Background Previous studies found that sodium benzoate (the pivotal D‐amino acid oxidase DAO inhibitor) improved cognitive function in patients with mild Alzheimer's disease (AD); however, its efficacy for mild cognitive impairment (MCI) remained inconclusive. This study aims to evaluate the efficacy and safety of sodium benzoate in treating amnestic MCI (aMCI). Methods Data were pooled from three randomized, double‐blind, placebo‐controlled trials. One hundred thirty‐three patients with aMCI were enrolled from three major medical centers in Taiwan to receive 24‐week treatment of 250–1500 mg/day of sodium benzoate or placebo. The cognitive outcome was Alzheimer's disease assessment scale‐cognitive subscale (ADAS‐cog), and the functional outcome was Instrumental Activities of Daily Living (IADL). Both were measured at weeks 0, 8, 16, and 24. Results Among 133 participants, sodium benzoate therapy improved ADAS‐cog scores more than placebo ( P = 0.033 at week 16, 0.026 at week 24). Among 84 women, benzoate surpassed placebo in ADAS‐cog ( P = 0.046 at week 16, 0.029 at week 24), as well as IADL ( P = 0.043 at week 24). In contrast, among 49 men, the two treatment groups did not differ significantly in both ADAS‐cog and IADL scores. Both sodium benzoate and placebo were well tolerated and benzoate therapy produced no additional side effect. Conclusions This study is the first to demonstrate that a DAO inhibitor, sodium benzoate herein, can enhance overall cognitive function in MCI individuals. Furthermore, it can improve female patients' IADL. The finding lends support for DAO inhibition as a novel approach for early dementing processes.
Lin et al. (2026) studied this question.