Ergothioneine
L-Ergothioneine
Novel 'longevity vitamin' antioxidant found in mushrooms that accumulates in cells under oxidative stress — emerging longevity compound.
Ergothioneine is a unique amino acid antioxidant produced by fungi and certain bacteria, not by humans. The body has a dedicated transporter (OCTN1) that concentrates it in tissues under oxidative stress. Some researchers propose it as a longevity vitamin. Found primarily in mushrooms, it protects mitochondria and has been linked to reduced cognitive decline and mortality in observational studies.
Mechanisms of Action
Cytoprotection
Protects cells from oxidative damage
Mitochondrial Protection
Concentrates in and protects mitochondria
Selective Accumulation
Body actively concentrates it where needed
Recommended Dose
5-25mg daily
Optimal Timing
- Any time
- With or without food
Can be taken without food
Best Form
Synthetic L-ergothioneine capsules
Alternatives: Mushroom extracts (lower content), Fermented production
Pure ergothioneine supplements provide consistent dosing. Mushrooms vary in content (king trumpet/oyster highest).
Duration
Minimum: ongoing
Optimal: ongoing
Cycling: Not required
Note: Stable compound that can be taken any time.
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Cellular Protection
Reduced oxidative damage
Cognitive Support
Potential brain protection
Generally considered very safe; found naturally in diet
Who Should NOT Take This
- Known allergy or hypersensitivity to Ergothioneine or related compounds
Drug Interactions
Antioxidants may theoretically interfere with oxidative stress-based treatments; consult oncologist
May interact with anticonvulsants; consult healthcare provider
Theoretical interaction; both use organic cation transporters
May potentially affect efficacy; limited research available
Possible Side Effects
Tip: N/A
Warnings
- Emerging compound — long-term human data limited
- Expensive compared to other antioxidants
Top studies from 40+ peer-reviewed papers
Arslan NP et al. • Critical reviews in food science and nutrition (2025)
“This review summarizes the antioxidant potential of different fungi (mushrooms, yeasts, and molds)-derived natural compounds such as polysaccharides, pigments, peptides, ergothioneine, ergosterol, phenolics, alkaloids, etc.”
Key Findings:
- Fungi-derived antioxidants exhibit scavenging activities against DPPH, ABTS, hydroxyl, superoxide, hydrogen peroxide, and nitric oxide radicals in vitro.
- Furthermore, in vivo models, application of fungal-derived antioxidants increase the level of various antioxidant enzymes, such as catalases, superoxide dismutases, and glutathione peroxidases, and reduce the level of malondialdehyde.
- Therefore, fungi-derived antioxidants have potential to be used in the food, cosmetic, and pharmaceutical industries.
- This review summarizes the antioxidant potential of different fungi (mushrooms, yeasts, and molds)-derived natural compounds such as polysaccharides, pigments, peptides, ergothioneine, ergosterol, phenolics, alkaloids, etc.
Jędrejko M et al. • Nutrients (2025)
“Nevertheless, supplementation with anserine and ergothioneine shows promise for enhancing physical performance and recovery, though further research is required to better understand their mechanisms and optimize their use in sports and exercise.”
Key Findings:
- Although balenine has been less extensively studied, it has shown promise in enhancing muscle regeneration and antioxidative defense in animal models.
- Ergothioneine, a sulfur-containing histidine derivative, displayed antioxidant and anti-inflammatory properties in both animal and human studies, suggesting its potential role in reducing exercise-induced oxidative stress and aiding recovery.
- The diversity of the presented studies and their limitations do not provide an opportunity to confirm the ergogenic properties of the histidine-containing compounds studied.
- Nevertheless, supplementation with anserine and ergothioneine shows promise for enhancing physical performance and recovery, though further research is required to better understand their mechanisms and optimize their use in sports and exercise.
Halliwell B et al. • Annual review of food science and technology (2023)
“By contrast, α-tocopherol has demonstrated in vivo antioxidant effects in humans.”
Key Findings:
- The various possible functions of ET in vivo are explored.
- Much emphasis has been placed on the antioxidant properties of ET, but although these are well established in vitro, the evidence that antioxidant activity is the principal function of ET in vivo is weak.
- ET is not unique in this: The evidence for the antioxidant roles of vitamin C and polyphenols such as the flavonoids in vivo is also weak.
- By contrast, α-tocopherol has demonstrated in vivo antioxidant effects in humans.
Ba DM et al. • Nutrition journal (2021)
“In a meta-analysis of prospective cohort studies, mushroom consumption was associated with a lower risk of all-cause mortality.”
Key Findings:
- The meta-analysis of prospective cohort studies, including 601,893 individuals, showed that mushroom consumption was associated with a lower risk of all-cause mortality (pooled risk ratio: 0.94; 95% CI: 0.91, 0.98).
- Published in Nutrition journal (2021)
- Further research warranted to confirm findings
Holeček M • Nutrients (2020)
“Of concern should be findings of hepatic enlargement and increases in ammonia and glutamine and of decrease in branched-chain amino acids (valine, leucine, and isoleucine) in blood plasma indicating that HIS supplementation is inappropriate in patients with liver disease.”
Key Findings:
- Several decades of experience have confirmed the effectiveness of HIS as a component of solutions used for organ preservation and myocardial protection in cardiac surgery.
- Further studies are needed to elucidate the effects of HIS supplementation on neurological disorders, atopic dermatitis, metabolic syndrome, diabetes, uraemic anaemia, ulcers, inflammatory bowel diseases, malignancies, and muscle performance during strenuous exercise.
- Signs of toxicity, mutagenic activity, and allergic reactions or peptic ulcers have not been reported, although HIS is a histamine precursor.
- Of concern should be findings of hepatic enlargement and increases in ammonia and glutamine and of decrease in branched-chain amino acids (valine, leucine, and isoleucine) in blood plasma indicating that HIS supplementation is inappropriate in patients with liver disease.
Study Type Distribution
Goals This Supplement Supports
Related Goals
This information is for educational purposes only and is not intended as medical advice. Always consult a qualified healthcare provider before starting any supplement.