Reducing the Risk of CAC and Atherosclerosis with Vitamin K

Foods rich in vitamin K and vitamin K2 supplements could help reduce risk of atherosclerosis, CAC, and heart disease.

Evidence of Benefit

Low levels of vitamin K have been linked to coronary artery calcification (CAC) and atherosclerosis in some people. Certain drugs, in combination with low vitamin K levels, appear to greatly increase the risk of CAC. Research also suggests that vitamin K deficiency may increase the risk of cardiovascular disease.^{(1, 86, 88-90)}

This may be because vitamin K is essential for the activation (carboxylation) of certain types of proteins in in blood vessel walls.^(1, 86)

Table 8: Effect of Activated & Inactive Vitamin K-Dependent Proteins on Blood Vessels
Vitamin K-Dependent Protein	Effects on Cardiovascular Disease
Matrix Gla-Protein (MGP)	Activated MGP:⁽⁸⁶⁾ ↓ Calcification on blood vessels. Inactive MGP has been linked to:^{(87-88, 90-91)} ↑ Arterial stiffness ↑ Atherosclerosis ↑ Cardiovascular disease (CVD) ↑ Coronary artery calcification (CAC) ↑ Heart failure ↑ Peripheral arterial disease (PAD) Higher levels of inactive MGP linked to these risk factors are especially noted in people who are at risk of or have heart disease already. Vitamin K deficiency also increases the amount of under-carboxylated MGP.^{(1, 86-87, 90-92)}
Osteocalcin	Inactive osteocalcin (in healthy men with no symptoms of CAC) is linked to:⁽⁹³⁾ ↑ Coronary artery calcification.

MGP status does not seem to correlate to the development or progression of coronary artery calcification (CAC) in otherwise healthy people. Despite this, vitamin K supplements help prevent the progression of CAC. This means vitamin K works in other ways to slow CAC which are not yet understood.⁽⁸⁶⁾

Preclinical & Clinical Evidence of Vitamin K Benefit

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In animal studies, warfarin (a blood thinner) inhibits activation of MGP and leads to arterial calcification. Increasing dietary vitamin K can reverse this effect.⁽⁸⁶⁾

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Population Studies

Analysis of diets in population studies suggest that higher intake of vitamin K2 (but not vitamin K1) is linked to reduced incidence of coronary calcification and mortality from coronary heart disease. Vitamin K2 is found in cheese, milk products, and meat. The lower risk of coronary calcification appeared to be mostly in those who ate more cheese.⁽¹⁾

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However, vitamin K1 levels appear to be important in people taking medication for high blood pressure. Vitamin K1 levels were low in these study participants, and they were more likely to have extreme progression of atherosclerosis.⁽⁸⁹⁾

Vitamin K may also reduce the risk of other conditions that may increase the risk of CAC. For example, population studies show that insulin resistance is independently linked to CAC. This link was found in men - both diabetic and non-diabetic. In a clinical trial, vitamin K prevented insulin resistance in men, as measured by fasting blood sugar (glucose) levels.^(34, 94)

Clinical Studies

Coronary artery calcification (CAC) increases the risk of atherosclerosis. Results of clinical studies suggest that vitamin K1 and vitamin K2 may help people at risk of atherosclerosis, CAC, and other heart disease involving calcification:

Table 9: Clinical Evidence of Vitamin K Effects on Atherosclerosis
Study Details	Study Results
Randomized, Double-Blind, Controlled Clinical Trial 3 year study; 388 older male and female participants:⁽⁸⁶⁾ 200 taking daily multivitamin supplements containing 500 µg vitamin K. Control group of 188 participants taking daily multivitamins without vitamin K.	Vitamin K reduced the progression of CAC in older men who already had coronary artery calcification.⁽⁸⁶⁾ These results are especially important since studies of standard treatments (e.g., cholesterol-lowering drugs or vitamins C and E) have not found any effect on minimizing CAC.⁽⁸⁶⁾
Randomized, Double-Blind, Placebo Controlled Clinical Trial 3 year study; 244 healthy postmenopausal female participants:⁽⁹⁵⁾ 120 participants took 180 µg vitamin K2 daily. 124 participants took a placebo capsule without vitamin K2 daily.	Vitamin K2 supplements:⁽⁹⁵⁾ ↓ Levels of inactive MGP and osteocalcin. ↓ Levels of arterial stiffness.
Clinical Study 9 month study; 42 patients with chronic kidney disease (stages 3-5, not on dialysis); participants divided into 2 groups given:⁽⁹⁶⁾ 90 µg vitamin K2 daily along with 10 µg vitamin D3 or 10 µg/day vitamin D3 alone	Vitamin K2 supplements reduced the progression of atherosclerosis. However, it did not significantly change the progression of CAC.⁽⁹⁶⁾
Open Label Single Arm Clinical Study 26 patients; average age 69 years; 65% female. All were given 45 mg/day of menaquinone-4, a form of vitamin K2, for one year.⁽⁹⁷⁾	Vitamin K2 reduced arterial stiffness in patients with low levels of vitamin K.⁽⁹⁷⁾ Vitamin K2 did not stop CAC progression. The rate of CAC progression (14%) was lower than the medians reported in a meta-analysis (17%) and literature (24-51%). However, since there was no control group in this study the researchers could not say if vitamin K2 slowed the progression.⁽⁹⁷⁾
Randomized, Placebo Controlled Clinical Trial 58 patients with confirmed aortic valve disease; average age 69 years:⁽⁹⁸⁾ 29 participants were given 2 mg/day of vitamin K1 for 12 months. Control group of 29 participants were given a placebo daily for the same time period.	At doses of 2 mg/day, vitamin K significantly reduced the progression of calcification in the aortic valve.⁽⁹⁸⁾

Such as high blood pressure medication and anticoagulants.⁽⁸⁹⁹⁰⁾

Uncarboxylated.⁽⁸⁸⁾

In hemodialysis patients, especially those who were also taking anticoagulants.⁽⁸⁷⁾

Such as people with type-2 diabetes or hemodialysis patients.^(87-88)

Menaquinone-7.⁽⁹⁵⁾

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