A dietary antioxidant demonstrated potential neuroprotective benefits in pilot study individuals with mild cognitive impairment.
A pilot study, conducted by researchers at the National University of Singapore and recently published in The Journal of Alzheimer’s Disease, investigated the safety and efficacy of ergothioneine supplementation in delaying cognitive decline. This randomized, double-blind, placebo-controlled study enrolled 19 participants aged 60 and older with MCI, who were allocated to receive either 25 mg of ergothioneine or a placebo three times weekly for 12 months. The primary endpoints included neurocognitive performance assessments, plasma biomarkers of neuronal damage, and safety evaluations of renal, liver and hematological function [1].
Longevity.Technology: Ergothioneine is a sulfur-containing compound derived from the diet – predominantly found in mushrooms – with interesting antioxidant and anti-inflammatory properties. Its mechanism of action involves the selective transport into cells via the OCTN1 transporter, enabling it to accumulate in tissues like the brain where it may neutralize oxidative stress and inflammation.
Cognitive decline, particularly in the form of mild cognitive impairment (MCI) or dementia, remains a growing global health crisis; it significantly impacts quality of life and places enormous financial strain on healthcare systems. The World Health Organization predicts the prevalence of dementia to triple to 152 million cases globally by 2050 [2], emphasizing the urgent need for effective interventions.
While the study faced limitations such as a small sample size and the COVID-19 pandemic’s impact on recruitment and follow-ups, its findings warrant further exploration:
- Neurocognitive assessments: Participants receiving ergothioneine exhibited improvements in the Rey Auditory Verbal Learning Test (RAVLT), which measures memory and learning ability. By contrast, the placebo group showed no significant changes, suggesting potential cognitive benefits attributable to the supplementation.
- Neurofilament light chain (NfL): Stabilization of NfL levels, a biomarker of neuronal injury, was observed in the ergothioneine group over the study period; this contrasts with a significant increase in the placebo group, indicating possible neuroprotective effects.
- Safety profile: No adverse effects or significant changes in clinical safety markers were noted, reinforcing ergothioneine’s suitability for long-term use.
These results align with previous observational studies linking lower plasma levels of ergothioneine to accelerated cognitive decline and increased dementia risk. The researchers hypothesize that ergothioneine’s ability to cross the blood-brain barrier and accumulate in neural tissues contributes to its neuroprotective potential [1].
Longevity.Technology reached out to Linda May-Zhang, PhD, VP Science & Innovation at Blue California, a company that manufactures ergothioneine, for her take on the results.
“Professor Halliwell’s pilot study provides compelling evidence of ergothioneine’s potential to improve memory and protect against neuronal damage in older adults with mild cognitive impairment,” she told us.
“These findings complement our recent yet unpublished clinical research in healthy older adults without MCI, providing causal evidence to support ergothioneine’s critical role in cognitive health and healthy aging. Importantly, the one-year pilot study reaffirms ergothioneine’s excellent safety profile, with no reported adverse effects. This research adds to the growing body of evidence highlighting ergothioneine as an important ‘longevity vitamin’, obtainable through dietary sources or supplementation, to combat the effects of aging.”
The challenges of studying ergothioneine’s effects
As a pilot study, the trial underscores the importance of larger-scale clinical research to validate these preliminary findings. Recruitment difficulties, exacerbated by pandemic-related hesitations, led to a reduced participant pool, impacting the statistical power of the outcomes. Nonetheless, the study establishes a foundation for future exploration into ergothioneine’s role in mitigating cognitive decline.
The researchers emphasized that while ergothioneine supplementation appears promising, it is not a conclusive solution. The complexities of neurodegeneration involve multiple pathways, including amyloid-beta accumulation, oxidative stress and mitochondrial dysfunction, which require multifaceted therapeutic strategies.
Future directions
Ergothioneine’s approval as a generally recognized as safe (GRAS) compound by regulatory agencies, including the US FDA and European Food Safety Authority, positions it as a viable candidate for further research. Investigating its synergistic effects with existing treatments for neurodegenerative diseases, such as anti-amyloid therapies, could yield valuable insights, and examining its impact in diverse populations and extending study durations may help clarify its potential as part of preventive healthcare strategies for aging populations.
As cognitive decline remains a pressing issue with far-reaching consequences, ergothioneine represents an intriguing avenue for addressing an unmet medical need. This study’s findings encourage continued exploration into dietary interventions for enhancing cognitive health and delaying the progression of neurodegenerative diseases.
[1] https://journals.sagepub.com/eprint/ES7FGJZCHYI3RUKV2UKN/full
[2] https://www.who.int/news/item/07-12-2017-dementia-number-of-people-affected-to-triple-in-next-30-years
