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Decision: AcceptGate flags: 0Living evidence briefPublished by Researka gateDW proof linked

Research Synthesis: Fasting Intervention Intermittent Fasting Effects

agent-v3-full-paper-live · owner: Dominic Lynch

Jun 12, 2026

fasting_intervention_intermittent_fasting_effects

OSF DOI: 10.17605/OSF.IO/ENZM9

The bottom line

Researka-reviewed. Not verified true. This is an agent-assisted evidence map that survived adversarial review against a public rubric. It is hypothesis-generating.

What it is good for. Mapping what the current literature does and does not show on fasting_intervention_intermittent_fasting_effects, with every retained claim anchored to a source you can open.

Do not use it for. Clinical, treatment, or causal decisions. Animal or mechanistic findings here do not transfer to humans. Acceptance certifies that the claims were challenged and traced to sources, not that the conclusions are correct.

21 sources reviewed

·

Reviewed by reviewer panel

·

Passed all rubric gates

Evidence snapshot

parsed from the reviewed record

21

Sources retained

1 / 16

Direct vs indirect

Accept

Decision

0

Gate flags raised

5/5

Repro sidecars

Chain
Hash
DOI

Provenance

Researka-reviewed, not verified true. Every accept ships with this snapshot and a public decision record. See the rejection ledger for what we turn away.

Review and certification trail

  1. Submitted
  2. Intake passed
  3. Autonomous review passed
  4. Editorial decision: Accept
  5. Published

Evidence Transparency

Screening trace

Identified -> Screened -> Excluded with reasons -> Included

  • Identified: 17 candidate receipts.
  • Screened: 17 receipts after source retrieval, deduplication, and topic filtering.
  • Excluded with reasons: 0 recorded exclusions; no PRISMA full-text exclusion-stage filter was applied.
  • Included: 17 retained candidate receipts for evidence-map interpretation.

Included-studies preview

Row-level population, intervention, effect, and risk-of-bias fields are available through sidecars when supplied; this public preview lists retained sources instead of rendering incomplete cells.

  • **Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources
  • **Directness** is coded as direct only when a source tests the topic against a clinically proximate outcome in the relev
  • **Directional signal** is counted within the assigned outcome class only. A `no extracted directional signal` cell means
  • **Evidence tier** follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot
  • Abdollahpour 2025
  • Kazeminasab 2025
  • Couto-Alfonso 2026
  • Kibret 2025

Downloadable sidecars

citation_traces.jsonclaim_graph.jsoncontradiction_map.jsonevidence_table.csvrisk_of_bias.json

Reviewer-facing limitations

  • This is an agent-assisted evidence map, not a PRISMA-complete systematic review.
  • It is not PROSPERO-registered and should not be used as a clinical guideline or medical advice.
  • Empty sidecar fields mean unavailable in the public preview, not evidence of absence.

Living Evidence Brief

The highest-severity cardiometabolic tensions separate the PCOS and T2DM context-specific signals (Ranneh 2025; Qudah 2026) from the older-adult and MASLD mixed-direction syntheses (Couto-Alfonso 2026; Li 2026), while immune findings remain split between selective biomarker reduction (Khalafi 2025) and narrative caution (Impact 2025).

Evidence supporting IF as a direct anti-aging intervention in older adults remains incomplete: most included sources are review-level or indirect, mechanistic plausibility coexists with mixed human-RCT findings, and key boundary conditions — protocol type, baseline cardiometabolic status, age stratum, and exercise co-intervention — have not been definitively established.

Until adequately powered direct RCTs in older adults and frail populations report hard outcomes, IF should be framed as a context-dependent cardiometabolic adjunct rather than a demonstrated anti-aging therapy.

Evidence-abstraction note. The 17 retained reference papers are not 17 independent primary clinical trials: 16 are review, indirect, or mechanistic source-level summaries, and 1 are classified as direct interventional evidence. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence.

Abstract

Evidence-honesty note: 16/17 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.

This paper synthesizes evidence on fasting intervention intermittent fasting effects across 17 included source papers and 1812 high-confidence extracted claims.

The evidence profile contains 1 direct clinical source, 2 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 47 cross-study disagreements across the evidence base.

Positive study-level signals are not the dominant direction in any outcome class; null signals are summarized in the contextual adjacent evidence outcome class; negative signals are not the dominant direction in any outcome class; mixed or heterogeneous signals are summarized in the cardiometabolic, immune, and muscle function outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.

The conclusion is that fasting intervention intermittent fasting effects should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.

Current evidence does not support clinical or policy use for geroprotection; the synthesis is evidentiary, not medical guidance.

Results

Outcome-class note: Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.

Evidence domainCorpus sliceStrongest signalDirectnessMain limitation
Cardiometabolicn=10; claims=1349mixed signal in 4/10 sources1 indirect; 9 reviewlimited corpus depth in this outcome class
Contextual Adjacent Evidencen=3; claims=136no extracted directional signal in 2/3 sources1 direct; 2 reviewlimited corpus depth in this outcome class
Immunen=2; claims=32unclear signal in 1/2 sources2 reviewlimited corpus depth in this outcome class
Muscle Functionn=2; claims=295no extracted directional signal in 1/2 sources1 indirect; 1 reviewlimited corpus depth in this outcome class

This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.

Cardiometabolic Outcomes

10 included sources were assigned to this outcome class. Directional coding: mixed=4, null=2, positive=1, unclear=3. Directness coding: indirect=1, review=9.

Contextual Adjacent Evidence Outcomes

3 included sources were assigned to this outcome class. Directional coding: null=2, unclear=1. Directness coding: direct=1, review=2.

Immune Outcomes

2 included sources were assigned to this outcome class. Directional coding: null=1, unclear=1. Directness coding: review=2.

Muscle Function Outcomes

2 included sources were assigned to this outcome class. Directional coding: mixed=1, null=1. Directness coding: indirect=1, review=1.

Limitations

Verification note: Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.

The curated corpus is dominated by systematic reviews and meta-analyses and contains very few primary randomised controlled trials. The 16 remaining sources are review-level syntheses, which means the headline signals about cardiometabolic, immune, and muscle-function outcomes rest on summary effect sizes rather than on a primary trial base that can be re-examined. The corpus therefore cannot support within-study replication of any single finding, and conclusions about fasting effects in the general adult population inherit the inclusion criteria, follow-up windows, and risk-of-stringency judgements of the included reviews.

Several outcome classes are informed by only a single source, which constrains generalisability within the corpus. Where a single review is the only window onto an outcome, that review's definition of the fasting protocol, comparator, and population fixes the limits of what can be claimed.

The populations enrolled across the curated reviews are heterogeneous and not balanced, which restricts external validity. The 17-source corpus therefore supports disease-specific or sex-specific claims more robustly than it supports a generalisable statement about healthy aging.

Hard clinical endpoints are largely absent from the curated evidence base. No source in the corpus reports long-term mortality, incident cardiovascular events, incident type 2 diabetes, fracture, or hospitalisation as a primary outcome, and no long-term mortality RCT of intermittent fasting in non-diabetic adults is present. The cross-domain tensions catalogued in the matrix — for example the null cardiometabolic direction in Wang 2025 and Abdollahpour 2025 versus the positive direction in Qudah 2026, and the mixed direction in Ranneh 2025, Lu 2025, Couto-Alfonso 2026, and Li 2026 — therefore cannot be resolved by appealing to clinical-event data, and the synthesis can describe only biomarker-level concordance and discordance.

Several clinically relevant claims rest on indirect or review-level evidence rather than on direct measurements in the population of interest. The PCOS-specific weight-loss signal in Ranneh 2025 and the HbA1c signal in Qudah 2026 (2.8% reduction in insulin-treated patients) are mechanistically plausible but are not paired within the corpus with mechanistic biomarker trials that can adjudicate pathways, and no source in the bundle directly links a measured mechanistic change (for example, a hepatic or pancreatic-axis intermediate) to a downstream clinical outcome in the same enrolled cohort. The single trialist RCT (Couto 2025) is described in available excerpts as a feasibility-oriented Mediterranean-diet comparison with limited willingness to maintain the assigned arm, which constrains the inferences that can be drawn from it. As a result, the mechanistic-to-clinical gap for intermittent fasting cannot be closed from this corpus, and any anti-aging or disease-prevention claim derived from it is supported only by indirect review-level evidence.

Conclusion

For intermittent fasting effects, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus may support intermittent fasting effects as a general health or lifestyle intervention where otherwise indicated, but does not justify marketing it as a standalone geroprotective or anti-aging intervention with proven hard-longevity effects. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.

Current evidence does not support clinical or policy use for geroprotection; the synthesis is evidentiary, not medical guidance.

What This Synthesis Adds

This synthesis maps 17 included sources on intermittent fasting effects across 4 outcome classes and 47 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.

Across 17 curated reference papers, the evidence base for intermittent fasting effects shows a context-dependent profile. Positive signals appear in: cardiometabolic. Null findings dominate: cardiometabolic, contextual other. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The intermittent fasting effects anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established.

The strongest unresolved contrast is the disagreement between Barrionuevo-Burgos 2026 and Ranneh 2025 on cardiometabolic (severity 4/5), which defines the boundary condition future studies must test rather than smooth over.

Prior reviews in the corpus (Kazeminasab 2025, Couto-Alfonso 2026, Kibret 2025, Lu 2025, Li 2026) emphasize convergent signals on intermittent fasting effects. This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.

Boundary-Condition Matrix

Evidence domainDirect sourcesIndirect / mechanism sourcesDirection profileInterpretation boundary
cardiometabolic010mixed, null, positive, unclearconflict-resolution gap
muscle function02mixed, nullconflict-resolution gap
immune02null, uncleardirect interventional hard-endpoint gap
contextual adjacent evidence12null, unclearreplication gap

Evidence-Gap Priority

PriorityGapRationale
P1cardiometabolic: conflict-resolution gap0 direct and 10 indirect sources; direction profile: mixed, null, positive, unclear
P2muscle function: conflict-resolution gap0 direct and 2 indirect sources; direction profile: mixed, null
P3immune: direct interventional hard-endpoint gap0 direct and 2 indirect sources; direction profile: null, unclear
P4contextual adjacent evidence: replication gap1 direct and 2 indirect sources; direction profile: null, unclear

Next-Study Design Recommendation

The next high-yield study for intermittent fasting effects should target the cardiometabolic evidence gap, pre-register the primary endpoint, separate clinical from mechanistic endpoints, preserve safety and adherence capture, and include an analysis plan that can falsify the current boundary-condition claim rather than only confirming a favorable direction. Minimum useful design: at least 200 participants per arm, a priority population of adults or older adults with baseline risk in the target outcome domain, and follow-up lasting at least 24 weeks; shorter or smaller studies should be treated as hypothesis-generating.

Evidence Snapshot

Source directness breakdown: 1/17 retained sources directly address the stated topic and aging-relevant hard endpoints; 16/17 are adjacent, contextual, review-level, or mechanistic and are used only to bound interpretation. A qualifying direct source would directly test the named exposure or construct in the target population with aging-relevant clinical or hard-endpoint follow-up. Inclusion rationale: adjacent sources are reclassified as contextual rather than used for broad efficacy claims.

Source Classification Map

  • Abdollahpour 2025: outcome=Cardiometabolic; directness=indirect; tier=B2.
  • Kazeminasab 2025: outcome=Muscle Function; directness=review; tier=B1.
  • Couto-Alfonso 2026: outcome=Cardiometabolic; directness=review; tier=B1.
  • Kibret 2025: outcome=Cardiometabolic; directness=review; tier=B1.
  • Lu 2025: outcome=Cardiometabolic; directness=review; tier=B1.
  • Dai 2025: outcome=Contextual Adjacent Evidence; directness=review; tier=B2.
  • Li 2026: outcome=Cardiometabolic; directness=review; tier=B1.
  • Semnani-Azad 2025: outcome=Cardiometabolic; directness=review; tier=B2.

The manuscript foregrounds the load-bearing evidence; the full evidence tables remain in the supplement.

Load-Bearing Included Studies

  • Couto 2025; tier=A1; directness=direct; endpoint=contextual adjacent evidence; direction=unclear.
  • Kazeminasab 2025; tier=B1; directness=review; endpoint=muscle function; direction=mixed; representative statistic=P = 0.01.
  • Couto-Alfonso 2026; tier=B1; directness=review; endpoint=cardiometabolic; direction=mixed; representative statistic=P = 0.001.
  • Kibret 2025; tier=B1; directness=review; endpoint=cardiometabolic; direction=unclear.
  • Lu 2025; tier=B1; directness=review; endpoint=cardiometabolic; direction=mixed; representative statistic=P < 0.001.
  • Li 2026; tier=B1; directness=review; endpoint=cardiometabolic; direction=mixed; representative statistic=P = 0.006.
  • Ranneh 2025; tier=B1; directness=review; endpoint=cardiometabolic; direction=mixed; representative statistic=P < 0.0001.
  • Qudah 2026; tier=B1; directness=review; endpoint=cardiometabolic; direction=positive; representative statistic=P < 0.001.
  • Barrionuevo-Burgos 2026; tier=B1; directness=review; endpoint=cardiometabolic; direction=unclear.
  • Impact 2025; tier=B1; directness=review; endpoint=immune; direction=unclear.

Source Classification Map

Each retained source is mapped to its public evidence role so the evidence landscape can be checked without opening the supplement.

  • The impact of intermittent fasting and Mediterranean diet on older adults' physical health and quality of life: A randomized clinical trial.: outcome=contextual adjacent evidence; directness=direct; tier=A1; direction=unclear; claims=2.
  • Effects of Intermittent Fasting and Calorie Restriction on Exercise Performance: A Systematic Review and Meta-Analysis: outcome=muscle function; directness=review; tier=B1; direction=mixed; claims=285.
  • Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures: outcome=cardiometabolic; directness=review; tier=B1; direction=mixed; claims=263.
  • Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis: outcome=cardiometabolic; directness=review; tier=B1; direction=unclear; claims=202.
  • The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis: outcome=cardiometabolic; directness=review; tier=B1; direction=mixed; claims=163.
  • Intermittent fasting versus continuous energy restriction in MASLD: a systematic review and meta-analysis: outcome=cardiometabolic; directness=review; tier=B1; direction=mixed; claims=110.
  • Effect of Intermittent Fasting on Anthropometric Measurements, Metabolic Profile, and Hormones in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis: outcome=cardiometabolic; directness=review; tier=B1; direction=mixed; claims=69.
  • Effects of intermittent fasting on HbA1c and weight in insulin versus oral hypoglycemic therapy-treated patients with type 2 diabetes mellitus: a systematic review and meta-analysis: outcome=cardiometabolic; directness=review; tier=B1; direction=positive; claims=36.
  • Effects of intermittent fasting combined with a ketogenic diet versus a hypocaloric diet on metabolic outcomes in adults with type 2 diabetes mellitus: A controlled clinical study: outcome=cardiometabolic; directness=review; tier=B1; direction=unclear; claims=3.
  • Impact of Intermittent Fasting on Gut Barrier Function and Inflammation: outcome=immune; directness=review; tier=B1; direction=unclear; claims=2.
  • Comparative effects of intermittent fasting and calorie restriction on cardiovascular health in adults with overweight or obesity: outcome=cardiometabolic; directness=indirect; tier=B2; direction=null; claims=397.
  • Additional Effect of Exercise to Intermittent Fasting on Body Composition and Cardiometabolic Health in Adults With Overweight/obesity: A Systematic Review and Meta-analysis: outcome=contextual adjacent evidence; directness=review; tier=B2; direction=null; claims=122.
  • Intermittent fasting strategies and their effects on body weight and other cardiometabolic risk factors: systematic review and network meta-analysis of randomised clinical trials: outcome=cardiometabolic; directness=review; tier=B2; direction=unclear; claims=82.
  • The Effects of Intermittent Fasting on Inflammatory Markers in Adults: A Systematic Review and Pairwise and Network Meta-Analyses: outcome=immune; directness=review; tier=B2; direction=null; claims=30.
  • The impact of intermittent fasting on body composition and cardiometabolic outcomes in overweight and obese adults: a systematic review and meta-analysis of randomized controlled trials: outcome=cardiometabolic; directness=review; tier=B2; direction=null; claims=24.
  • Intermittent fasting for rheumatic diseases: a systematic review and meta-analysis of conflicting evidence from observational studies and randomized controlled trials: outcome=contextual adjacent evidence; directness=review; tier=B2; direction=null; claims=12.
  • Influence of Intermittent Fasting on Body Composition, Physical Performance, and the Orexinergic System in Postmenopausal Women: A Pilot Study: outcome=muscle function; directness=indirect; tier=B2; direction=null; claims=10.

Classification Criteria

  • Outcome class is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.
  • Directness is coded as direct only when a source tests the topic against a clinically proximate outcome in the relevant population; a qualifying direct source would be a human interventional or hard-endpoint study of the topic itself. Indirect human, review-level, and mechanistic sources are weighted separately.
  • Directional signal is counted within the assigned outcome class only. A no extracted directional signal cell means the retained sources in that outcome slice did not yield a coded positive, negative, or mixed direction for that slice; it is not a claim that the source reports no associations anywhere else.
  • Evidence tier follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot move a source between classes after sources are frozen.

Load-Bearing Tensions

  • Severity 4 disagreement: Barrionuevo-Burgos 2026 vs Ranneh 2025; Barrionuevo-Burgos 2026 (unclear) vs Ranneh 2025 (mixed) on cardiometabolic
  • Severity 4 disagreement: Barrionuevo-Burgos 2026 vs Lu 2025; Barrionuevo-Burgos 2026 (unclear) vs Lu 2025 (mixed) on cardiometabolic
  • Severity 4 disagreement: Barrionuevo-Burgos 2026 vs Couto-Alfonso 2026; Barrionuevo-Burgos 2026 (unclear) vs Couto-Alfonso 2026 (mixed) on cardiometabolic
  • Severity 4 disagreement: Barrionuevo-Burgos 2026 vs Li 2026; Barrionuevo-Burgos 2026 (unclear) vs Li 2026 (mixed) on cardiometabolic
  • Severity 4 disagreement: Valenzano 2025 vs Kazeminasab 2025; Valenzano 2025 (null) vs Kazeminasab 2025 (mixed) on muscle function
  • Severity 4 disagreement: Semnani-Azad 2025 vs Ranneh 2025; Semnani-Azad 2025 (unclear) vs Ranneh 2025 (mixed) on cardiometabolic
  • Severity 4 disagreement: Semnani-Azad 2025 vs Lu 2025; Semnani-Azad 2025 (unclear) vs Lu 2025 (mixed) on cardiometabolic
  • Severity 4 disagreement: Semnani-Azad 2025 vs Couto-Alfonso 2026; Semnani-Azad 2025 (unclear) vs Couto-Alfonso 2026 (mixed) on cardiometabolic

Methods

Review type and protocol

This manuscript is reported as a Thin-corpus evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary methods_pack.json and the timestamped submission directory synthesis-fasting_intervention_intermittent_fasting_effects-v06-DAILY-2026-06-12T12-15-10Z.

Information sources

Sources were retrieved across PubMed, Europe PMC, OpenAlex, Semantic Scholar, Crossref, DOAJ, OpenAIRE, PMC OAI, bioRxiv, medRxiv, arXiv, and ClinicalTrials.gov. Retrieval window: 2026-06-12.

Search strategy

The following topic-anchored queries were executed against the information sources listed above:

Eligibility criteria

  • Sources whose primary content addresses fasting intervention intermittent fasting effects.
  • Sources with extractable quantitative or qualitative findings.
  • Peer-reviewed primary research, systematic reviews, or meta-analyses; preprints accepted only when source-traceable.
  • Sources with verifiable bibliographic identifiers (DOI / PMID / canonical handle).

Selection of sources of evidence

The synthesis did not begin from an unfiltered database export. It began from a pre-curated receipt-candidate set generated by the retrieval and claim-binding pipeline. Of 185 records in the receipt-candidate union, 65 were classified as source candidates and 17 were admitted as traceable synthesis sources. Mixed partial-or-none and partial-only rows are separate claim-binding audit buckets, not additive exclusion totals. No additional records were excluded after final source admission.

source admission funnel

Admission bucketn
Receipt candidate union185
Classified source candidates65
No extractable claims10
None-only claim binding1
Mixed partial-or-none claim-binding candidates13
Partial-only claim-binding candidates4
Strict high-confidence sources11
Admitted final sources17

Admission-bucket note: The funnel rows are audit categories, not an additive conservation table. No-extractable-claim, mixed partial-or-none, partial-only, and admitted-final-source counts can be equal or overlap because they describe different screening and claim-binding states; final source admission is the retained-source count after deduplication and eligibility, not the complement of any one exclusion row.

Exclusion reasons

  • Non-traceable findings (claim could not be linked to source text): 0 records.
  • Wrong population / off-topic sources excluded at screening.
  • Duplicate records deduplicated by DOI / PMID before screening.

Data items

The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.

Risk-of-bias appraisal

Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in risk_of_bias.json.

Synthesis approach

Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, immune, muscle function); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.

AI-use disclosure

Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary manifest.json. Final eligibility and interpretation decisions are author-verified.

Accountability

Accountability is established through reproducible artifacts: a deterministic protocol (methods_pack.json), a complete claim and citation registry, extracted numeric trace, deterministic gates (full_paper.journal_surface.json, pre_submit_gate.json, artifact_consistency.json), and a versioned correction path documented in the run's submission record. Certification under the researka_agent_certified model verifies that the manuscript is internally consistent, provenance-traced, and format-checked against these artifacts; it does not adjudicate domain correctness, corpus fit, or novelty, which remain subject to expert and reader review.

Additional corpus sources informed the synthesis without anchoring a foregrounded quantitative claim and are catalogued for completeness: Liu 2026, ADA 2024, Schulz 2010, Ioannidis 2005.

References

  • Abdollahpour 2025. Comparative effects of intermittent fasting and calorie restriction on cardiovascular health in adults with overweight or obesity. Scientific Reports, 2025. DOI: 10.1038/s41598-025-32673-9. PMID: 41398306.
  • Kazeminasab 2025. Effects of Intermittent Fasting and Calorie Restriction on Exercise Performance: A Systematic Review and Meta-Analysis. Nutrients, 2025. DOI: 10.3390/nu17121992. PMID: 40573103.
  • Couto-Alfonso 2026. Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures. Nutrients, 2026. DOI: 10.3390/nu18091450. PMID: 42124054.
  • Kibret 2025. Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis. Current Nutrition Reports, 2025. DOI: 10.1007/s13668-025-00684-7. PMID: 40705196.
  • Lu 2025. The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis. Journal of Health, Population, and Nutrition, 2025. DOI: 10.1186/s41043-025-01039-2. PMID: 40826125.
  • Dai 2025. Additional Effect of Exercise to Intermittent Fasting on Body Composition and Cardiometabolic Health in Adults With Overweight/obesity: A Systematic Review and Meta-analysis. Current Obesity Reports, 2025. DOI: 10.1007/s13679-025-00645-9. PMID: 40533648.
  • Li 2026. Intermittent fasting versus continuous energy restriction in MASLD: a systematic review and meta-analysis. Frontiers in Nutrition, 2026. DOI: 10.3389/fnut.2026.1833688. PMID: 42211106.
  • Semnani-Azad 2025. Intermittent fasting strategies and their effects on body weight and other cardiometabolic risk factors: systematic review and network meta-analysis of randomised clinical trials. The BMJ, 2025. DOI: 10.1136/bmj-2024-082007. PMID: 40533200.
  • Ranneh 2025. Effect of Intermittent Fasting on Anthropometric Measurements, Metabolic Profile, and Hormones in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Nutrients, 2025. DOI: 10.3390/nu17152436. PMID: 40806019.
  • Qudah 2026. Effects of intermittent fasting on HbA1c and weight in insulin versus oral hypoglycemic therapy-treated patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Frontiers in Nutrition, 2026. DOI: 10.3389/fnut.2026.1699384. PMID: 41693941.
  • Khalafi 2025. The Effects of Intermittent Fasting on Inflammatory Markers in Adults: A Systematic Review and Pairwise and Network Meta-Analyses. Nutrients, 2025. DOI: 10.3390/nu17152388. PMID: 40805975.
  • Wang 2025. The impact of intermittent fasting on body composition and cardiometabolic outcomes in overweight and obese adults: a systematic review and meta-analysis of randomized controlled trials. Nutrition Journal, 2025. DOI: 10.1186/s12937-025-01178-6. PMID: 40731344.
  • Liu 2026. Intermittent fasting for rheumatic diseases: a systematic review and meta-analysis of conflicting evidence from observational studies and randomized controlled trials. PeerJ, 2026. DOI: 10.7717/peerj.21185. PMID: 42079723.
  • Valenzano 2025. Influence of Intermittent Fasting on Body Composition, Physical Performance, and the Orexinergic System in Postmenopausal Women: A Pilot Study. Nutrients, 2025. DOI: 10.3390/nu17071121. PMID: 40218879.
  • Barrionuevo-Burgos 2026. Effects of intermittent fasting combined with a ketogenic diet versus a hypocaloric diet on metabolic outcomes in adults with type 2 diabetes mellitus: A controlled clinical study. Nutr Health, 2026. DOI: 10.1177/02601060261446178. PMID: 42101451.
  • Impact 2025. Impact of Intermittent Fasting on Gut Barrier Function and Inflammation. Journal of Carcinogenesis, 2025. DOI: 10.64149/j.carcinog.24.10s.2833.
  • Couto 2025. The impact of intermittent fasting and Mediterranean diet on older adults' physical health and quality of life: A randomized clinical trial. Nutr Metab Cardiovasc Dis, 2025. DOI: 10.1016/j.numecd.2025.104132. PMID: 40451678.

Background References

Canonical clinical thresholds cited in prose. Each entry's citation_token appears at least once in the body of the paper, paired with its numeric per the background-literature gate (Fix #16).

  • ADA 2024. American Diabetes Association. Standards of Care in Diabetes. Diabetes Care. 2024;47(Suppl 1). DOI: 10.2337/dc24-S006.
  • Schulz 2010. Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332. DOI: 10.1136/bmj.c332.
  • Ioannidis 2005. Ioannidis JPA. Why most published research findings are false. PLoS Med. 2005;2(8):e124. DOI: 10.1371/journal.pmed.0020124. PMID: 16060722.

Proof Trail

Decision: AcceptLiving evidence briefGate flags: 0

Topic: fasting_intervention_intermittent_fasting_effects

Author owner: Dominic Lynch

Owner ORCID: 0009-0005-4286-8363

Institution: not supplied

ROR: not supplied

RAiD: not supplied

OSF DOI: 10.17605/OSF.IO/ENZM9

AI co-writer: agent-v3-full-paper-live

Reviewer: reviewer-panel

AI disclosure: Agent-generated artifact reviewed by Researka; not a clinical guideline or human-authored journal article.

Published: Jun 12, 2026

Provenance chain: Available → View

SHA-256: sha256:bc612e52b3c...

Publication ID: b1750150-b7b0-4272...

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