% (from 9.7% to 12.4%) while there was no change in iron replete subjects (5.9% and 5.6%). Conclusion Taken together, the increased Hb mass which increases iron requirements for erythropoiesis and circulating sTfR mass, the reduced iron absorption and blunted effect of ascorbic acid and the obese body’s failure to fully downregulate hepcidin secretion even if iron stores are low indicate that OW/OB individuals may have higher dietary iron requirements. Moreover, increased blood and plasma volume diluted serum iron affecting interpretation of iron biomarkers. Especially in developing and transition countries the current surge in OW/OB may significantly impair efforts to control iron deficiency in vulnerable population groups and new strategies are urgently needed.