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Oral iron therapy reduced unexplained fatigue in non-anaemic women with serum ferritin concentrations ⩽50 μg/l
  1. Lorne A Becker, MD
  1. SUNY Upstate Medical University
 Syracuse, New York, USA

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 Q Is iron therapy effective for non-anaemic women with unexplained fatigue?

    Clinical impact ratings GP/FP/Primary care ★★★★★★☆ IM/Ambulatory care ★★★★★★☆


    Embedded ImageDesign:

    randomised, placebo controlled trial.

    Embedded ImageAllocation:


    Embedded ImageBlinding:

    blinded {patients, clinicians, data collectors, and outcome assessors}.*

    Embedded ImageFollow up period:

    1 month.

    Embedded ImageSetting:

    an academic primary care centre and 8 private general practices in western Switzerland.

    Embedded ImagePatients:

    144 women 18–55 years of age (mean age 35 y, based on n = 136) whose primary reason for consulting was fatigue. Exclusion criteria: anaemia (haemoglobin concentration <117 g/l), other obvious physical or psychiatric causes of fatigue, or chronic fatigue syndrome.

    Embedded ImageInterventions:

    oral, long acting ferrous sulphate (Tardyferon, Robapharm, Boulogne, France), 80 mg/day, for 4 weeks (n = 75) or matching placebo (n = 69).

    Embedded ImageOutcomes:

    main outcome was perceived level of fatigue (10 point visual analogue scale [VAS] ranging from 1  =  no fatigue at all to 10  =  very severe fatigue). Secondary outcomes included adherence to treatment.

    Embedded ImagePatient follow up:



    Analysis was by intention to treat. 115 women (85%) had serum ferritin concentrations ⩽50 μg/l, and 69 women (51%) had concentrations ⩽20 μg/l. Mean decrease in the overall intensity of fatigue from baseline to 1 month was greater in the ferrous sulphate group than in the placebo group (table). However, subgroup analysis showed that only women with ferritin concentrations ⩽50 μg/l had decreased fatigue intensity. The groups did not differ for compliance rates (95% v 98%, p = 0.25)

    Oral ferrous sulphate v placebo for women with unexplained fatigue*


    Oral iron therapy improved perceived level of fatigue more than placebo in non-anaemic women with unexplained fatigue. It was unclear if improvement occurred in women with serum ferritin concentrations >50 μg/l.

    Abstract and commentary also appear in ACP Journal Club.


    The small randomised controlled trial by Verdon et al raises several questions.

    Firstly, are the results biologically plausible? Iron is an important component in a number of proteins involved in oxidative processes and muscle functioning, and a recent review of animal and human research found some evidence that iron deficiency without anaemia may lead to decreased physical functioning.1 Maximum oxygen consumption (VO2max) is decreased in non-anaemic women with low iron stores and improves with 6 weeks of iron supplementation.2

    Are the results clinically meaningful? The authors did not report improvement rates, so numbers needed to treat cannot be calculated. The reported 0.97 point decrease on a 10 point VAS is less than the 1.1 to 1.3 points found to represent the minimal clinically appreciable difference when a VAS was used to measure disability3 or pain.4

    How long should the treatment continue? Would more than 1 month of therapy lead to more impressive results?

    Is there a target ferritin concentration? The authors’ subgroup analysis is somewhat questionable, since only 21 women in their sample had ferritin concentrations >50 μg/l.


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    • * See glossary.

    • Information provided by author.

    • For correspondence: Dr B Favrat, University of Lausanne, Lausanne, Switzerland.

    • Source of funding: Robapharm.

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