Derivation Web

source_df5ce62abcf64936

by researka:v2 · 2026-06-16 20:42:09.568098+04:00

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The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "type": "claim"}, {"id": "claim_4", "text": "The conclusion is that NAD+ biomarker effects 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_5", "text": "For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.", "type": "claim"}, {"id": "claim_6", "text": "Mechanistically, the rationale for NAD+ interventions rests on the well-documented decline of nicotinamide adenine dinucleotide pools with age in multiple tissues, a decline that has been proposed to contribute to mitochondrial dysfunction, impaired stress responses, and the accumulation of senescent cells. The NAD+ precursor family includes nicotinamide riboside, nicotinamide mononucleotide, nicotinamide, and niacin, each of which feeds into the salvage or Preiss–Handler pathways at different points and with different pharmacokinetic signatures. Because several of these molecules are sold as dietary supplements, NAD+ interventions have entered widespread consumer use ahead of definitive clinical evidence, a pattern that complicates the interpretation of observational data. Regulatory pathways have so far treated most NAD+ precursors as foods rather than drugs, and the threshold at which dosing, indication, or formulation should trigger pharmaceutical-grade evaluation appears to be evolving. The combination of mechanistic plausibility and easy over-the-counter access has made NAD+ a particularly important test case for the geroscience hypothesis.", "type": "claim"}, {"id": "claim_7", "text": "Additional corpus sources included animal/preclinical evidence; a recurring issue in the NAD+ literature is that demonstrating a clean pharmacokinetic or biomarker effect does not automatically translate into measurable clinical benefit, and this is the central mechanistic-versus-clinical tension that the field is now grappling with. The NAD+ trial of Elhassan 2019, for example, reported that nicotinamide riboside augmented the skeletal-muscle NAD+ metabolome and induced anti-inflammatory transcriptional signatures in older men, whereas NAD+ supplementation in physically compromised older adults did not improve mitochondrial or muscle function (Connell 2021). Whether NAD+ effects on circulating NAD+ levels can be sustained over clinically meaningful durations, and whether they propagate into hard functional endpoints, remains uncertain. Population specificity, including baseline NAD+ status, age, sex, and comorbidity burden, may also modify the response, and the dose-response relationship for NAD+ has not been mapped in a way that supports evidence-based dosing recommendations. Until these questions are answered, the clinical translation of NAD+ biology will continue to lag behind the mechanistic narrative.", "type": "claim"}, {"id": "claim_8", "text": "The background evidence for NAD+ biomarker effects is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Yi 2022, Xue 2022 are interpreted separately from mechanistic studies such as the retained evidence base, because these evidence roles answer different questions about aging biology and clinical translation.", "type": "claim"}, {"id": "claim_9", "text": "The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect.", "type": "claim"}, {"id": "claim_10", "text": "Across the retained sources, positive signals cluster around the contextual adjacent evidence outcome class; null signals around the contextual adjacent evidence, dosing and pharmacokinetics, cardiometabolic outcome classes; and negative or adverse signals around the longevity and contextual adjacent evidence outcome classes. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.", "type": "claim"}, {"id": "claim_11", "text": "The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.", "type": "claim"}, {"id": "claim_12", "text": "The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.", "type": "claim"}, {"id": "claim_13", "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_14", "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_15", "text": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, dosing and pharmacokinetics, frailty, longevity, muscle function); 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_16", "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_17", "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_18", "text": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "type": "claim"}, {"id": "claim_19", "text": "| Contextual Adjacent Evidence | n=13; claims=659 | no extracted directional signal in 9/13 sources | 1 direct; 10 indirect; 2 review | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_20", "text": "Contextual Adjacent Evidence: n=13; claims=659; no extracted directional signal in 9/13 sources | directness: 1 direct; 10 indirect; 2 review; main limitation: directionally heterogeneous.", "type": "claim"}, {"id": "claim_21", "text": "Two clinical RCTs in the curated corpus provide the principal cardiometabolic evidence on NAD+ precursor supplementation. Martens 2018 was a randomized, placebo-controlled, crossover clinical trial of nicotinamide riboside (NR) supplementation at 500 mg twice daily in healthy middle-aged and older adults, with chronic tolerability and NAD+ elevation as the principal endpoints. Both studies are categorized in the curated corpus as indirect with respect to the broader anti-aging framing but direct with respect to cardiometabolic and biomarker physiology, providing the empirical anchor for this outcome class.", "type": "claim"}, {"id": "claim_22", "text": "Quantitative findings cluster around biomarker change rather than hard clinical events. The complete per-study p-value inventory is presented in the evidence synthesis (Per-Study Endpoint Evidence) and is not restated in full here. No clinical event rates (myocardial infarction, stroke, cardiovascular mortality) appear in either source, so the cardiometabolic synthesis is restricted to physiologic and biomarker endpoints.", "type": "claim"}, {"id": "claim_23", "text": "Within-corpus tensions in the cardiometabolic class are limited but informative. Directness is rated indirect in both Katayoshi 2023 and Martens 2018 relative to a hard clinical-event anti-aging endpoint, which constrains inference: the p-values reported above describe physiologic and biomarker change, not event reduction. Effect direction in Martens 2018 is recorded as unclear in the curated matrix even though the contrast-level p-values are conventionally significant, reflecting the chronic-tolerability framing of the trial rather than a null primary endpoint. Read together, the two sources converge on tolerability and biomarker feasibility while leaving the clinical-event translation unresolved.", "type": "claim"}, {"id": "claim_24", "text": "The synthesis therefore surfaces a definitional tension rather than a numerical one: longevity-class and contextual-other-class evidence both invoke NAD as a label but operationalise it in incompatible ways, and resolving the tension would require the corpus to disambiguate the acronym at intake.", "type": "claim"}, {"id": "claim_25", "text": "The evidence base for NAD supplementation on muscle function in physically compromised older adults is anchored in three randomized, double-blind, placebo-controlled trials that collectively enrolled 212 participants across distinct dosing and outcome paradigms. These trials were designed to detect functional changes in muscle performance (e.g., strength, endurance) and mitochondrial respiration, with dosing strategies spanning acute short-term supplementation to chronic administration in clinically compromised populations.", "type": "claim"}, {"id": "claim_26", "text": "In animal/preclinical evidence, quantitatively, the trials reported mixed findings with respect to muscle function endpoints, as summarized in the evidence synthesis. Elhassan 2019, however, identified statistically significant enhancements in NAD metabolome signatures and transcriptional anti-inflammatory responses (e.g., P < 0.001, P = 0.004), though these did not translate into measurable functional gains in muscle performance (P = 0.22, P = 0.31).", "type": "claim"}, {"id": "claim_27", "text": "Mechanistically, the disconnect between NAD metabolome augmentation and functional muscle outcomes may reflect the temporal and dose-dependent nature of NAD pathway activation, as well as the heterogeneity of the enrolled populations. Elhassan et al. 2019 demonstrated that NR supplementation increased intramuscular NAD+ levels and upregulated genes associated with oxidative phosphorylation and anti-inflammatory pathways, suggesting a plausible substrate for functional improvement. However, the absence of concurrent gains in muscle performance in Connell 2021 and Yu 2025 implies that NAD augmentation alone may be insufficient to reverse sarcopenic or disease-related declines without additional anabolic or exercise stimuli. Preclinical models consistently show that NAD+ precursors enhance mitochondrial biogenesis and muscle endurance, but these findings have not been consistently replicated in human RCTs, highlighting a translational gap.", "type": "claim"}, {"id": "claim_28", "text": "Additional corpus sources included animal/preclinical evidence; within the corpus, the most notable tension arises from Elhassan 2019’s mechanistic successes versus the null functional findings in Connell 2021 and Yu 2025. While Elhassan et al. 2019 reported robust increases in NAD metabolome signatures and transcriptional changes (e.g., P < 0.001), these biochemical effects did not translate to measurable improvements in muscle function metrics, contrasting with the study’s stated thesis of functional augmentation. Conversely, Connell 2021’s trial, which employed a multi-precursor approach over 12 weeks, reported uniformly non-significant p-values across mitochondrial and muscle function outcomes, further underscoring the lack of functional benefit despite theoretical mechanistic plausibility. These discrepancies suggest that the boundary conditions for NAD supplementation—including dose, duration, and baseline NAD status—remain poorly defined in human populations.", "type": "claim"}, {"id": "claim_29", "text": "Simic 2020 yielded three significant p-values: P = 0.05, P = 0.04, and P = 0.002 across the four escalating-dose steps in AKI patients. the evidence synthesis carries the per-endpoint mapping of each p-value to its study.", "type": "claim"}, {"id": "claim_30", "text": "Within-corpus tensions arise from the directness asymmetry: Yi 2022 is direct, whereas Simic 2020 functions as a review-style synthesis and Airhart 2017 is indirect. The Yi 2022 and Simic 2020 pair produces a direct-versus-review directness gap, and the Yi 2022 and Airhart 2017 pair produces a direct-versus-indirect directness gap; these asymmetries mean that dose-response claims should rest primarily on Yi 2022, with the other two sources serving complementary pharmacokinetic and safety-evidence roles.", "type": "claim"}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41598-023-29787-3", "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": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "type": "source", "url": "https://doi.org/10.1038/s41598-023-29787-3", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1093/jn/nxab193", "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": "NAD + -Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults", "type": "source", "url": "https://doi.org/10.1093/jn/nxab193", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1002/lary.70173", "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": "NAD+ Enhanced on Hearing Recovery in Sudden Sensorineural Hearing Loss: Randomized Controlled Trial", "type": "source", "url": "https://doi.org/10.1002/lary.70173", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41467-024-53292-4", "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": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "type": "source", "url": "https://doi.org/10.1038/s41467-024-53292-4", "year": 2024}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1038/s41598-025-95735-y", "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": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "type": "source", "url": "https://doi.org/10.1038/s41598-025-95735-y", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s11357-022-00705-1", "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": "The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial", "type": "source", "url": "https://doi.org/10.1007/s11357-022-00705-1", "year": 2022}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1186/s12882-020-02006-1", "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": "Nicotinamide riboside with pterostilbene (NRPT) increases NAD + in patients with acute kidney injury (AKI): a randomized, double-blind, placebo-controlled, stepwise safety study of escalating doses of NRPT in patients with AKI", "type": "source", "url": "https://doi.org/10.1186/s12882-020-02006-1", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/nu14112219", "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": "A Combination of Nicotinamide and D-Ribose (RiaGev) Is Safe and Effective to Increase NAD + Metabolome in Healthy Middle-Aged Adults: A Randomized, Triple-Blind, Placebo-Controlled, Cross-Over Pilot Clinical Trial", "type": "source", "url": "https://doi.org/10.3390/nu14112219", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/apt.70302", "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": "Refining Prognosis in Cirrhosis Patients With Ascites: Impact of Acute vs. Non‐Acute Decompensation", "type": "source", "url": "https://doi.org/10.1111/apt.70302", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.2147/NDT.S446034", "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": "Acupuncture as Add-on Therapy to SSRIs Can Improve Outcomes of Treatment for Anxious Depression: Subgroup Analysis of the AcuSDep Trial", "type": "source", "url": "https://doi.org/10.2147/NDT.S446034", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s40256-025-00764-7", "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": "Effect of Nicotinamide Adenine Dinucleotide on Heart Failure Caused by Ischemic Cardiomyopathy: A Randomized, Placebo-Controlled Trial", "type": "source", "url": "https://doi.org/10.1007/s40256-025-00764-7", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12894-022-01107-3", "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": "Relationship between sperm NAD + concentration and reproductive aging in normozoospermia men:A Cohort study", "type": "source", "url": "https://doi.org/10.1186/s12894-022-01107-3", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12970-021-00442-4", "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": "Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study", "type": "source", "url": "https://doi.org/10.1186/s12970-021-00442-4", "year": 2021}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1002/alz.71501", "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": "Synaptic biomarkers in Alzheimer's disease dementia and mild cognitive impairment: A systematic review and meta‐analysis", "type": "source", "url": "https://doi.org/10.1002/alz.71501", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/cimb47090722", "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": "A Liposomal Formulation Enhances the Anti-Senescence Properties of Nicotinamide Adenine-Dinucleotide (NAD + ) in Endothelial Cells and Keratinocytes", "type": "source", "url": "https://doi.org/10.3390/cimb47090722", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fragi.2026.1773667", "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": "Nicotinamide riboside and pterostilbene reduces frequency and severity of undesirable symptoms of the menopause transition: an open-label, pilot clinical trial", "type": "source", "url": "https://doi.org/10.3389/fragi.2026.1773667", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s42255-025-01421-8", "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": "The differential impact of three different NAD + boosters on circulatory NAD and microbial metabolism in humans", "type": "source", "url": "https://doi.org/10.1038/s42255-025-01421-8", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s42255-024-00997-x", "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": "Trigonelline is an NAD + precursor that improves muscle function during ageing and is reduced in human sarcopenia", "type": "source", "url": "https://doi.org/10.1038/s42255-024-00997-x", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1016/j.redox.2026.104146", "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": "SERPINE1 drives ferroptosis in acute respiratory distress syndrome by disrupting mitochondrial NAD + homeostasis and suppressing Sirt3 activity", "type": "source", "url": "https://doi.org/10.1016/j.redox.2026.104146", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1016/j.chemosphere.2021.132893", "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": "The impacts of continuous improvements in air quality on mortality in Beijing: A longitudinal comparative study.", "type": "source", "url": "https://doi.org/10.1016/j.chemosphere.2021.132893", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/acel.13754", "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": "Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin", "type": "source", "url": "https://doi.org/10.1111/acel.13754", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41467-018-03421-7", "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": "Chronic 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"population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD + Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures", "type": "source", "url": "https://doi.org/10.1016/j.celrep.2019.07.043", "year": 2019}, {"comparator": "not extracted", "directness": "citation", "doi": null, "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": "**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_26", "intervention_or_exposure": "not 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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_28", "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_29", "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": "10.1093/gerona/glp012", "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": "Cesari 2009", "type": "source", "url": "https://doi.org/10.1093/gerona/glp012", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1111/j.1532-5415.2006.00701.x", "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": "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_32", "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": "10.1093/ageing/26.1.15", "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": "Bohannon 1997", "type": "source", "url": "https://doi.org/10.1093/ageing/26.1.15", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1093/ageing/afy169", "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": "Cruz-Jentoft 2019", "type": "source", "url": "https://doi.org/10.1093/ageing/afy169", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "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": "Anisimov 2008", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1056/NEJMoa1504347", "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": "Tancredi 2015", "type": "source", "url": "https://doi.org/10.1056/NEJMoa1504347", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1371/journal.pmed.0020124", "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": "Ioannidis 2005", "type": "source", "url": "https://doi.org/10.1371/journal.pmed.0020124", "year": null}], "publication_id": "6c682498-cd30-4027-b53a-3d43bbb7eec1", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 24, "included": 24, "included_or_retained": 24, "screened": 24, "wording": "24 candidate receipts retained after source retrieval, deduplication, and topic filtering. 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