Iron deficiency without anemia: An underrecognized and undertreated clinical condition with special focus on colorectal cancer.

Abstract

Iron deficiency is the most common micronutrient deficiency worldwide, affecting approximately 2 billion individuals. Iron deficiency without anemia (IDNA), the stage in which iron stores are depleted but hemoglobin remains within the reference range, is estimated to affect approximately 1-2 billion individuals, although the precise prevalence varies by population, ferritin threshold, and inflammatory status. IDNA remains underrecognized because diagnostic evaluation often focuses on hemoglobin concentrations rather than iron stores. A growing body of evidence demonstrates that IDNA is associated with clinically significant fatigue, impaired cognitive function, anxiety, reduced exercise capacity, and diminished quality of life. Randomized controlled trials and meta-analyses of iron repletion in iron-deficient non-anemic cohorts demonstrate clinically meaningful reductions in fatigue. Emerging observational data have also identified an association between iron deficiency and colorectal neoplasia in selected higher-risk populations such as older adults, men, and postmenopausal women. However, the magnitude of this risk and the role of routine endoscopic evaluation in patients with IDNA remain incompletely defined. This narrative review examines the epidemiology, pathophysiology, origins of under-recognition, clinical manifestations, diagnostic approach, treatment, association with colorectal cancer, and future directions for IDNA in adults.