Trial reportThe American journal of clinical nutrition2023
Human fasting modulates macrophage function and upregulates multiple bioactive metabolites that extend lifespan in Caenorhabditis elegans: a pilot clinical study.
Trial report in The American journal of clinical nutrition, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03487679 (The Effects of Prolonged Fasting on the Microbiome and HDL Particles of Human Subjects), which is not on this map. Cited by 13 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.
The Effects of Prolonged Fasting on the Microbiome and HDL Particles of Human Subjects
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression.Frontiers in nutrition · 2026Pooled it
- A novel fasting mimetic (Mimio) creates fasting-like benefits to hunger control, oxidative stress, and cardiometabolic health in humans.Scientific reports · 2026Trial
- Spermidine Reproduces the Anti-Inflammatory Effects of Intermittent Fasting and Prevents Urate and Calcium Pyrophosphate Crystal-Induced Inflammation.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Intermittent and periodic fasting: molecular mechanisms, health benefits and research challenges.Frontiers in nutrition · 2026Review
- Article
- Simultaneous Isolation and Characterization of Lipoprotein Classes in Plasma, Including HDL Subclasses and the Uncharacterized Dense HDL.bioRxiv : the preprint server for biology · 2025Article
- Effects of fasting on HDL particle function and size distribution.Journal of lipid research · 2025Review
- Review
- HDL from 36-h fasted participants potently promotes efflux of cholesteryl ester from activated microglia.Frontiers in aging neuroscience · 2025Article
- HDL Function across the Lifespan: From Childhood, to Pregnancy, to Old Age.International journal of molecular sciences · 2023Review
- Precision Nutrition and Cardiovascular Disease Risk Reduction: the Promise of High-Density Lipoproteins.Current atherosclerosis reports · 2023Review
- A single 36-h water-only fast vastly remodels the plasma lipidome.Frontiers in cardiovascular medicine · 2023Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPeriodic prolonged fasting (PF) extends lifespan in model organisms and ameliorates multiple disease states both clinically and experimentally owing, in part, to its ability to modulate the immune system. However, the relationship between metabolic factors, immunity, and longevity during PF remains poorly characterized especially in humans.
objectiveThis study aimed to observe the effects of PF in human subjects on the clinical and experimental markers of metabolic and immune health and uncover underlying plasma-borne factors that may be responsible for these effects.
methodsIn this rigorously controlled pilot study (ClinicalTrial.gov identifier, NCT03487679), 20 young males and females participated in a 3-d study protocol including assessments of 4 distinct metabolic states: 1) overnight fasted baseline state, 2) 2-h postprandial fed state, 3) 36-h fasted state, and 4) final 2-h postprandial re-fed state 12 h after the 36-h fasting period. Clinical and experimental markers of immune and metabolic health were assessed for each state along with comprehensive metabolomic profiling of participant plasma. Bioactive metabolites identified to be upregulated in circulation after 36 h of fasting were then assessed for their ability to mimic the effects of fasting in isolated human macrophage as well as the ability to extend lifespan in Caenorhabditis elegans.
resultsWe showed that PF robustly altered the plasma metabolome and conferred beneficial immunomodulatory effects on human macrophages. We also identified 4 bioactive metabolites that were upregulated during PF (spermidine, 1-methylnicotinamide, palmitoylethanolamide, and oleoylethanolamide) that could replicate these immunomodulatory effects. Furthermore, we found that these metabolites and their combination significantly extended the median lifespan of C. elegans by as much as 96%.
conclusionsThe results of this study reveal multiple functionalities and immunological pathways affected by PF in humans, identify candidates for the development of fasting mimetic compounds, and uncover targets for investigation in longevity research.
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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.