Observational studyThe Journal of clinical investigation2016
Clinical iron deficiency disturbs normal human responses to hypoxia.
Observational study in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01847352 (Effect of Endogenous Iron Status on Hypoxic Pulmonary Vascular Responses and Their Attenuation by Intravenous Iron), which is not on this map. Cited by 62 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Endogenous Iron Status on Hypoxic Pulmonary Vascular Responses and Their Attenuation by Intravenous Iron
Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- The Role of Nutrition in COVID-19 Susceptibility and Severity of Disease: A Systematic Review.The Journal of nutrition · 2021Pooled it
- Supplementation with Iron in Pulmonary Arterial Hypertension. Two Randomized Crossover Trials.Annals of the American Thoracic Society · 2021Trial
- Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trial.BMJ open respiratory research · 2020Trial
- Intravenous iron delivers a sustained (8-week) lowering of pulmonary artery pressure during exercise in healthy older humans.Physiological reports · 2019Trial
- Iron Prevents Hypoxia-Associated Inflammation Through the Regulation of Nuclear Factor-κB in the Intestinal Epithelium.Cellular and molecular gastroenterology and hepatology · 2019Trial
- Oxygenaging: A Physiological Framework for Geroscience.Aging cell · 2026Review
- Gut microbiota and iron deficiency anemia: Mechanisms, microbial signatures, and dietary interactions (A narrative review).Asia Pacific journal of clinical nutrition · 2026Review
- Iron Homeostasis at High Altitude in Patients With Pulmonary Hypertension.Pulmonary circulation · 2026Article
- Iron Deficiency in Pulmonary Hypertension-Prevalence, Impact on Prognosis and Disease Burden in Pulmonary Arterial Hypertension and Pulmonary Hypertension Related to Hypoxia: A Review.International journal of molecular sciences · 2026Review
- Menstrual Health in Servicewomen: The Menstrual Cycle, Menstrual Disturbances, and Occupational Consequences.Sports medicine - open · 2026Review
- Addressing micronutrient deficiencies and vitamin metabolism disorders in pediatric pulmonary hypertension: a strategic proposal for low- and middle-income countries.Frontiers in cardiovascular medicine · 2026Review
- Iron Deficiency and All-Cause Hospitalization Risk in a Clinical Cohort of COPD.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2025Article
- Iron, Hepcidin, and Immunity.Advances in experimental medicine and biology · 2025Review
- Hepcidin and Tissue-Specific Iron Regulatory Networks.Advances in experimental medicine and biology · 2025Review
- Regulated vascular smooth muscle cell death in vascular diseases.Cell proliferation · 2024Review
- Oxygen-sensing pathways and the pulmonary circulation.The Journal of physiology · 2024Review
- Impact of Metal Ions on Cellular Functions: A Focus on Mesenchymal Stem/Stromal Cell Differentiation.International journal of molecular sciences · 2024Review
- Iron deficiency and supplementation in heart failure.Nature reviews. Cardiology · 2024Review
- Dietary mineral intakes predict Coronavirus-disease 2019 (COVID-19) incidence and hospitalization in older adults.BMC nutrition · 2024Article
- Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIron bioavailability has been identified as a factor that influences cellular hypoxia sensing, putatively via an action on the hypoxia-inducible factor (HIF) pathway. We therefore hypothesized that clinical iron deficiency would disturb integrated human responses to hypoxia.
methodsWe performed a prospective, controlled, observational study of the effects of iron status on hypoxic pulmonary hypertension. Individuals with absolute iron deficiency (ID) and an iron-replete (IR) control group were exposed to two 6-hour periods of isocapnic hypoxia. The second hypoxic exposure was preceded by i.v. infusion of iron. Pulmonary artery systolic pressure (PASP) was serially assessed with Doppler echocardiography.
resultsThirteen ID individuals completed the study and were age- and sex-matched with controls. PASP did not differ by group or study day before each hypoxic exposure. During the first 6-hour hypoxic exposure, the rise in PASP was 6.2 mmHg greater in the ID group (absolute rises 16.1 and 10.7 mmHg, respectively; 95% CI for difference, 2.7-9.7 mmHg, P = 0.001). Intravenous iron attenuated the PASP rise in both groups; however, the effect was greater in ID participants than in controls (absolute reductions 11.1 and 6.8 mmHg, respectively; 95% CI for difference in change, -8.3 to -0.3 mmHg, P = 0.035). Serum erythropoietin responses to hypoxia also differed between groups.
conclusionClinical iron deficiency disturbs normal responses to hypoxia, as evidenced by exaggerated hypoxic pulmonary hypertension that is reversed by subsequent iron administration. Disturbed hypoxia sensing and signaling provides a mechanism through which iron deficiency may be detrimental to human health.
trial registrationClinicalTrials.gov (NCT01847352).
fundingM.C. Frise is the recipient of a British Heart Foundation Clinical Research Training Fellowship (FS/14/48/30828). K.L. Dorrington is supported by the Dunhill Medical Trust (R178/1110). D.J. Roberts was supported by R&D funding from National Health Service (NHS) Blood and Transplant and a National Institute for Health Research (NIHR) Programme grant (RP-PG-0310-1004). This research was funded by the NIHR Oxford Biomedical Research Centre Programme.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.