Derivation Web

source_a84b952f8ab64d51

by researka:v2 · 2026-06-04 08:29:41.306716+04:00

{"publication_id": "9463fc73-49d4-41ec-b5f7-3087cedcb952", "traces": [{"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "Evidence-honesty note: 15/27 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. 25/27 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.", "claim_id": "claim_1"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "Intermittent and prolonged fasting interventions have been proposed to modify cardiometabolic risk factors and promote healthy aging, yet the magnitude, consistency, and clinical significance of these effects across diverse populations remain uncertain.", "claim_id": "claim_2"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "This synthesis applied an AI-assisted structured evidence-synthesis approach with a full audit trail, systematically extracting quantitative outcomes from 27 curated reference papers spanning systematic reviews, meta-analyses, randomized controlled trials, and observational cohorts across cardiometabolic, safety, and contextual outcome classes.", "claim_id": "claim_3"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "A fasting-mimicking-diet protocol in adults was associated with a decrease of 2.5 years in median biological age based on a validated predictor of morbidity and mortality (P = 0.003), and this diet also significantly reduced total and LDL cholesterol (P < 0.05) (Brandhorst 2024; Grant 2025).", "claim_id": "claim_4"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "Critically, cross-study disagreements were identified across the evidence base, with severity-4 disagreements between mixed-effect meta-analyses and positive-effect trials indicating that the fasting-effects cardiometabolic signal is context-dependent rather than uniform.", "claim_id": "claim_5"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence.", "claim_id": "claim_6"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "The global burden of age-related chronic disease has intensified interest in interventions that target fundamental biology rather than individual pathologies. Aging is the dominant risk factor for cardiovascular disease, metabolic dysfunction, neurodegeneration, and cancer, yet few therapeutic strategies address the underlying cellular processes that link these conditions. Fasting effects—encompassing intermittent fasting (IF), time-restricted eating (TRE), prolonged water-only fasting, and fasting-mimicking diets (FMDs)—have emerged as a candidate class with broad public accessibility and minimal regulatory barriers. The question of whether fasting effects can meaningfully extend human healthspan or lifespan remains unresolved, despite exponential growth in clinical investigation over the past decade. Understanding the scope and limitations of this evidence base is critical, given that millions of adults worldwide already practice some form of voluntary caloric restriction based on preliminary or mechanistic findings.", "claim_id": "claim_7"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "The geroscience hypothesis proposes that targeting the biological hallmarks of aging—cellular senescence, mitochondrial dysfunction, autophagy impairment, nutrient-sensing dysregulation—could simultaneously delay or prevent multiple age-related diseases. Fasting effects appear to engage several of these pathways, including AMPK activation, mTOR inhibition, and enhanced autophagic flux, positioning them as mechanistically plausible geroprotectors. This framework suggests that rather than developing novel pharmacological agents for each disease, repurposing behavioral interventions like fasting effects could offer a scalable anti-aging strategy with fewer off-target effects. However, it has been proposed that the translation from mechanistic promise to clinical benefit is far from guaranteed, as the magnitude and durability of these biological responses in humans remain uncertain. The tension between preclinical enthusiasm and clinical ambiguity is a defining feature of the fasting effects literature.", "claim_id": "claim_8"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "The regulatory and clinical history of fasting is unusual: it requires no prescription, carries no patent exclusivity, and has been practiced across cultures for millennia, yet its evidence base for health outcomes has only recently been subjected to systematic evaluation. Evidence suggests that the appeal of fasting effects lies partly in this accessibility, but the heterogeneity of protocols, durations, and comparators complicates synthesis. Whether fasting-mimicking formulations that replicate fasting biochemistry without complete food deprivation offer a more standardized therapeutic avenue remains an open empirical question.", "claim_id": "claim_9"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "Several unresolved questions constrain the clinical translation of fasting effects for aging populations. Third, the mechanistic translation problem persists: a fasting-mimicking diet was associated with a decrease of 2.5 years in median biological age using a validated algorithm (Brandhorst 2024), yet whether this surrogate endpoint predicts actual healthspan extension is unknown (Ioannidis 2005). Finally, the question of whether fasting effects interact with polypharmacy, frailty, or comorbid conditions common in aging has received almost no systematic investigation.", "claim_id": "claim_10"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "This synthesis addresses the fragmented evidence for fasting effects by applying structured evidence weighting across 27 curated reference papers spanning cardiometabolic, cognitive, anthropometric, safety, and functional outcomes. The evidence base reveals a context-dependent profile: positive signals emerge primarily in cardiometabolic domains, while null findings dominate in contextual and deficiency-prevalence outcomes. Across outcome classes, the synthesis identifies cross-study disagreements—including severity-level-4 disagreements between reviews reporting mixed effects and those reporting null effects—underscoring the heterogeneity that limits confident clinical recommendation. We separate mechanistic evidence from clinical trial evidence throughout, recognizing that fasting effects' biological plausibility (autophagy induction, metabolic switching, reduced oxidative stress) does not automatically translate to patient-relevant benefit. The fasting effects anti-aging case as currently constituted appears incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions under which fasting may benefit or harm older adults remain to be established.", "claim_id": "claim_11"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "The background evidence for fasting effects is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Couto 2025, Grant 2025 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_12"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "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_13"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "Across the retained sources, positive signals cluster around the cardiometabolic outcome class; null signals around the contextual adjacent evidence, deficiency prevalence and cardiometabolic outcome classes; and negative or adverse signals around no dominant outcome class. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.", "claim_id": "claim_14"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "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_15"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, direct interventional hard-endpoint signals, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.", "claim_id": "claim_16"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "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.", "claim_id": "claim_17"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "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_18"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "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_19"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, muscle function, 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.", "claim_id": "claim_20"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "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.", "claim_id": "claim_21"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "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.", "claim_id": "claim_22"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "claim_id": "claim_23"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "| Contextual Adjacent Evidence | n=12; claims=696 | no extracted directional signal in 8/12 sources | 1 direct; 7 indirect; 4 review | limited corpus depth in this outcome class |", "claim_id": "claim_24"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "Contextual Adjacent Evidence: n=12; claims=696; no extracted directional signal in 8/12 sources | directness: 1 direct; 7 indirect; 4 review; main limitation: directionally heterogeneous.", "claim_id": "claim_25"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "The corpus includes ten reference papers examining cardiometabolic endpoints in adults undergoing intermittent fasting (IF) or fasting-mimicking diet (FMD) interventions. These include six systematic reviews and meta-analyses (Couto-Alfonso 2026; Kibret 2025; Lu 2025; Li 2026; Semnani-Azad 2025; Wang 2025), two clinical RCTs (Burns 2025; Grant 2025), and two observational cohort studies (Brandhorst 2024; Qudah 2026). Populations range from general adults to specific subgroups such as those with type 2 diabetes (Qudah 2026) and older adults (Couto-Alfonso 2026). The network meta-analysis by Couto-Alfonso 2026 specifically included seven RCTs in its anthropometric synthesis. Intervention durations and specific IF protocols (e.g., time-restricted feeding, alternate-day fasting) varied considerably across the evidence base.", "claim_id": "claim_26"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "Mechanistically, the positive signals from clinical RCTs like Burns 2025 suggest that periods of nutrient deprivation, even when mimicked by a low-calorie diet, can transiently improve glucose homeostasis and lipid profiles. This aligns with proposed pathways involving enhanced insulin sensitivity and metabolic switching. However, the null findings from meta-analyses like Wang 2025 indicate that these acute benefits may not consistently translate into long-term changes in body composition when compared to control diets. The review by Couto-Alfonso 2026, which found mixed effects with multiple significant p-values (e.g., P = 0.001, P < 0.001) across its included studies, underscores that the cardiometabolic benefits of IF may be highly dependent on the specific protocol, population, and comparator used.", "claim_id": "claim_27"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "Within the corpus, clear tensions exist regarding the strength and consistency of cardiometabolic evidence. The positive effect direction reported by Qudah 2026 and Burns 2025 contrasts with the null findings of Wang 2025 and the mixed conclusions of several meta-analyses. Furthermore, the RCT by Grant 2025, which found a novel fasting mimetic reduced total and LDL cholesterol (P < 0.05), presents an alternative intervention approach whose findings are not directly comparable to the dietary IF protocols synthesized in the other reviews, highlighting the heterogeneous nature of the evidence base.", "claim_id": "claim_28"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "Mechanistically, the evidence points to several plausible pathways. Spermidine has been identified as essential for fasting-mediated autophagy, a key cellular recycling process linked to longevity (Hofer 2024).", "claim_id": "claim_29"}, {"candidate_sources": [{"doi": "10.3390/nu18091450", "study": "Couto-Alfonso 2026", "url": "https://doi.org/10.3390/nu18091450"}, {"doi": "10.1007/s13668-025-00684-7", "study": "Kibret 2025", "url": "https://doi.org/10.1007/s13668-025-00684-7"}, {"doi": "10.3389/fnut.2026.1772246", "study": "Camli 2026", "url": "https://doi.org/10.3389/fnut.2026.1772246"}, {"doi": "10.1038/s41467-024-45260-9", "study": "Brandhorst 2024", "url": "https://doi.org/10.1038/s41467-024-45260-9"}, {"doi": "10.1038/s41598-025-32851-9", "study": "Karol 2025", "url": "https://doi.org/10.1038/s41598-025-32851-9"}], "claim": "A clear tension exists within the corpus regarding the magnitude and consistency of effects. By contrast, several other reports, including those synthesizing shorter-duration or intermittent protocols, found null or mixed effects (Dai 2025, Wen 2026, Camli 2026). This disagreement is further illustrated by the null effect direction assigned to Gabriel 2024, which contrasts with the positive or mixed signals in Scharf 2022 and Chen 2022. The tension between the positive findings in prolonged fasting cohorts and the null or unclear findings in many systematic reviews and other cohorts underscores the critical influence of fasting duration and protocol design on outcomes.", "claim_id": "claim_30"}]}

{
  "researka_object_type": "publication_sidecar",
  "researka_publication_id": "9463fc73-49d4-41ec-b5f7-3087cedcb952",
  "researka_submission_id": "516520ce-f336-4b07-9629-a24daa543f38",
  "sidecar_name": "citation_traces.json",
  "sidecar_url": "https://api.researka.org/publications/9463fc73-49d4-41ec-b5f7-3087cedcb952/sidecars/citation_traces.json"
}