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Cited by 178Iron Metabolism and DisordersErythropoietin and Anemia TreatmentHemoglobinopathies and Related Disorders

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Daily iron supplementation for improving anaemia, iron status and health in menstruating women

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Low, Michael Sze Yuan, Speedy, Joanna, Styles, Claire E, De-Regil, Luz Maria, Pasricha, Sant-Rayn·2016·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd009747.pub2PMC PMC10182438
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Abstract

BACKGROUND: Iron-deficiency anaemia is highly prevalent among non-pregnant women of reproductive age (menstruating women) worldwide, although the prevalence is highest in lower-income settings. Iron-deficiency anaemia has been associated with a range of adverse health outcomes, which restitution of iron stores using iron supplementation has been considered likely to resolve. Although there have been many trials reporting effects of iron in non-pregnant women, these trials have never been synthesised in a systematic review. OBJECTIVES: To establish the evidence for effects of daily supplementation with iron on anaemia and iron status, as well as on physical, psychological and neurocognitive health, in menstruating women. SEARCH METHODS: In November 2015 we searched CENTRAL, Ovid MEDLINE, EMBASE, and nine other databases, as well as four digital thesis repositories. In addition, we searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and reference lists of relevant reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing daily oral iron supplementation with or without a cointervention (folic acid or vitamin C), for at least five days per week at any dose, to control or placebo using either individual- or cluster-randomisation. Inclusion criteria were menstruating women (or women aged 12 to 50 years) reporting on predefined primary (anaemia, haemoglobin concentration, iron deficiency, iron-deficiency anaemia, all-cause mortality, adverse effects, and cognitive function) or secondary (iron status measured by iron indices, physical exercise performance, psychological health, adherence, anthropometric measures, serum/plasma zinc levels, vitamin A status, and red cell folate) outcomes. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures of Cochrane. MAIN RESULTS: The search strategy identified 31,767 records; after screening, 90 full-text reports were assessed for eligibility. We included 67 trials (from 76 reports), recruiting 8506 women; the number of women included in analyses varied greatly between outcomes, with endpoint haemoglobin concentration being the outcome with the largest number of participants analysed (6861 women). Only 10 studies were considered at low overall risk of bias, with most studies presenting insufficient details about trial quality.Women receiving iron were significantly less likely to be anaemic at the end of intervention compared to women receiving control (risk ratio (RR) 0.39 (95% confidence interval (CI) 0.25 to 0.60, 10 studies, 3273 women, moderate quality evidence). Women receiving iron had a higher haemoglobin concentration at the end of intervention compared to women receiving control (mean difference (MD) 5.30, 95% CI 4.14 to 6.45, 51 studies, 6861 women, high quality evidence). Women receiving iron had a reduced risk of iron deficiency compared to women receiving control (RR 0.62, 95% CI 0.50 to 0.76, 7 studies, 1088 women, moderate quality evidence). Only one study (55 women) specifically reported iron-deficiency anaemia and no studies reported mortality. Seven trials recruiting 901 women reported on 'any side effect' and did not identify an overall increased prevalence of side effects from iron supplements (RR 2.14, 95% CI 0.94 to 4.86, low quality evidence). Five studies recruiting 521 women identified an increased prevalence of gastrointestinal side effects in women taking iron (RR 1.99, 95% CI 1.26 to 3.12, low quality evidence). Six studies recruiting 604 women identified an increased prevalence of loose stools/diarrhoea (RR 2.13, 95% CI 1.10, 4.11, high quality evidence); eight studies recruiting 1036 women identified an increased prevalence of hard stools/constipation (RR 2.07, 95% CI 1.35 to 3.17, high quality evidence). Seven studies recruiting 1190 women identified evidence of an increased prevalence of abdominal pain among women randomised to iron (RR 1.55, 95% CI 0.99 to 2.41, low quality evidence). Eight studies recruiting 1214 women did not find any evidence of an increased prevalence of nausea among women randomised to iron (RR 1.19, 95% CI 0.78 to 1.82). Evidence that iron supplementation improves cognitive performance in women is uncertain, as studies could not be meta-analysed and individual studies reported conflicting results. Iron supplementation improved maximal and submaximal exercise performance, and appears to reduce symptomatic fatigue. Although adherence could not be formally meta-analysed due to differences in reporting, there was no evident difference in adherence between women randomised to iron and control. AUTHORS' CONCLUSIONS: Daily iron supplementation effectively reduces the prevalence of anaemia and iron deficiency, raises haemoglobin and iron stores, improves exercise performance and reduces symptomatic fatigue. These benefits come at the expense of increased gastrointestinal symptomatic side effects.

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Research works printed but not linked: 15

  1. LaManca, 1989, Effects of Iron Supplementation on Aerobic Power, Endurance Performance, Blood Lactate, and Body Iron Stores in Women [Post doctoral thesis]
  2. Larocque, 2006, Iron Status and Cognitive Performance in Adolescent Females [thesis]
  3. Leonard, 2014, Iron Deficiency in Young Australian Women: Role of Iron Knowledge, Dietary Intake and Supplementation, and the Effects on Cognition [Thesis]
  4. Murray-Kolb, 2003, Iron Status, Cognitive Performance, and Behavioral Affect in Young Women [Doctoral thesis]
  5. Walsh, 1989, Effects of iron supplementation on iron status of young female swimmers during pre-season phase of competition, Journal of Swimming Research, 5, 13
  6. Greene, 1995, Effect of Iron Supplementation on Measures of Cognitive Functioning During Adolescence. [Thesis]
  7. Borenstein, 2008, Introduction to Meta-Analysis (Statistics in Practice)
  8. Brownlie, 2002, Marginal iron deficiency without anemia impairs aerobic adaptation among previously untrained women, American Journal of Clinical Nutrition, 75, 734, 10.1093/ajcn/75.4.734 · DOI
  9. Brownlie, 2004, Tissue iron deficiency without anemia impairs adaptation in endurance capacity after aerobic training in previously untrained women, American Journal of Clinical Nutrition, 79, 437, 10.1093/ajcn/79.3.437 · DOI
  10. Higgins JPT Deeks JJ (editors) Chapter 7: Selecting studies and collecting data. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011 Available from www.cochrane-handbook.org
  11. McNair, 1971, Manual for the Profile of Mood States
  12. The Nordic Cochrane Centre, The Cochrane Collaboration Review Manager (RevMan) 2014
  13. Sterne JAC Egger M Moher D on behalf of the Cochrane Bias Methods Group (editors) Chapter 10: Addressing reporting biases. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011 Available from www.cochrane-handbook.org
  14. World Health Organization, 2011, Prevention of Iron Deficiency Anaemia in Adolescents. Role of Weekly Iron and Folic Acid Supplementation, 1
  15. World Health Organization/United Nations Children's Fund/United Nations University, 2001, Iron Deficiency Anaemia: Assessment, Prevention, and Control. A Guide for Programme Managers

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Metadata

Authors
Low, M. S. Y., Speedy, J., Styles, C. E., De-Regil, L. M., & Pasricha, S.-R.
Affiliations
  • Walter and Eliza Hall Institute of Medical Research (AU)
  • Australian Red Cross Lifeblood (AU)
  • Micronutrient Initiative; Research and Evaluation; 180 Elgin Street, Suite 1000 Ottawa ON Canada K2P 2K3
  • University of Oxford (GB)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2016-04-18
Volume
2016
Issue
4
Pages
CD009747-CD009747
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd009747.pub2
PMC
PMC10182438
OpenAlex
W2336621515
Cited by
178
References
139
Citations by year
2026: 11 · 2025: 20 · 2024: 14 · 2023: 28 · 2022: 13 · 2021: 33 · 2020: 10 · 2019: 15 · 2018: 16 · 2017: 15 · 2016: 2
FWCI
2.27
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
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, menstruating women, iron status, hemoglobin levels, folic acid, vitamin C, cognitive function, iron deficiency, women's health
MeSH terms
Iron Deficiencies, Adolescent, Adult, Female, Hemoglobin A, Humans, Iron, Menstruation, Middle Aged, Randomized Controlled Trials as Topic, Anemia, Iron-Deficiency, Dietary Supplements

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