ArticleEuropean journal of clinical investigation2021
Nonalcoholic fatty liver disease, circulating ketone bodies and all-cause mortality in a general population-based cohort.
Article in European journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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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
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Fatty liver index (FLI): more than a marker of hepatic steatosis.Journal of physiology and biochemistry · 2024Pooled it
- Effect of Intermittent Fasting on Lipid Profile, Anthropometric and Hepatic Markers in Non-Alcoholic Fatty Liver Disease (NAFLD): A Systematic Review.Current vascular pharmacology · 2024Pooled it
- Effect of alternate day fasting combined with aerobic exercise on non-alcoholic fatty liver disease: A randomized controlled trial.Cell metabolism · 2023Trial
- Ketogenesis as a Metabolic Checkpoint in MASLD: Implications for Disease Progression and Therapy.Metabolites · 2026Review
- Continuously elevated plasma ketone bodies are linked to adverse outcomes in patients with heart failure.Clinical research in cardiology : official journal of the German Cardiac Society · 2026Article
- Metabolomic and lipidomic plasma profiles according to metabolic dysfunction-associated steatotic liver diseases (MASLD) stages in the absence of type 2 diabetes (T2D).Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Association between ketone body levels and chronic liver disease: Epidemiological studies and potential mechanisms.AIMS public health · 2026Review
- Ketone bodies and cancer risk in the general population: The prevention of renal and vascular end-stage disease (PREVEND) study.European journal of clinical investigation · 2025Article
- Targeting HMGCS2: Ketogenesis Suppression Accelerates NAFLD Progression in T2DM Comorbidity, While Cynaroside Ameliorates NASH in Concomitant T2DM.Biomolecules · 2025Article
- Ketone metabolites in metabolic dysfunction-associated steatotic liver disease progression: optimizing keto-therapeutic strategies.American journal of physiology. Endocrinology and metabolism · 2025Review
- Higher circulating FGF21, lower protein intake, and lower muscle mass: Associations with a higher risk of mortality.Journal of internal medicine · 2025Article
- Circulating FGF21 and Ketone Bodies Modify the Risk of MASLD and Mortality: Insights from the PREVEND Cohort Study.International journal of molecular sciences · 2025Article
- Plasma Beta-Hydroxybutyrate and All-Cause Mortality in Patients with Liver Cirrhosis.Biomedicines · 2025Article
- Enhanced Chronic Inflammation and Increased Branched-Chain Amino Acids in Adrenal Disorders: A Cross-Sectional Study.The Journal of clinical endocrinology and metabolism · 2025Article
- Characteristics of Cardiac Ketone Body Metabolism Throughout the Life Cycle.Cardiovascular therapeutics · 2025Review
- Metabolic dysfunction-associated steatotic liver disease-induced changes in the antioxidant system: a review.Archives of toxicology · 2025Review
- Dietary Influences on Gut Microbiota and Their Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Nutrients · 2024Review
- Metabolomic Hallmarks of Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2024Review
- Relationship between serum β-hydroxybutyrate and hepatic fatty acid oxidation in individuals with obesity and NAFLD.American journal of physiology. Endocrinology and metabolism · 2024Article
- Bridging Metabolic-Associated Steatotic Liver Disease and Cardiovascular Risk: A Potential Role for Ketogenesis.Biomedicines · 2024Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNonalcoholic fatty liver disease (NAFLD) is increasingly prevalent, paralleling the obesity epidemic. Ketone bodies are produced in the liver, but it is currently uncertain whether circulating ketone bodies are increased in the context of NAFLD. We investigated the association between NAFLD and circulating ketone bodies and determined the extent to which NAFLD and circulating ketone bodies are associated with all-cause mortality.
methodsPlasma ketone bodies were measured by nuclear magnetic resonance spectroscopy in participants of the general population-based PREVEND study. A fatty liver index (FLI) ≥60 was regarded as a proxy of NAFLD. Associations of an elevated FLI and ketone bodies with all-cause mortality were investigated using Cox regression analyses.
resultsThe study included 6,297 participants aged 54 ± 12 years, of whom 1,970 (31%) had elevated FLI. Participants with elevated FLI had higher total ketone bodies (194 [153-259] vs 170 [133-243] µmol/L; P < .001) than participants without elevated FLI. During 7.9 [7.8-8.9] years of follow-up, 387 (6%) participants died. An elevated FLI was independently associated with an increased risk of mortality (HR: 1.34 [1.06-1.70]; P = .02). Higher total ketone bodies were also associated with an increased mortality risk (HR per doubling: 1.29 [1.12-1.49]; P < .001). Mediation analysis suggested that the association of elevated FLI with all-cause mortality was in part mediated by ketone bodies (proportion mediated: 10%, P < .001).
conclusionCirculating ketone bodies were increased in participants with suspected NAFLD. Both suspected NAFLD and higher circulating ketone bodies are associated with an increased risk of all-cause mortality.
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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.