- Ergothioneine is a naturally occurring amino acid derivative with potent antioxidant and cytoprotective properties. It is classified as a thiol compound (containing a sulfur group) and is synthesized exclusively by certain fungi and bacteria, though it accumulates in high concentrations in various plant and animal tissues through the food chain.
- Chemically known as (S)-2-mercaptohistidine trimethylbetaine, ergothioneine is structurally related to histidine but distinguished by its unique sulfur-containing imidazole ring, which underlies its stability and antioxidant function.
- Dietary sources of ergothioneine are primarily mushrooms, particularly oyster, shiitake, king bolete, and white button mushrooms, which are among the richest sources known. It is also present in oats, kidney beans, liver, and black and red beans, albeit in lower amounts. After ingestion, ergothioneine is efficiently transported across cell membranes via a highly specific transporter called ETT (ergothioneine transporter), encoded by the SLC22A4 gene. This transporter ensures selective accumulation of ergothioneine in tissues prone to oxidative stress, such as the liver, kidneys, brain, lungs, eyes, and erythrocytes.
- One of ergothioneine’s most remarkable features is its long half-life and resistance to oxidation, making it a stable intracellular antioxidant. Unlike other antioxidants, it is not consumed in redox reactions but can be recycled, allowing it to neutralize reactive oxygen species (ROS) and reactive nitrogen species (RNS) repeatedly. Additionally, ergothioneine chelates divalent metal ions such as iron and copper, reducing metal-catalyzed free radical formation. Its role in mitochondrial protection, DNA stability, and inflammation modulation has made it the subject of growing interest in the context of aging, neurodegeneration, cardiovascular disease, and chronic inflammation.
- Although ergothioneine is not currently classified as a vitamin, some researchers propose it may qualify as a “longevity vitamin” or conditionally essential micronutrient, due to its specific transporter, selective tissue accumulation, and protective effects in vivo. Studies in animals and observational human studies suggest that higher levels of ergothioneine are associated with reduced risk of cognitive decline, cardiovascular disease, and age-related frailty, though more clinical trials are needed to establish causal relationships and therapeutic dosages.
- In the food and supplement industries, ergothioneine is increasingly being marketed as a nutraceutical for its potential roles in brain health, skin protection, immune function, and anti-aging applications. Because it is naturally derived and has shown no toxicity in animal or human studies even at high doses, it is considered safe for consumption, and regulatory agencies in several countries have approved its use as a novel food or supplement ingredient.
