An increased risk of cognitive decline and dementia in older adults may be predicted by low levels of ergothioneine in blood plasma, suggests a recent study. The results point to potential therapeutic or early detection methods for dementia and cognitive impairment in the elderly.
More than a century ago, the French pharmacist Charles Joseph Tanret discovered ergothioneine (ET), a unique diet-derived substance. But it was in 2005 that researchers identified a transporter that makes it easier for ET to enter the body and build up there.
Barry Halliwell, professor of biochemistry at the National University of Singapore, and his colleagues demonstrated that the human body retains ergothioneine following oral supplementation. They also showed that ET is transported to almost all organs in preclinical models, with higher levels found in specific cells and tissues such as blood cells, eyes, liver, lungs, and even the brain.
Ergothioneine From Mushrooms
Earlier research by Halliwell demonstrated ET’s potent antioxidant properties, as well as its ability to protect cells from a variety of stress and toxins. Because mushrooms are ergothioneine’s primary dietary source, researchers discovered that increasing consumption of mushrooms – such as golden, oyster, shiitake, and white button mushrooms – is associated with a lower risk of mild cognitive impairment in elderly Singaporeans.
Halliwell’s team discovered lower ET levels in blood plasma in participants with mild cognitive impairment in 2016. In collaboration with Mitchell Lai and Christopher Chen, associate professors from NUHS’ Memory, Ageing, and Cognition Centre, this was confirmed in a much larger group of cognitively impaired participants with and without dementia.
However, there was no evidence that a low level of ergothioneine in blood plasma could predict the progression of cognitive impairment and dementia.
The most recent study fills these knowledge gaps in ergothioneine research by demonstrating ET’s potential as a predictive biomarker for cognitive impairment and dementia in elderly Singaporeans.
Increased Cognitive Problems Risk
Credit: Wu L-Y, Kan CN, et al CC-BY
The Memory, Aging, and Cognition Centre recruited 470 elderly patients and followed them for up to five years in the most recent study.
The participants’ blood plasma was tested for ET levels, and the researchers monitored the participant’s cognitive and functional abilities over time. They then looked at the connection between low ergothioneine levels and the possibility of long-term mental and functional decline.
“Before this study, there was little evidence that ET levels in the blood can predict the risk of developing cognitive issues. The current study is significant because it measured the ET levels of elderly participants before developing dementia. Our findings demonstrate that if your ET levels are low, your risk of developing cognitive problems increases,”
Halliwell said.
Brain Structural Alterations
The results showed that participants with lower levels of ET had worse cognitive performance at the beginning of the study and experienced a faster decline in cognitive and functional abilities throughout the follow-up period.
The researchers also noticed structural alterations in the participants’ brains during MRI (magnetic resonance imaging) scans, which suggests that the pathology of an underlying disease caused the link between a low blood level of ET and cognitive decline.
Structural alterations, including decreased cortical thickness, hippocampus volume, and white matter hyperintensities characterize neurodegenerative diseases.
“This points to the possibility of using a simple blood test to detect ET levels for early screening in the elderly to identify those who may have higher risk of cognitive decline,”
Halliwell said. Because frailty, cardiovascular disease, and macular degeneration are all age-related diseases linked to low ergothioneine levels, ET may play a more general role in preserving health.
Further Study
Based on the findings of this study, which demonstrated that plasma ET levels in the blood can be used to predict the risk of cognitive and functional decline, the research team hopes to gather additional evidence of ET’s preventive and therapeutic potential through a double-blind placebo-controlled clinical trial.
The team is currently recruiting volunteers for this clinical trial who are over 60 and have mild cognitive impairment. Over a set period, the researchers will administer either pure ET supplements or a placebo to study participants to assess the effect and causal relationship of ET supplementation on elderly patients with mild cognitive impairment.
“If the deficiency in ET is leading to an increased risk of cognitive decline, then we would have the potential to intervene, and that is what we are trying to find out by undertaking this clinical trial,”
said Irwin Cheah, senior biochemistry research fellow.
Reference: Wu L-Y, Kan CN, Cheah IK, Chong JR, Xu X, Vrooman H, Hilal S, Venketasubramanian N, Chen CP, Halliwell B, Lai MKP. Low Plasma Ergothioneine Predicts Cognitive and Functional Decline in an Elderly Cohort Attending Memory Clinics. Antioxidants. 2022; 11(9):1717.
Last Updated on February 13, 2023