ArticleSleep medicine2017
Iron and restless legs syndrome: treatment, genetics and pathophysiology.
Article in Sleep medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
49 citing papers in PubMed, 3 syntheses or guidelines pooled it, 127 citations in OpenAlex.
- Neuromodulation for Restless Legs Syndrome: A Systematic Review and Mechanistic Considerations for Spinal Cord Stimulation.Sleep & breathing = Schlaf & Atmung · 2026Pooled it
- Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.Nature genetics · 2024Pooled it
- Putative Animal Models of Restless Legs Syndrome: A Systematic Review and Evaluation of Their Face and Construct Validity.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Pooled it
- Altered iron metabolism and iron therapy in restless legs syndrome.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Hypoxia-Associated Remodeling of the Arginine-Citrulline-Ornithine Axis in Parkinson's Disease and Restless Legs Syndrome: A Targeted LC-MS/MS and HIF-1α Profiling Study.Medicina (Kaunas, Lithuania) · 2026Article
- Iron therapy & restless legs syndrome: a narrative review.Sleep & breathing = Schlaf & Atmung · 2026Review
- Sleeping green: an Italian survey for the assessment of the relationship between sleep and vegetarian diet.Sleep & breathing = Schlaf & Atmung · 2026Article
- Restless legs syndrome and inflammatory bowel disease: A systematic review and meta-analysis.IBRO neuroscience reports · 2025Article
- Aripiprazole Has Potential Efficacy for Antidepressant-induced Restless Legs Syndrome: A Case Series.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2025Article
- From Normal Variation in Sleep to Clinical Sleep Disorders: Genetic Insights from Over One Million Individuals.medRxiv : the preprint server for health sciences · 2025Article
- Neural Correlates of Restless Legs Syndrome (RLS) Based on Electroencephalogram (EEG)-A Mechanistic Review.International journal of molecular sciences · 2025Review
- Fresh Genetic Insights Into Micronutrients Influences on Restless Legs Syndrome Risk.Food science & nutrition · 2025Article
- Review
- Associations Between Lifetime Histories of Iron Deficiency, Anxiety, Depression and Multiple Pain Conditions: An Observational Study Using a Large-Scale National Database.Journal of pain research · 2025Article
- On the optimization of 3D inflow-based vascular-space-occupancy (iVASO) MRI for the quantification of arterial cerebral blood volume (CBVa).Magnetic resonance in medicine · 2024Article
- Restless leg syndrome in spinal cord injury: case report.Spinal cord series and cases · 2023Article
- Vitamin D and Restless Legs Syndrome: A Review of Current Literature.Tremor and other hyperkinetic movements (New York, N.Y.) · 2023Review
- Intravenous iron therapy alleviates symptoms of sleep-related movement disorders in children with minimal side effects.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2022Article
- Leveraging genetic discoveries for sleep to determine causal relationships with common complex traits.Sleep · 2022Review
- Restless leg syndrome prevalence in epilepsy patients and its impact on quality of sleep.Sleep and biological rhythms · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
In this article, we review the original findings from MRI and autopsy studies that demonstrated brain iron status is insufficient in individuals with restless legs syndrome (RLS). The concept of deficient brain iron status is supported by proteomic studies from cerebrospinal fluid (CSF) and from the clinical findings where intervention with iron, either dietary or intravenous, can improve RLS symptoms. Therefore, we include a section on peripheral iron status and how peripheral status may influence both the RLS symptoms and treatment strategy. Given the impact of iron in RLS, we have evaluated genetic data to determine if genes are directly involved in iron regulatory pathways. The result was negative. In fact, even the HFE mutation C282Y could not be shown to have a protective effect. Lastly, a consistent finding in conditions of low iron is increased expression of proteins in the hypoxia pathway. Although there is lack of clinical data that RLS patients are hypoxic, there are intriguing observations that environmental hypoxic conditions worsen RLS symptoms; in this chapter we review very compelling data for activation of hypoxic pathways in the brain in RLS patients. In general, the data in RLS point to a pathophysiology that involves decreased acquisition of iron by cells in the brain. Whether the decreased ability is genetically driven, activation of pathways (eg, hypoxia) that are designed to limit cellular uptake is unknown at this time; however, the data strongly support a functional rather than structural defect in RLS, suggesting that an effective treatment is possible.
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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.