There has been a recent surge of interest in the unique low molecular weight dietary thiol/thione, ergothioneine. This compound can accumulate at high levels in the body from diet and may play important physiological roles in human health and development, and possibly in prevention and treatment of disease. Blood levels of ergothioneine decline with age and onset of various diseases. Here we highlight recent advances in our knowledge of ergothioneine.

Low blood concentrations of the diet-derived compound ergothioneine (ET) have been associated with cognitive impairment and cerebrovascular disease (CeVD) in cross-sectional studies, but it is unclear whether ET levels can predict subsequent cognitive and functional decline. Here, we examined the temporal relationships between plasma 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 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, the longitudinal associations were found only in non-demented individuals. Mediation analyses showed that the 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.

Infection with SARS-CoV-2 causes the coronavirus infectious disease 2019 (COVID-19), a pandemic that has, at present, infected more than 11 million people globally. Some COVID-19 patients develop a severe and critical illness, spurred on by excessive inflammation that can lead to respiratory or multiorgan failure. Numerous studies have established the unique array of cytoprotective properties of the dietary amino acid ergothioneine. Based on studies in a range of in vitro and in vivo models, ergothioneine has exhibited the ability to modulate inflammation, scavenge free radicals, protect against acute respiratory distress syndrome, prevent endothelial dysfunction, protect against ischemia and reperfusion injury, protect against neuronal damage, counteract iron dysregulation, hinder lung and liver fibrosis, and mitigate damage to the lungs, kidneys, liver, gastrointestinal tract, and testis, amongst many others. When compiled, this evidence suggests that ergothioneine has a potential application in the treatment of the underlying pathology of COVID-19. We propose that ergothioneine could be used as a therapeutic to reduce the severity and mortality of COVID-19, especially in the elderly and those with underlying health conditions. This review presents evidence to support that proposal.

Background: Dementia, particularly Alzheimer's disease, is a major healthcare challenge in ageing societies. Objective: This study aimed to investigate the efficacy and safety of a dietary compound, ergothioneine, in delaying cognitive decline in older individuals. Methods: Nineteen subjects aged 60 or above with mild cognitive impairment were recruited for this double-blinded, randomized, and placebo-controlled study (ClinicalTrials.gov identifier: NCT03641404, registration date: 19/08/2018). Subjects received either ergothioneine (25 mg per capsule) or a placebo, taken 3 times a week for one year. The whole blood profile, markers of renal and liver functions, neurocognitive performance, plasma levels of ergothioneine and its metabolites, and plasma biomarkers related to neurodegeneration were measured across the study. Results: Ergothioneine intake did not alter clinical safety markers (blood counts, kidney and liver function) throughout the study, further validating its safety for human consumption. Subjects receiving ergothioneine demonstrated improved performance in assessment of learning ability and stabilized plasma levels of neurofilament light chain, compared with the placebo group, which saw no improvement in cognitive assessments and a significant increase in neurofilament light chain levels. Conclusions: Prolonged intake of ergothioneine showed no toxicity in elderly people. Enhanced Rey Auditory Verbal Learning Test performance and stabilized neurofilament light chain levels suggest improvements in memory and learning abilities and a deceleration of neuronal damage, respectively. Our results add to existing data that ergothioneine is safe for extended consumption and may hold the potential to delay cognitive decline in elderly adults.