Efficacy of Iron Therapy on Fatigue and Work Capacity in Non-Anemic Iron Deficient Adults: A Systematic Review of Randomized Controlled Trials
Bibliographic record
Abstract
Abstract INTRODUCTION: Iron supplementation in iron deficiency anemia is standard practice, but the benefits of iron supplementation in iron deficient non-anemic (IDNA) individuals remains controversial. We conducted a systematic review and meta-analysis to identify the effects of iron therapy on fatigue and work capacity in iron deficient non-anemic adults. METHODS: We included randomized controlled trials of adults (≥18 years) who were iron deficient but non-anemic. Interventions included oral, intramuscular or intravenous iron supplementation; all therapy doses, frequencies and durations were included. We included trials that evaluated outcomes at least 1 month from the initiation of iron therapy. Comparators included placebo or active therapy. Our primary outcome measures were self-reported fatigue and objective measures of work capacity. Secondary outcomes included the incidence of anemia, change in hemoglobin concentration and serum ferritin, and the incidence of adverse outcomes including iron toxicity, constipation, diarrhea, gastrointestinal intolerance and nausea. We searched Medline, Embase, CENTRAL, CINAHL, SportDiscus, and CAB Abstracts from inception to October 31, 2016. We searched the World Health Organization's ICTRP for relevant ongoing trials and performed forward searches of included trials and relevant reviews in Web of Science. We assessed internal validity of included trials using the Cochrane Risk of Bias tool, and the external validity using the GRADE methodology. RESULTS: From 11580 citations we included 18 unique trials, and 2 companion papers enrolling 1162 patients (Table 1). Trials were published between 1989 and 2015, and all trials were published in peer-reviewed journals. Exclusively healthy females (aged 17 to 55 years old) with varying levels of fitness (sedentary to well-trained) were enrolled in all but three studies. Iron interventions consisted of iron supplementation administered orally, intramuscularly or intravenously. Of the trials evaluating oral supplements, all but one used ferrous sulfate (13 trials, 721 participants). Intravenous iron was administered in three trials (395 participants), and intramuscular iron in one trial (16 participants). In trials using oral iron, the mean daily elemental iron dose was 86.9mg (± 49.1mg; range: 16 to 200mg). In trials reporting intravenous iron, the mean daily elemental iron dose was 566mg (± 330mg; range 200 to 1000mg) and mean total elemental iron dose 767mg (± 206mg; range 500 to 1000mg). Among all studies, the mean duration of iron therapy was 46 days (± 30 days; range 1 to 112 days), and mean duration of follow-up was 57 days (± 24 days; range 28 to 112 days). Fatigue was evaluated in four trials enrolling 714 participants. Iron supplementation was associated with a reduction in subjective measures of fatigue when assessed by either the Piper Fatigue Scale (PFS), the Current and Past Psychological State scale (CAPPS), visual analog scale or Brief Fatigue Inventory questionnaire (BFI) (SMD -0.38; 95% CI -0.52 to -0.23; I2 0%). Work capacity was reported in 10 trials (291 participants); all but one of the trials employed at least one of three common aerobic tests of work capacity: time trial, time to exhaustion, or VO2 max performance from a graded exercise test. In two trials (79 participants) that used 15 km time trials, iron supplementation was not associated with improved exercise capacity (SMD -0.09; 95% CI -0.53 to 0.35; I2 0%). In four trials (69 participants) that used time-to-exhaustion tests, iron supplementation did not significantly improve exercise capacity (SMD 0.25; 95% CI -0.22 to 0.73; I2 0%). Nine trials (235 participants) reported VO2 max as a surrogate measure of work capacity. Iron supplementation did not increase VO2 max (SMD 0.11; 95% CI -0.15 to 0.37; I2 0%). CONCLUSION: In iron deficient non-anemic adults, iron supplementation is associated with reduced subjective measures of fatigue, but not with objective improvements in work capacity. Given the global prevalence of both iron deficiency and fatigue, patients and practitioners could consider a course of iron supplementation to improve symptoms of fatigue in presence or absence of documented anemia. Download : Download high-res image (262KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.016 | 0.060 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.017 | 0.015 |
| Bibliometrics | 0.006 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".