Ingredient Reference
Ergothioneine: Chemistry, the OCTN1 Transporter, Food Sources and Safety
Reference facts on ergothioneine: chemistry, the SLC22A4 (OCTN1) transporter, mushroom sources, how supplement L-ergothioneine is made, human trials by amount, safety and regulatory status.
Pre-order Brain Energy CapsulesErgothioneine on the Label
What our planned label lists, per serving.
Planned formula. Pre-order, no payment taken now. The product page reads: "Pre-order to join the launch list. No payment is taken now." How this compares with research amounts: 25 mg a day is the higher of the two amounts in Cheah 2017 and Zajac 2025, and under the EU ceiling of 30 mg a day for adult food supplements. Use as directed on the label once it ships.
Ergothioneine at a Glance
| Item | Details |
|---|---|
| Names | Ergothioneine, L-ergothioneine, EGT or ET. |
| Chemistry | C9H15N3O2S, 229.30 Da, CAS 497-30-3. A sulfur-bearing betaine of histidine. |
| Made by | Certain fungi and bacteria, such as Neurospora crassa, mycobacteria and some cyanobacteria. People take it in from food. |
| Transporter | OCTN1, coded by the SLC22A4 gene; also called ETT. |
| Food sources | Mushrooms; porcini had the most of 13 species in one analysis. |
| Amounts in human trials | 5 to 25 mg a day; one 52 week trial used 25 mg three times a week. |
| Regulatory | EU novel food since 2017, up to 30 mg a day in adult supplements. Three FDA GRAS notices, no questions. |
Here for benefits or dosage advice? What ergothioneine is studied for and how people take it are covered in Ergothioneine Benefits: What It Is, Food Sources, Dosage and Safety. This page sticks to reference facts.
Chemistry, Biosynthesis and the OCTN1 Transporter
Charles Tanret isolated ergothioneine in 1909 from ergot, the Claviceps purpurea fungus that gave it its name, and Barger and Ewins proposed its betaine structure in 1911. Structurally it is histidine carrying three methyl groups on its amino nitrogen, with a sulfur atom at position 2 of the imidazole ring; its systematic name describes that sulfur as a thioxo group. Supplement grade material is a white crystalline powder.
How organisms build it
In Mycobacterium smegmatis five genes, egtA to egtE, do the work. EgtD methylates histidine three times to make hercynine, EgtB attaches a sulfur donor from gamma-glutamylcysteine, and EgtC and EgtE trim the intermediate down to ergothioneine. Fungi such as Neurospora crassa and Schizosaccharomyces pombe use two enzymes, Egt1 and Egt2. Cyanobacteria, including spirulina, also contain it.
SLC22A4 and OCTN1
The SLC22A4 gene codes for OCTN1, a protein long grouped with organic cation and carnitine transporters. In 2005 Gründemann and colleagues showed that its main substrate is ergothioneine, moved with high efficiency, while the related carnitine transporter OCTN2 did not carry it. They proposed the name ETT. Expression was strong in CD71 positive cells, which include immature red blood cells, and in monocytes. In one human study, whole blood ergothioneine kept climbing for weeks after dosing stopped, peaking around day 28.
Mushrooms as the main food source
Penn State researchers measured ergothioneine and glutathione in 13 mushroom species. Porcini, a wild species, had the most of both; white button mushrooms had less than porcini but more than most other foods. Cooking did not appear to significantly change the levels, since ergothioneine is heat stable. A 2022 review lists oyster mushrooms with porcini among the richest sources.
How It Is Made and How to Read a Label
| Source | How it is made | Examples on record |
|---|---|---|
| Fermentation | Engineered E. coli given ergothioneine genes turns histidine into ergothioneine, which is purified by ion exchange, crystallization and decolorizing. | GRN 734: E. coli K-12 with four cloned genes, at least 98% pure, sold as a 5% powder on maltodextrin. GRNs 1191 and 1270: other E. coli strains carrying fungal or bacterial egt genes. |
| Chemical synthesis | Built from protected histidine; only the L form has been synthesized. | Tetrahedron's synthetic L-ergothioneine, the material behind the 2017 EU authorisation. |
| Mushroom extracts | Dried or extracted mushroom. | One Pleurotus eryngii formulation supplied 0.75 mg per 500 mg capsule, so content varies widely. |
What to look for
- The name L-ergothioneine, the designation EU rules require.
- Milligrams of ergothioneine itself, not of a powder or extract. 500 mg of a 5% powder gives 25 mg.
- The source: fermentation, synthesis or a named mushroom, with a purity figure.
- Ingredient testing for heavy metals and microbes.
Human Research, Study by Study
Trials of pure ergothioneine, plus one whole food trial, in adults.
| Study | Who | Amount a day | Length | Measured | Result |
|---|---|---|---|---|---|
| Cheah 2017, Antioxid Redox Signal | 45 healthy men aged 21 to 35, placebo controlled | 5 or 25 mg | 7 days, followed to day 35 | Blood and urine levels, oxidative damage and inflammation markers, liver tests, lipids | Plasma rose with dose; whole blood peaked near day 28; under 4% of the dose appeared in urine; damage markers trended lower; no adverse effects |
| Okumura 2025, Food Sci Nutr | Adults, double blind, placebo controlled | 8 mg | 16 weeks | Subjective sleep quality | Sleep quality ratings better than placebo |
| Zajac 2025, Nutraceuticals | 147 adults aged 55 to 79 with memory complaints, placebo controlled | 10 or 25 mg | 16 weeks | Memory and other cognitive tests, self rated memory and sleep, blood markers | Plasma levels rose with dose; composite memory up from baseline at week 4 on 25 mg; reaction time, prospective memory and sleep onset ratings improved; well tolerated |
| Yau 2024, J Alzheimers Dis | 19 adults aged 60 to 90 with mild cognitive impairment, placebo controlled pilot | 25 mg, three times a week | 52 weeks | Cognitive tests, plasma levels, neurofilament light (NfL), safety labs | Plasma about fivefold higher by 26 weeks; word recall above baseline at 52 weeks; NfL steady while it rose on placebo; safety labs unchanged |
| Cha 2026, Food Funct | 80 adults aged 60 to 80 | Oyster mushrooms, 4 portions a week (food) | 12 weeks | Memory, mood, metabolic and inflammation markers | Delayed recall and recognition improved and mood held steadier than with placebo |
Amounts Used in Human Studies
Study amounts, not directions. Follow your product's label.
| Setting | Amount |
|---|---|
| Short term uptake study | 5 or 25 mg a day for 7 days |
| Sleep trial | 8 mg a day for 16 weeks |
| Memory complaints trial | 10 or 25 mg a day for 16 weeks |
| One year pilot | 25 mg three times a week (75 mg a week) |
| EU maximum, food supplements | 30 mg a day for adults; 20 mg a day for children over 3 |
| US GRAS food uses (GRN 734, 1191) | 5 mg per serving in listed foods |
Safety, Side Effects and Interactions
In Cheah 2017 no adverse effects were reported and liver tests and lipids did not change. Safety labs were unchanged over a year in Yau 2024, and Zajac 2025 described the supplement as well tolerated.
Toxicology
EFSA's 2016 opinion on synthetic L-ergothioneine set a no observed adverse effect level of 800 mg per kg of body weight a day, giving safety margins of 470 for adults and 216 for children over 3. A 2017 EFSA statement found that the conclusion also holds for infants, toddlers, and women who are pregnant or breastfeeding, at the expected intakes.
Side effects and who should ask first
WebMD notes that allergic reactions are possible, with a higher risk in people allergic to mold or mushrooms, that ergothioneine passes into breast milk, and that interactions with medicines are not well understood. Ask a clinician first if you have a mushroom or mold allergy, a kidney or liver condition, are pregnant or breastfeeding, or take prescription or over the counter medicine. Stop and get help right away if you notice swelling, hives, rash or trouble breathing.
Regulatory Status in the US and EU
United States
Ergothioneine is sold in dietary supplements under the Dietary Supplement Health and Education Act of 1994, and FDA does not approve supplements before sale. For conventional foods, FDA answered three GRAS notices with no questions: GRN 734 from Blue California (May 7, 2018), GRN 1191 from Shanghai EGT Synbio (January 30, 2025) and GRN 1270 from Gene III Biotechnology (January 2026), all for fermentation made ergothioneine in foods such as baked goods, coffee, tea and soft drinks. A no questions letter is not FDA's own GRAS determination.
European Union
Implementing Decision (EU) 2017/1281 of 13 July 2017 authorised synthetic L-ergothioneine in food supplements at up to 30 mg a day for the general population, excluding pregnant and breastfeeding women, and 20 mg a day for children over 3, labeled as L-ergothioneine.
Ergothioneine FAQ
What is the OCTN1 transporter?
OCTN1 is a membrane protein made from the SLC22A4 gene. It moves ergothioneine into cells together with sodium, far more efficiently than the other molecules it was first linked to, which is why it is also called the ergothioneine transporter (ETT).
Is ergothioneine an amino acid?
It is a derivative of the amino acid histidine: histidine with three methyl groups on its amino nitrogen and a sulfur atom on its ring. Its formula is C9H15N3O2S.
How is L-ergothioneine for supplements made?
Mostly by fermentation with engineered E. coli carrying ergothioneine genes from fungi or bacteria, or by chemical synthesis. Mushroom extracts also contain it, at amounts that depend on the species and extract.
Does cooking destroy the ergothioneine in mushrooms?
Penn State researchers reported that cooking did not appear to significantly affect it, since ergothioneine is heat stable.
What does a 5% ergothioneine powder mean?
Ergothioneine makes up 5% of the powder by weight, with a carrier such as maltodextrin making up the rest. 500 mg of such a powder supplies 25 mg of ergothioneine.
What is the regulatory status of ergothioneine in the US?
It is sold in dietary supplements, and FDA has answered three GRAS notices for ergothioneine in conventional foods with no questions, in 2018, 2025 and 2026.
How much ergothioneine is in Brain Energy Capsules?
The planned formula lists L-ergothioneine 25 mg per serving, alongside 500 mg citicoline and 20 mg PQQ. It is a pre-order, and no payment is taken now.
More on Ergothioneine
Shop and ingredients
Mushroom ingredient pages
Sources
- Cordell GA, Lamahewage SNS. Ergothioneine, ovothiol A, and selenoneine: histidine-derived, biologically significant, trace global alkaloids. Molecules, 2022. DOI 10.3390/molecules27092673
- Gründemann D, et al. Discovery of the ergothioneine transporter. PNAS, 2005. PubMed 15795384
- Kalaras MD, et al. Mushrooms: a rich source of the antioxidants ergothioneine and glutathione. Food Chemistry, 2017, as reported by Penn State News, November 2017. psu.edu
- Cheah IK, et al. Administration of pure ergothioneine to healthy human subjects. Antioxidants and Redox Signaling, 2017. DOI 10.1089/ars.2016.6778
- Okumura H, et al. Estimation and validation of an effective ergothioneine dose for improved sleep quality using a physiologically based pharmacokinetic model. Food Science and Nutrition, 2025. PubMed 40475978
- Zajac IT, et al. The effect of ergothioneine supplementation on cognitive function, memory, and sleep in older adults with subjective memory complaints. Nutraceuticals, 2025. DOI 10.3390/nutraceuticals5030015
- Yau YF, et al. Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: a pilot study. Journal of Alzheimer's Disease, 2024. DOI 10.1177/13872877241291253
- Cha S, et al. A randomised controlled study of oyster mushroom in older adults. Food and Function, 2026. PubMed 42299921
- US FDA. GRAS Notice GRN 734, ergothioneine (Blue California), notice and response letter, 2018. fda.gov
- US FDA. Response letter, GRN 1191, ergothioneine (Shanghai EGT Synbio), 2025. fda.gov
- US FDA. Response letter, GRN 1270, L-ergothioneine (Gene III Biotechnology), 2026. fda.gov
- EFSA NDA Panel. Safety of synthetic L-ergothioneine (Ergoneine) as a novel food. EFSA Journal, 2016. DOI 10.2903/j.efsa.2016.4629
- EFSA NDA Panel. Statement on the safety of synthetic L-ergothioneine as a novel food. EFSA Journal, 2017. PubMed 32625352
- Nutrition Insight. Synthetic antioxidant L-ergothioneine safe as a novel food for pregnant women and children: EFSA. November 2017. nutritioninsight.com
- Commission Implementing Decision (EU) 2017/1281 authorising synthetic L-ergothioneine as a novel food ingredient. eur-lex.europa.eu
- WebMD. Ergothioneine. Vitamins and Supplements. webmd.com
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. If you are pregnant, breastfeeding, allergic to mushrooms or mold, taking medication or managing a health condition, talk with a qualified healthcare professional before use.