In Focus - Micronutrients and Obesity: iron deficiency & obesity. Ana Carla Cepeda López MD PhD Universidad de Monterrey, Vicerrectoría de Ciencias de la Salud, Departamento de Ciencias Básicas. Monterrey, NL, México.
Outline Backgroud Objetives: study 1, 2 & 3 Methods: studies 1 and 2 Results: studies 1 and 2 Methods: study 3 Results: study 3 Summay of findings Conclusions
Background: double burden of malnutrition Geneva: World Health Organization, 2017.
Background: double burden of malnutrition Coexistence of undernutrition with overweight/obesity, throughout the life course. At the individual, the double burden of malnutrition may manifest itself as two or more simultaneous forms for example, obesity with iron deficiency. Population Household Individual - Environmental - Behavioral - Biological Geneva: World Health Organization, 2017.
Obesity and iron deficiency 1960s: Researchers observed a strong correlation between increased adiposit and decreased serum iron (sfe) y in children and adolescents. 1989: Body size was found to be associated with lower sfe and Tsat, but higher Hb and HCT, in US women. 2003: Overweight Israeli children and adolescents were 1.75 times more likely to have decreased sfe, than those of a normal weight. 2004: US overweight children and adolescents were two times more likely to be ID, than those of a normal weight. 2006: In Iranian children with obesity, ID was three times more prevalent compared to those of normal weight. 2010: Obese Mexican women and children had 2-4 times higher risk of ID compared to normal weight. Am J Clin Nutr. 1963;13. Pediatrics. 2004;114(1). Int J Obes Relat Metab Disord. 2003;27(3):. Eur J Pediatr. 2006; 165(11): J Adolesc Health. 2005;37(4): J Am Diet Assoc. 2009;109(2); Am J Clin Nutr. 1989;50(6). Am J Clin Nutr. 2011,
How it is all linked? There are two possible mechanisms: 1) Hemodilution 2) Hepcidin Brittenham G., Hematology, 2013
How it is all linked: hemodilution? Greater blood volume in OW/OB individuals could be responsible for low iron status and increase iron requirements. Obes Facts. 2014 Apr; 7(2): 82 95.
How it is all linked: Hepcidin? Hepcidin is the main regulator or iron status in our body Iron status regulates hepcidin secretion iron absorption in the gut & storage at macrophages and liver. Hepcidin production: mainly in the liver, small amounts in adipose tissue. Other regulators of hepcidin: Inflammation, hypoxia. Adipose tissue secretes pro-inflammatory cytokines hepcidin expression.
High amounts of adipose tissue trigers chronic low grade inflammation (IL6), IL6 induces HEPCIDIN expression which may reduce iron absorption in overweight/obese persons. Iron deficiency Iron excess / Inflammation IL6 JAK / STAT3 enterocytes macrophages enterocytes macrophages ferroportin ferroportin ferroportin ferroportin Fe Tf, iron transferrin complex HJV, hemojuvelin TFR2, transferrin receptor 2. Nat. Rev. Endocrinol. 6, 26 33 (2010)
Objectives To study iron metabolism in obesity using stable iron isotopes: 1) To identify if greater blood volume (hemodilution) is responsible for low iron status in overweight and obese (OW/OB) individuals. 2) To assess 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) To identify if the effect of OB on iron absorption is reversible by weight/fat loss.
Oral isotopes (Absorption from diet) labelled test meal (2-6 mg 57 Fe) Blood sample after 14 days IV isotopes (systemic utilization) Labelled infusion (100 μg 58 Fe) Shift in the enrichment of 57 Fe and 58 Fein natural 56 Fe in erythrocytes Natural iron in the body ( 56 Fe) Fe absorption + Fe utilization = Fe bioavailability 11
Methods: studies 1 and 2 In 62 healthy, non-anemic women in Switzerland we determined: - Blood volume: the carbon monoxide (CO) rebreathing method. - Body composition: dual energy X-ray absorptiometry (DXA). - Hepcidin, iron and inflammatory status: Blood sample. - Iron absorption: from 2 test meals using stable iron isotopes. The test meals consisted of bread with butter and honey, with or without ascorbic acid (+AA/-AA).
Methods: studies 1 and 2 VISIT 2 Test Meal Administration G1: Fe57 G2: Fe58 + Vit C VISIT 3 Test Meal Administration G1: Fe58 + Vit C G2: Fe57 Screening Day 0 Day 14 Day 15 Day 30 VISIT 1 Blood volume 2 weeks 2 weeks VISIT 4 DXA (+/- 1 week) VISIT 5 Blood sample
Results: study 1 OW/OB participants had significantly higher blood and plasma volume compared to normal weight (** p<0.05; ***p<0.001). Blood Volume Plasma Volume Cepeda-Lopez et al. AJCN. 2018
Results: study 1 Circulating masses of hepcidin, stfr and hemoglobin were higher in OW/OB that in NW participants (*** p<0.001). Cepeda-Lopez et al. AJCN. 2018
Results: study 1 Total mass of serum iron was lower in OW/OB that in NW participants. Cepeda-Lopez et al. AJCN. 2018
Fractional iron absorption (%) Results: study 2 Iron absorption in OW/OB participants was two-thirds that in NW participants (p=0.049). 100 90 80 p < 0.001 p = 0.049 p = 0.004 p = 0.006 70 60 50 The increase in absorption with ascorbic acid was 56% in NW and only 28% in OW/OB (p<0.05 compared to AA). 40 30 20 10 0 NW (n=24) -AA 56% NW (n=24) +AA OW/OB (n=38) -AA 28% OW/OB (n=38) +AA Cepeda-Lopez et al. AJCN. 2015
Influence of vitamin C on iron absorption Action of vitamin C Action of inflammation 12.12.2018 Brittenham G., Hematology, 2013
Methods: study 3 In 38 obese participants during weight loss induced by sleeve gastrectomy at 2 and 8 months in Mexico we determined: Body composition: dual energy X-ray absorptiometry (DXA). Iron absorption: stable isotopes (100μg 58Fe & 6 mg 57Fe) Hepcidin, iron and inflammatory status: Blood samples.
VISIT 1 Test Meal (6mg Fe57) Infusion (100μg Fe58) Administration DXA Blood Sample VISIT 2 Blood sample VISIT 3 Test Meal (6mg Fe57) Infusion (100μg Fe58) Administration DXA Blood Sample VISIT 4 Blood sample Bariatric Surgery Screening 2 months after bariatric surgery 2 weeks 8 months after bariatric surgery 2 weeks
Body fat (%) C-reactive protein (mg/l) Results: study 3 Total body fat and CRP were significantly reduced 8 months after surgery compared to 2 months. 60 P < 0.001 25 P < 0.001 50 20 40 15 30 20 10 10 5 0 Baseline Follow-up 0 Baseline Follow-up Cepeda-Lopez et al. AJCN. 2016
IL 6 (pg/ml) Hepcidin (ng/ml) Results: study 3 IL6 and hepcidin were significantly reduced 8 months after surgery compared to 2 months. 10 P = 0.004 1.3 25 P = 0.03 1.8 8 20 6 15 4 10 2 5 0 Baseline Follow-up 0 Baseline Follow-up Cepeda-Lopez et al. AJCN. 2016
Fractional Iron Absorption (%) Fractional Iron Absorption (%) Results: study 3 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%). A. P = 0.03 42 40 38 36 34 32 30 28 26 24 22 20 18 16 14 12 10 8 6 4 2 0 9.7% Iron Deficent Iron Deficient 12.4% 0 Baseline Follow-up Baseline Follow-up (n=17) (n=17) (n=21) (n=21) B. 42 40 38 36 34 32 30 28 26 24 22 20 18 16 14 12 10 8 6 4 2 Iron Replete Iron Sufficient 5.9% 5.6% Cepeda-Lopez et al. AJCN. 2016
Summay of findings Overweight and obese subjects have increased Hb mass which increases iron requirements for erythropoiesis. Overweight and obese subjects have a reduction in iron absorption and the enahncing effect of ascorbic acid is blunted. The overweight body fails to fully downregulate hepcidin secretion even if iron stores are low. Increased blood/plasma volume leads to diluted serum iron and affects interpretation of iron biomarkers.
Why is this important? Overweight and Obesity: Can worsen iron deficiency through an impairment of iron absorption, and greater catabolic losses of the nutrient. Can deplete iron concentrations, leading to deficiency (anemia). Can influence 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.
Michael B Zimmermann, Isabelle Herter- Aeberli, Alida Melse-Boonstra, Saskia Osendarp, Diego Moretti, Christophe Zeder. Human Nutrition Laboratory, Institute of Food, Nutrition and Health, ETH Zürich, Switzerland. Division of Human Nutrition, Wageningen University, Wageningen, Netherlands. Division of Health Sciences, University of Monterrey, Monterrey, Mexico.