The Relationship Between Ferritin and BMI is Mediated by Inflammation Among Women in Higher-Income Countries, But Not in Most Lower-Income Countries Nor Among Young Children: A Multi-Country Analysis

Jennie N Davis; Anne Williams; Charles D Arnold; Fabian Rohner; James P Wirth; Yaw Addo; Rafael C Flores-Ayala; Brietta M Oaks; Melissa F Young; Parminder S Suchdev; Reina Engle-Stone

doi:10.1093/cdn/nzac139

The Relationship Between Ferritin and BMI is Mediated by Inflammation Among Women in Higher-Income Countries, But Not in Most Lower-Income Countries Nor Among Young Children: A Multi-Country Analysis

Curr Dev Nutr. 2022 Sep 9;6(10):nzac139. doi: 10.1093/cdn/nzac139. eCollection 2022 Oct.

Authors

Affiliations

¹ University of California, Davis Department of Nutrition, Institute for Global Nutrition, Davis, CA, USA.
² University of Otago, Department of Human Nutrition, Dunedin, New Zealand.
³ GroundWork, Fläsch, Switzerland.
⁴ Division of Nutrition, Physical Activity and Obesity, Centers for Disease Control and Prevention, Chamblee, GA, USA.
⁵ Rollins School of Public Health, Emory University, Atlanta, GA, USA.
⁶ Department of Nutrition and Food Sciences, University of Rhode Island, Kingston, RI, USA.
⁷ Global Health Department, Emory University, Atlanta, GA, USA.
⁸ Department of Pediatrics and Global Health, Emory University, Atlanta, GA, USA.
⁹ Division of Global Health Protection, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Abstract

Background: In the presence of inflammation, the serum or plasma ferritin concentration ("ferritin" hereafter) transiently increases, confounding its interpretation as an iron status marker. The extent to which adiposity-related inflammation may influence ferritin interpretation is uncertain.

Objectives: We describe relationships between weight status, inflammation, and ferritin among nonpregnant women of reproductive age (WRA; 15-49 years) and preschool-age children (PSC; 6-59 months) with normal weight to overweight or obesity (OWOB) in differing geographic settings.

Methods: Cross-sectional data were separately analyzed from 18 surveys (WRA) and 25 surveys (PSC) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project, excluding observations with underweight, wasting, pregnancy, or malaria. Relationships were assessed between BMI (in WRA) or BMI-for-age z-score (BAZ; in PSC), inflammatory biomarkers of C-reactive protein (CRP) and/or α-1-acid glycoprotein (AGP), ferritin by linear regression, and potential mediation by CRP and/or AGP in relationships between BMI or BAZ and ferritin with structural equation modeling. Regression and mediation models accounted for complex survey designs. Results were grouped by World Bank income classifications.

Results: In 5 of 6 surveys among WRA from upper-middle and high-income countries, ferritin was significantly positively associated with BMI, and this relationship was partially (or fully, in the United States) mediated by CRP and/or AGP. Mediation was present in 4 of 12 surveys for WRA in low- and lower-middle income countries. Among PSC, ferritin was positively associated with CRP and/or AGP in all surveys, but there were no significant CRP- or AGP-mediated relationships between ferritin and BAZ, except a negative relationship in the Philippines.

Conclusions: Where having OWOB is common among WRA, measurements of inflammatory biomarkers and their uses in interpreting ferritin may improve iron status assessments. While these relationships were inconsistent among PSC, inflammation was common and should be measured to interpret iron status. Included Kenyan trial data are registered at clinicaltrials.gov as NCT01088958.

Keywords: acute phase proteins; assessment; biomarker; ferritin; inflammation; iron status; obesity; overweight.

Associated data

ClinicalTrials.gov/NCT01088958