Iron deficiency is defined by a group of international experts as "a health-related condition in which iron availability is insufficient to meet the body's needs which can be present with or without anemia."¹ Iron is critical for the generation and functioning of numerous proteins, especially in cells with high energy demand, such as cardiac and skeletal myocytes. Also vulnerable to iron depletion are cells with a high mitogenic potential, including hematopoietic, epithelial, and immune cells.²

Iron deficiency (ID) and iron deficiency anemia (IDA) continue to be of worldwide concern. Among children in the developing world, iron is the most common single-nutrient deficiency.³ Even in industrialized countries, despite a demonstrable decline in prevalence, it is more prevalent in medically underserved populations. ID remains a common cause of anemia in young children, and in National Health and Examination Survey (NHANES) 2003-2010, IDA occurs in up to 3% of children age 1 to 2 years⁴ and 2.4% of adolescent girls in the United States.⁵ ID is more common: 13.5% of 1- to 2-year-old girls, 3.7% of 3- to 5-year-old girls, and up to 16% in adolescent girls. ID is twice as likely in overweight adolescents than in those with normal weight. ID in early life, with or without anemia, is associated with long-term neurodevelopment and behavior impairment, which may persist into adulthood.^5,6,7,8 A recent prospective, observational study in Canada with children 12 to 40 months old showed that children with chronic iron deficiency at baseline or persistent nonanemic iron deficiency despite treatment had cognitive scores 6 to 7 points lower at 4 and 12 months, compared with children with iron sufficiency. This implicates that early detection and/or prevention may be critical.⁹ In adolescents with ID, iron fortification has demonstrated improved verbal learning, concentration, and memory.⁷ Iron supplementation has also improved aerobic capacity,¹⁰ decreased fatigue scores,¹¹ and decreased restless leg syndrome (RLS)¹² among nonanemic but iron-deficient girls.