We use essential cookies (authentication, your saved goals/stack) by default. With your permission we'll also enable privacy-respecting analytics (Vercel Web Analytics, anonymous load-time metrics) and error-replay diagnostics (Sentry — DOM snapshots only when an error fires) so we can fix bugs faster. Learn more
Vk7.5
Vitamin K2 Research
Likely helpsModerate safety
46 peer-reviewed studies
What the evidence says
Likely helps
Vitamin K2 appears to help in 10 of 12 studies with measurable effects — the evidence leans clearly favourable.
Most evidence is from high-quality meta-analyses and randomised trials published 2004–2026 with a typical study size of 156 participants.
Based on 46 studies · 12 meta-analyses · 23 RCTs · 254,449 total participants
Confidence
High
What the studies found
10helped2unclear· 34 more without graded effect data
By outcome
Bone healthSupports bone mineral density and skeletal strength · 8-12 weeks
Likely helps29 studies
Heart & blood pressureActivates MGP to redirect calcium from arteries to bones · 8-12 weeks
Probably helps15 studies
Therapeutic & clinical
Likely helps15 studies
Women's healthMay help manage menopausal symptoms like hot flashes and mood changes · 4-8 weeks · Provides essential nutrients for healthy pregnancy · Ongoing
Likely helps8 studies
Kidney & renal health
Mostly mechanism / observational7 studies
Glucose & metabolic
Likely helps7 studies
Cholesterol & lipidsActivates MGP to redirect calcium from arteries to bones · 8-12 weeks
Mostly mechanism / observational3 studies
InflammationSupports bone density and calcium metabolism · 6-12 months
Mostly mechanism / observational3 studies
Safety profile
Mostly mechanism / observational3 studies
Muscle cramps & function
Too few graded studies2 studies
Longevity & agingSupports cardiovascular and bone health long-term · Months to years
Too few graded studies2 studies
Joint pain & arthritis
Too few graded studies1 study
By the numbers
Pulled from 29 studies with measurable effects
Likely real effects
71%
across studies
People studied
254k
typical study: 156 people
Strongest designs
35
12 pooled, 23 randomised
Showed benefit
83%
10/12 studies
How long studies ran
1–3 months
1
3+ months
8
Populations Studied
Postmenopausal women3
General population2
Postmenopausal osteoporosis patients1
Postmenopausal women with osteoporosis1
Active research area
29 studies in the last 5 years · Latest meta-analysis: 2026
200420152026
1Bone turnover biomarkers improvementMeta-AnalysisCited 1×n=2,570 · very large study2025
Vitamin K2 supplementation improves key bone turnover biomarkers, particularly OC and ucOC.
Zhang Z et al. · Frontiers in endocrinology (2025)
Noticeable benefit
← WorseNo effectBetter →
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.
3Lumbar spine BMD improvementMeta-AnalysisCited 44×n=6,425 · very large study2022
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.
Ma ML et al. · Frontiers in public health (2022)
Likely real
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).
4Lumbar BMD percentage changeMeta-AnalysisCited 18×n=6,853 · very large study2022
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.
Zhou M et al. · Journal of bone and mineral metabolism (2022)
Noticeable benefit
← WorseNo effectBetter →
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.
5Coronary heart disease riskMeta-AnalysisCited 58×n=222,592 · very large study2019
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.
Chen HG et al. · European journal of nutrition (2019)
Barely noticeable benefit
← WorseNo effectBetter →
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.
6Total BMD increaseMeta-AnalysisCited 31×n=971 · large study2020
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.
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.
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.
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.
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.
Hashim MH et al. · Medicina (Kaunas, Lithuania) (2025)
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.
Zhao QY et al. · Journal of nutritional science (2024)
Noticeable benefit
← WorseNo effectBetter →
Likely real
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.
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.
Chin KY · Nutrients (2020)
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.
11Systematic ReviewCited 36×n=2,000 · very large study2009
There is currently large uncertainty over whether vitamin K1 is more cost-effective than alendronate; further research is required.
Stevenson M et al. · Health technology assessment (Winchester, England) (2009)
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.
However, quantification of clinical efficacy in the pre-diabetic population and among individuals with comorbidities requires further investigation.
Karamzad N et al. · BioFactors (Oxford, England) (2020)
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 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 proces...
Palermo A et al. · Metabolism: clinical and experimental (2017)
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.
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.
Ahmed SR et al. · Nutrients (2026)
Noticeable benefit
← WorseNo effectBetter →
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.
15disease recurrence and mortality in hepatocellular carcinomaMeta-Analysisn=1,030 · large study2025
This study suggests substantial benefits associated with VK supplementation in HCC patients, particularly in reducing DR and mortality across one, two, and three years.
de Moraes FCA et al. · Nutrition and cancer (2025)
Large benefit
← WorseNo effectBetter →
Likely real
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).
This review synthesizes current mechanistic, observational, and interventional evidence, aiming to clarify whether vitamin D should be reclassified-from a micronutrient to a pharmacologically relevant agent-in cardiometabolic prevention and therapy, proposing a paradigm shift toward personalized and targeted dosing strategies, characteristic of precision pharmacology.
D'Elia S et al. · International journal of molecular sciences (2025)
On the contrary, clinical efficacy is strongly dependent on baseline deficiency status and the presence of metabolic cofactors.
In this context, high-dose supplementation of Vitamin D, in combination with Vitamin K2 to prevent vascular calcification, elevates the supplement to a genuine pharmacological agent, with a distinct therapeutic potential for modulating cardiometabolic risk in selected patient subgroups.
Future research is needed to extend the dietary VK database and explore the pharmacological safety of VK and factors affecting VK bioavailability to provide more support for the bone health benefits of VK through more clinical trials.
Wang H et al. · Nutrients (2023)
Moreover, researchers continue to explore the role of VK as an emerging novel bioactive molecule with the potential function of improving bone health.
This review focuses on the effects of VK on bone health and related mechanisms, covering VK research history, homologous analogs, dietary sources, bioavailability, recommended intake, and deficiency.
The information summarized here could contribute to the basic and clinical research on VK as a natural dietary additive and drug candidate for bone health.
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.
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.
To confirm the beneficial role of vitamin A or K analogues in the chemoprevention of HCC further and larger randomised trials are now required.
To confirm these results, a larger well design RCT using fractures as the primary endpoint is clearly needed.
Ishida Y · Clinical calcium (2008)
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.