Alzheimer's, ergothioneine and the mushroom question — what a 2025 preprint actually shows

By Dr (TCM) Attilio D'Alberto | Traditional Chinese Medicine Practitioner, Wokingham, Berkshire

Chinese medicine cannot prevent, halt or reverse Alzheimer's disease, and this article does not claim it can. A recent preprint from the National University of Singapore reports that people whose bodies handle a specific dietary antioxidant — ergothioneine (ET) — more actively appear to have better cognitive resilience in the face of Alzheimer's amyloid pathology. Ergothioneine is concentrated in mushrooms, including the two most-used mushrooms in Chinese herbal medicine — Cordyceps (Dong Chong Xia Cao) and Lion's Mane (Hou Tou Gu / Hericium erinaceus). The finding is interesting; the appropriate interpretation is cautious. This article summarises what the study actually reports, what ergothioneine is, and where mushrooms and Chinese medicine sit in this picture — without over-claiming.

On this page

1. The 2025 preprint — what it actually reports
2. What is ergothioneine?
3. Food sources — mushrooms lead by a wide margin
4. Cordyceps (Dong Chong Xia Cao)
5. Lion's Mane (Hou Tou Gu / Hericium erinaceus)
6. The TCM view — brain, marrow and Kidney essence
7. Important caveats — what the study does not show
8. Practical takeaways — sensible, hedged
9. Working alongside conventional dementia care
10. Cautions and interactions
11. Frequently asked questions
12. Related reading
13. References

1. The 2025 preprint — what it actually reports

The study is Chong et al., "Metabolism of the antioxidant micronutrient ergothioneine as a plasma biomarker of cognitive resilience in older people with Alzheimer's disease amyloid pathology", posted on medRxiv in July 2025 (version 4, DOI: 10.1101/2025.07.31.25332054). The senior authors are based at the Yong Loo Lin School of Medicine, the Memory Aging and Cognition Centre at the National University Health System, and the Life Sciences Institute at the National University of Singapore.^[1]

The design is a prospective cohort study of 259 initially dementia-free older adults recruited from memory clinics and the community in Singapore. Participants had:

• Baseline plasma measurements of L-ergothioneine (ET), its metabolite L-hercynine (HC), and their ratio (HC:ET — taken as an index of how actively the body was metabolising ergothioneine).
• Baseline plasma phospho-tau (p-Tau181 or p-Tau217) — a well-validated biomarker of Alzheimer's amyloid pathology.
• Annual neuropsychological assessments over up to five years, tracked using Clinical Dementia Rating-Sum of Boxes (CDR-SB) slopes to identify who declined cognitively over time.

Reported results, quoting the authors' summary:

• A high HC:ET ratio (i.e., more active ergothioneine metabolism) attenuated the well-known positive correlation between plasma p-Tau and cognitive decline.
• Among participants with high amyloid burden, the risk of cognitive decline compared with low-amyloid participants was:
  • Hazard ratio 2.33 (p = 0.002) when HC:ET was low.
  • Hazard ratio 1.47 (p = 0.32, not statistically significant) when HC:ET was high.
• The authors' conclusion is measured: they identify ET metabolism as a novel biomarker of cognitive resilience and call for further investigation of the mechanisms and for evaluation of ET as a potential candidate for countering amyloid pathology-associated decline.

In plain terms: in this Singapore cohort, older adults who had biomarker evidence of Alzheimer's amyloid pathology and who were metabolising ergothioneine actively at baseline held on to their cognitive function better over five years than those who were not. The effect was statistically clear and clinically meaningful.

The study is a preprint — it has been posted online for scientific scrutiny but has not yet completed formal peer review at the time of writing. Preprints are useful for rapid dissemination but conclusions can change before final publication.

2. What is ergothioneine?

Ergothioneine is a naturally occurring sulphur-containing amino acid derivative that acts as a potent antioxidant. It is not produced by human cells; we obtain it entirely from the diet, primarily via fungi. Once ingested, ergothioneine is absorbed through a dedicated transporter protein (OCTN1/SLC22A4) that is expressed in tissues under high oxidative stress — notably the brain, eyes, liver and mitochondria — suggesting a physiological role in protecting these tissues from oxidative damage.

The proposed mechanisms by which ergothioneine may support cognitive health, as summarised in the wider literature, include scavenging of free radicals, protection of mitochondrial function, reduction of neuroinflammation, and preservation of neuronal viability under oxidative stress — all of which are relevant to the underlying biology of Alzheimer's. Barry Halliwell (one of the co-authors of the 2025 preprint) has published extensively on ergothioneine as a "longevity vitamin" candidate over the past decade.^[2]

The study above does not measure whether ergothioneine caused the better outcomes — it measures an association between plasma metabolism markers and cognitive trajectories. That distinction matters and is discussed in the caveats below.

3. Food sources — mushrooms lead by a wide margin

Ergothioneine is present in trace amounts in many foods — the microbes in soil and plant symbionts synthesise it — but the food category that outstrips everything else is mushrooms. Approximate ergothioneine content (per kg dry weight, drawn from the food-chemistry literature):

• Oyster mushroom (Pleurotus ostreatus) and related species — among the highest known dietary sources.
• King oyster (Pleurotus eryngii) — comparable levels; particularly ergothioneine-dense.
• Shiitake and maitake — substantial content.
• Lion's Mane (Hericium erinaceus) — contains ergothioneine, plus other bioactives it is specifically valued for.
• Cordyceps — also contains ergothioneine, alongside its own distinctive nucleoside constituents.
• Portobello, chestnut, chanterelle, porcini, enoki — commonly-available mushrooms all contribute meaningful ergothioneine.
• White button mushrooms — the most consumed mushroom in the UK; the lowest-ergothioneine of the widely-eaten mushrooms but still by far the highest of the "non-mushroom" foods.
• Trace amounts also occur in some plants that host ergothioneine-producing microbes (black beans, oat bran, some grains), organ meats and certain fermented foods.

Cooking is generally kind to ergothioneine — it survives normal cooking temperatures rather better than most B vitamins. A regular habit of eating a wide range of cooked mushrooms is the simplest and safest way to raise dietary ergothioneine intake.

4. Cordyceps (Dong Chong Xia Cao)

Cordyceps — Dong Chong Xia Cao (冬蟲夏草), literally "winter worm, summer grass" — is one of the most prized substances in Chinese materia medica. The traditional wild-harvested product is a parasitic fungus, Ophiocordyceps sinensis, that infects the larvae of ghost moths on the high plateaux of Tibet, Bhutan, Nepal and western China. In modern practice, most clinical Cordyceps is the cultivated mycelial biomass of Cordyceps militaris or fermented C. sinensis — both provide the same major bioactive constituents (cordycepin, adenosine, polysaccharides, ergosterol precursors) without the sustainability and ethical issues of wild harvest.

Classically, Cordyceps is described as tonifying Kidney Yang and Lung Yin — used for chronic respiratory weakness, low back weakness, fatigue, low libido, post-illness convalescence, and, importantly for the current context, the constitutional depletion associated with cognitive decline in older age. It is one of the herbs most commonly incorporated into TCM protocols for supporting cognitive function alongside conventional care.

The relevance of the 2025 preprint to Cordyceps specifically is that Cordyceps species, like other cultivated medicinal mushrooms, are a natural source of ergothioneine. This does not mean Cordyceps prevents Alzheimer's — a claim no responsible practitioner will make — but it does provide one plausible biological input among many for the way traditional practice has valued it in older-age constitutional care.

5. Lion's Mane (Hou Tou Gu / Hericium erinaceus)

Lion's Mane — Hou Tou Gu (猴頭菇), "monkey head mushroom" — is Hericium erinaceus, an edible mushroom native to Europe, North America and Asia. It has a long history of use as both a food and a medicinal in Chinese and Japanese traditions, particularly for the Stomach and Spleen (traditional indications include chronic gastritis and appetite loss), and more recently for cognitive and neurological support.

Lion's Mane has attracted contemporary research interest for two distinctive constituent families — erinacines and hericenones — that in preclinical work have been associated with modulation of nerve growth factor (NGF) activity. Human trial data for Lion's Mane in mild cognitive impairment and cognitive decline are early and inconsistent; systematic reviews suggest a signal of possible benefit for mild cognitive symptoms but no evidence that Lion's Mane treats or reverses Alzheimer's disease.^[3] Like other cultivated mushrooms, Lion's Mane is also a dietary source of ergothioneine, which is a separate potentially relevant mechanism from its NGF-related constituents.

6. The TCM view — brain, marrow and Kidney essence

Traditional Chinese medicine understands the brain as the "Sea of Marrow" (Sui Hai, 髓海), nourished and sustained by Kidney essence (Jing). Age-related cognitive decline is understood as a manifestation of Kidney essence and marrow depletion, often compounded by Spleen deficiency (poor nourishment of the brain through inadequate Blood generation) and by Phlegm and Blood stasis obstructing the clear orifices of the head.

This framework mapped onto older-age cognitive decline long before the modern amyloid model existed. It is not a description of Alzheimer's pathology in molecular terms — TCM cannot describe amyloid plaques — but it does describe a clinical trajectory (progressive cognitive weakening, physical depletion, loss of vitality) that overlaps meaningfully with what modern medicine calls dementia. The traditional herbs and formulae used to nourish Kidney essence, boost Marrow and clear obstruction of the head include a substantial proportion of medicinal mushrooms and mushroom-based formulae — among them Cordyceps and Lion's Mane, but also Reishi (Ling Zhi) and Poria (Fu Ling) — and a range of non-mushroom herbs like He Shou Wu, Gou Qi Zi, Shu Di Huang and Yuan Zhi.

The 2025 preprint offers one specific mechanistic point in favour of the traditional emphasis on mushrooms in cognitive support — ergothioneine metabolism appears to be associated with cognitive resilience. It does not validate every claim ever made for medicinal mushrooms in dementia, and it does not translate directly into "eat more mushrooms and you will not get Alzheimer's". What it does is add to a slowly growing body of evidence that the food category traditional East Asian medicine emphasised for cognitive longevity has plausible biological relevance.

7. Important caveats — what the study does not show

Reading the preprint carefully, several things are worth stating explicitly:

• The study is an association, not a causal experiment. It shows that people with more active ergothioneine metabolism at baseline had better cognitive trajectories over five years. It does not show that giving people ergothioneine (as a supplement or via increased mushroom intake) would produce the same protection.
• Better ET metabolism may reflect other things. Higher HC:ET could be a marker of a healthier gut microbiome (which produces some ET-related compounds), better nutrition overall, more physical activity, higher socioeconomic status, or lower oxidative stress from other causes. Any of these could independently protect cognition. The study adjusted for age, sex and other measured variables but no observational study can fully rule out residual confounding.
• It is a preprint. Not yet peer-reviewed. Findings may be modified before final publication.
• The Singapore cohort is not a UK population. Dietary patterns, background ergothioneine intake and gene variants in the OCTN1 transporter can differ; direct translation to UK diets is reasonable but not guaranteed.
• The study does not evaluate any supplement. Commercial ergothioneine supplements, mushroom powders and combination cognitive supplements have not been shown in randomised trials to prevent or treat Alzheimer's disease. The trials that would confirm or refute this are needed and have not yet been done.
• Alzheimer's has many drivers. Age, genetics (particularly APOE-e4), cardiovascular risk factors, sleep, exercise, education, hearing loss and depression are all more strongly established risk factors than any single dietary compound. A "mushroom strategy" is not a substitute for the well-established Lancet Commission modifiable risk factors framework.^[4]
• The finding is about resilience in people who already have amyloid pathology. It suggests that among those with amyloid burden, some are protected against cognitive decline for longer — it does not show ergothioneine prevents amyloid pathology developing in the first place.

8. Practical takeaways — sensible, hedged

What can you reasonably do with this information?

• Eat mushrooms regularly. Adding a modest portion of cooked mushrooms — oyster, chestnut, shiitake, portobello, chanterelle or any UK-available variety — two to four times a week is a safe, evidence-supported way to raise dietary ergothioneine. Variety matters; different species offer different bioactive profiles.
• Include medicinal mushrooms if you already work with a TCM practitioner. Cordyceps and Lion's Mane are traditional cognitive-support foods and are available as pharmaceutical-grade granules from Sun Ten and other reputable suppliers in supervised prescriptions.
• Focus on the well-established Lancet dementia risk factors first. Hearing correction, treating high blood pressure and diabetes, regular aerobic and strength exercise, avoiding excessive alcohol, treating depression, maintaining social engagement and cognitive activity, and adequate sleep are all better-supported than any specific supplement.
• Consider isolated ergothioneine supplements only cautiously. They exist commercially but the clinical trial evidence for their use in Alzheimer's prevention is currently absent. Food sources are safer and cheaper.
• Do not stop or reduce prescribed dementia medication. Nothing in this preprint changes the case for cholinesterase inhibitors, memantine or the newer anti-amyloid therapies where a specialist has prescribed them.
• Talk to your doctor before adding anything. Some mushroom supplements interact with anticoagulants, immunosuppressants and diabetes medications. A brief conversation avoids problems.

9. Working alongside conventional dementia care

Anyone with cognitive concerns — memory changes, new difficulty with familiar tasks, personality changes, disorientation — should be seen by their GP, referred where appropriate to a memory service and, if needed, an old-age psychiatrist or specialist cognitive neurology clinic. Early diagnosis matters: it opens access to disease-modifying therapy where indicated, allows time for advance care planning, and identifies treatable contributors (thyroid disease, B12 deficiency, depression, sleep apnea, medication effects) that account for a meaningful minority of "memory clinic" referrals.

Chinese medicine, mushroom-based diet strategies, and any other complementary approach sit alongside this pathway. They do not replace it. Anyone claiming that mushrooms, herbs or diet alone can cure or reverse established Alzheimer's disease is not telling the truth.

10. Cautions and interactions

• Foraging. Never eat foraged mushrooms unless identified by an experienced mycologist. Amanita and other toxic species can be mistaken for edible varieties with fatal consequences.
• Blood thinners. Some medicinal mushroom extracts (particularly Reishi) can potentiate anticoagulant effect. Check with your prescriber before adding concentrated mushroom supplements if on warfarin, apixaban, rivaroxaban or edoxaban.
• Immunosuppressants. Mushroom polysaccharides can modulate immune activity. Discuss with your specialist if you are on immunosuppressive medication.
• Diabetes medications. Some medicinal mushrooms have mild hypoglycaemic effects. Monitor glucose more carefully when introducing concentrated supplements.
• Allergy. Mushroom allergy exists, particularly to spores. Discontinue if any hives, wheezing or respiratory symptoms develop.
• Autoimmune disease. Immunologically active mushroom compounds can theoretically flare autoimmune disease — discuss with your specialist first.
• Cost and quality. Supplement quality varies enormously. Choose products with third-party testing and disclosed extract standardisation rather than the cheapest available.

11. Frequently asked questions

Does eating more mushrooms prevent Alzheimer's?

No, we cannot say that. What we can say is that regular mushroom consumption is a safe way to raise dietary ergothioneine, and this 2025 preprint suggests active ergothioneine metabolism may support cognitive resilience in older people with amyloid pathology. Prevention of Alzheimer's would need a randomised trial that has not yet been done.

Should I take a Lion's Mane supplement?

Lion's Mane is generally considered safe and has some early trial data for mild cognitive complaints. It is not established as a treatment or preventive for Alzheimer's disease. If you are drawn to it, a modest daily supplement or regular consumption of the fresh mushroom (available in some UK farmers' markets and specialist grocers) is reasonable. Check with your GP if you are on any medication.

What about Cordyceps?

Cordyceps is a traditional Chinese medicinal used for constitutional support in the elderly, and it also provides ergothioneine among its bioactives. It is best used within a prescribed TCM formula that fits your individual pattern rather than a stand-alone supplement.

Are white button mushrooms good enough or do I need "medicinal" mushrooms?

White button mushrooms provide ergothioneine, though at lower levels than oyster or king oyster mushrooms. For general dietary ergothioneine, a mix of everyday mushrooms is sensible. For specific traditional cognitive-support use in TCM, medicinal mushrooms have their own additional constituents that go beyond ergothioneine alone.

Is ergothioneine an official vitamin?

No. It has been proposed as a "longevity vitamin" in the scientific literature (particularly by Bruce Ames and Barry Halliwell) but it does not have vitamin status. There is no established daily requirement or recommended intake in the UK.

My family member already has Alzheimer's. Would mushrooms help?

Please do not stop or replace prescribed dementia medication with mushroom-based interventions. Adding regular mushroom-containing meals to the diet is safe and provides nutritional benefit; whether it will slow cognitive decline in an established Alzheimer's picture is not known. Discuss with the specialist team.

Can I take an ergothioneine supplement directly?

Isolated ergothioneine supplements exist commercially. There is currently no randomised trial evidence in Alzheimer's disease. Food sources are safer and cheaper. If you are considering a supplement, discuss with your doctor and choose a reputable, third-party-tested product.

Does the study apply to younger adults?

The Singapore cohort was older adults already recruited from memory clinics and community settings. Whether the same finding applies to younger adults is not established. That said, a diet rich in mushrooms is unlikely to be harmful and may support broader antioxidant status across the life course.

12. Related reading

• Dementia — acupuncture and Chinese medicine
• Chinese herbs for cognitive function
• Medicinal mushrooms — benefits and evidence
• Ginkgo biloba benefits
• Cordyceps (Dong Chong Xia Cao)
• Lion's Mane (Hou Tou Gu / Hericium erinaceus)
• Alzheimer's Society (UK)
• NICE Guideline NG97 — Dementia: assessment, management and support

13. References

1. Chong JR, Cheah IK, Tang RM, Halliwell B, Chen CP, Lai MKP. Metabolism of the antioxidant micronutrient ergothioneine as a plasma biomarker of cognitive resilience in older people with Alzheimer's disease amyloid pathology. medRxiv preprint, version 4, July 2025. DOI: 10.1101/2025.07.31.25332054. medrxiv.org. Note: preprint, not yet peer-reviewed.
2. Halliwell B, Cheah IK, Tang RM. Ergothioneine — a diet-derived antioxidant with therapeutic potential. FEBS Letters. 2018;592(20):3357-3366. Wider review of ergothioneine physiology.
3. Mori K, Inatomi S, Ouchi K, et al. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytotherapy Research. 2009;23(3):367-372. Small trial in mild cognitive impairment.
4. Livingston G, Huntley J, Liu KY, et al. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet. 2024;404(10452):572-628. The current authoritative summary of modifiable risk factors for dementia.
5. NICE Guideline NG97, Dementia: assessment, management and support for people living with dementia and their carers. 2018, updated 2024.
6. Alzheimer's Society (UK), alzheimers.org.uk — patient and family information.

This article is for general information and does not constitute medical advice. If you or someone you care for is worried about cognitive changes, please speak to your GP and seek proper diagnostic assessment. Do not use dietary or complementary interventions as a substitute for evidence-based dementia care.