Key findings from detailed records
Human trials now examine sleep and memory as well as absorption. A 16-week trial found better perceived sleep length and refreshing scores with 8 mg/day versus placebo. These were exploratory questionnaire outcomes; separate trials explore subjective memory and learning. PMID 40475978
KNOWLEDGE RECORD
- Category
- Ingredients and research
- Last Reviewed
OUTCOME-SPECIFIC EVIDENCE
Scientific Evidence Profile
Editorial pilot · selected evidence; not a systematic review or formal GRADE assessment.
Subjective sleep quality in middle-aged and older adults
Limited
Trials report improvements in selected sleep questionnaire measures. These are promising exploratory findings, rather than consistent evidence of longer objectively measured sleep.
Basis of this assessment
- Human study quality
- Two randomized, double-blind, placebo-controlled trials; sleep outcomes were exploratory or secondary.
- Scale and replication
- Okumura: 100 enrolled, 92 usable questionnaires, 8 mg/day. Zajac: 147 randomized, 10 or 25 mg/day. Both lasted 16 weeks.
- Consistency of findings
- Different questionnaire domains and analyses; not a replicated effect on one identical sleep endpoint.
- Clinical relevance
- Perceived refreshment, sleep length or initiation; not objectively measured extra minutes of sleep.
- Systematic reviews / meta-analyses
- No sleep-specific systematic synthesis has been verified for this profile. This is not a claim that none exists.
- Limitations / funding / COI
- Multiple outcomes and analysis exclusions. Funding: Suntory/JSPS and Blue California; company-employed authors in both reports.
Assessment sources
Profile reviewed:
This profile concerns the stated outcome and population, not the ingredient as a whole. It is not a probability of benefit, a safety rating, a product efficacy rating or an indication of product adoption.
How we assess evidenceIngredient Profile
- What is it?
- Ergothioneine is a sulfur-containing derivative of histidine. It is made by certain microorganisms; its presence in food connects microbial biology with human exposure. [1]
Sources for this profile
Compound properties and formulation properties are different. These sources do not establish the efficacy of a finished supplement.
- PubChem — Ergothioneine (CID 5351619) Chemical identity reference. Maintained by NCBI, U.S. National Library of Medicine. Database record; not a clinical trial.
Profile sources checked:
Read the evidence in context
- Evidence: what was measured in the stated population or experimental model.
- Inference: an interpretation connecting findings; its applicability depends on the study conditions.
- Hypothesis: a proposed explanation or effect that remains to be tested.
Why It Matters #
Ergothioneine is taken up by a dedicated transporter and retained in the body. The next question is functional: does supplementation change how people sleep, learn or remember? Recent intervention trials address these questions directly. PMID 40475978
What Was Studied #
The 2025 sleep study randomized 100 Japanese adults aged 40–64 to 8 mg/day or placebo for 16 weeks. The sleep analysis included 92 questionnaires. A separate 147-person trial used 10 or 25 mg/day for 16 weeks, and a 19-person cognitive pilot used 25 mg three times weekly for one year. PMID 40475978
What Was Found #
The sleep trial favored ergothioneine for perceived sleep length and refreshing on waking. The separate 25 mg trial reported a subjective prospective-memory advantage in its per-protocol analysis. The smaller cognitive pilot reported learning and neurofilament-light signals. These outcomes measure different aspects of function. DOI 10.3390/nutraceuticals5030015
What the Evidence Means #
The most useful interpretation is endpoint-specific: the sleep findings were exploratory, the MRI endpoints did not differ, and the larger memory trial did not improve its primary composite-memory outcome versus placebo. These boundaries help identify which promising signals deserve replication. PMID 40475978
What We Can Learn #
Sleep questionnaires capture how rested a person feels; memory tests capture particular abilities. Linking these outcomes with absorption studies creates a more informative picture than blood concentrations alone.
What Remains Unknown #
Independent replication, longer follow-up and prespecified functional outcomes will clarify who benefits, at which dose and for how long. The available studies do not establish lifelong safety or dementia prevention.
LITERATURE MAP / 13 PAPERS
Compare papers by conditions and findings.
A literature map distinguishing supplementation trials from observational studies of blood concentrations. Associations with disease or cognition do not directly demonstrate benefits of supplementation.
Initial selection: 2026-09-21; human-study additions: 2026-10-11. Editorial selection spans populations and research questions. The source-review scope is recorded per study; this is not a systematic review.
13 RECORDS
A dash marks fields outside the bibliographic record. Use detailed records to compare findings and design records to connect mechanisms.
| Paper and topic | Study conditions | Findings and scope |
|---|---|---|
| Estimation and Validation of an Effective Ergothioneine Dose for Improved Sleep Quality Using Physiologically Based Pharmacokinetic Model. | 100 Japanese adults aged 40–64; 92 had usable sleep questionnaires. · L-ergothioneine 8 mg/day versus placebo · 16 weeks · OSA-MA subjective sleep scores; registered primary endpoint: MRI-derived brain-health measures. | Refreshing and perceived sleep-length scores improved versus placebo (p=0.026 and 0.007). These are questionnaire scores, not measured extra minutes of sleep. Explore the research |
| The Effect of Ergothioneine Supplementation on Cognitive Function, Memory, and Sleep in Older Adults with Subjective Memory Complaints: A Randomized Placebo-Controlled Trial. | 147 adults aged 55–79 with subjective memory complaints · ErgoActive® ergothioneine 10 or 25 mg/day versus placebo · 16 weeks | In the per-protocol analysis, subjective prospective memory favored 25 mg versus placebo. Sleep initiation showed an overall treatment effect. The primary composite-memory outcome did not differ from placebo. Explore the research |
| Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study. | 19 adults aged 60 or older with mild cognitive impairment · Ergothioneine 25 mg three times weekly versus placebo · 1 year · Learning tests, neurofilament light chain and laboratory safety markers | The authors reported improved verbal learning and stable neurofilament light chain in the ergothioneine arm, alongside less favorable changes in the placebo arm. Explore the research |
| Mechanism and designThe unusual amino acid L-ergothioneine is a physiologic cytoprotectantPMID 19911007 # | Study conditions Cultured cells / Oxidative stress and mtDNA — | Findings and scope Reducing the ergothioneine transporter in cells increased sensitivity to oxidative stress and mitochondrial DNA damage. This informs the focus on cellular stress responses. A cell study manipulating a transporter, not a trial of oral effects at 25 mg/day. |
| Immunity and inflammationAdministration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation.PMID 27488221 # | Study conditions Placebo-controlled administration study in healthy people
| Findings and scope Increased blood concentrations and retention were observed. Many changes in oxidative damage and inflammation markers were not significant. View findings and limitations |
| The bioavailability of ergothioneine from mushrooms (Agaricus bisporus) and the acute effects on antioxidant capacity and biomarkers of inflammation.PMID 22230474 # | Study conditions — | Findings and scope — Open original paper |
| Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration?PMID 27444382 # | Study conditions — | Findings and scope — Open original paper |
| Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease.PMID 31672783 # | Study conditions — | Findings and scope — Open original paper |
| Low plasma ergothioneine levels are associated with neurodegeneration and cerebrovascular disease in dementia.PMID 34673145 # | Study conditions — | Findings and scope — Open original paper |
| Low Plasma Ergothioneine Predicts Cognitive and Functional Decline in an Elderly Cohort Attending Memory Clinics.PMID 36139790 # | Study conditions — | Findings and scope — Open original paper |
| TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans.PMID 38321007 # | Study conditions — | Findings and scope — Open original paper |
| Serum ergothioneine and risk of dementia in a general older Japanese population: the Hisayama Study.PMID 40908798 # | Study conditions — | Findings and scope — Open original paper |
| Higher scores of the Kessler Psychological Distress Scale (K10) are associated with lower serum ergothioneine and higher serum asymmetric dimethyl-l-arginine concentrations in a cohort of middle-aged and older adults.PMID 39349102 # | Study conditions — | Findings and scope — Open original paper |
No papers match. Change the search conditions.
The literature map is an index of research questions and references. Individual assessment of results, doses, funding and COI is limited to the detailed study records. Related reports from the same trial may be included; paper counts are not counts of independent trials.
Explore the research Study Records
Listed doses describe study conditions, not recommended intake.
Estimation and Validation of an Effective Ergothioneine Dose for Improved Sleep Quality Using Physiologically Based Pharmacokinetic Model.
PMID 40475978DOI: 10.1002/fsn3.70382
- Authors
- Okumura H, Araragi Y, Nishioka K, Yamashita R, Suzuki T, Watanabe H, Kato Y, Murayama N.
- Journal
- Food Science & Nutrition
- Publication year
- 2025
- Study design
- Study 2: randomized, double-blind, placebo-controlled trial
- Participants
- 100 Japanese adults aged 40–64; 92 had usable sleep questionnaires.
- Dose and intervention
- L-ergothioneine 8 mg/day versus placebo
- Duration
- 16 weeks
- Outcomes and their role in the study
- OSA-MA subjective sleep scores; registered primary endpoint: MRI-derived brain-health measures.
- Findings
- Refreshing and perceived sleep-length scores improved versus placebo (p=0.026 and 0.007). These are questionnaire scores, not measured extra minutes of sleep.
- Limitations
- Exploratory sleep findings; registered MRI outcomes did not differ. Questionnaire exclusions and multiple outcomes warrant replication. No significant difference in adverse-event incidence was observed over 16 weeks; this is not a lifelong safety assessment.
- Funding
- Suntory Global Innovation Center and JSPS grant 22H02781 supported the study.
- Conflict of Interest
- Five authors were employees of Suntory Global Innovation Center. The other authors declared no relevant commercial or financial relationships.
- Scope of source review
- Methods, results and funding/COI sections of the public full text reviewed on 2026-10-11.
The Effect of Ergothioneine Supplementation on Cognitive Function, Memory, and Sleep in Older Adults with Subjective Memory Complaints: A Randomized Placebo-Controlled Trial.
DOI 10.3390/nutraceuticals5030015
- Authors
- Zajac IT, Kakoschke N, Kuhn-Sherlock B, May-Zhang LS.
- Journal
- Nutraceuticals
- Publication year
- 2025
- Study design
- Randomized, double-blind, placebo-controlled trial
- Participants
- 147 adults aged 55–79 with subjective memory complaints
- Dose and intervention
- ErgoActive® ergothioneine 10 or 25 mg/day versus placebo
- Duration
- 16 weeks
- Outcomes and their role in the study
- Primary: composite memory. Secondary: other cognition, subjective memory and sleep.
- Findings
- In the per-protocol analysis, subjective prospective memory favored 25 mg versus placebo. Sleep initiation showed an overall treatment effect. The primary composite-memory outcome did not differ from placebo.
- Limitations
- Secondary, subjective and per-protocol signals; multiple analyses and a primary-outcome amendment limit certainty.
- Funding
- Phyto Tech Corp (Blue California).
- Conflict of Interest
- May-Zhang is a Blue California employee; other authors reported study funding without other conflicts.
- Scope of source review
- Publisher-hosted methods, results, figure legends and funding/COI sections checked on 2026-10-11; supplementary tables not fully reviewed.
Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study.
PMID 39544014DOI: 10.1177/13872877241291253
- Authors
- Yau YF, Cheah IK, Mahendran R, et al.
- Journal
- Journal of Alzheimer’s Disease
- Publication year
- 2024
- Study design
- Randomized, double-blind, placebo-controlled pilot
- Participants
- 19 adults aged 60 or older with mild cognitive impairment
- Dose and intervention
- Ergothioneine 25 mg three times weekly versus placebo
- Duration
- 1 year
- Outcomes and their role in the study
- Learning tests, neurofilament light chain and laboratory safety markers
- Findings
- The authors reported improved verbal learning and stable neurofilament light chain in the ergothioneine arm, alongside less favorable changes in the placebo arm.
- Limitations
- Very small pilot. The abstract does not establish every between-group contrast; findings do not demonstrate prevention of dementia.
- Funding
- Not verified in the sources reviewed.
- Conflict of Interest
- Not verified in the sources reviewed.
- Scope of source review
- Original abstract and bibliographic record reviewed on 2026-10-11; full text not reviewed.
Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation.
PubMed 27488221DOI: 10.1089/ars.2016.6778
- Authors
- Cheah IK, Tang RM, Yew TS, Lim KH, Halliwell B.
- Journal
- Antioxidants & redox signaling
- Publication year
- 2017
- Study design
- Placebo-controlled administration study in healthy people
- Participants
- Healthy men, 15 per group
- Dose and intervention
- Placebo, 5 mg and 25 mg compared
- Duration
- Daily dosing for 7 days; follow-up through day 35.
- Outcomes and their role in the study
- Absorption, metabolism, oxidative damage and inflammation markers. Prespecified primary/secondary classification was not verified.
- Findings
- Increased blood concentrations and retention were observed. Many changes in oxidative damage and inflammation markers were not significant.
- Limitations
- Early research focused on pharmacokinetics and biomarkers. It does not establish long-term health benefits or disease prevention.
- Funding
- Singapore National Medical Research Council funded the study; Tetrahedron supplied ergothioneine, placebo and analytical standards.
- Conflict of Interest
- The authors declared no competing financial interests.
- Scope of source review
- Publisher methods, participant flow and disclosures checked on 2026-10-24.
Cite this page
LÍFSVARÐA. Ergothioneine: what do human trials tell us about sleep, memory and absorption? / Updated 2026-10-24
https://lifsvarda.com/knowledge/ergothioneine/Edited by LÍFSVARÐA (product brand).Editorial policy
Sources and updates
- Estimation and Validation of an Effective Ergothioneine Dose for Improved Sleep Quality Using Physiologically Based Pharmacokinetic Model.
- The Effect of Ergothioneine Supplementation on Cognitive Function, Memory, and Sleep in Older Adults with Subjective Memory Complaints: A Randomized Placebo-Controlled Trial.
- Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study.
- Cheah et al. (2017): human ergothioneine administration, absorption, metabolism and related measuresPublisher methods, participant flow and disclosures checked on 2026-10-24.
- Original paper PDF: participants and treatment groupsRelevant sections of the primary study and methods checked
2026-10-11: Human-study coverage, findings and comparisons reviewed. Source-review scope is stated for each study.