Plasma Ferritin and Hepcidin Are Lower at 4 Months Postpartum among Women with Elevated C-Reactive Protein or α1-Acid Glycoprotein

The Journal of Nutrition. First published ahead of print April 26, 2017 as doi: 10.3945/jn.116.245803. The Journal of Nutrition Community and International Nutrition Plasma Ferritin and Hepcidin Are Lower at 4 Months Postpartum among Women with Elevated C-Reactive Protein or a1-Acid Glycoprotein 1,2 Josh M Jorgensen, 3 * Zhenyu Yang, 4 Bo Lo¨nnerdal, 3 Caroline J Chantry, 5 and Kathryn G Dewey 3 Department of Nutrition, University of California, Davis, Davis, CA; 4 National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Key Laboratory of Trace Element Nutrition, Ministry of Health of China, Beijing, China; and Department of Pediatrics, University of California, Davis, Medical Center, Sacramento, CA Downloaded from jn.nutrition.org at UNIVERSITY OF CALIFORNIA DAVIS on May 30, 2017 Abstract Background: Ferritin and hepcidin are markers of iron status that typically increase during inflammation or infection. The postpartum period is a physiologically unique life stage in which the relations between these proteins and other markers of inflammation have not been extensively studied. Objective: We aimed to determine whether 2 markers of inflammation [high-sensitivity C-reactive protein (CRP) and a1-acid glycoprotein (AGP)] were associated with ferritin or hepcidin in postpartum women in California. Methods: This is a secondary analysis of a randomized controlled iron-intervention trial. Plasma CRP, AGP, ferritin, and hepcidin were analyzed at 2 and 17 wk postpartum in 114 lactating women. We examined Pearson correlation coefficients between all biomarkers at both time points and differences in mean values of ferritin and hepcidin between those with and without elevated CRP and/or AGP. Results: At 2 and 17 wk postpartum, 58% and 26% of women had CRP >5 mg/L and 78% and 29% had AGP >1 g/L, respectively. Neither CRP nor AGP was significantly correlated with ferritin (r = 0.07 and 20.06; n = 114 at 2 wk; 20.14 and 20.14; n = 95 at 17 wk) or hepcidin (r = 0.18 and 20.03 at 2 wk; 20.05 and 20.14 at 17 wk; P > 0.05 for all). At 2 wk, geometric mean plasma ferritin and hepcidin concentrations did not differ between women with and without elevated CRP or AGP (P > 0.5), but at 17 wk women with elevated CRP or AGP had lower mean (95% CI) ferritin and hepcidin than did women without either elevated CRP or AGP [ferritin: 30.3 ng/mL (23.4, 39.1 ng/mL) compared with 40.2 ng/mL (32.9, 49.2 ng/mL); P < 0.01; hepcidin: 44.3 ng/mL (32.3, 60.9 ng/mL) compared with 67.6 ng/mL (56.1, 81.5 ng/mL); P = 0.02]. Conclusion: Lower ferritin and hepcidin among women with elevated CRP or AGP at 17 wk postpartum suggests that these markers of iron status react differently to physiologic immune activation than to pathologic inflammatory states. J Nutr doi: 10.3945/jn.116.245803. Keywords: iron, ferritin, hepcidin, inflammation, C-reactive protein, a1-acid glycoprotein, postpartum, breastfeeding, lactation Introduction Acute phase proteins (APPs) 6 are a class of proteins whose plasma concentrations increase or decrease in response to inflammation. Plasma ferritin and hepcidin are 2 iron-related APPs, which, in addition to increasing with increased iron status, Supported by the Center for Health and Nutrition Research at the University of California, Davis. Author disclosures: JM Jorgensen, Z Yang, B Lo¨nnerdal, CJ Chantry, and KG Dewey, no conflicts of interest. *To whom correspondence should be addressed. E-mail: jjorgensen@ucdavis. edu. Abbreviations used: AGP, a1-acid glycoprotein; APP, acute phase protein; CRP, C-reactive protein; PNV, prenatal vitamin-mineral supplement; TfSat, transferrin saturation; UCDMC, University of California, Davis, Medical Center. have been shown to increase in an inflammatory state (1, 2). Plasma ferritin, a biomarker of iron storage, increases during infection as iron is sequestered, presumably to prevent patho- gens from utilizing circulating iron for growth. Hepcidin is an iron-regulatory hormone that is stimulated by inflammation or by iron overload. It decreases iron absorption and circulating plasma iron by inhibiting the release of iron from gut enterocytes and reticuloendothelial cells (3). Plasma C-reactive protein (CRP) and a1-acid glycoprotein (AGP) are APPs that are commonly used as indicators of inflammation or infection. CRP rapidly increases within hours of an inflammatory stimulus, reaching a peak 48 h after the initiation of hepatic synthesis. It has a relatively short half-life, a 2017 American Society for Nutrition. Manuscript received December 7, 2016. Initial review completed January 20, 2017. Revision accepted March 20, 2017. doi: 10.3945/jn.116.245803. Copyright (C) 2017 by the American Society for Nutrition 1 of 6