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Investigating the Efficacy of Ergothioneine to Delay Cognitive Decline in Mild Cognitively Impaired Subjects: A Pilot Study.

Fung Yau Yu,Irwin K Cheah,Rathi Mahendran, Richard MY Tang,Ru Yuan Chua, Rachel ES Goh,Lei Feng,Jialiang Li,Ee Heok Kua, Christopher Chen,Barry Halliwell

medrxiv(2024)

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摘要
Background and objective: Dementia, particularly Alzheimer's disease, is a major healthcare challenge in ageing societies. Therefore, this study aimed to investigate the efficacy and safety of a dietary compound, ergothioneine, in delaying cognitive decline in elderly individuals. Design, intervention and measurements: Nineteen subjects aged 60 or above with mild cognitive impairment were recruited for this double-blinded, randomized, and placebo-controlled study. Subjects received either ergothioneine (25mg 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. Result: 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 placebo group which saw no improvement in cognitive assessments and a significant increase in neurofilament light chain. Conclusion: Prolonged intake of ergothioneine showed no toxicity in elderly individuals. Enhanced Rey Auditory Verbal Learning Test performance and stabilized neurofilament light chain levels suggest improvements in memory and learning abilities, alongside a deceleration of neuronal damage. Our results add to existing data that ergothioneine is safe for extended consumption and may hold the potential to delay cognitive decline in the elderly. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT03641404 ### Funding Statement This study was funded by the Ministry of Education AcRF Tier 1, grant number NUHSRO/2017/055/T1; the Tan Chin Tuan Centennial Foundation; the Ministry of Health, National Academy of Medicine Healthy Longevity Catalyst Award (HLCA20Jan-0057); and the National Medical Research Council (Individual Research Grants NMRC/1264/2010/082/12 and NMRC/OFYIRG/0081/2018). Yau Y.F. was supported by the Yong Loo Lin School of Medicine, NUS, PhD scholarship. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Domain Specific Review Board of the National Healthcare Group (Singapore) have given ethical approval for this work (Protocol 2017/00982). Clinical trial approval has also been provided by the Health Science Authority (Singapore) according to clinical trial certificate number (CTC1800036). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.
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