Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study.

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.

Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons.

Cell death involving oxidative stress and mitochondrial dysfunction is a major cause of dopaminergic neuronal loss in the substantia nigra (SN) of Parkinson's disease patients. Ergothioneine (ET), a natural dietary compound, has been shown to have cytoprotective functions, but neuroprotective actions against PD have not been well established. 6-Hydroxydopamine (6-OHDA) is a widely used neurotoxin to simulate the degeneration of dopaminergic (DA) neurons in Parkinson's disease.

Ergothioneine and mitochondria: An important protective mechanism?

Mitochondrial dysfunction is implicated in a wide range of human disorders including many neurodegenerative and cardiovascular diseases, metabolic diseases, cancers, and respiratory disorders. Studies have suggested the potential of l-ergothioneine (ET), a unique dietary thione, to prevent mitochondrial damage and improve disease outcome. Despite this, no studies have definitively demonstrated uptake of ET into mitochondria.

Are age-related neurodegenerative diseases caused by a lack of the diet-derived compound ergothioneine?

We propose that the diet-derived compound ergothioneine (ET) is an important nutrient in the human body, especially for maintenance of normal brain function, and that low body ET levels predispose humans to significantly increased risks of neurodegenerative (cognitive impairment, dementia, Parkinson's disease) and possibly other age-related diseases (including frailty, cardiovascular disease, and eye disease). Hence, restoring ET levels in the body could assist in mitigating these risks, which are rapidly increasing due to ageing populations globally. Prevention of neurodegeneration is especially important, since by the time dementia is usually diagnosed damage to the brain is extensive and likely irreversible.

Blood-based biomarkers of cerebral small vessel disease.

Age-associated cerebral small vessel disease (CSVD) represents a clinically heterogenous condition, arising from diverse microvascular mechanisms. These lead to chronic cerebrovascular dysfunction and carry a substantial risk of subsequent stroke and vascular cognitive impairment in aging populations. Owing to advances in neuroimaging, in vivo visualization of cerebral vasculature abnormities and detection of CSVD, including lacunes, microinfarcts, microbleeds and white matter lesions, is now possible, but remains a resource-, skills- and time-intensive approach.

Superior Photoprotection of Cyanine Dyes with Thio-imidazole Amino Acids.

Preventing fluorophore photobleaching and unwanted blinking is crucial for single-molecule fluorescence (SMF) studies. Reductants achieve photoprotection quenching excited triplet states, yet either require counteragents or, for popular alkyl-thiols, are limited to cyanine dye Cy3 protection. Here, we provide mechanistic and imaging results showing that the naturally occurring amino acid ergothioneine and its analogue dramatically enhance photostability for Cy3, Cy5, and their conformationally restrained congeners, providing a biocompatible universal solution for demanding fluorescence imaging.

Protective Effect of Ergothioneine against 7-Ketocholesterol-Induced Mitochondrial Damage in hCMEC/D3 Human Brain Endothelial Cells.

Recent findings have suggested that the natural compound ergothioneine (ET), which is synthesised by certain fungi and bacteria, has considerable cytoprotective potential. We previously demonstrated the anti-inflammatory effects of ET on 7-ketocholesterol (7KC)-induced endothelial injury in human blood-brain barrier endothelial cells (hCMEC/D3). 7KC is an oxidised form of cholesterol present in atheromatous plaques and the sera of patients with hypercholesterolaemia and diabetes mellitus.

Protection against Doxorubicin-Induced Cardiotoxicity by Ergothioneine.

Anthracyclines such as doxorubicin remain a primary treatment for hematological malignancies and breast cancers. However, cardiotoxicity induced by anthracyclines, possibly leading to heart failure, severely limits their application. The pathological mechanisms of anthracycline-induced cardiac injury are believed to involve iron-overload-mediated formation of reactive oxygen species (ROS), mitochondrial dysfunction, and inflammation.

Diet-Derived Antioxidants: The Special Case of Ergothioneine.

This article reviews what is presently known about the biological roles of the diet-derived compound ergothioneine (ET). ET seems important to humans because it is rapidly taken up from the diet by a transporter largely or completely specific for ET, and once taken up it is retained within the body for weeks or months. The various possible functions of ET in vivo are explored.

Protective Effect of Ergothioneine Against Stroke in Rodent Models.

Ergothioneine (ET) is a naturally occurring antioxidant and cytoprotective agent that is synthesized by fungi and certain bacteria. Recent studies have shown a beneficial effect of ET on neurological functions, including cognition and animal models of depression. The aim of this study is to elucidate a possible effect of ET in rodent models of stroke.

Low Plasma Ergothioneine Predicts Cognitive and Functional Decline in an Elderly Cohort Attending Memory Clinics.

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.

Does Lactobacillus reuteri influence ergothioneine levels in the human body?

The dietary thione-thiol, ergothioneine (ET), accumulates in human and animal tissues and may play important roles in disease prevention. ET biosynthesis has only been described in fungi and certain bacteria, and humans and animals are widely assumed to accumulate ET solely from diet. However, a recent study suggested that Lactobacillus/Limosilactobacillus reuteri, a commensal gut bacterium, may produce ET, thereby protecting the host against social defeat stress and sleep disturbances.

Low plasma ergothioneine levels are associated with neurodegeneration and cerebrovascular disease in dementia.

Ergothioneine (ET) is a dietary amino-thione with strong antioxidant and cytoprotective properties and has possible therapeutic potential for neurodegenerative and vascular diseases. Decreased blood concentrations of ET have been found in patients with mild cognitive impairment, but its status in neurodegenerative and vascular dementias is currently unclear. To address this, a cross-sectional study was conducted on 496 participants, consisting of 88 with no cognitive impairment (NCI), 201 with cognitive impairment, no dementia (CIND) as well as 207 with dementia, of whom 160 have Alzheimer's Disease (AD) and 47 have vascular dementia.

Mindfulness Awareness Practice (MAP) to Prevent Dementia in Older Adults with Mild Cognitive Impairment: Protocol of a Randomized Controlled Trial and Implementation Outcomes.

Background: With an aging population, developing non-pharmacological interventions (NPIs) to delay dementia has become critical. Apart from cognitive decline, dementia is associated with multiple pathophysiology, including increased oxidative stress, dysregulated gene expressions, cytokine, neurotrophin, and stress markers, telomere shortening, and deteriorations in brain connectivity. Although mindfulness practices have been proposed to ameliorate these biological changes, no empirical studies were conducted.

Ergothioneine, recent developments.

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.

Effects of choral singing versus health education on cognitive decline and aging: a randomized controlled trial.

We conducted a randomized controlled trial to examine choral singing's effect on cognitive decline in aging. Older Singaporeans who were at high risk of future dementia were recruited: 47 were assigned to choral singing intervention (CSI) and 46 were assigned to health education program (HEP). Participants attended weekly one-hour choral singing or weekly one-hour health education for two years.

Cohort profile: the Diet and Healthy Aging (DaHA) study in Singapore.

How diet is related with cognition and health has not been systematically examined in Asians whose eating habits are very different from their counterparts in the West and the biological mechanisms underlying such links are not well known yet. The diet and healthy aging (DaHA) study is a community-based longitudinal study conducted to examine the role of diet and nutrition in promoting cognitive, emotional, and physical health among community-living elderly Singaporeans. The first wave of DaHA, conducted from 2011 to 2017, provided detailed information on diet and baseline cognitive function and health from 1010 community-living elderly in Singapore.

Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury.

Ergothioneine (ET) is a naturally occurring antioxidant that is synthesized by non-yeast fungi and certain bacteria. ET is not synthesized by animals, including humans, but is avidly taken up from the diet, especially from mushrooms. In the current study, we elucidated the effect of ET on the hCMEC/D3 human brain endothelial cell line.

Effects of Antimalarial Drugs on Neuroinflammation-Potential Use for Treatment of COVID-19-Related Neurologic Complications.

The SARS-CoV-2 virus that is the cause of coronavirus disease 2019 (COVID-19) affects not only peripheral organs such as the lungs and blood vessels, but also the central nervous system (CNS)-as seen by effects on smell, taste, seizures, stroke, neuropathological findings and possibly, loss of control of respiration resulting in silent hypoxemia. COVID-19 induces an inflammatory response and, in severe cases, a cytokine storm that can damage the CNS. Antimalarials have unique properties that distinguish them from other anti-inflammatory drugs.

Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

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.

Mindfulness improves inflammatory biomarker levels in older adults with mild cognitive impairment: a randomized controlled trial.

Few randomized controlled trials investigated the effects of mindfulness intervention on older adults diagnosed with mild cognitive impairment (MCI). Furthermore, there have been hypotheses and theoretical mechanisms on the benefits of mindfulness intervention on biomarkers of stress, inflammation, and neuroplasticity implicated in MCI that warrant empirical evidence. We conducted a pilot randomized controlled trial to examine whether Mindful Awareness Practice (MAP) improved biomarker levels in older adults with MCI.

Inhibition of amyloid-induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model.

The abnormal accumulation of β-amyloid peptide (Aβ) is recognized as a central component in the pathogenesis of Alzheimer disease. While many aspects of Aβ-mediated neurotoxicity remain elusive, Aβ has been associated with numerous underlying pathologies, including oxidative and nitrosative stress, inflammation, metal ion imbalance, mitochondrial dysfunction, and even tau pathology. Ergothioneine (ET), a naturally occurring thiol/thione-derivative of histidine, has demonstrated antioxidant and neuroprotective properties against various oxidative and neurotoxic stressors.

Specificity of the ergothioneine transporter natively expressed in HeLa cells.

Ergothioneine is a biologically important compound that has been shown to be transported by the organic cation transporter novel type 1 (OCTN1). Following this discovery, a variety of alternate functions for OCTN1 have been suggested including an integral function in the extra-neuronal cholinergic system. The present study reaffirms the primacy of ergothioneine over these alternate substrates using natively expressed OCTN1 in HeLa cells.

The Association between Mushroom Consumption and Mild Cognitive Impairment: A Community-Based Cross-Sectional Study in Singapore.

We examined the cross-sectional association between mushroom intake and mild cognitive impairment (MCI) using data from 663 participants aged 60 and above from the Diet and Healthy Aging (DaHA) study in Singapore. Compared with participants who consumed mushrooms less than once per week, participants who consumed mushrooms >2 portions per week had reduced odds of having MCI (odds ratio = 0.43, 95% CI 0.