Benefits
Antioxidant protection
Ergothioneine is a strong antioxidant in laboratory studies, and the body absorbs and keeps it well. In healthy volunteers given pure ergothioneine, blood levels rose markedly and markers of oxidative damage to DNA, fats and proteins tended to fall, but most of those changes were not statistically significant.
Memory and learning in older adults
In a pilot trial, 19 adults aged 60 or older with mild cognitive impairment took 25 mg of ergothioneine or placebo three times a week for a year. The ergothioneine group scored better on a learning test and kept a blood marker of nerve damage steady, while it rose on placebo. Observational studies also link low blood levels to faster cognitive decline, which does not prove cause.
Healthy aging and blood ergothioneine levels
In a Swedish population study of 3,236 adults followed for a median 21 years, higher blood ergothioneine was linked to lower risk of coronary disease, cardiovascular death and death from any cause. Blood levels also fall after age 60. These are observational links that may reflect a healthier diet; no trial has shown that supplements slow aging.
Mechanism of action
OCTN1 transporter uptake
Humans absorb ergothioneine from food through a selective transporter, OCTN1 (SLC22A4), and keep it in tissues, with little lost in urine. Reviews describe higher levels in cells that express this transporter, such as red blood cells, and possible build-up at sites of tissue injury.
Antioxidant chemistry
In laboratory studies ergothioneine scavenges reactive oxygen species and protects cells. Claims that it is carried into mitochondria rest on weak and conflicting evidence, according to a detailed review.
Metal binding
Laboratory studies show ergothioneine binds metal ions such as copper, mercury, zinc, cadmium, cobalt and nickel, and copper binding prevented copper-driven DNA damage in test-tube experiments. This has not been measured in people.
Clinical trials
Observational cohort with baseline plasma ergothioneine, brain imaging and up to five years of cognitive follow-up (Wu et al. 2022, Antioxidants)
470 older adults attending memory clinics in Singapore.
Lower plasma ergothioneine went with poorer baseline cognition and faster decline in function, memory, executive function, attention and other areas, mainly in people without dementia. Much of the link was explained by blood vessel disease in the brain and brain atrophy. Observational, so it cannot show that supplements help.
Prospective population cohort with 112 plasma metabolites measured and a median follow-up of 21.4 years (Smith et al. 2020, Heart)
3,236 adults without cardiovascular disease or diabetes at baseline in Malmö, Sweden.
Ergothioneine was the metabolite most tied to a health-conscious diet. Each standard deviation higher was linked to lower risk of coronary disease (HR 0.85), cardiovascular death (HR 0.79) and death from any cause (HR 0.86). Observational; it may mainly reflect a healthier diet.
Double-blind, randomized, placebo-controlled pilot trial: 25 mg ergothioneine or placebo three times a week for one year (Yau et al. 2024, Journal of Alzheimer's Disease)
19 adults aged 60 or older with mild cognitive impairment.
The ergothioneine group improved on the Rey Auditory Verbal Learning Test and its plasma neurofilament light, a nerve damage marker, stayed stable, while the placebo group showed no cognitive improvement and a significant rise in neurofilament light. Safety blood tests did not change. Very small; needs confirmation.
Human uptake and pharmacokinetic study of oral pure ergothioneine with oxidative damage and inflammation markers (Cheah et al. 2017, Antioxidants and Redox Signaling)
Healthy adult volunteers.
Ergothioneine was readily absorbed and retained, with less than 4% excreted in urine. Markers of oxidative damage to DNA, fats and proteins and C-reactive protein tended to fall, but most changes were not significant.