source · application/json
source_e130a5d9526f4a18
sha256 fefe0a1567cc3b85c406045cfb6763be0d6b51fb46be762f3178c5d3710710e5
by researka:v2 · 2026-06-25 05:41:09.059081+04:00
{"publication_id": "2bd9802d-ec9a-4e3b-b941-43a68cda6945", "traces": [{"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "This paper synthesizes evidence on metabolism biomarker effects across 15 accepted source papers and 491 high-confidence extracted claims.", "claim_id": "claim_1"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "The evidence profile contains 2 direct clinical sources, 12 adjacent clinical sources, and 1 mechanistic or model-system source, with 26 cross-study disagreements across the evidence base.", "claim_id": "claim_2"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "No single positive outcome class dominates the retained corpus; null signals cluster in the contextual adjacent evidence, longevity and deficiency prevalence outcome classes, and negative signals cluster in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "claim_id": "claim_3"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "The conclusion is that metabolism biomarker effects remains a bounded geroscience case: the retained clinical and mechanistic evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.", "claim_id": "claim_4"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "This manuscript is reported as a Thin-corpus evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-metabolism_biomarker_effects-v06-DAILY-2026-06-25T01-34-20Z-R2`.", "claim_id": "claim_5"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "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 sidecar when populated, and claim registry) rather than from re-parsed full text.", "claim_id": "claim_6"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "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.", "claim_id": "claim_7"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, frailty, immune and inflammation, longevity, mechanism); 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_8"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "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_9"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "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_10"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "claim_id": "claim_11"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "| Contextual Adjacent Evidence | n=6; claims=230 | no extracted directional signal in 6/6 sources | 1 direct; 5 indirect | limited corpus depth in this outcome class |", "claim_id": "claim_12"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.", "claim_id": "claim_13"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "6 included sources were assigned to this outcome class. Directional coding: null=6. Directness coding: direct=1, indirect=5.", "claim_id": "claim_14"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "4 included sources were assigned to this outcome class. Directional coding: null=3, unclear=1. Directness coding: indirect=4.", "claim_id": "claim_15"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.", "claim_id": "claim_16"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.", "claim_id": "claim_17"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.", "claim_id": "claim_18"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: direct=1.", "claim_id": "claim_19"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: mechanistic=1.", "claim_id": "claim_20"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.", "claim_id": "claim_21"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "A first limitation concerns corpus scope. Studies such as Gordon-Dseagu 2015 and Lei 2023 provide longitudinal mortality associations, but they are observational and cannot substitute for a randomized evaluation. The headline inferences about the metabolism–biomarker–anti-aging case are therefore drawn from indirect, cross-sectional, or short-term mechanistic data, and any extension to disease prevention or lifespan in healthy adults is not supported by the admitted evidence. The four FDA-grade, hard-endpoint RCTs that would normally anchor such a synthesis are absent from this corpus.", "claim_id": "claim_22"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "A second limitation is single-trial generalization risk. Findings anchored on a single trial cannot be replicated within this corpus, and the absence of a corroborating second study is itself a limitation. Citing such findings as evidence for a synthesis-level claim is not warranted.", "claim_id": "claim_23"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "A fourth limitation is endpoint scope. The admitted sources overwhelmingly report biomarker or surrogate endpoints, which carry known validity concerns as proxies for hard clinical outcomes (Ioannidis 2005). For example, Pacella 2025 reports reductions in LDL-C, fasting plasma glucose, HbA1c, and HOMA-IR, and Ma 2022 reports resveratrol effects on glucose metabolism, insulin resistance, inflammation, and renal function; the ADA 2024 HbA1c targets of 7% (general adults) and 6.5% (younger / lower-risk patients) appear in the corpus only as contextual thresholds, not as achieved outcomes. None of the sources reports adjudicated cardiovascular events, incident dementia, fractures, or all-cause mortality as a randomized comparison. Surrogate-endpoint results dominate the evidence base, and the inference that biomarker improvement will translate into reduced hard-outcome incidence in this population is not supported by any trial in the corpus.", "claim_id": "claim_24"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "A fifth limitation is the mechanism-to-clinic gap. The 0.8 m/s gait-speed threshold (Studenski 2011), the 0.1 m/s substantial-improvement marker (Perera 2006), and the EWGSOP2 grip-strength sarcopenia cutoffs of 27 kg for men and 16 kg for women (Cruz-Jentoft 2019) appear in the corpus only as analytical anchors; the trials themselves did not test whether modifying a metabolism biomarker shifts any of these functional endpoints. Translational inference from mechanistic source to clinical recommendation is therefore not warranted by the admitted evidence.", "claim_id": "claim_25"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "For metabolism biomarker effects, the final interpretation is deliberately tiered: the retained clinical and mechanistic evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus is non-supportive for clinical efficacy or general health-intervention claims; it supports only hypothesis generation and structured follow-up within the limits of indirect evidence. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.", "claim_id": "claim_26"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "This synthesis maps 15 included sources on Metabolism Biomarker Effects across 7 outcome classes and 26 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.", "claim_id": "claim_27"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "Across 15 curated reference papers, the evidence base for Metabolism shows a context-dependent profile. Null findings dominate: contextual other, longevity. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Metabolism anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established.", "claim_id": "claim_28"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "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.", "claim_id": "claim_29"}, {"candidate_sources": [{"doi": "10.1113/EP093162", "study": "Acute systemic and energy metabolism responses to velocity‐based resistance training following an oral glucose load in individuals with excess body weight", "url": "https://doi.org/10.1113/EP093162"}, {"doi": "10.1186/s12916-025-04276-8", "study": "Associations of one-carbon metabolism, related B-vitamins and ApoE genotype with cognitive function in older adults: identification of a novel gene-nutrient interaction", "url": "https://doi.org/10.1186/s12916-025-04276-8"}, {"doi": "10.1038/s41598-021-93214-8", "study": "Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults", "url": "https://doi.org/10.1038/s41598-021-93214-8"}, {"doi": "10.2196/46385", "study": "The Effect of Sleep on Metabolism, Musculoskeletal Disease, and Mortality in the General US Population: Analysis of Results From the National Health and Nutrition Examination Survey", "url": "https://doi.org/10.2196/46385"}, {"doi": "10.1002/alz.70984", "study": "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study", "url": "https://doi.org/10.1002/alz.70984"}], "claim": "| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |", "claim_id": "claim_30"}]}
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