Table 1

Role of vitamin K on markers of CVD

StudySample sizePatient populationStudy methodsStudy findings
Arterial stiffness
Braam et al94181Healthy postmenopausal Caucasians between 50 and 60 years of age
Sex: female only
Age: 55
Design: double-blind RCT
Intervention: vitamin D3 (8 µg)
+K1 (1 mg) supplementation
Follow-up (years): 3
↑Distensibility (+8.8%, p<0.05)
↑Compliance (+8.6%, p<0.05)
↓Pulse pressure (−6.3%, p<0.05)
↓CCA elasticity (−13.2%, p<0.01)
Knapen et al90244Healthy, postmenopausal subjects aged 55–65 years
Sex: female only
Age: 60
Design: double-blind RCT
Intervention: vitamin K2 (MK-7) supplementation (180 µg)
Follow-up (years): 3
↓Carotid–femoral PWV
↓Stiffness Index β
(p<0.02)
Ikari et al9626Patients with coronary calcification and at least 1 coronary risk factor
Sex: 65% female
Age: 69
Design: open-label, single arm
Intervention: vitamin K2 (MK-4) supplementation (45 mg)
Follow-up (years): 1
↓Brachial–ankle PWV by 18% only in patients with vitamin K2 deficiency (p=0.03)
Mansour et al2760Adult renal transplant recipients with functioning graft for ≥3 months
Sex: 43% female
Age: 50
Design: prospective, single-centre, single-arm trial
Intervention: vitamin K2 (MK-7) supplementation (360 µg)
Follow-up (weeks): 8
↓Mean carotid–femoral PWV by 14.2% (p<0.001)
Vermeer and Hogne95243Healthy adults without a history of cardiovascular disease
Sex: 54%
Age: 61
Design: double-blind, placebo-controlled RCT
Intervention: vitamin K2 (MK-7) supplementation (180 µg)
Follow-up (years): 1
↑Mean carotid–femoral PWV in placebo group (p<0.005) but no significant change in MK-7 group
Cardiac output
McFarlin et al10126Aerobically trained athletes with normal body composition
Sex: 31% male
Age: 21
Design: double-blind RCT
Intervention: vitamin K2 supplementation (300 mg for 4 weeks, then 150 mg for 4 weeks)
Follow-up (weeks): 8
↑Maximal cardiac output by 12% (p=0.03)
Metabolic syndrome
Beulens et al10238 094Dutch subjects without diabetes aged 20–70 years from the Prospect-EPIC and MORGEN-EPIC cohorts (1993–1997)
Sex: 26% male
Age: 49
Design: prospective, population-based cohort study
Intervention: dietary vitamin K1 and K2 intake using FFQ
Follow-up (years): 10
↓Risk of incident type 2 diabetes with 10 µg increment increase in dietary vitamin K2 intake
(HR=0.93, p=0.04)
Choi et al10342Healthy young volunteers
Sex: Male only
Age (median): 29
Design: Placebo-controlled trial
Intervention: vitamin K2 supplementation (30 mg)
Follow-up (weeks): 4
 ↑Insulin sensitivity index (p=0.01)
 ↑Disposition index (p<0.01)
 ↑cOC (p=0.01)
Asemi et al11966Overweight patients with diabetes with CHD, aged 40–85 years, living in Iran
Sex: 47% female
Age: 65
Design: Double-blind RCT
Intervention: vitamin D (5 µg)
+K (90 µg)+calcium (500 mg) supplementation
Follow-up (weeks): 12
↓Maximum carotid intima media thickness (p=0.02)
↓HOMA-IR (p=0.01)
↓HOMA-B (p=0.01)
↑QUICKI (p=0.01)
Knapen et al51214Healthy, postmenopausal women
Sex: female only
Age: 55–65
Design: randomised, placebo-controlled trial
Intervention: vitamin K2 (MK-7) 180 µg/day or placebo
Follow-up (years): 3
Only in good responders (↑ cOC):
↑Total and HMW adiponectin
↓Abdominal fat mass (waist circumference and VAT)
Vascular calcification
Beulens et al85564Healthy Dutch subjects aged 49–70 years not on HRT or contraceptives, sampled (2002–2004) from the PROSPECT-EPIC Study
Sex: female only
Age: 67
Design: population-based, cross-sectional study
Intervention: vitamin K1 and K2 (MK-4–MK-10) intake using FFQ
Follow-up:
↓Coronary calcification with MK intake only
(RR=0.80 (0.65 to 0.98), p trend=0.03)
Shea et al86388Asymptomatic, ambulatory community-dwelling subjects aged 60–80 years
Sex: 60% female
Age: 68
Design: double-blind RCT
Intervention: vitamin K1 supplementation (500 µg)
Follow-up (years): 3
↓CAC progression in those >85% adherent to supplementation (p=0.03)
Fusaro et al58387Patients on haemodialysis for ≥1 year
Sex: 37% female
Age: 64
Design: prospective observational study
Comparison groups: patients with or without vitamin K1 or vitamin K2 (MK-4, MK-5 or MK-7) deficiency
Follow-up (years): 3
↑Risk of abdominal aortic calcification with MK-4 deficiency (OR=2.8, p=0.026)
↑Risk of iliac calcification with MK-7 deficiency (OR=1.6, p=0.042)
Kurnatowska et al12042Non-smoking, non-dialysed Caucasians with CKD stages 3–5, stable renal function for ≥6 months and CAC ≥10 AU
Sex: 48% female
Age: 58
Design: double-blind RCT
Intervention: vitamins K2 (MK-7, 90 µg)+D3 (10 µg) vs D3 (10 µg)
Follow-up (months): 9
↓Change in CCA intima-media thickness in vitamin K2 +D group (0.06±0.08 vs 0.14±0.05 mm, p=0.005)
Nonsignificant decrease in ΔCAC score in K2 +D group (p=0.7)
Ikari et al9626Patients with coronary calcification and at least 1 coronary risk factor
Sex: 65% female
Age: 69
Design: open-label, single arm
Intervention: vitamin K2 (MK-4) supplementation (45 mg)
Follow-up (years): 1
↑CAC score by 14% (p=0.02)
Zwakenberg et al11068Subjects aged >40 years with CVD, type 2 diabetes, and eGFR >30
Sex: 24% female
Age: 69
Design: double-blind RCT
Intervention: vitamin K2 (MK-7) supplementation (360 µg)
Follow-up (months): 6

 No change in femoral arterial calcification on18F-NaF PET scan (p=0.06) or CT scan (p=0.18)
Oikonomaki et al109102Adults with ESRD on haemodialysis
Sex: not specified
Age: 67
Design: prospective, randomised, open-label clinical trial
Intervention: vitamin K2 supplementation (200 µg)
Follow-up (years): 1
No change in abdominal aortic calcification via CT-measured Agatston score
De Vriese et al108132Chronic haemodialysis patients with non-valvular atrial fibrillation and CHA2DS2-VASc score ≥2
Sex: 33% female
Age: 80
Design: multicentre, prospective, randomised, open-label trial
Intervention: VKA vs rivaroxaban vs rivaroxaban +vitamin K2 (2000 µg three times per week)
Follow-up (months): 18
No differences in change of PWV or coronary artery, thoracic aorta, or cardiac valve calcium scores at follow-up, or all-cause death, stroke or cardiovascular events between groups
Bartstra et al11168Subjects aged >40 years with CVD, type 2 diabetes, and eGFR >30
Sex: 24% female
Age: 69
Design: post-hoc analysis of double-blind RCT
Intervention: vitamin K2 (MK-7) supplementation (360 µg)
Follow-up (months): 6

 No change in total arterial calcification, assessed by CT scan in several large arterial beds
Valvular calcification
Geleijnse et al914807Dutch subjects >55 years without prior MI at baseline (1990–1993)
Sex: 38% male
Age: 67
Design: prospective, population-based
Intervention: dietary vitamin K1 and K2 using FFQ
Follow-up (years): 7
↓Severe aortic calcification in mid and upper tertials of vitamin K2 intake (OR=0.71 and 0.48, respectively; p<0.05)
Brandenburg et al10799Asymptomatic or mildly symptomatic patients without CKD with aortic valve PFV >2 m/s
Sex: 82% male
Age: 69
Design: prospective, single-centre, open-label RCT
Intervention: vitamin K1 supplementation (2 mg)
Follow-up (years): 1
↓Progression in aortic valve calcification volume score (10% vs 22%, p=0.04)
  • Both ages and follow-up times are presented as mean years, unless otherwise specified, and rounded to the nearest whole number. All RCT study designs are placebo controlled unless otherwise specified. All provided dosages are per daily unless otherwise noted. P values <0.05 denote significance.

  • AU, Agtston units; CAC, coronary artery calcification; CCA, common carotid artery; CHD, coronary heart disease; CKD, chronic kidney disease; cOC, carboxylated osteocalcin; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; FFQ, Food Frequency Questionnaire; 18F-NaF PET, 18sodium fluoride positron emission tomography; HMW, human molecular weight; HOMA-B, homeostasis model for assessment of B-cell function; HOMA-IR, homeostasis model for assessment of insulin resistance; HRT, hormone replacement therapy; MI, myocardial infarction; MK, menaquinone; N/A, not applicable; PFV, peak flow velocity; PWV, pulse wave velocity; QUICKI, quantitative insulin sensitivity check index; RCT, randomised control trial; RR, relative risk; VAT, estimated visceral adipose tissue area; VKA, vitamin K antagonist.