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Endogenous antioxidants predicted outcome and increased after treatment: A benzoate dose‐finding, randomized, double‐blind, placebo‐controlled trial for Alzheimer's disease

AIM: Previous pilot studies suggest that sodium benzoate may be a potential cognitive enhancer for patients with Alzheimer's disease (AD), schizophrenia, or late‐life depression. Especially for AD treatment, a confirmatory trial with predictive biomarkers is urgently needed. This study aimed to...

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Autores principales: Lane, Hsien‐Yuan, Wang, Shi‐Heng, Lin, Chieh‐Hsin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099492/
https://www.ncbi.nlm.nih.gov/pubmed/36335573
http://dx.doi.org/10.1111/pcn.13504
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author Lane, Hsien‐Yuan
Wang, Shi‐Heng
Lin, Chieh‐Hsin
author_facet Lane, Hsien‐Yuan
Wang, Shi‐Heng
Lin, Chieh‐Hsin
author_sort Lane, Hsien‐Yuan
collection PubMed
description AIM: Previous pilot studies suggest that sodium benzoate may be a potential cognitive enhancer for patients with Alzheimer's disease (AD), schizophrenia, or late‐life depression. Especially for AD treatment, a confirmatory trial with predictive biomarkers is urgently needed. This study aimed to confirm benzoate as a novel treatment for AD and to discover its optimal dose and biomarkers. METHODS: A 24‐week, dose‐finding, randomized, double‐blind, placebo‐controlled trial, with clinical measurements at weeks 0, 8, 16, and 24, was conducted in three major medical centers in Taiwan. Among 154 patients screened for AD, 149 were eligible and randomized to one of the four treatments: (i) benzoate 500 group (fixed 500 mg/day); (ii) benzoate 750 (500 mg/day for the first 4 weeks, 750 mg/day from the 5th week); (iii) benzoate 1000 (500 mg/day for the first 4 weeks, 1000 mg/day from the 5th week); and (iv) placebo. The primary outcome measure was AD assessment scale‐cognitive subscale (ADAS‐cog). RESULTS: The benzoate 1000 group performed best in improving ADAS‐cog (P = 0.026 at week 24), with female advantage. Higher plasma catalase at baseline predicted better outcome. Benzoate receivers tended to have higher catalase and glutathione than placebo recipients after treatment. The four intervention groups showed similar safety profiles. CONCLUSIONS: By enhancing two vital endogenous antioxidants, catalase and glutathione, sodium benzoate therapy improved cognition of patients with AD, with higher baseline catalase predicting better response. Supporting the oxidative stress theory, the results show promise for benzoate as a novel treatment for AD.
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spelling pubmed-100994922023-04-14 Endogenous antioxidants predicted outcome and increased after treatment: A benzoate dose‐finding, randomized, double‐blind, placebo‐controlled trial for Alzheimer's disease Lane, Hsien‐Yuan Wang, Shi‐Heng Lin, Chieh‐Hsin Psychiatry Clin Neurosci Regular Articles AIM: Previous pilot studies suggest that sodium benzoate may be a potential cognitive enhancer for patients with Alzheimer's disease (AD), schizophrenia, or late‐life depression. Especially for AD treatment, a confirmatory trial with predictive biomarkers is urgently needed. This study aimed to confirm benzoate as a novel treatment for AD and to discover its optimal dose and biomarkers. METHODS: A 24‐week, dose‐finding, randomized, double‐blind, placebo‐controlled trial, with clinical measurements at weeks 0, 8, 16, and 24, was conducted in three major medical centers in Taiwan. Among 154 patients screened for AD, 149 were eligible and randomized to one of the four treatments: (i) benzoate 500 group (fixed 500 mg/day); (ii) benzoate 750 (500 mg/day for the first 4 weeks, 750 mg/day from the 5th week); (iii) benzoate 1000 (500 mg/day for the first 4 weeks, 1000 mg/day from the 5th week); and (iv) placebo. The primary outcome measure was AD assessment scale‐cognitive subscale (ADAS‐cog). RESULTS: The benzoate 1000 group performed best in improving ADAS‐cog (P = 0.026 at week 24), with female advantage. Higher plasma catalase at baseline predicted better outcome. Benzoate receivers tended to have higher catalase and glutathione than placebo recipients after treatment. The four intervention groups showed similar safety profiles. CONCLUSIONS: By enhancing two vital endogenous antioxidants, catalase and glutathione, sodium benzoate therapy improved cognition of patients with AD, with higher baseline catalase predicting better response. Supporting the oxidative stress theory, the results show promise for benzoate as a novel treatment for AD. John Wiley & Sons Australia, Ltd 2022-11-24 2023-02 /pmc/articles/PMC10099492/ /pubmed/36335573 http://dx.doi.org/10.1111/pcn.13504 Text en © 2022 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Regular Articles
Lane, Hsien‐Yuan
Wang, Shi‐Heng
Lin, Chieh‐Hsin
Endogenous antioxidants predicted outcome and increased after treatment: A benzoate dose‐finding, randomized, double‐blind, placebo‐controlled trial for Alzheimer's disease
title Endogenous antioxidants predicted outcome and increased after treatment: A benzoate dose‐finding, randomized, double‐blind, placebo‐controlled trial for Alzheimer's disease
title_full Endogenous antioxidants predicted outcome and increased after treatment: A benzoate dose‐finding, randomized, double‐blind, placebo‐controlled trial for Alzheimer's disease
title_fullStr Endogenous antioxidants predicted outcome and increased after treatment: A benzoate dose‐finding, randomized, double‐blind, placebo‐controlled trial for Alzheimer's disease
title_full_unstemmed Endogenous antioxidants predicted outcome and increased after treatment: A benzoate dose‐finding, randomized, double‐blind, placebo‐controlled trial for Alzheimer's disease
title_short Endogenous antioxidants predicted outcome and increased after treatment: A benzoate dose‐finding, randomized, double‐blind, placebo‐controlled trial for Alzheimer's disease
title_sort endogenous antioxidants predicted outcome and increased after treatment: a benzoate dose‐finding, randomized, double‐blind, placebo‐controlled trial for alzheimer's disease
topic Regular Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099492/
https://www.ncbi.nlm.nih.gov/pubmed/36335573
http://dx.doi.org/10.1111/pcn.13504
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