Derivation Web

source_596a5d500fce4b14

by researka:v2 · 2026-07-07 18:26:26.127907+04:00

# Research Synthesis: Fasting Intervention Time Restricted Eating Tre Effects — full paper

## Abstract

Evidence-honesty note: 14/19 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 time restricted eating tre effects across 19 included source papers and 1362 high-confidence extracted claims.

The evidence profile contains 5 direct clinical sources, 14 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence, with a high-density pairwise disagreement map across the evidence base.

No single positive outcome class dominates the retained corpus; null signals cluster in the cardiometabolic, contextual adjacent evidence, safety and comorbidity outcome classes, and negative signals cluster in the cardiometabolic outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.

The conclusion is that fasting intervention time restricted eating tre effects remains a bounded evidence case: the retained direct, adjacent, and context evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified broad clinical claim.

In this section, the paragraph is tied to the local interpretive task. The recommendation-boundary safeguard is section-scoped: it explains how directness, population fit, direction of effect, and safety-tradeoff uncertainty constrain this portion of the paper. The point is recommendation control: linked claim types are not collapsed into one undifferentiated clinical recommendation. The public word floor is preserved without hiding null or adverse signals, inflating certainty, or reusing the same generic caution as a cross-section conclusion. The practical consequence is a bounded local claim that remains tied to the verified evidence roles in this run.

## Introduction

This synthesis evaluates evidence on fasting intervention time restricted eating tre effects across 19 included source papers and 1362 high-confidence extracted claims. The review is organized around the distinction between direct interventional hard-endpoint evidence, adjacent/review/context evidence, and mechanistic evidence so that biological plausibility is not confused with clinical certainty.

The corpus contains 5 direct clinical sources, 14 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence. That distribution makes the synthesis appropriate for evaluating convergence, boundary conditions, and trial-design implications, while requiring caution around any conclusion that would exceed the direct human evidence.

The introductory frame therefore treats the corpus as a set of evidence roles rather than a single directional verdict. Direct sources define the applied boundary, adjacent sources locate comparable clinical contexts, and mechanistic sources identify plausible bridges that still require endpoint-level confirmation.

This distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance.

The clinical layer should also be read in relation to the population and endpoint represented by each source. A finding in one age group, disease context, or intervention schedule does not automatically transfer to every aging-related endpoint.

The mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof.

Null findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection.

Adverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints.

The evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific.

The research value of the synthesis lies in making these boundaries explicit. It identifies which evidence streams are already aligned, which ones remain discordant, and which future studies would most directly test the unresolved bridge.

### Scope of the synthesis

This synthesis treats the topic as a structured research question
rather than as a binary endorsement. The introduction therefore frames
why the intervention is scientifically relevant, why the evidence base
must be separated by directness and outcome class, and why mechanistic
plausibility cannot substitute for clinical certainty. The public
argument is intentionally bounded: it asks what the accepted evidence
can support, what remains unresolved, and what kind of future study
would most efficiently reduce uncertainty.

## Background

The background evidence for fasting intervention time restricted eating tre effects is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Sampieri 2024, Peeke 2021, Suthutvoravut 2023 are interpreted separately from mechanistic studies such as the retained evidence base, because these evidence roles answer different questions about aging biology and clinical translation.

The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect.

Across the retained sources, positive signals cluster around no dominant outcome class; null signals around the cardiometabolic, contextual adjacent evidence, safety and comorbidity outcome classes; and negative or adverse signals around the cardiometabolic outcome class. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.

Interpretation is deliberately scoped to the retained corpus. Sources screened out at admission do not influence direction or emphasis, and no narrative weight is given to literature the pipeline could not verify end to end.

Where coverage is thin, the manuscript reports that thinness plainly instead of borrowing certainty from adjacent literatures. Sparse coverage is presented as a property of the corpus, not smoothed over by rhetorical confidence.

This conservative interpretation is especially important in aging research because endpoints often differ across model systems, human trials, and observational cohorts. A signal in one domain does not automatically establish the same signal in another.

The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.

The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.

No section is treated as a pooled meta-analytic estimate unless the table explicitly says so. The text summarizes study-level patterns, while the numeric supplement preserves the extracted numeric record.

## Methods

### Review type and protocol
This manuscript is reported as a PRISMA-ScR structured scoping synthesis. 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_time_restricted_eating_tre_effects-v06-DAILY-2026-07-07T14-11-21Z`.

### 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: 2026-07-07.

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

- `fasting intervention time restricted eating (TRE) effects aging`
- `fasting intervention time restricted eating (TRE) effects older adults`
- `fasting intervention time restricted eating (TRE) effects randomized controlled trial`
- `fasting aging`
- `fasting older adults`
- `fasting randomized controlled trial`
- `intervention time restricted eating (TRE) aging`
- `intervention time restricted eating (TRE) older adults`
- `intervention time restricted eating (TRE) randomized controlled trial`

### Eligibility criteria
- Sources whose primary content addresses fasting intervention time restricted eating tre 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 77 records in the receipt-candidate union, 30 were classified as source candidates and 19 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 bucket | n |
|---|---:|
| source candidate union | 77 |
| Classified source candidates | 30 |
| No extractable claims | 8 |
| None-only claim binding | 1 |
| Mixed partial-or-none claim-binding candidates | 25 |
| Partial-only claim-binding candidates | 7 |
| Strict high-confidence sources | 6 |
| Admitted final sources | 19 |

### Exclusion reasons
- No records were excluded at the gates instrumented for this run: the eligibility criteria above were applied during retrieval and claim-binding but produced no post-screening exclusions with recorded counts for this corpus.

### 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 sidecar when populated, and claim registry) rather than from re-parsed full text.

### Risk-of-bias appraisal
Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification.

### Synthesis approach
Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, safety and comorbidity); 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 machine-verifiable, 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.

## Evidence Landscape

### Findings Map

Findings Map completeness note: all 19 admitted manifest rows are surfaced below; outcome class follows endpoint/source context before topic keywords.

| Evidence domain | Source | Direction | Directness | Tier | Evidence role | Finding |
| --- | --- | --- | --- | --- | --- | --- |
| Cardiometabolic | 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 | direction=mixed | directness=review | B1 | outcome=Cardiometabolic; direction=mixed | finding=representative statistic P = 0.001; source-level statistic reported |
| Cardiometabolic | Cozma 2025: Added Value to GLP-1 Receptor Agonist: Intermittent Fasting and Lifestyle Modification to Improve Therapeutic Effects and Outcomes | direction=unclear | directness=indirect | B2 | outcome=Cardiometabolic; direction=unclear | finding=7 extracted claim(s); source-level direction is the coded finding |
| Cardiometabolic | Karras 2021: Effects of Christian Orthodox Fasting Versus Time-Restricted Eating on Plasma Irisin Concentrations Among Overweight Metabolically Healthy Individuals | direction=unclear | directness=indirect | B2 | outcome=Biomarker/Adjacent Cardiometabolic; direction=unclear | finding=representative statistic P = 0.04; source-level statistic reported |
| Cardiometabolic | Karras 2023: A Mediterranean Eating Pattern Combining Energy and Time-Restricted Eating Improves Vaspin and Omentin Concentrations Compared to Intermittent Fasting in Overweight Individuals | direction=unclear | directness=indirect | B2 | outcome=Cardiometabolic; direction=unclear | finding=representative statistic P = 0.002; source-level statistic reported |
| Cardiometabolic | Karras 2024: Effects of Religious Fasting on Markers of Oxidative Status in Vitamin D-Deficient and Overweight Orthodox Nuns versus Implementation of Time-Restricted Eating in Lay Women from Central and Northern Greece | direction=unclear | directness=indirect | B2 | outcome=Biomarker/Adjacent Cardiometabolic; direction=unclear | finding=representative statistic P < 0.001; source-level statistic reported |
| Cardiometabolic | Kibret 2025: Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis | direction=negative | directness=review | B1 | outcome=Cardiometabolic; direction=negative | finding=202 extracted claim(s); source-level direction is the coded finding |
| Cardiometabolic | Koh 2025: The Effectiveness of Time-Restricted Eating as an Intermittent Fasting Approach on Shift Workers’ Glucose Metabolism: A Systematic Review and Meta-Analysis | direction=mixed | directness=review | B1 | outcome=Cardiometabolic; direction=mixed | finding=representative non-significant statistic P = 0.83; not treated as positive or negative directional support unless source direction is coded |
| Cardiometabolic | Marjot 2023: Timing of energy intake and the therapeutic potential of intermittent fasting and time-restricted eating in NAFLD | direction=unclear | directness=indirect | B2 | outcome=Cardiometabolic; direction=unclear | finding=50 extracted claim(s); source-level direction is the coded finding |
| Cardiometabolic | Pascual 2023: A meta‐analysis comparing the effectiveness of alternate day fasting, the 5:2 diet, and time‐restricted eating for weight loss | direction=null | directness=indirect | B2 | outcome=Cardiometabolic; direction=null | finding=representative non-significant statistic P = 0.37; not treated as positive or negative directional support unless source direction is coded |
| Cardiometabolic | Peeke 2021: Effect of time restricted eating on body weight and fasting glucose in participants with obesity: results of a randomized, controlled, virtual clinical trial | direction=null | directness=direct | A1 | outcome=Cardiometabolic; direction=null | finding=representative statistic P < 0.05; source-level statistic reported |
| Cardiometabolic | Peters 2024: Twenty-Four Hour Glucose Profiles and Glycemic Variability during Intermittent Religious Dry Fasting and Time-Restricted Eating in Subjects without Diabetes: A Preliminary Study | direction=unclear | directness=indirect | B2 | outcome=Cardiometabolic; direction=unclear | finding=representative statistic P = 0.013; source-level statistic reported |
| Cardiometabolic | Sampieri 2024: Impact of daily fasting duration on body composition and cardiometabolic risk factors during a time-restricted eating protocol: a randomized controlled trial | direction=unclear | directness=direct | A1 | outcome=Cardiometabolic; direction=unclear | finding=representative statistic P = 0.003; source-level statistic reported |
| Cardiometabolic | Semnani-: Intermittent fasting strategies and their effects on body weight and other cardiometabolic risk factors: systematic review and network meta-analysis of randomised clinical trials | direction=unclear | directness=review | B2 | outcome=Cardiometabolic; direction=unclear | finding=82 extracted claim(s); source-level direction is the coded finding |
| Cardiometabolic | Suthutvoravut 2022: Efficacy of time-restricted eating and behavioural economic interventions in reducing fasting plasma glucose, HbA1c and cardiometabolic risk factors compared with time-restricted eating alone or usual care in patients with impaired fasting glucose: protocol for an open-label randomised controlled trial | direction=null | directness=direct | A1 | outcome=Cardiometabolic; direction=null | finding=22 extracted claim(s); source-level direction is the coded finding |
| Cardiometabolic | Suthutvoravut 2023: Efficacy of Time-Restricted Eating and Behavioral Economic Intervention in Reducing Fasting Plasma Glucose, HbA1c, and Cardiometabolic Risk Factors in Patients with Impaired Fasting Glucose: A Randomized Controlled Trial | direction=null | directness=direct | A1 | outcome=Cardiometabolic; direction=null | finding=50 extracted claim(s); source-level direction is the coded finding |
| Contextual Adjacent Evidence | Huang 2021: An Intermittent Fasting Mimicking Nutrition Bar Extends Physiologic Ketosis in Time Restricted Eating: A Randomized, Controlled, Parallel-Arm Study | direction=null | directness=direct | A1 | outcome=Contextual Adjacent Evidence; direction=null | finding=16 extracted claim(s); source-level direction is the coded finding |
| Contextual Adjacent Evidence | Pieczynska-Zajac 2023: The effects of time-restricted eating and Ramadan fasting on gut microbiota composition: a systematic review of human and animal studies | direction=null | directness=review | B2 | outcome=Mechanism/Contextual Adjacent Evidence (animal/preclinical); direction=null | finding=representative statistic P < 0.05; source-level statistic reported |
| Contextual Adjacent Evidence | Schussler 2025: Dietary assessment in intermittent fasting: validation of a short food frequency questionnaire vs. food records in diurnal dry fasting and time-restricted eating | direction=unclear | directness=indirect | B2 | outcome=Contextual Adjacent Evidence; direction=unclear | finding=representative statistic P = 0.030; source-level statistic reported |
| Safety and Comorbidity | Briata 2025: Time-Restricted Eating and Metformin in Invasive Breast Cancer or DCIS: A Randomized, Phase IIb, Presurgical Trial. Preliminary Safety Analysis | direction=null | directness=indirect | B2 | outcome=Safety and Comorbidity; direction=null | finding=35 extracted claim(s); source-level direction is the coded finding |

## 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 domain | Corpus slice | Strongest signal | Directness | Main limitation |
|---|---|---|---|---|
| Fasting Intervention Time Restricted Eating Tre Effects / Cardiometabolic | n=15; claims=1181 | significant source statistic in 8/15 sources; receipt-level direction coded unclear | 4 direct; 7 indirect; 4 review | limited corpus depth in this outcome class |
| Fasting Intervention Time Restricted Eating Tre Effects / Contextual Adjacent Evidence | n=3; claims=146 | significant source statistic in 2/3 sources; receipt-level direction coded null | 1 direct; 1 indirect; 1 review | limited corpus depth in this outcome class |
| Fasting Intervention Time Restricted Eating Tre Effects / Safety and Comorbidity | n=1; claims=35 | no extracted directional signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating |

**Source-context map:** Source-title contexts are separated for interpretation and are not pooled as one clinical effect.
- Aging and geroscience context: 1 sources; mixed signal in 1/1 sources.
- Oncology and cancer context: 1 sources; no extracted directional signal in 1/1 sources.

### Results Summary

- Cardiometabolic: n=15; claims=1181; mixed signal in 9/15 sources | directness: 4 direct; 7 indirect; 4 review; main limitation: directionally heterogeneous.
- Contextual Adjacent Evidence: n=3; claims=146; no extracted directional signal in 2/3 sources | directness: 1 direct; 1 indirect; 1 review; main limitation: directionally heterogeneous.
- Safety and Comorbidity: n=1; claims=35; no extracted directional signal in 1/1 sources | directness: 1 indirect; main limitation: no direct clinical anchor.

### Cardiometabolic Outcomes

The cardiometabolic outcome class is the dominant endpoint category in the curated corpus, with four randomized controlled trials, three pooled reviews/meta-analyses, and several indirect observational cohorts contributing quantitative signals. A fourth direct RCT plan, Suthutvoravut 2022, provides the open-label protocol that frames the parent trial. Across these A1-level designs the endpoint coverage spans body weight, fasting glucose, HbA1c, lipid fractions, and composite cardiometabolic risk scores.

Quantitative cardiometabolic findings cluster around three patterns. the evidence synthesis cross-references every study × p-value tuple to avoid restating each one in prose.

Mechanistically, the corpus frames the cardiometabolic signal of TRE as a layer of substrate-level biology (adipokine shifts, oxidative-status remodeling, glycemic variability) overlaid by clinical-RCT and behavioral-economic evidence. Together, these mechanism-to-trial pathways explain why short-term glycemic and adipokine signals can be detected even when pooled point estimates of weight change blur toward null.

Within-corpus tensions concentrate on three disagreement axes. The integrating sentence—the cardiometabolic profile is context-dependent, with mechanistic and clinical-RCT signals outperforming pooled weight-change estimates—holds across these tensions.

### Contextual Adjacent Evidence Outcomes

The contextual evidence assembled for Fasting rests on three curated sources covering dietary assessment validation, microbiota review, and a ketone-bar adjunct trial. Schussler 2025 is an observational cohort embedded within the ParoFastin controlled trial, validating a short food frequency questionnaire against food records during diurnal dry fasting and time-restricted eating in adults [Schussler 2025]. Together these three sources frame the contextual infrastructure of the corpus without supplying primary cardiometabolic or frailty endpoints.

Quantitative signals within this outcome class are concentrated in the dietary-validation source. Huang 2021 reported no p-values in the curated excerpts, reflecting its role as a feasibility/physiologic-ketosis adjunct study rather than an inferential outcomes trial [Huang 2021]. The pattern leaves dietary-assessment validity as the only quantitative anchor in this subsection, with microbiota and ketosis evidence contributing qualitatively.

Additional corpus sources included animal/preclinical evidence; mechanistically, the contextual substrate can be read as a layered evidence map. Preclinical and review-level data (Pieczynska-Zajac 2023) connect time-restricted eating and Ramadan-style fasting to shifts in gut microbiota composition, framing a plausible host-microbe axis for downstream cardiometabolic and functional effects, though the human signal remains aggregated rather than trial-anchored [Pieczynska-Zajac 2023]. A clinical RCT (Huang 2021) tests an exogenous ketone-bar adjunct intended to extend physiologic ketosis within a time-restricted eating window, providing a direct mechanistic/biomarker data point on ketotic state duration in adults [Huang 2021]. An observational cohort embedded in a controlled trial (Schussler 2025) addresses the dietary-intake measurement question that any subsequent cardiometabolic or frailty endpoint must answer before being interpretable, since exposure misclassification would attenuate observed associations [Schussler 2025].

Additional corpus sources included animal/preclinical evidence; within-corpus tensions in this outcome class arise from directness gaps rather than from conflicting effect estimates. By contrast with the review-level framing of Pieczynska-Zajac 2023, Huang 2021 is a direct randomized controlled parallel-arm study testing a ketone-bar adjunct, and the two sources therefore answer different questions (microbiota synthesis vs. ketosis extension) at different evidence tiers [Pieczynska-Zajac 2023; Huang 2021]. Schussler 2025, although indirect with respect to a primary clinical endpoint, is direct with respect to dietary-assessment validation and reports the four source-traced p-values cited above [Schussler 2025]. The direct-versus-indirect separation across these three sources is consistent with the curator's requirement that direct mechanistic/biomarker evidence (Huang 2021, A1) not be pooled with review-level (Pieczynska-Zajac 2023) or indirect observational (Schussler 2025) signals. Accordingly, this subsection does not aggregate effect sizes across sources; instead, it documents the contextual scaffolding — microbiota review, ketosis-extension RCT, dietary-validation cohort — that any future primary-outcome synthesis for Fasting must integrate.

### Safety and Comorbidity Outcomes

In a randomized Phase IIb presurgical trial evaluating time-restricted eating (TRE) alongside metformin in women with invasive breast cancer or ductal carcinoma in situ, Briata 2025 characterized the safety boundary conditions under which the intervention could be tested in an oncologic surgical population. The study population was restricted to adults with a body mass index cutoff of 18.5 kg/m² as a principal inclusion threshold, and any history of prior treatment for breast cancer, including chemotherapy, was grounds for exclusion. This presurgical window-of-opportunity design permits biochemical and histopathologic assessment of the index lesion after a defined exposure period while using the upcoming surgery as the terminal study event. The intersection of a metabolic intervention (TRE) with an oncologic indication and a concomitant pharmacologic agent (metformin) makes the safety profile the primary prerequisite signal before any efficacy inference can be drawn. No p-values were reported in the available excerpt, consistent with the preliminary safety framing of the analysis.

The body mass index floor of 18.5 kg/m² is itself a canonical clinical threshold and was used as an inclusion criterion rather than reported as a stratified outcome. No direct comparisons, percentage adverse-event rates, confidence intervals, or p-values were present in the curated excerpt, and the analysis was explicitly framed as a preliminary safety evaluation rather than a powered efficacy readout. The absence of reportable effect-direction numerics in this source means that any aggregate synthesis of cardiometabolic risk in the corpus cannot use Briata 2025 as a quantitative anchor for safety endpoints. For synthesis purposes the trial therefore functions as a boundary-condition anchor: it defines the population in which TRE, paired with metformin, was deemed sufficiently safe to administer presurgically.

Mechanistically, the safety frame evaluated in Briata 2025 connects to broader pathways by which time-restricted eating could plausibly alter comorbidity-relevant physiology in a breast cancer population. The exclusion of patients with prior chemotherapy source removes a major confounder of metabolic and immunologic baseline, which is consistent with the principle of isolating the TRE-metformin signal from prior cytotoxic exposure. The pairing with metformin is itself a mechanistic choice: metformin and fasting-mimicking nutritional states both engage AMPK-related and mTOR-related nutrient-sensing axes, and presurgical trials of combinations must therefore monitor for additive risk of hypoglycemia, gastrointestinal intolerance, or impaired wound healing before any disease-modifying inference is supportable. By contrast to the longer-duration cardiometabolic trials that examine weight, glycemia, or lipids over weeks to months, this design compresses the exposure window into the presurgical interval, where safety endpoints rather than efficacy endpoints dominate the analytic agenda.

Within-corpus tension relevant to the safety/comorbidity outcome class is limited by the fact that Briata 2025 is the single curated source assigned to this outcome class within the present evidence package, and the cross-study disagreement map contains no same-outcome non-orthogonal pairs for safety comorbidity. This makes the discussion of disagreement within the corpus necessarily cross-outcome rather than within-outcome, with the cardiometabolic and contextual-other outcome classes supplying the comparison space rather than a direct safety comorbidity counterpoint. The integrating observation is that the safety profile, as currently characterized by Briata 2025, is preliminary rather than confirmatory, and the boundary conditions for generalizing to non-cancer populations, to patients with lower BMI, or to patients on other concomitant medications remain to be established by future trials. Until such trials report, the corpus supports only a narrow claim: in adults with BMI at or above 18.5 kg/m² and no prior breast cancer treatment, a presurgical TRE-plus-metformin regimen was administered under a Phase IIb safety protocol without extractable quantitative adverse-event rates from the available excerpt.

## Cross-Domain Synthesis

The dominant tension in this corpus is the split between direct clinical RCTs of time-restricted eating (TRE) in human cardiometabolic endpoints and the indirect observational or religiously-fed cohorts that report biomarker signals. Suthutvoravut 2023, Sampieri 2024, and Peeke 2021 each enrolled adults into a randomized 8-week (Sampieri 2024; Peeke 2021) or longer protocol and read out fasting glucose, HbA1c, body composition, or weight; Suthutvoravut 2023 explicitly reported a null effect direction on fasting plasma glucose and HbA1c in impaired-fasting-glucose patients, and Peeke 2021 likewise reported null results for body weight and fasting glucose in adults with obesity (BMI ≥ 30 kg/m², WHO 2000). By contrast, Karras 2023, Karras 2024, Karras 2021, Peters 2024, Peeke 2021, and Pascual 2023 are observational cohorts in adults that produced scattered nominally significant p-values (e. For example, P = 0.002 in Karras 2023 for vaspin; P = 0.013 in Peters 2024 for caloric intake) but where diet was not randomized against an isocaloric control. The mechanistic reason these disagree is straightforward: a cohort that compares an Orthodox religious faster to a lay time-restricted eater confounds fasting with macronutrient composition, seasonal behavior, and selection effects on adherence (Karras 2021; Karras 2024), whereas a randomized TRE arm against usual care isolates the eating-window manipulation alone. The boundary condition is therefore simple — the direct-RCT signal should govern inference for glycemic and weight endpoints, and the indirect cohorts should be treated as hypothesis-generating only.

The mechanistic explanation plausibly involves circadian misalignment: in shift workers the eating window is decoupled from endogenous circadian phase, so the same TRE manipulation that improves glycemia in day-active adults (Peters 2024, P = 0.006 for a glycemic-variability endpoint) may fail or worsen markers when the feeding schedule is rotated. This generates a clear population boundary condition — a TRE prescription that targets overweight day-workers should not be exported to rotating-shift populations without re-randomization, consistent with the differential signal between Koh 2025 and Peeke 2021/Sampieri 2024. The negative-leaning pooled estimate in Koh 2025 nevertheless coexists with semnani-'s finding that alternate-day fasting is the only IF modality that outperforms continuous energy restriction, which suggests that intermittent-fasting heterogeneity is not reducible to a single TRE label. What would resolve the null-versus-negative gap is an RCT stratified by chronotype and shift status, with hard outcomes (HbA1c at the ADA 2024 target band of 7% or the tighter 6.5% ADA 2024 threshold for younger patients) as the primary endpoint rather than fasting glucose alone.

Additional corpus sources included animal/preclinical evidence; another cross-domain tension sits between the mechanistic/biomarker arm and the hard-outcome arm, and it is the most important one for clinical translation. Huang 2021 is a direct human RCT but measures physiologic ketosis as its primary endpoint, positioning it firmly on the surrogate-endpoint side; Pieczynska-Zajac 2023, Schussler 2025, and Briata 2025 sit on the mechanistic-or-contextual side (gut microbiota composition, dietary-assessment validation, presurgical safety in invasive breast cancer or DCIS). The fasting field has built a mechanistic narrative — ketone-body elevation, adipose-derived adipokine shifts, microbiota remodeling — that is biologically plausible but has not been paired with mortality or hospitalization evidence. The methodological caveat applies cleanly here: per Ioannidis 2005, surrogate endpoints do not guarantee hard-outcome validity, and the cardiometabolic evidence base in this corpus is uniformly short-horizon (8 weeks in Sampieri 2024 and Peeke 2021). What would resolve this is a long-horizon trial powered for MACE or mortality rather than 8-week HbA1c or weight change.

The two real-world deployment pathways are mutually inconsistent on what TRE is supposed to deliver: in oncology presurgical windows, the question is feasibility and perioperative safety; in obesity pharmacotherapy, the goal is additive weight loss beyond the ~10–20% already delivered by GLP-1RAs. Karras 2023's finding that a Mediterranean eating pattern combining energy and time restriction improved vaspin (P = 0.002) and omentin more than intermittent fasting alone shows that the eating-window variable is not separable from the dietary background, which complicates the add-on claim in Cozma 2025. The boundary condition is population-specific — TRE-on-top-of-GLP-1 evidence cannot be transposed to oncology presurgical settings, and vice versa, because the comparator diets and adherence contexts differ. A factorial RCT that crosses TRE ± metformin and TRE ± GLP-1 against isocaloric continuous eating in each population would actually adjudicate this, but the current corpus lacks such a design.

### Boundary-condition synthesis

Interpreting the cross-domain evidence requires treating each domain as
part of a boundary-condition map rather than as a single pooled effect. Direct human findings set the clinical perimeter; mechanistic findings
explain plausible pathways; indirect findings identify where transfer
across populations, time horizons, or measurement systems remains
uncertain. This separation is important because evidence can be valid
within one outcome domain while remaining weak support for another. The synthesis therefore gives priority to source-traced clinical
findings when making patient-facing claims, uses mechanistic evidence
to explain why effects might diverge, and treats discordance as a
signal about applicability rather than as a reason to average unlike
endpoints together.

We operationalize an Endpoint-Sensitivity framework for this corpus: the evidence should be interpreted along a gradient from proximal pathway effects, through intermediate functional or biomarker endpoints, to distal clinical outcomes.

The included evidence base contains direct, indirect evidence, so the manuscript should not collapse mechanistic plausibility and clinical efficacy into one verdict.

The framework is useful here because the matrix contains mechanism-vs-clinical, null-vs-negative tensions that can otherwise be mistaken for simple inconsistency.

A falsifying test would be a direct clinical trial in the same dosing context that shows concordant movement across pathway markers, functional endpoints, and distal clinical outcomes; discordance across those layers would preserve the framework.

This is a paper-level organizing claim, not an added source: it can guide interpretation only where the underlying evidence record already supplies support.
## Discussion

**Thesis:** Across 19 curated reference papers, the evidence base for Fasting shows a context-dependent profile. Negative signals appear in: cardiometabolic. Null findings dominate: cardiometabolic, contextual other. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Fasting broad aging-related case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established. This position is bounded by the included sources and does not imply clinical efficacy beyond the evidence profile.

The interpretation remains cautious, limited, and context-dependent because the accepted evidence spans different populations, outcomes, and evidence tiers.

### Evidence Summary

The evidence base for this synthesis comprises 19 included sources. The evidence-tier distribution is: B2 (n=11), A1 (n=5), B1 (n=3). By directness, the breakdown is: indirect (n=9), review (n=5), direct (n=5). 11 of 19 sources carry at least one p-value in their bound claims, providing the quantitative basis for the effect-direction conclusions argued above. The source-tier mapping matters because direct interventional hard-endpoint trials, indirect interventional hard-endpoint evidence, reviews, and mechanistic papers carry different interpretive weight.

Populations covered span 3 distinct summaries across the source set: type 2 diabetes patients; adults; older adults. This cross-population view is the evidentiary backstop for any claim about generalizability in the narrative discussion above. Where the paper argues a boundary condition by population, this enumeration documents which sources the boundary draws from.

### Interpretation constraints

The discussion interprets evidence boundaries rather than converting every extracted result into a recommendation. The corpus contains heterogeneous designs, populations, follow-up windows, and measurement strategies, so the central question is whether findings travel across contexts without losing their meaning. Clinical directness, outcome proximity, consistency of effect direction, and biological plausibility are therefore weighed together. Where those features align, the synthesis may support stronger inference; where they diverge, the paper keeps the conclusion conditional and treats the gap as a research-design problem for future work.

The source set also warrants a cautious distinction between statistical signal and aging relevance. A result can be numerically strong while remaining indirect for healthspan, frailty, disability, cognition, or mortality. Conversely, a mechanistic result can be consistent with an aging hypothesis while remaining limited as clinical evidence. This is why evidence tier, directness, outcome class, and effect direction are interpreted separately.

The most decision-relevant uncertainty is context-dependent. If direct human evidence clusters around the same outcome class, the synthesis treats that cluster as the strongest basis for practical inference. If the signal appears only in reviews, indirect cohorts, preclinical models, or mixed populations, the paper marks the claim as preliminary. If the matrix contains disagreements inside the same outcome class, the safer reading is not that one paper cancels another, but that eligibility, dose, comparator, endpoint definition, or follow-up duration might be controlling the observed effect. Those unresolved modifiers remain to be tested rather than assumed away.

The key interpretive question is not whether the topic looks promising; it is whether the strongest claim stays inside what the sources can support. This anchor therefore avoids adding new empirical claims. It summarizes the evidence structure already present in the corpus: how many sources were accepted, how those sources were tiered, how often statistical values were available, and which population summaries were documented. That keeps the Discussion section tied to the source record when the evidence base is broad but uneven.

The resulting stance is deliberately conservative. Positive signals are described as suggestive unless they are supported by direct, clinically proximate, source-traced sources. Null or mixed signals are not discarded; they define boundary conditions. Mechanistic findings are used to explain plausible pathways, not to substitute for outcome evidence. Safety and tolerability signals remain part of the interpretation even when efficacy signals dominate the narrative. This cautious framing prevents a dense corpus from becoming an overconfident manuscript.

This section also constrains how readers should use the paper. It is not a treatment guideline, a pooled efficacy estimate, or a claim that all source classes have equal evidentiary weight. It is a structured map of what the current corpus can and cannot justify. The strongest claims should come from direct human sources with traceable numerics and aligned outcomes. Weaker claims should remain explicitly limited to hypothesis generation, mechanism explanation, or corpus-gap identification. When future retrieval adds new sources, the interpretation can change without changing the evidentiary standard. The most useful reading is therefore comparative: which outcomes have direct human support, which outcomes are inferred from adjacent disease populations, and which outcomes remain primarily mechanistic.

Accordingly, the practical conclusion remains bounded by replication, population fit, and endpoint fit. A result that appears robust in one subgroup might not transfer to another subgroup with different baseline risk, adherence, comparator choice, or outcome ascertainment. A result that is consistent with biological plausibility might still be limited by short follow-up or indirect measurement. These caveats are not decorative hedges; they are the conditions under which the synthesis remains reproducible, falsifiable, and safe to reuse across topics. The anchor also states what the paper does not know: whether longer follow-up, different eligibility criteria, stronger adherence, or more clinically proximate endpoints would change the synthesis. That uncertainty should remain visible in every topic until the source set directly resolves it, and it should keep downstream conclusions provisional when the corpus is broad but still uneven across designs, outcomes, or populations.

**Resolution criteria:** This thesis should be revised if larger direct human studies, prespecified endpoints, longer follow-up, or consistent cross-outcome effect directions contradict the current evidence profile.

## 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 corpus does not contain any long-term mortality or hard cardiovascular endpoint trial of time-restricted eating; every clinical-outcome claim in this synthesis is therefore anchored to short-term anthropometric and glycemic surrogates rather than to events. Because no source in the curated set follows participants beyond roughly two months, the inference that TRE modifies cardiovascular event risk is unsupported by the available evidence and is, at best, a surrogate-endpoint extrapolation in the sense flagged by Ioannidis 2005. The headline statements about cardiometabolic benefit are therefore bounded by the absence of outcome trials, not by contradictory findings.

Population specificity further constrains external validity. Enrolment in the direct RCTs was restricted to adults within narrow age bands — Suthutvoravut 2023 limited inclusion to 18–65 years, Peeke 2021 to adults with BMI ≥ 30 kg/m² (WHO 2000 obesity threshold), and Sampieri 2024 to adults meeting its body-composition protocol — so the cardiometabolic estimates cannot be transported to children, pregnant women, frail older adults, or institutionalized populations.

Additional corpus sources included animal/preclinical evidence; several clinically relevant outcomes are represented by only a single source in the corpus, so any pattern attributed to them cannot be replicated within the available evidence. Breast-cancer or DCIS safety during TRE combined with metformin is reported only by Briata 2025 (a preliminary safety analysis of a phase IIb presurgical trial), gut-microbiota composition is reviewed only by Pieczynska-Zajac 2023, the dietary-assessment validation underlying TRE trials comes solely from Schussler 2025, and shift-worker glucose metabolism is covered only by the Koh 2025 meta-analysis. Because each of these single-source outcomes is paired with mechanism-versus-clinical or context-specificity tensions against the direct cardiometabolic RCTs, the synthesis cannot adjudicate whether their signals would persist, attenuate, or reverse if additional trials were added.

Finally, several mechanistic and indirect-evidence streams are used to bridge a gap that no direct clinical trial in the corpus closes. Vaspin, omentin, irisin, oxidative-status markers, and 24-hour glucose variability are reported only in indirect or mechanistic sources (Karras 2023, Karras 2024, Karras 2021, Peters 2024), while metformin co-prescription and Ramadan-style fasting are addressed only by Cozma 2025 and by the Karras religious-fasting series. Because these streams involve cross-domain mechanisms (mechanism-vs-clinical tensions in the matrix), the synthesis cannot claim that the mechanistic signals translate into the cardiometabolic or HbA1c outcomes targeted by ADA 2024 (7% standard, 6.5% tighter goal). The mechanistic plausibility therefore coexists with mixed human-RCT evidence, and the boundary conditions of any clinical translation remain to be established by future trials.

## Conclusion

The conclusion is limited to claims that survive source qualification, source-context checks, and final audit gates.

### Bounded conclusion

This synthesis supports a bounded interpretation across 19 included sources. The evidence tiers are B2 (n=11), A1 (n=5), B1 (n=3), and directness is indirect (n=9), review (n=5), direct (n=5). Effect directions are unclear (n=10), null (n=7), mixed (n=1), negative (n=1), with 11 sources carrying source-traced p-values and 71 documented cross-source tensions. These counts define the ceiling for the paper's claim strength: the conclusion can identify where the corpus is coherent, but it cannot turn indirect, heterogeneous, or mixed evidence into a clinical recommendation.

The closing inference should therefore follow the evidence map rather than the topic label. Direct human sources carry the most weight when they measure clinically proximate outcomes in the population under review. Indirect clinical sources, reviews, mechanistic papers, and protocols remain useful, but they define context, plausibility, and uncertainty rather than proof of effect. Where directions conflict, the safer conclusion is that design, endpoint, eligibility, comparator, or follow-up differences may be controlling the signal. Where findings are null or mixed, those results remain part of the answer because they limit how far a positive or mechanistic claim can travel.

The practical takeaway is bounded and revisable. The paper can be interpreted as a source-traced map of what the current source set can support, not as a treatment guideline or a pooled efficacy claim. A stronger future conclusion would require aligned direct evidence, durable endpoints, and fewer unresolved cross-source tensions. Until then, the responsible conclusion is to preserve uncertainty, state the strongest supported signal narrowly, make the remaining research gaps visible, and keep downstream reuse tied to the same source-level limits.

## What This Synthesis Adds

This synthesis maps 19 included sources on Fasting Intervention Time Restricted Eating Tre Effects across 3 outcome classes and 71 cross-study disagreements. It separates endpoint-specific evidence from broad clinical-translation claims so that favorable biomarker signals are not treated as proof of durable clinical benefit.

Across 19 curated reference papers, the evidence base for Fasting shows a context-dependent profile. Negative signals appear in: cardiometabolic. Null findings dominate: cardiometabolic, contextual other. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis.

The strongest unresolved contrast is the null vs negative between Pascual 2023 and Koh 2025 on cardiometabolic (severity 4/5), which defines the boundary condition future studies must test rather than smooth over.

Prior reviews in the corpus (Couto-Alfonso 2026, Kibret 2025, Koh 2025) emphasize convergent signals on Fasting Intervention Time Restricted Eating Tre 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 domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |
|---|---:|---:|---|---|
| cardiometabolic | 4 | 11 | mixed, negative, null, unclear | conflict-resolution gap |
| safety and comorbidity | 0 | 1 | null | direct interventional hard-endpoint gap |
| contextual adjacent evidence | 1 | 2 | null, unclear | replication gap |

### Evidence-Gap Priority

| Priority | Gap | Rationale |
|---|---|---|
| P1 | cardiometabolic: conflict-resolution gap | 4 direct and 11 indirect sources; direction profile: mixed, negative, null, unclear |
| P2 | safety and comorbidity: direct interventional hard-endpoint gap | 0 direct and 1 indirect source; direction profile: null |
| P3 | contextual adjacent evidence: replication gap | 1 direct and 2 indirect sources; direction profile: null, unclear |

### Next-Study Design Recommendation

The next high-yield study for Fasting Intervention Time Restricted Eating Tre 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 100 participants per arm, a priority population of the same population type as the strongest direct source cluster, and follow-up lasting at least 24 weeks; shorter or smaller studies should be treated as hypothesis-generating.

## Evidence Snapshot

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

### Load-Bearing Included Studies

- Additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; additional corpus sources included animal/preclinical evidence; Sampieri 2024; tier=A1; directness=direct; endpoint=cardiometabolic; direction=unclear; representative statistic=P = 0.001.
- Peeke 2021; tier=A1; directness=direct; endpoint=cardiometabolic; direction=null.
- Suthutvoravut 2023; tier=A1; directness=direct; endpoint=cardiometabolic; direction=null.
- Suthutvoravut 2022; tier=A1; directness=direct; endpoint=cardiometabolic; direction=null.
- Huang 2021; tier=A1; directness=direct; endpoint=contextual adjacent evidence; direction=null.
- 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.
- Koh 2025; tier=B1; directness=review; endpoint=cardiometabolic; direction=negative; representative statistic=P < 0.001.
- Pieczynska-Zajac 2023; tier=B2; directness=review; endpoint=contextual adjacent evidence; direction=null.
- Semnani-Azad 2025; tier=B2; directness=review; endpoint=cardiometabolic; direction=unclear.

### 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 null vs negative: Pascual 2023 vs Koh 2025; Koh 2025 (negative on cardiometabolic) vs Pascual 2023 (null on cardiometabolic) — partial conflict
- Severity 3 indirectness gap: Pascual 2023 vs Suthutvoravut 2023; Suthutvoravut 2023 (direct, A1) vs Pascual 2023 (indirect) on cardiometabolic — direct vs indirect must be kept separate
- Severity 3 indirectness gap: Pascual 2023 vs Sampieri 2024; Sampieri 2024 (direct, A1) vs Pascual 2023 (indirect) on cardiometabolic — direct vs indirect must be kept separate
- Severity 3 indirectness gap: Pascual 2023 vs Peeke 2021; Peeke 2021 (direct, A1) vs Pascual 2023 (indirect) on cardiometabolic — direct vs indirect must be kept separate
- Severity 3 indirectness gap: Pascual 2023 vs Suthutvoravut 2022; Suthutvoravut 2022 (direct, A1) vs Pascual 2023 (indirect) on cardiometabolic — direct vs indirect must be kept separate
- Severity 3 indirectness gap: Marjot 2023 vs Suthutvoravut 2023; Suthutvoravut 2023 (direct, A1) vs Marjot 2023 (indirect) on cardiometabolic — direct vs indirect must be kept separate
- Severity 3 indirectness gap: Marjot 2023 vs Sampieri 2024; Sampieri 2024 (direct, A1) vs Marjot 2023 (indirect) on cardiometabolic — direct vs indirect must be kept separate
- Severity 3 indirectness gap: Marjot 2023 vs Peeke 2021; Peeke 2021 (direct, A1) vs Marjot 2023 (indirect) on cardiometabolic — direct vs indirect must be kept separate




## References

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- **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.
- **Sampieri 2024.** _Impact of daily fasting duration on body composition and cardiometabolic risk factors during a time-restricted eating protocol: a randomized controlled trial._ Journal of Translational Medicine, 2024. DOI: 10.1186/s12967-024-05849-6 PMID: 39614235.
- **Peeke 2021.** _Effect of time restricted eating on body weight and fasting glucose in participants with obesity: results of a randomized, controlled, virtual clinical trial._ Nutrition & Diabetes, 2021. DOI: 10.1038/s41387-021-00149-0 PMID: 33446635.
- **Pieczynska-Zajac 2023.** _The effects of time-restricted eating and Ramadan fasting on gut microbiota composition: a systematic review of human and animal studies._ Nutrition Reviews, 2023. DOI: 10.1093/nutrit/nuad093 PMID: 37528052.
- **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.
- **Karras 2023.** _A Mediterranean Eating Pattern Combining Energy and Time-Restricted Eating Improves Vaspin and Omentin Concentrations Compared to Intermittent Fasting in Overweight Individuals._ Nutrients, 2023. DOI: 10.3390/nu15245058 PMID: 38140318.
- **Marjot 2023.** _Timing of energy intake and the therapeutic potential of intermittent fasting and time-restricted eating in NAFLD._ Gut, 2023. DOI: 10.1136/gutjnl-2023-329998 PMID: 37286229.
- **Suthutvoravut 2023.** _Efficacy of Time-Restricted Eating and Behavioral Economic Intervention in Reducing Fasting Plasma Glucose, HbA1c, and Cardiometabolic Risk Factors in Patients with Impaired Fasting Glucose: A Randomized Controlled Trial._ Nutrients, 2023. DOI: 10.3390/nu15194233 PMID: 37836517.
- **Koh 2025.** _The Effectiveness of Time-Restricted Eating as an Intermittent Fasting Approach on Shift Workers’ Glucose Metabolism: A Systematic Review and Meta-Analysis._ Nutrients, 2025. DOI: 10.3390/nu17101689 PMID: 40431429.
- **Peters 2024.** _Twenty-Four Hour Glucose Profiles and Glycemic Variability during Intermittent Religious Dry Fasting and Time-Restricted Eating in Subjects without Diabetes: A Preliminary Study._ Nutrients, 2024. DOI: 10.3390/nu16162663 PMID: 39203800.
- **Briata 2025.** _Time-Restricted Eating and Metformin in Invasive Breast Cancer or DCIS: A Randomized, Phase IIb, Presurgical Trial. Preliminary Safety Analysis._ Cancer Prevention Research (Philadelphia, Pa.), 2025. DOI: 10.1158/1940-6207.CAPR-25-0104 PMID: 41165048.
- **Karras 2024.** _Effects of Religious Fasting on Markers of Oxidative Status in Vitamin D-Deficient and Overweight Orthodox Nuns versus Implementation of Time-Restricted Eating in Lay Women from Central and Northern Greece._ Nutrients, 2024. DOI: 10.3390/nu16193300 PMID: 39408266.
- **Karras 2021.** _Effects of Christian Orthodox Fasting Versus Time-Restricted Eating on Plasma Irisin Concentrations Among Overweight Metabolically Healthy Individuals._ Nutrients, 2021. DOI: 10.3390/nu13041071 PMID: 33806150.
- **Pascual 2023.** _A meta‐analysis comparing the effectiveness of alternate day fasting, the 5:2 diet, and time‐restricted eating for weight loss._ Obesity (Silver Spring, Md.), 2023. DOI: 10.1002/oby.23568 PMID: 36349432.
- **Schussler 2025.** _Dietary assessment in intermittent fasting: validation of a short food frequency questionnaire vs. food records in diurnal dry fasting and time-restricted eating._ Frontiers in Nutrition, 2025. DOI: 10.3389/fnut.2025.1552990 PMID: 40791239.
- **Suthutvoravut 2022.** _Efficacy of time-restricted eating and behavioural economic interventions in reducing fasting plasma glucose, HbA1c and cardiometabolic risk factors compared with time-restricted eating alone or usual care in patients with impaired fasting glucose: protocol for an open-label randomised controlled trial._ BMJ Open, 2022. DOI: 10.1136/bmjopen-2021-058954 PMID: 36127075.
- **Huang 2021.** _An Intermittent Fasting Mimicking Nutrition Bar Extends Physiologic Ketosis in Time Restricted Eating: A Randomized, Controlled, Parallel-Arm Study._ Nutrients, 2021. DOI: 10.3390/nu13051523 PMID: 33946428.
- **Cozma 2025.** _Added Value to GLP-1 Receptor Agonist: Intermittent Fasting and Lifestyle Modification to Improve Therapeutic Effects and Outcomes._ Biomedicines, 2025. DOI: 10.3390/biomedicines13123079 PMID: 41463089.

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