Dietary K1 Research Articles

Positive Effects of Vitamin K on Arterial Calcification, Cerebral Blood Flow, and Cognition in a Murine Model of Arterial Calcification

Abstract Objectives Investigate whether VK can attenuate cognitive impairment associated with arterial stiffness, and assess its effect on arterial calcification and resting cerebral blood flow (rCBF). Methods Ten to 12 wk-old male C57BL/6 mice (n = 12/diet gp) were fed diets containing either 0.1, 1 or 10 mg/kg of K1, or 10, 50 or 100 mg/kg of MK-4 for 4 wks. Arterial calcification was induced by the local application of CaCl2 (3 M), sham animals were treated with NaCl (0.9%). Learning abilities over 5 days and memory retention were assessed using the Morris water maze, 3 wks after surgery. rCBF was determined by quantitative autoradiography (iodoantipirine 4-N-Methyl-14C as a diffusible tracer) in key brain regions. Carotid Ca2+ content was determined by a colorimetric method, brain K1 and MK4 were assessed by HPLC and brain expression of carboxylated Gas6 and PS by Western blot. Results Learning performances did not differ between CaCl2 and NaCl-treated mice at any of the K1 and MK4 doses although when groups were combined, MK-4100 mg/kg fed mice had better cognitive abilities compared to K1 0.1 mg/kg group (P < 0.05). In contrast, memory retention was altered by arterial calcification in the lower VK diet groups (K1 0.1 and MK-4 10 mg/kg) (P < 0.05). MK-4 was the main form of VK in brain (at least 98.5%) irrespective of diet. Expression of carboxylated Gas6 and PS increased with dietary MK-4 but not dietary K1. Carotid Ca2 + content decreased as a function of dietary K1 and MK-4 in a dose dependent manner (P < 0.05). Ca2 + treatment significantly decreased rCBF in several brain regions of mice fed the K1 0.1 mg/kg diet including visual and somatosensory cortex, thalamus, hippocampus, dentate gyrus and corpus callosum (P < 0.05); negative effects were also observed in K1 1 mg/kg fed mice. Conclusions These results suggest that VK can oppose the detrimental effects of vascular calcification on cognition in part by limiting vascular calcification, restoring rCBF, and increasing Gas6 and PS carboxylation in brain. Funding Sources CIHR.

Vitamin K Metabolism in a Rat Model of Chronic Kidney Disease

Background: Patients with chronic kidney disease (CKD) have very high levels of uncarboxylated, inactive, extra-hepatic vitamin K-dependent proteins measured in circulation, putting them at risk for complications of vitamin K deficiency. The major form of vitamin K found in the liver is phylloquinone (K1). Menaquinone-4 (MK-4) is the form of vitamin K that is preferentially found in extra-hepatic tissues. Methods: In the present study, we assessed tissue concentrations of K1 and MK-4 and the expression of vitamin K-related genes in a rat model of adenine-induced CKD. Results: It was found that rats with both mild and severe CKD had significantly lower amounts of K1 measured in liver, spleen and heart and higher levels of MK-4 measured in kidney cortex and medulla. All animals treated with high dietary K1 had an increase in tissue levels of both K1 and MK-4; however, the relative increase in K1 differed suggesting that the conversion of K1 to MK-4 may be a regulated/limiting process in some tissues. There was a decrease in the thoracic aorta expression of vitamin K recycling (Vkor) and utilization (Ggcx) enzymes, and a decrease in the kidney level of vitamin K1 to MK-4 bioconversion enzyme Ubiad1 in CKD. Conclusion: Taken together, these findings suggest that CKD impacts vitamin K metabolism, and this occurs early in the disease course. Our findings that vitamin K metabolism is altered in the presence of CKD provides further support that sub-clinical vitamin K deficiency may represent a modifiable risk factor for vascular and bone health in this population.

Prevalence of subclinical vitamin K deficiency in Thai newborns: relationship to maternal phylloquinone intakes and delivery risk

BackgroundVitamin K deficiency bleeding (VKDB) in infants is a rare but serious worldwide problem, particularly in Southeast Asia. Apart from exclusive breast feeding, little is known of the maternofetal risk...

Plasma vitamin K levels are associated with coronary calcification in older adults.

Vitamin K is involved in regulation of vascular calcification, as mediated by γ-carboxylation of matrix Gla protein (MGP), which inhibits calcification in vivo. Associations between MGP and calcification are equivocal in humans; less is known about interrelationships among vitamin K, MGP, and calcification. Vitamin K status, assessed by plasma levels and self-reported vitamin K1 intake, and serum MGP were measured in 452 older men and women free of symptomatic coronary artery disease (60–80y, mean 68y). Coronary artery calcification score (CAC) was determined by computed tomography. Analysis of variance was used to determine age- and gender-adjusted associations among vitamin K status, serum MGP, and CAC. Plasma K1, further adjusted for serum triglycerides, was inversely associated with CAC (p-trend= 0.009). Those in lowest quartile (Q1) of plasma K1 had 2.1 times more CAC than those in Q4 [plasma K1 (nmol/l): Q1= 0.08, Q4 = 2.92; adjusted mean CAC score: Q1= 57.4, Q4 = 122.3]. Dietary K1 was not associated with CAC. Serum MGP was not associated with either measure of vitamin K status or with CAC. Higher plasma K1 in older men and women were associated with lower CAC. Vitamin K status was not associated with serum MGP nor was serum MGP associated with CAC. Until assays are developed to differentiate the carboxylated from undercarboxylated MGP, the mechanism by which K1 has a protective role in CAC is uncertain.

Effect of Dietary Vitamin K1 on Selected Plasma Characteristics and Bone Ash in Young Turkeys Fed Diets Adequate or Deficient in Vitamin D3

Three experiments were conducted to determine the effect of dietary vitamin K1 (K1) on selected plasma characteristics and bone ash in poults. In Experiment 1, diets were supplemented with 0, 0.5, 1.0, or 2.0 mg of K1/kg. All diets contained 1,650 IU of vitamin D3 (D3)/kg. Dietary K1 had no effect on tibia ash at 7 d or incidence of a severe, rickets-like condition. Tibia ash of poults fed 2.0 mg of K1/kg, however, was greater at 14 d of age than that of poults fed the basal diet. Dietary inclusion of 0.5 mg of K1/kg was as effective as 1 or 2 mg of K1/kg in reducing plasma prothrombin time. In Experiment 2, a 2 x 4 factorial arrangement was used consisting of 1,650 or 550 IU of D3/kg and 0.1, 0.45, 1.0, and 2.0 mg of K1/kg. Dietary D3 and K1 had no effect on bone ash. Dietary inclusion of 0.1 mg of K1/kg seemed to be enough to minimize plasma prothrombin time. In Experiment 3, dietary treatments consisted of a control (1,650 IU of D3 and 2.0 mg of K1/kg) and K1 concentrations of 0, 0.37, 2.28, or 5.33 mg/kg in diets containing 275 IU of D3/kg. Poults fed the low-D3 diet without K1 consumed less feed, gained less weight, and had increased plasma alkaline phosphatase activity, decreased inorganic phosphorus level, and decreased tibia ash (P < 0.05) compared with those of poults fed the control diet. Feed intake and body weight gain were improved, plasma alkaline phosphatase activity decreased, and plasma inorganic phosphorus increased or tended to increase when poults were fed the low-D3 diet supplemented with 0.37 or 2.88 mg of K1/kg compared with poults fed the low-D3 diet without K1 supplementation. Tibia ash of poults fed the low-D3 diet was not affected by K1 supplementation. The results of this research show that dietary K1 concentration had little, if any, effect on bone development in 1- to 14-d-old turkeys.

Dietary Vitamin K1 Requirement and Comparison of Biopotency of Different Vitamin K Sources for Young Turkeys

In a preliminary experiment, the inclusion of vitamin K1 (K1) at a dietary level of 0.1 mg/kg was as effective as 1 or 2 mg/kg in reducing plasma prothrombin time (PT). To obtain an estimate of the dietary K1 requirement and to compare the biopotency of different vitamin K sources for poults, three additional experiments were conducted. In Experiment 1, an incomplete factorial arrangement of treatments was used in which five dietary concentrations of K1 (0, 0.1, 0.25, 0.5, or 2.0 mg/kg) were tested and two concentrations of neomycin (0 or 75 mg/L) in drinking water were used in conjunction with 0, 0.1, and 0.5 mg of K1/kg of diet. Thus, we used a total of eight treatments. Each treatment was given to two pens of poults, with eight poults per pen. Prothrombin time and prothrombin concentration (PC) in plasma were not influenced by inclusion of neomycin in drinking water. The K1 requirement was estimated, on the basis of PT and PC, to be 0.099 and 0.13 mg/kg, respectively, in Experiment 1. Dietary K1 concentrations tested in Experiment 2 were 0, 0.08, 0.31, or 0.44 mg/kg. A similar protocol to that of Experiment 1 was used in this experiment. The results of Experiment 2 indicated that the dietary K1 requirement was 0.079 mg, based on the influence of dietary K1 on PT. In Experiment 3, dietary treatments consisted of the equivalent of 0.22, 0.55, or 1.11 microM of menadione equivalent/kg from vitamin K1, menadione dimethypyrimidinol bisulfite (MPB) or menadione nicotinamide bisulfite (MNB), respectively, and a control without supplementation of any vitamin K source. The results of Experiment 3 showed that the biopotency of K1 was greater than that of MPB or MNB. The biopotencies of MPB and MNB were similar, although MNB was more potent in reducing plasma PT when supplemented at the level of 0.1 mg of menadione/kg. A nadir of PT and a plateau of PC were evident with a dietary supplementation of MPB or MNB at a level of 0.25 mg of menadione/kg. Results of this research show that the dietary K1 requirement of young turkeys is in the range of 0.079 to 0.13 mg/kg, and ingestion of neomycin did not affect estimates of the requirement. The biopotency of vitamin K1 in reducing plasma PT and increasing plasma PC was greater than that of MPB or MNB. The biopotency of MNB was greater than that of MPB when menadione supplementation was equivalent to 0.10 mg of K1/kg.