Vitamin K2 (Arterial Calcium)

Background/Objectives: Post-menopausal women are at an increased risk of developing cardiovascular disease. Menaquinone-7 (MK-7) is a fat-soluble vitamin involved in coagulation and maintaining vascular health. The aim of the post hoc analysis of this one-year study is to investigate the effects of MK-7 supplementation on the vascular parameters in pre-, peri-, and post-menopausal women. Methods: In a clinical intervention trial (NCT02404519), a total of 165 women with a low vitamin K status received either 180 µg of MK-7 daily (n = 82) or a matching placebo (n = 83) for one year. Established vascular parameters were measured before and after one year of vitamin K2 supplementation. Pre-, peri-, and post-menopausal women were subdivided according to arterial stiffness, with a high b-stiffness index defined as being greater than the overall median of 9.83. Results: The post hoc analyses showed a significant decrease in desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) plasma levels after MK-7 supplementation (pre/peri, p = 0.009; post, p < 0.001). MK-7 treatment significantly attenuated vascular stiffness in post-menopausal women (placebo +49.1% ± 77.4; MK-7 +9.4% ± 67.1; p = 0.035). Post-menopausal women with a high stiffness index showed significantly improved vascular markers after MK-7 treatment, e.g., a decreased blood pressure at brachialis (-3.0% ± 9.0; p = 0.007) and an increased distensibility coefficient (+13.3% ± 32.3; p = 0.040). Conclusions: Our results confirm that menopause affects vascular health status. Post-menopausal women with an increased stiffness benefit most from MK-7 supplementation, with a significantly improved blood pressure. Further research is needed to unravel the beneficial effects of MK-7 in post-menopausal women.

BACKGROUND: Vitamin K activates matrix Gla protein (MGP), a key inhibitor of vascular calcification. There is a high prevalence of sub-clinical vitamin K deficiency in patients with end-stage kidney disease. METHODS: A parallel randomized placebo-controlled pilot trial was designed to determine whether 10 mg of phylloquinone thrice weekly versus placebo modifies coronary artery calcification progression over 12 months in patients requiring hemodialysis with a coronary artery calcium score (CAC) ≥30 Agatston Units (ClinicalTrials.gov identifier NCT01528800). The primary outcome was feasibility (recruitment rate, compliance with study medication, study completion and adherence overall to study protocol). CAC score was used to assess calcification at baseline and 12 months. Secondary objectives were to explore the impact of phylloquinone on vitamin K-related biomarkers (phylloquinone, dephospho-uncarboxylated MGP and the Gla-osteocalcin to Glu-osteocalcin ratio) and events of clinical interest. RESULTS: A total of 86 patients with a CAC score ≥30 Agatston Units were randomized to either 10 mg of phylloquinone or a matching placebo three times per week. In all, 69 participants (80%) completed the trial. Recruitment rate (4.4 participants/month) and medication compliance (96%) met pre-defined feasibility criteria of ≥4.17 and ≥90%, respectively. Patients randomized to phylloquinone for 12 months had significantly reduced levels of dephospho-uncarboxylated MGP (86% reduction) and increased levels of phylloquinone and Gla-osteocalcin to Glu-osteocalcin ratio compared with placebo. There was no difference in the absolute or relative progression of coronary artery calcification between groups. CONCLUSION: We demonstrated that phylloquinone treatment improves vitamin K status and that a fully powered randomized trial may be feasible. © The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.

OBJECTIVE: Vascular calcification is an independent risk factor for cardiovascular disease. Once thought to be a passive process, vascular calcification is now known to be actively prevented by proteins acting systemically (fetuin-A) or locally (matrix Gla protein). Warfarin is a vitamin K antagonist, widely prescribed to reduce coagulation by inhibiting vitamin K-dependent coagulation factors. Recently, it became clear that vitamin K antagonists also affect vascular calcification by inactivation of matrix Gla protein. Here, we investigated functional cardiovascular characteristics in a mouse model with warfarin-induced media calcification. APPROACH AND RESULTS: DBA/2 mice received diets with variable concentrations of warfarin (0.03, 0.3, and 3 mg/g) with vitamin K1 at variable time intervals (1, 4, and 7 weeks). Von Kossa staining revealed that warfarin treatment induced calcified areas in both medial layer of aorta and heart in a dose- and time-dependent fashion, which could be inhibited by simultaneous vitamin K2 treatment. With ongoing calcification, matrix Gla protein mRNA expression decreased, and inactive matrix Gla protein expression increased. TdT-mediated dUTP-biotin nick end labeling-positive apoptosis increased, and vascular smooth muscle cell number was concomitantly reduced by warfarin treatment. On a functional level, warfarin treatment augmented aortic peak velocity, aortic valve-peak gradient, and carotid pulse-wave velocity. CONCLUSION: Warfarin induced significant calcification with resulting functional cardiovascular damage in DBA/2 wild-type mice. The model would enable future researchers to decipher mechanisms of vascular calcification and may guide them in the development of new therapeutic strategies.

AIM: Vascular calcification is a common feature in patients with advanced atherosclerosis, postmenopausal women and patients with renal failure, which results in reduced elasticity of arteries. Pamidronate, a bisphosphonate, is used as a therapeutic agent for anti-osteoporosity, although there are adverse side effects, such as renal damage and aortic inflamed plaque rupture. In the present study, we demonstrated the effects of vitamin K(2) alone or in combination with pamidronate in an arterial calcification model induced using inorganic phosphate in cultured bovine aortic smooth muscle cells (BASMCs). METHODS: Calcification was induced by the addition of Pi (3 mM) in BASMCs. Calcium deposition was determined by Calcium C-test Wako and von Kossa staining. mRNA expression was assessed by semi-quantitative reverse transcription-polymerase chain reaction. RESULTS: Calcium deposition assay and von Kossa staining showed that calcification could be inhibited in a dose-dependent manner by treatment with vitamin K(2) alone, and that its inhibitory effect was enhanced when combined with pamidronate. It was found that the expression of tropoelastin mRNA was synergistically enhanced by combined treatment with vitamin K(2) and pamidronate, and the expression matrix Gla protein mRNA and osteopontin mRNA expression were also enhanced and suppressed, respectively, by treatment with vitamin K(2) or pamidronate. Moreover, our data showed that the suppression of TE expression by siRNA significantly increased Pi-induced vascular calcification. CONCLUSION: Taken together, our study suggests that vitamin K(2) in combination with pamidronate synergistically inhibits arterial calcification via the increased expression of tropoelastin, which would be a useful marker for developing effective therapeutic or prophylactic agents for arterial calcification.

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.

BACKGROUND: A deficiency in vitamin K has been associated with increased calcium deposition and coronary artery calcification, which may lead to cardiovascular disease. OBJECTIVES: To determine the effectiveness of vitamin K supplementation as a single nutrient supplement for the primary prevention of cardiovascular disease. SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 8 of 12, 2014); MEDLINE (Ovid, 1946 to September week 2 2014); EMBASE Classic + EMBASE (Ovid, 1947 to September 18 2014); Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index, Science (CPCI-S) (both 1990 to 17 September 2014) on Web of Science (Thomson Reuters); Database of Abstracts of Reviews of Effects (DARE); Health Technology Assessment Database and Health Economics Evaluations Database (Issue 3 of 4, 2014). We searched trial registers and reference lists of reviews for further studies. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials of vitamin K supplementation as a single nutrient supplement, lasting at least three months, and involving healthy adults or adults at high risk of cardiovascular disease. The comparison group was no intervention or placebo. The outcomes of interest were cardiovascular disease clinical events and cardiovascular disease risk factors. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias. MAIN RESULTS: We included only one small trial (60 participants randomised) which overall was judged to be at low risk of bias. The study examined two doses of menaquinone (vitamin K2) over 3 months in healthy participants aged 40 to 65 years. The primary focus of the trial was to examine the effects of menaquinone (subtype MK7) on different matrix Gla proteins (MGP - vitamin K dependent proteins in the vessel wall) at different doses, but the authors also reported blood pressure and lipid levels. The trial did not report on our primary outcomes (cardiovascular disease clinical events) as it was small, short term and conduc

PURPOSE: Vitamin K2 supplementation has emerged as a strategy to enhance recovery and modulate postexercise physiological responses. This study aimed to assess the effects of vitamin K2 on recovery from muscle-damaging exercise in young and older adults. METHODS: Healthy young (18-40 yr) and older (65+ yr) adults were randomly assigned to either vitamin K2 (menaquinone-7, MK-7, 240 μg/d) or placebo (cellulose) for 12 wk in this double-blind randomized controlled trial. Before and after supplementation, knee extensor maximal torque, functional ability, muscle soreness, and systemic blood markers of muscle damage and inflammation were measured before (0 h) and 3, 24, 48, and 72-h postexercise. Data were analyzed using regression and mixed models. RESULTS: Seventy-one participants (35 young and 36 older) completed the study, with 12 wk of vitamin K2 supplementation increasing circulating MK-7 levels (P-value <0.001). There were no supplement × time effects for any variables. Significant supplement × time × older age interaction effects were noted for electromechanical delay (EMD) (P-value = 0.03), electromyography root mean square (RMS) (P-value = 0.01), interleukin-6 (IL-6) concentrations (P-value <0.001), and creatine kinase (CK) levels (P-value = 0.02). In older adults, after 12 wk, EMD appeared lower at all time points and RMS higher postexercise in the vitamin K2 group. No clear pattern in IL-6 or CK was observed, but at 72-h postexercise CK was lower in older adults in the vitamin K2 group. CONCLUSIONS: Vitamin K2 supplementation had no effect on muscle strength, physical function, muscle soreness, or inflammatory responses in the recovery period after a bout of resistance exercise. Effects of supplementation were observed on EMD, RMS, IL-6, and CK by age and warrant further investigation.

Background: Vitamin K has emerged as a promising regulator of glucose metabolism in preclinical studies. There is, however, scant evidence to support this promising potential in a clinical setting. Aim: The aim of this study was to confirm the effects of vitamin K supplementation on glycaemic parameters such as fasting blood glucose (FBG), fasting insulin (FI), glycated haemoglobin (HbA1c), insulin resistance (HOMA-IR), and homeostatic model of beta cell function (HOMA-β) across randomised controlled trials (RCTs). Materials and Methods: This meta-analysis used evidence from PubMed, Scopus, and manual screening. Only RCTs were considered for this meta-analysis of interventional studies. The Meta online tool was used to analyse data, with the results reported as either the mean or the standardised mean difference (SMD), alongside 95% confidence intervals (CI). Results: Only eight RCTs were found relevant and analysed; the age of those in the vitamin K group was 50.58 ± 6.91 years, and in the control group, it was 48.19 ± 5.41. The evidence showed a significant reduction in FBG, SMD = -0.22 (-0.39 to -0.05), HbA1c, MD = -1.00%, 95% CI (-1.92 to -0.07), and HOMA-IR, MD = -0.63, 95% CI (-1.20 to -0.06). However, no effect was observed on insulin (SMD = -0.39, 95% CI: -0.91 to 0.13, p = 0.15) and HOMA-β (MD = 6.56, 95% CI (-3.89 to 17.01), p = 0.2184. Low doses of vitamin K2 and vitamin K1 were associated with reduced HbA1c and HOMA-IR, respectively. An intervention of less than 12 weeks was associated with reduced HOMA-IR. Conclusions: This study showed a significant decrease in FBG, HbA1c, and HOMA-IR without affecting insulin or HOMA-β. Nevertheless, the limited number of trials with moderate quality warrants larger, longer-term RCTs with rigorous methodology and direct comparisons of vitamin K isoforms to better assess therapeutic potential.

PURPOSE: The aim of the MultiVeg study, a double-blind, randomised controlled trial (RCT), was to investigate the nutritional status of healthy vegans following 4 months of multinutrient supplementation. METHODS: A double-blind, RCT was conducted with 72 vegan adults (19-57 years) in Germany. Data on anthropometric parameters, dietary nutrient intake, and nutritional status were collected. The nutritional status of the participants was assessed at baseline and after 4 months. The results were compared between groups using ANCOVA. The results for vitamins and choline are presented here. RESULTS: After adjustment for baseline values, age, sex, and multiple testing, no significant between-group differences in biomarker concentration changes from baseline to 4 months were observed for vitamin A, retinol-binding protein, transthyretin, beta-carotene, methylmalonic acid, homocysteine, choline, total osteocalcin, carboxylated and undercarboxylated osteocalcin, and folate. In contrast, significant between-group differences in changes were observed for flavin adenine dinucleotide (FAD), serum vitamin B12, holotranscobalamin, and the combined vitamin B12 status indicator (cB12) after adjustment. CONCLUSION: A multinutrient supplement containing 82 µg of vitamin B12 per day significantly positively affected vitamin B12 blood biomarkers in healthy vegans. REGISTRATION: This study was registered in the German Clinical Trials Register (DRKS00028151). © 2025. The Author(s).

BACKGROUND: Osteoporosis is a metabolic bone disease characterized by decreased bone mass and increased fracture risk. Bone turnover markers, such as osteocalcin (OC), undercarboxylated osteocalcin (ucOC), and other biochemical indicators, are important for assessing bone metabolism. Vitamin K2 influences bone metabolism by enhancing osteocalcin γ-carboxylation. METHODS: This study followed PRISMA guidelines and included randomized controlled trials on the effects of vitamin K2 supplementation on bone turnover biomarkers in postmenopausal osteoporosis patients. Key outcomes included changes in OC, ucOC, and other bone metabolism markers. RESULTS: Nine studies with 2,570 participants were included. Vitamin K2 (VK2) increased osteocalcin (OC; MD 1.86, 95% CI 1.17-2.56) and bone-specific alkaline phosphatase (BAP; MD 1.49, 95% CI 0.98-2.00). It reduced undercarboxylated OC (ucOC; WMD -1.54, 95% CI -2.44 to -0.64) and tartrate-resistant acid phosphatase (TRAP; MD -0.83, 95% CI -1.21 to -0.46). C-terminal telopeptide (CTX) showed a small, statistically significant reduction (MD -0.09, 95% CI -0.14 to -0.05) with uncertain clinical relevance. N-telopeptide (NTX) showed no significant change. CONCLUSIONS: Vitamin K2 supplementation improves key bone turnover biomarkers, particularly OC and ucOC. These findings support its role in bone metabolism, though further long-term studies are needed to confirm clinical benefits, such as increased bone mineral density. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251087067, identifier CRD420251087067.

BACKGROUND AND AIMS: Vitamins K2 and D3 may improve cardiovascular health by modulating inflammation and vascular calcification. Inflammation contributes to atherosclerosis and can be assessed through imaging and systemic biomarkers. This study investigated whether vitamin K2 and D3 supplementation reduces inflammation in epicardial adipose tissue (EAT), including pericoronary adipose tissue (PCAT), and systemic inflammation in elderly men at cardiovascular risk. METHODS: In the Aortic Valve DECalcification (AVADEC) trial, 388 men aged 65-74 received daily vitamin K2 (720 μg) and D3 (25 μg) or placebo for 24 months. EAT inflammation was assessed using non-contrast CT [EAT volume and attenuation] and contrast-enhanced CT [PCAT attenuation]. Systemic inflammation was evaluated via hs-CRP, IL-6, TNF-α, Fetuin-A, and osteopontin (OPN). Dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), the inactive form of MGP, served as a proxy for vitamin K2 status. RESULTS: After 24 months, EAT volume increased in the placebo group (Δ5.66 cm3,95% CI 1.35; 9.98) and non-significantly in the vitamin group (Δ3.44 cm3, 95% CI -0.44; 7.33), with an intergroup difference of -2.22 cm3 (95% CI -8.01; 3.57). EAT attenuation declined similarly (intergroup difference: 0.32 HU, 95% CI -0.23; 0.87). PCAT attenuation remained unchanged. No significant changes were seen in systemic markers, though OPN increased modestly in the vitamin group (Δ25.72 pg/mL, 95% CI 2.40; 49.05). dp-ucMGP decreased significantly with supplementation (intergroup difference: 255.31 pmol/L, 95% CI -289.56; -221.05). CONCLUSIONS: Despite reduction in dp-ucMGP, high-dose vitamin K2 and D3 supplementation did not affect EAT, PCAT or systemic inflammation over 24 months. Alternative strategies may be needed to target inflammatory pathways in cardiovascular disease prevention.

BACKGROUND AND OBJECTIVE: Nordic skiers represent a low-impact, weight-sensitive sport and may be inclined to engage in weight-controlling behavior, hence increasing their risk for low energy availability and impairment in health and performance. Jarlsberg cheese (J) is rich in vitamin K₂ from fermentation by Propionibacterium freudenreichii subsp. shermanii LMGT 2951 (Pf) and lactic acid bacteria and increases the osteocalcin (OC) level. Vitamin K is essential for activating OC, which is described to be associated positively with muscle strength, whereas propionic acid bacteria are found to enhance endurance. Except for Pf and its by-products, J and Norvegia (N) cheeses have almost identical nutrient content. The objective of this study was to compare the effects of Jarlsberg and N as potential supplements to training on muscle strength (MS), lean body mass (LBM) and VO2 max. METHODS: Thirty female and 30 male Nordic skiers were block randomized 1:1 to either J or N and studied during a 24-week offseason training schedule. The Norvegia group served as a control group. Females and males were treated with 75 and 90 grams/day, respectively. MS by seated pulldown and half-squat, LBM by DXA, and VO2 max were measured at baseline and after the 24 weeks off-season period. Dietary intake and training hours were registered and monitored at baseline and every eight weeks during the study. RESULTS: MS significantly increased in both groups after 24 weeks (p < 0.01). The mean increase difference in MS-upper body favored Jarlsberg by 0.95 kg (95% CI: -0.02-1.46), approaching significance (p = 0.06). No significant difference was found between groups in MS-lower body. LBM and VO2-max both increased significantly in each group (p ≤ 0.05), with no notable differences between groups. Correlation analysis identified LBM as the dominant outcome variable at both baseline and 24 weeks. Endurance training was the dominant input variable and correlated significantly positively both multiply and partially to LBM, (p = 0.04, p = 0.02), respectively. At baseline and 24-weeks sex, endurance training along with OC-level explained 65% and 68% of the LBM variations, respectively. CONCLUSION

BACKGROUND: Menaquinone-7 (MK-7) is a type of vitamin K that has a longer half-life and stays in the body for a more extended period compared to other types of vitamin K. Recently, the effects of this vitamin on body weight, glycemic control, and lipid profiles have garnered much attention. AIM OF THE REVIEW: This systematic review and meta-analysis were performed to evaluate the effects of MK-7 on anthropometric measurements, glycemic indices, and lipid profiles. METHODS: A systematic search via appropriate keywords was conducted in electronic databases including PubMed, Scopus, Web of Science, and Google Scholar up to October 2023 to obtain relevant original articles. The quality of studies was evaluated using the Cochrane Collaboration tool. Six original articles met our criteria and were included in the analysis. RESULTS: Statistical analysis showed that MK-7 had a desirable effect on inulin (SMD= -0.56; 95 % CI: -0.77, -0.36; P = 0.000, I2 = 84 %, P = 0.000), HbA1c (SMD=-0.32; 95 % CI: -0.55, -0.09; P = 0.007, I2 = 86.8 %, P = 0.000), and homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (SMD= -0.56; 95 % CI: -0.76, -0.35; P = 0.000, I2 = 84.3 %, P = 0.000). Additionally, subgroup analysis revealed negligible effects of MK-7 on total cholesterol (TC), insulin, HbA1c, and HOMA-IR in both genders of patients who received ≤ 90 mg MK-7 for less than 12 weeks. However, MK-7 didn't have any meaningful effect on other factors. CONCLUSION: Based on the findings of the present systematic review and meta-analysis, MK-7 may have beneficial effects on glycemic control and TC, although further highly qualified original research is needed for a consistent conclusion.

OBJECTIVE: Patients on dialysis treatment have poor functional vitamin K status, and this may increase the risk of vascular calcification. Vitamin K supplementation may therefore be relevant in patients on dialysis, but the procoagulant effects have not been studied. We evaluated effects of menaquinone-7 (MK-7) supplementation on biomarkers of coagulation in patients on dialysis. METHODS: Double-blinded, placebo-controlled study in 123 patients on dialysis randomized to 52 weeks of vitamin K (MK-7, 360 μg/daily, n = 61) or placebo (n = 62). Measurements at baseline and after 52 weeks of intervention included thrombin generation (endogenous thrombin potential, peak thrombin concentration, time to peak, and lag time); clot activities of vitamin K-dependent coagulation factors (F) II, VII, IX, and X; prothrombin fragment 1 + 2 (F1+2); and proteins induced by vitamin K absence II (PIVKA-II). Between-group differences (vitamin K vs. placebo) at 52 weeks were determined with an analysis of covariance. Within-group changes in vitamin K and placebo groups were analyzed with a paired t-test. Vascular adverse events and serious adverse events were registered based on hospital records, laboratory data, and participant interviews and compared between groups using Fisher's exact test or Pearson's Chi-Squared test. RESULTS: A between-group difference at 52 weeks was observed for PIVKA-II (P < .001). PIVKA-II decreased significantly from baseline to 52 weeks in the vitamin K group, but not in the placebo group. We observed no between-group differences or within-group changes for biomarkers of coagulation, except for FVII clot activity which was reduced in the placebo group (P = .04), and no between-group differences in adverse events and serious adverse events. CONCLUSION: One year of vitamin K supplementation in patients on dialysis has no detectable effects on biomarkers of coagulation activation, clot activities of vitamin K-dependent coagulation factors, and vascular events or death, indicating no procoagulant effects of this treatment.

BACKGROUND AND AIMS: Experimental studies suggested that vitamin K supplementation may retard arterial calcification. Recently, serum calcification propensity time (T50) has been suggested as a functional biomarker for arterial wall calcification propensity. In this post-hoc analysis of a clinical trial, we evaluated the effect of six-month oral vitamin K supplementation on T50 and assessed the correlation between T50 and imaging arterial calcification parameters in people with type 2 diabetes (T2DM). METHODS: This double-blind, randomized, placebo-controlled trial included 68 participants (age = 69 ± 8 years, 76% male) with T2DM. Participants were assigned to menaquinone-7 (360 μg/day; n = 35) or placebo (n = 33). T50 was measured via nephelometry in serum collected at baseline, three and six months. Arterial calcification was measured at baseline and six months via 18F-Na PET-CT and conventional CT using Target-to-Background ratio (TBR) and Agatston score. Longitudinal analysis of covariance adjusted for baseline T50 was used to study the treatment effect. Spearman's correlation was used to assess the correlation between T50 and imaging calcification parameters. RESULTS: Median baseline T50 was similar in the vitamin K (350 [321-394] minutes) and placebo groups (363 [320-398]). There was no significant difference in T50 between treatment arms over time (ẞ = 1.00, 95%C.I. = 0.94-1.07, p = 0.982). The correlation coefficient of T50 with TBR and Agatston score at baseline were -0.185 (p = 0.156) and -0.121 (p = 0.358), respectively. CONCLUSIONS: No effect of vitamin K supplementation on T50 was observed in T2DM. Moreover, T50 did not correlate with TBR and Agatston score. Further research on vitamin K in arterial calcification and on the validity of T50 as arterial calcification marker is warranted.

BACKGROUND: COVID-19 has caused morbidity, hospitalisation and mortality worldwide. Despite effective vaccines, there is still a need for effective treatments, especially for people in the community. Dietary supplements have long been used to treat respiratory infections, and preliminary evidence indicates some may be effective in people with COVID-19. We sought to evaluate whether a combination of vitamin C, vitamin D3, vitamin K2 and zinc could improve overall health and decrease symptom burden in outpatients diagnosed with COVID-19. METHODS: Participants were randomised to receive either vitamin C (6 g), vitamin D3 (1000 units), vitamin K2 (240 μg) and zinc acetate (75 mg) or placebo daily for 21 days and were followed for 12 weeks. An additional loading dose of 50 000 units vitamin D3 (or placebo) was given on day one. The primary outcome was participant-reported overall health using the EuroQol Visual Assessment Scale summed over 21 days. Secondary outcomes included health status, symptom severity, symptom duration, delayed return to usual health, frequency of hospitalisation and mortality. RESULTS: 90 patients (46 control, 44 treatment) were randomised. The study was stopped prematurely due to insufficient capacity for recruitment. The mean difference (control-treatment) in cumulative overall health was -37.4 (95% CI -157.2 to 82.3), p=0.53 on a scale of 0-2100. No clinically or statistically significant differences were seen in any secondary outcomes. INTERPRETATION: In this double-blind, placebo-controlled, randomised trial of outpatients diagnosed with COVID-19, the dietary supplements vitamin C, vitamin D3, vitamin K2 and zinc acetate showed no clinically or statistically significant effects on the documented measures of health compared with a placebo when given for 21 days. Termination due to feasibility limited our ability to demonstrate the efficacy of these supplements for COVID-19. Further research is needed to determine clinical utility. TRIAL REGISTRATION NUMBER: NCT04780061. © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

INTRODUCTION: Coronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction and cardiovascular mortality. Supplementation with vitamin K2 and D3 has been suggested to have a protective role in the progression of CAC. In this study, we will examine the effect of vitamins K2 and D3 in men and women with severe CAC. We hypothesise that supplementation with vitamins K2 and D3 will slow down the calcification process. METHOD AND ANALYSIS: In this multicentre and double-blinded placebo-controlled study, 400 men and women with CAC score≥400 are randomised (1:1) to treatment with vitamin K2 (720 µg/day) and vitamin D3 (25 µg/day) or placebo treatment (no active treatment) for 2 years. Among exclusion criteria are treatment with vitamin K antagonist, coagulation disorders and prior coronary artery disease. To evaluate progression in coronary plaque, a cardiac CT-scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is progression in CAC score from baseline to follow-up at 2 years. Among secondary outcomes are coronary plaque composition and cardiac events. Intention-to-treat principle is used for all analyses. ETHICS AND DISSEMINATION: There are so far no reported adverse effects associated with the use of vitamin K2. The protocol was approved by the Regional Scientific Ethical Committee for Southern Denmark and the Data Protection Agency. It will be conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported. TRIAL REGISTRATION NUMBER: NCT05500443. © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K1 supplementation led to a modest effect on parameters of hip geometry. PURPOSE: Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment. METHODS: We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K1 ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K1 (1 mg/day) arm, vitamin K2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed. RESULTS: Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K1 arm: -1.02[5.07], p = 0.03). CONCLUSION: The addition of vitamin K1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed. TRIAL REGISTRATION: The study was registered at Clinicaltrial.gov:NCT01232647. © 2023. The Auth

BACKGROUND: There is a very high prevalence of subclinical vitamin K deficiency in patients requiring hemodialysis (HD), and this problem is associated with vascular calcification and arterial stiffness. Vitamin K2 (MK-7) supplementation can improve vitamin K status in HD patients. However, the benefits of vitamin K supplementation on arterial stiffness have still not been established. The present study was conducted to evaluate the efficacy of menaquinone-7 (MK-7) supplementation on arterial stiffness in chronic HD patients. METHODS: This open-label multicenter randomized clinical trial was conducted in 96 HD patients who had arterial stiffness, defined by high carotid femoral pulse wave velocity (cfPWV ≥ 10 m/s). The patients were randomly assigned to receive oral MK-7 (375 mcg once daily) for 24 weeks (n = 50) or standard care (control group; n = 46). The change in cfPWV was the primary outcome. RESULTS: Baseline parameters were comparable between the two groups. There was no significant difference in the change in cPWV at 24 weeks between the MK-7 group and standard care [-6.0% (-20.2, 2.3) vs. -6.8% (-19.0, 7.3), p = 0.24]. However, we found that MK-7 significantly decreased cPWV in patients with diabetes [-10.0% (-15.9, -0.8) vs. 3.8% (-5.8, 11.6), p = 0.008]. In addition, the MK-7 group had a lower rate of arterial stiffness progression, compared to controls (30.2% vs. 39.5%, p = 0.37), especially in diabetes patients (21.4% vs. 72.7%, p = 0.01). No serious adverse events were observed during the 24 weeks. CONCLUSION: Vitamin K supplements provided a beneficial impact in lowering the rate of arterial stiffness progression in chronic hemodialysis patients with diabetes. Possible benefits on cardiovascular outcomes require further investigation.

INTRODUCTION: Vitamin K has been suggested to have protective effects against progression of vascular calcification and development of cardiovascular disease (CVD). However, few well-powered randomised controlled trials have examined whether vitamin K prevents progression of vascular calcification in individuals from the general population. The aim of the InterVitaminK trial is to investigate the effects of vitamin K supplementation (menaquinone-7, MK-7) on cardiovascular, metabolic, respiratory and bone health in a general ageing population with detectable vascular calcification. METHODS AND ANALYSIS: The InterVitaminK trial is a randomised, double-blinded, placebo-controlled, trial. A total of 450 men and women aged 52-82 years with detectable coronary artery calcification (CAC), but without manifest CVD, will be randomised (1:1) to receive daily MK-7 (333 µg/day) or placebo tablets for 3 years. Health examinations are scheduled at baseline, and after 1, 2 and 3 years of intervention. Health examinations include cardiac CT scans, measurements of arterial stiffness, blood pressure, lung function, physical function, muscle strength, anthropometric measures, questionnaires on general health and dietary intake, and blood and urine sampling. The primary outcome is progression of CAC from baseline to 3-year follow-up. The trial has 89% power to detect a between-group difference of at least 15%. Secondary outcomes are bone mineral density, pulmonary function and biomarkers of insulin resistance. ETHICS AND DISSEMINATION: Oral MK-7 supplementation is considered safe and has not been found to cause severe adverse events. The Ethical Committee of the Capital Region (H-21033114) approved the protocol. Written informed consent is obtained from all participants and the trial is conducted in accordance with the Declaration of Helsinki II. Both negative and positive findings will be reported. TRIAL REGISTRATION NUMBER: NCT05259046. © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.