{"publication_id":"49fee64b-298a-43fc-b595-36c94c769e98","screening":{"identified":22,"screened":22,"excluded":0,"included":22,"included_or_retained":22,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"22 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]},"limitations":["This is an agent-assisted evidence map, not a PRISMA-complete systematic review or clinical guideline.","It is not PROSPERO-registered and should not be read as medical advice.","Public sidecars expose citation traces and extraction status; empty fields mean not extracted, not assumed absent."],"contradictions":["The conclusion is that Longevity vitamin 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.","In animal/preclinical evidence, a defining limitation of this synthesis is the near-total absence of long-term, hard-outcome randomized trials of ergothioneine supplementation in non-diabetic older adults. No source in the curated corpus represents a mortality, incident-frailty, or incident-dementia randomized trial in humans, so any translation of the Katsube 2024 mechanism-of-action findings into a clinical anti-aging claim rests on an inferential chain that the present evidence cannot close. The headline synthesis therefore describes a context-dependent profile (positive on cardiometabolic and mechanism, null or mixed on immune-inflammation and contextual endpoints) but cannot anchor that profile to a human efficacy benchmark.","Finally, the corpus contains a mechanism-to-clinic gap: claims with direct human-health relevance are currently backed only by mechanistic or preclinical evidence, while the sources coded to the most clinically actionable endpoints are non-interventional. The dementia-risk association in Meng 2025 is observational and cannot establish that raising serum ergothioneine would lower dementia incidence; the AMD signal in Cheah 2026 is likewise observational; the oxaliplatin-induced peripheral neuropathy attenuation in Yamada 2025 (P = 0.011) is a murine chemotherapy-neuropathy model; and the spinal-muscular-atrophy pup phenotype work in Cadile 2025 is preclinical. Five sources (Liu 2026, Wang 2025, Yu 2020, Fu 2025, Villalain 2025) describe bioprocess engineering, bibliometric mapping, or membrane biophysics rather than clinical outcomes, and they are retained only as boundary context; they do not extend the clinical-evidence map. Until a human RCT closes the mechanism-to-clinic loop, the synthesis can describe plausibility but cannot quantify clinical benefit.","The strongest supportive evidence is the Katsube 2024 preclinical lifespan and frailty signal, whereas the strongest counter-evidence is the absence of direct human randomized trials and the divergent mechanistic readouts between Katsube 2024 (positive) and Roda 2023 (null on mechanism, P < 0.01 to P < 0.05). Observational dose-response in older adults — Meng 2025 reporting an inverse association between serum ergothioneine and dementia risk, and Cheah 2026 reporting lower serum ergothioneine in age-related macular degeneration — strengthens the hypothesis without supplying interventional confirmation. Pending such trials, current evidence supports a hypothesis that ergothioneine may contribute to healthy aging but does not yet justify marketing a proven standalone anti-aging intervention; dietary patterns that elevate ergothioneine — including mushroom intake — retain their general-health support independent of any anti-aging claim.","Additional corpus sources included animal/preclinical evidence; the most load-bearing caveat is the gap between mechanistic plausibility and clinical RCT confirmation: the cross-study disagreements catalogued in the synthesis span cardiometabolic, mechanism, and contextual outcome classes, and several of the most-cited entries (Liu 2026, Wang 2025, Yu 2020, Fu 2025, Villalain 2025) are bioprocess or bibliometric in nature and can be interpreted as boundary or methods context rather than efficacy evidence. Off-label geroprotective use of ergothioneine supplements is not supported by the current evidence base and should remain pending further trials; the absence of a single high-confidence human efficacy trial — combined with heterogeneous doses (e. For example, 4–5 mg/kg/day in Katsube 2024 versus 100 mg/kg/day in Li 2026) and heterogeneous populations — means the synthesis cannot yet set dose, duration, or target-population boundaries for clinical recommendation. In practice, clinicians may reasonably monitor serum ergothioneine as a candidate biomarker of dietary and oxidative-stress status, and counsel patients that mushroom-rich dietary patterns remain sensible on general-health grounds, but they should not represent ergothioneine supplementation as a validated anti-aging therapy. The field's most tractable near-term contribution is therefore infrastructural — standardized serum assays, consensus dose-ranging, and adjudicated endpoints — rather than therapeutic, so that a future RCT can resolve whether the mechanistic and observational signals translate into measurable clinical benefit.","Across 22 curated reference papers, the evidence base for ergothioneine shows a context-dependent profile. Positive signals appear in: cardiometabolic, mechanism. Null findings dominate: contextual other, immune inflammation. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The ergothioneine 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."]}