Adjacent Evidence Brief: Longevity vitamin

Adjacent Evidence Brief: Longevity vitamin

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.

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.

Methods

Review type and protocol

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.

Information sources

Sources 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.

Search strategy

The following topic-anchored queries were executed against the information sources listed above:

• ergothioneine AND aging AND human
• ergothioneine AND older adults
• ergothioneine AND randomized controlled trial
• longevity vitamin AND aging AND human
• longevity vitamin AND older adults
• longevity vitamin AND randomized controlled trial
• antioxidant AND aging AND human
• antioxidant AND older adults
• antioxidant AND randomized controlled trial
• cell protection AND aging AND human

Eligibility criteria

• Sources whose primary content addresses ergothioneine.
• Sources with extractable quantitative or qualitative findings.
• Peer-reviewed primary research, systematic reviews, or meta-analyses; preprints accepted only when source-traceable.
• Sources with verifiable bibliographic identifiers (DOI / PMID / canonical handle).

Selection of sources of evidence

The 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.

source admission funnel

Admission bucket	n
Receipt candidate union	379
Classified source candidates	109
No extractable claims	107
None-only claim binding	26
Mixed partial-or-none claim-binding candidates	88
Partial-only claim-binding candidates	40
Strict high-confidence sources	9
Admitted final sources	22

Admission-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.

Exclusion reasons

• 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.

Data items

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.

Risk-of-bias appraisal

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.

Synthesis approach

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.

AI-use disclosure

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.

Accountability

Accountability 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.

Results

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.

Evidence domain	Corpus slice	Strongest signal	Directness	Main limitation
Contextual Adjacent Evidence	n=12; claims=244	no extracted directional signal in 11/12 sources	12 indirect	limited corpus depth in this outcome class
Cardiometabolic	n=3; claims=67	positive signal in 2/3 sources	2 indirect; 1 review	limited corpus depth in this outcome class
Population / prevalence	n=2; claims=32	no extracted directional signal in 2/2 sources	2 indirect	limited corpus depth in this outcome class
Immune and Inflammation	n=2; claims=66	no extracted directional signal in 2/2 sources	2 mechanistic	limited corpus depth in this outcome class
Mechanism	n=2; claims=147	positive signal in 1/2 sources	2 mechanistic	limited corpus depth in this outcome class
Frailty	n=1; claims=3	no extracted directional signal in 1/1 sources	1 indirect	single-source slice; hypothesis-generating

This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.

Contextual Adjacent Evidence Outcomes

12 included sources were assigned to this outcome class. Directional coding: null=11, positive=1. Directness coding: indirect=12.

Cardiometabolic Outcomes

3 included sources were assigned to this outcome class. Directional coding: null=1, positive=2. Directness coding: indirect=2, review=1.

Population / prevalence Outcomes

2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: indirect=2.

Immune Inflammation Outcomes

2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: mechanistic=2.

Mechanism Outcomes

2 included sources were assigned to this outcome class. Directional coding: null=1, positive=1. Directness coding: mechanistic=2.

Frailty Outcomes

1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.

Limitations

Verification note: Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main 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.

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.

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.

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.

Conclusion

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.

What This Synthesis Adds

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.

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.

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.

This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.

Boundary-Condition Matrix

Evidence domain	Direct sources	Indirect / mechanism sources	Direction profile	Interpretation boundary
cardiometabolic	0	3	null, positive	conflict-resolution gap
frailty	0	1	null	direct interventional hard-endpoint gap
mechanism	0	2	null, positive	conflict-resolution gap
contextual adjacent evidence	0	12	null, positive	conflict-resolution gap
deficiency prevalence	0	2	null	direct interventional hard-endpoint gap
immune and inflammation	0	2	null	direct interventional hard-endpoint gap

Evidence-Gap Priority

Priority	Gap	Rationale
P1	cardiometabolic: conflict-resolution gap	0 direct and 3 indirect sources; direction profile: null, positive
P2	frailty: direct interventional hard-endpoint gap	0 direct and 1 indirect source; direction profile: null
P3	mechanism: conflict-resolution gap	0 direct and 2 indirect sources; direction profile: null, positive
P4	contextual adjacent evidence: conflict-resolution gap	0 direct and 12 indirect sources; direction profile: null, positive
P5	deficiency prevalence: direct interventional hard-endpoint gap	0 direct and 2 indirect sources; direction profile: null

Next-Study Design Recommendation

The 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.

Evidence Snapshot

Source 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.

Source Classification Map

• In animal/preclinical evidence, Katsube 2024: outcome=Mechanism; directness=mechanistic; tier=C1.
• Gao 2026: outcome=Immune and Inflammation; directness=mechanistic; tier=C1.
• Ding 2026: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.
• Ding 2026b: outcome=Cardiometabolic; directness=indirect; tier=B2.
• Fu 2025: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.
• Liu 2026: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.
• Cadile 2025: outcome=Cardiometabolic; directness=indirect; tier=B2.
• Yu 2020: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.

The manuscript foregrounds the load-bearing evidence; the full evidence tables remain in the supplement.

Load-Bearing Included Studies

• Additional corpus sources included animal/preclinical evidence; Ding 2026; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=positive; representative statistic=P < 0.01.
• Ding 2026b; tier=B2; directness=indirect; endpoint=cardiometabolic; direction=positive; representative statistic=P < 0.0001.
• Fu 2025; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.
• Liu 2026; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.
• Cadile 2025; tier=B2; directness=indirect; endpoint=cardiometabolic; direction=positive.
• Yu 2020; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.
• Li 2026; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.
• Wang 2025; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.
• Cheah 2026; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.
• Meng 2025; tier=B2; directness=indirect; endpoint=deficiency prevalence; direction=null.

Source Classification Map

Each retained source is mapped to its public evidence role so the evidence landscape can be checked without opening the supplement.

• 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.
• 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.
• 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.
• Engineering Escherichia coli for Ergothioneine Production via Metabolic Engineering and Fermentation Optimization: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=31.
• 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.
• 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.
• 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.
• Enhanced production of ergothioneine in Aspergillus oryzae: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=23.
• 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.
• 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.
• Ergothioneine Attenuates Oxaliplatin-Induced Peripheral Neuropathy Without Compromising Antitumor Efficacy: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=16.
• 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.
• 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.
• Advances and prospects of ergothioneine in the treatment of cognitive frailty: outcome=frailty; directness=indirect; tier=B2; direction=null; claims=3.
• Ergothioneine Thione Spontaneously Binds to and Detaches from the Membrane Interphase: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=3.
• 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.
• Potential Protection Against Parkinson’s Disease by Ergothioneine—Nature’s Multifactorial Neuroprotectant: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=2.
• Ergothioneine: An Antioxidative, Neuroprotective and Anti-Inflammatory Compound from Mushroom Residuals: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=1.
• Ergothioneine promotes longevity and healthy aging in male mice: outcome=mechanism; directness=mechanistic; tier=C1; direction=positive; claims=138.
• 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.
• 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.
• 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.

Classification Criteria

• Outcome class is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.
• 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.
• 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.
• 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.

Load-Bearing Tensions

• 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
• Severity 4 null vs positive: Jedrejko 2025 vs Cadile 2025; Cadile 2025 (positive on cardiometabolic) vs Jedrejko 2025 (null on cardiometabolic) — partial conflict
• Severity 4 null vs positive: Jedrejko 2025 vs Ding 2026b; Ding 2026b (positive on cardiometabolic) vs Jedrejko 2025 (null on cardiometabolic) — partial conflict
• 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
• 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
• 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
• 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
• 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

In 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.

Additional corpus sources informed the synthesis without anchoring a foregrounded quantitative claim and are catalogued for completeness: Cao 2026, Gede 2025.

References

• Katsube 2024. Ergothioneine promotes longevity and healthy aging in male mice. GeroScience, 2024. DOI: 10.1007/s11357-024-01111-5. PMID: 38446314.
• 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.
• 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.
• 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.
• 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.
• Liu 2026. Engineering Escherichia coli for Ergothioneine Production via Metabolic Engineering and Fermentation Optimization. Microorganisms, 2026. DOI: 10.3390/microorganisms14051088. PMID: 42197473.
• 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.
• 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.
• Wang 2025. Enhanced production of ergothioneine in Aspergillus oryzae. Applied Microbiology and Biotechnology, 2025. DOI: 10.1007/s00253-025-13505-2. PMID: 40493205.
• 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.
• 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.
• 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.
• Yamada 2025. Ergothioneine Attenuates Oxaliplatin-Induced Peripheral Neuropathy Without Compromising Antitumor Efficacy. International Journal of Molecular Sciences, 2025. DOI: 10.3390/ijms262110263. PMID: 41226299.
• 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.
• 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.
• 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.
• 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.
• 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.
• Villalain 2025. Ergothioneine Thione Spontaneously Binds to and Detaches from the Membrane Interphase. Membranes, 2025. DOI: 10.3390/membranes15110328. PMID: 41295031.
• 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.
• Tng 2026. Potential Protection Against Parkinson’s Disease by Ergothioneine—Nature’s Multifactorial Neuroprotectant. Antioxidants, 2026. DOI: 10.3390/antiox15040519. PMID: 42072160.
• Harasym 2025. Ergothioneine: An Antioxidative, Neuroprotective and Anti-Inflammatory Compound from Mushroom Residuals. Molecules, 2025. DOI: 10.3390/molecules30234621. PMID: 41375218.

Background References

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).

• 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.
• 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.
• 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.