Exploring the Link Between Vitamin K and Depression: A Systematic Review

<i>Background and Objectives:</i> 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,...

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Main Authors: Mohamad Hisham Hashim, Nik Nasihah Nik Ramli, Siti Nur Atiqah Zulaikah Nasarudin, Maisarah Abdul Mutalib, Muhammad Najib Mohamad Alwi, Aswir Abd Rashed, Rajesh Ramasamy
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Language:English
Published: MDPI AG 2025-05-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/61/5/861
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author Mohamad Hisham Hashim
Nik Nasihah Nik Ramli
Siti Nur Atiqah Zulaikah Nasarudin
Maisarah Abdul Mutalib
Muhammad Najib Mohamad Alwi
Aswir Abd Rashed
Rajesh Ramasamy
author_facet Mohamad Hisham Hashim
Nik Nasihah Nik Ramli
Siti Nur Atiqah Zulaikah Nasarudin
Maisarah Abdul Mutalib
Muhammad Najib Mohamad Alwi
Aswir Abd Rashed
Rajesh Ramasamy
author_sort Mohamad Hisham Hashim
collection DOAJ
description <i>Background and Objectives:</i> 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. <i>Materials and Methods:</i> 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. <i>Results:</i> 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. <i>Conclusions:</i> 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.
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spelling doaj-art-028d6a0e00044d598fb87d9fc1775c462025-08-20T02:33:51ZengMDPI AGMedicina1010-660X1648-91442025-05-0161586110.3390/medicina61050861Exploring the Link Between Vitamin K and Depression: A Systematic ReviewMohamad Hisham Hashim0Nik Nasihah Nik Ramli1Siti Nur Atiqah Zulaikah Nasarudin2Maisarah Abdul Mutalib3Muhammad Najib Mohamad Alwi4Aswir Abd Rashed5Rajesh Ramasamy6School of Graduate Studies, Management and Science University, Shah Alam 40100, MalaysiaSchool of Graduate Studies, Management and Science University, Shah Alam 40100, MalaysiaSchool of Graduate Studies, Management and Science University, Shah Alam 40100, MalaysiaSchool of Graduate Studies, Management and Science University, Shah Alam 40100, MalaysiaInternational Medical School, Management and Science University, Shah Alam 40100, MalaysiaNutrition, Metabolism and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Malaysia, No.1, Jalan Setia Murni U13/52, Seksyen U13 Setia Alam, Shah Alam 40170, MalaysiaDepartment of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia<i>Background and Objectives:</i> 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. <i>Materials and Methods:</i> 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. <i>Results:</i> 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. <i>Conclusions:</i> 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.https://www.mdpi.com/1648-9144/61/5/861vitamin Kdepressionoxidative stressosteocalcinneuroinflammation
spellingShingle Mohamad Hisham Hashim
Nik Nasihah Nik Ramli
Siti Nur Atiqah Zulaikah Nasarudin
Maisarah Abdul Mutalib
Muhammad Najib Mohamad Alwi
Aswir Abd Rashed
Rajesh Ramasamy
Exploring the Link Between Vitamin K and Depression: A Systematic Review
Medicina
vitamin K
depression
oxidative stress
osteocalcin
neuroinflammation
title Exploring the Link Between Vitamin K and Depression: A Systematic Review
title_full Exploring the Link Between Vitamin K and Depression: A Systematic Review
title_fullStr Exploring the Link Between Vitamin K and Depression: A Systematic Review
title_full_unstemmed Exploring the Link Between Vitamin K and Depression: A Systematic Review
title_short Exploring the Link Between Vitamin K and Depression: A Systematic Review
title_sort exploring the link between vitamin k and depression a systematic review
topic vitamin K
depression
oxidative stress
osteocalcin
neuroinflammation
url https://www.mdpi.com/1648-9144/61/5/861
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