This page shows what was measured, who it was measured in, and what that does not settle.
What Vitamin K2 MK-7 does in the body
One of those proteins locks calcium into bone; another patrols artery walls and stops calcium crystallising there.
A handful of proteins in your body are made with a chemical clamp that only closes after vitamin K modifies them. If vitamin K is short, both proteins are still made but sit around uncarboxylated and useless, and you can measure exactly how much of the inactive form is circulating. Supplementing MK-7 activates them, and the inactive fraction drops by about half — which is a real and impressive biochemical result. The question the trials asked next is whether activating those proteins changes the calcium in anybody's arteries, and the imaging says no.
Why people take it. Taken with vitamin D for bone density and to keep calcium out of the arteries
What happened in people
Three years of 180 micrograms daily reduced age-related bone mineral density decline at lumbar spine and femoral neck
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
Everything downstream of the biomarker has failed when measured by imaging
Where it acts
Hepatocyte endoplasmic reticulum for the clotting factors; osteoblasts for osteocalcin; vascular smooth muscle cells of the arterial media for matrix Gla protein
Kind of result
A number that stands in for health
Supervision
Not usually supervised: sold as a supplement or food ingredient where recorded. That is a legal category, not a safety judgement.
What the registries record it as
The supplement label database classes it as vitamin, under the name Vitamin K (menaquinone).
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 142 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Change in aortic valve calcification score on non-contrast cardiac CT
✗ The study did not show it
Who was studied
Diederichsen 2022 — vitamin K2 and D in aortic valve calcification
How many people
365
Study design
Randomised double-blind multicentre, 24 months
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Mean difference 17 AU (95% CI -86 to 53), P = 0.64; aortic valve area difference 0.02 cm2, P = 0.78; peak jet velocity 0.04 m/s, P = 0.21
Repeated elsewhere
Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. The dose was 720 micrograms of MK-7, four times that used in the positive bone and stiffness trials, given with vitamin D, in exactly the population the product targets. Aortic and coronary artery calcification progression also did not differ.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule or softgel, usually as fermentation-derived all-trans MK-7 in an oil base, frequently combined with vitamin D3
Interval reported. 95% CI -86 to 53), P = 0
Written into the record, not signed off as a reviewed claim.
Bone mineral density and content at lumbar spine, total hip and femoral neck by DXA
✓ The study showed what it set out to show
Who was studied
Knapen 2013 — three-year MK-7 and bone health in postmenopausal women
How many people
244
Study design
Randomised placebo-controlled, 3 years
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Significantly decreased age-related decline in bone mineral content and density at lumbar spine and femoral neck; not at total hip
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The endpoint is bone density rather than fracture, and the trial was not powered for fractures. It used a branded MK-7 ingredient and shares its cohort and investigators with the arterial stiffness trial, so the two are not independent.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule or softgel, usually as fermentation-derived all-trans MK-7 in an oil base, frequently combined with vitamin D3
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Carotid-femoral pulse wave velocity and local carotid stiffness indices
✓ The study showed what it set out to show
Who was studied
Knapen 2015 — three-year MK-7 and arterial stiffness in postmenopausal women
How many people
244
Study design
Randomised double-blind placebo-controlled, 3 years
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Carotid-femoral pulse wave velocity and Stiffness Index beta significantly decreased in the total group; dp-ucMGP decreased 50% versus placebo
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The larger improvements in distension, compliance, distensibility and local carotid pulse wave velocity were confined to women with a baseline Stiffness Index above the median, which is a subgroup finding. Acute phase and endothelial dysfunction markers were unaffected.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule or softgel, usually as fermentation-derived all-trans MK-7 in an oil base, frequently combined with vitamin D3
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Target-to-background ratio tended to increase on MK-7 versus placebo, 0.25 (95% CI -0.02 to 0.51), P = 0.06; CT calcification mass did not decrease
Repeated elsewhere
Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Only 33 of 35 in the MK-7 group and 27 of 33 on placebo completed follow-up. The trend is in the opposite direction to the hypothesis and does not reach significance, so it is uninformative about harm and informative about absence of benefit.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule or softgel, usually as fermentation-derived all-trans MK-7 in an oil base, frequently combined with vitamin D3
Interval reported. 95% CI -0
Written into the record, not signed off as a reviewed claim.
Higher dietary menaquinone intake associated with reduced risk of coronary heart disease
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Observational. Dietary menaquinone intake in a free-living population tracks fermented and animal food consumption and many correlated factors. Sample size recorded as zero because this was a cohort analysis rather than an enrolled trial. This is the observation the whole supplement category was built on.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule or softgel, usually as fermentation-derived all-trans MK-7 in an oil base, frequently combined with vitamin D3
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 5 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Vitamin K2 MK-7
What a person takes: Oral capsule or softgel, usually as fermentation-derived all-trans MK-7 in an oil base, frequently combined with vitamin D3.
The measurement behind this step
Sold in the United States as a dietary supplement under DSHEA, so no agency reviewed efficacy, safety or content before sale. A label reading "vitamin K2" may contain MK-4, MK-7 or a blend, and these differ by more than an order of magnitude in half-life with entirely separate trial literatures. Synthetic MK-7 can contain the biologically inactive cis isomer, which fermentation-derived material does not, and neither the isomer content nor the chain length is typically disclosed. Absorption is strongly fat-dependent, and MK-7's multi-day half-life means several weeks are needed to reach steady state.
Getting in
Absorbed with fat, and MK-7 stays around for days
Vitamin K needs dietary fat to be absorbed. The long-tailed MK-7 form then lingers in the blood for days, where the short forms are gone in hours.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Menaquinones are absorbed into chylomicrons and require dietary lipid. MK-7's seven-isoprene tail gives it strong lipoprotein binding and a plasma half-life measured in days, against hours for MK-4 and phylloquinone. This is the genuine pharmacological argument for the form, and it means steady state takes weeks, so short trials measure accumulation rather than a stable exposure.
It powers an enzyme that adds a calcium-binding hook to proteins
Reduced vitamin K lets one enzyme add an extra chemical group to certain proteins, turning a plain amino acid into one that grips calcium.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Gamma-glutamyl carboxylase uses reduced vitamin K as cofactor to convert glutamate to gamma-carboxyglutamate, and vitamin K epoxide reductase regenerates the reduced form. Warfarin inhibits that recycling step, which is why vitamin K antagonises warfarin and why the interaction is certain rather than theoretical.
Two proteins matter outside the liver: one for bone, one for arteries
Osteocalcin locks calcium into bone. Matrix Gla protein sits in artery walls and stops calcium crystallising there. Both need the vitamin K modification to work.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
Osteocalcin is secreted by osteoblasts and its carboxylated form binds hydroxyapatite. Matrix Gla protein is expressed by vascular smooth muscle cells and is a potent local calcification inhibitor — MGP-null mice die within weeks of massive arterial calcification, which is the strongest evidence that this pathway matters and is the mechanistic backbone of every K2 claim.
The inactive fraction falls by half, and that is easy to measure
Supplementing MK-7 activates these proteins, and the amount of the inactive form circulating in blood drops by around fifty percent. This is real and reproducible.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
MK-7 at 180 micrograms daily decreased dephosphorylated-uncarboxylated matrix Gla protein by 50% against placebo over three years, and improved the uncarboxylated to carboxylated osteocalcin ratio. The biomarker response is large enough to serve as a compliance measure, which is exactly how the diabetes calcification trial used it.
Despite fully activating the anti-calcification protein, imaging of actual arterial and valve calcium found no difference across three randomised trials.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Aortic valve calcification score difference 17 AU (95% CI -86 to 53, P = 0.64) over 24 months in 365 men; aortic valve area difference 0.02 cm2 (P = 0.78); femoral 18F-NaF PET target-to-background ratio tending upward on MK-7 (0.25, 95% CI -0.02 to 0.51, P = 0.06) in diabetes. The most likely explanation is that established mineral does not regress, and matrix Gla protein carboxylation prevents rather than reverses.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
People taking vitamin D or calcium who have been told K2 directs the calcium, postmenopausal women concerned about bone density, and people with coronary or valvular calcification found incidentally on a scan.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
Where the result stopped carrying
The vascular calcification hypothesis, in three randomised imaging trials across aortic valve, coronary and femoral disease
The transfer of high-dose MK-4 Japanese bone data to low-dose MK-7 products sold as the same thing
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment.
On this record: Vitamin K needs dietary fat to be absorbed. The long-tailed MK-7 form then lingers in the blood for days, where the short forms are gone in hours.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
The product may not be what it says
Contents of a sold product are not always what the label states.
On this record: This is sold as a supplement, so no agency checked what is in a given tub before it was sold.
Other reasons RNAWiki checked and found nothing for (9)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Varies by country
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral capsule or softgel, usually as fermentation-derived all-trans MK-7 in an oil base, frequently combined with vitamin D3
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Not usually supervised: sold as a supplement or food ingredient where recorded. That is a legal category, not a safety judgement.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
The identity record classes it as a supplement ingredient; no medicines register records an approval.
No source is stored against this line.
What is in the pack
Sold in the United States as a dietary supplement under DSHEA, so no agency reviewed efficacy, safety or content before sale. A label reading "vitamin K2" may contain MK-4, MK-7 or a blend, and these differ by more than an order of magnitude in half-life with entirely separate trial literatures. Synthetic MK-7 can contain the biologically inactive cis isomer, which fermentation-derived material does not, and neither the isomer content nor the chain length is typically disclosed. Absorption is strongly fat-dependent, and MK-7's multi-day half-life means several weeks are needed to reach steady state.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No register entry is recorded.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Generally well tolerated with no established toxicity at supplemental doses, and no signal of harm in trials running to three years at 180 micrograms or two years at 720 micrograms. The one certain and clinically important effect is the warfarin interaction: vitamin K in any form directly opposes warfarin's mechanism, and MK-7's long half-life makes the interference more persistent and slower to clear than with vitamin K1. Anyone on warfarin who starts or stops a K2 supplement should expect their INR to move. There is no comparable interaction with direct oral anticoagulants, which do not act on vitamin K recycling.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear∅Nothing found in the sources checked
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral capsule or softgel, usually as fermentation-derived all-trans MK-7 in an oil base, frequently combined with vitamin D3
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
A label reading "vitamin K2" may contain MK-4, MK-7 or a blend, and these differ by more than an order of magnitude in half-life with entirely separate trial literatures. Synthetic MK-7 can contain the biologically inactive cis isomer, which fermentation-derived material does not, and neither the isomer content nor the chain length is typically disclosed. Absorption is strongly fat-dependent, and MK-7's multi-day half-life means several weeks are needed to reach steady state.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
Watching one thing carefully can tell you whether it moved. It cannot tell you what moved it.
This is sold without a prescription, so a person can sensibly watch one thing and see whether it moves.
Pick one goal. One goal only. Two at once cannot be told apart afterwards.
Pick one thing to watch. No registered study lists a measure RNAWiki could read for this.
Measure before you start. Take the same measurement several times first. One reading is not a starting point.
Know the swing. Write down how much it moves on its own across a normal week.
Change one thing. Change nothing else at the same time, including training and sleep.
Give it the study length. No finished study window is recorded, so no length is suggested here.
Track whether you took it. Missed days are the most common reason a home test shows nothing.
Read the trend. Look at the line across weeks. A single reading tells you almost nothing.
What not to measure
Anything that swings more day to day than the change you are looking for.
A wearable estimate of sleep stages, which is an estimate and not a measurement.
Weight on one morning, which mostly records water.
A feeling you did not write down before starting.
When to stop
Stop if something new and unpleasant starts, and ask a pharmacist or doctor.
Stop if you cannot keep everything else steady, because the result will not mean anything.
Stop at the end of the window you set, and read the trend then.
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki does not work out an amount for anyone.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That correcting matrix Gla protein carboxylation reduces arterial or valvular calcification, which three imaging trials tested and none supported
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the Rotterdam dietary association transfers to supplementation in a replete population
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That bone mineral density results imply fracture reduction, which no MK-7 trial has been powered to test
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That "vitamin K2" names a single agent, when MK-4 and MK-7 differ more than tenfold in half-life and have separate literatures
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Vitamin K2 MK-7 are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
365 men, two years, aortic valve calcium: a difference of 17 arbitrary units
In plain words
The largest randomised trial of MK-7 gave it with vitamin D to 365 men with calcified aortic valves for two years and measured the calcium on CT scans. There was no difference.
What was measured
Change in aortic valve calcification score on non-contrast cardiac CT over 24 months
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A randomised, double-blind, multicentre trial randomised 365 community-dwelling men with an aortic valve calcification score above 300 arbitrary units on non-contrast cardiac CT to 720 micrograms of MK-7 plus 25 micrograms of vitamin D daily, or matching placebo, for 24 months. Mean age was 71.0 years. The primary outcome, change in aortic valve calcification score, increased by 275 AU (95% CI 225 to 326) in the intervention group and 292 AU (95% CI 246 to 338) in placebo, a mean difference of 17 AU (95% CI -86 to 53, P = 0.64). Change in aortic valve area was 0.02 cm2 (95% CI -0.09 to 0.12, P = 0.78) and in peak aortic jet velocity 0.04 m/s (95% CI -0.11 to 0.02, P = 0.21). Progression of aortic and coronary artery calcification did not differ significantly between groups. This is the exact population, the exact mechanism and the exact endpoint the product is sold on, at a dose four times that of the bone trials, and the confidence interval on the primary result excludes any clinically meaningful effect.
Written into the record, not signed off as a reviewed claim
The biomarker moves dramatically — inactive matrix Gla protein falls by half
In plain words
MK-7 reliably activates the protein that stops calcium depositing in artery walls, cutting the circulating inactive form by about fifty percent.
What was measured
Percentage change in circulating dephosphorylated-uncarboxylated matrix Gla protein versus placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the three-year arterial stiffness trial, MK-7 at 180 micrograms daily decreased circulating dephosphorylated-uncarboxylated matrix Gla protein by 50% compared with placebo. At baseline, dp-ucMGP was associated with carotid intima-media thickness, arterial diameter, carotid-femoral pulse wave velocity and with composite scores for acute phase markers and endothelial dysfunction. This is a genuine, large, reproducible biochemical effect: the supplement unambiguously does what it says at the level of protein carboxylation, and compliance can be verified from it. The vascular calcification trial in type 2 diabetes used dp-ucMGP measurement for exactly that purpose. The audit point is not that this biomarker is fake. It is that it moves by 50% while the imaging endpoints move by nothing, which is as clean a dissociation between a surrogate and an outcome as this file contains.
Written into the record, not signed off as a reviewed claim
Three years of MK-7 reduced age-related bone loss in postmenopausal women
In plain words
In 244 healthy postmenopausal women, three years of MK-7 slowed the normal age-related decline in bone density and strength at the spine and hip.
What was measured
Bone mineral density and content at lumbar spine, total hip and femoral neck over three years by DXA
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Knapen and colleagues randomised 244 healthy postmenopausal women to placebo or 180 micrograms of MK-7 daily for three years, measuring bone mineral density of lumbar spine, total hip and femoral neck by DXA, calculating femoral neck bone strength indices, assessing vertebral fractures by DXA, and tracking vitamin K status through the uncarboxylated to carboxylated osteocalcin ratio at baseline and years 1, 2 and 3. MK-7 significantly improved vitamin K status and decreased the age-related decline in bone mineral content and bone mineral density at the lumbar spine and femoral neck, but not at total hip. The authors note that EFSA had accepted a health claim for vitamin K in maintenance of normal bone. Three years is a genuinely long trial and the endpoint is objective. Two qualifications: the outcome is bone density rather than fracture, and this trial and the arterial stiffness trial come from the same group using the same branded ingredient in the same cohort, so they are not independent replications of each other.
Written into the record, not signed off as a reviewed claim
In type 2 diabetes, PET calcification tended the wrong way
In plain words
A randomised trial used a sensitive scan to look for active calcification in people with diabetes and heart disease. After six months of MK-7 the signal had, if anything, increased.
What was measured
Femoral arterial 18F-sodium-fluoride PET target-to-background ratio and CT calcification mass at six months
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Zwakenberg and colleagues randomised 68 men and women with type 2 diabetes and known cardiovascular disease to 360 micrograms per day of MK-7 or placebo for six months, with 33 and 27 completing follow-up respectively. Femoral arterial calcification was measured by 18F-sodium-fluoride PET as target-to-background ratio, a technique sensitive to active mineralisation rather than established mineral, with CT calcification mass as a secondary outcome, and dp-ucMGP measured to confirm compliance. After six months, target-to-background ratio tended to increase in the MK-7 group compared with placebo (0.25, 95% CI -0.02 to 0.51, P = 0.06), and log-transformed CT calcification mass did not decrease. A non-significant trend in the wrong direction in a small trial is not evidence of harm and should not be read as one. It is, however, the second independent randomised imaging study to find no benefit, and the compliance biomarker confirms the supplement was being taken and was working biochemically.
Written into the record, not signed off as a reviewed claim
The Rotterdam observation that started it, and what randomisation did to it
In plain words
A large population study found people eating more vitamin K2 had less coronary heart disease. Every randomised trial that has since tested it against imaging has found nothing.
What was measured
That an observational association between dietary menaquinone intake and coronary heart disease establishes a benefit of MK-7 supplementation on arterial calcification
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Geleijnse and colleagues reported in the Rotterdam Study that dietary menaquinone intake was associated with reduced risk of coronary heart disease, and that observation is the origin of the entire K2 supplement category and of the "directs calcium away from arteries" framing. The subsequent randomised record runs the other way. In 365 men with aortic valve calcification over 24 months, the difference in calcium score progression was 17 AU (P = 0.64). In 68 people with type 2 diabetes and cardiovascular disease over six months, PET target-to-background ratio tended to increase on MK-7 (P = 0.06). This is the standard shape of a nutritional epidemiology finding: dietary menaquinone intake in a free-living population tracks fermented and animal food consumption, socioeconomic position and dozens of other correlates, and the compound itself carries only some of the association. The mechanism connecting matrix Gla protein to arterial calcification is real and was never the weak link; the inference that supplementing a replete population would move calcification was.
Written into the record, not signed off as a reviewed claim
MK-4 and MK-7 are different drugs, and so are their trial literatures
In plain words
Vitamin K2 comes in forms with different tail lengths. They have half-lives differing more than tenfold and separate bodies of evidence, and labels often just say "K2".
What was measured
That "vitamin K2" is a single agent whose trial evidence applies regardless of chain length or dose
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
MK-4 carries four isoprene units and is cleared within hours; MK-7 carries seven and has a plasma half-life measured in days, which is why 180 micrograms daily of MK-7 achieves what milligram doses of MK-4 were used for. The Japanese bone literature that supplies much of vitamin K2's reputation used MK-4 at 45 mg per day — a dose 250 times the MK-7 trials, in a different population, with a different molecule. The Knapen group explicitly framed their MK-7 work as an extension of earlier high-dose K1 and MK-4 studies "because of the longer half-life and greater potency of the long-chain MK-7," which is an honest statement that these are separate agents. A product labelled only "vitamin K2" may contain either, and neither form's evidence transfers to the other. Synthetic MK-7 can also contain the biologically inactive cis isomer, which fermentation-derived material does not.
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Other ways to the same goal — found nothing in the sources checked.
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The record as stored
The full record, for auditing
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The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
MK-7 halves circulating inactive matrix Gla protein and, in two three-year trials using the same branded ingredient, reduced bone loss and arterial stiffness in postmenopausal women — but in 365 men with aortic valve calcification followed for two years the difference in calcium score progression was 17 arbitrary units (P = 0.64), and two other randomised imaging trials in diabetes and coronary disease also found nothing.
Recorded evidence blocks (0)
Where it is registeredIdentifiers, relations and other names
Trade name
Menaquinone-7; the dominant branded ingredient in the trial literature is MenaQ7
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