Ergothioneine

Ergothioneine is a sulfur-containing compound (a histidine betaine), mostly in its 'thione' form. Only fungi, certain bacteria, and cyanobacteria can make it. You get it from your diet, and mushrooms (porcini, oyster, shiitake) are the richest common source. Once you eat it, a transporter called OCTN1 (SLC22A4) actively pulls it into your cells. OCTN1 is highly active in demanding tissues like your brain, bone marrow, kidney, and muscle, and ergothioneine is its main natural cargo. Unlike typical thiols, it does not auto-oxidize at body pH. And it does not fuel hydroxyl-radical formation through the Fenton reaction. So it protects cells against reactive oxygen and nitrogen species, without the pro-oxidant downside. Bruce Ames proposed it as a possible 'longevity vitamin' in 2018, under his triage theory. His argument: too little of it silently speeds aging-related damage, long before a frank deficiency shows up. Your plasma ergothioneine declines with age and in frailty. In the Malmö Diet and Cancer cohort (n = 3,236; median 21.4-year follow-up), it was the metabolite most strongly tied to lower heart death (HR about 0.79 per SD) and all-cause death (HR about 0.86 per SD) (Smith et al. 2020). A Singapore memory-clinic cohort (n = 470; about 4-year follow-up) found that lower levels predicted faster decline in memory, executive function, and processing speed (Wu et al. 2022). But human randomized trials are limited, and cause is not established.

Last reviewed: June 22, 2026

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