ReviewAmerican journal of physiology. Endocrinology and metabolism2021
Bilirubin as a metabolic hormone: the physiological relevance of low levels.
Review in American journal of physiology. Endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
142 citing papers in PubMed, 2 syntheses or guidelines pooled it, 213 citations in OpenAlex.
- The role of bilirubin as a biomarker of rheumatic diseases: a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- Causal validation of the relationship between 35 blood and urine biomarkers and hyperthyroidism: a bidirectional Mendelian randomization study and meta-analysis.Frontiers in endocrinology · 2024Pooled it
- Bilirubin and the Yellow Players in Ferroptosis: A Delicate Balance in Human Health and Disease, with a Focus on the Liver, Cardiovascular System, and Brain.Biomolecules · 2026Review
- Article
- Association Between Gut Microbiota Dysbiosis and Bilirubin Metabolism Dysregulation in Children with Heart Failure.Journal of cardiovascular translational research · 2026Article
- Prognostic characteristics of preoperative serum total bilirubin concentration in myxomatous mitral valve disease in dogs undergoing mitral valve repair.Journal of veterinary internal medicine · 2026Article
- Scientific Report on consumer health-based guidance values for trifluoroacetic acid.EFSA journal. European Food Safety Authority · 2026Article
- Exploring Tetrazolium Salt Reduction by Mono- and Bimetallic Nanoparticles as an Alternative Signal-Generation Strategy for Point-of-Care Diagnostics.Biosensors · 2026Article
- Identification of the complete pathway for conversion of bilirubin to urobilinogen by human gut bacteria.bioRxiv : the preprint server for biology · 2026Article
- Subchronic Cadmium-Induced Xenobiotic Toxicity in Male Wistar Rats: Antioxidant and Reproductive Protection by Standardized Silymarin with Molecular Docking Insights.Journal of xenobiotics · 2026Article
- Integrated multi-omics implicates the gut microbiota and bilirubin in abdominal fat deposition in Huainan yellow chickens.Poultry science · 2026Article
- Kinase signaling in liver disease via clinical-trial-on-a-PamChip: A distinctive methodology for drug mechanisms and personalized medicine.The Journal of biological chemistry · 2026Article
- Transforming Toxicity into Therapy: Exploring Bilirubin's Benefits and Its Molecular Role in Cardiac Health and Disease.Biomolecules · 2026Review
- Metabolic Flexibility and Exercise Performance in Adults with Gilbert's Syndrome-Associated Hyperbilirubinemia.Sports medicine - open · 2026Article
- Association of serum total bilirubin with recurrent cardiovascular events in patients with in-stent restenosis: a stratified analysis by inflammatory status.BMC cardiovascular disorders · 2026Observational
- Microbiome-derived cancer: the catabolism of bilirubin to urobilin in the liver-gut axis and its consequences.Gastroenterology report · 2026Review
- Development of a Physiologically Based Model of Bilirubin Metabolism in Health and Disease and Its Comparison With Real-World Data.CPT: pharmacometrics & systems pharmacology · 2026Article
- Association of short-term exposure to ambient air pollutants with liver function and mediation by fasting insulin: evidence from a rural cohort in China.BMC medicine · 2026Article
- Neuroprotective role of bilirubin in Parkinson's disease.Frontiers in aging neuroscience · 2026Review
- Association Between Pulmonary Function, Respiratory Muscle Strength and Cognitive Function in Chinese Community-Dwelling Older Adults.Clinical interventions in aging · 2026Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Recent research on bilirubin, a historically well-known waste product of heme catabolism, suggests an entirely new function as a metabolic hormone that drives gene transcription by nuclear receptors. Studies are now revealing that low plasma bilirubin levels, defined as "hypobilirubinemia," are a possible new pathology analogous to the other end of the spectrum of extreme hyperbilirubinemia seen in patients with jaundice and liver dysfunction. Hypobilirubinemia is most commonly seen in patients with metabolic dysfunction, which may lead to cardiovascular complications and possibly stroke. We address the clinical significance of low bilirubin levels. A better understanding of bilirubin's hormonal function may explain why hypobilirubinemia might be deleterious. We present mechanisms by which bilirubin may be protective at mildly elevated levels and research directions that could generate treatment possibilities for patients with hypobilirubinemia, such as targeting of pathways that regulate its production or turnover or the newly designed bilirubin nanoparticles. Our review here calls for a shift in the perspective of an old molecule that could benefit millions of patients with hypobilirubinemia.
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What Socratic holds
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 Socratic graph.