Intake Of Vitamin K2 Research Articles

The Associations of Dietary Vitamin K Intake and Circulating Vitamin 25(OH)D with Serum Lipoprotein Levels: The Vitamin Deficiency Matters.

A synergistic interplay between vitamins K and D appears to exist. We aimed to investigate for the first time whether the associations of dietary vitamin K intake and circulating 25(OH)D with serum lipoprotein levels are influenced by the existence of deficiency of either or both vitamins K and D. Sixty individuals [24 males, 36(18-79) years old] were examined. Vitamin deficiency of K1 and D were defined as vitamin K1 intake/body weight (BW)<1.00 μg/kg/day and circulating 25(OH)D<20 ng/ml, respectively. In individuals with vitamin K1 deficiency, the vitamin K1 intake/BW correlated positively with high density lipoprotein-cholesterol (HDL-C) (r=0.509, p=0.008) and negatively with serum triglycerides (TG) (r=-0.638, p=0.001), whereas circulating 25(OH)D correlated negatively with TG (r=-0.609, p=0.001). In individuals with vitamin D deficiency, the vitamin K1 intake/BW correlated positively with HDL-C (r=0.533, p=0.001) and negatively with TG (r=-0.421, p=0.009), while circulating 25(OH)D correlated negatively with TG (r=-0.458, p=0.004). The above-mentioned associations of vitamin K1 intake/BW and circulating 25(OH)D with serum lipoproteins were not detected in individuals without vitamin K1 deficiency or the ones without vitamin D deficiency. The vitamin K2 intake/BW correlated negatively with low density lipoprotein-cholesterol (LDL-C) (r=-0.404, p=0.001). In conclusion, the associations of vitamin K1 intake with TG and HDL-C and of circulating 25(OH)D with TG were more pronounced in individuals with deficiency of either or both vitamins K1 and D. Increased dietary vitamin K2 intake was associated with decreased LDL-C.

Higher Dietary Vitamin K Intake is Associated with Better Physical Function and Lower Long-Term Injurious Falls Risk in Community-Dwelling Older Women

BackgroundIn recent years, a potential beneficial role of Vitamin K in neuromuscular function has been recognised. However, the optimal dietary intake of Vitamin K to support muscle function in the context of falls prevention remains unknown.ObjectiveTo examine the relationship of dietary Vitamin K1 and K2 with muscle function and long-term injurious fall-related hospitalisations in older women.DesignCohort study.Participants1347 community-dwelling older Australian women ≥70 years.MeasurementsA new Australian Vitamin K nutrient database, supplemented with published data, was used to calculate Vitamin K1 and K2 intake from a validated food frequency questionnaire at baseline (1998). Muscle function (grip strength and timed-up-and-go; TUG) as well plasma Vitamin D status (25OHD) were also assessed at baseline. Fall-related hospitalisations over 14.5 years were obtained from linked health records. Multivariable-adjusted logistic regression and Cox-proportional hazard models were used to analyse the data.ResultsOver 14.5 years of follow-up (14,774 person-years), 535 (39.7%) women experienced a fall-related hospitalisation. Compared to women with the lowest Vitamin K1 intake (Quartile 1, median 49 µg/d), those with the highest intake (Quartile 4, median 120 µg/d) had 29% lower odds (OR 0.71 95%CI 0.52–0.97) for slow TUG performance (>10.2 s), and 26% lower relative hazards of a fall-related hospitalisation (HR 0.74 95%CI 0.59–0.93) after multivariable adjustment. These associations were non-linear and plateaued at moderate intakes of ∼70–100 µg/d. There was no relation to grip strength. Vitamin K2 intakes were not associated with muscle function or falls.ConclusionA higher habitual Vitamin K1 intake was associated with better physical function and lower long-term injurious falls risk in community-dwelling older women. In the context of musculoskeletal health, Vitamin K1 found abundantly in green leafy vegetables should be promoted.

Vitamin K1 and K2 in the Diet of Patients in the Long Term after Kidney Transplantation

Vitamin K, especially its K2 form, is considered to be a protective factor against developing vascular changes and bone lesions that are common complications in kidney transplant (KTx) recipients. There is a growing number of studies showing that KTx patients are at risk of vitamin K deficiency. The aim of this study was to evaluate the intake of vitamin K1 and K2 in the diet of patients in the late period after KTx. During a routine visit at one outpatient transplantation clinic in Central Europe, a diet survey questionnaire was filled in by 151 clinically stable KTx recipients and compared with medical history, anthropometric measurements and laboratory tests. Mean vitamin K1 intake was 120.9 ± 49 μg/day and vitamin K2 (MK, menaquinone) intake 28.69 ± 11.36 μg/day, including: MK-4: 25.9 ± 9.9 μg/day; MK-5: 0.1 ± 0.2 μg/day; MK-6: 0.2 ± 0.4 μg/day; MK-7: 0.2 ± 0.23 μg/day; MK-8: 1 ± 1.9 μg/day; MK-9: 0.9 ± 2.3 μg/day; and MK-10: 0.2 ± 0.5 μg/day. Our study showed that KTx recipients' diets contained adequate amounts of vitamin K1, whereas the intake of vitamin K2 seemed insufficient.

Vitamin K Intake and Atherosclerotic Cardiovascular Disease in the Danish Diet Cancer and Health Study.

BackgroundDietary vitamin K (K1 and K2) may reduce atherosclerotic cardiovascular disease (ASCVD) risk via several mechanisms. However, studies linking vitamin K intake with incident ASCVD are limited. We aimed to determine the relationship between dietary vitamin K intake and ASCVD hospitalizations.Methods and ResultsIn this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study, with no prior ASCVD, completed a food‐frequency questionnaire at baseline and were followed up for hospital admissions of ASCVD; ischemic heart disease, ischemic stroke, or peripheral artery disease. Intakes of vitamin K1 and vitamin K2 were estimated from the food‐frequency questionnaire, and their relationship with ASCVD hospitalizations was determined using Cox proportional hazards models. Among 53 372 Danish citizens with a median (interquartile range) age of 56 (52–60) years, 8726 individuals were hospitalized for any ASCVD during 21 (17–22) years of follow‐up. Compared with participants with the lowest vitamin K1 intakes, participants with the highest intakes had a 21% lower risk of an ASCVD‐related hospitalization (hazard ratio, 0.79; 95% CI: 0.74–0.84), after multivariable adjustments for relevant demographic covariates. Likewise for vitamin K2, the risk of an ASCVD‐related hospitalization for participants with the highest intakes was 14% lower than participants with the lowest vitamin K2 intake (hazard ratio, 0.86; 95% CI, 0.81–0.91).ConclusionsRisk of ASCVD was inversely associated with diets high in vitamin K1 or K2. The similar inverse associations with both vitamin K1 and K2, despite very different dietary sources, highlight the potential importance of vitamin K for ASCVD prevention.

CHANGE IN HEMODYNAMIC PARAMETERS AND CAROTID STIFFNESS INDICES AFTER VITAMIN K2 SUPPLEMENTATION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Objective: Vitamin K2 is a cofactor of gamma-carboxylase activating group of vitamin K-dependent proteins involved in vascular calcification and arterial stiffness. Data on the protective effects of vitamin K2 supplementation in the progression of vascular damage in patients with type 2 diabetes mellitus (T2DM) are scarce. Aim: to investigate the change in systolic (SAP), diastolic (DAP), pulse (PP), mean (MAP) blood pressure, central systolic aortic pressure (CASP), pulse wave velocity (PWV) and beta-stiffness index (BSI) in patients with T2DM after vitamin K2 supplementation. Design and method: We included 18 patients with T2DM (mean age 59.09 ± 8.5 men 38.8%) who received Vitamin K2 (Menaquinone-7) 75 μg once daily for a period of 4 weeks. Patients with overt cardio-vascular diseases, uncontrolled blood pressure and vitamin K-antagonists intake were excluded from the study. Hemodynamic parameters were measured using an A-pulse CASP-AL device. Carotid stiffness indices were measured by one-point echo-tracking method with Aloka Hitachi Prosound on the both common carotid arteries (CA). Results: All hemodynamic parameters showed increased values compared to the baseline: SAP (+5 mmHg) (p = 0.1), DAP (+2.9mmHg) (p = 0.19), PP (+1.4mmHg) (p = 1.4), MAP (+3.4 mmHg) (p = 0.08). CASP increased from 119.8 ± 12.1mmHg to 126.8 ± 11.4 mmHg (+5 mmHg), and this change was significant (p = 0.02). PWV on the right CA did not change significantly before (7.0 ± 1.48 m/s) and after (7.19 ± 1.28 m/s) supplementation (p = 0.47), similar to BSI 10.08 ± 3.41 and respectively 10.51 ± 3.99 (p = 0.61). PWV on the left CA before supplementation is 7.01 ± 1.22 m/c, respectively after 7.19 ± 1.56 m/c (p = 0.49). BSI on the left CA is 9.97 ± 2.79, resp. 10.69 ± 5.07 (p = 0.43). Conclusions: Vitamin K2 supplementation for four weeks showed significant increase in CASP in our cohort of patients with T2DM. The other hemodynamic parameters as well as the indicators of carotid stiffness do not change significantly. A limitation of our study is the small number of patients included and the short period of intake of vitamin K2, which may not lead to morphological changes in the vessel wall. More extensive research is needed in the field.

Association of dietary vitamin K and risk of coronary heart disease in middle-age adults: the Hordaland Health Study Cohort

ObjectiveThe role of vitamin K in the regulation of vascular calcification is established. However, the association of dietary vitamins K1 and K2 with risk of coronary heart disease (CHD) is...

Vitamin K-induced effects on body fat and weight: results from a 3-year vitamin K2 intervention study.

Vitamin K status has been linked to fat and glucose metabolism by several authors, but whether high vitamin K intake influences body weight or composition has remained unclear. Here we tested the hypothesis that increased vitamin K intake decreases body fat or fat distribution. In a randomized placebo-controlled human intervention trial, 214 postmenopausal women, 55-65 years of age, received either 180 mcg/day of vitamin K2 (menaquinone-7, MK-7) or placebo for 3 years. Osteocalcin (OC) carboxylation was used as a marker for vitamin K status, and fat distribution was assessed by dual-energy X-ray absorptiometry total body scan. In the total cohort, MK-7 supplementation increased circulating carboxylated OC (cOC) but had no effect on body composition. In those with an above-median response in OC carboxylation ('good responders'), MK-7 treatment resulted in a significant increase in total and human molecular weight adiponectin and a decrease in abdominal fat mass and in the estimated visceral adipose tissue area compared with the placebo group and the poor responders. The fact that changes in body composition measures or markers for fat or glucose metabolism were not associated with changes in uncarboxylated OC (ucOC) does not support the assumption that ucOC stimulates fat metabolism in humans. Instead, high vitamin K2 intake may support reducing body weight, abdominal and visceral fat, notably in subjects showing a strong increase in cOC. A causal relation between the changes in cOC and body fat or distribution cannot be concluded from these data.

Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms.

AIMTo assess the rate of matrix Gla-protein carboxylation in patients with small intestinal bacterial overgrowth (SIBO) and to decipher its association with subclinical atherosclerosis.METHODSPatients with suspected SIBO who presented with a low risk for cardiovascular disease and showed no evidence of atherosclerotic plaques were included in the study. A glucose breath test was performed in order to confirm the diagnosis of SIBO and vascular assessment was carried out by ultrasound examination. Plasma levels of the inactive form of MGP (dephosphorylated-uncarboxylated matrix Gla-protein) were quantified by ELISA and vitamin K2 intake was estimated using a food frequency questionnaire.RESULTSThirty-nine patients were included in the study. SIBO was confirmed in 12/39 (30.8%) patients who also presented with a higher concentration of dephosphorylated-uncarboxylated matrix Gla-protein (9.5 μg/L vs 4.2 μg/L; P = 0.004). Arterial stiffness was elevated in the SIBO group (pulse-wave velocity 10.25 m/s vs 7.68 m/s; P = 0.002) and this phenomenon was observed to correlate linearly with the levels of dephosphorylated-uncarboxylated matrix Gla-protein (β = 0.220, R2 = 0.366, P = 0.03). Carotid intima-media thickness and arterial calcifications were not observed to be significantly elevated as compared to controls.CONCLUSIONSIBO is associated with reduced matrix Gla-protein activation as well as arterial stiffening. Both these observations are regarded as important indicators of subclinical atherosclerosis. Hence, screening for SIBO, intestinal decontamination and supplementation with vitamin K2 has the potential to be incorporated into clinical practice as additional preventive measures.

Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stages 3-5.

Observational studies have shown that high dietary intake of vitamin K2 is associated with reduced risk of coronary vascular disease and vascular calcification. We assessed the effect of vitamin K2 substitution on the progression of atherosclerosis and calcification in nondialyzed patients with CKD stages 3-5. The study included 42 nondialyzed patients with CKD. The following measurements were taken at baseline and after 270 ±12 days of supplementation with vitamin K2 at a dose of 90 μg (menaquinone, MK-7) together with 10 μg of cholecalciferol (K+D group) or 10 μg of cholecalciferol (group D): common carotid intima-media thickness (CCA-IMT), coronary artery calcification score (CACS), basic biochemical parameters, lipids, and calcification modulators: matrix Gla protein (MGP), desphosphorylated-uncarboxylated MGP (dp-ucMGP), osteoprotegerin (OPG), fetuin A, osteocalcin (OC), and fibroblast growth factor 23. The increase of CCA-IMT was significantly lower in the K+D group compared with the D group: from 0.95 ±0.2 mm to 1.01 ±0.3, P = 0.003 vs from 1.02 ±0.2 mm to 1.16 ±0.3, P = 0.003 (ΔCCA-IMT, 0.06 ±0.08 vs 0.136 ±0.05 mm, P = 0.005, respectively). The increase in CACS was slightly lower in the K+D group than in the D group (ΔCACS, 58.1 ±106.5 AU vs 74.4 ±127.1 AU, P = 0.7). In the K+D group, a significant decrease in the level of dp-ucMGP and total OC was observed. A 270-day course of vitamin K2 administration in patients with CKD stages 3-5 may reduce the progression of atherosclerosis, but does not significantly affect the progression of calcification. Vitamin K2 significantly changes the levels of calcification promoters and inhibitors: dp-ucMGP, OC, and OPG.

Scientific Opinion on the substantiation of a health claim related to vitamin K2 and contribution to the normal function of the heart and blood vessels (ID 125, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

Following a request from the European Commission, pursuant to Article 13 of Regulation (EC) No 1924/2006, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a health claim related to vitamin K2 and contribution to the normal function of the heart and blood vessels. The food constituent that is the subject of the claim, vitamin K2, is sufficiently characterised. The claimed effect, contribution to the normal function of the heart and blood vessels, is a beneficial physiological effect. The proposed target population is the general population. In weighing the evidence, the Panel took into account the absence of human intervention studies from which conclusions could be drawn for the scientific substantiation of the claim, the inconsistency of the results reported in two cross-sectional studies regarding arterial calcification in women, that the results of two prospective cohort studies are in conflict regarding the risk of coronary heart disease associated with vitamin K2 intakes, that high intakes of vitamin K2 were associated with a significantly lower degree of aortic calcification in one prospective cohort study after adjustment for confounders, and that the evidence provided for a proposed mechanism is weak. On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the dietary intake of vitamin K2 and contribution to the normal function of the heart and blood vessels.

Intake of vitamin K1 and K2 and risk of hip fractures: The Hordaland Health Study

Evidence of the effect of vitamin K on bone health is conflicting. The aim was to investigate the association between intake of vitamins K1 and K2 and subsequent risk of hip fracture in a general population sample, as well as potential effect modification by apolipoprotein E gene (APOE) status by presence of the E4 allele. 1238 men and 1569 women 71-75 years of age were included in the community-based Hordaland Health Study 1997-1999 in Western Norway. Information on hip fracture was obtained from hospitalizations in the region from enrolment until 31 December 2009. Information on intake of vitamins K1 and K2 collected at baseline was used as potential predictors of hip fracture in Cox proportional hazards regression analyses. Participants in the lowest compared to the highest quartile of vitamin K1 intake had increased risk of suffering a hip fracture (hazard ratio (HR)=1.57 [95% CI 1.09, 2.26]). Vitamin K2 intake was not associated with hip fracture. Presence of APOE4-allele did not increase the risk of hip fracture, nor was there any effect modification with vitamin K1 in relation to risk of hip fracture. A low intake of vitamin K1, but not K2, was associated with an increased risk of hip fractures.

The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children

Vitamin K contributes to bone health, probably through its role as cofactor in the carboxylation of osteocalcin. Intervention studies in adults have demonstrated that markedly higher osteocalcin carboxylation is obtained by intakes of vitamin K well above the current recommended dietary intake. However, the relationship between increased vitamin K2 intake and enhanced osteocalcin carboxylation has never been shown in healthy children. The objective was to study the effect of 45 microg menaquinone-7 (MK-7; one of the vitamin K2 species) on the circulating levels of undercarboxylated osteocalcin (ucOC) and carboxylated osteocalcin (cOC) in healthy prepubertal children. We hypothesised that MK-7 supplementation will reduce the ucOC:cOC ratio (UCR), indicating an improved vitamin K status. The present study is a double-blind randomised placebo-controlled trial examining the effect of 8 weeks MK-7 supplementation on the carboxylation of osteocalcin in healthy children (n 55). Serum levels of ucOC, cOC and MK-7 were measured at baseline and after 8 weeks, together with bone markers and coagulation parameters. The UCR was used as an indicator of vitamin K status. In the MK-7-supplemented group (n 28), the circulating concentration of inactive ucOC reduced and the UCR improved whereas the concentration of MK-7 increased. Within the placebo group, ucOC, cOC, UCR and MK-7 did not significantly change over time. In both groups, bone markers and coagulation parameters remained constant over time. These findings demonstrate that in healthy, prepubertal children, modest supplementation with MK-7 increases circulating concentrations of MK-7 and increases osteocalcin carboxylation.

606 発育期における力学的負荷とビタミンK2摂取の骨成長に対する影響の検討(GS-2・11 成長・成育と動作解析)

606 発育期における力学的負荷とビタミンK2摂取の骨成長に対する影響の検討(GS-2・11 成長・成育と動作解析)

Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women.

SummaryVitamin K mediates the synthesis of proteins regulating bone metabolism. We have tested whether high vitamin K2 intake promotes bone mineral density and bone strength. Results showed that K2 improved BMC and femoral neck width, but not DXA-BMD. Hence high vitamin K2 intake may contribute to preventing postmenopausal bone loss.IntroductionVitamin K is involved in the synthesis of several proteins in bone. The importance of K vitamins for optimal bone health has been suggested by population-based studies, but intervention studies with DXA-BMD as a clinical endpoint have shown contradicting results. Unlike BMC, DXA-BMD does not take into account the geometry (size, thickness) of bone, which has an independent contribution to bone strength and fracture risk. Here we have tested whether BMC and femoral neck width are affected by high vitamin K intake.MethodsA randomized clinical intervention study among 325 postmenopausal women receiving either placebo or 45 mg/day of vitamin K2 (MK-4, menatetrenone) during three years. BMC and hip geometry were assessed by DXA. Bone strength indices were calculated from DXA-BMD, femoral neck width (FNW) and hip axis length (HAL).ResultsK2 did not affect the DXA-BMD, but BMC and the FNW had increased relative to placebo. In the K2-treated group hip bone strength remained unchanged during the 3-year intervention period, whereas in the placebo group bone strength decreased significantly.ConclusionsVitamin K2 helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW, whereas it has little effect on DXA-BMD.

Vitamin K intake and calcifications in breast arteries

Objectives Vitamin K is an important co-factor in the production of proteins that inhibit vascular calcification. A low dietary Vitamin K intake has been associated with aortic and coronary calcifications and an elevated cardiovascular risk. Calcifications in the arteries of the breasts have also been associated with cardiovascular risk, but whether there is a relation with a low Vitamin K intake has not yet been studied. Methods We conducted a cross-sectional study among 1689 women, aged 49–70 years. Dietary Vitamins K1 and K2 intake was calculated from a validated food frequency questionnaire. Breast arterial calcifications (BAC) were assessed on standard screening mammograms by two independent radiologists. With a general linear model mean Vitamins K1, K2 and Vitamin K2 subtypes were calculated for women with BAC and without, adjusted for age, smoking, diabetes, intake of saturated fat, mono-unsaturated fat, poly-unsaturated fat and protein- and calcium-intake. Results BAC was less common in the highest (9%) quartile of Vitamin K2 intake, compared to the lowest (13%) (OR 0.7, 95% CI 0.5–1.1) and not different across quartiles of Vitamin K1 intake. Mean Vitamin K2 levels and mean levels of Vitamin K2 subtypes MK-5 through MK-10 were lower in the participants with BAC ( p = 0.01) compared to participants without BAC. However, after adjustment for aging, smoking, diabetes and dietary factors the association of mean Vitamin K2 intake with BAC was no longer significant. Conclusion Calcifications in breast arteries are not associated with a lower dietary intake of Vitamin K.