The nutritional assessment of iron status

In nutritional studies to assess the prevalence of iron deficiency, it has been common practice to define 3 stages of increasing severity: iron storage depletion as defined by low serum ferritin, mild iron deficiency without anemia based on laboratory evidence of iron deficient erythropoiesis (IDE), and overt iron deficiency anemia (IDA). While this approach provides a broad perspective of impaired iron status, the main liabilities of iron lack are associated only with the more advanced stage of IDA. Consequently, the hemoglobin determination can be used to screen for nutritionally significant iron deficiency. Having identified anemia, more specific laboratory studies are needed to establish iron lack as the cause. The traditional measurements of iron deficient erythropoiesis (IDE) such as a low transferrin saturation, elevated erythrocyte protoporphyrin, or decreased mean corpuscular volume are commonly used. The major drawback in using these parameters is that they are affected similarly in individuals with the anemia of chronic disease (ACD), a common form of anemia in low socioeconomic populations. Because iron stores are invariably absent in individuals with uncomplicated IDA, a low serum ferritin concentration below 20 micrograms/L confirms the diagnosis of IDA when anemia is present. The main limitation of the serum ferritin is that it is falsely elevated to within the normal range when IDA develops in individuals with concurrent infection or chronic inflammation. When this occurs in a clinical setting, a bone marrow examination is commonly performed to identify IDA. Recent investigations indicate that this cumbersome procedure can be avoided by measuring an important new iron-related measurement, the serum transferrin receptor (TfR). Because the synthesis of TfR is upregulated with tissue iron deficiency, IDA can be identified readily by an elevated serum TfR. Importantly, the serum TfR is normal in individuals with the ACD but becomes elevated if these individuals develop IDA. The optimal combination of laboratory measurements for detecting IDA is the hemoglobin, serum ferritin and serum TfR.