02Research · Supplement
Vitamin K2
Measured against the 58-marker panel. Human studies found an effect on 7, no change in 12 and conflicting results on 2; 37 have no result yet.
Most studied for
General bone and vascular health maintenance (nutritional supplementation)
01Read first
Who should be careful
Cautions12
SeriousConcurrent vitamin K antagonist (warfarin, acenocoumarol, phenprocoumon) therapy without structured INR monitoringGrade A
Pharmacodynamic antagonism of anticoagulation — K2 is the direct substrate for VKORC1-dependent carboxylation of clotting factors II, VII, IX, X; reverses or blunts the target effect of VKA therapy
SeriousComplete biliary obstruction or severe cholestasisGrade B
Bile acids essential for micellar solubilization and absorption of fat-soluble vitamins; without adequate bile flow, oral K2 absorption approaches zero
SeriousConfirmed soy protein allergy (for MK-7 formulations derived from Bacillus subtilis natto fermentation of soybeans)Grade C
Anaphylaxis risk — MK-7 produced via natto fermentation may contain residual soy proteins; allergic sensitization reported in soy-allergic individuals exposed to natto-derived products
ModerateSevere fat malabsorption — short bowel syndrome, cystic fibrosis with pancreatic insufficiency, severe celiac disease (uncontrolled), extensive…Grade B
Impaired micellar formation and lymphatic uptake of fat-soluble vitamins; oral K2 bioavailability severely reduced in proportion to degree of fat malabsorption
Show 8 more
ModerateSevere hepatic impairment (Child-Pugh C / MELD >20)Grade C
Severe hepatocyte loss limits production of vitamin K-dependent clotting factors independently of K2 cofactor availability — supplementation cannot overcome synthetic capacity failure. K2 metabolism via CYP3A4 also impaired, potentially elevating K2 exposure.
ModeratePeri-operative period — VKA-managed patients within 7 days of scheduled surgeryGrade C
K2 supplementation in peri-operative VKA management complicates INR normalization and bridging therapy protocols; interference with planned acute reversal strategies
ModerateSolid organ transplant recipients on calcineurin inhibitors (tacrolimus, cyclosporine) without therapeutic drug monitoringGrade C
narrow therapeutic index of calcineurin inhibitors makes small PK changes clinically significant
ModerateConcurrent sevelamer carbonate therapy without temporal separationGrade C
Sevelamer's polyallylamine backbone sequesters fat-soluble vitamins in the GI lumen, reducing K2 absorption by up to 50%. Pierce 2010 demonstrated 57% calcitriol AUC reduction.
ModeratePregnancy — pharmacological doses (>1mg/day) in first trimesterGrade D
ModerateLactation — pharmacological doses (>1mg/day)Grade D
K2 is transferred to breast milk; nutritional supplementation enhances neonatal K2 status (beneficial).
ModeratePediatric patients — pharmacological doses (>1mg/kg/day MK-4 equivalent) without specialist supervisionGrade D
hepatic CYP3A4 enzyme maturation varies by age.
ModerateActive or high-risk hypercoagulable states (antiphospholipid syndrome, Factor V Leiden homozygous, active DVT/PE) without anticoagulation coverageGrade D
Theoretical potentiation of procoagulant factors II, VII, IX, X via enhanced gamma-carboxylation in states of baseline thrombophilia; K2 also activates anticoagulant Protein C and S, but net procoagulant effect may dominate in prothrombotic genetic backgrounds
Interactions12
SeriousWarfarin and all vitamin K antagonists (acenocoumarol, phenprocoumon, fluindione)Grade A
Direct pharmacodynamic antagonism — vitamin K2 is the obligate substrate for VKORC1-mediated gamma-carboxylation of clotting factors II, VII, IX, X and anticoagulant proteins C and S; VKAs competitively inhibit VKORC1.
ModerateOrlistat (tetrahydrolipstatin)Grade A
Inhibits pancreatic lipase, reducing dietary fat absorption by ~30%; proportionally reduces absorption of all fat-soluble vitamins (A, D, E, K) via impaired micelle formation
ModerateBile acid sequestrants — cholestyramine, colestipol, colesevelamGrade B
Bile acid sequestrants bind fat-soluble vitamins in GI lumen via non-specific ionic and hydrophobic interactions, impairing micellar formation and absorption of vitamin K2
ModerateMineral oil (liquid paraffin)Grade B
Mineral oil solubilizes fat-soluble vitamins in GI lumen, trapping them within a non-absorbable lipid phase; prevents micellar uptake of all fat-soluble vitamins
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ModerateBroad-spectrum antibiotics — fluoroquinolones, cephalosporins, metronidazole, clindamycinGrade C
Disruption of colonic microbiome reduces endogenous MK synthesis by intestinal bacteria (MK-7, MK-8, MK-9, MK-10); clinically significant primarily in patients with marginal dietary K intake or concurrent VKA therapy
ModerateCYP3A4 inducers — rifampicin, carbamazepine, phenytoin, phenobarbital, primidone, St. John's WortGrade C
Strong CYP3A4 induction accelerates oxidative metabolism of MK-4 sidechain, reducing circulating K2 levels. Antiepileptics (phenytoin, carbamazepine, phenobarbital) independently deplete vitamin K via accelerated catabolism of K-dependent proteins — additive deficiency risk
ModerateCyclosporine A and tacrolimusGrade C
CYP3A4 substrates and inhibitors (cyclosporine/tacrolimus); reduced CYP3A4 activity may increase MK-4 exposure.
Moderatesevelamer carbonateGrade C
Sevelamer's polyallylamine backbone sequesters fat-soluble vitamins (A, D, E, K) in the GI lumen via hydrophobic and electrostatic interactions. Pierce 2010 demonstrated sevelamer carbonate reduced calcitriol (vitamin D) AUC by 57% (p=0.024) in healthy volunteers.
MinorGlucocorticoids — prednisone, dexamethasone (chronic systemic use ≥3 months)Grade C
Chronic glucocorticoids suppress osteocalcin gene transcription and osteoblast activity; K2 partially counteracts via RUNX2-mediated osteocalcin promoter activation.
MinorProton pump inhibitors — omeprazole, pantoprazole, lansoprazole (chronic use >1 year)Grade C
Chronic PPI-induced hypochlorhydria reduces peptic release of protein-bound vitamin K from food, modestly impairing bioavailability of food-derived K2 (e.g., natto); effect on supplemental K2 (free, lipid-formulated) is minimal as acid-mediated protein release is not required
Minorlanthanum carbonateGrade C
Lanthanum carbonate showed no statistically significant effect on fat-soluble vitamin absorption in the Pierce 2010 crossover study (calcitriol AUC: no significant change vs. control).
MinorStatins — simvastatin, atorvastatin, lovastatin (CYP3A4 substrates)Grade D
Statins inhibit mevalonate pathway, reducing geranylgeranyl pyrophosphate (GGPP) — a shared precursor for both CoQ10 and endogenous MK-4 synthesis via UBIAD1.
02What it moves
21 markers studied
Read with this in mind
All HCC recurrence RCTs pooled in both Riaz 2012 and Zhong 2013 were conducted exclusively in Japan in patients with viral hepatitis (HBV/HCV)-associated HCC and liver cirrhosis.
All vitamin K2 forms (particularly long-chain MK-7 due to 72hr half-life enabling cumulative accumulation) antagonize warfarin and other vitamin K antagonist anticoagulants.
Blood sugar4 of 4 studied
HbA1cLowersGrade B
Vitamin K2 lowers HbA1c.
Small effect · 1 study linked
Fasting glucoseLowersGrade B
Vitamin K2 lowers fasting glucose.
Small effect · 1 study linked
All RCTs in MA involved T2DM patients; effect magnitude modest; extrapolation to normoglycemic individuals is speculative
Fasting insulinLowersGrade B
Vitamin K2 lowers fasting insulin.
Small effect · 1 study linked
HOMA-IRLowersGrade A
Vitamin K2 lowers HOMA-IR.
Meta-analysis or review · Small to moderate effect · 6 studies linked
K1 study; direct K2 translation uncertain. Sex-specific effect raises hypothesis that K-insulin axis may be androgen-dependent or driven by sex-specific adipose/muscle differences.
- Phylloquinone intake, insulin sensitivity, and glycemic status in men and women
- Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis. (2017)
- Vitamin K2 (menaquinone-7) increases plasma adiponectin but does not affect insulin sensitivity in postmenopausal women: a randomized controlled trial. (2021)
- Glycemic control improvement in individuals with type 2 diabetes with vitamin K (2021)
- Beneficial health effects of Menaquinone-7 on body composition, glycemic indices, lipid profile, and endocrine markers in polycystic ovary syndrome patients. (2020)
- Suksomboon N, et al. (2017)
Lipids4 of 6 studied
LDL-CNo changeGrade B
Studies of Vitamin K2 found no change in LDL-C.
Meta-analysis or review · 2 studies linked
Consolidated with LDL_cholesterol entry. Hartley 2015: null. 2 studies in corpus.
HDL-CNo changeGrade B
Studies of Vitamin K2 found no change in HDL-C.
Meta-analysis or review · 1 study linked
Consolidated with HDL_cholesterol entry. Hartley 2015: null. 1 study in corpus.
TriglyceridesNo changeGrade B
Studies of Vitamin K2 found no change in triglycerides.
Meta-analysis or review · 2 studies linked
Consolidated with triglycerides entry. Hartley 2015: null. 7 studies in corpus — no positive directional signal.
Total cholesterolNo changeGrade B
Studies of Vitamin K2 found no change in total cholesterol.
Meta-analysis or review · 1 study linked
Hartley 2015 Cochrane (single RCT, n=60): no significant effect. Consolidated with total_cholesterol entry. 4 studies with TC data in corpus.
Inflammation3 of 5 studied
hs-CRPNo changeGrade A
Studies of Vitamin K2 found no change in hs-CRP.
Meta-analysis or review · 7 studies linked
Consolidated CRP and hs_crp entries. Shea 2008 (K1, n=379, 3yr): null (p=0.59). Karamzad 2022 (MK-7, n=45, T2DM): inconsistent/null. 9 studies in corpus. In-vitro NF-κB data do not translate to systemic anti-inflammatory effect in non-inflammatory populations.
- Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis. (2017)
- Effects of vitamin K2 and D3 supplementation on epicardial adipose tissue and systemic inflammation: A substudy of the AVADEC trial. (2025)
- The effect of menaquinone-7 supplementation on dp-ucMGP, PIVKAII, inflammatory markers, and body composition in type 2 diabetes patients: a randomized clinical trial (2022)
- Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. (2015)
- Menaquinone-7 as a novel pharmacological therapy in the treatment of rheumatoid arthritis: A clinical study. (2015)
- Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial
- +1 more studies
IL-6No changeGrade A
Studies of Vitamin K2 found no change in IL-6.
Meta-analysis or review · 4 studies linked
Consolidated IL6 and il_6 entries. Shea 2008 (K1, n=379, 3yr): null (p=0.61) despite robust ucOC reduction. 14 studies reference IL-6 but primarily in-vitro. Cross-sectional associations confounded by dietary quality.
- Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis. (2017)
- The Effects of Vitamin K2 on Recovery from Muscle-Damaging Resistance Exercise in Young and Older Adults: The TAKEOVER Randomized Controlled Trial. (2026)
- Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial
- Vitamin K, circulating cytokines, and bone mineral density in older men and women (2008)
ESRLowersGrade B
Vitamin K2 lowers ESR.
Human trials · 1 study linked
2 studies with ESR data. Insufficient for directional assessment.
Liver3 of 6 studied
ALTNo changeGrade B
Studies of Vitamin K2 found no change in ALT.
2 studies linked
ASTNo changeGrade A
Studies of Vitamin K2 found no change in AST.
Meta-analysis or review · 16 studies linked
2 studies with AST data per corpus coverage; no elevation signal. Thin evidence base but no safety concern.
- 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. (2025)
- Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis. (2017)
- Vitamin K2 Supplementation in Hospitalised COVID-19 Patients: A Randomised Controlled Trial. (2024)
- Vitamin K2 supplementation improves impaired glycemic homeostasis and insulin sensitivity for type 2 diabetes through gut microbiome and fecal metabolites. (2023)
- Glycemic control improvement in individuals with type 2 diabetes with vitamin K (2021)
- Beneficial health effects of Menaquinone-7 on body composition, glycemic indices, lipid profile, and endocrine markers in polycystic ovary syndrome patients. (2020)
- +10 more studies
ALPMixed resultsGrade A
Studies of Vitamin K2 and ALP disagree.
Meta-analysis or review · Small effect · 5 studies linked
36 studies reference ALP; however, ALP in K2 literature predominantly reflects bone-specific ALP (BSAP), not hepatic ALP. Increases reflect enhanced osteoblast activity (formation marker), not hepatic injury. Total ALP direction depends on population context (bone vs liver disease).
- Should We Recommend Vitamin K2 Supplement to Prevent Coronary Artery Calcification for Patients Receiving Statins and/or Warfarin? (2025)
- Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma. (2009)
- Effect of vitamin K2 treatment on carboxylation of osteocalcin in early postmenopausal women. (2006)
- Vitamin K2 inhibits glucocorticoid-induced bone loss partly by preventing the reduction of osteoprotegerin (OPG). (2005)
- Pharmacodynamics of menatetrenone and effects on bone metabolism in continuous ambulatory peritoneal dialysis patients. (2002)
Kidney1 of 4 studied
CreatinineNo changeGrade B
Studies of Vitamin K2 found no change in creatinine.
0 studies linked
This result is graded, but no study is linked to it yet. Treat it as unconfirmed.
No nephrotoxicity signal. 4 studies with creatinine data; monitored as safety parameter in renal population K2 trials (De Vriese, Oikonomaki, Westenfeld). No creatinine elevation attributed to K2.
Hormones1 of 5 studied
TestosteroneLowersGrade B
Vitamin K2 lowers testosterone.
Human trials · 1 study linked
Minerals3 of 5 studied
SodiumNo changeGrade D
Studies of Vitamin K2 found no change in sodium.
0 studies linked
This result is graded, but no study is linked to it yet. Treat it as unconfirmed.
10 studies reference sodium (likely as baseline or safety lab in renal population trials). No K2 mechanism for sodium modulation.
CalciumNo changeGrade B
Studies of Vitamin K2 found no change in calcium.
9 studies linked
77 studies reference calcium — most extensively studied electrolyte in K2 context. K2 redirects calcium deposition (from arteries to bone) via MGP/osteocalcin mechanisms but does NOT raise serum calcium levels. No hypercalcemia signal in any K2 trial.
- Efficacy of Recombinant Human Parathyroid Hormone 1-34 and Vitamin K2 Combination Therapy in Postmenopausal Osteoporosis. (2025)
- Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study. (2020)
- Effect of Low-Dose Vitamin K2 Supplementation on Bone Mineral Density in Middle-Aged and Elderly Chinese: A Randomized Controlled Study. (2020)
- Protective effect of vitamins K2 and D3 on prednisolone-induced loss of bone mineral density in the lumbar spine. (2004)
- Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency. (2002)
- Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis. (2000)
- +3 more studies
MagnesiumRaisesGrade C
Vitamin K2 raises magnesium.
Human trials · 1 study linked
12 studies reference magnesium (likely as cofactor context or baseline lab in bone/renal trials). No direct K2 effect on serum magnesium expected.
Body2 of 2 studied
Blood pressureNo changeGrade B
Studies of Vitamin K2 found no change in blood pressure.
Meta-analysis or review · 3 studies linked
Weight and BMIMixed resultsGrade B
Studies of Vitamin K2 and weight and BMI disagree.
Meta-analysis or review · 2 studies linked
- 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. (2025)
- Effect of vitamin K2 on cortical and cancellous bone mass and hepatic lipids in rats with combined methionine-choline deficiency (2011)
Also measured29 outcomes
Outcomes these studies measured that are not on the shared panel, so they are not on the map.
HCC Recurrence Rate (2-year)LowersGrade A
Vitamin K2 lowers HCC Recurrence Rate (2-year).
Moderate effect · 2 studies linked
MK-4 45mg/day; all source RCTs from Japan; underlying HBV/HCV aetiology in all populations; generalizability to Western NASH-associated or non-viral HCC unknown
HCC Recurrence Rate (3-year)LowersGrade A
Vitamin K2 lowers HCC Recurrence Rate (3-year).
Moderate effect · 2 studies linked
Carboxylated Osteocalcin (cOC)RaisesGrade A
Vitamin K2 raises carboxylated Osteocalcin (cOC).
Moderate effect · 1 study linked
Femoral Neck BMDRaisesGrade A
Vitamin K2 raises femoral Neck BMD.
Small effect · 1 study linked
Lumbar Spine Bone Mineral Density (LS-BMD)RaisesGrade A
Vitamin K2 raises lumbar Spine Bone Mineral Density (LS-BMD).
Small effect · 1 study linked
Effect size smaller than pharmacological agents (bisphosphonates, PTH); consistency across Asian populations high; Western-population BMD data sparse in this batch
Undercarboxylated Osteocalcin (ucOC)LowersGrade A
Vitamin K2 lowers undercarboxylated Osteocalcin (ucOC).
Large effect · 1 study linked
ucOC/cOC ratio used as primary PD endpoint in Japanese regulatory trials; reliable proxy for K2 tissue activity
Vertebral Fracture IncidenceLowersGrade A
Vitamin K2 lowers vertebral Fracture Incidence.
Moderate effect · 1 study linked
Japanese MK-4 fracture data considered highest quality for this compound; Western MK-7 fracture endpoint data absent from this batch
Bone-Specific Alkaline Phosphatase (BSAP)RaisesGrade B
Vitamin K2 raises bone-Specific Alkaline Phosphatase (BSAP).
Small effect · 1 study linked
Show 21 more
C-Terminal Telopeptide of Type I Collagen (CTX)LowersGrade B
Vitamin K2 lowers C-Terminal Telopeptide of Type I Collagen (CTX).
Small effect · 1 study linked
Disposition index diRaisesGrade B
Vitamin K2 raises disposition index di.
Moderate effect · 1 study linked
DI reflects integrated beta-cell function relative to insulin sensitivity; improvement suggests enhanced metabolic reserve
- Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial
Dp ucMGPLowersGrade B
Vitamin K2 lowers dp ucMGP.
1 study linked
Zwakenberg 2019 confirms dose-dependent K2-dependent MGP carboxylation in a high-risk T2DM/CVD population. dp-ucMGP reduction of 202.7 pmol/L is consistent with prior MK-7 dose-response literature. Functional biomarker response confirmed even when hard vascular calcification endpoints were null — supports dp-ucMGP a...
Fracture riskLowersGrade B
Vitamin K2 lowers fracture risk.
Moderate effect · 1 study linked
Fracture reduction without BMD improvement suggests effect through bone quality rather than density (e.g., osteocalcin-mediated collagen crosslinking, trabecular microarchitecture). If generalizable to K2, this would be a clinically meaningful effect independent of DXA readouts.
- Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial
Hip Fracture IncidenceLowersGrade B
Vitamin K2 lowers hip Fracture Incidence.
Small effect · 1 study linked
Insulin sensitivity siRaisesGrade B
Vitamin K2 raises insulin sensitivity si.
Moderate effect · 1 study linked
- Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial
N-terminal Propeptide of Type I Procollagen (P1NP)RaisesGrade B
Vitamin K2 raises N-terminal Propeptide of Type I Procollagen (P1NP).
Small effect · 1 study linked
Total Hip BMDRaisesGrade B
Vitamin K2 raises total Hip BMD.
Small effect · 1 study linked
Total Osteocalcin (tOC)RaisesGrade B
Vitamin K2 raises total Osteocalcin (tOC).
Small effect · 1 study linked
Urinary Deoxypyridinoline (DPD)LowersGrade B
Vitamin K2 lowers urinary Deoxypyridinoline (DPD).
Small effect · 1 study linked
Waist CircumferenceLowersGrade B
Vitamin K2 lowers waist Circumference.
Human trials · 1 study linked
Carboxylated osteocalcin cOCRaisesGrade B
Vitamin K2 raises carboxylated osteocalcin cOC.
0 studies linked
This result is graded, but no study is linked to it yet. Treat it as unconfirmed.
cOC increase concurrent with ucOC decrease — shift from undercarboxylated to carboxylated pool; cOC baseline level predicted Si response
Prothrombin Time / INRLowersGrade B
Vitamin K2 lowers prothrombin Time / INR.
Moderate effect · 0 studies linked
This result is graded, but no study is linked to it yet. Treat it as unconfirmed.
CRITICAL SAFETY FLAG: K2 antagonizes warfarin/VKAs; MK-7 ≥50mcg/day has clinically significant warfarin interaction; INR monitoring mandatory if co-administered
Undercarboxylated osteocalcin ucOCLowersGrade B
Vitamin K2 lowers undercarboxylated osteocalcin ucOC.
0 studies linked
This result is graded, but no study is linked to it yet. Treat it as unconfirmed.
Both K1 (ECKO, -21.4% at 2yr) and MK-4 (Choi 2011, significant at 4wk) reduce ucOC. ucOC reduction is a reliable pharmacodynamic marker across K forms. ECKO: ucOC decreased despite null BMD effect — dissociation notable.
Coronary Artery Calcification (CAC Score)LowersGrade C
Vitamin K2 lowers coronary Artery Calcification (CAC Score).
Small effect · 1 study linked
Observational association strong; interventional RCT evidence on CAC absent; dp-ucMGP reduction is mechanistic surrogate only
Pulse Wave Velocity (PWV)LowersGrade C
Vitamin K2 lowers pulse Wave Velocity (PWV).
Small effect · 1 study linked
Promising single RCT signal; requires replication; not captured in Hartley 2015 pooled analysis
AdiponectinRaisesGrade D
Vitamin K2 raises adiponectin.
Small effect · 1 study linked
Pathway proposed in rodent models; human data insufficient; Grade D
Vascular calcification CACNo changeGrade B
Studies of Vitamin K2 found no change in vascular calcification CAC.
2 studies linked
Likely a measurement artifact rather than a real change; see the note.
Zwakenberg 2019: MK-7 360 mcg/day ×6mo in T2DM+CVD adults. CT CAC: null (p=0.18). 18F-NaF PET TBR: unexpected trend toward increase (p=0.06) — may reflect active calcification remodeling or methodological artifact. dp-ucMGP was significantly reduced confirming K2 biological activity was present. Null vascular calcif...
- Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study
- Zwakenberg SR, de Jong PA, Bartstra JW, van Asperen R, Westerink J, de Valk H, Nathoe H, Vernooij RWM, Slart RHJA, Luurtsema G, Wolterink JM, Lam MGEH, Leiner T, van der Schouw YT, Beulens JWJ (2019)
HCC Recurrence Rate (1-year)No changeGrade B
Studies of Vitamin K2 found no change in HCC Recurrence Rate (1-year).
1 study linked
Absence of 1yr effect may reflect time required for anti-proliferative mechanism to manifest; supports chronic suppressive rather than acute action
Bone mineral densityNo changeGrade B
Studies of Vitamin K2 found no change in bone mineral density.
0 studies linked
This result is graded, but no study is linked to it yet. Treat it as unconfirmed.
Overall Survival (HCC patients)Mixed resultsGrade B
Studies of Vitamin K2 and overall Survival (HCC patients) disagree.
Small effect · 2 studies linked
CONTESTED: recurrence consistently reduced but OS benefit unclear; short follow-up and crossover may explain discordance between recurrence and survival endpoints
How it might work4
Proposed mechanisms. Most rest on lab and animal work, so read them as explanations, not proof of an effect.
- Carboxylation of osteocalcin (OCN) via gamma-glutamyl carboxylase (GGCX); converts undercarboxylated osteocalcin (ucOC) to carboxylated osteocalcin (cOC), enabling calcium binding in bone matrix hydroxyapatite
- Matrix Gla Protein (MGP) carboxylation - activated cMGP inhibits vascular smooth muscle cell calcification by binding and sequestering calcium-phosphate crystals and BMP-2/4; dp-ucMGP (inactive form) accumulates when K2 is deficient, correlating with calcification burden
- Gas6 (Growth Arrest Specific 6) Gla-domain carboxylation enabling TAM receptor (Tyro3/Axl/Mer) activation; regulates apoptosis, platelet aggregation, and innate immune signalling - proposed mechanism for MK-4 anti-proliferative effects in HCC
- Protein S carboxylation - K2-dependent Gla activation required for Protein S anticoagulant cofactor function (activated Protein C pathway); K2 preferentially traffics to extrahepatic tissues vs K1, potentially providing superior extrahepatic Gla protein activation
03No result yet
37 markers
Not yet reviewed37
No study in this dossier reported these, and they haven't been searched for one by one yet.
- Inflammation
- TNF-αFibrinogen
- Kidney
- eGFRBUNCystatin C
- Thyroid
- TSHFree T3Free T4Reverse T3
- Oxidative stress
- MDAF2-isoprostanes8-OHdGGlutathione
- B vitamins
- HomocysteineFolateVitamin B12MMA
Open questions4
- Does the dp-ucMGP → calcification prevention mechanistic chain function in pre-calcification populations, or is the consistent null finding in established-calcification RCTs indicative of a fundamental limitation of MGP-mediated vascular protection?
- Do K2 bone and glycemic effects replicate in Western (European/American) populations at equivalent doses, or are the Japanese positive findings population-specific?
- What is the effect of K2 supplementation on insulin sensitivity in pre-diabetic, insulin-resistant, and female populations?
- What is the long-term safety profile of MK-7 at doses >360mcg/day (the emerging 'high-dose nutritional' range used in vascular calcification trials)?
04The studies and genetics
Go deeper
Every study and gene finding
Open the strongest papers with their populations and findings, and the gene differences human studies measured.
Compare with
- Omega-321 shared
- Ashwagandha20 shared
- Creatine20 shared
- HIIT20 shared
- L-carnitine20 shared
Each marker shows the strongest record in the dossier. Records are extracted from published studies by a model pipeline and graded A to D; records whose own notes say no usable human data exists count as no result yet. Research summaries for education, not medical advice. How this page is sourced