Iron deficiency without anaemia is a potential cause of fatigue: meta-analyses of randomised controlled trials and cross-sectional studies
Open accessAbstract
Fe deficiency is a prevalent nutritional disease, and fatigue is a common complaint in the general and patient population. The association between Fe deficiency without anaemia (IDNA) and fatigue is unclear. Here, we performed a meta-analysis to evaluate the therapeutic effect of Fe on fatigue in patients with IDNA and the association between IDNA and fatigue in the population. Articles from the PubMed database up to 19 January 2016 were systematically searched. A total of six relevant randomised controlled trials (RCT) and six relevant cross-sectional studies were identified. All outcomes were converted into effect sizes. In the meta-analysis of the six RCT, we identified a significant therapeutic effect of Fe in fatigue patients with IDNA (pooled effect size 0·33; 95 % CI 0·17, 0·48; I 2=0·0 %; P<0·0001). A sensitivity analysis found that the overall results (i.e. significant association) were robust. In the meta-analysis of the six cross-sectional studies, the association between IDNA and fatigue was not significant (pooled effect size 0·10; 95 % CI -0·11, 0·31; I 2=57·4 %; P=0·362). A sensitivity analysis found that the overall results (i.e. no significant association) were not robust; removal of one study made the outcomes significant. These meta-analyses suggest that improving Fe status may decrease fatigue. Further research is necessary to identify diagnostic criteria for selecting fatigue patients who might benefit from Fe therapy and to assess the prevalence of IDNA with fatigue in the general population.
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Two systematic reviews including pregnant women, blood donors and children concluded benefit of iron supplementation, although in the review by Yokoi and Konomi, the benefit was limited to randomised controlled trials.
“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.”
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 [39]
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)
Experimental — accuracy not yet measuredIron deficiency, with or without anemia, is associated with fatigue and weakness.
“Numerous studies report fatigue and weakness when anemia due to iron deficiency is present, i.e., when hemoglobin levels are below 120 g/L in women or 130 g/L in men, and also during iron deficiency without anemia, i.e., with normal or borderline hemoglobin levels [112].”
From Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020) · cites this paper as [112]
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- Authors
- Yokoi, K., & Konomi, A.
- Affiliations
- Seitoku University (JP)
- Yasuda Women's University (JP)
- Corresponding author
- Yokoi, Katsuhiko
- ORCID
- Yokoi, Katsuhiko
- Venue
- British Journal Of Nutrition
- Publisher
- Cambridge University Press (CUP)
- Published
- 2017-05-28
- Volume
- 117
- Issue
- 10
- Pages
- 1422-1431
- ISSN
- 0007-1145 (ISSN-L)
- 1475-2662
- OpenAlex
- W2626884782
- Cited by
- 62
- References
- 45
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 15 · 2021: 4 · 2020: 16 · 2019: 4 · 2018: 7
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal Of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (25350137)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- iron deficiency without anemia, fatigue, iron supplementation, iron status, iron therapy
- MeSH terms
- Iron Deficiencies, Fatigue, Humans, Iron
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