Beyond flavor: dietary vanillyl alcohol, a D₂ receptor antagonist promoting sleep.

Authors

Lijing Zhang, Yujie Yang, Dongmei Yang, Richard Ward, Zhenshuai Hu, Hao Chen, Mengli Lan, Cheng Xiang, Su An, Jiameng Dai, Ying Zhu, Xianrun Sun, Tian-Rui Xu, Yang Yang

Published in

Food research international (Ottawa, Ont.). Volume 242. Issue Pt 2. Pages 119840. Oct 31, 2026. Epub Jun 26, 2026.

Abstract

Sleep disturbances have become a prevalent public health challenge globally, spurring the demand for safe, naturally derived food-based interventions as alternatives to synthetic agents. Vanillyl alcohol (VA), a widely distributed bioactive compound in edible plants and a key constituent of Vanilla planifolia and the traditional sedative herb Gastrodia elata, is extensively used as a food additive for its characteristic vanilla aroma. Despite its long-term use in dietary and traditional contexts, the molecular mechanism underlying its potential sleep-regulating effects remains unclear. Given the critical role of dopamine receptor D2 (D₂) in sleep-wake modulation, we systematically investigated the sleep-promoting activity of VA using a cross-disciplinary approach integrating in vitro biochemical assays, in silico simulations, and in vivo validation in D₂-knockdown and chemically induced insomnia mouse models. Our results demonstrated that VA significantly prolonged total sleep time and shortened sleep latency in insomnia mice, which was dependent on D₂-mediated signaling pathways. Mechanistically, VA interacted with D2R to inhibit its activity, thereby rebalancing the levels of key sleep-related neurotransmitters in the brain. This work not only elucidates the scientific basis for the traditional use of VA-containing foods in alleviating sleep disturbances but also positions VA as a promising naturally derived food ingredient for the development of sleep-promoting functional foods and dietary strategies. Collectively, our findings provide novel insights into the neuro-nutritional effects of food bioactives and offer a translational approach for addressing sleep disorders through dietary intervention.

PMID:
42632662
Bibliographic data and abstract were imported from PubMed on 23 Aug 2026.

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