Cited by 126Iron Metabolism and DisordersErythropoietin and Anemia TreatmentHemoglobinopathies and Related Disorders

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index; 3 of the 8 sources its claims cite were checked for support.

Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials

Open access

Houston, Brett L, Hurrie, Daryl, Graham, Jeff, Perija, Brittany, Rimmer, Emily, Rabbani, Rasheda, Bernstein, Charles N, Turgeon, Alexis F, Fergusson, Dean A, Houston, Donald S, Abou-Setta, Ahmed M, Zarychanski, Ryan·2018·BMJ Open

DOI 10.1136/bmjopen-2017-019240PMC PMC5892776

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Abstract

Objective Iron supplementation in iron-deficiency anaemia is standard practice, but the benefits of iron supplementation in iron-deficient non-anaemic (IDNA) individuals remains controversial. Our objective is to identify the effects of iron therapy on fatigue and physical capacity in IDNA adults. Design Systematic review and meta-analysis of randomised controlled trials (RCTs). Setting Primary care. Participants Adults (≥18 years) who were iron deficient but non-anaemic. Interventions Oral, intramuscular or intravenous iron supplementation; all therapy doses, frequencies and durations were included. Comparators Placebo or active therapy. Results We identified RCTs in Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health, SportDiscus and CAB Abstracts from inception to 31 October 2016. We searched the WHO’s International Clinical Trials Registry Platform 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 Grading of Recommendations Assessment, Development and Evaluation methodology. From 11 580 citations, we included 18 unique trials and 2 companion papers enrolling 1170 patients. Using a Mantel-Haenszel random-effects model, iron supplementation was associated with reduced self-reported fatigue (standardised mean difference (SMD) −0.38; 95% CI −0.52 to −0.23; I 2 0%; 4 trials; 714 participants) but was not associated with differences in objective measures of physical capacity, including maximal oxygen consumption (SMD 0.11; 95% CI −0.15 to 0.37; I 2 0%; 9 trials; 235 participants) and timed methods of exercise testing. Iron supplementation significantly increased serum haemoglobin concentration (MD 4.01 g/L; 95% CI 1.22 to 6.81; I 2 48%; 12 trials; 298 participants) and serum ferritin (MD 9.23 µmol/L; 95% CI 6.48 to 11.97; I 2 58%; 14 trials; 616 participants). Conclusion In IDNA adults, iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity. Given the global prevalence of both iron deficiency and fatigue, patients and practitioners could consider consumption of iron-rich foods or iron supplementation to improve symptoms of fatigue in the absence of documented anaemia. PROSPERO registration number CRD42014007085 .

AI snapshot

Written from the paper’s full text.

TL;DR

In non-anaemic iron-deficient adults, iron supplementation reduced self-reported fatigue but did not improve objective physical capacity. It increased haemoglobin and ferritin, with evidence graded moderate for fatigue and low for physical capacity.

Key findings

From 11,580 citations, the review included 18 unique trials and 2 companion papers enrolling 1170 patients. Iron supplementation reduced self-reported fatigue (SMD −0.38; 95% CI −0.52 to −0.23; I² 0%; 4 trials; 714 participants).
Iron did not significantly improve objective physical capacity: VO₂ max (SMD 0.11; 95% CI −0.15 to 0.37; I² 0%; 9 trials; 235 participants), 15 km time trial (SMD −0.09; 95% CI −0.53 to 0.35; I² 0%; 2 trials; 79 participants), or time to exhaustion (SMD 0.25; 95% CI −0.22 to 0.73; I² 0%; 4 trials; 69 participants).
Iron significantly increased serum haemoglobin (MD 4.01 g/L; 95% CI 1.22 to 6.81; I² 48%; 12 trials; 298 participants) and serum ferritin (MD 9.23 µmol/L; 95% CI 6.48 to 11.97; I² 58%; 14 trials; 616 participants). Adverse events were sparsely reported; adherence did not differ (RR 1.0; 95% CI 0.99 to 1.01; I² 0%; 12 trials; 958 participants).

Methods

Systematic review and meta-analysis of randomised controlled trials in adults (≥18 years) who were iron deficient but non-anaemic, comparing oral, intramuscular, or intravenous iron with placebo or active therapy; outcomes assessed at least 28 days after starting therapy.
Searched Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health, SportDiscus, and CAB Abstracts from inception to 31 October 2016, plus trial registries and forward searches.
Used Mantel-Haenszel random-effects meta-analysis, mean difference or standardised mean difference for continuous outcomes, I² for heterogeneity, Cochrane Risk of Bias tool, and GRADE; PROSPERO registration CRD42014007085.

Limitations

Stated by the paper: search was limited to English studies; dietary iron fortification studies were excluded; masking oral iron was difficult due to predictable gastrointestinal side effects and stool colour changes; healthy women comprised the population in 15 of 18 trials; follow-up was relatively short (mean 57 days; range 28–112 days); adverse events were sparsely reported; most trials were at unclear risk of bias; publication bias could not be assessed for fatigue because of the low number of included trials.
Evident from the text: subgroup analyses for biological sex, athletic status, and risk of bias were often unevaluable because contributing trials enrolled women of uncharacterised athletic status and were of unclear risk of bias; the fatigue outcome was subjective and potentially vulnerable to imperfect blinding.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1136/bmjopen-2017-019240

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

3 of 8 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured

The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In trials where a proportion of participants were anaemic at enrolment and with the knowledge that anaemia results in decreased physical capacity, iron supplementation has previously been associated with improved maximal and submaximal exercise performance.5–8”
§ Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials > Discussion
What the sources say
- Not checked — no full text of the sourcecites [5] source
- Not checked — no full text of the sourcecites [6] Eichner, 2001, Fatigue of anemia, Nutr Rev source
- Not checked — no full text of the sourcecites [7] source
- Supported
  Table 4 (p. 690S) reports improved maximal oxygen uptake after iron supplementation in a trial that included participants with anemia. The Energetic efficiency section reports improved efficiency across five cycle-ergometer workloads in the same trial and notes that this analysis did not separate anemic from nonanemic participants. The submaximal finding concerns exercise efficiency, not endurance time. (LLM, conf=0.87)
  cites [8] Haas, 2001, Iron deficiency and reduced work capacity: a critical review of the research to determine a causal relationship, J Nutr source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using a Mantel-Haenszel random-effects model, iron supplementation was associated with reduced self-reported fatigue (standardised mean difference (SMD) −0.38; 95% CI −0.52 to −0.23; I2 0%; 4 trials; 714 participants)”
- Also stated in: § Primary outcomes · plain
  “Iron supplementation was associated with a reduction in subjective measures of fatigue when assessed by either the Piper Fatigue Scale,28 the Current and Past Psychological State scale,32 visual analogue scale33 or Brief Fatigue Inventory questionnaire (BFI)31 (SMD −0.38; 95% CI −0.52 to −0.23; I2 0%) (figure 2).”
- Also stated in: § Conclusion · plain
  “In IDNA adults, iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity.”
§ Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials > Abstract > Results
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibratedn = 714
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Iron supplementation significantly increased serum haemoglobin concentration (MD 4.01 g/L; 95% CI 1.22 to 6.81; I2 48%; 12 trials; 298 participants)”
- Also stated in: § Secondary outcomes and adverse events · plain
  “Despite the absence of baseline anaemia, iron supplementation significantly increased serum haemoglobin concentration (MD 4.01 g/L; 95% CI 1.22 to 6.81; I2 48%; 12 trials; 298 participants)18–27 30 34 (see online supplementary appendix 8).”
§ Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials > Abstract > Results
Strength:plain· not yet calibratedCausal:direct· not yet calibratedn = 298
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes

Show all 26 claims

It may state two separate claims as one. 16
Probably not a substantial claim. 16

The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Two systematic reviews included studies of pregnant women, blood donors and children and included data from both randomised and non-randomised trials.38 39 These studies concluded benefit of iron supplementation, although in the review by Yokoi and Konomi39, the benefit was limited to randomised controlled trials.”
§ Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials > Discussion
What the sources say
- Not checked — no full text of the sourcecites [38] Pratt, 2016, Non-anaemic iron deficiency—a disease looking for recognition of diagnosis: a systematic review, Eur J Haematol source
- Partly supported
  The Study selection and characteristics section reports six randomised controlled trials and six cross-sectional studies, including an RCT involving blood donors. The Meta-analysis section reports a significant benefit of iron treatment for fatigue in the RCTs. This paper does not establish that its included studies involved pregnant women or children, and its cross-sectional studies were observational studies, not non-randomised trials. (LLM, conf=0.85)
  cites [39] Yokoi, 2017, Iron deficiency without anaemia is a potential cause of fatigue: meta-analyses of randomised controlled trials and cross-sectional studies, Br J Nutr sourceExperimental — accuracy not yet measured
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In a systematic review of healthy menstruating women, iron supplementation, irrespective of iron status or anaemia, improved haemoglobin and measures of iron stores.37”
§ Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials > Discussion
What the sources say
- Partly supported
  The Discussion (Summary of main results; page unavailable) reports increased haemoglobin and iron stores among women receiving iron. But the Subgroup analysis (page unavailable) says iron did not improve haemoglobin in iron-replete women, so the claim's ‘irrespective of iron status’ qualification is not supported. (LLM, conf=0.88)
  cites [37] Low, 2016, Daily iron supplementation for improving anaemia, iron status and health in menstruating women, Cochrane Database Syst Rev sourceExperimental — accuracy not yet measured
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“From 11 580 citations, we included 18 unique trials and 2 companion papers enrolling 1170 patients.”
- Also stated in: § Trial characteristics and study populations · plain
  “Of the 11 580 citations identified, we included 18 unique trials and 2 companion papers,17 18 enrolling 1170 subjects (figure 1; table 1).”
§ Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials > Abstract > Results
Strength:plain· not yet calibratedn = 1,170
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“While the duration of follow-up in most studies was modest, the mean daily elemental iron dose (86.9±49.1 mg) reflects a recommended ‘treatment’ for patients with iron-deficiency anaemia.41”
§ Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials > Discussion
What the sources say
- Not checked — no full text of the sourcecites [41] source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We used a comprehensive search strategy, an a priori protocol and adhered to established methodological (eg, Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Grading of Recommendations Assessment, Development and Evaluation) guidelines.”
- Also stated in: § Discussion · plain
  “We used an a priori published protocol and followed established methodological guidelines concerning the conduct and reporting of this review.”
§ Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials > Abstract > PROSPERO registration number
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

25 of 25

The paper relies on this without support.
It is unclear whether iron supplementation affects fatigue and physical capacity in iron-deficient but non-anaemic individuals.
“While iron replacement can normalise haemoglobin concentration, restore work capacity and improve fatigue in iron-deficiency anaemia, it is unclear if supplementation affects fatigue and physical capacity in iron-deficient but non-anaemic (IDNA) individuals.”
The paper relies on this without support.
The use of iron supplements is common in the general population and routinely recommended to high performance athletes to enhance performance.
“In the absence of compelling efficacy data on well-being or muscle function, the use of iron supplements is common in the general population and are routinely recommended to high performance athletes to enhance performance.”

2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

Oral-iron trial described as using intramuscular iron
Major
The adverse-events section describes trial 29 as using intramuscular iron, but Table 1 identifies Flink et al (trial 29) as using oral iron.
Not all trials had placebo controls
Minor
The statement that all trials were placebo controlled conflicts with Table 1, which lists zinc gluconate as the control for Donangelo et al.

2 of 2

Quantifying heterogeneity in a meta‐analysis
Higgins, J. P. T., & Thompson, S. G. (2002) · Statistics in Medicine · doi:10.1002/sim.1186 · Cited by 36,763
The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration
Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gøtzsche, P. C., Ioannidis, J. P. A., Clarke, M., Devereaux, P. J., Kleijnen, J., & Moher, D. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000100 · Cited by 28,164
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration
Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gotzsche, P. C., Ioannidis, J. P. A., Clarke, M., Devereaux, P. J., Kleijnen, J., & Moher, D. (2009) · BMJ · doi:10.1136/bmj.b2700 · Cited by 17,648
Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993–2005
McLean, E., Cogswell, M., Egli, I., Wojdyla, D., & de Benoist, B. (2009) · Public Health Nutrition · doi:10.1017/s1368980008002401 · Cited by 2,734
Investigating and dealing with publication and other biases in meta-analysis
Sterne, J. A. C., Egger, M., & Smith, G. D. (2001) · BMJ · doi:10.1136/bmj.323.7304.101 · Cited by 2,225 · cited 1×
“For the primary outcomes of fatigue and work capacity, we evaluated potential publication bias using funnel plot analysis.(16) All tests of statistical inference reflect a two-sided alpha of 0.”
Method
A systematic analysis of global anemia burden from 1990 to 2010
Kassebaum, N. J., Jasrasaria, R., Naghavi, M., Wulf, S. K., Johns, N. E., Lozano, R., Regan, M. C., Weatherall, D. J., Chou, D. P., Eisele, T. P., et al. (2013) · Blood · doi:10.1182/blood-2013-06-508325 · Cited by 2,115
Iron-Deficiency Anemia
Camaschella, C. (2015) · New England Journal of Medicine · doi:10.1056/nejmra1401038 · Cited by 1,678
Iron deficiency and reduced work capacity: A critical review of the research to determine a causal relationship
Haas, J. D., & Brownlie, T. (2001) · The Journal of Nutrition · doi:10.1093/jn/131.2.676s · Cited by 1,186
Vitamin and mineral status: effects on physical performance
Lukaski, H. C. (2004) · Nutrition · doi:10.1016/j.nut.2004.04.001 · Cited by 587
The epidemiology of fatigue: more questions than answers.
Lewis, G., & Wessely, S. C. (1992) · Journal of Epidemiology & Community Health · doi:10.1136/jech.46.2.92 · Cited by 498 · cited 1×
“Unfortunately, patient-reported fatigue is common in community and primary care settings with a prevalence ranging from 7% to 45%.(10) It is estimated that the indirect annual economic consequence of chronic fatigue in the USA is 9.”
Background
Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial
Verdon, F., Burnand, B., Stubi, C.-L. F., Bonard, C., Graff, M., Michaud, A., Bischoff, T., de Vevey, M., Studer, J.-P., Herzig, L., et al. (2003) · BMJ · doi:10.1136/bmj.326.7399.1124 · Cited by 320
Anemia—still a major health problem in many parts of the world!
Milman, N. T. (2011) · Annals of Hematology · doi:10.1007/s00277-010-1144-5 · Cited by 307 · cited 1×
“blood cell haemoglobin content.(3) Reduction in haemoglobin concentration below a threshold (conventionally defined by the WHO as 120 g/L for women and 130 g/L for men) signifies anaemia.”
Background
Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration
Krayenbuehl, P., Battegay, E., Breymann, C., Furrer, J., & Schulthess, G. (2011) · Blood · doi:10.1182/blood-2011-04-346304 · Cited by 270 · cited 1×
“In one trial using the BFI score, fatigue was not significantly different between groups after 12 weeks, although it was improved in the subgroup of participants with the lowest iron stores (ferritin ≤15 ng/mL or transferrin saturation ≤20%).(31) Evaluation of publication bias was not possible due to the low number of…”
Background
Marginal iron deficiency without anemia impairs aerobic adaptation among previously untrained women
Brownlie, T., Utermohlen, V., Hinton, P. S., Giordano, C., & Haas, J. D. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/75.4.734 · Cited by 233 · cited 1×
“Biological sex, duration of follow-up and risk of bias were unevaluable as all trials enrolled women with follow-up of less than 2 months and all were of unclear risk of bias.(19) 22–27 30 34”
Background
Iron supplementation improves endurance after training in iron-depleted, nonanemic women
Hinton, P. S., Giordano, C., Brownlie, T., & Haas, J. D. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.3.1103 · Cited by 228
Daily iron supplementation for improving anaemia, iron status and health in menstruating women
Low, M. S. Y., Speedy, J., Styles, C. E., De-Regil, L. M., & Pasricha, S.-R. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009747.pub2 · Cited by 178 · cited 2×
“In contrast to the systematic review of Low et al,(37) we excluded studies that enrolled patients with anaemia at baseline.(37) While cut-offs for anaemia varied slightly among included trials, this important inclusion criteria reduces (but may not eliminate) the probability that changes in fatigue or muscle function…”
BackgroundResult
Iron supplementation improves progressive fatigue resistance during dynamic knee extensor exercise in iron-depleted, nonanemic women
Brutsaert, T. D., Hernandez-Cordero, S., Rivera, J., Viola, T., Hughes, G., & Haas, J. D. (2003) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/77.2.441 · Cited by 175
What is Fatigue? Pathological and Nonpathological Fatigue
Jason, L. A., Evans, M. A., Brown, M. M., & Porter, N. S. (2010) · PM&R · doi:10.1016/j.pmrj.2010.03.028 · Cited by 172
Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: A randomized controlled trial
Vaucher, P., Druais, P.-L., Waldvogel, S., & Favrat, B. (2012) · Canadian Medical Association Journal · doi:10.1503/cmaj.110950 · Cited by 163
Evaluation of a Single Dose of Ferric Carboxymaltose in Fatigued, Iron-Deficient Women – PREFER a Randomized, Placebo-Controlled Study
Favrat, B., Balck, K., Breymann, C., Hedenus, M., Keller, T., Mezzacasa, A., & Gasche, C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094217 · Cited by 130 · cited 1×
“Biological sex, athletic status (athlete vs non-athlete) and risk of bias could not be evaluated as all trials contributing data to the meta-analyses enrolled women of uncharacterised athletic status and were of unclear risk of bias.(28) 31–33 Subgroup analyses evaluating athletic status and method of iron administrat…”
Non‐anaemic iron deficiency – a disease looking for recognition of diagnosis: a systematic review
Pratt, J. J., & Khan, K. S. (2016) · European Journal of Haematology · doi:10.1111/ejh.12645 · Cited by 126 · cited 1×
“Two systematic reviews included studies of pregnant women, blood donors and children and included data from both randomised and non-randomised trials.(38) 39 These studies concluded benefit of iron supplementation, although in the review by Yokoi and Konomi(39), the benefit was limited to randomised controlled trials.”
Background
Effect of iron injections on aerobic-exercise performance of iron-depleted female athletes
Peeling, P., Blee, T., Goodman, C., Dawson, B., Claydon, G., Beilby, J., & Prins, A. (2007) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.17.3.221 · Cited by 125
Iron supplementation maintains ventilatory threshold and improves energetic efficiency in iron-deficient nonanemic athletes
Hinton, P. S., & Sinclair, L. M. (2006) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602479 · Cited by 121 · cited 1×
“Exclusively healthy women (aged 17 to 55 years old) with varying levels of fitness (sedentary to well trained) were enrolled in all but three studies.(22) 27 29 The WHO cut-off for anaemia (haemoglobin concentration >130 g/L (males) and >120 g/L (females)) was used by nine studies,(19) 22–25 30–32 35 whereas seven stu…”
Method
Effects of iron repletion on blood volume and performance capacity in young athletes
FRIEDMANN, B., WELLER, E., URL, H. M., & rtsch, P. B. (2001) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200105000-00010 · Cited by 114 · cited 2×
“These findings were postulated to be secondary to iron-mediated improvements in muscle oxidative capacity and improved mitochondrial function, the validity of which is unclear.(40) A potential weakness our systematic review is the difficulty masking oral iron due to predictable gastrointestinal side effects and change…”
Background
Effect of iron supplementation on endurance capacity in iron-depleted female runners
KLINGSHIRN, L. A., PATE, R. R., BOURQUE, S. P., DAVIS, J. M., & SARGENT, R. G. (1992) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-199207000-00013 · Cited by 104
Altered metabolic response of iron-depleted nonanemic women during a 15-km time trial
Zhu, Y., & Haas, J. D. (1998) · Journal of Applied Physiology · doi:10.1152/jappl.1998.84.5.1768 · Cited by 99
Supplemental Zinc Lowers Measures of Iron Status in Young Women with Low Iron Reserves
Donangelo, C. M., Woodhouse, L. R., King, S. M., et al. (2002) · Journal of Nutrition · doi:10.1093/jn/132.7.1860 · Cited by 95
Iron deficiency: does it matter?
DALLMAN, P. R. (1989) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.1989.tb01410.x · Cited by 92
Iron Supplementation Maintains Ventilatory Threshold And Improves Energetic Efficiency In Iron-deficient Nonanemic Athletes
Hinton, P. S., & Sinclair, L. M. (2005) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-200505001-02297 · Cited by 84
Effects of iron repletion on &OV0312;O2max, endurance, and blood lactate in women
LaMANCA, J. J., & HAYMES, E. M. (1993) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-199312000-00012 · Cited by 81 · cited 1×
“27 29 The WHO cut-off for anaemia (haemoglobin concentration >130 g/L (males) and >120 g/L (females)) was used by nine studies,(19) 22–25 30–32 35 whereas seven studies used lower values ranging from >110 to <120 g/L,(20) 21 27 28 33 34 36 and baseline haemoglobin concentration was not provided in two trial reports.(2…”
Method
The effects of prelatent/latent iron deficiency on physical work capacity.
Newhouse, I., Clement, D. B., Taunton, J. E., & McKenzie, D. C. (1989) · PubMed · Cited by 77
Effect of Intravenous Iron on Aerobic Capacity and Iron Metabolism in Elite Athletes
Burden, R. J., Pollock, N., Whyte, G. P., Richards, T., MOORE, B., Busbridge, M., Srai, S. K., Otto, J. M., & Pedlar, C. R. (2014) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000568 · Cited by 74
Effects of iron supplementation in female athletes with low serum ferritin concentration
Fogelholm, M., Jaakkola, L., & Lampisjärvi, T. (1992) · International Journal of Sports Medicine · doi:10.1055/s-2007-1021248 · Cited by 70
The effects of prelatent/latent iron deficiency on physical work capacity
Newhouse, I., Clement, D. B., TAUNTON, J. E., & McKenzie, D. C. (1989) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-198906000-00006 · Cited by 70
Iron deficiency without anaemia is a potential cause of fatigue: meta-analyses of randomised controlled trials and cross-sectional studies
Yokoi, K., & Konomi, A. (2017) · British Journal Of Nutrition · doi:10.1017/s0007114517001349 · Cited by 62
A Study of the Effects of Latent Iron Deficiency on Measures of Cognition: A Pilot Randomised Controlled Trial of Iron Supplementation in Young Women
Leonard, A., Chalmers, K. A., Collins, C. E., & Patterson, A. J. (2014) · Nutrients · doi:10.3390/nu6062419 · Cited by 43
Comparison of Two Doses of Elemental Iron in the Treatment of Latent Iron Deficiency: Efficacy, Side Effects and Blinding Capabilities
Leonard, A., Chalmers, K. A., Collins, C. E., & Patterson, A. J. (2014) · Nutrients · doi:10.3390/nu6041394 · Cited by 19
Effect of oral iron supplementation on unstimulated salivary flow rate: a randomized, double‐blind, placebo‐controlled trial
Flink, H., Tegelberg, Å., Thörn, M., & Lagerlöf, F. (2006) · Journal of Oral Pathology and Medicine · doi:10.1111/j.1600-0714.2006.00450.x · Cited by 14
Effects of Iron and Ascorbic Acid Supplementation on Hemoglobin Level and Work Efficiency of Anemic Women
Florencio, C. A. (1981) · Journal of Occupational and Environmental Medicine · doi:10.1097/00043764-198110000-00014 · Cited by 10
Fatigue of anemia
Eichner, E. R. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.2001.tb01886.x · Cited by 9
The effects of supplemental iron on educational achievements of students with "iron deficiency without anemia": a randomized, double-blind, placebo-controlled trial.
Moafi, A., Rahgozar, S., Hajian, M. R., et al. (2012) · HealthMed · Cited by 3

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Hurrie D , Graham J , Rimmer E , et al . Efficacy of iron replacement therapy on fatigue and work capacity in non-anemic adults with iron depletion: a systematic review of randomized controlled trials. PROSPERO International prospective register of systematic reviews, 2014.

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Iron deficiency
Pasricha, S.-R., Tye-Din, J., Muckenthaler, M. U., & Swinkels, D. W. (2021) · The Lancet · doi:10.1016/s0140-6736(20)32594-0 · Cited by 1,069
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Sim, M., Garvican-Lewis, L. A., Cox, G. R., Govus, A., McKay, A. K. A., Stellingwerff, T., & Peeling, P. (2019) · European Journal of Applied Physiology · doi:10.1007/s00421-019-04157-y · Cited by 274

See all 126

Authors: Houston, B. L., Hurrie, D., Graham, J., Perija, B., Rimmer, E., Rabbani, R., Bernstein, C. N., Turgeon, A. F., Fergusson, D. A., Houston, D. S., Abou-Setta, A. M., & Zarychanski, R.
Affiliations: CancerCare Manitoba (CA)
University of Manitoba (CA)
Winnipeg Regional Health Authority (CA)
Université Laval (CA)
University of Ottawa (CA)
Corresponding author: Zarychanski, Ryan
ORCID: Houston, Brett L
Rimmer, Emily
Rabbani, Rasheda
Bernstein, Charles N
Turgeon, Alexis F
Fergusson, Dean A
Abou-Setta, Ahmed M
Zarychanski, Ryan
Venue: BMJ Open
Publisher: BMJ
Published: 2018-04
Volume: 8
Issue: 4
Pages: e019240
ISSN: 2044-6055 (ISSN-L)
DOI: 10.1136/bmjopen-2017-019240
PMC: PMC5892776
OpenAlex: W2796265630
Semantic Scholar: 8c1c95bc5457146c9432f1a5ac8b1bb28520eeaa
Cited by: 126
References: 41
Citations by year: 2026: 12 · 2025: 16 · 2024: 20 · 2023: 13 · 2022: 16 · 2021: 17 · 2020: 15 · 2019: 13 · 2018: 4
FWCI: 2.89
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc
Locations: BMJ Open (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (submittedVersion, other-oa)
PubMed Central (submittedVersion, cc-by-nc)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
Keywords: iron supplementation, iron deficiency anemia, fatigue, physical capacity, VO2max, exercise testing, serum ferritin, oral iron, intramuscular iron, intravenous iron, adverse effects, iron deficiency in pregnancy, iron deficiency in children
MeSH terms: Iron Deficiencies, Adult, Fatigue, Female, Ferritins, Humans, Iron, Male, Randomized Controlled Trials as Topic

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Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials

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