What is the relationship between Vitamin K, Vitamin D, and atherosclerosis?

From the Guidelines

Vitamin K and D supplementation is not recommended for preventing atherosclerosis in patients with extracranial carotid and vertebral artery disease, as the current evidence does not support its benefit in this specific context. When considering the management of patients with extracranial cerebrovascular atherosclerosis, the focus should be on established treatments such as anticoagulation for those with indications like atrial fibrillation or mechanical prosthetic heart valves, as suggested by the 2011 guideline on the management of patients with extracranial carotid and vertebral artery disease 1. The guideline recommends administering a vitamin K antagonist, such as warfarin, dose-adjusted to achieve a target international normalized ratio (INR) of 2.5 (range 2.0 to 3.0), for the prevention of thromboembolic ischemic events in patients with an indication for anticoagulation 1. Key points to consider in the management of atherosclerosis include:

• The use of anticoagulants like warfarin for patients with specific indications, underlining the importance of vitamin K in this context, but not as a supplement for atherosclerosis prevention.
• Alternative antiplatelet therapies such as clopidogrel or ticlopidine for patients in whom aspirin is contraindicated, highlighting the complexity of managing atherosclerosis and the need for personalized treatment approaches 1. Given the potential for vitamin K supplementation to interfere with the effectiveness of anticoagulant medications like warfarin, it is crucial for patients on such medications to consult with their healthcare providers before initiating any vitamin K or D supplementation. In the context of atherosclerosis management, the primary focus should remain on evidence-based treatments that have been shown to improve outcomes in terms of morbidity, mortality, and quality of life, rather than on supplementation with vitamins K and D, for which the evidence in this specific context is not strong 1.

From the Research

Vitamin K, D, and Atherosclerosis

• The relationship between vitamins K and D and atherosclerosis has been studied in various research papers 2, 3, 4, 5, 6.
• Vitamin D has been shown to exert protective effects on atherosclerosis through multiple mechanisms, including protecting against endothelial dysfunction and vascular smooth muscle cell proliferation and migration 2.
• Vitamin D deficiency has been linked to an increased risk of hypertension, diabetes, congestive heart failure, peripheral arterial disease, myocardial infarction, stroke, and related mortality 3.
• Vitamin K intake has been inversely associated with the risk of atherosclerotic cardiovascular disease (ASCVD), with both vitamin K1 and K2 showing similar inverse associations 4.
• The role of vitamin K in calcification remains controversial, although biologically plausible, results from human studies have not consistently supported this hypothesis 5.
• Vitamin K2 supplementation has been shown to reduce the progression of atherosclerosis in nondialyzed patients with chronic kidney disease stages 3-5 6.

Mechanisms and Associations

• Vitamin D has systemic effects on insulin resistance, dyslipidemia, and hypertension, which are all risk factors for atherosclerosis 2.
• Vitamin K2 has been shown to change the levels of calcification promoters and inhibitors, including dp-ucMGP, OC, and OPG 6.
• The exact mechanism by which vitamin D may influence the atherosclerotic disease process has not yet been completely elucidated 3.
• Large-scale, well-conducted, placebo-controlled clinical trials testing the efficacy of vitamin D supplementation in delaying, slowing, or reverting the atherosclerotic disease process have not yet been conducted 3.

Study Findings

• A prospective cohort study found that high dietary intake of vitamin K1 and K2 was associated with a lower risk of ASCVD hospitalizations 4.
• An observational study found that high dietary intake of vitamin K2 was associated with reduced risk of coronary vascular disease and vascular calcification 6.
• A study found that vitamin K2 supplementation reduced the progression of atherosclerosis in nondialyzed patients with chronic kidney disease stages 3-5 6.