Three 2022 papers on amino acid ergothioneine, starting with a human study:
“We examined temporal relationships between plasma ergothioneine (ET) status and cognition in a cohort of 470 elderly subjects attending memory clinics in Singapore. All participants underwent baseline plasma ET measurements as well as neuroimaging for cerebrovascular disease (CeVD) and brain atrophy. Neuropsychological tests of cognition and function were assessed at baseline and follow-up visits for up to five years.
Lower plasma ET levels were associated with poorer baseline cognitive performance and faster rates of decline in function as well as in multiple cognitive domains including memory, executive function, attention, visuomotor speed, and language. In subgroup analyses, longitudinal associations were found only in non-demented individuals.
Mediation analyses showed that effects of ET on cognition seemed to be largely explainable by severity of concomitant CeVD, specifically white matter hyperintensities, and brain atrophy. Our findings support further assessment of plasma ET as a prognostic biomarker for accelerated cognitive and functional decline in pre-dementia and suggest possible therapeutic and preventative measures.”
https://www.mdpi.com/2076-3921/11/9/1717 “Low Plasma Ergothioneine Predicts Cognitive and Functional Decline in an Elderly Cohort Attending Memory Clinics”
Earlier this year, two of the study’s coauthors put together a collection of 11 ergothioneine papers:
“One catalyst for this upsurge of interest was the discovery in 2005 of a transporter for ET (OCTN1, often now called the ergothioneine transporter, ETT), which accounts for the fact that animals (including humans) take up and avidly retain ET from the diet. The presence of a specific transporter together with the avid retention of ET in the body implies that this compound is important to us.
To quote an old phrase ‘correlation does not imply causation.’ Low ET levels may predispose to disease, but disease could also lead to low ET levels. Possible reasons could include:
- Alterations in diet due to illness so that less ET is consumed;
- Decreases in ETT activity in the gut (leading to less ET uptake) or kidney (impairing ET reabsorption) with age and disease.
- Changes in gut microbiota might influence uptake and accumulation in the body.
- ET is being consumed as it scavenges oxygen radicals and other reactive oxygen species, the production of which is known to increase in these diseases and during ageing in general.
Only the gold standard of placebo-controlled double-blinded clinical studies can definitively establish the value (if any) of ET in preventing or treating human disease. Several such trials are being planned or in progress; we await the results with interest, and a streak of optimism.”
https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14350 “Ergothioneine, where are we now?”
One of the collection’s papers focused on what ETT research findings could or could not be replicated:
“ETT is not expressed ubiquitously and only cells with high ETT cell-surface levels can accumulate ET to high concentration. Without ETT, there is no uptake because the plasma membrane is essentially impermeable. We review substrate specificity and localization of ETT, which is prominently expressed in neutrophils, monocytes/macrophages, and developing erythrocytes.
Comparison of transport efficiency (TE) for acknowledged substrates of the ETT. Bar length represents approximate TE of wild-type human ETT.
We have not found in the literature any other ET transporters. However, it is highly probable that additional ET transporters work in the human body:
- Uptake of ET from the small intestine into epithelial cells occurs through apically localized ETT. The very hydrophilic ET cannot then exit these cells toward the blood without help – a basolateral efflux transporter is required.
- After oral administration of 3H-ET, a considerable amount of ET was still absorbed into the body in the ETT KO [knockout] mice. There must be another transporter for apical uptake at least in the small intestine of the mouse.
- When ET was administered intravenously, ETT KO mice showed no change in ET concentration in the brain compared to wild type. The little ET that enters the brain must therefore pass through the BBB via a different transporter.”
https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14269 “The ergothioneine transporter (ETT): substrates and locations, an inventory”
It’s persuasive that there’s an evolutionarily conserved transmitter specific to ergothioneine. It isn’t persuasive that this compound once consumed is almost always in stand-by mode to do: what?
Ergothioneine isn’t a substitute for the related glutathione, especially since its supply isn’t similarly available from an endogenous source. It isn’t an active participant in day-to-day human life.
Still, I hedge my bets. I eat ergothioneine every day via white button mushrooms in AGE-less chicken vegetable soup at a cost of about $1.30.