Zinc Protoporphyrin Is a Reliable Marker of Functional Iron Deficiency in Patients with Inflammatory Bowel Disease

Diagnostics (Basel). 2021 Feb 21;11(2):366. doi: 10.3390/diagnostics11020366.

Eleni Leventi 1, Aysegül Aksan 2 3, Carl Thomas Nebe 4, Jürgen Stein 2 5, Karima Farrag 2 5


Author information

  • 1Klinik für Gastroenterologie, Diabetologie und Infektiologie, Klinikum Hanau, 63450 Hanau, Germany.
  • 2Interdisziplinäres Crohn Colitis Centrum Rhein-Main, 60594 Frankfurt am Main, Germany.
  • 3Institute of Nutritional Science, Justus-Liebig University, 35392 Giessen, Germany.
  • 4Facharztpraxis für Laboratoriumsmedizin, 68161 Mannheim, Germany.
  • 5DGD Kliniken Sachsenhausen, Teaching Hospital of the Goethe-Universität, 60594 Frankfurt am Main, Germany.


Iron deficiency (ID) is a common manifestation of inflammatory bowel disease (IBD), arising primarily due to chronic inflammation and/or blood loss. There is no gold standard for ID diagnosis, which is often complicated by concomitant inflammation. Zinc protoporphyrin (ZnPP) correlates with parameters of iron homeostasis and has been identified as a promising marker for ID, irrespective of inflammation. We investigated the diagnostic performance of ZnPP in ID, iron deficiency anemia, anemia of chronic disease and mixed anemia in a cross-sectional study in 130 patients with IBD. Different parameters were compared by receiver operator characteristic (ROC) analysis as detectors of iron-restricted erythropoiesis (IRE). IRE was detected in 91 patients (70.0%); fifty-nine (64.8%) had absolute ID and 23 (25.4%) functional ID. When inflammation was present, ZnPP was a more reliable sole biomarker of IRE than MCV, transferrin saturation (TSAT) or ferritin (AUC; 0.855 vs. 0.763, 0.834% and 0.772, respectively). The specificity of TSAT was significantly lower than ZnPP when inflammation was present (38% vs. 71%, respectively). We conclude that ZnPP is a reliable biomarker of functional ID in patients with IBD and more dependable than ferritin or TSAT, which are influenced by chronic inflammation. We propose that ZnPP may also have utility in patients with other chronic diseases.

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