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sha256 900b945a0a1e7ae7f773c4df2b44e22f049d5317640ea7b7d763566b9db6dd28
by researka:v2 · 2026-06-14 16:25:50.733497+04:00
{"publication_id": "5670918d-5c09-4049-9dbb-4a25f38ca78d", "traces": [{"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "Evidence-honesty note: The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.", "claim_id": "claim_1"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "This paper synthesizes evidence on fasting biomarker effects across 15 included source papers and 1464 high-confidence extracted claims.", "claim_id": "claim_2"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 3 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 9 cross-study disagreements across the evidence base.", "claim_id": "claim_3"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "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 outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "claim_id": "claim_4"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "The conclusion is that fasting biomarker 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.", "claim_id": "claim_5"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.", "claim_id": "claim_6"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "The global demographic shift toward aging populations has intensified the search for interventions that can extend healthspan and compress morbidity, with fasting regimens emerging as a leading candidate. Against this backdrop, Fasting Biomarker Effects—encompassing intermittent fasting, time-restricted eating, and fasting-mimicking diets—have been proposed as a pragmatic strategy to modulate aging biology at the organismal level. Whether such dietary patterns can translate mechanistic benefits into durable improvements in cardiometabolic health, cognitive function, or physical resilience remains uncertain, and the field has yet to converge on standardized protocols or endpoints. The stakes are high: the absence of clear, clinically actionable evidence limits the feasibility of integrating Fasting Biomarker Effects into routine geriatric care, particularly for older adults with multimorbidity or polypharmacy. Moreover, the extent to which these metabolic shifts translate into clinically meaningful outcomes such as reduced frailty progression or extended healthspan remains unsettled (Ioannidis 2005). The question of whether Fasting Biomarker Effects can deliver on its anti-aging promise thus frames a critical unmet need in translational geroscience.", "claim_id": "claim_7"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "Key unresolved questions about Fasting Biomarker Effects center on mechanism-to-function translation, dose-response relationships, and population specificity. Mechanistic studies suggest that fasting-induced ketogenesis and NAD+ metabolism may improve mitochondrial function, but whether these changes translate into reduced frailty progression or lower incidence of cardiovascular events remains uncertain. Dose and duration effects are particularly contentious: some analyses indicate that fasting periods longer than three days may worsen lipid profiles, with HDL reductions observed in longer fasts (Camli 2026). Tradeoffs between metabolic benefits and potential adverse effects—such as muscle loss, fatigue, or micronutrient deficiencies—are inconsistently reported and may be population-specific. The role of exercise co-intervention further complicates interpretation, as meta-analyses report conflicting findings on whether adding exercise to Fasting Biomarker Effects enhances or diminishes cardiometabolic outcomes (Dai 2025). Age-specific effects are also poorly characterized, with few trials stratifying by decade of life or frailty status, leaving open the question of whether older, more vulnerable adults respond similarly to younger cohorts.", "claim_id": "claim_8"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "The background evidence for fasting biomarker effects is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as the retained evidence base 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.", "claim_id": "claim_9"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "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.", "claim_id": "claim_10"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "Across the retained sources, positive signals cluster around the cardiometabolic outcome class; null signals around the contextual adjacent evidence and cardiometabolic outcome classes; and negative or adverse signals around the contextual adjacent evidence outcome class. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.", "claim_id": "claim_11"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "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.", "claim_id": "claim_12"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "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.", "claim_id": "claim_13"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "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.", "claim_id": "claim_14"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "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`.", "claim_id": "claim_15"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence); within-class agreement, disagreement, and directness gaps surfaced explicitly. 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claims=621; no extracted directional signal in 6/7 sources | directness: 2 indirect; 5 review; main limitation: no direct clinical anchor.", "claim_id": "claim_21"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "The retained fasting biomarker effects corpus is reported by outcome class before any cross-domain interpretation. 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Directional coding within this packet is mixed=3, null=1, positive=2, unclear=2, and directness coding is indirect=1, review=7. These counts describe the frozen evidence state for this outcome, not a pooled treatment estimate.", "claim_id": "claim_23"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "Directional coding within this packet is negative=1, null=6, and directness coding is indirect=2, review=5.", "claim_id": "claim_24"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "Across outcome classes, the manuscript treats disagreement as part of the evidence rather than as noise to smooth away. A null or adverse signal in one section does not cancel a favorable signal in another; it defines the boundary condition for interpretation.", "claim_id": "claim_25"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "Descriptive findings remain separate from interpretation and endpoint-specific boundaries. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation", "claim_id": "claim_26"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "Contextual Adjacent Evidence remains a separate Results slice (n=7; claims=621; no extracted directional signal in 6/7 sources; 2 indirect; 5 review; limited corpus depth in this outcome class) and is not pooled into adjacent endpoint classes.", "claim_id": "claim_27"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "A central tension in the Fasting Biomarker Effects literature arises from the discordance between mechanistic plausibility and the limited or inconsistent human evidence for cardiometabolic benefit. Model-organism studies consistently demonstrate that fasting regimens activate autophagy and improve insulin sensitivity through pathways such as AMPK and SIRT1, yet human meta-analyses reveal only mixed or context-dependent effects on clinically relevant cardiometabolic markers (Couto-Alfonso 2026, Kibret 2025, Lu 2025). In older adults, fasting interventions show statistically significant improvements in fasting blood glucose and HbA1c in some trials (Qudah 2026, Burns 2025), but these effects are not universally replicated across populations or fasting protocols (Wang 2025). The boundary condition for mechanistic plausibility appears to be duration and adherence: longer fasting windows (>16 hours) and structured fasting-mimicking diets align more closely with autophagy induction, whereas shorter or irregular fasts may fail to trigger these pathways consistently. Resolution of this tension will require head-to-head trials that pair biomarker endpoints (e.g., NAD+ flux, AMPK activation) with hard cardiometabolic outcomes and rigorous adherence monitoring to determine whether biomarker shifts translate into durable clinical benefit.", "claim_id": "claim_28"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "Another cross-domain tension emerges between biomarker-focused fasting interventions and their impact on broader functional or contextual outcomes, where negative or null effects dominate despite cardiometabolic improvements. For example, Grundler 2026 reports significant reductions in blood pressure alongside weight loss in a five-day fasting program, but the clinical relevance of these changes is undermined by the absence of sustained functional gains in older adults. Conversely, multiple meta-analyses and cohorts show null effects on body composition or cardiometabolic markers when fasting is combined with exercise or delivered via time-restricted feeding (Dai 2025, Xing 2026, Liu 2026). Future trials should stratify by baseline metabolic phenotype and incorporate functional outcomes such as gait speed (Perera 2006) to determine whether biomarker changes translate into clinically meaningful improvements.", "claim_id": "claim_29"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "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", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Intermittent Fasting for the Prevention of Cardiovascular Disease Risks: Systematic Review and Network Meta-Analysis", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Duration-dependent effects of water-only fasting on blood lipids: a systematic review, meta-analysis, and threshold meta-regression", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1186/s41043-025-01039-2", "study": "The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis", "url": "https://doi.org/10.1186/s41043-025-01039-2"}, {"doi": "10.1186/s13073-026-01681-3", "study": "Health benefits of a five-day at-home modified fasting program: a randomised controlled trial", "url": "https://doi.org/10.1186/s13073-026-01681-3"}], "claim": "Another tension centers on the cardiometabolic outcome class itself, where positive signals in glycemic control and lipid profiles conflict with null findings in broader cardiometabolic risk reduction. This discrepancy likely reflects heterogeneity in fasting protocols, population characteristics, and outcome definitions. For instance, fasting-mimicking diets with structured protein restriction (Burns 2025) may activate autophagy more effectively than time-restricted feeding, leading to greater glycemic improvements. The boundary condition for positive cardiometabolic effects appears to be the presence of insulin resistance or prediabetes, where fasting-induced improvements in insulin sensitivity are most pronounced. To resolve this tension, future research should standardize fasting protocols (e.g., 5:2 vs daily time-restricted feeding) and prioritize hard outcomes such as cardiovascular events or diabetes complications, rather than relying solely on surrogate markers like HbA1c.", "claim_id": "claim_30"}]}
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