Symptomatic Iron Deficiency Without Anemia

Summary and Comment |
August 23, 2012

Symptomatic Iron Deficiency Without Anemia

  1. Allan S. Brett, MD

Oral iron improved fatigue symptoms in nonanemic menstruating women with low ferritin levels.

  1. Allan S. Brett, MD

Does iron deficiency cause fatigue in the absence of anemia? If so, can oral iron therapy improve symptoms? To find out, Swiss researchers identified 198 menstruating women with fatigue who had normal hemoglobin levels (≥12.0 g/dL; mean, 13.5 g/dL), low or low-normal serum ferritin levels (<50 µg/L; mean, 23 µg/L), and no other obvious cause of fatigue. Participants were randomized to receive either daily ferrous sulfate (80-mg elemental iron) or placebo.

At baseline, the average score on a standardized fatigue index was 25 (maximum score, 40). At 12 weeks, mean decrease in fatigue score was significantly greater in the iron group than in the placebo group (–12.2 vs. –8.7). In the iron group, mean hemoglobin concentration increased by 0.3 g/dL and mean ferritin level increased by 12 µg/L. These changes, although modest, were statistically significant relative to the essentially unchanged levels in the placebo group.


In this study, low-dose iron improved fatigue in nonanemic, menstruating women whose iron stores were marginal (as assessed by serum ferritin levels). The findings suggest that clinicians should check both blood counts and serum ferritin levels when menstruating women present with fatigue. However, several caveats should be noted: The placebo effect was substantial, blinding might have been compromised (because iron can change stool color), we don't know whether the 4-point difference in fatigue scores is clinically important, and scores on several quality-of-life indicators were not significantly different between the iron and placebo groups.


Reader Comments (2)

Walter Doege

The article is important for daily clinical practice disregarding methodological issues (acute or chronic fatigue is not mentioned, age is not mentionated and so on). Fatigue is a common symptom. Acute fatigue with no other noticed cause with normal hemoglobin level and low ferritin level is improved with iron supplementation. Chronic fatigue requires a detailed evaluation for seeking other causes. Chronic fatigue is a common complaint in depressive and anxiety disorders. And chronic fatigue syndrome is a complex diagnosis that requires psychiatric evaluation and treatment and can be considered a psychiatric disorder with few guidelines for good clinical practice. This article points out the role of careful medical evaluation of any symptomalogy. I mention fatigue as a common and heterogeneous symptom and even as a psychiatric disorder when presenting chronic evolution with few guidelines for evaluation and treatment in primary attention care and specialty practice.

Competing interests: None declared

Sandeep Saluja

I thought we already knew this and were regularly implementing in clinical practice.

Competing interests: None declared

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