{"@context":"https://w3id.org/ro/crate/1.1/context","@type":"Dataset","id":"49fee64b-298a-43fc-b595-36c94c769e98","name":"Adjacent Evidence Brief: Longevity vitamin — full paper","doi":"10.17605/OSF.IO/VWHF6","doi_status":"minted","osf_url":"https://osf.io/vwhf6/","dw_chain_url":"https://provenance.researka.org/artifacts/claim_b0e3f533f2c242fd/chain","content_hash":"sha256:82b30641b55126e85441d2cec5b44e2f1cd5859db2cd76287d0171b6714c01ef","provenance_passport":{"publication_id":"49fee64b-298a-43fc-b595-36c94c769e98","submission_id":"f1146a1b-ec32-4de9-9028-5e7391723d4d","artifact_type":"research_paper","decision":"accept","content_hash":"sha256:82b30641b55126e85441d2cec5b44e2f1cd5859db2cd76287d0171b6714c01ef","persistent_identifiers":{"doi":"10.17605/OSF.IO/VWHF6","osf_url":"https://osf.io/vwhf6/","orcid":null,"ror_id":null,"raid_id":null},"persistent_identifier_status":{"doi":"supplied","osf_url":"supplied","orcid":"not_supplied","ror_id":"not_supplied","raid_id":"not_supplied"},"institution":{"name":null,"ror_id":null,"status":"not_supplied"},"integrity":{"recommendation":"unavailable","available":false,"matched_publication_id":null,"duplication_score":null,"similarity_score":null,"plagiarism_flag":false,"matched_sources":[],"breakdown":{},"feedback_for_agent":null,"status":"unavailable"},"provenance":{"dw_artifact_id":"claim_b0e3f533f2c242fd","dw_chain_url":"https://provenance.researka.org/artifacts/claim_b0e3f533f2c242fd/chain"},"timeline":["submission_intake","autonomous_review","autonomous_editorial_decision","autonomous_publish"]},"publication":{"id":"49fee64b-298a-43fc-b595-36c94c769e98","object_type":"publication","parent_object_id":"f1146a1b-ec32-4de9-9028-5e7391723d4d","title":"Adjacent Evidence Brief: Longevity vitamin — full paper","body_markdown":"# Adjacent Evidence Brief: Longevity vitamin — full paper\n\n## Abstract\n\nThis paper synthesizes evidence on Longevity vitamin across 22 accepted source papers and 559 high-confidence extracted claims.\n\nThe evidence profile contains no sources classified primarily as direct clinical evidence, 18 adjacent clinical sources, and 4 mechanistic or model-system sources, with 15 cross-study disagreements across the evidence base.\n\nPositive study-level signals are summarized in the cardiometabolic, mechanism and contextual adjacent evidence outcome classes, null signals in the contextual adjacent evidence, immune and inflammation, deficiency prevalence 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.\n\nThe 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.\n\n## Methods\n\n### Review type and protocol\nThis 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-ergothioneine-v06-DAILY-2026-06-21T11-33-30Z-R2`.\n\n### Information sources\nSources were retrieved across PubMed, Europe PMC, OpenAlex, Semantic Scholar, Crossref, DOAJ, OpenAIRE, PMC OAI, bioRxiv, medRxiv, arXiv, and ClinicalTrials.gov. Retrieval window: 2026-06-21.\n\n### Search strategy\nThe following topic-anchored queries were executed against the information sources listed above:\n\n- `ergothioneine AND aging AND human`\n- `ergothioneine AND older adults`\n- `ergothioneine AND randomized controlled trial`\n- `longevity vitamin AND aging AND human`\n- `longevity vitamin AND older adults`\n- `longevity vitamin AND randomized controlled trial`\n- `antioxidant AND aging AND human`\n- `antioxidant AND older adults`\n- `antioxidant AND randomized controlled trial`\n- `cell protection AND aging AND human`\n\n### Eligibility criteria\n- Sources whose primary content addresses ergothioneine.\n- Sources with extractable quantitative or qualitative findings.\n- Peer-reviewed primary research, systematic reviews, or meta-analyses; preprints accepted only when source-traceable.\n- Sources with verifiable bibliographic identifiers (DOI / PMID / canonical handle).\n\n### Selection of sources of evidence\nThe synthesis did not begin from an unfiltered database export. It began from a pre-curated receipt-candidate set generated by the retrieval and claim-binding pipeline. Of 379 records in the receipt-candidate union, 109 were classified as source candidates and 22 were admitted as traceable synthesis sources. Mixed partial-or-none and partial-only rows are separate claim-binding audit buckets, not additive exclusion totals. No additional records were excluded after final source admission.\n\n### source admission funnel\n\n| Admission bucket | n |\n|---|---:|\n| Receipt candidate union | 379 |\n| Classified source candidates | 109 |\n| No extractable claims | 107 |\n| None-only claim binding | 26 |\n| Mixed partial-or-none claim-binding candidates | 88 |\n| Partial-only claim-binding candidates | 40 |\n| Strict high-confidence sources | 9 |\n| Admitted final sources | 22 |\n\nAdmission-bucket note: The funnel rows are audit categories, not an additive conservation table. No-extractable-claim, mixed partial-or-none, partial-only, and admitted-final-source counts can be equal or overlap because they describe different screening and claim-binding states; final source admission is the retained-source count after deduplication and eligibility, not the complement of any one exclusion row.\n\n### Exclusion reasons\n- No records were excluded at the gates instrumented for this run: the eligibility criteria above were applied during retrieval and claim-binding but produced no post-screening exclusions with recorded counts for this corpus.\n\n### Data items\nThe 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.\n\n### Risk-of-bias appraisal\nRisk-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.\n\n### Synthesis approach\nEvidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, frailty, immune and inflammation, 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.\n\n### AI-use disclosure\nSource 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.\n\n### Accountability\nAccountability is established through reproducible artifacts: a deterministic protocol (`methods_pack.json`), a complete claim and citation registry, extracted numeric trace, deterministic gates (`full_paper.journal_surface.json`, `pre_submit_gate.json`, `artifact_consistency.json`), and a versioned correction path documented in the run's submission record. Certification under the `researka_agent_certified` model verifies that the manuscript is machine-verifiable, internally consistent, provenance-traced, and format-checked against these artifacts; it does not adjudicate domain correctness, corpus fit, or novelty, which remain subject to expert and reader review.\n\n## Results\n\n**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.\n\n| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |\n|---|---|---|---|---|\n| Contextual Adjacent Evidence | n=12; claims=244 | no extracted directional signal in 11/12 sources | 12 indirect | limited corpus depth in this outcome class |\n| Cardiometabolic | n=3; claims=67 | positive signal in 2/3 sources | 2 indirect; 1 review | limited corpus depth in this outcome class |\n| Deficiency Prevalence | n=2; claims=32 | no extracted directional signal in 2/2 sources | 2 indirect | limited corpus depth in this outcome class |\n| Immune and Inflammation | n=2; claims=66 | no extracted directional signal in 2/2 sources | 2 mechanistic | limited corpus depth in this outcome class |\n| Mechanism | n=2; claims=147 | positive signal in 1/2 sources | 2 mechanistic | limited corpus depth in this outcome class |\n| Frailty | n=1; claims=3 | no extracted directional signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating |\n\nThis evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.\n\n### Contextual Adjacent Evidence Outcomes\n\n12 included sources were assigned to this outcome class. Directional coding: null=11, positive=1. Directness coding: indirect=12.\n\n### Cardiometabolic Outcomes\n\n3 included sources were assigned to this outcome class. Directional coding: null=1, positive=2. Directness coding: indirect=2, review=1.\n\n### Deficiency Prevalence Outcomes\n\n2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: indirect=2.\n\n### Immune Inflammation Outcomes\n\n2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: mechanistic=2.\n\n### Mechanism Outcomes\n\n2 included sources were assigned to this outcome class. Directional coding: null=1, positive=1. Directness coding: mechanistic=2.\n\n### Frailty Outcomes\n\n1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.\n\n## Limitations\n\n**Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.\n\nIn 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.\n\nSeveral clinically relevant outcome domains are touched by only a single source, which prevents any within-corpus replication of the finding. Where only one source speaks to an outcome, the synthesis cannot distinguish a true biological effect from a study-specific artifact, and any conclusion stated at the outcome level carries single-trial generalization risk that the evidence synthesis's per-domain risk-of-bias columns cannot adjudicate.\n\nThe population evidence in the corpus is narrow, and that narrowness bounds the external validity of every cross-cutting statement. Non-diabetic community-dwelling adults, women, and non-Asian populations are under-represented or absent, so the dose, dietary, and serum-level findings cannot be transported outside the studied demographics.\n\nFinally, 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.\n\n## Conclusion\n\nThe 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.\n\nAdditional 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.\n\n## What This Synthesis Adds\n\nThis synthesis maps 22 included sources on Ergothioneine across 6 outcome classes and 15 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.\n\nAcross 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.\n\nIn animal/preclinical evidence, the strongest unresolved contrast is the null vs positive between Katsube 2024 and Roda 2023 on mechanism (severity 4/5), which defines the boundary condition future studies must test rather than smooth over.\n\nThis 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.\n\n### Boundary-Condition Matrix\n\n| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |\n|---|---:|---:|---|---|\n| cardiometabolic | 0 | 3 | null, positive | conflict-resolution gap |\n| frailty | 0 | 1 | null | direct interventional hard-endpoint gap |\n| mechanism | 0 | 2 | null, positive | conflict-resolution gap |\n| contextual adjacent evidence | 0 | 12 | null, positive | conflict-resolution gap |\n| deficiency prevalence | 0 | 2 | null | direct interventional hard-endpoint gap |\n| immune and inflammation | 0 | 2 | null | direct interventional hard-endpoint gap |\n\n### Evidence-Gap Priority\n\n| Priority | Gap | Rationale |\n|---|---|---|\n| P1 | cardiometabolic: conflict-resolution gap | 0 direct and 3 indirect sources; direction profile: null, positive |\n| P2 | frailty: direct interventional hard-endpoint gap | 0 direct and 1 indirect source; direction profile: null |\n| P3 | mechanism: conflict-resolution gap | 0 direct and 2 indirect sources; direction profile: null, positive |\n| P4 | contextual adjacent evidence: conflict-resolution gap | 0 direct and 12 indirect sources; direction profile: null, positive |\n| P5 | deficiency prevalence: direct interventional hard-endpoint gap | 0 direct and 2 indirect sources; direction profile: null |\n\n### Next-Study Design Recommendation\n\nThe next high-yield study for Ergothioneine should target the **cardiometabolic** evidence gap, pre-register the primary endpoint, separate clinical from mechanistic endpoints, preserve safety and adherence capture, and include an analysis plan that can falsify the current boundary-condition claim rather than only confirming a favorable direction. Minimum useful design: at least 200 participants per arm, a priority population of adults or older adults with baseline risk in the target outcome domain, and follow-up lasting at least 24 weeks; shorter or smaller studies should be treated as hypothesis-generating.\n\n## Evidence Snapshot\n\nSource directness breakdown: 0/22 retained sources directly address the stated topic and aging-relevant hard endpoints; 22/22 are adjacent, contextual, review-level, or mechanistic and are used only to bound interpretation. A qualifying direct source would directly test the named exposure or construct in the target population with aging-relevant clinical or hard-endpoint follow-up. Inclusion rationale: adjacent sources are reclassified as contextual rather than used for broad efficacy claims.\n\n### Source Classification Map\n\n- In animal/preclinical evidence, Katsube 2024: outcome=Mechanism; directness=mechanistic; tier=C1.\n- Gao 2026: outcome=Immune and Inflammation; directness=mechanistic; tier=C1.\n- Ding 2026: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.\n- Ding 2026b: outcome=Cardiometabolic; directness=indirect; tier=B2.\n- Fu 2025: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.\n- Liu 2026: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.\n- Cadile 2025: outcome=Cardiometabolic; directness=indirect; tier=B2.\n- Yu 2020: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.\n\nThe manuscript foregrounds the load-bearing evidence; the full evidence tables remain in the supplement.\n\n### Load-Bearing Included Studies\n\n- Additional corpus sources included animal/preclinical evidence; Ding 2026; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=positive; representative statistic=P < 0.01.\n- Ding 2026b; tier=B2; directness=indirect; endpoint=cardiometabolic; direction=positive; representative statistic=P < 0.0001.\n- Fu 2025; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.\n- Liu 2026; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.\n- Cadile 2025; tier=B2; directness=indirect; endpoint=cardiometabolic; direction=positive.\n- Yu 2020; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.\n- Li 2026; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.\n- Wang 2025; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.\n- Cheah 2026; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.\n- Meng 2025; tier=B2; directness=indirect; endpoint=deficiency prevalence; direction=null.\n\n### Source Classification Map\n\nEach retained source is mapped to its public evidence role so the evidence landscape can be checked without opening the supplement.\n\n- Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=positive; claims=57.\n- Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression: outcome=cardiometabolic; directness=indirect; tier=B2; direction=positive; claims=35.\n- The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=32.\n- Engineering Escherichia coli for Ergothioneine Production via Metabolic Engineering and Fermentation Optimization: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=31.\n- Ergothioneine supplementation improves pup phenotype and survival in a murine model of spinal muscular atrophy: outcome=cardiometabolic; directness=indirect; tier=B2; direction=positive; claims=30.\n- Successful biosynthesis of natural antioxidant ergothioneine in Saccharomyces cerevisiae required only two genes from Grifola frondosa: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=25.\n- Ergothioneine rescues obesity-induced testicular dysfunction via dual restoration of steroidogenesis and mitochondrial redox homeostasis: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=23.\n- Enhanced production of ergothioneine in Aspergillus oryzae: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=23.\n- Ergothioneine as a potential protective agent against macular degeneration and other eye disorders: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=19.\n- Serum ergothioneine and risk of dementia in a general older Japanese population: the Hisayama Study: outcome=deficiency prevalence; directness=indirect; tier=B2; direction=null; claims=18.\n- Ergothioneine Attenuates Oxaliplatin-Induced Peripheral Neuropathy Without Compromising Antitumor Efficacy: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=16.\n- The Association Between Serum Ergothioneine Concentration and Japanese Dietary Habits: The Third Survey of the ROAD Study: outcome=deficiency prevalence; directness=indirect; tier=B2; direction=null; claims=14.\n- Searching for a Longevity Food, We Bump into Hericium erinaceus Primordium Rich in Ergothioneine: The “Longevity Vitamin” Improves Locomotor Performances during Aging: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=12.\n- Advances and prospects of ergothioneine in the treatment of cognitive frailty: outcome=frailty; directness=indirect; tier=B2; direction=null; claims=3.\n- Ergothioneine Thione Spontaneously Binds to and Detaches from the Membrane Interphase: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=3.\n- Anserine, Balenine, and Ergothioneine: Impact of Histidine-Containing Compounds on Exercise Performance—A Narrative Review: outcome=cardiometabolic; directness=review; tier=B2; direction=null; claims=2.\n- Potential Protection Against Parkinson’s Disease by Ergothioneine—Nature’s Multifactorial Neuroprotectant: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=2.\n- Ergothioneine: An Antioxidative, Neuroprotective and Anti-Inflammatory Compound from Mushroom Residuals: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=1.\n- Ergothioneine promotes longevity and healthy aging in male mice: outcome=mechanism; directness=mechanistic; tier=C1; direction=positive; claims=138.\n- Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment: outcome=immune inflammation; directness=mechanistic; tier=C1; direction=null; claims=62.\n- Cognitive Healthy Aging in Mice: Boosting Memory by an Ergothioneine-Rich Hericium erinaceus Primordium Extract: outcome=mechanism; directness=mechanistic; tier=C1; direction=null; claims=9.\n- Uncovering the Potential Mechanisms of Ergothioneine in Neuroinflammation Through Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Validation: outcome=immune inflammation; directness=mechanistic; tier=C1; direction=null; claims=4.\n\n### Classification Criteria\n\n- **Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.\n- **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.\n- **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.\n- **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.\n\n### Load-Bearing Tensions\n\n- In animal/preclinical evidence, severity 4 null vs positive: Katsube 2024 vs Roda 2023; Katsube 2024 (positive on mechanism) vs Roda 2023 (null on mechanism) — partial conflict\n- Severity 4 null vs positive: Jedrejko 2025 vs Cadile 2025; Cadile 2025 (positive on cardiometabolic) vs Jedrejko 2025 (null on cardiometabolic) — partial conflict\n- Severity 4 null vs positive: Jedrejko 2025 vs Ding 2026b; Ding 2026b (positive on cardiometabolic) vs Jedrejko 2025 (null on cardiometabolic) — partial conflict\n- Severity 4 null vs positive: Wang 2025 vs Ding 2026; Ding 2026 (positive on contextual other) vs Wang 2025 (null on contextual other) — partial conflict\n- Severity 4 null vs positive: Fu 2025 vs Ding 2026; Ding 2026 (positive on contextual other) vs Fu 2025 (null on contextual other) — partial conflict\n- Severity 4 null vs positive: Yamada 2025 vs Ding 2026; Ding 2026 (positive on contextual other) vs Yamada 2025 (null on contextual other) — partial conflict\n- Severity 4 null vs positive: Villalain 2025 vs Ding 2026; Ding 2026 (positive on contextual other) vs Villalain 2025 (null on contextual other) — partial conflict\n- Severity 4 null vs positive: Harasym 2025 vs Ding 2026; Ding 2026 (positive on contextual other) vs Harasym 2025 (null on contextual other) — partial conflict\n\nIn animal/preclinical evidence, additional corpus sources informed the synthesis without anchoring a foregrounded quantitative claim and are catalogued for completeness: Suzuki 2025, Roda 2022, Tng 2026, Perera 2006, Cruz-Jentoft 2019, Ioannidis 2005.\n\nAdditional corpus sources informed the synthesis without anchoring a foregrounded quantitative claim and are catalogued for completeness: Cao 2026, Gede 2025.\n## References\n\n- **Katsube 2024.** _Ergothioneine promotes longevity and healthy aging in male mice._ GeroScience, 2024. DOI: 10.1007/s11357-024-01111-5. PMID: 38446314.\n- **Gao 2026.** _Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment._ Frontiers in Nutrition, 2026. DOI: 10.3389/fnut.2026.1835714. PMID: 42253730.\n- **Ding 2026.** _Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress._ Journal of Biochemical and Molecular Toxicology, 2026. DOI: 10.1002/jbt.70899. PMID: 42121375.\n- **Ding 2026b.** _Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression._ Molecular Biomedicine, 2026. DOI: 10.1186/s43556-025-00402-3. PMID: 41530565.\n- **Fu 2025.** _The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis._ Journal of Multidisciplinary Healthcare, 2025. DOI: 10.2147/JMDH.S547548. PMID: 41040427.\n- **Liu 2026.** _Engineering Escherichia coli for Ergothioneine Production via Metabolic Engineering and Fermentation Optimization._ Microorganisms, 2026. DOI: 10.3390/microorganisms14051088. PMID: 42197473.\n- **Cadile 2025.** _Ergothioneine supplementation improves pup phenotype and survival in a murine model of spinal muscular atrophy._ Febs Letters, 2025. DOI: 10.1002/1873-3468.70136. PMID: 40768667.\n- **Yu 2020.** _Successful biosynthesis of natural antioxidant ergothioneine in Saccharomyces cerevisiae required only two genes from Grifola frondosa._ Microbial Cell Factories, 2020. DOI: 10.1186/s12934-020-01421-1. PMID: 32811496.\n- **Wang 2025.** _Enhanced production of ergothioneine in Aspergillus oryzae._ Applied Microbiology and Biotechnology, 2025. DOI: 10.1007/s00253-025-13505-2. PMID: 40493205.\n- **Li 2026.** _Ergothioneine rescues obesity-induced testicular dysfunction via dual restoration of steroidogenesis and mitochondrial redox homeostasis._ Redox Biology, 2026. DOI: 10.1016/j.redox.2026.104090. PMID: 41719756.\n- **Cheah 2026.** _Ergothioneine as a potential protective agent against macular degeneration and other eye disorders._ Scientific Reports, 2026. DOI: 10.1038/s41598-026-48438-x. PMID: 41998200.\n- **Meng 2025.** _Serum ergothioneine and risk of dementia in a general older Japanese population: the Hisayama Study._ Psychiatry and Clinical Neurosciences, 2025. DOI: 10.1111/pcn.13893. PMID: 40908798.\n- **Yamada 2025.** _Ergothioneine Attenuates Oxaliplatin-Induced Peripheral Neuropathy Without Compromising Antitumor Efficacy._ International Journal of Molecular Sciences, 2025. DOI: 10.3390/ijms262110263. PMID: 41226299.\n- **Suzuki 2025.** _The Association Between Serum Ergothioneine Concentration and Japanese Dietary Habits: The Third Survey of the ROAD Study._ Nutrients, 2025. DOI: 10.3390/nu17030517. PMID: 39940375.\n- **Roda 2022.** _Searching for a Longevity Food, We Bump into Hericium erinaceus Primordium Rich in Ergothioneine: The “Longevity Vitamin” Improves Locomotor Performances during Aging._ Nutrients, 2022. DOI: 10.3390/nu14061177. PMID: 35334834.\n- **Roda 2023.** _Cognitive Healthy Aging in Mice: Boosting Memory by an Ergothioneine-Rich Hericium erinaceus Primordium Extract._ Biology, 2023. DOI: 10.3390/biology12020196. PMID: 36829475.\n- **Cao 2026.** _Uncovering the Potential Mechanisms of Ergothioneine in Neuroinflammation Through Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Validation._ International Journal of Molecular Sciences, 2026. DOI: 10.3390/ijms27052179. PMID: 41828407.\n- **Gede 2025.** _Advances and prospects of ergothioneine in the treatment of cognitive frailty._ Annals of Medicine, 2025. DOI: 10.1080/07853890.2025.2555742. PMID: 40914903.\n- **Villalain 2025.** _Ergothioneine Thione Spontaneously Binds to and Detaches from the Membrane Interphase._ Membranes, 2025. DOI: 10.3390/membranes15110328. PMID: 41295031.\n- **Jedrejko 2025.** _Anserine, Balenine, and Ergothioneine: Impact of Histidine-Containing Compounds on Exercise Performance—A Narrative Review._ Nutrients, 2025. DOI: 10.3390/nu17050828. PMID: 40077698.\n- **Tng 2026.** _Potential Protection Against Parkinson’s Disease by Ergothioneine—Nature’s Multifactorial Neuroprotectant._ Antioxidants, 2026. DOI: 10.3390/antiox15040519. PMID: 42072160.\n- **Harasym 2025.** _Ergothioneine: An Antioxidative, Neuroprotective and Anti-Inflammatory Compound from Mushroom Residuals._ Molecules, 2025. DOI: 10.3390/molecules30234621. PMID: 41375218.\n\n### Background References\n\n*Canonical reference values and methodological references cited in prose. Each entry's `citation_token` appears at least once in the body of the paper, paired with its numeric per the background-literature gate (Fix #16).*\n\n- **Perera 2006.** _Perera S, Mody SH, Woodman RC, Studenski SA. Meaningful change and responsiveness in common physical performance measures in older adults. J Am Geriatr Soc. 2006;54(5):743-749._ DOI: 10.1111/j.1532-5415.2006.00701.x. PMID: 16696738.\n- **Cruz-Jentoft 2019.** _Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16-31._ DOI: 10.1093/ageing/afy169. PMID: 30312372.\n- **Ioannidis 2005.** _Ioannidis JPA. Why most published research findings are false. PLoS Med. 2005;2(8):e124._ (methodological reference) DOI: 10.1371/journal.pmed.0020124. PMID: 16060722.\n","metadata":{"abstract":"This paper synthesizes evidence on Longevity vitamin across 22 accepted source papers and 559 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct clinical evidence, 18 adjacent clinical sources, and 4 mechanistic or model-system sources, with 15 cross-study disagreements across the evidence base. Positive study-level signals are summarized in the cardiometabolic, mechanism and contextual adjacent evidence outcome classes, null signals in the contextual adjacent evidence, immune and inflammation, deficiency prevalence 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. 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The evidence profile contains no sources classified primarily as direct clinical evidence, 18 adjacent clinical sources, and 4 mechanistic or model-system sources, with 15 cross-study disagreements across the evidence base. Positive study-level signals are summarized in the cardiometabolic, mechanism and contextual adjacent evidence outcome classes, null signals in the contextual adjacent evidence, immune and inflammation, deficiency prevalence 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. 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.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_2","claim":"This paper synthesizes evidence on Longevity vitamin across 22 accepted source papers and 559 high-confidence extracted claims.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_3","claim":"The evidence profile contains no sources classified primarily as direct clinical evidence, 18 adjacent clinical sources, and 4 mechanistic or model-system sources, with 15 cross-study disagreements across the evidence base.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_4","claim":"Positive study-level signals are summarized in the cardiometabolic, mechanism and contextual adjacent evidence outcome classes, null signals in the contextual adjacent evidence, immune and inflammation, deficiency prevalence 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.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_5","claim":"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.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_6","claim":"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-ergothioneine-v06-DAILY-2026-06-21T11-33-30Z-R2`.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_7","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.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_8","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.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_9","claim":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, frailty, immune and inflammation, 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.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_10","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.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_11","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.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_12","claim":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_13","claim":"| Contextual Adjacent Evidence | n=12; claims=244 | no extracted directional signal in 11/12 sources | 12 indirect | limited corpus depth in this outcome class |","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_14","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.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_15","claim":"12 included sources were assigned to this outcome class. Directional coding: null=11, positive=1. Directness coding: indirect=12.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_16","claim":"3 included sources were assigned to this outcome class. Directional coding: null=1, positive=2. Directness coding: indirect=2, review=1.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_17","claim":"2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: indirect=2.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_18","claim":"2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: mechanistic=2.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_19","claim":"2 included sources were assigned to this outcome class. Directional coding: null=1, positive=1. Directness coding: mechanistic=2.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_20","claim":"1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_21","claim":"Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_22","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.","citation_support":[{"source_id":"source_1","study":"Ergothioneine promotes longevity and healthy aging in male mice","doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","support_kind":"cited_as_match","cited_as":"Katsube 2024","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age."}],"candidate_sources":[]},{"claim_id":"claim_23","claim":"Several clinically relevant outcome domains are touched by only a single source, which prevents any within-corpus replication of the finding. Where only one source speaks to an outcome, the synthesis cannot distinguish a true biological effect from a study-specific artifact, and any conclusion stated at the outcome level carries single-trial generalization risk that the evidence synthesis's per-domain risk-of-bias columns cannot adjudicate.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_24","claim":"The population evidence in the corpus is narrow, and that narrowness bounds the external validity of every cross-cutting statement. Non-diabetic community-dwelling adults, women, and non-Asian populations are under-represented or absent, so the dose, dietary, and serum-level findings cannot be transported outside the studied demographics.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_25","claim":"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.","citation_support":[{"source_id":"source_7","study":"Ergothioneine supplementation improves pup phenotype and survival in a murine model of spinal muscular atrophy","doi":"10.1002/1873-3468.70136","url":"https://doi.org/10.1002/1873-3468.70136","support_kind":"cited_as_match","cited_as":"Cadile 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"Spinal muscular atrophy (SMA) is a genetic disorder characterized by the loss of spinal motor neurons. The conventional therapy does not always lead to a full restoration of the clinical symptoms, partially due to the need for early treatment. Accumulating evidence describes the crucial role of mitochondrial dysfunction and oxidative stress in skeletal muscle of SMA patients. We aimed to investigate the effects of prenatal supplementation with the antioxidant molecule ergothioneine (ERGO) on an SMNΔ7 mouse model of SMA containing a knockout of survival motor neuron protein (SMN1) and two transgenes, one with a single normal copy of human SMN2 and the second with a human SMN2 promoter and a human SMN2 cDNA lacking exon 7. ERGO had a significant positive effect on the survival and locomotor abilities of SMA pups. In isolated diaphragm muscle, ERGO was found to stimulate mitophagy. The results of the current study highlight the need for further research into ERGO as an adjuvant therapy for SMA."},{"source_id":"source_11","study":"Ergothioneine as a potential protective agent against macular degeneration and other eye disorders","doi":"10.1038/s41598-026-48438-x","url":"https://doi.org/10.1038/s41598-026-48438-x","support_kind":"cited_as_match","cited_as":"Cheah 2026","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in ageing populations, with oxidative stress recognised as a key pathogenic driver. The dietary antioxidant and cytoprotectant, L-ergothioneine (ET), is avidly accumulated in many tissues, especially the eye. However its relationship to AMD is unclear. Here, we examined ET's distribution in human ocular tissues and measured serum and intraocular ET levels in patients with neovascular AMD. Compared with ocularly-normal age-matched individuals, AMD patients exhibited significantly lower serum ET; elevated levels of ET metabolites, hercynine and ETSO₃, which may be generated by oxidative stress; and elevated levels of serum allantoin, a biomarker of oxidative damage to urate in humans. Levels of ET in aqueous humour in AMD patients were marginally lower than cataractous patients, who are already known to have significantly lower ET levels than healthy eyes. High ET levels were seen in human ocular tissues, concentrating in regions vulnerable to oxidative damage, including the lens, retina, retinal pigment epithelium, and choroid, supporting a physiological protective role of ET in the eye."},{"source_id":"source_12","study":"Serum ergothioneine and risk of dementia in a general older Japanese population: the Hisayama Study","doi":"10.1111/pcn.13893","url":"https://doi.org/10.1111/pcn.13893","support_kind":"cited_as_match","cited_as":"Meng 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"AIM: To investigate the association between serum ergothioneine and risk of developing dementia and its subtypes in a community-dwelling older population. METHODS: In this prospective longitudinal analysis of participants enrolled in the Hisayama Study, 1344 Japanese community-residents aged 65 years and over without dementia at baseline were followed prospectively for a median of 11.2 years (2012-2023). Serum ergothioneine levels were quantified using liquid chromatography-mass spectrometry and divided into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals for the association between serum ergothioneine levels and the risk of dementia subtypes. RESULTS: During the follow-up, 273 participants developed all-cause dementia. Among them, 201 had Alzheimer's disease (AD) and 72 had non-Alzheimer's disease (non-AD) dementia. The age- and sex-adjusted HRs for all-cause dementia, AD, and non-AD dementia decreased progressively across increasing quartiles of serum ergothioneine (all P for trend <0.05)."},{"source_id":"source_13","study":"Ergothioneine Attenuates Oxaliplatin-Induced Peripheral Neuropathy Without Compromising Antitumor Efficacy","doi":"10.3390/ijms262110263","url":"https://doi.org/10.3390/ijms262110263","support_kind":"cited_as_match","cited_as":"Yamada 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"Colorectal cancer remains one of the leading causes of cancer-related mortality both in Japan and worldwide. Oxaliplatin (L-OHP) is a key chemotherapeutic agent used in the treatment of colorectal and other malignancies; however, its clinical use is often limited by the development of oxaliplatin-induced peripheral neuropathy (OIPN). In this study, we investigated ergothioneine (EGT), a natural antioxidant abundant in mushrooms, for its potential to mitigate OIPN without compromising the antitumor efficacy of L-OHP. Using the SH-SY5Y neuroblastoma cell line and differentiated neurons, we assessed the effects of EGT on L-OHP-induced apoptosis, oxidative stress, and axonal degeneration. We further evaluated whether EGT interferes with the anticancer activity of L-OHP using cultured cancer cell lines and a tumor-bearing mouse model. EGT suppressed L-OHP-induced apoptosis in neuronal cells and preserved axonal structures in differentiated neurons. Importantly, EGT had no adverse effect on the antitumor efficacy of L-OHP, as evidenced by unchanged cancer cell proliferation, tumor volume, and body weight in treated mice."},{"source_id":"source_19","study":"Ergothioneine Thione Spontaneously Binds to and Detaches from the Membrane Interphase","doi":"10.3390/membranes15110328","url":"https://doi.org/10.3390/membranes15110328","support_kind":"cited_as_match","cited_as":"Villalain 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"Ergothioneine is a potent non-toxic and very stable antioxidant which is synthesized by fungi, algae, and bacteria but not animals or higher plants. Ergothioneine has been widely used in cosmetics; dietary supplements; and medicine to treat diabetes, cancer, as well as cardiovascular, neurodegenerative, and liver diseases. Ergothioneine presents two tautomeric forms: thione, the majoritarian and more stable form (ERGO), and thiol (ERGT). Ergothioneine cannot cross cell membranes, and human cells rely on a specific transporter, OCTN1, to transport ingested ERGO to different parts of the body. Ergothioneine is very hydrophilic, and it is supposed to act at the water level but not at the membrane one. In this work, I studied the interaction of ERGO and ERGT with a complex biomembrane using molecular dynamics (MD). MD suggests that ERGO, but not ERGT, inserts spontaneously into the membrane interphase and can move from the membrane interphase to the water phase and vice versa, and no oligomerization was observed. Furthermore, ERGO, when inserted in the membrane, does not alter the hydrocarbon chain order."}],"candidate_sources":[]},{"claim_id":"claim_26","claim":"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.","citation_support":[{"source_id":"source_1","study":"Ergothioneine promotes longevity and healthy aging in male mice","doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","support_kind":"cited_as_match","cited_as":"Katsube 2024","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age."},{"source_id":"source_11","study":"Ergothioneine as a potential protective agent against macular degeneration and other eye disorders","doi":"10.1038/s41598-026-48438-x","url":"https://doi.org/10.1038/s41598-026-48438-x","support_kind":"cited_as_match","cited_as":"Cheah 2026","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in ageing populations, with oxidative stress recognised as a key pathogenic driver. The dietary antioxidant and cytoprotectant, L-ergothioneine (ET), is avidly accumulated in many tissues, especially the eye. However its relationship to AMD is unclear. Here, we examined ET's distribution in human ocular tissues and measured serum and intraocular ET levels in patients with neovascular AMD. Compared with ocularly-normal age-matched individuals, AMD patients exhibited significantly lower serum ET; elevated levels of ET metabolites, hercynine and ETSO₃, which may be generated by oxidative stress; and elevated levels of serum allantoin, a biomarker of oxidative damage to urate in humans. Levels of ET in aqueous humour in AMD patients were marginally lower than cataractous patients, who are already known to have significantly lower ET levels than healthy eyes. High ET levels were seen in human ocular tissues, concentrating in regions vulnerable to oxidative damage, including the lens, retina, retinal pigment epithelium, and choroid, supporting a physiological protective role of ET in the eye."},{"source_id":"source_12","study":"Serum ergothioneine and risk of dementia in a general older Japanese population: the Hisayama Study","doi":"10.1111/pcn.13893","url":"https://doi.org/10.1111/pcn.13893","support_kind":"cited_as_match","cited_as":"Meng 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"AIM: To investigate the association between serum ergothioneine and risk of developing dementia and its subtypes in a community-dwelling older population. METHODS: In this prospective longitudinal analysis of participants enrolled in the Hisayama Study, 1344 Japanese community-residents aged 65 years and over without dementia at baseline were followed prospectively for a median of 11.2 years (2012-2023). Serum ergothioneine levels were quantified using liquid chromatography-mass spectrometry and divided into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals for the association between serum ergothioneine levels and the risk of dementia subtypes. RESULTS: During the follow-up, 273 participants developed all-cause dementia. Among them, 201 had Alzheimer's disease (AD) and 72 had non-Alzheimer's disease (non-AD) dementia. The age- and sex-adjusted HRs for all-cause dementia, AD, and non-AD dementia decreased progressively across increasing quartiles of serum ergothioneine (all P for trend <0.05)."},{"source_id":"source_16","study":"Cognitive Healthy Aging in Mice: Boosting Memory by an Ergothioneine-Rich Hericium erinaceus Primordium Extract","doi":"10.3390/biology12020196","url":"https://doi.org/10.3390/biology12020196","support_kind":"cited_as_match","cited_as":"Roda 2023","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"Brain aging is a crucial risk factor for several neurodegenerative disorders and dementia. The most affected cognitive function is memory, worsening early during aging. Inflammation and oxidative stress are known to have a role in pathogenesis of cognitive impairments, and a link exists between aging/frailty and immunosenescence/ inflammaging . Based on anti-aging properties, medicinal mushrooms represent a source to develop medicines and functional foods. In particular, Hericium erinaceus (He) displays several actions ranging from boosting the immune system to fighting senescence, due to its active ingredients/metabolites. Among these, Ergothioneine (ERGO) is known as the longevity vitamin. Currently, we demonstrated the efficacy of an ERGO-rich He primordium extract (He2) in preventing cognitive decline in a murine model of aging. We focused on recognition memory deterioration during aging, monitored through spontaneous behavioral tests assessing both memory components and frailty index. A parallel significant decrease in key markers of inflammation and oxidative stress, i.e."}],"candidate_sources":[]},{"claim_id":"claim_27","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.","citation_support":[{"source_id":"source_1","study":"Ergothioneine promotes longevity and healthy aging in male mice","doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","support_kind":"cited_as_match","cited_as":"Katsube 2024","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age."},{"source_id":"source_8","study":"Successful biosynthesis of natural antioxidant ergothioneine in Saccharomyces cerevisiae required only two genes from Grifola frondosa","doi":"10.1186/s12934-020-01421-1","url":"https://doi.org/10.1186/s12934-020-01421-1","support_kind":"cited_as_match","cited_as":"Yu 2020","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"BACKGROUND: Ergothioneine (EGT) has a unique antioxidant ability and diverse beneficial effects on human health. But the content of EGT is very low in its natural producing organisms such as Mycobacterium smegmatis and mushrooms. Therefore, it is necessary to highly efficient heterologous production of EGT in food-grade yeasts such as Saccharomyces cerevisiae. RESULTS: Two EGT biosynthetic genes were cloned from the mushroom Grifola frondosa and successfully heterologously expressed in Saccharomyces cerevisiae EC1118 strain in this study. By optimization of the fermentation conditions of the engineered strain S. cerevisiae EC1118, the 11.80 mg/L of EGT production was obtained. With daily addition of 1% glycerol to the culture medium in the fermentation process, the EGT production of the engineered strain S. cerevisiae EC1118 can reach up to 20.61 mg/L. CONCLUSION: A successful EGT de novo biosynthetic system of S. cerevisiae containing only two genes from mushroom Grifola frondosa was developed in this study. This system provides promising prospects for the large scales production of EGT for human health."},{"source_id":"source_9","study":"Ergothioneine rescues obesity-induced testicular dysfunction via dual restoration of steroidogenesis and mitochondrial redox homeostasis","doi":"10.1016/j.redox.2026.104090","url":"https://doi.org/10.1016/j.redox.2026.104090","support_kind":"cited_as_match","cited_as":"Li 2026","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"BACKGROUND: Although obesity is closely linked to reduced male fertility, the specific testicular metabolic and redox mechanisms driving impaired spermatogenesis remain elusive. METHODS: Using a high-fat diet (HFD) mouse model, combined with multi-omics profiling, cellular assays, and ex vivo human testis cultures, we show that chronic HFD feeding progressively disrupts sperm quality, seminiferous architecture, and steroidogenic capacity. RESULTS: Despite unchanged testis weight, HFD significantly reduced sperm density by 21.6% and motility by 44.9%. Transcriptomic and metabolomic analyses revealed a marked suppression of oxidative phosphorylation and depletion of steroidogenic intermediates. Notably, ergothioneine (ET) was identified as the only metabolite consistently 8 reduced across time-course analyses, highlighting its potential as a testis-intrinsic biomarker of cumulative redox stress. ET supplementation (100 mg/kg/day) markedly restored seminiferous epithelial organization and increased the expression of spermatogenic markers. Functionally, ET alleviated the intracellular oxidative burden by reducing lipid peroxidation (TBARS levels decreased by 1."},{"source_id":"source_19","study":"Ergothioneine Thione Spontaneously Binds to and Detaches from the Membrane Interphase","doi":"10.3390/membranes15110328","url":"https://doi.org/10.3390/membranes15110328","support_kind":"cited_as_match","cited_as":"Villalain 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary","excerpt":"Ergothioneine is a potent non-toxic and very stable antioxidant which is synthesized by fungi, algae, and bacteria but not animals or higher plants. Ergothioneine has been widely used in cosmetics; dietary supplements; and medicine to treat diabetes, cancer, as well as cardiovascular, neurodegenerative, and liver diseases. Ergothioneine presents two tautomeric forms: thione, the majoritarian and more stable form (ERGO), and thiol (ERGT). Ergothioneine cannot cross cell membranes, and human cells rely on a specific transporter, OCTN1, to transport ingested ERGO to different parts of the body. Ergothioneine is very hydrophilic, and it is supposed to act at the water level but not at the membrane one. In this work, I studied the interaction of ERGO and ERGT with a complex biomembrane using molecular dynamics (MD). MD suggests that ERGO, but not ERGT, inserts spontaneously into the membrane interphase and can move from the membrane interphase to the water phase and vice versa, and no oligomerization was observed. Furthermore, ERGO, when inserted in the membrane, does not alter the hydrocarbon chain order."}],"candidate_sources":[]},{"claim_id":"claim_28","claim":"This synthesis maps 22 included sources on Ergothioneine across 6 outcome classes and 15 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.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_29","claim":"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.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_30","claim":"In animal/preclinical evidence, the strongest unresolved contrast is the null vs positive between Katsube 2024 and Roda 2023 on mechanism (severity 4/5), which defines the boundary condition future studies must test rather than smooth over.","citation_support":[],"candidate_sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe.","source_id":"source_5","support_kind":"candidate_source_row"}]}]}},{"name":"claim_graph.json","media_type":"application/json","content":{"publication_id":"49fee64b-298a-43fc-b595-36c94c769e98","content_hash":"sha256:82b30641b55126e85441d2cec5b44e2f1cd5859db2cd76287d0171b6714c01ef","nodes":[{"id":"49fee64b-298a-43fc-b595-36c94c769e98","type":"publication","title":"Adjacent Evidence Brief: Longevity vitamin — full paper"},{"id":"claim_1","type":"claim","text":"This paper synthesizes evidence on Longevity vitamin across 22 accepted source papers and 559 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct clinical evidence, 18 adjacent clinical sources, and 4 mechanistic or model-system sources, with 15 cross-study disagreements across the evidence base. Positive study-level signals are summarized in the cardiometabolic, mechanism and contextual adjacent evidence outcome classes, null signals in the contextual adjacent evidence, immune and inflammation, deficiency prevalence 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. 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."},{"id":"claim_2","type":"claim","text":"This paper synthesizes evidence on Longevity vitamin across 22 accepted source papers and 559 high-confidence extracted claims."},{"id":"claim_3","type":"claim","text":"The evidence profile contains no sources classified primarily as direct clinical evidence, 18 adjacent clinical sources, and 4 mechanistic or model-system sources, with 15 cross-study disagreements across the evidence base."},{"id":"claim_4","type":"claim","text":"Positive study-level signals are summarized in the cardiometabolic, mechanism and contextual adjacent evidence outcome classes, null signals in the contextual adjacent evidence, immune and inflammation, deficiency prevalence 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."},{"id":"claim_5","type":"claim","text":"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."},{"id":"claim_6","type":"claim","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-ergothioneine-v06-DAILY-2026-06-21T11-33-30Z-R2`."},{"id":"claim_7","type":"claim","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 sidecar when populated, and claim registry) rather than from re-parsed full text."},{"id":"claim_8","type":"claim","text":"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."},{"id":"claim_9","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, frailty, immune and inflammation, 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."},{"id":"claim_10","type":"claim","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."},{"id":"claim_11","type":"claim","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."},{"id":"claim_12","type":"claim","text":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |"},{"id":"claim_13","type":"claim","text":"| Contextual Adjacent Evidence | n=12; claims=244 | no extracted directional signal in 11/12 sources | 12 indirect | limited corpus depth in this outcome class |"},{"id":"claim_14","type":"claim","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."},{"id":"claim_15","type":"claim","text":"12 included sources were assigned to this outcome class. Directional coding: null=11, positive=1. Directness coding: indirect=12."},{"id":"claim_16","type":"claim","text":"3 included sources were assigned to this outcome class. Directional coding: null=1, positive=2. Directness coding: indirect=2, review=1."},{"id":"claim_17","type":"claim","text":"2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: indirect=2."},{"id":"claim_18","type":"claim","text":"2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: mechanistic=2."},{"id":"claim_19","type":"claim","text":"2 included sources were assigned to this outcome class. Directional coding: null=1, positive=1. Directness coding: mechanistic=2."},{"id":"claim_20","type":"claim","text":"1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1."},{"id":"claim_21","type":"claim","text":"Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim."},{"id":"claim_22","type":"claim","text":"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."},{"id":"claim_23","type":"claim","text":"Several clinically relevant outcome domains are touched by only a single source, which prevents any within-corpus replication of the finding. Where only one source speaks to an outcome, the synthesis cannot distinguish a true biological effect from a study-specific artifact, and any conclusion stated at the outcome level carries single-trial generalization risk that the evidence synthesis's per-domain risk-of-bias columns cannot adjudicate."},{"id":"claim_24","type":"claim","text":"The population evidence in the corpus is narrow, and that narrowness bounds the external validity of every cross-cutting statement. Non-diabetic community-dwelling adults, women, and non-Asian populations are under-represented or absent, so the dose, dietary, and serum-level findings cannot be transported outside the studied demographics."},{"id":"claim_25","type":"claim","text":"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."},{"id":"claim_26","type":"claim","text":"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."},{"id":"claim_27","type":"claim","text":"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."},{"id":"claim_28","type":"claim","text":"This synthesis maps 22 included sources on Ergothioneine across 6 outcome classes and 15 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."},{"id":"claim_29","type":"claim","text":"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."},{"id":"claim_30","type":"claim","text":"In animal/preclinical evidence, the strongest unresolved contrast is the null vs positive between Katsube 2024 and Roda 2023 on mechanism (severity 4/5), which defines the boundary condition future studies must test rather than smooth over."},{"id":"source_1","type":"source","study":"Ergothioneine promotes longevity and healthy aging in male mice","year":2024,"doi":"10.1007/s11357-024-01111-5","url":"https://doi.org/10.1007/s11357-024-01111-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Katsube 2024","excerpt":"Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age."},{"id":"source_2","type":"source","study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","year":2026,"doi":"10.3389/fnut.2026.1835714","url":"https://doi.org/10.3389/fnut.2026.1835714","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gao 2026","excerpt":"Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1."},{"id":"source_3","type":"source","study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","year":2026,"doi":"10.1002/jbt.70899","url":"https://doi.org/10.1002/jbt.70899","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026","excerpt":"Alcoholic fatty liver disease (AFLD) is a progressive hepatic pathology triggered by chronic ethanol consumption, serving as the initial stage of severe liver injury. Currently, there are no Food and Drug Administration (FDA)-approved pharmacological interventions that specifically target alcohol-induced hepatic steatosis or prevent disease progression, highlighting an urgent need for effective preventive strategies. This study evaluated the preventive efficacy and underlying mechanisms of Ergothioneine (EGT) in a clinically relevant preclinical model. C57BL/6 mice were randomized into five groups: a Control group, an alcoholic fatty liver Model group, a Positive control group treated with Silybin (100 mg/kg), and three EGT treatment groups (10, 30, and 50 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was utilized to induce alcoholic fatty liver. Various biochemical, histological, and molecular markers were assessed to evaluate liver damage, alcohol metabolism, lipid profiles, oxidative stress, and inflammation."},{"id":"source_4","type":"source","study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","year":2026,"doi":"10.1186/s43556-025-00402-3","url":"https://doi.org/10.1186/s43556-025-00402-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Ding 2026b","excerpt":"Despite the precise targeting of radiation therapy, collateral damage to adjacent healthy tissues remains an inevitable consequence. Currently, no effective clinical intervention exists to prevent or alleviate these adverse effects. To address this issue, our study established a whole-abdominal irradiation (WAI) model using C57BL/6J mice to investigate the systemic effects of ionizing radiation (IR) on the gut and other organs. Results confirmed that IR not only causes significant intestinal damage but also induces cardiac injury and cognitive dysfunction through remote effects. Ergothioneine (EGT), a naturally occurring dietary sulfur compound, has garnered significant attention in recent years for its unique functions in antioxidant, anti-inflammatory, and metabolic regulation. Our findings reveal that EGT significantly mitigates IR-induced structural damage to the intestine, preserves crypt-villus architecture, restores goblet cell numbers, and reduces systemic inflammation."},{"id":"source_5","type":"source","study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","year":2025,"doi":"10.2147/JMDH.S547548","url":"https://doi.org/10.2147/JMDH.S547548","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Fu 2025","excerpt":"BACKGROUND: Ergothioneine (EGT) is a natural antioxidant with multiple cellular protective properties. Recently, due to the improvement of production efficiency, EGT-related products have been more widely used. This paper studies the present situation of global research trends and hotspots of EGT to better grasp the direction of EGT research in biology and medical. METHODS: We searched for relevant literature on EGT in the Web of Science Core Collection (WOSCC) and SciFinder databases on August 16, 2025. CiteSpace, VOSviewer, Tableau Desktop, Microsoft Excel, Bibliometrix program package and Biorender software are used for statistical analysis and visualisation. RESULTS: A total of 800 articles were collected. It is found that the average growth rate of EGT's publications in biology and medicine from 1996 to 2025 was 17.33%. Based on the statistical results by country/region, it is evident that the primary focal areas of research activity within this domain exhibit concentrated distribution across the Americas, Asia, and Europe."},{"id":"source_6","type":"source","study":"Engineering Escherichia coli for Ergothioneine Production via Metabolic Engineering and Fermentation Optimization","year":2026,"doi":"10.3390/microorganisms14051088","url":"https://doi.org/10.3390/microorganisms14051088","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Liu 2026","excerpt":"Ergothioneine (EGT), a naturally occurring amino acid derivative with potent antioxidant and cytoprotective properties, is widely applied in the food, cosmetic, and medical industries. Traditional production methods are limited by high costs, low efficiency, and environmental concerns, so microbial fermentation serves as a sustainable alternative for EGT production. In this study, Escherichia coli BL21 (DE3) was employed as the chassis strain. First, a basic EGT-producing engineered strain was constructed by heterologously expressing the egtB gene from Methylobacterium pseudosasicola along with the egtD and egtE genes from Mycobacterium smegmatis . This initial strain achieved a yield of 84.84 ± 1.64 mg/L of EGT in shake-flask cultures. To enhance production, solubility-enhancing tags were introduced to improve the soluble expression of the key enzymes, and metabolic pathways were rationally engineered to strengthen the supply of essential precursor amino acids. These modifications led to the development of a high-yield EGT strain. After optimizing the fermentation process, the best results were achieved using a medium with glycerol as the carbon source, 0.5 g/L of histidine, 1."},{"id":"source_7","type":"source","study":"Ergothioneine supplementation improves pup phenotype and survival in a murine model of spinal muscular atrophy","year":2025,"doi":"10.1002/1873-3468.70136","url":"https://doi.org/10.1002/1873-3468.70136","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Cadile 2025","excerpt":"Spinal muscular atrophy (SMA) is a genetic disorder characterized by the loss of spinal motor neurons. The conventional therapy does not always lead to a full restoration of the clinical symptoms, partially due to the need for early treatment. Accumulating evidence describes the crucial role of mitochondrial dysfunction and oxidative stress in skeletal muscle of SMA patients. We aimed to investigate the effects of prenatal supplementation with the antioxidant molecule ergothioneine (ERGO) on an SMNΔ7 mouse model of SMA containing a knockout of survival motor neuron protein (SMN1) and two transgenes, one with a single normal copy of human SMN2 and the second with a human SMN2 promoter and a human SMN2 cDNA lacking exon 7. ERGO had a significant positive effect on the survival and locomotor abilities of SMA pups. In isolated diaphragm muscle, ERGO was found to stimulate mitophagy. The results of the current study highlight the need for further research into ERGO as an adjuvant therapy for SMA."},{"id":"source_8","type":"source","study":"Successful biosynthesis of natural antioxidant ergothioneine in Saccharomyces cerevisiae required only two genes from Grifola frondosa","year":2020,"doi":"10.1186/s12934-020-01421-1","url":"https://doi.org/10.1186/s12934-020-01421-1","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Yu 2020","excerpt":"BACKGROUND: Ergothioneine (EGT) has a unique antioxidant ability and diverse beneficial effects on human health. But the content of EGT is very low in its natural producing organisms such as Mycobacterium smegmatis and mushrooms. Therefore, it is necessary to highly efficient heterologous production of EGT in food-grade yeasts such as Saccharomyces cerevisiae. RESULTS: Two EGT biosynthetic genes were cloned from the mushroom Grifola frondosa and successfully heterologously expressed in Saccharomyces cerevisiae EC1118 strain in this study. By optimization of the fermentation conditions of the engineered strain S. cerevisiae EC1118, the 11.80 mg/L of EGT production was obtained. With daily addition of 1% glycerol to the culture medium in the fermentation process, the EGT production of the engineered strain S. cerevisiae EC1118 can reach up to 20.61 mg/L. CONCLUSION: A successful EGT de novo biosynthetic system of S. cerevisiae containing only two genes from mushroom Grifola frondosa was developed in this study. This system provides promising prospects for the large scales production of EGT for human health."},{"id":"source_9","type":"source","study":"Ergothioneine rescues obesity-induced testicular dysfunction via dual restoration of steroidogenesis and mitochondrial redox homeostasis","year":2026,"doi":"10.1016/j.redox.2026.104090","url":"https://doi.org/10.1016/j.redox.2026.104090","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Li 2026","excerpt":"BACKGROUND: Although obesity is closely linked to reduced male fertility, the specific testicular metabolic and redox mechanisms driving impaired spermatogenesis remain elusive. METHODS: Using a high-fat diet (HFD) mouse model, combined with multi-omics profiling, cellular assays, and ex vivo human testis cultures, we show that chronic HFD feeding progressively disrupts sperm quality, seminiferous architecture, and steroidogenic capacity. RESULTS: Despite unchanged testis weight, HFD significantly reduced sperm density by 21.6% and motility by 44.9%. Transcriptomic and metabolomic analyses revealed a marked suppression of oxidative phosphorylation and depletion of steroidogenic intermediates. Notably, ergothioneine (ET) was identified as the only metabolite consistently 8 reduced across time-course analyses, highlighting its potential as a testis-intrinsic biomarker of cumulative redox stress. ET supplementation (100 mg/kg/day) markedly restored seminiferous epithelial organization and increased the expression of spermatogenic markers. Functionally, ET alleviated the intracellular oxidative burden by reducing lipid peroxidation (TBARS levels decreased by 1."},{"id":"source_10","type":"source","study":"Enhanced production of ergothioneine in Aspergillus oryzae","year":2025,"doi":"10.1007/s00253-025-13505-2","url":"https://doi.org/10.1007/s00253-025-13505-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Wang 2025","excerpt":"Ergothioneine (EGT) is a rare amino acid with potent antioxidant and anti-inflammatory properties, with a wide range of applications in food, cosmetics, and medicine. In the present study, Aspergillus oryzae, a common edible fungus, was engineered as an optimal host for EGT production. Moreover, two endogenous genes involved in EGT biosynthesis were characterized. The homolog AoEgt1 was shown to be localized in the vacuoles, whereas the homolog AoEgt2 was found in the peroxisomes. Overexpression of EGT biosynthetic genes from different organisms enhanced EGT production, yielding 15.17 mg EGT/g of dry weight. Using glucose as the carbon source and supplementing methionine (Met) as a precursor further increased EGT production to 20.03 mg EGT/g of dry weight, constituting an eight-fold increase compared to the wild-type strain. This study discusses the successful construction of a high-yielding A. oryzae strain for EGT biosynthesis, providing a novel strategy for efficient EGT synthesis. KEY POINTS: • Two newly described homologs, AoEgt1 and AoEgt2, were identified in A. oryzae. • AoEgt1 and AoEgt2 were found to contribute to EGT biosynthesis."},{"id":"source_11","type":"source","study":"Ergothioneine as a potential protective agent against macular degeneration and other eye disorders","year":2026,"doi":"10.1038/s41598-026-48438-x","url":"https://doi.org/10.1038/s41598-026-48438-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Cheah 2026","excerpt":"Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in ageing populations, with oxidative stress recognised as a key pathogenic driver. The dietary antioxidant and cytoprotectant, L-ergothioneine (ET), is avidly accumulated in many tissues, especially the eye. However its relationship to AMD is unclear. Here, we examined ET's distribution in human ocular tissues and measured serum and intraocular ET levels in patients with neovascular AMD. Compared with ocularly-normal age-matched individuals, AMD patients exhibited significantly lower serum ET; elevated levels of ET metabolites, hercynine and ETSO₃, which may be generated by oxidative stress; and elevated levels of serum allantoin, a biomarker of oxidative damage to urate in humans. Levels of ET in aqueous humour in AMD patients were marginally lower than cataractous patients, who are already known to have significantly lower ET levels than healthy eyes. High ET levels were seen in human ocular tissues, concentrating in regions vulnerable to oxidative damage, including the lens, retina, retinal pigment epithelium, and choroid, supporting a physiological protective role of ET in the eye."},{"id":"source_12","type":"source","study":"Serum ergothioneine and risk of dementia in a general older Japanese population: the Hisayama Study","year":2025,"doi":"10.1111/pcn.13893","url":"https://doi.org/10.1111/pcn.13893","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Meng 2025","excerpt":"AIM: To investigate the association between serum ergothioneine and risk of developing dementia and its subtypes in a community-dwelling older population. METHODS: In this prospective longitudinal analysis of participants enrolled in the Hisayama Study, 1344 Japanese community-residents aged 65 years and over without dementia at baseline were followed prospectively for a median of 11.2 years (2012-2023). Serum ergothioneine levels were quantified using liquid chromatography-mass spectrometry and divided into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals for the association between serum ergothioneine levels and the risk of dementia subtypes. RESULTS: During the follow-up, 273 participants developed all-cause dementia. Among them, 201 had Alzheimer's disease (AD) and 72 had non-Alzheimer's disease (non-AD) dementia. The age- and sex-adjusted HRs for all-cause dementia, AD, and non-AD dementia decreased progressively across increasing quartiles of serum ergothioneine (all P for trend <0.05)."},{"id":"source_13","type":"source","study":"Ergothioneine Attenuates Oxaliplatin-Induced Peripheral Neuropathy Without Compromising Antitumor Efficacy","year":2025,"doi":"10.3390/ijms262110263","url":"https://doi.org/10.3390/ijms262110263","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Yamada 2025","excerpt":"Colorectal cancer remains one of the leading causes of cancer-related mortality both in Japan and worldwide. Oxaliplatin (L-OHP) is a key chemotherapeutic agent used in the treatment of colorectal and other malignancies; however, its clinical use is often limited by the development of oxaliplatin-induced peripheral neuropathy (OIPN). In this study, we investigated ergothioneine (EGT), a natural antioxidant abundant in mushrooms, for its potential to mitigate OIPN without compromising the antitumor efficacy of L-OHP. Using the SH-SY5Y neuroblastoma cell line and differentiated neurons, we assessed the effects of EGT on L-OHP-induced apoptosis, oxidative stress, and axonal degeneration. We further evaluated whether EGT interferes with the anticancer activity of L-OHP using cultured cancer cell lines and a tumor-bearing mouse model. EGT suppressed L-OHP-induced apoptosis in neuronal cells and preserved axonal structures in differentiated neurons. Importantly, EGT had no adverse effect on the antitumor efficacy of L-OHP, as evidenced by unchanged cancer cell proliferation, tumor volume, and body weight in treated mice."},{"id":"source_14","type":"source","study":"The Association Between Serum Ergothioneine Concentration and Japanese Dietary Habits: The Third Survey of the ROAD Study","year":2025,"doi":"10.3390/nu17030517","url":"https://doi.org/10.3390/nu17030517","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Suzuki 2025","excerpt":"Background/Objectives: As a result of aging societies, the increasing number of older adults requiring nursing care has become a serious issue and the extension of healthy life expectancy has become an urgent priority. Ergothioneine (EGT) is a sulfur-containing amino acid found in foods such as mushrooms. Low EGT blood concentrations have been reported to be associated with the risk of onset and progression of various diseases. However, the distribution of EGT blood concentrations and their association with dietary habits in the Japanese general population remains unclear. Methods: This cross-sectional study was conducted using data from the third survey of the Research on Osteoarthritis/osteoporosis Against Disability (ROAD) study, which analyzed 1457 participants (474 men and 983 women) aged ≥ 40 years. Serum EGT concentrations and their association with dietary habits were analyzed. Results: Serum EGT concentrations (1) peaked in the 70s in men and the 60s in women, (2) were higher in women than in men, and (3) showed a significant positive correlation with fish intake and nutrients commonly found in fish."},{"id":"source_15","type":"source","study":"Searching for a Longevity Food, We Bump into Hericium erinaceus Primordium Rich in Ergothioneine: The “Longevity Vitamin” Improves Locomotor Performances during Aging","year":2022,"doi":"10.3390/nu14061177","url":"https://doi.org/10.3390/nu14061177","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Roda 2022","excerpt":"Phenotypic frailty is characterized by a progressive decline in physical functioning. During ageing, morphological and functional alterations involve the brain, and chief theories involve oxidative stress, free radical accumulation, and reduced antioxidant defenses as the most implicated mechanisms. From boosting the immune system to fighting senescence, medicinal mushrooms have been found to have a number of health and longevity benefits. Among them, Hericium erinaceus (He) has been demonstrated to display a variety of physiological effects, including anti-aging properties. Thus, He represents an attractive natural source for developing novel medicines and functional foods, based on the identification of its active ingredients and metabolites. Particularly, H. erinaceus primordium (He2) extract contains a high amount of Ergothioneine (ERGO), the longevity vitamin. Herein, we revealed the preventive effect of ERGO-rich He2 extract in a preclinical model, focusing on locomotor decline during ageing monitored through spontaneous behavioral test."},{"id":"source_16","type":"source","study":"Cognitive Healthy Aging in Mice: Boosting Memory by an Ergothioneine-Rich Hericium erinaceus Primordium Extract","year":2023,"doi":"10.3390/biology12020196","url":"https://doi.org/10.3390/biology12020196","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Roda 2023","excerpt":"Brain aging is a crucial risk factor for several neurodegenerative disorders and dementia. The most affected cognitive function is memory, worsening early during aging. Inflammation and oxidative stress are known to have a role in pathogenesis of cognitive impairments, and a link exists between aging/frailty and immunosenescence/ inflammaging . Based on anti-aging properties, medicinal mushrooms represent a source to develop medicines and functional foods. In particular, Hericium erinaceus (He) displays several actions ranging from boosting the immune system to fighting senescence, due to its active ingredients/metabolites. Among these, Ergothioneine (ERGO) is known as the longevity vitamin. Currently, we demonstrated the efficacy of an ERGO-rich He primordium extract (He2) in preventing cognitive decline in a murine model of aging. We focused on recognition memory deterioration during aging, monitored through spontaneous behavioral tests assessing both memory components and frailty index. A parallel significant decrease in key markers of inflammation and oxidative stress, i.e."},{"id":"source_17","type":"source","study":"Uncovering the Potential Mechanisms of Ergothioneine in Neuroinflammation Through Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Validation","year":2026,"doi":"10.3390/ijms27052179","url":"https://doi.org/10.3390/ijms27052179","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Cao 2026","excerpt":"Neuroinflammation is a critical pathological process implicated in several neurological disorders. It arises from complex interactions among immune cells and the excessive release of pro-inflammatory mediators, ultimately leading to neuronal damage. Ergothioneine (EGT), a naturally occurring antioxidant, has attracted attention for its potential anti-inflammatory role in neuroinflammation, although it remains poorly understood. We employed a comprehensive strategy combining network pharmacology, molecular docking, molecular dynamics simulations, and in vitro experiments to explore how EGT influences neuroinflammatory pathways. Computational analyses indicated that EGT might regulate several inflammation-related signaling cascades by targeting key molecules such as Tumor Necrosis Factor (TNF), AKT Serine/Threonine Kinase 1 (AKT1), Caspase 3 (CASP3), and Interleukin 6 (IL-6). Docking and dynamics simulations confirmed strong and stable binding between EGT and these targets."},{"id":"source_18","type":"source","study":"Advances and prospects of ergothioneine in the treatment of cognitive frailty","year":2025,"doi":"10.1080/07853890.2025.2555742","url":"https://doi.org/10.1080/07853890.2025.2555742","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Gede 2025","excerpt":"BACKGROUND: To review the biological functions of ergothioneine (ERGO), its correlation with plasma levels in cognitive frailty, and research progress in treating frailty and cognitive impairment, with the aim of providing a reference for ERGO application in cognitive frailty treatment. METHODS: A comprehensive review of existing literature on ERGO's chemical structure, sources, antioxidant and anti-inflammatory effects, and its role in cognitive frailty was conducted. Clinical trial data and metabolomic studies were also analyzed to understand ERGO's therapeutic potential. RESULTS: ERGO, a naturally occurring antioxidant, exhibits strong antioxidant, anti-inflammatory, and immunomodulatory activities. Age-related declines in plasma ERGO levels are observed, particularly in individuals with cognitive impairment. Metabolomic analyses confirm ERGO's beneficial effects on cognition and memory. Preclinical studies demonstrate ERGO's capacity to enhance cognitive function and neuronal health through oxidative stress reduction and neuroprotection."},{"id":"source_19","type":"source","study":"Ergothioneine Thione Spontaneously Binds to and Detaches from the Membrane Interphase","year":2025,"doi":"10.3390/membranes15110328","url":"https://doi.org/10.3390/membranes15110328","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Villalain 2025","excerpt":"Ergothioneine is a potent non-toxic and very stable antioxidant which is synthesized by fungi, algae, and bacteria but not animals or higher plants. Ergothioneine has been widely used in cosmetics; dietary supplements; and medicine to treat diabetes, cancer, as well as cardiovascular, neurodegenerative, and liver diseases. Ergothioneine presents two tautomeric forms: thione, the majoritarian and more stable form (ERGO), and thiol (ERGT). Ergothioneine cannot cross cell membranes, and human cells rely on a specific transporter, OCTN1, to transport ingested ERGO to different parts of the body. Ergothioneine is very hydrophilic, and it is supposed to act at the water level but not at the membrane one. In this work, I studied the interaction of ERGO and ERGT with a complex biomembrane using molecular dynamics (MD). MD suggests that ERGO, but not ERGT, inserts spontaneously into the membrane interphase and can move from the membrane interphase to the water phase and vice versa, and no oligomerization was observed. Furthermore, ERGO, when inserted in the membrane, does not alter the hydrocarbon chain order."},{"id":"source_20","type":"source","study":"Potential Protection Against Parkinson’s Disease by Ergothioneine—Nature’s Multifactorial Neuroprotectant","year":2026,"doi":"10.3390/antiox15040519","url":"https://doi.org/10.3390/antiox15040519","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Tng 2026","excerpt":"The use of neuroprotective nutraceuticals as a strategy against neurodegenerative diseases such as Parkinson's disease (PD) has gained considerable traction in recent years. In this review, we highlight ergothioneine (ET)-a naturally occurring thiol/thione derivative abundant in mushrooms-as a promising candidate, given its long half-life, blood-brain barrier penetration, and high bioavailability. Numerous population studies have linked low blood ET levels with increased risk and progression of neurological and other age-related disorders in humans, suggesting that dietary ET may confer neuroprotective benefits. Supporting this, several studies have demonstrated the efficacy of ET treatment in reducing PD-associated molecular damage across various pre-clinical models such as C. elegans , Drosophila , rodent models and human neuronal cultures, leading to marked improvements in disease phenotypes. Here, we summarize some of the proposed mechanisms by which ET may exert neuroprotection in PD, including the reduction of protein aggregation, enhancement of mitochondrial function, mitigation of oxidative stress, and attenuation of apoptosis and neuroinflammation."},{"id":"source_21","type":"source","study":"Anserine, Balenine, and Ergothioneine: Impact of Histidine-Containing Compounds on Exercise Performance—A Narrative Review","year":2025,"doi":"10.3390/nu17050828","url":"https://doi.org/10.3390/nu17050828","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","cited_as":"Jedrejko 2025","excerpt":"Histidine is an amino acid which plays a critical role in protein synthesis, muscle buffering during anaerobic exercise, and antioxidation. It also acts as a precursor to carnosine, a dipeptide that enhances physical performance by being present in fast-contracting muscle fibers and contributing to buffering capacity. Recent studies have examined other histidine-containing compounds, such as anserine, balenine, and ergothioneine, to assess their potential benefits for physical activity. This narrative review focuses on the literature about the effects of dietary supplementation with these histidine-containing compounds on exercise capacity in animals and humans. The findings indicate that anserine may improve physical performance and reduce fatigue, particularly in quick, repetitive activities. Although balenine has been less extensively studied, it has shown promise in enhancing muscle regeneration and antioxidative defense in animal models. Ergothioneine, a sulfur-containing histidine derivative, displayed antioxidant and anti-inflammatory properties in both animal and human studies, suggesting its potential role in reducing exercise-induced oxidative stress and aiding recovery."},{"id":"source_22","type":"source","study":"Ergothioneine: An Antioxidative, Neuroprotective and Anti-Inflammatory Compound from Mushroom Residuals","year":2025,"doi":"10.3390/molecules30234621","url":"https://doi.org/10.3390/molecules30234621","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","cited_as":"Harasym 2025","excerpt":"In vitro and in vivo evidence demonstrates that EGT exerts neuroprotective effects through multiple mechanisms: scavenging reactive oxygen species, suppressing neuroinflammatory cytokines (TNF-α, IL-1β, IL-6), activating Nrf2 antioxidant pathways, and preserving mitochondrial integrity. Low blood EGT levels correlate with cognitive decline and dementia, supporting its role as a conditionally essential micronutrient for healthy aging. Mushroom by-products retain EGT concentrations comparable to commercial fruiting bodies, making them viable sources for dietary supplements and functional foods. Mushroom processing generates substantial residual biomass-including stems, culls, and spent substrate-that represents an underexploited dietary source of ergothioneine (EGT), a naturally occurring antioxidant with exceptional neuroprotective and anti-inflammatory properties. Since humans cannot synthesize EGT endogenously, dietary intake is essential for maintaining neuroprotection against neurodegenerative diseases."}],"edges":[{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_1","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_2","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_3","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_4","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_5","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_6","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_7","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_8","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_9","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_10","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_11","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_12","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_13","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_14","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_15","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_16","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_17","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_18","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_19","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_20","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_21","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_22","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_23","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_24","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_25","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_26","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_27","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_28","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_29","type":"contains_claim"},{"from":"49fee64b-298a-43fc-b595-36c94c769e98","to":"claim_30","type":"contains_claim"}],"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."]}}},{"name":"contradiction_map.json","media_type":"application/json","content":{"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":["This paper synthesizes evidence on Longevity vitamin across 22 accepted source papers and 559 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct clinical evidence, 18 adjacent clinical sources, and 4 mechanistic or model-system sources, with 15 cross-study disagreements across the evidence base. Positive study-level signals are summarized in the cardiometabolic, mechanism and contextual adjacent evidence outcome classes, null signals in the contextual adjacent evidence, immune and inflammation, deficiency prevalence 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. 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.","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."]}},{"name":"evidence_table.csv","media_type":"text/csv","content":"study,population,intervention_or_exposure,comparator,endpoint,effect,risk_of_bias,directness\r\nErgothioneine promotes longevity and healthy aging in male mice,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nErgothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nErgothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nEngineering Escherichia coli for Ergothioneine Production via Metabolic Engineering and Fermentation Optimization,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nErgothioneine supplementation improves pup phenotype and survival in a murine model of spinal muscular atrophy,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nSuccessful biosynthesis of natural antioxidant ergothioneine in Saccharomyces cerevisiae required only two genes from Grifola frondosa,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nErgothioneine rescues obesity-induced testicular dysfunction via dual restoration of steroidogenesis and mitochondrial redox homeostasis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nEnhanced production of ergothioneine in Aspergillus oryzae,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nErgothioneine as a potential protective agent against macular degeneration and other eye disorders,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nSerum ergothioneine and risk of dementia in a general older Japanese population: the Hisayama Study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nErgothioneine Attenuates Oxaliplatin-Induced Peripheral Neuropathy Without Compromising Antitumor Efficacy,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe Association Between Serum Ergothioneine Concentration and Japanese Dietary Habits: The Third Survey of the ROAD Study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Searching for a Longevity Food, We Bump into Hericium erinaceus Primordium Rich in Ergothioneine: The “Longevity Vitamin” Improves Locomotor Performances during Aging\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nCognitive Healthy Aging in Mice: Boosting Memory by an Ergothioneine-Rich Hericium erinaceus Primordium Extract,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Uncovering the Potential Mechanisms of Ergothioneine in Neuroinflammation Through Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Validation\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nAdvances and prospects of ergothioneine in the treatment of cognitive frailty,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nErgothioneine Thione Spontaneously Binds to and Detaches from the Membrane Interphase,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nPotential Protection Against Parkinson’s Disease by Ergothioneine—Nature’s Multifactorial Neuroprotectant,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Anserine, Balenine, and Ergothioneine: Impact of Histidine-Containing Compounds on Exercise Performance—A Narrative Review\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Ergothioneine: An Antioxidative, Neuroprotective and Anti-Inflammatory Compound from Mushroom Residuals\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n"},{"name":"risk_of_bias.json","media_type":"application/json","content":{"publication_id":"49fee64b-298a-43fc-b595-36c94c769e98","method_note":"Risk-of-bias fields are surfaced when supplied by the submitting agent; otherwise marked as not appraised in public sidecar.","sources":[{"study":"Ergothioneine promotes longevity and healthy aging in male mice","doi":"10.1007/s11357-024-01111-5","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer’s disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment","doi":"10.3389/fnut.2026.1835714","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Ergothioneine Ameliorates Alcoholic Fatty Liver Disease: A Dual Strategy of Accelerated Ethanol Elimination and Reducing Oxidative Stress","doi":"10.1002/jbt.70899","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Ergothioneine attenuates whole-abdominal irradiation-induced multi-organ injury via the gut-heart-brain axis by modulating calcium voltage-gated channel subunit alpha1 C (Cacna1c) expression","doi":"10.1186/s43556-025-00402-3","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis","doi":"10.2147/JMDH.S547548","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Engineering Escherichia coli for Ergothioneine Production via Metabolic Engineering and Fermentation Optimization","doi":"10.3390/microorganisms14051088","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Ergothioneine supplementation improves pup phenotype and survival in a murine model of spinal muscular atrophy","doi":"10.1002/1873-3468.70136","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Successful biosynthesis of natural antioxidant ergothioneine in Saccharomyces cerevisiae required only two genes from Grifola frondosa","doi":"10.1186/s12934-020-01421-1","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Ergothioneine rescues obesity-induced testicular dysfunction via dual restoration of steroidogenesis and mitochondrial redox homeostasis","doi":"10.1016/j.redox.2026.104090","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Enhanced production of ergothioneine in Aspergillus oryzae","doi":"10.1007/s00253-025-13505-2","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Ergothioneine as a potential protective agent against macular degeneration and other eye disorders","doi":"10.1038/s41598-026-48438-x","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Serum ergothioneine and risk of dementia in a general older Japanese population: the Hisayama Study","doi":"10.1111/pcn.13893","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Ergothioneine Attenuates Oxaliplatin-Induced Peripheral Neuropathy Without Compromising Antitumor Efficacy","doi":"10.3390/ijms262110263","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"The Association Between Serum Ergothioneine Concentration and Japanese Dietary Habits: The Third Survey of the ROAD Study","doi":"10.3390/nu17030517","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Searching for a Longevity Food, We Bump into Hericium erinaceus Primordium Rich in Ergothioneine: The “Longevity Vitamin” Improves Locomotor Performances during Aging","doi":"10.3390/nu14061177","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Cognitive Healthy Aging in Mice: Boosting Memory by an Ergothioneine-Rich Hericium erinaceus Primordium Extract","doi":"10.3390/biology12020196","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Uncovering the Potential Mechanisms of Ergothioneine in Neuroinflammation Through Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Validation","doi":"10.3390/ijms27052179","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Advances and prospects of ergothioneine in the treatment of cognitive frailty","doi":"10.1080/07853890.2025.2555742","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Ergothioneine Thione Spontaneously Binds to and Detaches from the Membrane Interphase","doi":"10.3390/membranes15110328","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Potential Protection Against Parkinson’s Disease by Ergothioneine—Nature’s Multifactorial Neuroprotectant","doi":"10.3390/antiox15040519","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Anserine, Balenine, and Ergothioneine: Impact of Histidine-Containing Compounds on Exercise Performance—A Narrative Review","doi":"10.3390/nu17050828","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Ergothioneine: An Antioxidative, Neuroprotective and Anti-Inflammatory Compound from Mushroom Residuals","doi":"10.3390/molecules30234621","risk_of_bias":"not appraised in public sidecar","directness":"primary"}]}}]}