Evidence map›Paper›PMID 40268190›Full record

ArticleMolecular metabolism2025

Prolonged fasting promotes systemic inflammation and platelet activation in humans: A medically supervised, water-only fasting and refeeding study.

Serena Commissati, Maria Lastra Cagigas, Andrius Masedunskas, Giovanna Petrucci, Valeria Tosti, Isabella De Ciutiis, Gayathiri Rajakumar, Kristopher M Kirmess, Matthew R Meyer, Alan Goldhamer and 5 more

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Article in Molecular metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Serena CommissatiDepartment of Medicine, University of Verona, Italy.
Maria Lastra CagigasCharles Perkins Center, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Andrius MasedunskasCharles Perkins Center, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Giovanna PetrucciSection of Pharmacology, Department of Safety and Bioethics, Catholic University School of Medicine, Rome, Italy.
Valeria TostiDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Isabella De CiutiisCharles Perkins Center, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Gayathiri RajakumarCharles Perkins Center, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Kristopher M KirmessC(2)N Diagnostics, St Louis, MO, USA.
Matthew R MeyerC(2)N Diagnostics, St Louis, MO, USA.
Alan GoldhamerTrueNorth Health Center, Santa Rosa, CA, USA.
Brian K KennedyHealthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Centre for Healthy Longevity, National University Health System, Singapore; Departments of Biochemistry and Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Duaa HatemSection of Pharmacology, Department of Safety and Bioethics, Catholic University School of Medicine, Rome, Italy.
Bianca RoccaSection of Pharmacology, Department of Safety and Bioethics, Catholic University School of Medicine, Rome, Italy; NeuroFarBa Department, University of Florence, Florence, Italy.
Giovanni FioritoClinical Bioinformatics unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy; MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
Luigi FontanaCharles Perkins Center, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia. Electronic address: luigi.fontana@sydney.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveProlonged fasting (PF), defined as abstaining from energy intake for ≥4 consecutive days, has gained interest as a potential health intervention. However, the biological effects of PF on the plasma proteome are not well understood.

methodsIn this study, we investigated the effects of a medically supervised water-only fast (mean duration: 9.8 ± 3.1 days), followed by 5.3 ± 2.4 days of guided refeeding, in 20 middle-aged volunteers (mean age: 52.2 ± 11.8 years; BMI: 28.8 ± 6.4 kg/m

resultsFasting resulted in a 7.7% mean weight loss and significant increases in serum beta-hydroxybutyrate (BHB), confirming adherence. Untargeted high-dimensional plasma proteomics (SOMAScan, 1,317 proteins) revealed multiple adaptations to PF, including preservation of skeletal muscle and bone, enhanced lysosomal biogenesis, increased lipid metabolism via PPARα signaling, and reduced amyloid fiber formation. Notably, PF significantly reduced circulating amyloid beta proteins Aβ40 and Aβ42, key components of brain amyloid plaques. In addition, PF induced an acute inflammatory response, characterized by elevated plasma C-reactive protein (CRP), hepcidin, midkine, and interleukin 8 (IL-8), among others. A retrospective cohort analysis of 1,422 individuals undergoing modified fasting confirmed increased CRP levels (from 2.8 ± 0.1 to 4.3 ± 0.2 mg/L). The acute phase response, associated with transforming growth factor (TGF)-β signaling, was accompanied by increased platelet degranulation and upregulation of the complement and coagulation cascade, validated by ELISAs in blood and urine.

conclusionsWhile the acute inflammatory response during PF may serve as a transient adaptive mechanism, it raises concerns regarding potential cardiometabolic effects that could persist after refeeding. Further investigation is warranted to elucidate the long-term molecular and clinical implications of PF across diverse populations.

Indexed as

FastingInflammationPlatelet Activation3-Hydroxybutyric AcidAdultFemaleHumansMaleMiddle AgedProteomics3-Hydroxybutyric AcidCardiometabolicInflammationProlonged fastingProteomics

Identifiers

PMID40268190
PMCPMC12088818

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Registered trials

None linked

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.