A recent randomized controlled trial found that vitamin K supplementation in conjunction to vitamin D supplementation reduced the progression of atherosclerosis in patients with chronic kidney disease (CKD) significantly more so than supplementing with vitamin D alone.
Vascular calcification is a measure of atherosclerosis, a disease characterized by the buildup of plaque in the arterial walls. This buildup narrows the arteries, restricting blood flow to the heart and brain and increasing the risk for heart attack or stroke. Atherosclerosis is a common complication of patients with CKD and a significant risk factor for cardiovascular disease and mortality.
Vitamin K is a cofactor of vitamin D, meaning it helps vitamin D function optimally. Low vitamin D status has been linked to an increased risk of atherosclerosis. Researchers recently proposed that vitamin K supplementation may modulate the effects of vitamin D on atherosclerosis.
Both vitamin K and vitamin D play vital roles in regulating the mineralization of arterial walls. Vitamin D increases the expression of matrix Gla protein (MGP), a protein that inhibits vascular calcification. MGP relies on the availability of vitamin K to achieve full biologic activity. In cases of vitamin K deficiency, MGP remains inactive and is associated with arterial calcification.
A randomized controlled trial recently evaluated the effects of vitamin K2 supplementation in combination with a low dose of vitamin D compared to vitamin D alone on the progression of atherosclerosis and coronary artery calcification.
The researchers enrolled 42 non-dialysis CKD patients who were between the ages of 18 and 70 years old. Twenty nine patients were randomly assigned to receive a daily oral dose of 90 πg of vitamin K2 plus 400 IU of vitamin D per day for about 270 days. The remaining thirteen patients were assigned to receive 400 IU of vitamin D.
The researchers measured various markers of atherosclerosis, such as Common Carotid Intima Media Thickness (CCA-IMT) and Coronary Artery Calcification Score (CACS). Increased CCA-IMT typically indicates an increased buildup has occurred in the carotid artery, and the CACS reflects the presence and extent of plaque in the arteries. The researchers also assessed calcification modulators, including total MGP and inactive MGP. These measurements were performed at baseline and after treatment.
Did vitamin K2 supplementation reduce the progression of atherosclerosis? Here is what the researchers found:
- The increase of CCA-IMT was significantly lower in the K+D group compared to the D group (P = 0.005).
- The increase in CACS was lower in the K+D group than the D group, but this was insignificant (P = 0.7).
- The level of inactive MGP decreased in the K+D group only.
The researchers summarized the findings of their study,
“It shows that the progression of CCA-IMT is significantly slower in patients treated with both vitamin K2 and cholecalciferol compared with patients substituted with vitamin D alone.”
They went on to explain the possible mechanism for the positive effects of vitamin K2 supplementation,
“In our study the serum level of [inactive MGP] decreased significantly during vitamin K2 supplementation. The substitution of vitamin K2 could possibly cause the increase of MGP [activation] in vessel’s wall and could slow down the progression of atherosclerosis.”
While the results are fascinating, there are a few important limitations to acknowledge. The follow-up was relatively short to analyze the effects of treatment on atherosclerosis, a disease which develops over many decades. Also, the study had a very small sample size. Lastly, the vitamin D dosage was very low.
Future studies using higher dosages of vitamin D along with larger sample sizes and longer observation periods are warranted to understand the effects of vitamin D and vitamin K supplementation on the progression of atherosclerosis in patients with CKD.
Kurnatowska I., et al. Effect of vitamin K progression of atherosclerosis and vascular calcification in non-dialyzed patients with chronic kidney disease stage 3-5. Polish Archives of Internal Medicine, 2015.