— August 28, 2026 · Vitamin K2 Plus D3 Slowed the Growth of Coronary Calcium in the DANCODE Trial

Table of Contents

1. DANCODE at a Glance
2. What the Trial Did and Measured
3. What Was Found, Number by Number
4. How Vitamin K2 Acts on Artery Calcium
5. How It Fits With Earlier Research
6. Safety and the Blood-Thinner Question
7. Vitamin K2 in Whole Foods
8. What the Trial Cannot Show
9. What the Researchers Concluded and What Remains Unknown
10. Sources and Primary Documents
11. Key Research Papers
12. Connections

DANCODE at a Glance

• Paper — Hasific S, Øvrehus KA, Mejldal A, et al. “Vitamin K2 and D3 Supplementation in Patients With Severe Coronary Artery Calcification: The DANCODE Trial.” Circulation, published online August 28, 2026 (PMID 42661461).
• Who ran it — cardiologists at Odense University Hospital and the University of Southern Denmark, with Svendborg and Vejle hospitals; sponsor Odense University Hospital; registry number NCT05500443.
• Design — randomised, double-blind, placebo-controlled, three Danish hospitals; enrolment February 2023 to February 2024.
• Who took part — 398 adults with a calcium score of at least 400 Agatston units (the level the paper calls severe); median age 71; 30% women; median starting score 903; 44% at 1,000 or more.
• Treatment — menaquinone-7 (MK-7) 720 micrograms plus vitamin D3 25 micrograms a day, or placebo, for 24 months.
• Main result — calcium score rose 196 vs 248 Agatston units; difference −52 (95% CI −79 to −24), about 21% less growth.
• Plaque substudy — in 143 people with CT angiography, total and soft (noncalcified) plaque changed alike in both groups; calcified plaque grew less on the vitamins (−8 mm³, 95% CI −13 to −2).
• Not tested — whether heart attacks, strokes or deaths become less frequent.

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What the Trial Did and Measured

The researchers recruited adults who had already had a heart CT scan showing a calcium score of at least 400 Agatston units. A score of zero means no calcium is visible in the coronary arteries; scores in the hundreds and thousands mean widespread calcified atherosclerosis, the hardened plaque of coronary artery disease. The published protocol excluded people who had already had a stent or bypass operation, people taking vitamin K antagonist blood thinners (the warfarin family), and people with clotting disorders or disorders of calcium and phosphate metabolism such as primary hyperparathyroidism.

Each participant took two tablets a day. In the active group each tablet held 360 micrograms of MK-7 and 12.5 micrograms of vitamin D3, giving 720 micrograms and 25 micrograms a day; the placebo tablets looked the same. Neither the participants nor the staff knew who was getting which.

Every participant had a plain (non-contrast) heart CT scan at the start, at 12 months and at 24 months. The primary end point was the change in calcium score over 24 months. Planned secondary analyses looked at men and women separately, at people starting between 400 and 999 versus 1,000 or more, at heart events, and at calcium on the aortic valve. A subset whose starting score was under 1,000 also had coronary CT angiography, a contrast scan that can see soft plaque as well as calcified plaque, at the start and at two years; 143 people make up that substudy.

The Agatston score, introduced in 1990, adds up every calcified spot in the coronary arteries, weighting each by its area and by how dense its brightest point is on the scan. In large population studies a higher score, and a faster-rising score, has been linked with more heart disease and deaths, which is why the authors open their paper by calling calcium progression “a strong predictor of cardiovascular events.”

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What Was Found, Number by Number

All figures in the list below and the two paragraphs after it are from the paper’s abstract, analysed by intention to treat (everyone counted in the group they were assigned to).

• Calcium score, vitamin group: rose by a mean of 196 Agatston units over 24 months (95% CI 178 to 214).
• Calcium score, placebo group: rose by a mean of 248 units (95% CI 225 to 271).
• Difference: −52 units (95% CI −79 to −24). Because the whole confidence interval sits below zero, the difference is unlikely to be chance. Fifty-two divided by 248 is 21%, the “21% slower” figure in the coverage. Over two years it works out to about 26 points a year, against a median starting score of 903.
• Subgroups: the abstract states that the effect “was consistent across sex and baseline CAC subgroups.”

The calcium score went up in both groups. Despite the trial’s name (“decalcification”), neither group’s average score fell; the vitamins slowed the rise rather than reversing it.

In the 143-person CT-angiography substudy, the abstract reports “a similar increase in total plaque volume and no change in noncalcified plaque volume between groups,” while calcified plaque volume grew less on the vitamins (between-group difference −8 mm³, 95% CI −13 to −2). This matters because one worry about slowing calcification is that plaque might stay soft instead. In this subset, soft plaque did not increase.

Reported from the full paper and the congress presentation (not read directly here; the full text is behind a paywall). Two published summaries agree that about 87% of participants were taking statins, that major cardiovascular events numbered 2 on the vitamins and 3 on placebo, and that the calcified-plaque difference was −7.8 mm³ (95% CI −13.5 to −2.2; P = 0.007). A cardiologist’s report from the congress adds that there was no significant difference at 12 months (−20 units, 95% CI −49 to 8), so the gap opened during the second year; that the blood level of inactive matrix Gla protein (dp-ucMGP), a marker of low vitamin K activity in the vessel wall, fell markedly on the vitamins; that blood 25-hydroxyvitamin D rose by about 25 nmol/L; and that there were no relevant changes in calcium, phosphate, parathyroid hormone, INR clotting time or kidney function.

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How Vitamin K2 Acts on Artery Calcium

The key protein is matrix Gla protein (MGP), made by the smooth-muscle cells in artery walls. MGP binds calcium minerals and stops them from crystallising where they do not belong. In 1997, researchers showed how much depends on it: mice bred without MGP developed calcified arteries and died within two months, when the hardened vessels ruptured. The authors concluded that calcification “must be actively inhibited in soft tissues.”

MGP only works after a chemical step called carboxylation, which needs vitamin K (the same step activates the liver’s clotting factors; see the vitamin K cycle animation). When vitamin K is short, inactive MGP circulates in the blood and can be measured as dp-ucMGP. Vitamin K comes in two main natural families: K1 (phylloquinone), mostly from green leafy vegetables, and K2 (the menaquinones), from fermented foods and animal foods. MK-7 is a long-chain menaquinone; in a 2007 comparison with K1 in healthy volunteers, MK-7 had a very long half-life, gave much more stable blood levels and built up seven- to eightfold during prolonged intake.

Vitamin D3 was added because, as the DANCODE protocol explains, it stimulates the production of MGP. The trial compared the combination with placebo, so it cannot say how much each vitamin contributed.

The reverse case supports the same mechanism. Warfarin-type drugs block the recycling of vitamin K, and so block MGP activation. A pooled analysis of eight trials that tracked coronary plaque by ultrasound found that the 171 patients on warfarin had a faster rise in coronary calcium than the 4,129 who were not (odds ratio 1.16, 95% CI 1.05 to 1.28), with no difference in total plaque volume.

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How It Fits With Earlier Research

The Rotterdam Study (2004). In 4,807 Dutch adults enrolled in 1990–1993 and followed until the start of 2000, those in the top third of dietary menaquinone (K2) intake had a 57% lower risk of dying from coronary heart disease than those in the bottom third (relative risk 0.43, 95% CI 0.24 to 0.77), lower all-cause mortality (0.74) and less severe aortic calcification (odds ratio 0.48). Phylloquinone (K1) intake was not related to any of these outcomes. This was an observational study: it showed an association, not that K2 caused the difference.

Arterial stiffness in postmenopausal women (2015). A three-year double-blind trial in 244 healthy postmenopausal women found that 180 micrograms a day of MK-7 lowered pulse-wave velocity, a measure of arterial stiffness, and halved dp-ucMGP compared with placebo. Stiffness, not calcium, was the end point.

AVADEC (2022 and 2023). The same Odense group had earlier tested the identical dose (720 micrograms of MK-7 plus 25 micrograms of vitamin D) for two years in 365 men with calcified aortic valves. The primary result, published in Circulation in 2022, was null: valve calcium rose 275 vs 292 units (difference 17, 95% CI −86 to 53; P = 0.64), and the change in coronary calcium was not significantly different either. A 2023 analysis of the same trial’s coronary scans, in 304 men without known heart disease, found no significant difference in coronary calcium growth overall (203 vs 254 units, P = 0.089), but in men starting at 400 or more the rise was smaller (288 vs 380, P = 0.047). The authors called that subgroup result “hypothesis-generating.” DANCODE was designed to test exactly that hypothesis, using the AVADEC numbers to calculate how many participants it needed.

VitaK-CAC (2026). A Dutch trial published in JAMA Cardiology randomised 180 patients with symptomatic coronary artery disease and calcium scores between 50 and 400 to 360 micrograms a day of MK-7 or placebo for two years. Median scores rose from 145 to 214 on placebo and from 135 to 184 on MK-7 (P = .02). The authors wrote that the clinical significance “in terms of plaque stability remains to be determined.”

Among the trials described here, DANCODE is the largest and the only one to enrol people chosen for severe coronary calcification. The AVADEC investigators had called their finding in men with scores of 400 or more hypothesis-generating; DANCODE tested that finding as its primary question, and in this trial it held.

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Safety and the Blood-Thinner Question

The DANCODE abstract does not report adverse events. Reports of the full paper and the congress presentation describe few problems over two years: 2 vs 3 major cardiovascular events, 0 vs 1 deaths, no serious bleeding in either group, 5 vs 9 new cancers (not a significant difference), and 3 vs 1 people stopping because of side effects, all described as mild. With numbers this small the trial cannot rule out uncommon harms or show benefit on events. In AVADEC, deaths were 1 vs 4 and cardiovascular events 10 vs 10, also with no significant difference; in VitaK-CAC “no significant adverse effects were observed.”

Vitamin K antagonists. Warfarin and the related drugs work by blocking vitamin K, so vitamin K intake changes their effect on the INR clotting test. DANCODE excluded people on these drugs; the congress report gives the reason as the direct interference of vitamin K2 with how they work. Research in healthy volunteers has measured that interference: a 2007 study warned that MK-7 at 50 micrograms a day or more “may interfere with oral anticoagulant treatment in a clinically relevant way,” and a 2013 dose-finding study in 18 volunteers given a warfarin-type drug found that 45 micrograms a day of MK-7 lowered the average INR by about 40%, while 10 and 20 micrograms a day caused a clinically relevant fall in at least 40% and 60% of people. Those authors concluded that “the use of MK-7 supplements needs to be avoided in patients receiving VKA therapy.” The DANCODE dose, 720 micrograms a day, is 16 times the 45 micrograms that the 2013 paper described as the usual retail dose.

Newer blood thinners. The direct oral anticoagulants (such as apixaban and rivaroxaban) do not act through vitamin K. They were not a reason for exclusion. According to the congress report, about one in five DANCODE participants took one, and among them there was no serious bleeding and no different response to the treatment.

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Vitamin K2 in Whole Foods

A Maastricht food analysis published in 2000 found vitamin K2 “in meat, liver, butter, egg yolk, natto, cheese and curd cheese,” and vitamin K1 mainly in green vegetables. Natto, the Japanese fermented soybean dish made with Bacillus subtilis, stands out in that research: after a meal of 400 g of spinach and 200 g of natto, which supplied similar amounts of K1 and K2, blood K2 rose about ten times higher than blood K1. The 2007 supplement comparison used natto-derived MK-7. More on the food side is on the site’s pages on natto as a source of MK-7 and eggs.

The Rotterdam findings concern menaquinone eaten as food. DANCODE tested a supplement at a dose far above what the volunteer studies call a usual retail dose, given together with vitamin D3, so its result cannot be read as a statement about the amounts found in a normal diet. The research on vitamin K and warfarin-type drugs applies to food as well: the site’s natto safety page covers natto’s vitamin K2 content and the warfarin-type drugs.

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What the Trial Cannot Show

• A surrogate, not events. The trial measured the calcium score. It was not designed or powered to show fewer heart attacks, strokes or deaths, and with 2 vs 3 major events there is no signal either way.
• What the score itself means. The Agatston score rises with both the area and the density of calcium. In the large US MESA cohort, denser calcium was linked with lower heart risk at any given calcium volume (hazard ratio 0.73 per standard deviation of density for coronary heart disease), and statins, which lower heart events, have been found to increase coronary calcification, a change their researchers linked to plaque stabilisation. So a lower score does not automatically mean lower risk. Reports of the presentation note that DANCODE did not measure calcium density and volume separately, so it cannot say which part of the score changed.
• The soft-plaque check is partial. The finding that noncalcified plaque did not increase comes from 143 people, all with starting scores under 1,000; it does not cover the 44% with the heaviest calcium.
• Combination only. K2 and D3 were given together, so the separate effect of each is unknown.
• Who was studied. Danish adults with a median age of 71 and severe calcification, most on statins, none on warfarin-type drugs and none with prior stents or bypass. The result may not apply to people with low calcium scores, younger people, or other populations.
• Two years. The reported gap opened in the second year; whether it widens, holds or narrows after that is not known.
• Funding. The protocol states that two supplement companies supplied the tablets and placebo free of charge and had no part in the design, conduct, analysis or reporting of the trial. The lead investigator has disclosed, in an earlier paper from the same programme, service on an expert panel reviewing the safety of vitamin K2 for use in foods in the United States.

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What the Researchers Concluded and What Remains Unknown

The paper’s conclusion, verbatim: “Among patients with severe CAC, supplementation with vitamin K2 and vitamin D3 reduced progression of CAC over 24 months. The reduction in calcification progression was not associated with an increase in noncalcified plaque volume.”

The American Heart Association’s media alert for the congress listed the paper for Friday, August 28, at 9:00 CEST under the heading “Vitamin D3 and K2 Supplementation May Slow Calcium Build up in the Arteries.” The alert described participants as having “moderate to severe” calcification; the paper itself enrolled only scores of 400 or more, which it calls severe.

The authors of the smaller Dutch VitaK-CAC trial, published earlier in 2026, reached a similarly cautious conclusion about their own positive result: MK-7 “may slow calcification in noncalcified plaques,” with clinical significance still to be determined.

Still Unknown

• Whether slowing the calcium score with vitamin K2 and D3 leads to fewer heart attacks, strokes or deaths. That needs a trial with clinical events as its end point.
• Whether the lower score reflects less calcium, less dense calcium, or a change in plaque that makes it more or less stable.
• Which vitamin did the work, and whether a lower dose, or K2 alone, would do the same.
• Whether the effect continues past two years, and whether it applies to people with mild or no calcification.
• How the result relates to K2 eaten as food, such as natto, over a lifetime.

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Sources and Primary Documents

Figures attributed to DANCODE come from the paper’s abstract, the published protocol and the trial registry, all read in full. The Circulation full text is paywalled; the few details marked above as “reported” come from the congress report and summary listed below, and were included only where they did not conflict with the abstract.

1. Hasific S, Øvrehus KA, Mejldal A, Hosbond S, Lambrechtsen J, Kumarathurai P, Dey D, Ravn EJ, Rasmussen LM, Gerke O, Mickley H, Diederichsen A (2026). Vitamin K2 and D3 Supplementation in Patients With Severe Coronary Artery Calcification: The DANCODE Trial. Circulation, published online August 28, 2026. — doi:10.1161/CIRCULATIONAHA.126.082363 · PubMed PMID: 42661461
2. Hasific S, Øvrehus KA, Hosbond S, Lambrechtsen J, Kumarathurai P, Mejldal A, Ravn EJ, Rasmussen LM, et al. (2023). Effects of vitamins K2 and D3 supplementation in patients with severe coronary artery calcification: a study protocol for a randomised controlled trial. BMJ Open 13(7):e073233. — doi:10.1136/bmjopen-2023-073233 · PubMed PMID: 37451735
3. ClinicalTrials.gov. The DANish COronary DEcalcification (DANCODE) Trial, NCT05500443; sponsor Odense University Hospital; started February 8, 2023; completed July 4, 2026. — NCT05500443
4. American Heart Association media alert for ESC Congress 2026, Munich, August 28–31, listing DANCODE for August 28, 9:00 CEST. — AlphaGalileo item 277297
5. Congress report (in Spanish) by a Madrid cardiologist, August 30, 2026: 12-month result, statin use, biomarkers and safety counts. — Estudio DANCODE (cardioteca.com)
6. Summary of the DANCODE paper: statin use, plaque substudy confidence interval and event counts. — Pharmacally summary

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Key Research Papers

Background papers on vitamin K2, matrix Gla protein and the coronary calcium score, in the order they appear above. Each was checked against PubMed and Crossref before it was written down.

1. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R (1990). Quantification of coronary artery calcium using ultrafast computed tomography. Journal of the American College of Cardiology 15(4):827-832. — PubMed PMID: 2407762
2. Budoff MJ, Hokanson JE, Nasir K, Shaw LJ, Kinney GL, Chow D, et al. (2010). Progression of coronary artery calcium predicts all-cause mortality. JACC: Cardiovascular Imaging 3(12):1229-1236. — PubMed PMID: 21163451
3. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G (1997). Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386(6620):78-81. — PubMed PMID: 9052783
4. Schurgers LJ, Teunissen KJ, Hamulyák K, Knapen MH, Vik H, Vermeer C (2007). Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 109(8):3279-3283. — PubMed PMID: 17158229
5. Andrews J, Psaltis PJ, Bayturan O, Shao M, Stegman B, Elshazly M, et al. (2018). Warfarin Use Is Associated With Progressive Coronary Arterial Calcification: Insights From Serial Intravascular Ultrasound. JACC: Cardiovascular Imaging 11(9):1315-1323. — PubMed PMID: 28734922
6. Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC (2004). Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. Journal of Nutrition 134(11):3100-3105. — PubMed PMID: 15514282
7. Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C (2015). Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thrombosis and Haemostasis 113(5):1135-1144. — PubMed PMID: 25694037
8. Diederichsen ACP, Lindholt JS, Möller S, Øvrehus KA, Auscher S, Lambrechtsen J, et al. (2022). Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial. Circulation 145(18):1387-1397. — PubMed PMID: 35465686
9. Hasific S, Oevrehus KA, Lindholt JS, Mejldal A, Dey D, Dahl JS, et al. (2023). Effects of Vitamin K2 and D Supplementation on Coronary Artery Disease in Men: A RCT. JACC: Advances 2(9):100643. — PubMed PMID: 38938724
10. Vossen LM, de Leeuw PW, Schurgers LJ, Heuts S, Adriaans BP, de Haan C, van Varik BJ, Kroon AA (2026). Two Years of Menaquinone-7 Supplementation and Coronary Artery Calcification: A Randomized Clinical Trial. JAMA Cardiology 11(8):719-726. — PubMed PMID: 42268593
11. Theuwissen E, Teunissen KJ, Spronk HM, Hamulyák K, Ten Cate H, Shearer MJ, Vermeer C, Schurgers LJ (2013). Effect of low-dose supplements of menaquinone-7 (vitamin K2) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. Journal of Thrombosis and Haemostasis 11(6):1085-1092. — PubMed PMID: 23530987
12. Schurgers LJ, Vermeer C (2000). Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis 30(6):298-307. — PubMed PMID: 11356998
13. Criqui MH, Denenberg JO, Ix JH, McClelland RL, Wassel CL, Rifkin DE, Carr JJ, Budoff MJ, Allison MA (2014). Calcium density of coronary artery plaque and risk of incident cardiovascular events. JAMA 311(3):271-278. — PubMed PMID: 24247483
14. Puri R, Nicholls SJ, Shao M, Kataoka Y, Uno K, Kapadia SR, Tuzcu EM, Nissen SE (2015). Impact of statins on serial coronary calcification during atheroma progression and regression. Journal of the American College of Cardiology 65(13):1273-1282. — PubMed PMID: 25835438

PubMed Topic Searches

1. PubMed: Menaquinone-7 and coronary artery calcification
2. PubMed: Matrix Gla protein and vascular calcification
3. PubMed: Vitamin K2 plus vitamin D3 randomised trials
4. PubMed: Coronary calcium density, volume and events
5. PubMed: Menaquinone-7 and vitamin K antagonist anticoagulation

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Connections

• News Archive
• Vitamin K2 (Menaquinone) — the menaquinones, MK-4 and MK-7
• Vitamin K2, Heart and Arterial Calcification — the research on K2 and the arteries
• Vitamin K — K1 and K2, clotting, bone and vessels
• Vitamin K and Arterial Calcification — matrix Gla protein and calcium in vessel walls
• Vitamin D3 — the vitamin given alongside K2 in the trial
• Coronary Calcium Score (CAC) — the CT test the trial used as its end point
• Soft Plaque and CAC Limitations — what a calcium score does not see
• Coronary Artery Disease — the condition behind coronary calcium
• Atherosclerosis — how artery plaque forms and hardens
• Aortic Stenosis — the valve disease tested in the earlier AVADEC trial
• Natto — the fermented soybean food rich in MK-7
• Natto for Vitamin K2 (MK-7) — natto as a whole-food MK-7 source
• Natto Safety and Interactions — vitamin K and blood thinners
• PT/INR Test — the clotting test vitamin K intake affects
• Vitamin K Cycle Animation — how vitamin K is recycled and how warfarin blocks it
• Calcium and Cardiovascular Health — where calcium goes in the body
• Statins After 70: The STAREE Trial — another heart trial from the same congress

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