Trial reportThe Journal of clinical investigation2015
Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects.
Trial report in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 117 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.
Procurement and Analysis of Blood, Bone Marrow, and Buccal Mucosa Samples From Healthy Volunteers to Support Clinical and Translational Research Projects in the NHLBI
Pilot Study to Evaluate the Effect of Fasting on the NLRP3 Inflammasome
Study to Evaluate the Effect of Nicotinamide Riboside on Immunity
Who cites it
117 citing papers in PubMed, 1 synthesis or guideline pooled it, 178 citations in OpenAlex.
- Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.PLoS genetics · 2019Pooled it
- A fasting-mimicking diet in patients with mild-to-moderate Crohn's disease: a randomized controlled trial.Nature medicine · 2026Trial
- Dapagliflozin reduces systemic inflammation in patients with type 2 diabetes without known heart failure.Cardiovascular diabetology · 2024Trial
- Association of plasma cytokines and antidepressant response following mild-intensity whole-body hyperthermia in major depressive disorder.Translational psychiatry · 2023Trial
- Human fasting modulates macrophage function and upregulates multiple bioactive metabolites that extend lifespan in Caenorhabditis elegans: a pilot clinical study.The American journal of clinical nutrition · 2023Trial
- Short Term Isocaloric Ketogenic Diet Modulates NLRP3 InflammasomeFrontiers in immunology · 2022Trial
- Is muscle and protein loss relevant in long-term fasting in healthy men? A prospective trial on physiological adaptations.Journal of cachexia, sarcopenia and muscle · 2021Trial
- Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure.The Journal of clinical investigation · 2020Trial
- A Pilot Study To Investigate the Immune-Modulatory Effects of Fasting in Steroid-Naive Mild Asthmatics.Journal of immunology (Baltimore, Md. : 1950) · 2018Trial
- Time-restricted eating, immunomodulation and ketone metabolism in humans.Metabolism: clinical and experimental · 2026Review
- Trained immunity in chronic, relapsing and low-grade joint inflammation.Nature reviews. Rheumatology · 2026Review
- SIRT5-dependent regulation of ASL controls arginine metabolism and T cell function.bioRxiv : the preprint server for biology · 2026Article
- AMPK-NLRP3 Inflammasome Crosstalk: Structural Insights, Molecular Mechanisms, and Therapeutic Implications for Inflammation and Neuroinflammation.Molecular neurobiology · 2026Review
- Article
- Effects of Time-Restricted Eating on Ketone Metabolism and Immunoregulation in Premenopausal Women: Protocol for a Pilot, Prospective, Single-Arm Dietary Intervention Study.JMIR research protocols · 2026Article
- Spermidine Reproduces the Anti-Inflammatory Effects of Intermittent Fasting and Prevents Urate and Calcium Pyrophosphate Crystal-Induced Inflammation.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Fasting as a Multisystem Health Modulator: A Narrative Review of Metabolic, Cardiovascular, Immune, Neurocognitive, and Psychospiritual Effects.Current nutrition reports · 2026Review
- Prolonging Partial Remission in Type 1 Diabetes: The Role of Low-Carbohydrate Diet: A Literature Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Molecular pathways, tissue-specific roles, and therapeutic opportunities in mitochondrial resilience-based strategies for insulin resistance.Frontiers in clinical diabetes and healthcare · 2026Review
- Alternate-day fasting ameliorates α-synuclein pathology and suppresses inflammation via the gut-brain axis in an MPTP-induced subacute mouse model of Parkinson's disease.NPJ biofilms and microbiomes · 2025Article
57 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
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundActivation of the NLRP3 inflammasome is associated with metabolic dysfunction, and intermittent fasting has been shown to improve clinical presentation of NLRP3 inflammasome-linked diseases. As mitochondrial perturbations, which function as a damage-associated molecular pattern, exacerbate NLRP3 inflammasome activation, we investigated whether fasting blunts inflammasome activation via sirtuin-mediated augmentation of mitochondrial integrity.
methodsWe performed a clinical study of 19 healthy volunteers. Each subject underwent a 24-hour fast and then was fed a fixed-calorie meal. Blood was drawn during the fasted and fed states and analyzed for NRLP3 inflammasome activation. We enrolled an additional group of 8 healthy volunteers to assess the effects of the sirtuin activator, nicotinamide riboside, on NLRP3 inflammasome activation.
resultsIn the fasting/refeeding study, individuals showed less NLRP3 inflammasome activation in the fasted state compared with that in refed conditions. In a human macrophage line, depletion of the mitochondrial-enriched sirtuin deacetylase SIRT3 increased NLRP3 inflammasome activation in association with excessive mitochondrial ROS production. Furthermore, genetic and pharmacologic SIRT3 activation blunted NLRP3 activity in parallel with enhanced mitochondrial function in cultured cells and in leukocytes extracted from healthy volunteers and from refed individuals but not in those collected during fasting.
conclusionsTogether, our data indicate that nutrient levels regulate the NLRP3 inflammasome, in part through SIRT3-mediated mitochondrial homeostatic control. Moreover, these results suggest that deacetylase-dependent inflammasome attenuation may be amenable to targeting in human disease.
trial registrationClinicalTrials.gov NCT02122575 and NCT00442195.
fundingDivision of Intramural Research, NHLBI of the NIH.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.