There is a compound that is so important to humans that we evolved a dedicated molecular transport system just to collect it from food. It's a single transporter, built specifically for one molecule.
That molecule is ergothioneine. And the science around it has moved fast enough in the last two years that it deserves a proper update.
What Is Ergothioneine?
Ergothioneine (usually shortened to EGT) is a naturally occurring compound produced almost exclusively by fungi and certain soil bacteria. Your body cannot make it. So you have to consume it, typically from plants that grew in a fungal rich environment, animals that fed on plants that grew in a fungal rich environment, or directly from mushrooms.
Once you consume it, your gut absorbs it and it gets picked up by a protein called OCTN1, a transporter found throughout your body. This transporter's job is to take ergothioneine from your bloodstream and concentrate it in the tissues most vulnerable to damage: the brain, eyes, liver, bone marrow, red blood cells, and mitochondria (the energy-producing structures inside your cells).
This matters because most antioxidants your body encounters are opportunistic. They neutralise harmful molecules when they happen to cross paths. Ergothioneine is different. Your body actively seeks it out and stockpiles it in the places it is needed most.
The comparison researchers keep making is to vitamins. Vitamin C has several different transporters. Ergothioneine has one, and that transporter appears to exist primarily for it.
When Johns Hopkins researchers deprived human cells of ergothioneine in the lab, those cells suffered accelerated DNA damage and died faster. Some researchers have called it a candidate for the first new vitamin classification since B12 was isolated in 1948 - though no specific deficiency disease has been formally established yet.
Chemically, it is a sulphur-containing histidine derivative that exists in a stable "thione" form at body temperature. Unlike vitamin C (which oxidises quickly) or vitamin E (which degrades in UV light), ergothioneine is remarkably stable. Your body can hold onto it for weeks after supplementation stops.
The Broken Food Chain: How Industrial Farming Cut Us Off From It
Here is the part of the ergothioneine story that rarely gets told outside of soil science journals. Ergothioneine does not just come from mushrooms. It travels through an entire ecosystem before it ever reaches you.
Fungi and soil bacteria produce it underground. Plants cannot make it themselves, but many absorb it through their root systems from the fungal networks (mycelium) in the soil around them. Grains, vegetables, and legumes contain ergothioneine precisely because of this underground transfer. The fungi pass it along, the plants take it up, and you eat the plants (or the animals that ate the plants) and receive some of it.
That system depends on healthy, undisturbed soil with an active fungal community. But industrial farming breaks it.
A Penn State study compared ergothioneine concentrations in maize, soybeans, and oats grown under three different tillage regimes. Concentrations declined in all three crops as tillage intensity increased, with reductions of approximately 30% between no-till and the most intensive ploughing method. And because intensive tillage also reduces crop yields overall, ergothioneine yield per hectare was reduced even further.
The mechanism is straightforward. Excessive tillage disrupts the mycelial network, the fungal filaments that pass ergothioneine along to the roots of crops. Plough the soil repeatedly and you shred those networks. No fungal network, no transfer. No transfer, no ergothioneine in your wheat, oats, or beans.
Conventional agricultural practices that negatively impact soil fungi, such as excessive soil disturbance, can significantly reduce ergothioneine content of food crops compared to regenerative practices such as no-till farming.
The knock-on effect for human health may be significant. Porcini mushrooms have particularly high levels, which could explain why Italians average more than four times the ergothioneine intake of Americans. That is a population-level dietary gap driven in part by how food is grown, not just what people choose to eat.
The implication is that modern populations eating a standard Western diet may be chronically undersupplied with a compound their bodies were built to depend on. Whether that shortfall contributes meaningfully to rates of neurodegeneration, cardiovascular disease, and accelerated aging is something researchers are now actively investigating.
Mushrooms remain the most reliable source because they are the producers, not just the absorbers.
→ Try L-Ergothioneine — 60-day supply, £21.99
Why Researchers Care Now
The compound has been known since 1909, but scientific interest has accelerated sharply in the last few years. The reason is convergence of research. Observational studies linking low ergothioneine levels to disease, animal experiments showing remarkable protective effects, and, most recently, molecular studies finally revealing how it actually works inside cells.
A 2025 bibliometric analysis mapped the current research hotspots as: absorption and tissue distribution, anti-inflammatory mechanisms, disease associations, and fungal biosynthesis. Gede et al., Annals of Medicine, 2025. What that same review noted clearly: clinical trial evidence in humans remains limited. Most of what we know still comes from cells and animals.
The Newest Science (2024–2026)
Inside Your Mitochondria
The biggest mechanistic breakthrough of the period came from a Harvard-linked team in early 2025. They published their findings in Cell Metabolism (one of the most prestigious biology journals in the world) and it changed how researchers think about what ergothioneine is actually doing. Sprenger et al., Cell Metabolism, 2025.
The short version is they discovered that ergothioneine accumulates inside muscle mitochondria during exercise training, where it latches onto a specific enzyme called MPST and switches it on. That enzyme produces a signalling molecule (hydrogen sulphide) which directly boosts mitochondrial energy output.
This is not a story about neutralising free radicals. This is ergothioneine acting as a molecular switch for your cellular power generators.
In mice, this translated to a significant improvement in exercise endurance. Whether the same happens in human muscle at the doses people actually consume is not yet confirmed, but having identified the precise molecular mechanism is a major step forward.
NAD+, Muscle, and Lifespan
A companion paper in the same journal - Petrovic et al., Cell Metabolism, 2025 - found another mechanism. Inside cells, ergothioneine donates a sulphur atom that triggers a chain reaction increasing levels of NAD+, a coenzyme central to cellular energy and DNA repair. NAD+ declines with age, and its decline is associated with most hallmarks of aging. Strategies to raise it (like NMN or NR supplementation) have attracted enormous interest.
In middle-aged rats given ergothioneine for three weeks, muscle mass increased, running endurance nearly doubled, and muscle NAD+ levels rose measurably. In nematode worms, lifespan extended by around 20%.
Rats and worms are not humans. These findings need human replication. But the mechanisms they identify are real and biologically plausible.
The Human Cognitive Trial
The closest thing yet to a definitive human study came from Singapore. Yau et al., Journal of Alzheimer's Disease, 2024 recruited 19 older adults with mild cognitive impairment and gave them ergothioneine (25mg, three times a week) or placebo for roughly a year.
Results showed the ergothioneine group showed improved performance on a verbal learning test, and their levels of neurofilament light chain (a blood marker of brain cell damage) stabilised. The placebo group showed no cognitive improvement and their neurofilament marker rose significantly.
19 people is a small number. This is a pilot study, not definitive evidence. But stabilising a neurodegeneration biomarker in a population with cognitive impairment is promising and a result that justifies larger trials.
The First Dose-Ranging RCT
In June 2025, a randomised controlled trial - Zajac et al., Nutraceuticals, 2025 - enrolled 147 adults aged 55–79 with subjective memory complaints and gave them 10mg/day, 25mg/day, or placebo for 16 weeks.
This is the first study to properly test which dose works better in healthy older adults.
It found that 25mg/day produced significant positive effects in memory and sleep. Improvements in sleep quality has since been replicated in a separate Japanese study using 20mg/day.
One important note: this trial was funded by Blue California, a commercial ergothioneine ingredient supplier. That does not invalidate the results, but it is worth knowing when weighing them.
What the Human Evidence Actually Shows
The observational data (studies looking at existing populations) are fairly consistent. People with higher levels of ergothioneine in their blood tend to show better cognitive function, less cardiovascular disease, and slower biological aging markers.
A 2025 community-based longitudinal study in older Chinese adults linked higher plasma ergothioneine to a better cognitive trajectory over time.
The interventional data (where you give ergothioneine to people and measure what happens) are much thinner. The trials so far are small, short, and in at least one case funded by industry. There are no large independent phase III trials yet.
What is established is that ergothioneine is safe, it absorbs predictably and raises blood levels in proportion to the dose, and it concentrates in tissues relevant to brain and metabolic health via the OCTN1 transporter. The mechanisms for how it works are now considerably better understood. Whether it translates into meaningful health outcomes in humans at scale remains an open question.
What Is Not Yet Proven
Some claims circulating in the supplement world outrun the evidence. Worth being clear about:
"Ergothioneine prevents Alzheimer's or Parkinson's." There are strong animal model studies. Human trial evidence at this level of claim does not yet exist.
The optimal dose. The trials used 10–25mg/day. Long-term dose-response data in humans are absent. The dose that matters likely varies between individuals depending on genetics (OCTN1 transporter variants affect absorption efficiency) and diet.
NAD+ effects in humans. The rat and worm findings are exciting. Ergothioneine-driven NAD+ elevation has not been robustly demonstrated in human tissue at supplementation doses.
Long-term safety at higher doses. Short-term safety looks clean. Multi-year supplementation data do not yet exist.
What to Watch Next
The field is moving. A few things worth following:
Larger independent trials. The current human studies are pilot-scale or industry-funded. Independent replication at larger sample sizes will be the real test.
Genetics of absorption. There are known variations in the OCTN1 transporter gene. Some people may absorb ergothioneine much less efficiently than others. Personalised dosing based on genetics is a logical next step.
Regenerative agriculture connections. The Penn State tillage data opened a line of research connecting soil health to human health through ergothioneine. As regenerative farming practices expand, there is a genuine opportunity to restore population-level dietary ergothioneine through the food system rather than supplements alone.
Parkinson's disease trials. The preclinical evidence for neuroprotection is strong enough to justify human trials. Whether those are planned or funded is worth watching.
The Bigger Picture
Ergothioneine is one of those compounds that reveals something important when you zoom out.
It is produced by fungi. It moves through healthy, undisturbed soil into the plants above. Animals eat those plants and absorb it. Humans evolved a dedicated molecular shuttle to make sure none of it was wasted. For most of human history, this was a reliable background supply from the food system.
Industrial farming severed that chain. The fungal networks in the soil that delivered ergothioneine to plants were ploughed under. The compound retreated to the one source that does not depend on healthy soil: mushrooms themselves.
The research is now telling us that what we lost may matter more than we realised. Low ergothioneine levels track consistently with the diseases most associated with modern aging. The mechanistic story explains biologically why that correlation might be causal.
Mushrooms are not a trend. They are the part of the food system we evolved with. And ergothioneine is a clear example of a fungal nutrient we clearly need but we are slowly losing access to.
→ Try L-Ergothioneine — 60-day supply, £21.99
Key references
- Yau YF et al. Pilot study on ergothioneine in mild cognitive impairment. Journal of Alzheimer's Disease, 2024. Link
- Sprenger HG et al. Ergothioneine controls mitochondrial function via direct activation of MPST. Cell Metabolism, 2025. Link
- Petrovic D et al. Ergothioneine improves healthspan via CSE-dependent persulfidation. Cell Metabolism, 2025. Link
- Zajac IT et al. Ergothioneine supplementation in older adults with memory complaints: RCT. Nutraceuticals, 2025. Link
- Gede AMMI et al. Ergothioneine in cognitive frailty. Annals of Medicine, 2025. Link
- Beelman RB et al. Health consequences of improving ergothioneine in the food supply. FEBS Letters, 2022. Link
- Beelman RB et al. Soil disturbance impact on crop ergothioneine content. Agronomy, 2021. Link
- PMC. Ergothioneine: neuroprotective and anti-inflammatory compound from mushroom residuals. 2025. Link
