L-Ergothioneine

evidence_access

Primary abstract

experimental_model

16-hour pretreatment, then 6-hour cytokine challenge.

limitations

Cell-culture result; not established prevention of human atherosclerosis.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The endothelial surface expressed fewer adhesion signals.

primary_references

The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 16-hour pretreatment, then 6-hour cytokine challenge. · source_derived_draft · unverified_draft

## ergothioneine-adhesion-human-icam1 The endothelial surface expressed fewer adhesion signals. Ergothioneine at 0.1-0.3 mM reduced IL-1beta-induced intercellular adhesion molecule 1 expression in human aortic endothelial cells. Model: 16-hour pretreatment, then 6-hour cytokine challenge. Limitations: Cell-culture result; not established prevention of human atherosclerosis. Evidence access: Primary abstract The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194

evidence_access

Primary abstract

experimental_model

16-hour pretreatment, then 6-hour cytokine challenge.

limitations

Cell-culture result; not established prevention of human atherosclerosis.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The endothelial surface expressed fewer adhesion signals.

primary_references

The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 16-hour pretreatment, then 6-hour cytokine challenge. · source_derived_draft · unverified_draft

## ergothioneine-adhesion-human-vcam1 The endothelial surface expressed fewer adhesion signals. Ergothioneine at 0.1-0.3 mM reduced IL-1beta-induced vascular cell adhesion molecule 1 expression in human aortic endothelial cells. Model: 16-hour pretreatment, then 6-hour cytokine challenge. Limitations: Cell-culture result; not established prevention of human atherosclerosis. Evidence access: Primary abstract The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194

evidence_access

Primary abstract

experimental_model

16-hour pretreatment, then 6-hour cytokine challenge.

limitations

Cell-culture result; not established prevention of human atherosclerosis.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The endothelial surface expressed fewer adhesion signals.

primary_references

The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 16-hour pretreatment, then 6-hour cytokine challenge. · source_derived_draft · unverified_draft

## ergothioneine-adhesion-sele The endothelial surface expressed fewer adhesion signals. Ergothioneine at 0.1-0.3 mM reduced IL-1beta-induced E-selectin expression in human aortic endothelial cells. Model: 16-hour pretreatment, then 6-hour cytokine challenge. Limitations: Cell-culture result; not established prevention of human atherosclerosis. Evidence access: Primary abstract The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194

evidence_access

Primary abstract

experimental_model

Biochemical protein-activity assay.

limitations

Preparation-specific result; no clinical lung-disease benefit established.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Oxidant defense can preserve a protein function.

primary_references

Antioxidant action of ergothioneine: assessment of its ability to scavenge peroxynitrite. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9070285/ · DOI 10.1006/bbrc.1997.6109

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biochemical protein-activity assay. · source_derived_draft · unverified_draft

## ergothioneine-antiproteinase-protection Oxidant defense can preserve a protein function. Ergothioneine limited peroxynitrite-mediated inactivation of alpha-1-antiproteinase in vitro. Model: Biochemical protein-activity assay. Limitations: Preparation-specific result; no clinical lung-disease benefit established. Evidence access: Primary abstract Antioxidant action of ergothioneine: assessment of its ability to scavenge peroxynitrite. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9070285/ · DOI 10.1006/bbrc.1997.6109

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Affinity-resin depletion and bacterial competition in vitro.

limitations

Controlled medium depletion; not a human nutritional diagnosis or infection outcome.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

External supply and uptake machinery act together.

primary_references

An affinity-based depletion strategy for evaluating the effects of ergothioneine on bacterial physiology. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40068683/ · DOI 10.1016/j.chembiol.2025.02.004

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Affinity-resin depletion and bacterial competition in vitro. · source_derived_draft · unverified_draft

## ergothioneine-bacterial-availability External supply and uptake machinery act together. In ergothioneine-controlled culture medium, wild-type Helicobacter pylori required available ergothioneine to outcompete its transporter-deficient strain. Model: Affinity-resin depletion and bacterial competition in vitro. Limitations: Controlled medium depletion; not a human nutritional diagnosis or infection outcome. Evidence access: Primary abstract An affinity-based depletion strategy for evaluating the effects of ergothioneine on bacterial physiology. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40068683/ · DOI 10.1016/j.chembiol.2025.02.004

evidence_access

Primary abstract

experimental_model

In vitro five-step bacterial enzyme system.

limitations

Environmental gene distribution does not quantify human intestinal flux.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The sulfur and carbon skeleton enter separate products.

primary_references

In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33544568/ · DOI 10.1021/acschembio.0c00968

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In vitro five-step bacterial enzyme system. · source_derived_draft · unverified_draft

## ergothioneine-catabolic-products The sulfur and carbon skeleton enter separate products. The reconstituted bacterial pathway converted ergothioneine into glutamate, trimethylamine, hydrogen sulfide, carbon dioxide and ammonia. Model: In vitro five-step bacterial enzyme system. Limitations: Environmental gene distribution does not quantify human intestinal flux. Evidence access: Primary abstract In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33544568/ · DOI 10.1021/acschembio.0c00968

evidence_access

Primary abstract

experimental_model

Cisplatin-exposed mice; cell experiments examined antioxidant signaling.

limitations

Does not establish safe cotreatment in cancer patients or preserved antitumor efficacy.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Protection extended to an experimental hearing injury.

primary_references

The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss Through the Nrf2 Pathway. · 2025 · https://pubmed.ncbi.nlm.nih.gov/38770822/ · DOI 10.1089/ars.2024.0648

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cisplatin-exposed mice; cell experiments examined antioxidant signaling. · source_derived_draft · unverified_draft

## ergothioneine-cochlear-defense Protection extended to an experimental hearing injury. Ergothioneine reduced cisplatin-associated auditory threshold shifts by about 30 dB in the mouse comparison. Model: Cisplatin-exposed mice; cell experiments examined antioxidant signaling. Limitations: Does not establish safe cotreatment in cancer patients or preserved antitumor efficacy. Evidence access: Primary abstract The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss Through the Nrf2 Pathway. · 2025 · https://pubmed.ncbi.nlm.nih.gov/38770822/ · DOI 10.1089/ars.2024.0648

evidence_access

Primary abstract

experimental_model

Spectroscopy and competition against histidine/phenanthroline.

limitations

This is not demonstrated copper depletion in humans.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Copper oxidation state matters for binding.

primary_references

Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21047085/ · DOI 10.1021/tx100214t

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Spectroscopy and competition against histidine/phenanthroline. · source_derived_draft · unverified_draft

## ergothioneine-copper-binding Copper oxidation state matters for binding. Ergothioneine bound copper(I), rather than copper(II), and formed a redox-inactive complex in the tested chemical systems. Model: Spectroscopy and competition against histidine/phenanthroline. Limitations: This is not demonstrated copper depletion in humans. Evidence access: Primary abstract Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21047085/ · DOI 10.1021/tx100214t

evidence_access

Primary abstract

experimental_model

Human iPSC-derived neurons and neuroblastoma cells.

limitations

These correlated outcomes do not identify a single direct mitochondrial target.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Protection involved energy and dopamine-related cell markers.

primary_references

Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human iPSC-derived neurons and neuroblastoma cells. · source_derived_draft · unverified_draft

## ergothioneine-dopaminergic-atp Protection involved energy and dopamine-related cell markers. Ergothioneine limited ATP loss, protein carbonylation and tyrosine hydroxylase loss in the human 6-OHDA cell experiments. Model: Human iPSC-derived neurons and neuroblastoma cells. Limitations: These correlated outcomes do not identify a single direct mitochondrial target. Evidence access: Primary abstract Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693

evidence_access

Primary abstract

experimental_model

Human cell cultures exposed to 6-OHDA.

limitations

A neurotoxin model is not a Parkinson disease clinical trial.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Mitochondrial function was protected in a neuronal injury model.

primary_references

Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell cultures exposed to 6-OHDA. · source_derived_draft · unverified_draft

## ergothioneine-dopaminergic-mitochondria Mitochondrial function was protected in a neuronal injury model. Ergothioneine limited 6-hydroxydopamine-associated mitochondrial depolarization and mitochondrial ROS increases in human iPSC-derived dopaminergic neurons and SH-SY5Y cells. Model: Human cell cultures exposed to 6-OHDA. Limitations: A neurotoxin model is not a Parkinson disease clinical trial. Evidence access: Primary abstract Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693

evidence_access

Primary abstract

experimental_model

Cultured human endothelial cells.

limitations

Not evidence that ergothioneine supplies heme or iron.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Peroxide-removing machinery was part of the response.

primary_references

Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured human endothelial cells. · source_derived_draft · unverified_draft

## ergothioneine-endothelial-catalase Peroxide-removing machinery was part of the response. Ergothioneine increased catalase expression in human brain microvascular endothelial cells. Model: Cultured human endothelial cells. Limitations: Not evidence that ergothioneine supplies heme or iron. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

evidence_access

Primary abstract

experimental_model

Cultured human endothelial cells.

limitations

GSR expression does not establish increased flux or correction of riboflavin deficiency.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

This connects the response to glutathione recycling.

primary_references

Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured human endothelial cells. · source_derived_draft · unverified_draft

## ergothioneine-endothelial-gsr This connects the response to glutathione recycling. Ergothioneine increased glutathione reductase expression in human brain microvascular endothelial cells. Model: Cultured human endothelial cells. Limitations: GSR expression does not establish increased flux or correction of riboflavin deficiency. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

evidence_access

Primary abstract

experimental_model

Human brain microvascular endothelial cells.

limitations

Expression change, not demonstrated direct NOX1 inhibition.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The response included a lower oxidant-generating enzyme signal.

primary_references

Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human brain microvascular endothelial cells. · source_derived_draft · unverified_draft

## ergothioneine-endothelial-nox1 The response included a lower oxidant-generating enzyme signal. Ergothioneine decreased NOX1 expression in the human endothelial-cell study. Model: Human brain microvascular endothelial cells. Limitations: Expression change, not demonstrated direct NOX1 inhibition. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

evidence_access

Primary abstract

experimental_model

Human brain microvascular endothelial cells.

limitations

Abstract does not resolve SOD1 versus SOD2; do not infer a specific copper, zinc or manganese requirement from this result.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Another oxidant-handling enzyme accompanied the response.

primary_references

Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human brain microvascular endothelial cells. · source_derived_draft · unverified_draft

## ergothioneine-endothelial-sod Another oxidant-handling enzyme accompanied the response. Ergothioneine increased superoxide dismutase expression in the human endothelial-cell experiment. Model: Human brain microvascular endothelial cells. Limitations: Abstract does not resolve SOD1 versus SOD2; do not infer a specific copper, zinc or manganese requirement from this result. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

evidence_access

Primary abstract

experimental_model

Healthy-volunteer pharmacokinetic study.

limitations

Some downward trends were reported; trends are not confirmed treatment effects.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Measured uptake did not establish a broad biomarker benefit.

primary_references

Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27488221/ · DOI 10.1089/ars.2016.6778

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Healthy-volunteer pharmacokinetic study. · source_derived_draft · unverified_draft

## ergothioneine-human-oxidation-null Measured uptake did not establish a broad biomarker benefit. Most oxidative-damage and inflammation marker changes after pure ergothioneine administration were not statistically significant. Model: Healthy-volunteer pharmacokinetic study. Limitations: Some downward trends were reported; trends are not confirmed treatment effects. Evidence access: Primary abstract Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27488221/ · DOI 10.1089/ars.2016.6778

evidence_access

Primary abstract

experimental_model

Human oral uptake/pharmacokinetic study.

limitations

Blood measurements do not establish tissue-specific sufficiency.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The body retained much of the measured exposure.

primary_references

Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27488221/ · DOI 10.1089/ars.2016.6778

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human oral uptake/pharmacokinetic study. · source_derived_draft · unverified_draft

## ergothioneine-human-retention The body retained much of the measured exposure. Oral pure ergothioneine increased plasma and whole-blood concentrations in healthy volunteers, with urinary recovery below 4% of the administered amount. Model: Human oral uptake/pharmacokinetic study. Limitations: Blood measurements do not establish tissue-specific sufficiency. Evidence access: Primary abstract Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27488221/ · DOI 10.1089/ars.2016.6778

evidence_access

Primary abstract

experimental_model

Same lifelong mouse experiment as the lifespan record.

limitations

These associations do not identify one necessary mediator.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Several brain changes accompanied the behavioral result.

primary_references

Ergothioneine promotes longevity and healthy aging in male mice. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38446314/ · DOI 10.1007/s11357-024-01111-5

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same lifelong mouse experiment as the lifespan record. · source_derived_draft · unverified_draft

## ergothioneine-male-mouse-brain-aging Several brain changes accompanied the behavioral result. Ergothioneine-treated aging male mice showed preserved learning/memory with changes in neurogenesis, TDP43 aggregation and microglial phenotype. Model: Same lifelong mouse experiment as the lifespan record. Limitations: These associations do not identify one necessary mediator. Evidence access: Primary abstract Ergothioneine promotes longevity and healthy aging in male mice. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38446314/ · DOI 10.1007/s11357-024-01111-5

evidence_access

Primary abstract

experimental_model

Male-mouse lifelong drinking-water exposure.

limitations

Not demonstrated human longevity or a human dose; sex and lifelong exposure matter.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

An animal lifespan experiment supports further investigation.

primary_references

Ergothioneine promotes longevity and healthy aging in male mice. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38446314/ · DOI 10.1007/s11357-024-01111-5

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Male-mouse lifelong drinking-water exposure. · source_derived_draft · unverified_draft

## ergothioneine-male-mouse-lifespan An animal lifespan experiment supports further investigation. Daily oral ergothioneine at approximately 4-5 mg/kg from seven weeks of age extended lifespan in male mice. Model: Male-mouse lifelong drinking-water exposure. Limitations: Not demonstrated human longevity or a human dose; sex and lifelong exposure matter. Evidence access: Primary abstract Ergothioneine promotes longevity and healthy aging in male mice. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38446314/ · DOI 10.1007/s11357-024-01111-5

evidence_access

Primary abstract

experimental_model

Same one-year trial as the verbal-learning record.

limitations

Not an independent replication or proof of reduced neurodegeneration.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A blood injury marker accompanied the learning result.

primary_references

Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39544014/ · DOI 10.1177/13872877241291253

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same one-year trial as the verbal-learning record. · source_derived_draft · unverified_draft

## ergothioneine-mci-nfl A blood injury marker accompanied the learning result. Plasma neurofilament light remained stable in the ergothioneine arm of the 19-person MCI pilot while increasing in placebo recipients. Model: Same one-year trial as the verbal-learning record. Limitations: Not an independent replication or proof of reduced neurodegeneration. Evidence access: Primary abstract Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39544014/ · DOI 10.1177/13872877241291253

evidence_access

Primary abstract

experimental_model

Double-blind placebo-controlled pilot; adults at least 60 years old.

limitations

Small trial, not established dementia prevention; blood safety markers cannot exclude uncommon adverse effects.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A small human trial found a preliminary cognitive signal.

primary_references

Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39544014/ · DOI 10.1177/13872877241291253

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Double-blind placebo-controlled pilot; adults at least 60 years old. · source_derived_draft · unverified_draft

## ergothioneine-mci-pilot A small human trial found a preliminary cognitive signal. A 19-person randomized MCI pilot reported improved verbal-learning performance with 25 mg ergothioneine three times weekly for one year. Model: Double-blind placebo-controlled pilot; adults at least 60 years old. Limitations: Small trial, not established dementia prevention; blood safety markers cannot exclude uncommon adverse effects. Evidence access: Primary abstract Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39544014/ · DOI 10.1177/13872877241291253

evidence_access

Primary abstract

experimental_model

Human cultured-cell binding assay.

limitations

High in vitro exposure; the cells and adhesion markers belong to one study.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A functional adhesion measurement followed the expression changes.

primary_references

The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cultured-cell binding assay. · source_derived_draft · unverified_draft

## ergothioneine-monocyte-binding A functional adhesion measurement followed the expression changes. At 1-3 mM pretreatment, ergothioneine reduced U937 monocyte attachment to IL-1beta-stimulated human aortic endothelial cells. Model: Human cultured-cell binding assay. Limitations: High in vitro exposure; the cells and adhesion markers belong to one study. Evidence access: Primary abstract The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21091247/ · DOI 10.1089/jmf.2009.0194

evidence_access

Primary abstract

experimental_model

Mouse chondrocytes; 10 ng/mL IL-1beta; DMM mouse OA model.

limitations

Not human osteoarthritis treatment evidence; direct Sirt6 binding is not established by this abstract.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Cartilage cells provide another signaling context.

primary_references

Ergothioneine inhibits the progression of osteoarthritis via the Sirt6/NF-κB axis both in vitro and in vivo. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37156032/ · DOI 10.1016/j.intimp.2023.110211

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 368–374

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse chondrocytes; 10 ng/mL IL-1beta; DMM mouse OA model. · source_derived_draft · unverified_draft

## ergothioneine-mouse-cartilage Cartilage cells provide another signaling context. Ergothioneine treatment reduced inflammatory and matrix-degrading responses in IL-1beta-stimulated mouse chondrocytes through a reported Sirt6/NF-kappaB axis. Model: Mouse chondrocytes; 10 ng/mL IL-1beta; DMM mouse OA model. Limitations: Not human osteoarthritis treatment evidence; direct Sirt6 binding is not established by this abstract. Evidence access: Primary abstract Ergothioneine inhibits the progression of osteoarthritis via the Sirt6/NF-κB axis both in vitro and in vivo. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37156032/ · DOI 10.1016/j.intimp.2023.110211

evidence_access

Primary abstract

experimental_model

Mouse gut-brain study with supplementation.

limitations

Abstract supports inhibition but does not establish a direct binding site or human efficacy.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A phosphatase links the compound to a brain signaling pathway.

primary_references

Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 440–446

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse gut-brain study with supplementation. · source_derived_draft · unverified_draft

## ergothioneine-mouse-ptp1b-inhibition A phosphatase links the compound to a brain signaling pathway. Ergothioneine supplementation inhibited hippocampal PTP1B-associated signaling and mitigated synaptic/cognitive impairment in olanzapine-treated mice. Model: Mouse gut-brain study with supplementation. Limitations: Abstract supports inhibition but does not establish a direct binding site or human efficacy. Evidence access: Primary abstract Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020

evidence_access

Primary abstract

experimental_model

Chemical antioxidant assays.

limitations

Not evidence of removal of all reactive nitrogen species in vivo.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Protection includes a nitrogen-derived oxidant.

primary_references

Antioxidant action of ergothioneine: assessment of its ability to scavenge peroxynitrite. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9070285/ · DOI 10.1006/bbrc.1997.6109

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 152–158

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Chemical antioxidant assays. · source_derived_draft · unverified_draft

## ergothioneine-peroxynitrite-nitration Protection includes a nitrogen-derived oxidant. Ergothioneine protected against peroxynitrite-induced tyrosine nitration in vitro. Model: Chemical antioxidant assays. Limitations: Not evidence of removal of all reactive nitrogen species in vivo. Evidence access: Primary abstract Antioxidant action of ergothioneine: assessment of its ability to scavenge peroxynitrite. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9070285/ · DOI 10.1006/bbrc.1997.6109

evidence_access

Primary abstract

experimental_model

Human placental explants; comparison with NLRP3 inhibitor MCC950.

limitations

Ex vivo result, not a pregnancy intervention trial or proof of direct NLRP3 binding.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Inflammatory output fell in tissue studied outside the body.

primary_references

L-ergothioneine reduces mitochondrial-driven NLRP3 activation in gestational diabetes mellitus. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38029485/ · DOI 10.1016/j.jri.2023.104171

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 376–382

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human placental explants; comparison with NLRP3 inhibitor MCC950. · source_derived_draft · unverified_draft

## ergothioneine-placenta-il18 Inflammatory output fell in tissue studied outside the body. Adding 1 mM ergothioneine for 24 hours reduced IL-18 production in placental explants from women with gestational diabetes. Model: Human placental explants; comparison with NLRP3 inhibitor MCC950. Limitations: Ex vivo result, not a pregnancy intervention trial or proof of direct NLRP3 binding. Evidence access: Primary abstract L-ergothioneine reduces mitochondrial-driven NLRP3 activation in gestational diabetes mellitus. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38029485/ · DOI 10.1016/j.jri.2023.104171

evidence_access

Primary abstract

experimental_model

Isolated arteries and streptozotocin-diabetic rats.

limitations

Separate from human cardiovascular outcome evidence.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The vascular effect was also measured at the artery level.

primary_references

Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 312–318

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated arteries and streptozotocin-diabetic rats. · source_derived_draft · unverified_draft

## ergothioneine-rat-vascular-function The vascular effect was also measured at the artery level. Ergothioneine protected isolated rat basilar-artery relaxation during oxidative/high-glucose stress and improved responses after chronic treatment in diabetic rats. Model: Isolated arteries and streptozotocin-diabetic rats. Limitations: Separate from human cardiovascular outcome evidence. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

evidence_access

Primary abstract

experimental_model

LC-MS analysis with a thermal singlet-oxygen donor.

limitations

Product-based reaction model; not proof that this is its exclusive physiological function.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The sulfur atom changes the reaction route.

primary_references

Ergothioneine stands out from hercynine in the reaction with singlet oxygen: Resistance to glutathione and TRIS in the generation of specific products indicates high reactivity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29074402/ · DOI 10.1016/j.freeradbiomed.2017.10.372

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 136–142

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · LC-MS analysis with a thermal singlet-oxygen donor. · source_derived_draft · unverified_draft

## ergothioneine-singlet-oxygen The sulfur atom changes the reaction route. At pH 7.4, ergothioneine and hercynine generated different products after chemically generated singlet oxygen exposure. Model: LC-MS analysis with a thermal singlet-oxygen donor. Limitations: Product-based reaction model; not proof that this is its exclusive physiological function. Evidence access: Primary abstract Ergothioneine stands out from hercynine in the reaction with singlet oxygen: Resistance to glutathione and TRIS in the generation of specific products indicates high reactivity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29074402/ · DOI 10.1016/j.freeradbiomed.2017.10.372

evidence_access

Primary abstract

experimental_model

0.01-1 mM pretreatment; highest protection at 0.5 mM, then 25 mM glucose.

limitations

Abstract does not identify the endothelial species; protein nodes remain preparation-specific.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Stress protection involved cell-regulatory enzymes.

primary_references

Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27101740/ · DOI 10.1016/j.freeradbiomed.2016.04.013

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 352–358

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 0.01-1 mM pretreatment; highest protection at 0.5 mM, then 25 mM glucose. · source_derived_draft · unverified_draft

## ergothioneine-sirtuin-expression Stress protection involved cell-regulatory enzymes. In the endothelial high-glucose experiment, ergothioneine increased SIRT1/SIRT6 expression and reduced senescence-associated responses. Model: 0.01-1 mM pretreatment; highest protection at 0.5 mM, then 25 mM glucose. Limitations: Abstract does not identify the endothelial species; protein nodes remain preparation-specific. Evidence access: Primary abstract Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27101740/ · DOI 10.1016/j.freeradbiomed.2016.04.013

evidence_access

Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.

experimental_condition

substrate-omission baseline controls present · L-Ergothioneine Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

substrate-omission baseline controls omitted · 3-Mercaptopyruvate Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "ergothioneine with 3-mercaptopyruvate omitted", "comparator": "substrate-omission baseline controls", "endpoint": "detectable H2S signal", "effect_direction": "no_detected_change", "combination": "joint", "conditions": [{"entity_slug": "ergothioneine", "state": "present"}, {"entity_slug": "3-mercaptopyruvate", "state": "omitted"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Recombinant MPST and isolated mitochondria; substrate-omission controls.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

This control is not evidence of a human 3-mercaptopyruvate deficiency threshold or a universal inability to release sulfur in other systems.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

Ergothioneine alone did not replace the substrate.

primary_references

Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/

source_locator

Figures S3K-S3L; Results

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 65–65

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Recombinant MPST and isolated mitochondria; substrate-omission controls. · source_derived_draft · unverified_draft

Without 3-mercaptopyruvate, ergothioneine produced no detected H2S in the MPST and isolated-mitochondria assays.

evidence_access

Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.

experimental_model

Purified recombinant human MPST mitochondrial isoform 2.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Binding is measured; docking poses and proposed sulfur-acceptor chemistry are not equivalent to a measured covalent intermediate. Ambiguous OCR binding constants are omitted.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

organism

Homo sapiens

plain_language

Ergothioneine has an experimentally identified enzyme target.

primary_references

Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/

protein_isoform

MPST2 · Human MPST mitochondrial isoform 2

source_locator

Figure 3E; Figures S3E-S3G; Results

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 49–49

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Purified recombinant human MPST mitochondrial isoform 2. · source_derived_draft · unverified_draft

Ergothioneine bound purified human MPST2 in ITC and NMR experiments.

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.

experimental_condition

vehicle in MPST-deleted HeLa cells 500 micromolar, 72 hours · L-Ergothioneine Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

vehicle in MPST-deleted HeLa cells CRISPR-Cas9 deletion · Human mercaptopyruvate sulfurtransferase / MPST Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "ergothioneine in MPST-deleted HeLa cells", "comparator": "vehicle in MPST-deleted HeLa cells", "endpoint": "basal and maximal oxygen consumption", "effect_direction": "no_detected_change", "combination": "joint", "conditions": [{"entity_slug": "ergothioneine", "state": "500 micromolar, 72 hours"}, {"entity_slug": "mpst", "state": "CRISPR-Cas9 deletion"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

CRISPR-Cas9 MPST-deleted human HeLa cells; 500 micromolar ergothioneine for 72 hours.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

The comparison is ergothioneine versus vehicle within knockout cells. It does not show that every protective action requires MPST, or that human dietary low intake mimics knockout.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

Loss of the target removed this measured response.

primary_references

Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/

source_locator

Figures S2E-S2F; Results

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 81–81

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · CRISPR-Cas9 MPST-deleted human HeLa cells; 500 micromolar ergothioneine for 72 hours. · source_derived_draft · unverified_draft

MPST-deleted HeLa cells showed no significant respiratory increase with ergothioneine versus vehicle.

dose

500 micromolar

duration

72 hours

evidence_access

Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.

experimental_condition

vehicle in wild-type HeLa cells added · L-Ergothioneine Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "500 micromolar ergothioneine for 72 hours", "comparator": "vehicle in wild-type HeLa cells", "endpoint": "basal and maximal oxygen consumption", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "ergothioneine", "state": "added"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human HeLa cells; 500 micromolar ergothioneine for 72 hours, as stated unambiguously in supplementary Figure S2.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Cancer-cell culture at this exposure is not a clinical supplementation result or proof of a nutritional requirement.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

organism

Homo sapiens

plain_language

A human cell model showed a respiratory response.

primary_references

Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/

source_locator

Figure S2E, wild-type panels

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 73–73

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Human HeLa cells; 500 micromolar ergothioneine for 72 hours, as stated unambiguously in supplementary Figure S2. · source_derived_draft · unverified_draft

Ergothioneine increased basal and maximal respiration in wild-type human HeLa cells.

evidence_access

Primary indexed abstract; numerical exposures and tissue-specific methods not available in the abstract.

experimental_model

Isolated mitochondria, treated cells and animals; tissue and dose details not extracted from the abstract.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Mitochondrial localisation alone does not establish disease prevention or identify the membrane transporter.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

Cell entry and mitochondrial entry are separate transport questions.

primary_references

Fong et al. Ergothioneine and mitochondria: An important protective mechanism? DOI 10.1016/j.bbrc.2024.150269; PMID 38909533; https://pubmed.ncbi.nlm.nih.gov/38909533/

source_locator

Abstract

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 25–25

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Isolated mitochondria, treated cells and animals; tissue and dose details not extracted from the abstract. · source_derived_draft · unverified_draft

Mass spectrometry detected ergothioneine entry into isolated mitochondria and mitochondrial presence after treating cells and animals.

evidence_access

Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.

experimental_condition

control diet during the same training training · Voluntary wheel endurance training in mice Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

control diet during the same training diet enrichment · L-Ergothioneine Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "ergothioneine-enriched diet during endurance training", "comparator": "control diet during the same training", "endpoint": "wheel-running endurance performance", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "ergothioneine", "state": "diet enrichment"}, {"entity_slug": "mouse-voluntary-wheel-training", "state": "training"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Diet pre-feeding followed by voluntary wheel endurance training in mice.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Diet plus training is a joint setting, not an ergothioneine-only sedentary intervention or a demonstrated human effect. The dose is not converted into a human recommendation.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

The target pathway has a measured mouse functional outcome.

primary_references

Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/

source_locator

Figure 4B-D; Figures S5C-S5D

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 113–113

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Diet pre-feeding followed by voluntary wheel endurance training in mice. · source_derived_draft · unverified_draft

An ergothioneine-enriched diet improved endurance performance in trained wild-type mice.

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.

experimental_condition

control diet in trained Mpst-null mice training · Voluntary wheel endurance training in mice Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

control diet in trained Mpst-null mice diet enrichment · L-Ergothioneine Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

control diet in trained Mpst-null mice null · Mouse mercaptopyruvate sulfurtransferase / Mpst Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "ergothioneine-enriched diet in trained Mpst-null mice", "comparator": "control diet in trained Mpst-null mice", "endpoint": "endurance performance", "effect_direction": "no_detected_change", "combination": "joint", "conditions": [{"entity_slug": "ergothioneine", "state": "diet enrichment"}, {"entity_slug": "mouse-mpst", "state": "null"}, {"entity_slug": "mouse-voluntary-wheel-training", "state": "training"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Mpst-null mouse diet and training comparison.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

This is a within-genotype diet comparison during training, not evidence of dietary ergothioneine deficiency or a universal requirement for all ergothioneine effects.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

Removing the mouse target removed the diet-associated performance benefit.

primary_references

Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/

source_locator

Figure 4G-J; Figures S5F-S5K

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 121–121

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Mpst-null mouse diet and training comparison. · source_derived_draft · unverified_draft

Mpst-null mice showed no endurance advantage from the ergothioneine-enriched diet versus control diet.

assay_pH

11

evidence_access

Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.

experimental_condition

substrate conditions without ergothioneine added · L-Ergothioneine Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

substrate conditions without ergothioneine present · 3-Mercaptopyruvate Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "ergothioneine plus 3-mercaptopyruvate", "comparator": "substrate conditions without ergothioneine", "endpoint": "AzMC H2S-associated signal", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "ergothioneine", "state": "added"}, {"entity_slug": "3-mercaptopyruvate", "state": "present"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Purified human MPST activity assay using AzMC; reported buffer pH 11.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

The alkaline biochemical assay does not establish the same flux at physiological pH. Product signal is not proof of a structurally identified ergothioneine persulfide.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

Enzyme activation still needs its sulfur substrate.

primary_references

Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/

source_locator

Figure 3G; Figure S3K; STAR Methods, Recombinant MPST activity

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 57–57

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Purified human MPST activity assay using AzMC; reported buffer pH 11. · source_derived_draft · unverified_draft

Ergothioneine plus 3-mercaptopyruvate supported H2S release by recombinant human MPST.

evidence_access

Primary abstract

experimental_model

Enzymes from a strictly anaerobic green sulfur bacterium.

limitations

Anaerobic production does not establish a non-antioxidant function in humans.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

An alternative microbial route does not need oxygen.

primary_references

Anaerobic Origin of Ergothioneine. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28786519/ · DOI 10.1002/anie.201705932

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 216–222

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Enzymes from a strictly anaerobic green sulfur bacterium. · source_derived_draft · unverified_draft

## ergothioneine-anaerobic-synthesis An alternative microbial route does not need oxygen. Chlorobium limicola enzymes synthesized ergothioneine without oxygen through a rhodanese-like sulfur-transfer route. Model: Enzymes from a strictly anaerobic green sulfur bacterium. Limitations: Anaerobic production does not establish a non-antioxidant function in humans. Evidence access: Primary abstract Anaerobic Origin of Ergothioneine. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28786519/ · DOI 10.1002/anie.201705932

evidence_access

Primary abstract

experimental_model

Bacterial transporter genetics and structure.

limitations

Not evidence that oral ergothioneine worsens a human infection.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Some bacteria acquire ergothioneine instead of making it.

primary_references

Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36481738/ · DOI 10.1038/s41467-022-35277-3

transport_effect

raises Encoded an ergothioneine-specific ABC uptake transporter.

transport_pool

the bacterial cytoplasm Encoded an ergothioneine-specific ABC uptake transporter.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 232–238

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bacterial transporter genetics and structure. · source_derived_draft · unverified_draft

## ergothioneine-bacterial-uptake Some bacteria acquire ergothioneine instead of making it. Streptococcus pneumoniae spd_1642-1643 encoded an ergothioneine-specific ABC uptake transporter. Model: Bacterial transporter genetics and structure. Limitations: Not evidence that oral ergothioneine worsens a human infection. Evidence access: Primary abstract Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36481738/ · DOI 10.1038/s41467-022-35277-3

evidence_access

Primary abstract

experimental_model

Ligand-bound bacterial transporter-domain structure.

limitations

Substrate recognition is distinct from ATP-driven translocation.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A binding component selects the cargo.

primary_references

Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36481738/ · DOI 10.1038/s41467-022-35277-3

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ligand-bound bacterial transporter-domain structure. · source_derived_draft · unverified_draft

## ergothioneine-egtuc-binding A binding component selects the cargo. The Streptococcus pneumoniae EgtUC domain recognized the betaine and thioimidazole portions of ergothioneine with high specificity. Model: Ligand-bound bacterial transporter-domain structure. Limitations: Substrate recognition is distinct from ATP-driven translocation. Evidence access: Primary abstract Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36481738/ · DOI 10.1038/s41467-022-35277-3

evidence_access

Primary abstract

experimental_model

Five-step in vitro bacterial pathway reconstruction.

limitations

This study does not establish human gut production of TMAO from dietary ergothioneine.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Bacterial breakdown can release a methylated amine.

primary_references

In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33544568/ · DOI 10.1021/acschembio.0c00968

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Five-step in vitro bacterial pathway reconstruction. · source_derived_draft · unverified_draft

## ergothioneine-ergothionase Bacterial breakdown can release a methylated amine. The reconstituted bacterial catabolic pathway began with ergothionase and generated trimethylamine as one endpoint. Model: Five-step in vitro bacterial pathway reconstruction. Limitations: This study does not establish human gut production of TMAO from dietary ergothioneine. Evidence access: Primary abstract In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33544568/ · DOI 10.1021/acschembio.0c00968

evidence_access

Primary abstract

experimental_model

Cell-free singlet-oxygen chemistry.

limitations

Regeneration was proposed; its complete cellular enzymatic cycle was not established.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Glutathione changes the fate of oxidized ergothioneine.

primary_references

Ergothioneine stands out from hercynine in the reaction with singlet oxygen: Resistance to glutathione and TRIS in the generation of specific products indicates high reactivity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29074402/ · DOI 10.1016/j.freeradbiomed.2017.10.372

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free singlet-oxygen chemistry. · source_derived_draft · unverified_draft

## ergothioneine-glutathione-preservation Glutathione changes the fate of oxidized ergothioneine. In the singlet-oxygen assay, 5 mM glutathione almost abolished net ergothioneine loss even though formation of selected products persisted. Model: Cell-free singlet-oxygen chemistry. Limitations: Regeneration was proposed; its complete cellular enzymatic cycle was not established. Evidence access: Primary abstract Ergothioneine stands out from hercynine in the reaction with singlet oxygen: Resistance to glutathione and TRIS in the generation of specific products indicates high reactivity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29074402/ · DOI 10.1016/j.freeradbiomed.2017.10.372

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

11 hemodialysis, 12 advanced CKD and 12 control participants.

limitations

Removal measured; clinical benefit from replacing the solute remains untested.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Dialysis can bypass the kidney retention mechanism.

primary_references

Depletion by Hemodialysis of the Antioxidant Ergothioneine. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39869777/ · DOI 10.34067/KID.0000000645

trigger_kind

biomarker_context Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 11 hemodialysis, 12 advanced CKD and 12 control participants. · source_derived_draft · unverified_draft

## ergothioneine-hemodialysis-clearance Dialysis can bypass the kidney retention mechanism. Hemodialysis cleared ergothioneine at 146 +/- 36 mL/min in the measured cohort, exceeding urinary removal in controls and CKD participants. Model: 11 hemodialysis, 12 advanced CKD and 12 control participants. Limitations: Removal measured; clinical benefit from replacing the solute remains untested. Evidence access: Primary abstract Depletion by Hemodialysis of the Antioxidant Ergothioneine. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39869777/ · DOI 10.34067/KID.0000000645

evidence_access

Primary abstract

experimental_model

Metabolomic screening and uptake assays in transfected human cells.

limitations

Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

An additional carrier connects ergothioneine to the transport network.

primary_references

Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

transport_effect

raises Expression enabled uptake in HEK293 substrate assays.

transport_pool

the expressing cell Expression enabled uptake in HEK293 substrate assays.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft

## ergothioneine-slc22a15-ergo An additional carrier connects ergothioneine to the transport network. Human SLC22A15 expression enabled uptake of ergothioneine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

evidence_access

Primary abstract

experimental_model

Human transporter expressed in HEK293 cells.

limitations

Expression experiments do not quantify uptake in every human tissue.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A specific carrier lets cells build an ergothioneine pool.

primary_references

Discovery of the ergothioneine transporter. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15795384/ · DOI 10.1073/pnas.0408624102

transport_effect

raises Sodium-dependent ergothioneine uptake with intracellular retention.

transport_pool

the expressing cell Sodium-dependent ergothioneine uptake with intracellular retention.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transporter expressed in HEK293 cells. · source_derived_draft · unverified_draft

## ergothioneine-slc22a4-uptake A specific carrier lets cells build an ergothioneine pool. Expression of human SLC22A4 in HEK293 cells produced efficient, sodium-dependent ergothioneine uptake and intracellular retention. Model: Human transporter expressed in HEK293 cells. Limitations: Expression experiments do not quantify uptake in every human tissue. Evidence access: Primary abstract Discovery of the ergothioneine transporter. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15795384/ · DOI 10.1073/pnas.0408624102

evidence_access

Primary abstract

experimental_model

Human wild-type transporters expressed in HEK293 cells.

limitations

Related sequence does not establish substrate interchangeability.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The main carnitine carrier cannot be assumed to carry ergothioneine.

primary_references

Substrate discrimination by ergothioneine transporter SLC22A4 and carnitine transporter SLC22A5: gain-of-function by interchange of selected amino acids. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19814996/ · DOI 10.1016/j.bbamem.2009.09.019

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human wild-type transporters expressed in HEK293 cells. · source_derived_draft · unverified_draft

## ergothioneine-slc22a5-not-ergo The main carnitine carrier cannot be assumed to carry ergothioneine. Wild-type human SLC22A5 did not transport ergothioneine in the comparative expression assay. Model: Human wild-type transporters expressed in HEK293 cells. Limitations: Related sequence does not establish substrate interchangeability. Evidence access: Primary abstract Substrate discrimination by ergothioneine transporter SLC22A4 and carnitine transporter SLC22A5: gain-of-function by interchange of selected amino acids. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19814996/ · DOI 10.1016/j.bbamem.2009.09.019

evidence_access

Primary abstract

experimental_model

Rat transporter in HEK293 cells; uptake also examined in rat PC12 cells.

limitations

Rat measurements; no demonstrated benefit from increasing dietary salt.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The carrier couples entry to sodium.

primary_references

Functional characterization of ergothioneine transport by rat organic cation/carnitine transporter Octn1 (slc22a4). · 2008 · https://pubmed.ncbi.nlm.nih.gov/18670092/ · DOI 10.1248/bpb.31.1580

transport_effect

raises Saturable, pH-sensitive, sodium-dependent ergothioneine uptake.

transport_pool

the expressing cell Saturable, pH-sensitive, sodium-dependent ergothioneine uptake.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat transporter in HEK293 cells; uptake also examined in rat PC12 cells. · source_derived_draft · unverified_draft

## ergothioneine-sodium-coupling-rat The carrier couples entry to sodium. Rat Slc22a4-mediated ergothioneine uptake was saturable, pH-sensitive and sodium-dependent, with approximately 1:1 sodium:substrate stoichiometry. Model: Rat transporter in HEK293 cells; uptake also examined in rat PC12 cells. Limitations: Rat measurements; no demonstrated benefit from increasing dietary salt. Evidence access: Primary abstract Functional characterization of ergothioneine transport by rat organic cation/carnitine transporter Octn1 (slc22a4). · 2008 · https://pubmed.ncbi.nlm.nih.gov/18670092/ · DOI 10.1248/bpb.31.1580

evidence_access

Primary abstract

experimental_model

Cell-free reaction; reported rate constant 6.3 x 10^8 M^-1 s^-1.

limitations

Chemical kinetics do not establish tissue flux or a required supplement combination.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Vitamin C can repair an oxidized ergothioneine intermediate.

primary_references

One-electron oxidation of ergothioneine and analogues investigated by pulse radiolysis: redox reaction involving ergothioneine and vitamin C. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8615839/ · DOI 10.1042/bj3150625

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free reaction; reported rate constant 6.3 x 10^8 M^-1 s^-1. · source_derived_draft · unverified_draft

## ergothioneine-ascorbate-repair Vitamin C can repair an oxidized ergothioneine intermediate. In pulse-radiolysis assays, ascorbate rapidly reduced the one-electron-oxidized ergothioneine transient back toward ergothioneine, forming ascorbyl radicals. Model: Cell-free reaction; reported rate constant 6.3 x 10^8 M^-1 s^-1. Limitations: Chemical kinetics do not establish tissue flux or a required supplement combination. Evidence access: Primary abstract One-electron oxidation of ergothioneine and analogues investigated by pulse radiolysis: redox reaction involving ergothioneine and vitamin C. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8615839/ · DOI 10.1042/bj3150625

evidence_access

Primary abstract

experimental_model

Purified bacterial pathway.

limitations

Does not mean iron supplements increase human synthesis.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Iron supports a microbial synthesis enzyme.

primary_references

In vitro reconstitution of Mycobacterial ergothioneine biosynthesis. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20420449/ · DOI 10.1021/ja101721e

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified bacterial pathway. · source_derived_draft · unverified_draft

## ergothioneine-bacterial-iron-step Iron supports a microbial synthesis enzyme. Reconstituted Mycobacterium smegmatis biosynthesis required an iron(II)-dependent oxidative sulfurization step. Model: Purified bacterial pathway. Limitations: Does not mean iron supplements increase human synthesis. Evidence access: Primary abstract In vitro reconstitution of Mycobacterial ergothioneine biosynthesis. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20420449/ · DOI 10.1021/ja101721e

evidence_access

Primary abstract

experimental_model

Enzyme structure within the reconstituted bacterial pathway.

limitations

Do not substitute a human histidine-degradation enzyme for this bacterial activity.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A related-looking enzyme handles a different intermediate.

primary_references

In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33544568/ · DOI 10.1021/acschembio.0c00968

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Enzyme structure within the reconstituted bacterial pathway. · source_derived_draft · unverified_draft

## ergothioneine-catabolic-hydratase A related-looking enzyme handles a different intermediate. Paenibacillus thiourocanate hydratase had structural features distinguishing it from histidine-pathway urocanate hydratases. Model: Enzyme structure within the reconstituted bacterial pathway. Limitations: Do not substitute a human histidine-degradation enzyme for this bacterial activity. Evidence access: Primary abstract In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33544568/ · DOI 10.1021/acschembio.0c00968

evidence_access

Primary abstract

experimental_model

Cell-free copper/ascorbate and copper/peroxide systems.

limitations

Exposure and free-metal speciation limit extrapolation.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Binding the catalyst can protect several targets.

primary_references

Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21047085/ · DOI 10.1021/tx100214t

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free copper/ascorbate and copper/peroxide systems. · source_derived_draft · unverified_draft

## ergothioneine-copper-oxidation Binding the catalyst can protect several targets. Ergothioneine at 0.1-1 mM protected DNA and albumin against 0.1 mM copper with ascorbate or peroxide. Model: Cell-free copper/ascorbate and copper/peroxide systems. Limitations: Exposure and free-metal speciation limit extrapolation. Evidence access: Primary abstract Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21047085/ · DOI 10.1021/tx100214t

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Malmo Diet and Cancer observational cohort; adjusted associations.

limitations

Healthy dietary pattern and other confounding prevent a causal supplement conclusion.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A higher blood marker tracked better long-term outcomes.

primary_references

Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31672783/ · DOI 10.1136/heartjnl-2019-315485

trigger_kind

biomarker_context Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Malmo Diet and Cancer observational cohort; adjusted associations. · source_derived_draft · unverified_draft

## ergothioneine-cv-observational A higher blood marker tracked better long-term outcomes. In 3236 initially CVD- and diabetes-free participants, higher baseline ergothioneine predicted lower coronary disease and mortality over a median 21.4 years. Model: Malmo Diet and Cancer observational cohort; adjusted associations. Limitations: Healthy dietary pattern and other confounding prevent a causal supplement conclusion. Evidence access: Primary abstract Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31672783/ · DOI 10.1136/heartjnl-2019-315485

evidence_access

Primary abstract

experimental_model

Bacterial enzyme crystal structure and kinetics.

limitations

Do not project this microbial enzyme onto human tissues.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Different machinery can produce the same compound.

primary_references

Structural and Mechanistic Basis for Anaerobic Ergothioneine Biosynthesis. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30943021/ · DOI 10.1021/jacs.8b12596

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bacterial enzyme crystal structure and kinetics. · source_derived_draft · unverified_draft

## ergothioneine-eanb-mechanism Different machinery can produce the same compound. Structural and kinetic analyses of Chlorobium limicola EanB supported sulfurization of hercynine in anaerobic ergothioneine synthesis. Model: Bacterial enzyme crystal structure and kinetics. Limitations: Do not project this microbial enzyme onto human tissues. Evidence access: Primary abstract Structural and Mechanistic Basis for Anaerobic Ergothioneine Biosynthesis. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30943021/ · DOI 10.1021/jacs.8b12596

evidence_access

Primary full text, pathway background citing original reconstitution

experimental_model

Pathway description in the primary EgtE paper, citing the original reconstitution.

limitations

This step is cited background, not a new EgtA experiment in this paper; microbial and human pathways remain separate.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A separately encoded enzyme prepares the sulfur donor.

primary_references

Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pathway description in the primary EgtE paper, citing the original reconstitution. · source_derived_draft · unverified_draft

## ergothioneine-egta-precursor A separately encoded enzyme prepares the sulfur donor. The described Mycobacterium smegmatis pathway uses EgtA to condense glutamate and cysteine into gamma-glutamylcysteine. Model: Pathway description in the primary EgtE paper, citing the original reconstitution. Limitations: This step is cited background, not a new EgtA experiment in this paper; microbial and human pathways remain separate. Evidence access: Primary full text, pathway background citing original reconstitution Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870

evidence_access

Primary abstract

experimental_model

Crystal structure and enzyme mechanism study.

limitations

Non-heme iron coordination supports a proposed radical mechanism, not direct observation of every intermediate.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A cysteine-containing precursor supplies sulfur.

primary_references

Structure of the sulfoxide synthase EgtB from the ergothioneine biosynthetic pathway. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25597398/ · DOI 10.1002/anie.201410045

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Crystal structure and enzyme mechanism study. · source_derived_draft · unverified_draft

## ergothioneine-egtb-sulfur-donor A cysteine-containing precursor supplies sulfur. Mycobacterium thermoresistibile EgtB coupled gamma-glutamylcysteine to hercynine through an oxygen-dependent C-S bond-forming reaction. Model: Crystal structure and enzyme mechanism study. Limitations: Non-heme iron coordination supports a proposed radical mechanism, not direct observation of every intermediate. Evidence access: Primary abstract Structure of the sulfoxide synthase EgtB from the ergothioneine biosynthetic pathway. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25597398/ · DOI 10.1002/anie.201410045

evidence_access

Primary abstract

experimental_model

Substrate-bound bacterial EgtC structure.

limitations

Not human glutathione breakdown; EgtC homologs can have other functions.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A separate enzyme removes the carrier part of the sulfur donor.

primary_references

Structure of the Ergothioneine-Biosynthesis Amidohydrolase EgtC. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26079795/ · DOI 10.1002/cbic.201500168

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Substrate-bound bacterial EgtC structure. · source_derived_draft · unverified_draft

## ergothioneine-egtc-amide A separate enzyme removes the carrier part of the sulfur donor. Mycobacterium smegmatis EgtC removes the glutamyl portion of the ergothioneine-pathway sulfur adduct. Model: Substrate-bound bacterial EgtC structure. Limitations: Not human glutathione breakdown; EgtC homologs can have other functions. Evidence access: Primary abstract Structure of the Ergothioneine-Biosynthesis Amidohydrolase EgtC. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26079795/ · DOI 10.1002/cbic.201500168

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mutant complementation in the 2015 study.

limitations

A phosphomimetic mutation is not direct evidence of physiological phosphorylation, particularly at an active-site residue.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Changing this residue disrupted restoration of synthesis.

primary_references

Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26229105/ · DOI 10.1074/jbc.M115.648642

trigger_kind

machinery_impairment Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mutant complementation in the 2015 study. · source_derived_draft · unverified_draft

## ergothioneine-egtd-mutant Changing this residue disrupted restoration of synthesis. EgtD T213E failed to restore ergothioneine synthesis in a Mycobacterium tuberculosis egtD-deletion strain, unlike T213A. Model: Mutant complementation in the 2015 study. Limitations: A phosphomimetic mutation is not direct evidence of physiological phosphorylation, particularly at an active-site residue. Evidence access: Primary abstract Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26229105/ · DOI 10.1074/jbc.M115.648642

evidence_access

Primary abstract

experimental_model

Apo and ligand-bound enzyme structures.

limitations

No evidence that human ergothioneine consumption drains SAM; humans lack this established synthesis pathway.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The microbial synthesis branch connects to methyl-donor chemistry.

primary_references

Structural insights into the histidine trimethylation activity of EgtD from Mycobacterium smegmatis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25251321/ · DOI 10.1016/j.bbrc.2014.09.058

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Apo and ligand-bound enzyme structures. · source_derived_draft · unverified_draft

## ergothioneine-egtd-sam The microbial synthesis branch connects to methyl-donor chemistry. Mycobacterium smegmatis EgtD uses SAM-dependent methyl transfer to convert histidine into hercynine. Model: Apo and ligand-bound enzyme structures. Limitations: No evidence that human ergothioneine consumption drains SAM; humans lack this established synthesis pathway. Evidence access: Primary abstract Structural insights into the histidine trimethylation activity of EgtD from Mycobacterium smegmatis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25251321/ · DOI 10.1016/j.bbrc.2014.09.058

evidence_access

Primary abstract

experimental_model

Purified bacterial EgtE with thioether/sulfoxide substrates and reductant comparisons.

limitations

No demonstrated B6-dependent synthesis in human cells.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The active vitamin B6 cofactor participates in microbial synthesis.

primary_references

Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 200–206

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified bacterial EgtE with thioether/sulfoxide substrates and reductant comparisons. · source_derived_draft · unverified_draft

## ergothioneine-egte-plp The active vitamin B6 cofactor participates in microbial synthesis. Purified Mycobacterium smegmatis EgtE catalyzed a PLP-dependent C-S lyase reaction in ergothioneine biosynthesis. Model: Purified bacterial EgtE with thioether/sulfoxide substrates and reductant comparisons. Limitations: No demonstrated B6-dependent synthesis in human cells. Evidence access: Primary abstract Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870

evidence_access

Primary abstract

experimental_model

In vitro enzyme characterization.

limitations

Intermediate assignment is mechanistically supported; full intracellular flux was not measured.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Sulfur is retained while the cysteine carbon scaffold is removed.

primary_references

Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 208–214

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In vitro enzyme characterization. · source_derived_draft · unverified_draft

## ergothioneine-egte-sulfenic Sulfur is retained while the cysteine carbon scaffold is removed. Biochemical characterization of Mycobacterium smegmatis EgtE supported sulfoxide substrate processing through a sulfenic-acid intermediate toward ergothioneine. Model: In vitro enzyme characterization. Limitations: Intermediate assignment is mechanistically supported; full intracellular flux was not measured. Evidence access: Primary abstract Mechanistic studies of a novel C-S lyase in ergothioneine biosynthesis: the involvement of a sulfenic acid intermediate. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26149121/ · DOI 10.1038/srep11870

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Cultured human cells challenged with oxidant generators or high glucose.

limitations

Transport dependence does not locate ergothioneine inside mitochondria.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Protection depended on getting the compound inside.

primary_references

Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 280–286

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured human cells challenged with oxidant generators or high glucose. · source_derived_draft · unverified_draft

## ergothioneine-endothelial-entry-loss Protection depended on getting the compound inside. SLC22A4 siRNA reduced ergothioneine uptake and abolished its cytoprotection in human brain microvascular endothelial cells. Model: Cultured human cells challenged with oxidant generators or high glucose. Limitations: Transport dependence does not locate ergothioneine inside mitochondria. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human cultured cells with transporter knockdown.

limitations

Not a human dietary deficiency syndrome; linked outcomes share one study.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The consequences extend beyond DNA.

primary_references

The unusual amino acid L-ergothioneine is a physiologic cytoprotectant. · 2010 · https://pubmed.ncbi.nlm.nih.gov/19911007/ · DOI 10.1038/cdd.2009.163

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 88–94

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cultured cells with transporter knockdown. · source_derived_draft · unverified_draft

## ergothioneine-hela-lipid-loss The consequences extend beyond DNA. SLC22A4-depleted human cells showed increased protein oxidation and lipid peroxidation under oxidative stress. Model: Human cultured cells with transporter knockdown. Limitations: Not a human dietary deficiency syndrome; linked outcomes share one study. Evidence access: Primary abstract The unusual amino acid L-ergothioneine is a physiologic cytoprotectant. · 2010 · https://pubmed.ncbi.nlm.nih.gov/19911007/ · DOI 10.1038/cdd.2009.163

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human cell RNA-interference and oxidant challenges.

limitations

Does not establish the identity of a mitochondrial membrane transporter.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Removing the entry route weakens cellular protection.

primary_references

The unusual amino acid L-ergothioneine is a physiologic cytoprotectant. · 2010 · https://pubmed.ncbi.nlm.nih.gov/19911007/ · DOI 10.1038/cdd.2009.163

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 80–86

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell RNA-interference and oxidant challenges. · source_derived_draft · unverified_draft

## ergothioneine-hela-transporter-loss Removing the entry route weakens cellular protection. RNA-interference depletion of SLC22A4 made human cultured cells more susceptible to oxidant-associated mitochondrial DNA damage. Model: Human cell RNA-interference and oxidant challenges. Limitations: Does not establish the identity of a mitochondrial membrane transporter. Evidence access: Primary abstract The unusual amino acid L-ergothioneine is a physiologic cytoprotectant. · 2010 · https://pubmed.ncbi.nlm.nih.gov/19911007/ · DOI 10.1038/cdd.2009.163

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Cross-group measurements plus clearance assessment.

limitations

Diet, disease and clearance may all contribute; no universal deficiency cutoff.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The blood-cell pool was substantially lower.

primary_references

Depletion by Hemodialysis of the Antioxidant Ergothioneine. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39869777/ · DOI 10.34067/KID.0000000645

trigger_kind

biomarker_context Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 536–542

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cross-group measurements plus clearance assessment. · source_derived_draft · unverified_draft

## ergothioneine-hemodialysis-rbc The blood-cell pool was substantially lower. Erythrocyte ergothioneine averaged 8% of control levels in hemodialysis participants and 24% in advanced CKD participants. Model: Cross-group measurements plus clearance assessment. Limitations: Diet, disease and clearance may all contribute; no universal deficiency cutoff. Evidence access: Primary abstract Depletion by Hemodialysis of the Antioxidant Ergothioneine. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39869777/ · DOI 10.34067/KID.0000000645

evidence_access

Primary abstract

experimental_model

Recombinant bacterial enzyme pathway.

limitations

Humans have no established equivalent ergothioneine biosynthetic pathway.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Microbes first modify histidine before adding sulfur.

primary_references

In vitro reconstitution of Mycobacterial ergothioneine biosynthesis. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20420449/ · DOI 10.1021/ja101721e

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 168–174

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant bacterial enzyme pathway. · source_derived_draft · unverified_draft

## ergothioneine-histidine-methylation Microbes first modify histidine before adding sulfur. Reconstituted Mycobacterium smegmatis biosynthesis used a methyltransferase to add three methyl groups to the histidine alpha-amino group, producing hercynine. Model: Recombinant bacterial enzyme pathway. Limitations: Humans have no established equivalent ergothioneine biosynthetic pathway. Evidence access: Primary abstract In vitro reconstitution of Mycobacterial ergothioneine biosynthesis. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20420449/ · DOI 10.1021/ja101721e

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human oral-administration study.

limitations

Correlation does not identify the human enzymes or prove every conversion direction.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Related molecules may help trace its fate.

primary_references

Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27488221/ · DOI 10.1089/ars.2016.6778

trigger_kind

biomarker_context Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 472–478

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human oral-administration study. · source_derived_draft · unverified_draft

## ergothioneine-human-metabolite-markers Related molecules may help trace its fate. Human whole-blood ergothioneine correlated with hercynine and S-methyl-ergothioneine, consistent with possible metabolism. Model: Human oral-administration study. Limitations: Correlation does not identify the human enzymes or prove every conversion direction. Evidence access: Primary abstract Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27488221/ · DOI 10.1089/ars.2016.6778

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Cell-type-specific mouse genetic intervention.

limitations

Does not mean ergothioneine reproduces every consequence of genetic deletion.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Removing the proposed target tested its role in the injury pathway.

primary_references

Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 448–454

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-type-specific mouse genetic intervention. · source_derived_draft · unverified_draft

## ergothioneine-mouse-ptp1b-deletion Removing the proposed target tested its role in the injury pathway. Hippocampal neuronal-specific PTP1B deletion prevented olanzapine-induced synaptic and cognitive deficits in mice. Model: Cell-type-specific mouse genetic intervention. Limitations: Does not mean ergothioneine reproduces every consequence of genetic deletion. Evidence access: Primary abstract Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020

evidence_access

Primary abstract

experimental_model

Acute human mushroom-meal study.

limitations

Grams refer to mushroom powder, not pure ergothioneine; food-matrix effects cannot be assigned to this compound alone.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Food-derived ergothioneine reaches the blood-cell pool.

primary_references

The bioavailability of ergothioneine from mushrooms (Agaricus bisporus) and the acute effects on antioxidant capacity and biomarkers of inflammation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22230474/ · DOI 10.1016/j.ypmed.2011.12.028

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 456–462

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Acute human mushroom-meal study. · source_derived_draft · unverified_draft

## ergothioneine-mushroom-bioavailability Food-derived ergothioneine reaches the blood-cell pool. In a 10-man crossover study, mushroom meals containing 8 or 16 grams of mushroom powder produced postprandial erythrocyte ergothioneine uptake. Model: Acute human mushroom-meal study. Limitations: Grams refer to mushroom powder, not pure ergothioneine; food-matrix effects cannot be assigned to this compound alone. Evidence access: Primary abstract The bioavailability of ergothioneine from mushrooms (Agaricus bisporus) and the acute effects on antioxidant capacity and biomarkers of inflammation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22230474/ · DOI 10.1016/j.ypmed.2011.12.028

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

6-OHDA challenge with verapamil hydrochloride.

limitations

Verapamil is nonspecific; this experiment alone cannot prove exclusive SLC22A4 mediation.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A transport-inhibiting drug weakened protection.

primary_references

Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 400–406

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 6-OHDA challenge with verapamil hydrochloride. · source_derived_draft · unverified_draft

## ergothioneine-neuronal-verapamil A transport-inhibiting drug weakened protection. Verapamil abrogated ergothioneine protection in the human neuronal-cell study. Model: 6-OHDA challenge with verapamil hydrochloride. Limitations: Verapamil is nonspecific; this experiment alone cannot prove exclusive SLC22A4 mediation. Evidence access: Primary abstract Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Cell and mouse ototoxicity study; abstract does not resolve species of the silenced preparation.

limitations

No direct NRF2 binding demonstrated; preparation-specific node avoids assigning this silencing result to a human protein.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Disabling antioxidant signaling weakened protection.

primary_references

The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss Through the Nrf2 Pathway. · 2025 · https://pubmed.ncbi.nlm.nih.gov/38770822/ · DOI 10.1089/ars.2024.0648

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 416–422

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell and mouse ototoxicity study; abstract does not resolve species of the silenced preparation. · source_derived_draft · unverified_draft

## ergothioneine-nrf2-dependence Disabling antioxidant signaling weakened protection. Nrf2 silencing supported Nrf2 dependence of ergothioneine protection in the cisplatin ototoxicity study. Model: Cell and mouse ototoxicity study; abstract does not resolve species of the silenced preparation. Limitations: No direct NRF2 binding demonstrated; preparation-specific node avoids assigning this silencing result to a human protein. Evidence access: Primary abstract The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss Through the Nrf2 Pathway. · 2025 · https://pubmed.ncbi.nlm.nih.gov/38770822/ · DOI 10.1089/ars.2024.0648

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Patient blood comparison within a mainly mechanistic animal study.

limitations

Not evidence that supplementation improves cognition in these patients.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A human blood observation accompanied the mouse work.

primary_references

Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020

trigger_kind

biomarker_context Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 432–438

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Patient blood comparison within a mainly mechanistic animal study. · source_derived_draft · unverified_draft

## ergothioneine-olanzapine-human-marker A human blood observation accompanied the mouse work. The study also found lower blood ergothioneine in olanzapine-treated patients. Model: Patient blood comparison within a mainly mechanistic animal study. Limitations: Not evidence that supplementation improves cognition in these patients. Evidence access: Primary abstract Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse treatment, multi-omics and microbiota-transplant experiments.

limitations

Association among microbial taxa and metabolite levels does not resolve every biosynthetic flux.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A medicine-associated ecosystem change coincided with a lower pool.

primary_references

Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020

trigger_kind

biomarker_context Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 424–430

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse treatment, multi-omics and microbiota-transplant experiments. · source_derived_draft · unverified_draft

## ergothioneine-olanzapine-mouse-pool A medicine-associated ecosystem change coincided with a lower pool. Chronic olanzapine treatment in mice reduced blood and brain ergothioneine alongside altered microbiota and cognitive deficits. Model: Mouse treatment, multi-omics and microbiota-transplant experiments. Limitations: Association among microbial taxa and metabolite levels does not resolve every biosynthetic flux. Evidence access: Primary abstract Gut microbiota-derived ergothioneine alleviates antipsychotic-induced synaptic and cognitive impairments. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42013837/ · DOI 10.1016/j.chom.2026.03.020

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

16 peritoneal dialysis, 16 hemodialysis and 15 controls.

limitations

Percentages belong to this cohort, not a contradiction of the earlier study; replacement benefits remain unknown.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Different dialysis routes were associated with different depletion.

primary_references

Ergothioneine Depletion in Peritoneal Dialysis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41411056/ · DOI 10.34067/KID.0000001105

trigger_kind

biomarker_context Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 544–550

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 16 peritoneal dialysis, 16 hemodialysis and 15 controls. · source_derived_draft · unverified_draft

## ergothioneine-peritoneal-rbc Different dialysis routes were associated with different depletion. In a later comparison, erythrocyte ergothioneine averaged 34% of control levels during peritoneal dialysis versus 10% during hemodialysis. Model: 16 peritoneal dialysis, 16 hemodialysis and 15 controls. Limitations: Percentages belong to this cohort, not a contradiction of the earlier study; replacement benefits remain unknown. Evidence access: Primary abstract Ergothioneine Depletion in Peritoneal Dialysis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41411056/ · DOI 10.34067/KID.0000001105

evidence_access

Primary abstract

experimental_model

In vitro kinase reassessment; active-site accessibility considered structurally.

limitations

A negative in vitro result does not alone exclude every cellular condition; matched protocols are needed.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

A later study did not reproduce the proposed kinase reaction.

primary_references

Reexamination of the Ergothioneine Biosynthetic Methyltransferase EgtD from Mycobacterium tuberculosis as a Protein Kinase Substrate. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32614492/ · DOI 10.1002/cbic.202000232

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 584–590

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In vitro kinase reassessment; active-site accessibility considered structurally. · source_derived_draft · unverified_draft

## ergothioneine-pknd-negative A later study did not reproduce the proposed kinase reaction. The 2020 reexamination found that Mycobacterium tuberculosis EgtD was not a PknD substrate under its in vitro conditions. Model: In vitro kinase reassessment; active-site accessibility considered structurally. Limitations: A negative in vitro result does not alone exclude every cellular condition; matched protocols are needed. Evidence access: Primary abstract Reexamination of the Ergothioneine Biosynthetic Methyltransferase EgtD from Mycobacterium tuberculosis as a Protein Kinase Substrate. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32614492/ · DOI 10.1002/cbic.202000232

evidence_access

Primary abstract

experimental_model

Bacterial kinase assays and cell-based phosphorylation evidence.

limitations

The kinase-substrate assignment was directly challenged by the 2020 reexamination; not settled regulation.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

One study reported a kinase-controlled synthesis switch.

primary_references

Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26229105/ · DOI 10.1074/jbc.M115.648642

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 576–582

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bacterial kinase assays and cell-based phosphorylation evidence. · source_derived_draft · unverified_draft

## ergothioneine-pknd-positive One study reported a kinase-controlled synthesis switch. The 2015 Mycobacterium tuberculosis study reported PknD phosphorylation of EgtD at Thr213 in vitro and in a cell-based system. Model: Bacterial kinase assays and cell-based phosphorylation evidence. Limitations: The kinase-substrate assignment was directly challenged by the 2020 reexamination; not settled regulation. Evidence access: Primary abstract Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26229105/ · DOI 10.1074/jbc.M115.648642

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Endothelial-cell pharmacological and genetic perturbation.

limitations

Dependence is stronger than expression association, but does not show direct binding or supply of NAD.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Blocking the regulatory machinery removed protection.

primary_references

Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27101740/ · DOI 10.1016/j.freeradbiomed.2016.04.013

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 360–366

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Endothelial-cell pharmacological and genetic perturbation. · source_derived_draft · unverified_draft

## ergothioneine-sirtuin-dependence Blocking the regulatory machinery removed protection. SIRT1 activity inhibition or SIRT6 siRNA abolished ergothioneine protection against high-glucose-induced endothelial senescence. Model: Endothelial-cell pharmacological and genetic perturbation. Limitations: Dependence is stronger than expression association, but does not show direct binding or supply of NAD. Evidence access: Primary abstract Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27101740/ · DOI 10.1016/j.freeradbiomed.2016.04.013

evidence_access

Primary abstract

experimental_model

Metabolomic screening and uptake assays in transfected human cells.

limitations

Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

An additional carrier connects carnitine to the transport network.

primary_references

Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

transport_effect

raises Expression enabled uptake in HEK293 substrate assays.

transport_pool

the expressing cell Expression enabled uptake in HEK293 substrate assays.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 64–70

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft

## ergothioneine-slc22a15-carnitine An additional carrier connects carnitine to the transport network. Human SLC22A15 expression enabled uptake of carnitine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

evidence_access

Primary abstract

experimental_model

Metabolomic screening and uptake assays in transfected human cells.

limitations

Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

An additional carrier connects carnosine to the transport network.

primary_references

Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

transport_effect

raises Expression enabled uptake in HEK293 substrate assays.

transport_pool

the expressing cell Expression enabled uptake in HEK293 substrate assays.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 56–62

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft

## ergothioneine-slc22a15-carnosine An additional carrier connects carnosine to the transport network. Human SLC22A15 expression enabled uptake of carnosine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

evidence_access

Primary abstract

experimental_model

Metabolomic screening and uptake assays in transfected human cells.

limitations

Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

An additional carrier connects thiamine to the transport network.

primary_references

Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

transport_effect

raises Expression enabled uptake in HEK293 substrate assays.

transport_pool

the expressing cell Expression enabled uptake in HEK293 substrate assays.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 72–78

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Metabolomic screening and uptake assays in transfected human cells. · source_derived_draft · unverified_draft

## ergothioneine-slc22a15-thiamine An additional carrier connects thiamine to the transport network. Human SLC22A15 expression enabled uptake of thiamine in HEK293 substrate assays. Model: Metabolomic screening and uptake assays in transfected human cells. Limitations: Higher Km for ergothioneine, carnitine and carnosine than their established carriers; substrate sharing does not prove competition at dietary exposures. Evidence access: Primary abstract Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33124720/ · DOI 10.1096/fj.202001497R

evidence_access

Primary abstract

experimental_model

Wild-type human SLC22A4/SLC22A5 transport comparison.

limitations

Assay-specific discrimination; engineered mutants have different properties.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

The historical carrier name does not mean carnitine uses this route.

primary_references

Substrate discrimination by ergothioneine transporter SLC22A4 and carnitine transporter SLC22A5: gain-of-function by interchange of selected amino acids. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19814996/ · DOI 10.1016/j.bbamem.2009.09.019

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 32–38

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Wild-type human SLC22A4/SLC22A5 transport comparison. · source_derived_draft · unverified_draft

## ergothioneine-slc22a4-not-carnitine The historical carrier name does not mean carnitine uses this route. Wild-type human SLC22A4 did not mediate carnitine transport in the comparative HEK293 expression assay. Model: Wild-type human SLC22A4/SLC22A5 transport comparison. Limitations: Assay-specific discrimination; engineered mutants have different properties. Evidence access: Primary abstract Substrate discrimination by ergothioneine transporter SLC22A4 and carnitine transporter SLC22A5: gain-of-function by interchange of selected amino acids. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19814996/ · DOI 10.1016/j.bbamem.2009.09.019

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Retroviral insertion into transporter exon 1.

limitations

No obvious gross morphology or behavior difference was reported; do not transfer sole-transporter status to humans.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

In this animal model, the transporter controls nearly the entire pool.

primary_references

Knockout of the ergothioneine transporter ETT in zebrafish results in increased 8-oxoguanine levels. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25746775/ · DOI 10.1016/j.freeradbiomed.2015.02.026

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 96–102

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Retroviral insertion into transporter exon 1. · source_derived_draft · unverified_draft

## ergothioneine-zebrafish-loss In this animal model, the transporter controls nearly the entire pool. Zebrafish ETT knockout lowered ergothioneine content by more than 1000-fold. Model: Retroviral insertion into transporter exon 1. Limitations: No obvious gross morphology or behavior difference was reported; do not transfer sole-transporter status to humans. Evidence access: Primary abstract Knockout of the ergothioneine transporter ETT in zebrafish results in increased 8-oxoguanine levels. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25746775/ · DOI 10.1016/j.freeradbiomed.2015.02.026

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Whole-fish and skin analyses; basal versus metal-stressed conditions.

limitations

A stress-dependent phenotype does not identify one exclusive antioxidant reaction.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Loss of protection can become clearer under stress.

primary_references

Knockout of the ergothioneine transporter ETT in zebrafish results in increased 8-oxoguanine levels. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25746775/ · DOI 10.1016/j.freeradbiomed.2015.02.026

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 104–110

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Whole-fish and skin analyses; basal versus metal-stressed conditions. · source_derived_draft · unverified_draft

## ergothioneine-zebrafish-oxidation Loss of protection can become clearer under stress. ETT-knockout zebrafish had 3.8-fold higher skin 8-oxoguanine; lipid-oxidation differences appeared after lead or copper stress. Model: Whole-fish and skin analyses; basal versus metal-stressed conditions. Limitations: A stress-dependent phenotype does not identify one exclusive antioxidant reaction. Evidence access: Primary abstract Knockout of the ergothioneine transporter ETT in zebrafish results in increased 8-oxoguanine levels. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25746775/ · DOI 10.1016/j.freeradbiomed.2015.02.026

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary indexed abstract; numerical exposures and tissue-specific methods not available in the abstract.

experimental_condition

non-knockout mitochondrial comparison knockout · Mouse ergothioneine transporter Octn1 / Slc22a4 Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "Octn1/Slc22a4 knockout", "comparator": "non-knockout mitochondrial comparison", "endpoint": "mitochondrial ergothioneine uptake", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "mouse-slc22a4", "state": "knockout"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Mitochondria isolated from Octn1-knockout mouse tissues.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Residual uptake does not prove which alternative transporter operates, nor that OCTN1 normally resides on the mitochondrial membrane.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

An alternative mitochondrial uptake route remains possible.

primary_references

Fong et al. Ergothioneine and mitochondria: An important protective mechanism? DOI 10.1016/j.bbrc.2024.150269; PMID 38909533; https://pubmed.ncbi.nlm.nih.gov/38909533/

source_locator

Abstract, knockout comparison

trigger_kind

machinery_impairment Imported condition classification; unverified.

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 33–33

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Mitochondria isolated from Octn1-knockout mouse tissues. · source_derived_draft · unverified_draft

Slc22a4 knockout impaired but did not abolish ergothioneine uptake by isolated mouse mitochondria.

evidence_access

Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.

experimental_condition

wild-type mice muscle overexpression · Mouse PGC-1alpha / Ppargc1a Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "muscle-specific PGC-1alpha overexpression", "comparator": "wild-type mice", "endpoint": "whole-muscle ergothioneine concentration", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "mouse-ppargc1a", "state": "muscle overexpression"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

MCK-PGC-1alpha mice; whole gastrocnemius metabolomics.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Whole-muscle concentration is not the isolated mitochondrial pool. This does not establish that transporter upregulation is the only causal route.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

The muscle pool changed alongside transporter expression.

primary_references

Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/

source_locator

Figure 2F

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 105–105

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · MCK-PGC-1alpha mice; whole gastrocnemius metabolomics. · source_derived_draft · unverified_draft

PGC-1alpha-overexpressing mouse muscle contained more ergothioneine than control muscle.

evidence_access

Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.

experimental_condition

wild-type mice muscle overexpression · Mouse PGC-1alpha / Ppargc1a Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "muscle-specific PGC-1alpha overexpression", "comparator": "wild-type mice", "endpoint": "Slc22a4 mRNA and protein", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "mouse-ppargc1a", "state": "muscle overexpression"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

MCK-PGC-1alpha mice, gastrocnemius muscle, versus wild-type controls.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Overexpression differs from physiological exercise and human diet; increased transporter abundance is not itself a measured transport flux.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

A regulatory programme can alter transporter abundance.

primary_references

Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/

source_locator

Figure 2D-E

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 97–97

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · MCK-PGC-1alpha mice, gastrocnemius muscle, versus wild-type controls. · source_derived_draft · unverified_draft

Muscle PGC-1alpha overexpression increased Slc22a4 mRNA and protein in mice.

evidence_access

Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.

experimental_condition

sedentary MITO-Tag mice four weeks · Voluntary wheel endurance training in mice Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "four-week voluntary wheel training", "comparator": "sedentary MITO-Tag mice", "endpoint": "muscle mitochondrial ergothioneine concentration", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "mouse-voluntary-wheel-training", "state": "four weeks"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

MITO-Tag mice; gastrocnemius mitochondrial immunoprecipitation and targeted metabolomics.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

This is tissue-specific metabolite enrichment, not proof of a human deficiency threshold or the transport mechanism.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

Exercise changed the mitochondrial pool, not just intake.

primary_references

Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/

source_locator

Figure 1D-F

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 89–89

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · MITO-Tag mice; gastrocnemius mitochondrial immunoprecipitation and targeted metabolomics. · source_derived_draft · unverified_draft

Four weeks of endurance training enriched ergothioneine in mouse skeletal-muscle mitochondrial isolates.