Vitamin K Supplementation for the Prevention of Cardiovascular Disease: Where Is the Evidence? A Systematic Review of Controlled Trials

Abstract

Matrix gla protein (MGP) is an important vitamin K-dependent inhibitor of vascular calcification. High levels of uncarboxylated, dephosphorylated MGP have been associated with vascular calcification and are responsive to vitamin K treatment. In this systematic review, we summarize the available evidence examining whether vitamin K supplementation improves surrogate measures of cardiovascular disease including artery and valve calcification, atherosclerosis and artery stiffening. Data from controlled trials of adults were obtained by searching Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Web of Science Core Collection. We identified nine randomized controlled trials for review, including trials of vitamin K1 or vitamin K2 supplementation, that assessed a surrogate measure of cardiovascular disease including arterial calcification, atherosclerosis or arterial stiffening. For each trial, the risk of bias was assessed applying Cochrane Collaboration methodology. The findings indicate that vitamin K does not consistently prevent progression of calcification, atherosclerosis or arterial stiffness. There may be some benefit in people with calcification at study entry. Studies were heterogenous, with relatively short follow-up and outcome measures were varied. While vitamin K supplementation clearly improves the carboxylation of dephosphoylated MGP, its role in mitigating vascular calcification is uncertain, based on current evidence.

Effects of vitamin K2 supplementation on atherogenic status of individuals with type 2 diabetes: a randomized controlled trial

“…However, no significant association between dietary intakes of vitamin K and CVD mortality and stroke was found [ 23 ]. A small number of clinical trials examined the effects of vitamin K supplementation on CVD markers [ 11 ]. Recently, a study systematically reviewed clinical trials’ findings for the effects of vitamin K supplementation on the clinical proxy of CVD.…”

“…Recently, a study systematically reviewed clinical trials’ findings for the effects of vitamin K supplementation on the clinical proxy of CVD. Vitamin K supplementation could reduce dp-ucMPG significantly compared to the placebo in 7 out of 9 studies, but the effects of the supplementation on vascular calcification, atherosclerosis, and arterial stiffness were not convincing due to the scarcity of the studies [ 11 ].…”

“…However, the AIP values of 84.1% of our participants were more than 0.21, suggesting that they were at a high risk of CVD [ 9 ]; 4) this study’s sample size is calculated based on the primary outcomes of glycemic variables, so it may not be adequately powered to detect changes in IR-related indexes; 5) testing multiple hypotheses simultaneously causes multiplicity concerns, which may increase the probability of false-positive findings [ 29 , 30 ]. However, multiplicity adjustment was not considered in this study because of null findings; 6) the dose of vitamin K2 and the study duration was determined according to a study’s findings suggesting vitamin K status improvements following 360 μg/d MK-7 supplementations for 12 weeks [ 11 ]. However, this dose and duration may not be adequate to observe any significant effects on atherogenic status.…”

“…However, a systematic review of the effects of vitamin K supplementation on clinical measures of vascular calcification, atherosclerosis, and arterial stiffness, reported that while the supplementation can decrease the levels of dp-ucMGP, the beneficial effects of vitamin K on reducing the risk of CVD is uncertain, according to the results of the current studies. Of the nine studies included in the systematic review, one conducted among patients with type 2 diabetes mellitus (T2DM) [11]. Vitamin K and CVD risks in patients with T2DM deserve further investigations because of the lower levels of vitamin K in the blood [12] and higher susceptibility to vascular calcification in this cohort of patients than healthy ones [13].…”

The Emerging Role of Nutraceuticals in Cardiovascular Calcification: Evidence from Preclinical and Clinical Studies

“…The clinical studies are described in detail in Table 1 . Despite these positive preliminary findings, a recent systematic review has underlined the lack of sufficient evidence to support a beneficial effect of vitamin K in preventing the progression of calcification and atherosclerosis [ 116 ]. Moreover, in a very recent randomized study (K4Kidneys trial) involving patients with advanced CKD, vitamin K2 failed to improve vascular stiffness, a marker of vascular health [ 117 ].…”