L-Ergothioneine: OCTN1-Targeted
Cytoprotective Amino Acid
L-Ergothioneine is actively transported into cells via OCTN1 — a dedicated transporter expressed in tissues including erythrocytes, liver, brain, and skin. This active uptake mechanism distinguishes EGT from most dietary antioxidants.
≥99% Purity (HPLC)
Synthetic origin — not fermentation-derived. Free from biological contaminants and fermentation residuals.
White Crystalline Solid
C₉H₁₅N₃O₂S, MW 229.30 g/mol. Freely water-soluble. Stable under standard storage conditions.
Regulatory Status
FDA GRAS (GRN 000734) for food use. EU Novel Food authorized. Applicable to supplement, cosmetic, and food ingredient use cases (subject to local regulations).
Mechanism of Action
The OCTN1 Transport Mechanism
Most dietary antioxidants rely on passive diffusion and are rapidly metabolized. EGT is different: it has a dedicated high-affinity transporter (OCTN1/SLC22A4) that actively concentrates it in tissues under the greatest oxidative burden — and keeps it there. This transporter-guided biology is a key reason Bruce Ames proposed ergothioneine as a "longevity vitamin" in his 2018 framework.
The OCTN1 Advantage
Active Uptake, Not Passive Diffusion
OCTN1 (Organic Cation Transporter Novel 1, gene SLC22A4) was identified as the specific ergothioneine transporter by Gründemann et al. in 2005. It is expressed in virtually every mammalian tissue, with highest concentrations in:
- Erythrocytes (red blood cells) — primary circulatory reservoir
- Liver — detoxification hub
- Kidney — filtration and high metabolic demand
- Lens of the eye — photoprotection
- Brain — neurons and glial cells
- Skin — dermis and keratinocytes (high UV exposure)
- Mitochondria-rich tissues — high metabolic demand
Key property
Long half-life in humans
Unlike ascorbic acid or glutathione, EGT is not rapidly excreted. It accumulates over weeks of dietary intake and is retained in tissues — contributing to a sustained antioxidant presence distinct from other dietary antioxidants.
Key property
Not synthesized by mammals
Humans and other mammals cannot biosynthesize EGT — it must come entirely from the diet. Fungi (mushrooms) are the dominant dietary source; most Western diets provide insufficient amounts.
Free Radical Scavenging
EGT exists predominantly in the thione tautomeric form — a sulfur arrangement that contributes to strong radical-scavenging activity relative to other thiol antioxidants such as cysteine or glutathione. It efficiently neutralizes hydroxyl radicals, hypochlorous acid (HOCl), and peroxynitrite (ONOO⁻) — among the most reactive oxygen and nitrogen species in biological systems.
The thione tautomer is unique to ergothioneine among common dietary antioxidants.
Metal Chelation
EGT chelates redox-active transition metals — particularly Cu²⁺ and Fe²⁺ — preventing them from catalyzing Fenton-type reactions that generate hydroxyl radicals. This metal-chelating activity complements its direct radical-scavenging role and is especially relevant in tissues with high iron turnover (liver, erythrocytes).
Chelation is non-destructive: the EGT–metal complex is stable and does not generate secondary radicals.
Mitochondrial Protection
OCTN1 is highly expressed in metabolically active cells. EGT concentrates in mitochondria-rich compartments, where it provides protection against oxidative phosphorylation byproducts. In aging cell models, EGT supplementation preserved mitochondrial membrane potential and reduced markers of cellular senescence.
Mitochondrial dysfunction is a central driver of aging and neurodegeneration.
Neuroprotection
The brain is highly susceptible to oxidative damage due to its high oxygen consumption and lipid-rich membranes. OCTN1 is expressed in neurons and glial cells. A longitudinal study of 470 memory clinic participants found lower plasma EGT was associated with faster cognitive decline across multiple domains. Earlier cross-sectional data also showed declining plasma EGT with age and cognitive impairment.
EGT blood levels decline with age — and more sharply in individuals with cognitive decline.
H₂S Signaling & NAD⁺ Metabolism
Emerging 2025 evidence indicates EGT engages hydrogen sulfide (H₂S) signaling through the enzyme cystathionine gamma-lyase (CSE), driving protein persulfidation and activation of cytosolic glycerol-3-phosphate dehydrogenase (cGPDH). This pathway elevated NAD⁺ levels in aged animal muscle. These findings reposition EGT from a generic antioxidant toward a precision longevity molecule intersecting stress signaling and metabolic resilience.
Mechanistically complementary to NAD⁺ precursor strategies (NMN, NR) — though combination data has not been published.
Literature Evidence
What the Research Shows
EGT has been studied in population cohorts, cell models, and animal systems. We summarize the key findings below — with honest notes on study limitations, because the science matters more than the marketing.
Higher EGT Levels Associated with Lower CV Mortality (Observational)
Smith et al. followed 3,236 adults for a median of 21 years. Per 1 SD increment in plasma EGT, the adjusted hazard ratios were approximately 0.85 for coronary disease, 0.79 for cardiovascular mortality, and 0.86 for all-cause mortality — significant after multivariate adjustment.
Note: Observational study — association, not confirmed causation.
EGT Declines with Age; Lower in Mild Cognitive Impairment
Cheah et al. measured plasma EGT in an elderly population. Levels declined significantly beyond age 60. Individuals with mild cognitive impairment had significantly lower EGT than age-matched controls, suggesting low EGT status may be a risk factor for neurodegeneration.
Note: Observational; causality vs consequence of disease not established.
Lower EGT in Neurodegenerative Disease
Halliwell, Cheah & Tang reviewed data showing EGT is substantially lower in patients with mild cognitive impairment, Parkinson's disease, and other neurodegenerative conditions compared to healthy age-matched controls. OCTN1 expression is high in brain regions vulnerable to neurodegeneration.
Note: Causality vs. consequence not yet established; active research area.
Low Dietary EGT Intake Reported in US Population Surveys
Beelman et al. calculated that the average American diet provides only 1.1 mg/day of EGT — almost entirely from mushroom consumption. Studies linking health benefit to EGT status typically involve populations with much higher intakes (Japan, Mediterranean countries with higher mushroom consumption).
Note: Optimal intake levels are not formally established; dietary reference values are under development.
Where the Science Stands
Well-established
- — OCTN1-mediated active uptake
- — Tissue accumulation pattern
- — Thione radical-scavenging mechanism ,
- — Age-related decline in blood levels
- — Dietary source distribution ,
Promising, more data needed
- — Cardiovascular associations (observational)
- — Neural tissue accumulation and biomarkers
- — Optimal supplementation dose
- — Long-term supplementation outcomes
Active research areas
- — Human RCTs for long-term health endpoints
- — Cognitive function intervention trials
- — Skin photoprotection clinical data
- — Optimal dietary reference values
Applications
Where EGT Fits Your Formulation
EGT's regulatory status, solubility, and stability profile make it a versatile ingredient across supplements, cosmetics, and functional foods.
A High-Value Supplement Ingredient
EGT is increasingly positioned alongside NAD+ precursors (NMN, NR), CoQ10, and glutathione as a premium antioxidant supplement ingredient. Its FDA GRAS status (for specified food uses) and EU Novel Food authorization (for defined categories) provide a regulatory foundation in key markets. Synthetic EGT is preferred over fermentation-derived for consistency and purity.
Typical use level
5–30 mg/day (EU Novel Food upper limit: 30 mg/day for adults)
See , for regulatory status details.
Use Cases
- Antioxidant and healthy-aging capsule/tablet formulations
- Mitochondrial health supplements
- Brain health-positioned blends
- Antioxidant combination products (synergy with vitamin C, E)
- Sports recovery and cellular protection
Formulation Notes
- Highly water-soluble — easy to incorporate in liquid and powder formats
- Stable across a wide pH range
- Compatible with common excipients and co-ingredients
- No significant taste or odor at typical use levels
Quality & Manufacturing
Synthetic EGT — Why It Matters
Mironova Labs produces L-Ergothioneine via a defined synthetic chemical route — not fermentation. This gives us direct control over purity, consistency, and impurity profile at every step.
Synthetic vs. Fermentation-Derived EGT
| Criterion | Synthetic (Mironova) | Fermentation-Derived |
|---|---|---|
Batch-to-batch consistency Fermentation yields vary with strain, media, and process conditions | ||
Freedom from biological contaminants Fermentation cultures introduce cellular debris, residual media components | ||
No fermentation residuals Fermentation by-products (amino acids, vitamins, pigments) require extensive downstream processing | ||
Full structural characterization Both routes can achieve characterization; synthetic has simpler impurity profile | ||
Scalability Both scalable; synthetic process is more directly controllable | ||
Natural sourcing claim Fermentation can claim 'natural' or 'biotechnology-derived' positioning | ||
≥99% purity achievable Fermentation typically achieves 95–98% purity without extensive purification |
Product Specifications
| Chemical Name | (2S)-3-(2-thioxo-2,3-dihydro-1H-imidazol-4-yl)-2-(trimethylammonio)propanoate |
| Common Name | L-Ergothioneine (EGT) |
| CAS Number | 497-30-3 |
| Molecular Formula | C₉H₁₅N₃O₂S |
| Molecular Weight | 229.30 g/mol |
| Appearance | White to off-white crystalline powder |
| Purity (HPLC) | ≥99.0% |
| Specific Rotation | [α]D²⁰ = +116° (c = 1, H₂O) |
| Solubility | Freely soluble in water; slightly soluble in ethanol |
| pH (1% aq. solution) | 5.5–7.0 |
| Storage | Cool, dry place, away from light. Stable at room temperature. |
| Shelf Life | 3 years from manufacture date (sealed, ambient) |
Analytical Methods
Reverse-phase HPLC for purity and identity confirmation. Area normalization vs. reference standard.
Full structural confirmation against reference spectrum. Used for identity and to verify absence of structural isomers.
Molecular weight confirmation [M+H]⁺ = 230.09 Da. Used to detect trace impurities below HPLC detection threshold.
Confirms L-enantiomer configuration. Critical quality parameter for chiral purity.
ICH Q3C compliant; typical solvents tested: EtOH, EtOAc, acetone.
Elemental analysis for high-purity applications. Results reported per batch.
Water content determination. Anhydrous form: <1.0% H₂O.
Regulatory Status
Regulatory Status: Supplements, Cosmetics, and Food
USA — FDA GRAS
GRN No. 000734. L-Ergothioneine is Generally Recognized As Safe for use in conventional foods and dietary supplements. No quantity limits set by the GRAS notice for supplements; food use levels to be established as safe by the manufacturer.
EU — Novel Food
EFSA published a favorable safety opinion. EGT authorized as a novel food ingredient in food supplements in the EU. Maximum level: 30 mg/day for the general adult population. Not authorized for food fortification without separate application.
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Request a Sample or Technical Data Sheet
Whether you're evaluating EGT for the first time or qualifying a new supplier, we're ready to support your process with the technical detail you need.
- ≥99% purity CoA (HPLC, NMR, optical rotation)
- Research (gram) to commercial (kg) quantities
- Synthetic origin — free from fermentation residuals
- US-manufactured, Fairfield NJ — domestic supply chain
- SDS, TDS, and regulatory documentation on request
- Technical support from our PhD chemistry team
Contact Our Team
Our response time is typically 1–2 business days. Include your intended application and quantity range for the most relevant response.
Or email us directly at info@mironova.com
FAQ
Frequently Asked Questions
Common technical questions about this product line, answered by our scientific team.
Related Resources
Technical data, product specifications, and application guidance.
References
Literature & Sources
Technical and scientific claims on this page are grounded in peer-reviewed literature and official regulatory sources. DOIs are provided where available. We cite primary sources so you can verify everything we say.
Peer-Reviewed Literature
Discovery of the Ergothioneine Transporter
Gründemann D, Harlfinger S, Golz S, et al.
Identified OCTN1 (SLC22A4) as the dedicated high-affinity ergothioneine transporter. Established that EGT is actively accumulated in tissues — unlike most dietary antioxidants, which rely on passive diffusion. Foundational paper for understanding EGT's unique physiological role.
Ergothioneine; Antioxidant Potential, Physiological Function and Role in Disease
Cheah IK, Halliwell B.
Comprehensive review of EGT's antioxidant chemistry, tissue distribution (erythrocytes, liver, kidney, lens, brain), and mechanistic role in oxidative stress protection. Describes the thione tautomer's superior radical-scavenging properties compared to other thiol antioxidants.
Ergothioneine — A Diet-Derived Antioxidant with Therapeutic Potential
Halliwell B, Cheah IK, Tang RMY.
Updated review proposing EGT as a candidate 'longevity vitamin'. Covers mechanisms: scavenging hydroxyl radicals, hypochlorous acid, and peroxynitrite; chelating redox-active metals (Fe²⁺, Cu²⁺); and protecting mitochondria. Notes that EGT blood levels decline with age and in neurodegenerative disease.
Prolonging Healthy Aging: Longevity Vitamins and Proteins
Ames BN.
Proposed a class of 'longevity vitamins' — nutrients not essential for survival but important for long-term health and disease prevention. Ergothioneine is included alongside PQQ, CoQ10, and others. Argues that insufficient dietary EGT accelerates aging-associated damage.
Ergothioneine Levels in an Elderly Population Decrease with Age and Incidence of Cognitive Decline; a Risk Factor for Neurodegeneration?
Cheah IK, Feng L, Tang RMY, Lim KHC, Halliwell B.
Measured plasma EGT in elderly subjects. Levels declined significantly beyond age 60 and were lower in individuals with mild cognitive impairment compared to age-matched controls, suggesting low EGT status may be a risk factor for neurodegeneration.
Ergothioneine Is Associated with Reduced Mortality and Decreased Risk of Cardiovascular Disease
Smith E, Ottosson F, Hellstrand S, et al.
Prospective epidemiological study (n = 3,236). Higher plasma EGT was independently associated with significantly reduced all-cause mortality and lower incidence of major cardiovascular events after multivariate adjustment. One of the most-cited EGT epidemiology papers.
Is Ergothioneine a 'Longevity Vitamin' Limited in the American Diet?
Beelman RB, Phillips AT, Richie JP, et al.
Analysis of EGT content in common American foods. Mushrooms are overwhelmingly the dominant source; meat, eggs, and most vegetables contribute negligible amounts. Estimated typical US dietary intake is far below levels associated with health benefit in epidemiological studies.
Mushrooms: A Rich Source of the Antioxidants Ergothioneine and Glutathione
Kalaras MD, Richie JP, Calcagnotto A, Beelman RB.
Quantified EGT in 13 mushroom species. Porcini (Boletus edulis) contained the highest levels (~5 mg/g dry weight). King oyster, oyster, and shiitake also significant sources. White button mushrooms contained substantially less. Strong case for mushroom-derived dietary EGT.
The Unusual Amino Acid L-Ergothioneine Is a Physiologic Cytoprotectant
Paul BD, Snyder SH.
Demonstrated that EGT acts as a physiological cytoprotectant in mammalian cells under oxidative and UV stress. Depletion of OCTN1 (the EGT transporter) sensitized cells to oxidative damage, confirming the transporter is essential for EGT's protective function.
L-Ergothioneine Protects Retinal Pigment Epithelial Cells Against UV Radiation
Torregrossa AC, et al.
EGT significantly reduced UV-induced oxidative stress, DNA damage, and apoptosis in retinal pigment epithelial cells. Supports potential application in eye health formulations and photoprotective cosmetics.
Ergothioneine Prevents Oxidative Damage and Maintains Mitochondrial Function in Aging Cells
Kameda K, et al.
In cellular aging models, EGT supplementation preserved mitochondrial membrane potential, reduced ROS accumulation, and lowered markers of cellular senescence. Provides mechanistic support for the 'longevity vitamin' hypothesis at the cellular level.
Ergothioneine in the Prevention of Skin Aging: Mechanisms and Formulation Strategies
Oblong JE.
EGT protects dermal fibroblasts and keratinocytes from UV-induced oxidative damage and prevents degradation of extracellular matrix components. Skin is a primary target tissue (high OCTN1 expression). Reviews formulation compatibility with common cosmetic systems.
Ergothioneine Improves Healthspan via H₂S/Persulfidation-Dependent NAD⁺ Metabolism in Aged Animals
Hahm JH, Jeong I, Nguyen CDL, et al.
Ergothioneine acts as an alternative substrate for cystathionine gamma-lyase (CSE), increasing H₂S production and protein persulfidation. Activation of cytosolic glycerol-3-phosphate dehydrogenase (cGPDH) drives NAD⁺ increases in aged rat muscle. Effects abolished in models lacking CSE or cGPDH. Shifts EGT positioning from commodity antioxidant to precision longevity biochemistry.
Plasma Ergothioneine Is Associated with Cognitive Function and Decline in a Longitudinal Memory Clinic Cohort
Cheah IK, Lim KHC, Halliwell B, et al.
Longitudinal study of 470 memory clinic participants (up to 5 years). Lower baseline plasma EGT was associated with poorer cognition and faster decline across multiple domains. Mediation analysis suggests cerebrovascular disease burden partly explains the relationship.
Ergothioneine Supplementation in Older Adults with Subjective Memory Complaints: A 16-Week Randomized, Double-Blind, Placebo-Controlled Trial
Halliwell B, Cheah IK, et al.
RCT of n=147 adults (55–79 years) testing 10 mg and 25 mg daily EGT for 16 weeks. Primary cognitive composite did not sustain separation from placebo. Clear dose-dependent PK (∼6- and 16-fold plasma increases). Signals in subjective prospective memory and sleep initiation at 25 mg. No product-related adverse events.
Regulatory References
FDA GRAS Notice No. GRN 000734 — L-Ergothioneine
FDA issued a “no questions” response to the notifier’s conclusion that L-Ergothioneine is GRAS for specified food uses. This is not an affirmation of GRAS status under 21 CFR 170.35 but supports commercial use in the specified food categories.
EU Novel Food Authorization — L-Ergothioneine (Implementing Regulation (EU) 2018/462)
EFSA published a favorable opinion on L-Ergothioneine as a novel food ingredient. Implementing Regulation (EU) 2018/462 authorized use in food supplements at up to 30 mg/day for adults, with specific maximum levels for other food categories. Supports European market access for EGT-containing supplement products.
FDA GRAS Notice No. GRN 001270 — L-Ergothioneine (Updated Filing)
Updated GRAS notification expanding intended use conditions for L-Ergothioneine. Supplements earlier GRN 000734 with additional food category applications.