Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan.
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Psychiatry Clin Neurosci. 2023 Feb;77(2):102-109. doi: 10.1111/pcn.13504. Epub 2022 Nov 24.
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.
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).
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.
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.
先前的初步研究表明，苯甲酸钠可能是阿尔茨海默病（AD）、精神分裂症或老年期抑郁症患者潜在的认知增强剂。特别是对于 AD 的治疗，迫切需要进行有预测性生物标志物的验证性试验。本研究旨在确认苯甲酸钠是 AD 的一种新型治疗方法，并发现其最佳剂量和生物标志物。
在台湾的三个主要医疗中心进行了一项为期 24 周、剂量探索、随机、双盲、安慰剂对照试验，在第 0、8、16 和 24 周进行临床测量。在对 154 名 AD 患者进行筛查后，149 名符合条件并随机分为四组治疗之一：（i）苯甲酸钠 500 组（固定 500mg/天）；（ii）苯甲酸钠 750 组（第 4 周 500mg/天，第 5 周 750mg/天）；（iii）苯甲酸钠 1000 组（第 4 周 500mg/天，第 5 周 1000mg/天）；和（iv）安慰剂。主要结局测量指标为 AD 评估量表认知子量表（ADAS-cog）。
苯甲酸钠 1000 组在改善 ADAS-cog 方面表现最佳（第 24 周时 P=0.026），且女性具有优势。基线时更高的血浆过氧化氢酶水平预示着更好的结果。与安慰剂组相比，苯甲酸钠组治疗后过氧化氢酶和谷胱甘肽水平更高。四组干预组的安全性相似。
通过增强两种重要的内源性抗氧化剂过氧化氢酶和谷胱甘肽，苯甲酸钠治疗改善了 AD 患者的认知功能，基线时过氧化氢酶水平更高预示着更好的反应。支持氧化应激理论，结果表明苯甲酸钠作为 AD 的新型治疗方法具有潜力。
