Derivation Web

source_8c24d557c6f64dc5

by researka:v2 · 2026-06-20 10:19:32.881308+04:00

{"content_hash": "sha256:259fc5c5201345c13b9fef14f0b856e34339657122e85c238bac7b91bb4b1d3d", "edges": [{"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_1", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_2", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_3", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_4", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_5", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_6", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_7", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_8", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_9", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_10", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_11", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_12", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_13", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_14", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_15", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_16", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_17", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_18", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_19", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_20", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_21", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_22", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_23", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_24", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_25", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_26", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_27", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_28", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_29", "type": "contains_claim"}, {"from": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "to": "claim_30", "type": "contains_claim"}], "nodes": [{"id": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "title": "Research Synthesis: Alpha-ketoglutarate — full paper", "type": "publication"}, {"id": "claim_1", "text": "Evidence-honesty note: 46/53 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. 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.", "type": "claim"}, {"id": "claim_2", "text": "This paper synthesizes evidence on Alpha-ketoglutarate across 53 accepted source papers and 2847 high-confidence extracted claims.", "type": "claim"}, {"id": "claim_3", "text": "The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 45 adjacent clinical sources, and 8 mechanistic or model-system sources, with 1 cross-study disagreement across the evidence base.", "type": "claim"}, {"id": "claim_4", "text": "Positive study-level signals are summarized in the safety and comorbidity outcome class, null signals in the contextual adjacent evidence, cardiometabolic and mechanism outcome classes, and negative signals in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "type": "claim"}, {"id": "claim_5", "text": "The conclusion is that Alpha-ketoglutarate remains a bounded geroscience case: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.", "type": "claim"}, {"id": "claim_6", "text": "This manuscript is reported as a 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-alpha_ketoglutarate_akg-v06-DAILY-2026-06-20T04-00-35Z`.", "type": "claim"}, {"id": "claim_7", "text": "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.", "type": "claim"}, {"id": "claim_8", "text": "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).", "type": "claim"}, {"id": "claim_9", "text": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, immune and inflammation, immune and inflammation, mechanism, mortality and survival, muscle function, safety and comorbidity, skeletal, fracture, and bone); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.", "type": "claim"}, {"id": "claim_10", "text": "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.", "type": "claim"}, {"id": "claim_11", "text": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "type": "claim"}, {"id": "claim_12", "text": "| Contextual Adjacent Evidence | n=33; claims=1572 | no extracted directional signal in 31/33 sources | 30 indirect; 1 protocol; 2 review | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_13", "text": "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.", "type": "claim"}, {"id": "claim_14", "text": "This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.", "type": "claim"}, {"id": "claim_15", "text": "33 included sources were assigned to this outcome class. Directional coding: null=31, unclear=2. Directness coding: indirect=30, protocol=1, review=2.", "type": "claim"}, {"id": "claim_16", "text": "4 included sources were assigned to this outcome class. Directional coding: mixed=1, null=3. Directness coding: mechanistic=4.", "type": "claim"}, {"id": "claim_17", "text": "3 included sources were assigned to this outcome class. Directional coding: null=3. Directness coding: indirect=1, mechanistic=2.", "type": "claim"}, {"id": "claim_18", "text": "3 included sources were assigned to this outcome class. Directional coding: null=1, unclear=2. Directness coding: indirect=3.", "type": "claim"}, {"id": "claim_19", "text": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.", "type": "claim"}, {"id": "claim_20", "text": "Evidence for this outcome class is represented in the structured results table, but the retained narrative paragraphs were more strongly assigned to adjacent outcome classes. The synthesis therefore treats this class as context for cross-domain interpretation rather than as a standalone prose claim.", "type": "claim"}, {"id": "claim_21", "text": "3 included sources were assigned to this outcome class. Directional coding: null=2, unclear=1. Directness coding: indirect=3.", "type": "claim"}, {"id": "claim_22", "text": "2 included sources were assigned to this outcome class. Directional coding: null=1, positive=1. Directness coding: mechanistic=2.", "type": "claim"}, {"id": "claim_23", "text": "2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: indirect=2.", "type": "claim"}, {"id": "claim_24", "text": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.", "type": "claim"}, {"id": "claim_25", "text": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.", "type": "claim"}, {"id": "claim_26", "text": "Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.", "type": "claim"}, {"id": "claim_27", "text": "Additional corpus sources included animal/preclinical evidence; the most consequential scope gap is the near-absence of long-term, hard-outcome randomized evidence in non-diabetic, community-dwelling adults. Consequently, every human claim in this synthesis that is anchored to a clinical event — whether survival in flap surgery (Huang 2025), aneurysm progression (Liu 2022), or diabetic cardiomyopathy (Dhat 2023) — is supported only by indirect, indirect-directness sources, and the headline conclusions cannot be transported to general adult populations without a dedicated long-term mortality RCT, of which the corpus contains none.", "type": "claim"}, {"id": "claim_28", "text": "Finally, the corpus contains a mechanism-to-clinic gap for the most clinically relevant claim, namely that αKG influences cardiovascular, skeletal, and longevity outcomes in humans. Mechanistic plausibility is densely documented: PI3K/Akt/HIF-1α angiogenesis in skin flaps (Huang 2025), PHD1-dependent NF-κB suppression in osteoclastogenesis (Tian 2023b), epigenetic H3K27me3 reduction in periodontal regeneration (Hasegawa 2026), histone methylation rescue in age-related osteoporosis (Wang 2020), and Tnfrsf12a/Fn14 histone-modification protection against cancer cachexia (Ruiz 2023). However, each of these sources is either preclinical (An 2021, Iwaniak 2022, Bayliak 2017, Kalawaj 2020), mechanistic-only (Iniguez 2022, Cai 2016, Qiu 2025, Sekita 2021, Wu 2018, Burdyliuk 2017, Showalter 2017, Fiehn 2016), or review/protocol-level (Sandalova 2023, Lamichhane 2023, Doroftei 2024, Wu 2016). 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. Pending further trials, the intervention should not be used off-label for geroprotection or anti-aging purposes outside clinical-trial settings given current 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.", "type": "claim"}, {"id": "claim_29", "text": "This synthesis maps 53 included sources on Alpha Ketoglutarate Akg across 10 outcome classes and 1 cross-study disagreement. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.", "type": "claim"}, {"id": "claim_30", "text": "Across 53 curated reference papers, the evidence base for Alpha shows a context-dependent profile. Positive signals appear in: safety comorbidity. Null findings dominate: contextual other, cardiometabolic. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Alpha 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.", "type": "claim"}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/cimb45080410", "effect": "not extracted", "endpoint": "not extracted", "id": "source_1", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Different RONS Generation in MTC-SK and NSCL Cells Lead to Varying Antitumoral Effects of Alpha-Ketoglutarate + 5-HMF", "type": "source", "url": "https://doi.org/10.3390/cimb45080410", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ijms23169034", "effect": "not extracted", "endpoint": "not extracted", "id": "source_2", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-Ketoglutarate or 5-HMF: Single Compounds Effectively Eliminate Leukemia Cells via Caspase-3 Apoptosis and Antioxidative Pathways", "type": "source", "url": "https://doi.org/10.3390/ijms23169034", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fphar.2025.1656473", "effect": "not extracted", "endpoint": "not extracted", "id": "source_3", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-ketoglutarate rescues impaired endothelial progenitor cell-mediated angiogenesis in diabetic mice", "type": "source", "url": "https://doi.org/10.3389/fphar.2025.1656473", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/antiox10111804", "effect": "not extracted", "endpoint": "not extracted", "id": "source_4", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-Ketoglutarate and 5-HMF: A Potential Anti-Tumoral Combination against Leukemia Cells", "type": "source", "url": "https://doi.org/10.3390/antiox10111804", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fimmu.2022.915657", "effect": "not extracted", "endpoint": "not extracted", "id": "source_5", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Low Protein Diets Supplemented With Alpha-Ketoglutarate Enhance the Growth Performance, Immune Response, and Intestinal Health in Common Carp ( Cyprinus carpio )", "type": "source", "url": "https://doi.org/10.3389/fimmu.2022.915657", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1016/j.redox.2021.102088", "effect": "not extracted", "endpoint": "not extracted", "id": "source_6", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-ketoglutarate ameliorates pressure overload-induced chronic cardiac dysfunction in mice", "type": "source", "url": "https://doi.org/10.1016/j.redox.2021.102088", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ani10122420", "effect": "not extracted", "endpoint": "not extracted", "id": "source_7", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-Ketoglutarate: An Effective Feed Supplement in Improving Bone Metabolism and Muscle Quality of Laying Hens: A Preliminary Study", "type": "source", "url": "https://doi.org/10.3390/ani10122420", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fimmu.2021.690234", "effect": "not extracted", "endpoint": "not extracted", "id": "source_8", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Evaluation of Alpha-Ketoglutarate Supplementation on the Improvement of Intestinal Antioxidant Capacity and Immune Response in Songpu Mirror Carp ( Cyprinus carpio ) After Infection With Aeromonas hydrophila", "type": "source", "url": "https://doi.org/10.3389/fimmu.2021.690234", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/nu14102062", "effect": "not extracted", "endpoint": "not extracted", "id": "source_9", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Dietary Alpha-Ketoglutarate Partially Abolishes Adverse Changes in the Small Intestine after Gastric Bypass Surgery in a Rat Model", "type": "source", "url": "https://doi.org/10.3390/nu14102062", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1017/jns.2025.10059", "effect": "not extracted", "endpoint": "not extracted", "id": "source_10", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-ketoglutarate supplementation improves hyperglycemia and attenuates the decrease in GLUT4 and PGC-1α proteins in adipose tissue of streptozotocin-high-fat diet-induced diabetic mice", "type": "source", "url": "https://doi.org/10.1017/jns.2025.10059", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41467-025-64360-8", "effect": "not extracted", "endpoint": "not extracted", "id": "source_11", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-ketoglutarate mitigates insulin resistance and metabolic inflexibility in a mouse model of Ataxia-Telangiectasia", "type": "source", "url": "https://doi.org/10.1038/s41467-025-64360-8", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ijms21249406", "effect": "not extracted", "endpoint": "not extracted", "id": "source_12", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha Ketoglutarate Exerts In Vitro Anti-Osteosarcoma Effects through Inhibition of Cell Proliferation, Induction of Apoptosis via the JNK and Caspase 9-Dependent Mechanism, and Suppression of TGF-β and VEGF Production and Metastatic Potential of Cells", "type": "source", "url": "https://doi.org/10.3390/ijms21249406", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s13072-023-00489-4", "effect": "not extracted", "endpoint": "not extracted", "id": "source_13", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Epigenetic modifier alpha-ketoglutarate modulates aberrant gene body methylation and hydroxymethylation marks in diabetic heart", "type": "source", "url": "https://doi.org/10.1186/s13072-023-00489-4", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ani13040569", "effect": "not extracted", "endpoint": "not extracted", "id": "source_14", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Dietary Alpha-Ketoglutarate Supplementation Improves Bone Growth, Phosphorus Digestion, and Growth Performance in Piglets", "type": "source", "url": "https://doi.org/10.3390/ani13040569", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/cells15030281", "effect": "not extracted", "endpoint": "not extracted", "id": "source_15", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effects of N-Acetylcysteine and Alpha-Ketoglutarate on OVCAR3 Ovarian Cancer Cells: Insights from Integrative Bioinformatics and Experimental Validation", "type": "source", "url": "https://doi.org/10.3390/cells15030281", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s13619-025-00264-8", "effect": "not extracted", "endpoint": "not extracted", "id": "source_16", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-ketoglutarate promotes random-pattern skin flap survival by enhancing angiogenesis via PI3K/Akt/HIF-1α signaling pathway", "type": "source", "url": "https://doi.org/10.1186/s13619-025-00264-8", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41467-020-19360-1", "effect": "not extracted", "endpoint": "not extracted", "id": "source_17", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations", "type": "source", "url": "https://doi.org/10.1038/s41467-020-19360-1", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12967-022-03659-2", "effect": "not extracted", "endpoint": "not extracted", "id": "source_18", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways", "type": "source", "url": "https://doi.org/10.1186/s12967-022-03659-2", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s11357-023-00813-6", "effect": "not extracted", "endpoint": "not extracted", "id": "source_19", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-ketoglutarate supplementation and BiologicaL agE in middle-aged adults (ABLE)—intervention study protocol", "type": "source", "url": "https://doi.org/10.1007/s11357-023-00813-6", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/nu15030701", "effect": "not extracted", "endpoint": "not extracted", "id": "source_20", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Elevation of Intracellular Alpha-Ketoglutarate Levels Inhibits Osteoclastogenesis by Suppressing the NF-κB Signaling Pathway in a PHD1-Dependent Manner", "type": "source", "url": "https://doi.org/10.3390/nu15030701", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.4252/wjsc.v18.i2.113694", "effect": "not extracted", "endpoint": "not extracted", "id": "source_21", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-ketoglutarate enhances adipose-derived stem cells survival in wound healing by hypoxia-inducible factor 1-alpha-mediated redox homeostasis and glycogen-dependent bioenergetics", "type": "source", "url": "https://doi.org/10.4252/wjsc.v18.i2.113694", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/s26092753", "effect": "not extracted", "endpoint": "not extracted", "id": "source_22", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Development and First-in-Human Translation of Hyperpolarized [1- 13 C]Alpha-Ketoglutarate MR Spectroscopy in the Brain", "type": "source", "url": "https://doi.org/10.3390/s26092753", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ani15121723", "effect": "not extracted", "endpoint": "not extracted", "id": "source_23", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effects of Alpha-Ketoglutarate Supplementation on Growth Performance, Diarrhea Incidence, Plasma Amino Acid, and Nutrient Digestibility in Weaned Piglets", "type": "source", "url": "https://doi.org/10.3390/ani15121723", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/genes14091818", "effect": "not extracted", "endpoint": "not extracted", "id": "source_24", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-Ketoglutarate Regulates Tnfrsf12a/Fn14 Expression via Histone Modification and Prevents Cancer-Induced Cachexia", "type": "source", "url": "https://doi.org/10.3390/genes14091818", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/foods10030596", "effect": "not extracted", "endpoint": "not extracted", "id": "source_25", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Cholesterol Content, Fatty Acid Profile and Health Lipid Indices in the Egg Yolk of Eggs from Hens at the End of the Laying Cycle, Following Alpha-Ketoglutarate Supplementation", "type": "source", "url": "https://doi.org/10.3390/foods10030596", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/vetsci12121163", "effect": "not extracted", "endpoint": "not extracted", "id": "source_26", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effects of Dietary Alpha-Ketoglutarate Supplementation on Diarrhea Incidence and Nutrient Digestibility in Weaned Piglets Fed Low-Protein Diets", "type": "source", "url": "https://doi.org/10.3390/vetsci12121163", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/nu14061148", "effect": "not extracted", "endpoint": "not extracted", "id": "source_27", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-Ketoglutarate Promotes Goblet Cell Differentiation and Alters Urea Cycle Metabolites in DSS-Induced Colitis Mice", "type": "source", "url": "https://doi.org/10.3390/nu14061148", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.18632/aging.203736", "effect": "not extracted", "endpoint": "not extracted", "id": "source_28", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test", "type": "source", "url": "https://doi.org/10.18632/aging.203736", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/antiox10091501", "effect": "not extracted", "endpoint": "not extracted", "id": "source_29", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-Ketoglutarate: A Potential Inner Mitochondrial and Cytosolic Protector against Peroxynitrite and Peroxynitrite-Induced Nitration?", "type": "source", "url": "https://doi.org/10.3390/antiox10091501", "year": 2021}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1097/MS9.0000000000001188", "effect": "not extracted", "endpoint": "not extracted", "id": "source_30", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Lack of association of the alpha-ketoglutarate-dependent dioxygenase (FTO) gene polymorphisms with pulmonary tuberculosis risk: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.1097/MS9.0000000000001188", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s13287-021-02578-1", "effect": "not extracted", "endpoint": "not extracted", "id": "source_31", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "AKT signaling is associated with epigenetic reprogramming via the upregulation of TET and its cofactor, alpha-ketoglutarate during iPSC generation", "type": "source", "url": "https://doi.org/10.1186/s13287-021-02578-1", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/life11040321", "effect": "not extracted", "endpoint": "not extracted", "id": "source_32", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The Role of the Rare Variants in the Genes Encoding the Alpha-Ketoglutarate Dehydrogenase in Alzheimer’s Disease", "type": "source", "url": "https://doi.org/10.3390/life11040321", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41598-022-18660-4", "effect": "not extracted", "endpoint": "not extracted", "id": "source_33", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Foliar application of alpha-ketoglutarate plus nitrogen improves drought resistance in soybean ( Glycine max L. Merr. )", "type": "source", "url": "https://doi.org/10.1038/s41598-022-18660-4", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.4103/RPS.RPS_9_25", "effect": "not extracted", "endpoint": "not extracted", "id": "source_34", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Repurposing FDA-approved drugs to find a novel inhibitor of alpha-ketoglutarate-dependent dioxygenase FTO to treat esophageal cancer", "type": "source", "url": "https://doi.org/10.4103/RPS.RPS_9_25", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/molecules28010097", "effect": "not extracted", "endpoint": "not extracted", "id": "source_35", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha Ketoglutarate Downregulates the Neutral Endopeptidase and Enhances the Growth Inhibitory Activity of Thiorphan in Highly Aggressive Osteosarcoma Cells", "type": "source", "url": "https://doi.org/10.3390/molecules28010097", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/biology15050372", "effect": "not extracted", "endpoint": "not extracted", "id": "source_36", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-Ketoglutarate Drives an Osteogenic and Extracellular Matrix Gene Program in Periodontal Ligament Fibroblasts via Selective Reduction of H3K27me3", "type": "source", "url": "https://doi.org/10.3390/biology15050372", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41598-020-69178-6", "effect": "not extracted", "endpoint": "not extracted", "id": "source_37", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-ketoglutarate utilization in Saccharomyces cerevisiae : transport, compartmentation and catabolism", "type": "source", "url": "https://doi.org/10.1038/s41598-020-69178-6", "year": 2020}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1530/REP-24-0137", "effect": "not extracted", "endpoint": "not extracted", "id": "source_38", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "A scoping review regarding reproductive capacity modulation based on alpha-ketoglutarate supplementation", "type": "source", "url": "https://doi.org/10.1530/REP-24-0137", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fmicb.2018.01057", "effect": "not extracted", "endpoint": "not extracted", "id": "source_39", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-Ketoglutarate in Low-Protein Diets for Growing Pigs: Effects on Cecal Microbial Communities and Parameters of Microbial Metabolism", "type": "source", "url": "https://doi.org/10.3389/fmicb.2018.01057", "year": 2018}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ani9100838", "effect": "not extracted", "endpoint": "not extracted", "id": "source_40", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effects of Dietary Supplementation of Alpha-Ketoglutarate in a Low-Protein Diet on Fatty Acid Composition and Lipid Metabolism Related Gene Expression in Muscles of Growing Pigs", "type": "source", "url": "https://doi.org/10.3390/ani9100838", "year": 2019}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1155/2017/8754879", "effect": "not extracted", "endpoint": "not extracted", "id": "source_41", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effects of Long-Term Cultivation on Medium with Alpha-Ketoglutarate Supplementation on Metabolic Processes of Saccharomyces cerevisiae", "type": "source", "url": "https://doi.org/10.1155/2017/8754879", "year": 2017}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12974-018-1120-x", "effect": "not extracted", "endpoint": "not extracted", "id": "source_42", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Glutaminase 1 regulates the release of extracellular vesicles during neuroinflammation through key metabolic intermediate alpha-ketoglutarate", "type": "source", "url": "https://doi.org/10.1186/s12974-018-1120-x", "year": 2018}, {"comparator": "not extracted", "directness": "primary", "doi": "10.7554/eLife.26030", "effect": "not extracted", "endpoint": "not extracted", "id": "source_43", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Replication Study: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate", "type": "source", "url": "https://doi.org/10.7554/eLife.26030", "year": 2017}, {"comparator": "not extracted", "directness": "primary", "doi": "10.18632/oncotarget.16875", "effect": "not extracted", "endpoint": "not extracted", "id": "source_44", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-ketoglutarate suppresses the NF-κB-mediated inflammatory pathway and enhances the PXR-regulated detoxification pathway", "type": "source", "url": "https://doi.org/10.18632/oncotarget.16875", "year": 2017}, {"comparator": "not extracted", "directness": "primary", "doi": "10.18632/oncotarget.20555", "effect": "not extracted", "endpoint": "not extracted", "id": "source_45", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Administration of alpha-ketoglutarate improves epithelial restitution under stress injury in early-weaning piglets", "type": "source", "url": "https://doi.org/10.18632/oncotarget.20555", "year": 2017}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1155/2017/5792192", "effect": "not extracted", "endpoint": "not extracted", "id": "source_46", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Growth on Alpha-Ketoglutarate Increases Oxidative Stress Resistance in the Yeast Saccharomyces cerevisiae", "type": "source", "url": "https://doi.org/10.1155/2017/5792192", "year": 2017}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/srep26802", "effect": "not extracted", "endpoint": "not extracted", "id": "source_47", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-ketoglutarate promotes skeletal muscle hypertrophy and protein synthesis through Akt/mTOR signaling pathways", "type": "source", "url": "https://doi.org/10.1038/srep26802", "year": 2016}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/1750-1172-8-192", "effect": "not extracted", "endpoint": "not extracted", "id": "source_48", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase", "type": "source", "url": "https://doi.org/10.1186/1750-1172-8-192", "year": 2013}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/2049-3002-2-4", "effect": "not extracted", "endpoint": "not extracted", "id": "source_49", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "A strategically designed small molecule attacks alpha-ketoglutarate dehydrogenase in tumor cells through a redox process", "type": "source", "url": "https://doi.org/10.1186/2049-3002-2-4", "year": 2014}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/ncomms8768", "effect": "not extracted", "endpoint": "not extracted", "id": "source_50", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2", "type": "source", "url": "https://doi.org/10.1038/ncomms8768", "year": 2015}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1155/2013/294679", "effect": "not extracted", "endpoint": "not extracted", "id": "source_51", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Comparative Study of Various Delivery Methods for the Supply of Alpha-Ketoglutarate to the Neural Cells for Tissue Engineering", "type": "source", "url": "https://doi.org/10.1155/2013/294679", "year": 2013}, {"comparator": "not extracted", "directness": "primary", "doi": "10.4062/biomolther.2015.078", "effect": "not extracted", "endpoint": "not extracted", "id": "source_52", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alpha-Ketoglutarate: Physiological Functions and Applications", "type": "source", "url": "https://doi.org/10.4062/biomolther.2015.078", "year": 2016}, {"comparator": "not extracted", "directness": "primary", "doi": "10.7554/eLife.12626", "effect": "not extracted", "endpoint": "not extracted", "id": "source_53", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Registered report: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate", "type": "source", "url": "https://doi.org/10.7554/eLife.12626", "year": 2016}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_54", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_55", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Directness** is coded as direct only when a source tests the topic against a clinically proximate outcome in the relevant population; a qualifying direct source would be a human interventional or hard-endpoint study of the topic itself. Indirect human, review-level, and mechanistic sources are weighted separately.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_56", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Directional signal** is counted within the assigned outcome class only. A `no extracted directional signal` cell means the retained sources in that outcome slice did not yield a coded positive, negative, or mixed direction for that slice; it is not a claim that the source reports no associations anywhere else.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_57", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Evidence tier** follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot move a source between classes after sources are frozen.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1001/jama.2010.1923", "effect": "not extracted", "endpoint": "not extracted", "id": "source_58", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Studenski 2011", "type": "source", "url": "https://doi.org/10.1001/jama.2010.1923", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1111/j.1532-5415.2006.00701.x", "effect": "not extracted", "endpoint": "not extracted", "id": "source_59", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Perera 2006", "type": "source", "url": "https://doi.org/10.1111/j.1532-5415.2006.00701.x", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.2337/dc24-S006", "effect": "not extracted", "endpoint": "not extracted", "id": "source_60", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "ADA 2024", "type": "source", "url": "https://doi.org/10.2337/dc24-S006", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_61", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "WHO 2000", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1093/ageing/afy169", "effect": "not extracted", "endpoint": "not extracted", "id": "source_62", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Cruz-Jentoft 2019", "type": "source", "url": "https://doi.org/10.1093/ageing/afy169", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1371/journal.pmed.0020124", "effect": "not extracted", "endpoint": "not extracted", "id": "source_63", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Ioannidis 2005", "type": "source", "url": "https://doi.org/10.1371/journal.pmed.0020124", "year": null}], "publication_id": "eff2808f-cded-4bcd-b7a5-59a823b84f7b", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 53, "included": 53, "included_or_retained": 53, "screened": 53, "wording": "53 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit."}}

{
  "researka_object_type": "publication_sidecar",
  "researka_publication_id": "eff2808f-cded-4bcd-b7a5-59a823b84f7b",
  "researka_submission_id": "5e389f1a-19f8-469e-b6ec-4f1e60c38dc4",
  "sidecar_name": "claim_graph.json",
  "sidecar_url": "https://api.researka.org/publications/eff2808f-cded-4bcd-b7a5-59a823b84f7b/sidecars/claim_graph.json"
}