Ergothioneine and Parkinson's Disease Risk: Evidence Review

Mushrooms & Parkinson's Disease

470 patients

A Singapore Memory Clinic cohort of 470 elderly subjects, tracked for up to five years, found that low baseline plasma ergothioneine predicted faster cognitive and functional decline.

Wu et al., Antioxidants (Basel), 2022

35 PD patients

had significantly lower serum ergothioneine than 15 healthy controls in Hatano et al. 2016

5-year follow-up

of 470 elderly subjects found low baseline ergothioneine predicted greater cognitive and functional decline

3 model systems

Tng 2025 validated ergothioneine's protective effect across Drosophila, mouse, and human iPSC neurons

Wu et al., Antioxidants (Basel), 2022

View as image ↗

Ergothioneine is a dietary antioxidant found almost exclusively in mushrooms. In 2016, a Japanese research team examining novel biomarkers in Parkinson's disease made a quiet but pointed discovery: the 35 PD patients in their cohort had significantly lower serum ergothioneine than the 15 healthy age-matched controls.^[1] The finding appeared in a study of 50 people — not the kind of sample size that commands headlines. But the epidemiological evidence on ergothioneine and Parkinson's risk that has accumulated since — a 496-participant Singapore cross-sectional study, a 5-year longitudinal follow-up of 470 elderly subjects, and two major reviews — tells a coherent story that no consumer health source has assembled. This article is part of the broader cluster on mushrooms and brain health, zooming in specifically on what population data reveals about ergothioneine and Parkinson's risk.

Ergothioneine is not well known in nutrition conversations. It was first identified in 1909 but attracted serious research attention only in the past decade. Its most distinctive feature is that humans cannot synthesize it — it must come from diet, primarily from mushrooms. The human body has a dedicated transporter for it, called OCTN1, that pulls ergothioneine into cells including those in the brain. That a human body evolved a dedicated uptake mechanism for a single dietary compound is generally considered a clue that the compound matters.

The Biomarker Finding That Started the Conversation

Hatano et al. were not hunting specifically for ergothioneine when they published their 2016 Japanese biomarker study.^[1] They were conducting a broad metabolomic screen — a technique that measures hundreds of compounds simultaneously to find which ones differ between two groups. Their cohort consisted of 35 people with idiopathic Parkinson's disease and 15 age-matched healthy controls, a total of 50 people.

Ergothioneine emerged from that screen as one of the compounds that was significantly lower in PD patients. The finding was statistically significant but obviously limited by sample size. The right reading of a study this small is: hypothesis generation, not hypothesis confirmation. What it did contribute was a specific, measurable claim — Parkinson's disease is associated with lower circulating ergothioneine — that could now be tested at scale.

The mechanism that would later help explain this finding runs as follows. Ergothioneine accumulates in tissues that face high oxidative stress. The substantia nigra — the brain region where dopaminergic neurons are progressively destroyed in Parkinson's disease — is among the most metabolically active and oxidatively stressed regions in the brain. If ergothioneine normally accumulates there as a protective buffer, its depletion would leave dopaminergic neurons more exposed to exactly the kind of oxidative damage that characterizes PD pathology.

In 2016, this was speculation. The finding stood alone for several years. Then came the Singapore cohort.

A Larger Cohort Finds a Cleaner Signal

The Singapore Memory Clinic study, published in 2021 with Liu-Yun Wu as first author and ergothioneine pioneers Irwin Cheah and Barry Halliwell among the senior authors, operated at a different scale entirely.^[2] Rather than a narrow case-control comparison, it recruited 496 elderly participants across the cognitive spectrum — from no cognitive impairment through cognitive impairment without dementia to established dementia — and measured plasma ergothioneine alongside a comprehensive neurodegeneration battery: brain imaging, cognitive testing, functional assessments, and cerebrovascular markers.

The results extended well beyond replicating Hatano's finding. Plasma ergothioneine was lowest in participants with dementia and intermediate in those with cognitive impairment short of dementia. Low ergothioneine was associated with neurodegeneration markers including brain atrophy and white matter lesions, and with cerebrovascular disease. The lower the plasma ergothioneine, the more signs of neurodegeneration across multiple dimensions at once.

This distinction from Hatano matters. The Wu 2021 study was not asking "do PD patients have lower ergothioneine?" It was asking: "what does the overall picture of aging and neurodegeneration look like in relation to ergothioneine levels?" The answer was that the relationship held across multiple disease states — cognitive impairment, dementia, and cerebrovascular damage. Ergothioneine depletion appeared to be a general feature of aging brains under stress rather than a Parkinson's-specific biomarker, a point later reinforced by review evidence linking low ergothioneine to cognitive impairment, Parkinson's disease, and frailty alike.

The Singapore context gives this additional interpretive weight. Singapore has unusually high mushroom consumption relative to most Western countries, and a related Singapore cohort study reported that eating more than two portions of mushrooms per week was associated with lower odds of mild cognitive impairment. The Memory Clinic data sits within this same research ecosystem, using plasma ergothioneine as a proposed biological bridge between mushroom-eating habits and neurodegeneration outcomes. For more on that mushroom consumption research, see The Singapore Mushroom Study: Mushroom Intake and Cognitive Decline.

What the 2021 cross-sectional study cannot answer is the direction of causality. Low ergothioneine might contribute to neurodegeneration. Neurodegeneration might deplete ergothioneine. Or both might have a shared upstream cause. Cross-sectional data — a snapshot of one point in time — cannot distinguish between these possibilities.

Five Years of Follow-Up: Does Low Ergothioneine Predict What Comes Next?

The same research group, again with Liu-Yun Wu as first author, addressed the causality question with the tool best suited for it: a longitudinal follow-up.^[3] Published in 2022 in Antioxidants, their study tracked 470 elderly subjects from the Singapore Memory Clinic for up to five years. Baseline ergothioneine was measured at enrollment; cognitive and functional outcomes were assessed over the follow-up period.

The finding: low baseline plasma ergothioneine predicted poorer baseline cognition and faster subsequent decline across function and multiple cognitive domains, including memory, executive function, attention, visuomotor speed, and language. This is prospective data — the ergothioneine measurement came first, and the worse outcomes came later.

Two caveats keep this finding honest. First, the longitudinal associations were found specifically in non-demented individuals — the signal is about who declines faster among those not yet diagnosed, not about accelerating established dementia. Second, mediation analysis suggested the effect of ergothioneine on cognition was largely explainable by the severity of concomitant cerebrovascular disease, specifically white matter hyperintensities, together with brain atrophy. Low ergothioneine may be flagging vascular brain damage as much as acting through an independent pathway.

Even with those caveats, this is among the strongest human evidence available for the ergothioneine-neurodegeneration relationship, and it is underreported. The five-year prospective data exists in academic citations but has essentially no presence in consumer health media, despite being exactly the kind of longitudinal finding that nutritional epidemiology struggles to produce.

To be precise about what this study does and does not say: "predicts" is not "causes." A blood test that predicts a bad outcome does not mean correcting the test will prevent the outcome. The finding establishes that low ergothioneine is a meaningful marker of who will decline faster — it does not prove that raising ergothioneine through diet or supplementation will slow that decline. That intervention trial has not been done.

Why Ergothioneine Is Biologically Plausible Here

The epidemiological findings would be less compelling without a mechanism explaining why ergothioneine specifically might matter for dopaminergic neurons. Nakamichi and colleagues provided that mechanistic context in a comprehensive 2022 review of ergothioneine and central nervous system diseases.^[4]

OCTN1 — the carnitine/organic cation transporter also designated SLC22A4 — is the key protein. It moves ergothioneine across cell membranes, actively pulling it into tissues that express this transporter. Brain parenchymal cells, including neurons, express OCTN1, which means ergothioneine that permeates the blood-brain barrier has a direct route into brain tissue, including the neuronal populations relevant to Parkinson's disease.

Nakamichi's review documented that ergothioneine is a stable compound that permeates the blood-brain barrier and distributes to the brain via OCTN1, where it exerts neuroprotective effects. In multiple laboratory models, ergothioneine protected against neurotoxins and improved symptoms in animal models of cognitive impairment, depression, and epilepsy — with antioxidant and anti-inflammatory activity, promotion of neurogenesis, and induction of neurotrophic factors proposed as mechanisms.

The review also noted that ergothioneine concentrations in blood are lower in patients with cognitive impairment, Parkinson's disease, and frailty than in healthy subjects. Hatano's 2016 case-control finding was no longer alone. The synthesis: the mechanistic biology (ergothioneine reaches the brain via OCTN1) and the epidemiological biology (PD patients are depleted of ergothioneine) are internally consistent. They point in the same direction.

For a detailed walkthrough of how ergothioneine and other mushroom compounds protect dopaminergic neurons at the molecular level, see Mushroom Compounds and Dopaminergic Neuron Protection.

Could Ergothioneine Deficiency Actually Cause Parkinson's?

A 2024 review by Halliwell and Cheah in Free Radical Biology and Medicine asked the direct question implied by all the preceding data: could ergothioneine deficiency be a cause of neurodegenerative diseases, not just a correlate?^[5] They proposed that ergothioneine is an important nutrient for maintaining normal brain function, and that low body levels predispose humans to significantly increased risk of neurodegenerative disease — cognitive impairment, dementia, and Parkinson's disease — as well as frailty, cardiovascular disease, and eye disease.

Their argument drew on several observations working together. Ergothioneine levels tend to fall with age, in part because older people typically eat fewer mushrooms. This creates a compounding problem: aging populations may carry less of this antioxidant precisely when their brains face the highest cumulative oxidative pressure. The authors also suggested that ergothioneine and dietary vitamin E might act in parallel, or even synergistically, as "neuroprotective vitamins" protecting different parts of the brain.

The timing overlap is worth noting. Parkinson's disease incidence increases sharply with age. So does ergothioneine depletion. Halliwell and Cheah framed this not as coincidence but as a potential causal sequence: age-related ergothioneine deficiency leaves the brain without a key antioxidant buffer, increasing vulnerability to whatever triggers neurodegenerative pathology — and, because damage is usually extensive by the time dementia is diagnosed, they emphasized prevention over treatment.

This is a hypothesis, and the authors were explicit about that. Hypothesis papers are designed to be tested, and this particular hypothesis has not yet been subjected to a human clinical trial. What the framework provides is a biologically coherent explanation for why the epidemiological signal exists — and a testable prediction. That prediction found partial support the following year.

What the Most Recent Animal Evidence Shows

Tng et al., published in the Journal of Neurochemistry in 2025, ran the most comprehensive ergothioneine-Parkinson's experiment yet.^[6] They tested ergothioneine treatment across three independent Parkinson's model systems: Drosophila fruit flies carrying parkin and LRRK2 mutations, mouse PD models induced by the neurotoxin 6-OHDA, and human LRRK2 G2019S patient-derived iPSC dopaminergic neurons.

Ergothioneine improved outcomes across all three. The Drosophila with PD-associated mutations showed better climbing scores and preserved dopaminergic neuron numbers and mitochondrial integrity. The 6-OHDA mice showed rescued PD phenotypes — and, critically, that protection was abolished in mice lacking OCTN1, tying the benefit directly to the ergothioneine transporter. The human iPSC-derived neurons — grown from cells taken from actual PD patients carrying the LRRK2 G2019S mutation, a known Parkinson's genetic risk variant — were protected from rotenone-induced neurotoxicity, again in an OCTN1-dependent manner.

Three independent model systems reaching the same conclusion carries more weight than any single model. Each system has different limitations: a fruit fly is not a human, and a cultured neuron is not a brain. But if all three point in the same direction, the probability that the result is a model-specific artifact drops considerably. Tng 2025 is the strongest available preclinical evidence that ergothioneine treatment can protect the specific cellular system that Parkinson's disease targets.

For the epidemiological question, this matters because it supports causality in one direction: giving ergothioneine to Parkinson's disease models produces protective effects. This is not proof that dietary ergothioneine prevents PD in humans. It is evidence that the molecule does what the epidemiology suggests it should.

The Dietary Bridge: What the Evidence Translates To

Ergothioneine plasma levels respond to diet. Studies have shown that eating mushrooms — particularly culinary species like king oyster, shiitake, and button mushrooms, which are among the richest dietary sources — measurably increases plasma ergothioneine concentrations. This creates the dietary bridge the population data implies.

The question is whether raising plasma ergothioneine through mushroom consumption will reduce Parkinson's disease risk. That specific randomized trial has not been conducted. The Singapore longitudinal data establishes that people with lower ergothioneine face higher neurodegeneration risk. It does not establish that people who eat more mushrooms and thereby maintain higher ergothioneine are protected. The two findings connect logically but have not been connected experimentally.

What can be said with confidence: the epidemiological case for an ergothioneine-Parkinson's connection is unusually coherent for a nutritional science question. It spans multiple countries and study designs, a biologically credible pathway, and preclinical evidence of protective effects across multiple model systems. It is not proven in the clinical sense that a randomized trial would provide. It is evidence-based in the sense that each piece is documented, reproducible, and internally consistent.

For a practical guide to which mushroom species provide the most ergothioneine and how the research on specific species is structured, see Which Mushrooms Show Promise for Parkinson's? and Best Mushrooms for Brain Health in Older Adults.

Evidence quality — ergothioneine and Parkinson's risk

1. Cell & Lab Studiescompleted

   Human LRRK2-G2019S patient-derived iPSC dopaminergic neurons protected from rotenone toxicity in an OCTN1-dependent manner (Tng 2025)

2. Animal Studiescompleted

   Drosophila parkin/LRRK2 PD models and 6-OHDA-treated mice both rescued by ergothioneine, with protection abolished in OCTN1-null mice (Tng 2025)

3. Case-Control & Cross-Sectionalcompleted

   35 PD vs 15 controls with lower serum ergothioneine (Hatano 2016); low plasma ergothioneine across 496 elderly participants (Wu 2021)

4. Prospective Cohortcurrent

   470 Memory Clinic subjects followed up to 5 years — low baseline ergothioneine predicted faster decline, largely mediated by cerebrovascular disease (Wu 2022)

5. Randomized Controlled Trialmissing

   No trial has tested whether raising ergothioneine through diet or supplementation reduces Parkinson's risk or slows decline

6. Meta-Analyses & Systematic Reviewsmissing

   No human meta-analysis of ergothioneine and Parkinson's outcomes; the 2024 Halliwell-Cheah paper is a hypothesis review, not a quantitative synthesis

The evidence is coherent across cells, animals, and human observational cohorts, but it stops at prospective association. No randomized trial has tested whether adding ergothioneine changes Parkinson's outcomes — so the connection is evidence-based but not proven causal.

Aggregate of Hatano 2016, Wu 2021, Wu 2022, Nakamichi 2022, Halliwell & Cheah 2024, and Tng 2025

Safety — ergothioneine, mushrooms, and Parkinson's

Low

Low ergothioneine is a risk marker, not a treatment plan

Concern

The research here establishes that people with low ergothioneine tend to have worse neurodegeneration outcomes. It does not show that taking ergothioneine supplements or eating more mushrooms prevents or treats Parkinson's disease. No clinical trial has tested that, and a predictive biomarker is not the same as a proven intervention.

What the research says

Culinary mushrooms are a safe, well-studied dietary source of ergothioneine for most people. Ergothioneine supplements are a different matter and have not been tested for Parkinson's prevention. People with an existing Parkinson's diagnosis should not change or replace prescribed therapy based on this evidence.

Particularly relevant for: People with Parkinson's disease, those considering ergothioneine supplements, and anyone managing a neurodegenerative condition

What to do

Discuss any supplement or major dietary change with a physician, especially alongside Parkinson's medication. This article is educational and is not medical advice.

Safety framing based on the observational, non-interventional nature of Hatano 2016, Wu 2021, and Wu 2022

The Bottom Line

Across a 2016 case-control study, a 496-participant cross-sectional cohort, and a 5-year longitudinal follow-up of 470 elderly subjects, low plasma ergothioneine consistently associates with Parkinson's disease and broader neurodegeneration markers. The biological pathway — OCTN1-dependent transport across the blood-brain barrier into neurons, and antioxidant activity in high-oxidative-stress brain tissue — is mechanistically coherent, though the longitudinal signal appears substantially mediated by cerebrovascular damage. Whether dietary ergothioneine from mushrooms translates to reduced Parkinson's risk in humans is an open question that no clinical trial has yet answered.

Frequently Asked Questions

Is there an epidemiological link between ergothioneine and Parkinson's?

Yes. Multiple studies have found Parkinson's disease patients have significantly lower plasma or serum ergothioneine than age-matched healthy controls. The 2016 Hatano study documented this in a 50-person Japanese cohort, and a 2021 Singapore study (Wu et al.) found low ergothioneine associated with neurodegeneration and cerebrovascular disease across 496 elderly participants. A 2022 review by Nakamichi and colleagues noted that ergothioneine is lower in people with cognitive impairment, Parkinson's disease, and frailty than in healthy subjects. The relationship has been documented across different study populations and designs.

Do Parkinson's patients have lower ergothioneine levels?

In the studies that have measured it, yes. Hatano et al. 2016 found significantly lower serum ergothioneine in 35 PD patients compared to 15 healthy controls. Wu et al. 2021 found low plasma ergothioneine associated with neurodegeneration and cerebrovascular disease across 496 Memory Clinic participants, and Nakamichi's 2022 review reported the finding of lower ergothioneine in Parkinson's disease holds across the broader literature. Whether low ergothioneine is a cause of Parkinson's or a consequence of the disease process is still an open question.

Can mushroom consumption reduce Parkinson's risk?

That specific question has not been tested in a clinical trial. What the evidence shows is that eating mushrooms raises plasma ergothioneine, and that low ergothioneine is associated with higher neurodegeneration risk in population studies. The Halliwell and Cheah 2024 hypothesis paper proposed this as a causal chain. Whether raising ergothioneine through diet produces measurable protection against Parkinson's in humans remains unstudied.

What biomarkers are low in Parkinson's disease?

Ergothioneine is among the more consistently reported low biomarkers in PD, based on Hatano 2016 and the Wu 2021 Singapore cohort. Other research has focused on urate, DJ-1, and certain alpha-synuclein species as PD biomarkers, though these are not dietary compounds. Ergothioneine is notable because it comes almost entirely from diet — primarily mushrooms — which makes it theoretically modifiable in a way that genetic markers are not.

Does diet affect Parkinson's risk?

Diet is an active research area in Parkinson's disease. Mediterranean diet patterns have been associated with lower PD risk in some observational studies. Ergothioneine from mushrooms is a more specific dietary compound with mechanistic plausibility for dopaminergic neuron protection, supported by case-control data, cohort studies, and multi-model preclinical experiments. No randomized trial has yet tested dietary ergothioneine as a PD prevention or treatment strategy.

Sources & References

1. 1RTHM-00784·Hatano, Taku et al. (2016). “Identification of novel biomarkers for Parkinson's disease by metabolomic technologies..” Journal of neurology.Study breakdown →PubMed →↩
2. 2RTHM-01456·Wu, Liu-Yun et al. (2021). “Low plasma ergothioneine levels are associated with neurodegeneration and cerebrovascular disease in dementia..” Free radical biology & medicine.Study breakdown →PubMed →↩
3. 3RTHM-01634·Wu, Liu-Yun et al. (2022). “Low Plasma Ergothioneine Predicts Cognitive and Functional Decline in an Elderly Cohort Attending Memory Clinics..” Antioxidants (Basel.Study breakdown →PubMed →↩
4. 4RTHM-01589·Nakamichi, Noritaka et al. (2022). “Ergothioneine and central nervous system diseases..” Neurochemical research.Study breakdown →PubMed →↩
5. 5RTHM-01898·Halliwell, Barry et al. (2024). “Are age-related neurodegenerative diseases caused by a lack of the diet-derived compound ergothioneine?.” Free radical biology & medicine.Study breakdown →PubMed →↩
6. 6RTHM-02195·Tng, Teddy J W et al. (2025). “Ergothioneine Treatment Ameliorates the Pathological Phenotypes of Parkinson's Disease Models..” Journal of neurochemistry.Study breakdown →PubMed →↩