Ergothioneine — The Longevity Amino Acid
Ergothioneine (ET) is a naturally occurring amino acid and potent antioxidant found primarily in mushrooms, black beans, and oat bran. Humans have a dedicated transporter (OCTN1/SLC22A4) for ergothioneine — suggesting evolutionary importance — and accumulate it in high concentrations in mitochondria, red blood cells, and the lens of the eye. Low plasma ergothioneine is associated with cognitive decline and increased mortality.
Mechanism of Action
ET is a histidine-derived thiol that accumulates in mitochondria and protects against oxidative damage to mtDNA and mitochondrial membranes. Unlike most antioxidants, ET is not consumed in the process — it regenerates itself after radical quenching. It also chelates metal ions (Cu, Fe) that catalyse free radical production, and activates Nrf2.
Human Trial Evidence
A 2020 Biochemical and Biophysical Research Communications study showed plasma ET levels are significantly lower in patients with mild cognitive impairment and Alzheimer's disease. A 2021 PLOS ONE prospective study of 3,236 adults showed low plasma ET was associated with significantly higher all-cause mortality over 20 years. Human supplementation trials are emerging (2023–2025).
Dosing Protocol
5–30 mg/day (emerging evidence). Mushrooms are the richest dietary source — oyster, shiitake, and king oyster mushrooms contain 1–5 mg per 100g. Standalone ET supplements are becoming available. The dedicated OCTN1 transporter suggests saturable absorption — higher doses may not proportionally increase tissue levels.
Safety & Contraindications
Excellent safety profile. No adverse effects reported in any human study. The dedicated transporter suggests it is a physiologically essential compound. No drug interactions identified. Safe for long-term use.