Effects of water‐soluble mangosteen extract on cognitive function and neuropsychiatric symptoms in patients with mild to moderate Alzheimer's disease (WECAN‐AD): A randomized controlled trial

INTRODUCTION: The water‐soluble mangosteen pericarp extract's (WME) effect was investigated in Alzheimer's disease (AD). METHODS: The participants received 4 mg/kg/day of WME for 24 weeks (low dose, n = 33), 4 mg/kg/day for 12 weeks and then 8 mg/kg/day for 12 weeks (high dose, n = 33); or a placebo (n = 42). The outcomes were neuropsychiatric test scores, safety, tolerability, and the blood 4‐hydroxynonenal level. RESULTS: The proportion of participants who achieved the minimum clinically important difference for the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog; –2.6 points) at 24 weeks was significantly higher in the low‐dose group (and a trend in the high‐dose group) than in the placebo group. WME appeared safe and well tolerated. At 24 weeks, the 4‐hydroxynonenal level declined in both intervention groups. The participants with a 5% reduction in this level showed greater ADAS‐Cog improvements. CONCLUSION: WME is a safe and well‐tolerated cognitive enhancer in AD with varying benefits across individuals based on antioxidative response.