Vitamin K2 Research
43 peer-reviewed studies · Evidence score: 7.5/10
The effect of vitamin K2 supplementation on bone turnover biochemical markers in postmenopausal osteoporosis patients: a systematic review and meta-analysis
Zhang Z et al. • Frontiers in endocrinology (2025)
Vitamin K2 supplementation improves key bone turnover biomarkers, particularly OC and ucOC.
- Vitamin K2 (VK2) increased osteocalcin (OC; MD 1.86, 95% CI 1.17-2.56) and bone-specific alkaline phosphatase (BAP; MD 1.49, 95% CI 0.98-2.00).
- It reduced undercarboxylated OC (ucOC; WMD -1.54, 95% CI -2.44 to -0.64) and tartrate-resistant acid phosphatase (TRAP; MD -0.83, 95% CI -1.21 to -0.46).
- C-terminal telopeptide (CTX) showed a small, statistically significant reduction (MD -0.09, 95% CI -0.14 to -0.05) with uncertain clinical relevance.
Pharmacological Treatment for Dialysis-Related Muscle Cramps: A Systematic Review
Mantilla-Manosalva N et al. • Seminars in dialysis (2024)
Our review consolidates the existing evidence, elucidating the range of treatments along with their potential benefits and limitations.
- Our review consolidates the existing evidence, elucidating the range of treatments along with their potential benefits and limitations.
- Future studies should uphold high-quality standards, incorporate patient-reported outcomes, and utilize well-defined, robust samples to improve patient care.
- Further research warranted to confirm findings
Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials
Ma ML et al. • Frontiers in public health (2022)
The results of this meta-analysis seem to indicate that VK2 supplementation has a positive effect on the maintenance and improvement of BMD LS in postmenopausal women, and it can also reduce the fracture incidence, serum uc-OC levels and the ratio of uc-OC to cOC.
- The overall effect test of 10 studies showed a significant improvement in lumbar spine BMD (BMD LS) (P = 0.006) with VK2.
- The subgroup analysis of VK2 combination therapy showed that BMD LS was significantly maintained and improved with the administration of VK2 (P = 0.03).
- The overall effect test of the six RCTs showed no significant difference in fracture incidence between the two groups (RR=0.96, P=0.65).
Efficacy and safety of vitamin K2 for postmenopausal women with osteoporosis at a long-term follow-up: meta-analysis and systematic review
Zhou M et al. • Journal of bone and mineral metabolism (2022)
This meta-analysis and systematic review seemed to support the hypothesis that vitamin K2 plays an important role in the maintenance and improvement of BMD, and it decreases uc-OC and increases OC significantly at a long-term follow-up.
- Vitamin K2 was associated with a significantly increased percentage change of lumbar BMD and forearm BMD (WMD 2.17, 95% CI [1.59-2.76] and WMD 1.57, 95% CI [1.15-1.99]).
- There were significant differences in undercarboxylated osteocalcin (uc-OC) reduction (WMD -0.96, 95% CI [-0.70 to 0.21]) and osteocalcin (OC) increment (WMD 26.52, 95% CI [17.06-35.98]).
- Adverse reaction analysis showed that there seemed to be higher adverse reaction rates in the vitamin K2 group (RR = 1.33, 95% CI [1.11-1.59]), but no serious adverse events related to vitamin K2 supplementation.
Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis
Chen HG et al. • European journal of nutrition (2019)
Our findings showed that higher dietary vitamin K consumption was associated with a moderately lower risk of CHD, and higher plasma dp-ucMGP concentration, but not total circulating osteocalcin, was associated with increased risks of all-cause and CVD mortality.
- A significant association was found between dietary phylloquinone and total CHD (pooled HR 0.92; 95% CI 0.84, 0.99; I2 = 0%; four studies), as well as menaquinone and total CHD (0.70; 95% CI 0.53, 0.93; I2 = 32.1%; two studies).
- Elevated plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K deficiency, was associated with an increased risk of all-cause mortality (1.84; 95% CI 1.48, 2.28; I2 = 16.8%; five studies) and CVD mortality (1.96; 95% CI 1.47, 2.61; I2 = 0%; two studies).
- Our findings showed that higher dietary vitamin K consumption was associated with a moderately lower risk of CHD, and higher plasma dp-ucMGP concentration, but not total circulating osteocalcin, was associated with increased risks of all-cause and CVD mortality.
Menatetrenone for the treatment of osteoporosis
Iwamoto J et al. • Expert opinion on pharmacotherapy (2013)
The present review of the literature revealed some evidence of a positive effect of menatetrenone on the skeleton of postmenopausal women and in patients treated with glucocorticoid.
- The present review of the literature revealed some evidence of a positive effect of menatetrenone on the skeleton of postmenopausal women and in patients treated with glucocorticoid.
- Published in Expert opinion on pharmacotherapy (2013)
- Further research warranted to confirm findings
The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials
Kuang X et al. • Food & function (2020)
The combination of vitamin K and D can significantly increase the total BMD and significantly decrease undercarboxylated osteocalcin, and a more favorable effect is expected when vitamin K2 is used.
- The combination of vitamin K and D can significantly increase the total BMD and significantly decrease undercarboxylated osteocalcin, and a more favorable effect is expected when vitamin K2 is used.
- Published in Food & function (2020)
- Further research warranted to confirm findings
Effect of Menaquinone-7 (MK-7) Supplementation on Anthropometric Measurements, Glycemic Indices, and Lipid Profiles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Nikpayam O et al. • Prostaglandins & other lipid mediators (2025)
Based on the findings of the present systematic review and meta-analysis, MK-7 may have beneficial effects on glycemic control and TC, although further highly qualified original research is needed for a consistent conclusion.
- Based on the findings of the present systematic review and meta-analysis, MK-7 may have beneficial effects on glycemic control and TC, although further highly qualified original research is needed for a consistent conclusion.
- Published in Prostaglandins & other lipid mediators (2025)
- Further research warranted to confirm findings
Exploring the Link Between Vitamin K and Depression: A Systematic Review
Hashim MH et al. • Medicina (Kaunas, Lithuania) (2025)
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.
- 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.
- Conclusions: 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.
The effect of vitamin K supplementation on cardiovascular risk factors: a systematic review and meta-analysis
Zhao QY et al. • Journal of nutritional science (2024)
We demonstrated that supplementation with vitamin K has no effect on anthropometrics indexes, CRP, glucose metabolism, and lipid profile factors except HOMA-IR.© The Author(s) 2024.
- Pooled weighted mean difference (WMD) and 95 % confidence intervals (95 % CI) were achieved by random-model effect analysis for the best estimation of outcomes.
- The pooled findings showed that vitamin K supplementation can reduce homeostatic model assessment insulin resistance (HOMA-IR) (WMD: -0⋅24, 95 % CI: -0⋅49, -0⋅02, P = 0⋅047) significantly compared to the placebo group.
- Subgroup analysis showed a significant effect of vitamin K2 supplementation compared to vitamin K1 supplementation on HOMA-IR.
Identification of microbial markers across populations in early detection of colorectal cancer
Wu Y et al. • Nature communications (2021)
This work proves the validity of adenoma-specific markers across multi-populations, which would contribute to the early diagnosis and treatment of CRC.
- Moreover, we validate the classifiers in two independent cohorts achieving AUCs of 0.78 and 0.84, respectively.
- Functional analysis reveals that the altered microbiome is characterized with increased ADP-L-glycero-beta-D-manno-heptose biosynthesis in adenoma and elevated menaquinone-10 biosynthesis in CRC.
- These findings are validated in a newly-collected cohort of 43 samples using quantitative real-time PCR.
The Relationship between Vitamin K and Osteoarthritis: A Review of Current Evidence
Chin KY • Nutrients (2020)
Although the current data are insufficient to establish the optimal dose of vitamin K to prevent OA, ensuring sufficient dietary intake seems to protect the elderly from OA.
- However, evidence from clinical trials is limited.
- Mechanistic study shows that vitamin K activates matrix gla proteins that inhibit bone morphogenetic protein-mediated cartilage calcification.
- Gla-rich proteins also inhibit inflammatory cascade in monocytic cell lines, but this function might be independent of vitamin K-carboxylation.
Vitamin K to prevent fractures in older women: systematic review and economic evaluation
Stevenson M et al. • Health technology assessment (Winchester, England) (2009)
There is currently large uncertainty over whether vitamin K1 is more cost-effective than alendronate; further research is required.
- Phylloquinone was associated with a statistically significant reduction in the risk of clinical fractures relative to placebo [relative risk 0.46, 95% confidence interval (CI) 0.22 to 0.99]; morphometric vertebral fractures were not reported.
- There is currently large uncertainty over whether vitamin K1 is more cost-effective than alendronate; further research is required.
- It is unlikely that the present prescribing policy (i.e. alendronate as first-line treatment) would be altered.
A systematic review on the mechanisms of vitamin K effects on the complications of diabetes and pre-diabetes
Karamzad N et al. • BioFactors (Oxford, England) (2020)
However, quantification of clinical efficacy in the pre-diabetic population and among individuals with comorbidities requires further investigation.© 2019 International Union of Biochemistry and Molecular Biology.
- A statistically significant effect was also noted with vitamin K in improving dyslipidemia (three studies) as well as oxidative stress and inflammatory markers (five studies) in diabetic animals.
- However, no evidence of effect was observed for fasting blood sugar, insulin, HOMA-IR, and homeostatic model assessment-β-cell function index (two studies).
- In conclusion, clinical trials and animal studies confirm that vitamin K supplementation may improve both clinical features and complications of diabetes and pre-diabetes.
Vitamin K and osteoporosis: Myth or reality?
Palermo A et al. • Metabolism: clinical and experimental (2017)
All rights reserved.
- Vitamin K is in fact required for osteocalcin carboxylation that in turn regulates bone mineral accretion; it seems to promote the transition of osteoblasts to osteocytes and also limits the process of osteoclastogenesis.
- Several observational and interventional studies have examined the relationship between vitamin K and bone metabolism, but findings are conflicting and unclear.
- This systematic review aims to investigate the impact of vitamin K (plasma levels, dietary intake, and oral supplementation) on bone health with a particular interest in bone remodeling, mineral density and fragility fractures.Copyright © 2017 Elsevier Inc.
Vitamin K2 Supplementation and Clinical Outcomes in Hepatocellular Carcinoma Patients: A Meta-Analysis with Trial Sequential Analysis
de Moraes FCA et al. • Nutrition and cancer (2026)
This study suggests substantial benefits associated with VK supplementation in HCC patients, particularly in reducing DR and mortality across one, two, and three years.
- VK supplementation significantly reduced disease recurrence (DR) compared to control at 1 year (OR 0.55, 95% CI 0.32-0.97; p = 0.039), 2 years (OR 0.52, 95% CI 0.35-0.77; p = 0.001), and 3 years (OR 0.41, 95% CI 0.25-0.67; p = 0.000).
- Additionally, VK supplementation significantly decreased mortality at 1 year (OR 0.20, 95% CI 0.07-0.60; p = 0.004), 2 years (OR 0.38, 95% CI 0.18-0.82; p = 0.014), and 3 years (OR 0.37, 95% CI 0.21-0.66; p = 0.001).
- Notably, no significant difference in adverse events was observed between VK and control groups (OR 3.56, 95% CI 0.06-198.66; p = 0.536).
The Differential Effects of Vitamin K Across Glycaemic Outcomes in Prediabetes and Type 2 Diabetes Mellitus
Ahmed SR et al. • Nutrients (2026)
Nevertheless, the limited number of trials with moderate quality warrants larger, longer-term RCTs with rigorous methodology and direct comparisons of vitamin K isoforms to better assess therapeutic potential.
- The Meta online tool was used to analyse data, with the results reported as either the mean or the standardised mean difference (SMD), alongside 95% confidence intervals (CI).
- The evidence showed a significant reduction in FBG, SMD = -0.22 (-0.39 to -0.05), HbA1c, MD = -1.00%, 95% CI (-1.92 to -0.07), and HOMA-IR, MD = -0.63, 95% CI (-1.20 to -0.06).
- However, no effect was observed on insulin (SMD = -0.39, 95% CI: -0.91 to 0.13, p = 0.15) and HOMA-β (MD = 6.56, 95% CI (-3.89 to 17.01), p = 0.2184.
Efficacy of menatetrenone (vitamin K2) against non-vertebral and hip fractures in patients with neurological diseases: meta-analysis of three randomized, controlled trials
Iwamoto J et al. • Clinical drug investigation (2009)
The present meta-analysis of three RCTs suggests that there is efficacy for menatetrenone treatment against non-vertebral and hip fractures among patients with neurological diseases.
- According to the meta-analysis, the overall relative risks (95% confidence intervals) for non-vertebral and hip fractures with menatetrenone treatment compared with non-treatment were 0.13 (0.05, 0.35) and 0.14 (0.05, 0.43), respectively, in patients with neurological diseases.
- Further larger placebo-controlled trials are needed to confirm the results of the present study.
- Further research warranted to confirm findings
Vitamin analogues in chemoprevention of hepatocellular carcinoma after resection or ablation--a systematic review and meta-analysis
Chu KJ et al. • Asian journal of surgery (2010)
There is evidence to suggest that chemopreventive therapy after partial hepatectomy or local ablative therapy is beneficial in prolonging disease-free survival, but the evidence is less for an effect on the overall survival.
- There is evidence to suggest that chemopreventive therapy after partial hepatectomy or local ablative therapy is beneficial in prolonging disease-free survival, but the evidence is less for an effect on the overall survival.
- To confirm the beneficial role of vitamin A or K analogues in the chemoprevention of HCC further and larger randomised trials are now required.
- Further research warranted to confirm findings
[Vitamin K2]
Ishida Y • Clinical calcium (2008)
To confirm these results, a larger well design RCT using fractures as the primary endpoint is clearly needed.
- Vitamin K2 treatment in osteoporosis has been shown to inhibit the occurrence of new bone fractures and to maintain BMD.
- The uniqueness of the prevention of bone fractures by vitamin K2 is that there has been no direct evidence of the relationship between increase of BMD and a decrease in the occurrence of bone fractures.
- A recent systematic review of seven Japanese randomized controlled trials by Cockayne has also shown that supplementation with phytonadione (Vitamin K1) and menaquinone (Vitamin K2) , particularly menaquinone-4, is associated with increased BMD and reduced fracture incidence.