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

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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  • Oral iron therapy often causes significant gastrointestinal side effects such as constipation, abdominal pain, nausea, and bloating.

    “However, an important unexplained clinical limitation of oral iron therapy is that it often causes significant gastrointestinal (GI) side effects such as constipation, abdominal pain, nausea, and bloating [5-7].”

    From Oral Iron Supplementation—Gastrointestinal Side Effects and the Impact on the Gut Microbiota (2021) · cites this paper as [7]

    The 'Any gastrointestinal side effects' and 'Hard stools/constipation' sections report increased rates among women taking iron. The 'Abdominal pain' section finds no definitive increase, and the Main results find no evidence of increased nausea; the retrieved passages do not address bloating. The review therefore supports the general GI-side-effect claim, but not every symptom in the list as an established effect. (LLM, conf=0.86)

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  • In a systematic review of healthy menstruating women, iron supplementation, irrespective of iron status or anaemia, improved haemoglobin and measures of iron stores.

    “In a systematic review of healthy menstruating women, iron supplementation, irrespective of iron status or anaemia, improved haemoglobin and measures of iron stores.37”

    From Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials (2018) · cites this paper as [37]

    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)

    Experimental — accuracy not yet measured

  • Clinical trials and guidance on the manipulation of iron status have most often related to treatment of anemia.

    “Clinical trials and guidance on the manipulation of iron status have most often related to treatment of anemia [46], such as in the context of menstruation [52], pregnancy [53], and chronic kidney disease [54].”

    From Associations of genetically determined iron status across the phenome: A mendelian randomization study (2019) · cites this paper as [52]

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Research works printed but not linked: 1

  1. [8]8. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to Meta-Analysis (Statistics in Practice). Chichester, UK: John Wiley & Sons, 2008. Brainclinics 2015 [Computer program] Brainclinics Products. Neuropsychological tests: IntegNeuro. Nijmegen, The Netherlands: Brainclinics Product, 2015.

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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 · 2015: 1
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 › 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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