Hashim Mohamad Hisham, Ramli Nik Nasihah Nik, Nasarudin Siti Nur Atiqah Zulaikah, Abdul Mutalib Maisarah, Mohamad Alwi Muhammad Najib, Abd Rashed Aswir, Ramasamy Rajesh
School of Graduate Studies, Management and Science University, Shah Alam 40100, Malaysia.
International Medical School, Management and Science University, Shah Alam 40100, Malaysia.
Medicina (Kaunas). 2025 May 7;61(5):861. doi: 10.3390/medicina61050861.
Depression is a multifactorial mental health disorder involving inflammation, oxidative stress, neuroplasticity deficits, and metabolic dysfunction. Emerging research suggests that vitamin K, beyond its classical roles in coagulation and bone metabolism, may influence neurobiological processes relevant to mood regulation. This systematic review evaluates the association between vitamin K and depressive symptoms and explores potential underlying mechanisms. A systematic search was conducted across PubMed, Scopus, Cochrane Library, ScienceDirect, and Google Scholar, following PRISMA 2020 guidelines. Eligible studies included human or animal research examining associations between vitamin K status (dietary intake or serum levels) and depression-related outcomes. Fourteen studies met the inclusion criteria: eleven observational studies, one randomized controlled trial (RCT), and two preclinical animal studies. Most observational studies reported an inverse association between vitamin K intake or serum levels and depressive symptoms across diverse populations. One small RCT demonstrated modest improvements in depression scores following vitamin K2 (menaquinone-7) supplementation in women with polycystic ovary syndrome. Two preclinical studies using non-depression models reported behavioral improvements and reduced oxidative stress following vitamin K2 administration. While preliminary findings suggest a potential role for vitamin K in pathways relevant to depression, the current evidence is limited by cross-sectional designs, lack of isoform-specific analyses, and the absence of depression-focused preclinical models. Mechanisms including inflammation reduction, oxidative stress modulation, sphingolipid regulation, and vitamin K-dependent protein signaling (e.g., GAS6 and osteocalcin) were discussed based on indirect evidence and require further investigation in depression-specific contexts.
抑郁症是一种多因素的心理健康障碍，涉及炎症、氧化应激、神经可塑性缺陷和代谢功能障碍。新兴研究表明，维生素K除了在凝血和骨代谢中的经典作用外，可能会影响与情绪调节相关的神经生物学过程。本系统评价评估了维生素K与抑郁症状之间的关联，并探讨了潜在的潜在机制。按照PRISMA 2020指南，在PubMed、Scopus、Cochrane图书馆、ScienceDirect和谷歌学术上进行了系统检索。符合条件的研究包括检查维生素K状态（饮食摄入量或血清水平）与抑郁相关结果之间关联的人体或动物研究。十四项研究符合纳入标准：十一项观察性研究、一项随机对照试验（RCT）和两项临床前动物研究。大多数观察性研究报告了不同人群中维生素K摄入量或血清水平与抑郁症状之间的负相关。一项小型RCT表明，多囊卵巢综合征女性补充维生素K2（甲萘醌-7）后，抑郁评分有适度改善。两项使用非抑郁模型的临床前研究报告称，给予维生素K2后行为有改善，氧化应激减轻。虽然初步研究结果表明维生素K在与抑郁症相关的途径中可能发挥作用，但目前的证据受到横断面设计、缺乏异构体特异性分析以及缺乏针对抑郁症的临床前模型的限制。基于间接证据讨论了包括炎症减轻、氧化应激调节、鞘脂调节和维生素K依赖性蛋白信号传导（如GAS6和骨钙素）在内的机制，这些机制需要在抑郁症特定背景下进一步研究。
