Vitamin K2

We evaluated 208 human studies on Vitamin K2, including 70 randomised controlled trials and 10 meta-analyses or systematic reviews; the controlled studies include 8,801 participants in total. As of 15 October 2026.

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1. What Is Vitamin K2? Occurrence, Origin and Forms

Vitamin K2 is a group of fat-soluble compounds in the vitamin K family known as menaquinones. They occur in fermented foods and in animal products and are also formed by bacteria. It is commonly used as a dietary supplement, often together with vitamin D.

Menaquinones are found in fermented foods such as natto and cheese and in animal foods such as liver and egg yolk. Some of the menaquinones present in the body come from the gut flora.

For dietary supplements, menaquinones are produced by fermentation or synthetically. In human studies, menaquinone-4 and menaquinone-7 are the forms most often tested, in different amounts and over different periods of time.

Forms and Preparations Studied

• Menaquinone-4 (MK-4)
• Menaquinone-7 (MK-7)
• Longer-chain menaquinones (MK-8 to MK-13)
• Menaquinone-7 in the all-trans form and in the cis form

Not covered on this page:

• Vitamin K1 (phylloquinone), the form found in green leafy vegetables
• Menadione (vitamin K3), a synthetic precursor that is not a menaquinone
• Combination products of vitamin K2 with vitamin D, calcium or other substances
• Medicinal substances that inhibit vitamin K metabolism (vitamin K antagonists)

2. What Does Vitamin K2 Do? Results by Area

How to read the table: counted are human studies whose results concern the area. “High” means at least one meta-analysis and two controlled studies showing improvement, or at least three controlled studies of which three quarters show improvement, with at least 300 participants in total. “Moderate” means at least two controlled studies showing improvement, as a majority, or one meta-analysis alongside controlled studies. “Low” means one controlled study showing improvement. Where an area has no controlled study, the strength of evidence is at most “low” (result “reviews only” or “observational data only”). Everything else is “unclear”. A study counts as showing improvement when at least half of its outcomes in this area improved. Reviews of combination products do not count as meta-analyses; results that only describe side effects or shares of users do not count as an effect. The same study is counted only once.

3. What the Studies Show in Detail

Vitamin K2, Bone Density and Bone Metabolism: Human Studies

In postmenopausal women with osteoporosis, vitamin K2 improved bone density of the lumbar spine in two meta-analyses, in one also at the forearm 12. In healthy postmenopausal women, menaquinone-4 increased mineral content and width of the femoral neck compared with placebo 10; menaquinone-7 slowed the loss of density at the lumbar spine and femoral neck and had a favorable effect on bone strength 75. Undercarboxylated osteocalcin decreased compared with placebo under menaquinone-4 72 and menaquinone-7 2471, as well as in a meta-analysis on vitamin K2 4. The same meta-analysis found higher levels of osteocalcin and bone-specific alkaline phosphatase and lower resorption markers 4. In a non-randomized study in anorexia nervosa, the resorption marker deoxypyridinoline decreased more under menatetrenone than without treatment 82. In an open randomized study in osteoporosis, bone density of the lumbar spine was better preserved under menatetrenone than without treatment 14. In stroke patients with hemiplegia, it increased at the metacarpal bones under menaquinone-4, and decreased without treatment 28. In dialysis patients, menaquinone-7 prevented loss at the lumbar spine compared with placebo, but accelerated it at the forearm 27. Studies with menaquinone-4 in healthy postmenopausal women 10, with menaquinone-7 in osteopenia 24 and in type 2 diabetes 44 found no difference in bone density. Menaquinone-4 is used as menatetrenone in Japan in a high, pharmaceutical dose against osteoporosis, menaquinone-7 was tested at low dose 7275; findings cannot be transferred from one form to the other. An altered laboratory value is not a clinical effect; it remains open whether the bone density improvements prevent fractures.

Further studies in this area: 15 21 23 24 27 28 32 40 41 44 47 53 54 55 59 67 72 73 74 75 77 80 82 93 111 115 116 117 121 123 124 126 155 156 158 160 161 162 163 164 171 172 178 182 183 186 189 190 191 192 193 194

Vitamin K2 and Bone Fractures: Human Studies

In an open randomized study in osteoporosis, fewer new clinical fractures occurred with menatetrenone (menaquinone-4) than without treatment 14. Another open randomized study in osteoporosis found fewer vertebral fractures with vitamin K2 (form not specified) than without treatment 21. In Alzheimer's patients, all of whom received risedronate, menatetrenone reduced non-vertebral fractures compared with placebo 15. A meta-analysis of studies without placebo found fewer non-vertebral and hip fractures with menatetrenone in neurological diseases 8. In two meta-analyses in postmenopausal women, the fracture frequency overall did not differ; only after excluding one deviating study each did an advantage emerge 23. The fracture data come almost exclusively from studies with menatetrenone 81415; for menaquinone-7, one study in healthy postmenopausal women showed only a smaller loss of height of the lower thoracic vertebrae 75. The transferability of the findings between the menaquinone forms and the question of whether the results apply to healthy women without osteoporosis remain open.

Further studies in this area: 28 32 75 132 137 161 172 173 174 182 183 191 193

Vitamin K2 and Arterial Calcification: Human Studies

In dialysis patients, inactive matrix Gla protein decreased more with menaquinone-7 than in the control groups 3156; high levels of this protein indicate vitamin K deficiency in the vessels. Calcification itself progressed in dialysis patients with menaquinone-7 just as in the control groups, measured by aortic and coronary calcification 3156. Likewise, calcification remained unchanged in type 2 diabetes with cardiovascular disease, in a study that was analyzed twice 4469. Only one randomized controlled study in symptomatic coronary heart disease found a slower increase in coronary calcification with menaquinone-7 than with placebo 20. Combined with vitamin D, menaquinone-7 did not change the calcification of the aortic valve and coronary arteries compared with placebo; only in a subgroup with severe baseline calcification did it progress more slowly 912. A combination product of vitamin K2, omega-3 fatty acids, B vitamins, OPC and resveratrol lowered the fat content of removed carotid plaques 17; results of mixtures do not belong to vitamin K2 alone. Also in addition to a basic treatment that both groups received, vitamin K2 did not reliably change calcification and plaques: in dialysis patients with rivaroxaban 25 and in carotid artery stenoses with acetylsalicylic acid and statin 50. It remains open whether an improvement in vitamin K status influences clinical calcification or cardiovascular events in the long term.

Further studies in this area: 50 52 56 64 69 78 84 87 89 95 98 103 104 106 110 114 118 139 146 149 155 159 163 164 166 167 171 172 174 175 176 177 178 179 180 184 186 189 190 192

Vitamin K2, Arterial Stiffness and Blood Pressure: Human Studies

In this area, 10 controlled studies with a total of 1117 participants are available, including postmenopausal women as well as kidney, dialysis and transplant patients. A randomized controlled study with menaquinone-7 lowered pulse wave velocity and stiffness index in healthy postmenopausal women over three years; distensibility and elasticity improved only with high baseline stiffness 13. In a controlled follow-up analysis in women with low vitamin K status, vascular stiffness after menopause increased less with menaquinone-7 than with placebo 76. In kidney transplant recipients with vitamin K deficiency, menaquinone-7 prevented an increase in pulse wave velocity compared with placebo 64, and in hemodialysis patients it increased less with menaquinone (form not specified) than in the control group 29. In overweight young adults, systolic blood pressure was not reliably lower with menaquinone-4 than with placebo 57. No difference in pulse wave velocity was found in studies in chronic kidney disease 22, in dialysis patients 3456 and in older people with vascular disease 39. The overall strength of evidence is low: the studies are small, the populations heterogeneous and the menaquinone forms and doses tested differ. It remains open whether the observed vascular changes influence clinical endpoints such as heart attack or stroke.

Further studies in this area: 64 76 99 101 107 114 118 159

Vitamin K2 and Cardiovascular Events: Human Studies

Cardiovascular events have so far been recorded only as safety endpoints and did not differ there. A controlled study in dialysis patients with functional vitamin K deficiency found no differences in vascular events and death with menaquinone-7 26. Another controlled study in hemodialysis patients with atrial fibrillation found no differences in mortality, stroke and cardiovascular events with vitamin K2 in addition to rivaroxaban 25. Cardiovascular biomarkers remained without difference with unspecified vitamin K2 in adults with chronic kidney disease 22. In type 2 diabetes, risk indices calculated from blood lipids and blood glucose with menaquinone-7 did not differ from placebo after accounting for baseline values 45, as did other cardiovascular risk factors in middle-aged adults 52. A single small controlled study in trained athletes reported a better maximum cardiac output with unspecified vitamin K2, without a difference in stroke volume 66. The evidence is unclear: the controlled studies are small and short, and one tested menaquinone-7 only together with vitamin D 9. Forms studied were predominantly menaquinone-7 as well as unspecified menaquinone preparations; clinical endpoints are still pending for most forms and dosages.

Further studies in this area: 86 95 131 149 159 160 162 163 172 177 179 188 189

Vitamin K2 and Chronic Kidney Disease: Human Studies

Controlled studies in kidney and dialysis patients measured vascular, bone and coagulation values and are described there; studies on the course of kidney disease itself are still pending. A review reports a decrease in matrix Gla protein levels (dp-ucMGP) with vitamin K2 supplementation, although the menaquinone form was not specified 180. Another review on predominantly menaquinone-7 describes impaired transport of vitamin K2 in HDL of uremic patients 166. A cross-sectional study in children with chronic kidney disease, published in two versions, found higher levels of undercarboxylated osteocalcin than in healthy children, indicating poorer vitamin K status 132137. A single case report mentions vitamin K2 substitution without specifying the menaquinone form, but only together with local wound care, analgesics, dialysis, sodium thiosulfate, discontinuation of relevant medications and hyperbaric oxygen therapy, and therefore cannot be considered evidence of efficacy 127. It remains open whether supplementation with defined menaquinone forms influences clinical endpoints in kidney disease.

Further studies in this area: 171 180 188

Vitamin K2: Further Outcomes in Studies

Further investigations include 28 controlled studies and 3 meta-analyses with a total of 2271 participants, mainly on blood glucose, blood lipids and muscle cramps. In type 2 diabetes, menaquinone-7 lowered fasting blood glucose and HbA1c compared with placebo 4651; in polycystic ovary syndrome, it lowered fasting insulin, insulin resistance and triglycerides 37. A meta-analysis on menaquinone-7 found lower values for insulin, HbA1c and insulin resistance 6. Menaquinone-4 lowered total and LDL cholesterol in overweight young adults compared with placebo, without effect on blood glucose 57; with menaquinone-7, blood lipids remained unchanged in type 2 diabetes 4651. With menaquinone-7, nocturnal leg cramps in older people were less frequent than with placebo 19, as were muscle cramps in hemodialysis with vitamin K2 (form not specified) 61; recovery after strength training did not improve with menaquinone-7 42. It remains open whether the observed changes in laboratory values also improve clinical endpoints. Mixtures whose results do not belong to vitamin K2 alone were tested in one study with vitamin D 9, a combination preparation with omega-3 fatty acids and other substances 17, and a liposomal vitamin mixture in cystic fibrosis 33.

Further studies in this area: 19 22 26 30 35 36 37 38 42 46 48 51 53 54 57 58 59 60 61 62 63 65 68 70 73 77 78 79 81 83 88 90 91 92 94 95 96 97 99 100 101 102 104 105 107 108 109 111 112 113 114 119 120 122 124 125 126 128 129 130 133 134 135 136 138 140 141 142 143 144 145 147 148 150 151 152 153 154 155 156 157 158 162 165 167 168 169 170 172 174 180 181 185 187 189

4. How Is Vitamin K2 Dosed? Preparation, Dose and Duration in Studies

The studies investigated predominantly menaquinone-7 (MK-7) as a capsule or tablet, as well as menaquinone-4 (menatetrenone) orally. Some of the investigations gave menaquinone-7 only together with vitamin D 912; such results cannot be attributed to vitamin K2 alone. If, by contrast, both groups received calcium and vitamin D or risedronate, the difference belongs to vitamin K2 1524. The forms and preparations investigated differ between the studies, and findings on menaquinone-4 cannot be transferred to menaquinone-7.

5. Is Vitamin K2 Safe? Side Effects in Studies

The studies predominantly report good tolerability of menaquinone-4 and menaquinone-7, without serious adverse events 266372. Individual studies mention gastrointestinal complaints; in a dialysis study, these, combined with the unpleasant odor of the tablets, led to most dropouts 18. One meta-analysis found more side effects under vitamin K2, but no serious ones 1, two others found no confirmed difference 23; in dialysis patients, menaquinone-7 did not activate blood coagulation 26.

6. What Remains Open: Limits of the Evidence

• It remains open whether the improved bone density values and laboratory values actually prevent bone fractures.
• It is unclear whether an improvement in vitamin K status influences arterial calcification or cardiovascular events in the long term.
• The studies on vascular stiffness and blood pressure are small, short, and investigated different populations and menaquinone forms.
• Whether menaquinone-7 protects vessels or bones in kidney and dialysis patients beyond vitamin K status is still open.

7. Bottom Line: What Is Established About Vitamin K2

Vitamin K2 comprises the menaquinones, especially menaquinone-4 and menaquinone-7. The best-studied area is bone: in postmenopausal women with osteoporosis, vitamin K2 improved bone density of the lumbar spine in meta-analyses, and undercarboxylated osteocalcin decreased 124. In studies with menatetrenone, fewer fractures occurred in osteoporosis and neurological diseases than without treatment 814; meta-analyses in postmenopausal women found no confirmed difference overall 23.

For vascular calcification and vascular stiffness, the evidence is weak; for cardiovascular events, it is unclear. Although vitamin K status improved with menaquinone-7 compared with placebo 525663, calcification usually progressed unchanged 223156. Cardiovascular events did not differ in two dialysis studies, but were recorded there only as safety endpoints 2526. The forms tested were predominantly menaquinone-7 and menaquinone-4; results for menaquinone-4 cannot be transferred to menaquinone-7, and mixed preparations with vitamin D, calcium or other substances do not allow attribution to vitamin K2 alone.