Cardiovascular disease (CVD) is one of the most important diseases which controlling its related risk factors, such as metabolic and inflammatory biomarkers, is necessary because of the increased mortality risk of that. The aim of our meta-analysis is to reveal the general effect of vitamin K supplementation on its related risk factors. Original databases were searched using standard keywords to identify all randomized clinical trials (RCTs) investigating the effects of vitamin K on CVD. Pooled weighted mean difference (WMD) and 95 % confidence intervals (95 % CI) were achieved by random-model effect analysis for the best estimation of outcomes. The statistical heterogeneity was determined using the Cochran's Q test and I2 statistics. Seventeen studies were included in this systematic review and meta-analysis. The pooled findings showed that vitamin K supplementation can reduce homeostatic model assessment insulin resistance (HOMA-IR) (WMD: −0⋅24, 95 % CI: −0⋅49, −0⋅02, P = 0⋅047) significantly compared to the placebo group. However, no significant effect was observed on other outcomes. Subgroup analysis showed a significant effect of vitamin K2 supplementation compared to vitamin K1 supplementation on HOMA-IR. However, no significant effect was observed on other variables. Also, subgroup analysis showed no potential effect of vitamin K supplementation on any outcome and omitting any articles did not affect the final results. We demonstrated that supplementation with vitamin K has no effect on anthropometrics indexes, CRP, glucose metabolism, and lipid profile factors except HOMA-IR.

Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19.

Although dietary Ca, vitamin D and vitamin K are nutritional factors associated with osteoporosis, little is known about their effects on incident osteoporotic fractures in East Asian populations. This study aimed to determine whether intakes of these nutrients predict incident osteoporotic fractures. We adopted a cohort study design with a 5-year follow-up. Subjects were 12 794 community-dwelling individuals (6301 men and 6493 women) aged 40–74 years. Dietary intakes of Ca, vitamin D and vitamin K were assessed with a validated FFQ. Covariates were demographic and lifestyle factors. All incident cases of major osteoporotic limb fractures, including those of the distal forearm, neck of humerus, neck or trochanter of femur and lumbar or thoracic spine were collected. Hazard ratios (HR) for energy-adjusted Ca, vitamin D and vitamin K were calculated with the residual method. Mean age was 58·8 (sd 9·3) years. Lower energy-adjusted intakes of Ca and vitamin K in women were associated with higher adjusted HR of total fractures (Pfor trend = 0·005 and 0·08, respectively). When vertebral fracture was the outcome, Pfor trend values for Ca and vitamin K were 0·03 and 0·006, respectively, and HR of the lowest and highest (reference) intake groups were 2·03 (95 % CI 1·08, 3·82) and 2·26 (95 % CI 1·19, 4·26), respectively. In men, there were null associations between incident fractures and each of the three nutrient intakes. Lower intakes of dietary Ca and vitamin K were independent lifestyle-related risk factors for osteoporotic fracture in women but not men. These associations were robust for vertebral fractures, but not for limb fractures.

Both vitamin K and probiotics can promote the bone health of poultry and mammals. The present study was conducted to investigate the interactive effects between vitamin K3 (VK3) and Bacillus subtilis PB6 on the growth performance and tibia quality of broiler chickens with sex separate rearing. In a 3 × 2 × 2 factorial arrangement, 720 one-day-old broiler chicks (Arbor Acres) were assigned to 12 groups with three levels of dietary VK3 (0, 0.5 and 4.0 mg/kg), with or without probiotic supplementation (500 g/t) and with sex separation (male and female). Each group included 3 replicates with 20 birds per replicate. During day 1 to 21, 0.5 and 4.0 mg/kg of VK3 increased average daily gain (ADG) of all birds and average daily feed intake of male birds (P < 0.05). During day 22 to 42, probiotic supplementation increased the ADG of birds (P < 0.05). Probiotic addition increased the weight, length, diameter and strength of tibia in all birds, and 0.5 and 4.0 mg/kg of VK3 increased the tibial breaking strength of male birds at day 21 (P < 0.05). Vitamin K3 and probiotic synergistically increased tibial breaking strength at day 42 and ash content at day 21 (P < 0.05). Three factors exhibited interactive effects on the chemical composition of tibia at day 42, and female birds fed 4 mg/kg of VK3 and probiotic had the highest contents of ash, calcium and phosphorus (P < 0.05). Bacillus subtilis PB6 increased the serum phosphorus level of male birds at day 21 and serum calcium level of female ones at day 42 (P < 0.05). At day 21, in the probiotic-supplemented birds, serum osteocalcin (OCN) and bone-specific alkaline phosphatase (BALP) were increased by 0 and 4.0 mg/kg of VK3, respectively (P < 0.05). Probiotic increased serum OCN and cooperated with VK3 to increase the serum BALP at day 42 (P < 0.05). Vitamin K3 and probiotic synergistically down-regulated the mRNA expression of Runt-related transcription factor 2 and OCN at day 21 (P < 0.05). Vitamin K3 down-regulated the alkaline phosphatase (liver/bone/kidney) expression in male birds at day 21 and 42, but probiotic up-regulated the expression of these genes at day 42 (P < 0.05). In conclusion, VK3 and B. subtilis PB6 promoted the growth performance of broilers during starter and grower phases, respectively. They synergistically improved the physical and chemical traits of tibias, especially in grower phase, by modulating calcium and phosphorus metabolism as well as osteogenic gene expression.

The role of fat-soluble vitamins in the pathology of type 2 diabetes needs further research. Possible protective effects could be expected for vitamins A and E via their antioxidant properties, vitamin K via its modulating effects on cytokines and insulin resistance and vitamin D via the enhancement of insulin sensitivity. However, the evidence on association between fat-soluble vitamins from diet and risk of diabetes is limited. Therefore, among 19 168 healthy Japanese of both sexes aged 40–79 years, we used the logistic regression analyses to examine the prospective association between FFQ-estimated dietary fat-soluble vitamins (A, K, E and D) and the risk of type 2 diabetes incident over a 5-year period. During this 5-year period, 494 new cases of diabetes were self-reported. Vitamins K and E from diet were associated with lowered risk of incident diabetes, whereas no associations with dietary intake of vitamin A or D were observed. The multivariable OR in the highest v. lowest quartiles of intakes were 0·71 (95 % CI 0·54, 0·93, Ptrend=0·01) for vitamin K and 0·72 (95 % CI 0·55, 0·95, Ptrend=0·02) for vitamin E. Mutual adjustment for dietary intake of these vitamins did not change the association. There were no interactions with sex, age, smoking status, BMI or having a family history of diabetes, P were >0·10. In conclusion, higher dietary intake of fat-soluble vitamins K and E, but not vitamin A or D, were associated with lowered risk of type 2 diabetes among Japanese population.

Vitamin K is considered to be involved in the pathological mechanisms of coronary artery calcification (CAC). Correlation between CAC and plasma vitamin K levels was studied. A total of 103 patients, with at least one coronary risk factor, were studied. CAC was measured using 64-slice multislice computed tomography (MSCT) and divided into three groups: none (CAC score = 0; n 25), mild to moderate (0 < CAC score < 400; n 52) and severe (CAC score > 400; n 26). Phylloquinone (PK) and menaquinone (MK)-4 and MK-7 were measured by HPLC-tandem MS. Mean age of patients was 64 (sd 13) years, of which 57 % were male. Median CAC score was 57·2. Median levels of PK, MK-4 and MK-7 were 1·33, 0 and 6·99 ng/ml, showing that MK-7 was the dominant vitamin K in this population. MK-7 showed a significant inverse correlation with uncarboxylated osteocalcin (ucOC, P = 0·014), protein induced by vitamin K absence of antagonist-2 (PIVKA-2, P = 0·013), intact parathyroid hormone (P = 0·007) and bone-specific alkaline phosphatase (P = 0·018). CAC showed an inverse correlation with total circulating uncarboxylated matrix Gla protein (t-ucMGP, P = 0·018) and Hb (P = 0·05), and a positive correlation with age (P < 0·001), creatinine, collagen type 1 cross-linked N-terminal telopeptide (NTX, P = 0·03), pulse wave velocity (P < 0·001) and osteoprotegerin (P < 0·001). However, CAC did not have a significant correlation with plasma levels of PK, MK-4 or MK-7. In conclusion, plasma MK-7, MK-4 or PK level did not show significant correlation with CAC despite the association between plasma vitamin K levels and vitamin K-dependent proteins such as ucOC or PIVKA-2.

Recent reports have attributed the potential health benefits of vitamin K beyond its function to activate hepatic coagulation factors. Moreover, several studies have suggested that menaquinones, also known as vitamin K2, may be more effective in activating extra-hepatic vitamin K-dependent proteins than phylloquinone, also known as vitamin K1. Nevertheless, present dietary reference values (DRV) for vitamin K are exclusively based on phylloquinone, and its function in coagulation. The present review describes the current knowledge on menaquinones based on the following criteria for setting DRV: optimal dietary intake; nutrient amount required to prevent deficiency, maintain optimal body stores and/or prevent chronic disease; factors influencing requirements such as absorption, metabolism, age and sex. Dietary intake of menaquinones accounts for up to 25 % of total vitamin K intake and contributes to the biological functions of vitamin K. However, menaquinones are different from phylloquinone with respect to their chemical structure and pharmacokinetics, which affects bioavailability, metabolism and perhaps impact on health outcomes. There are significant gaps in the current knowledge on menaquinones based on the criteria for setting DRV. Therefore, we conclude that further investigations are needed to establish how differences among the vitamin K forms may influence tissue specificities and their role in human health. However, there is merit for considering both menaquinones and phylloquinone when developing future recommendations for vitamin K intake.

Osteocalcin (OC) is a vitamin K-dependent protein found in bone and in circulation. High serum γ-carboxylated OC reflects a high, and high uncarboxylated OC (ucOC) reflects a low vitamin K status. A revolutionary hypothesis is that ucOC acts as a hormone improving glucose handling and reducing fat mass. The objective was to test the logical extrapolation of the ucOC hormone hypothesis to humans that elevated ucOC is associated with higher body weight, BMI and fat mass. In a cross-sectional analysis, the associations of vitamin K status with circulating adiponectin and body composition were investigated in 244 postmenopausal women (study I). The effects of vitamin K treatment on adiponectin, body weight and BMI were investigated in archived samples from forty-two young men and women who received varying doses of menaquinone-7 during 12 weeks (study II) and from a cohort of 164 postmenopausal women who participated in a 3-year placebo-controlled trial on 45 mg menaquinone-4 (MK-4) (study III). No association was found between vitamin K status and circulating adiponectin before or after vitamin K supplementation. A higher carboxylation of OC was significantly correlated with lower body weight, BMI and fat mass of the trunk. Women taking MK-4 maintained their baseline body weight and BMI, whereas women taking placebo showed significant increases in both indices. These findings demonstrate that a high vitamin K status of bone has no effect on circulating adiponectin in healthy people and long-term vitamin K supplementation does not increase weight in healthy postmenopausal women.

There is some evidence for a nutritional interaction between vitamin D and vitamin K status. We have recently reported that serum percentage undercarboxylated osteocalcin (%ucOC; a marker of vitamin K status) was inversely correlated with serum 25-hydroxyvitamin D (25(OH)D) concentration (reflective of vitamin D status) in healthy Danish girls (aged 11–12 years), in line with a similar relationship reported in elderly women. While the causal nature of the relationship between vitamin D status and serum %ucOC has been tested in studies of elderly women, it has not been investigated in children. The objective of the present study was to test the hypothesis that improving vitamin D status significantly lowers serum %ucOC. Serum samples from sixty-seven healthy Danish girls (aged 11–12 years), who participated in a 12-month double-blind, placebo-controlled, vitamin D3 intervention trial were used for the present study. These girls were a subset of subjects which began and finished the intervention during wintertime, thus avoiding the influence of seasonality on vitamin D status. A total of thirty-three and thirty-four of the girls had been randomised to treatment with 10 μg vitamin D3 per d and placebo, respectively, for 12 months. Total osteocalcin and the fraction of ucOC in serum (via enzyme-immunoassay) as well as serum 25(OH)D (via HPLC) were assessed at baseline and end-point. Vitamin D3 supplementation significantly increased serum 25(OH)D (21·6 %; P < 0·002) but had no effect on serum %ucOC (P>0·8). In conclusion, the findings of the present intervention study in young girls suggest that vitamin D supplementation does not affect serum %ucOC, a marker of vitamin K status.

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 μg 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.

Nutrition is important to bone health, and a number of minerals and vitamins have been identified as playing a potential role in the prevention of bone diseases, particularly osteoporosis. Despite this, there is currently no consensus on maximum levels to allow in food or as dietary supplements. The benefits of supplementation of populations at risk of osteoporosis with Ca and vitamin D are well established. Prolonged supplementation of Ca and vitamin D in elderly has been shown to prevent bone loss, and in some intervention studies to prevent fragility fractures. Although P is essential to bone health, the average intake is considered to be more than sufficient and supplementation could raise intake to adverse levels. The role of vitamin K in bone health is less well defined, though it may enhance the actions of Ca and vitamin D. Sr administered in pharmacological doses as the ranelate salt was shown to prevent fragility fractures in postmenopausal osteoporosis. However, there is no hard evidence that supplementation with Sr salts would be beneficial in the general population. Mg is a nutrient implicated in bone quality, but the benefit of supplementation via foodstuffs remains to be established. A consensus on dietary supplementation for bone health should balance the risks, for example, exposure of vulnerable populations to values close to maximal tolerated doses, against evidence for benefits from randomised clinical trials, such as those for Ca and vitamin D. Feedback from community studies should direct further investigations and help formulate a consensus on dietary supplementation for bone health.

Vitamin K acts as a cofactor during the γ-carboxylation of vitamin K-dependent proteins. Undercarboxylated osteocalcin (ucOC) is a suggested biomarker of vitamin K status. The +2255 polymorphism of the vitamin K epoxide reductase gene (VKORC1) was shown to be associated with the recycling rate of the active form of vitamin K. We investigated the association between dietary vitamin K intake and serum ucOC and hypothesized that this association might vary by VKORC1 genotype. ucOC and total intact osteocalcin (iOC) concentrations were quantified using specific ELISA tests in serum samples of 548 male and female participants (aged 18–81 years) of the Bavarian Food Consumption Survey II. ucOC was expressed relative to iOC (ucOC/iOC ratio). Dietary intake of vitamin K (phylloquinone and menaquinones) was estimated from three 24 h dietary recalls using previously published food composition data. The association between dietary vitamin K intake and ucOC/iOC ratio was analysed using linear and non-linear regression models. Median intakes of phylloquinone/menaquinones were 83·4/37·6 μg/d in men and 79·6/29·8 μg/d in women, respectively. As expected, vitamin K intake was significantly inversely associated with the ucOC/iOC ratio. The ucOC/iOC ratio differed significantly across variants of the +2255 polymorphism in the VKORC1 gene. Stratification by VKORC1+2255 genotype revealed that only in carriers of the GG genotype (39 % of all participants) did the ucOC/iOC ratio significantly decrease with increasing intake of vitamin K. Thus, the results show that the inverse association between dietary vitamin K intake and serum ucOC depends on a functionally relevant allelic variant of the VKORC1 gene.

In adult bone, vitamin K contributes to bone health, probably through its role as co-factor in the carboxylation of osteocalcin. In children, the significance of vitamin K in bone-mass acquisition is less well known. The objective of this longitudinal study was to determine whether biochemical indicators of vitamin K status are related to (gains in) bone mineral content (BMC) and markers of bone metabolism in peripubertal children. In 307 healthy children (mean age 11·2 years), BMC of the total body, lumbar spine and femoral neck was determined at baseline and 2 years later. Vitamin K status (ratio of undercarboxylated (ucOC) to carboxylated (cOC) fractions of osteocalcin; UCR) was also measured at both time points. Markers of bone metabolism, sex steroids, vitamin D status and growth hormones were measured at baseline only. Large variations in the levels of the UCR were found at both time-points, indicating a substantial interindividual difference in vitamin K status. Improvement of vitamin K status over 2 years (n 281 children) was associated with a marked increase in total body BMC (r − 49·1, P < 0·001). The UCR was associated with pubertal stage, markers of bone metabolism, sex hormones and vitamin D status. A better vitamin K status was associated with more pronounced increase in bone mass in healthy peripubertal children. In order to determine the significance of these findings for childhood bone health, additional paediatric studies are needed.

Prothrombin complex concentrates are haemostatic blood products containing four vitamin K-dependent clotting factors (II, VII, IX and X). They are a useful, reliable and fast alternative to fresh frozen plasma for the reversal of the effects of oral anticoagulant treatments (vitamin K antagonists). They are sometimes used for factor II or factor X replacement in patients with congenital or acquired deficiencies. They are widely prescribed in Europe. Several retrospective and prospective studies have demonstrated their efficacy in normalizing coagulation and in helping to control life-threatening bleeding. Few side-effects, mainly thromboembolic events, have been reported. The link between these events and prothrombin complex concentrate infusion has, however, often been brought into question. The use of prothrombin complex concentrates in new promising indications such as the management of massive bleeding requires prospective studies providing a high level of evidence in a high-risk setting.

Throughout the life cycle the skeleton requires optimum development and maintenance of its integrity to prevent fracture. Bones break because the loads placed on them exceed the ability of the bone to absorb the energy involved. It is now estimated that one in three women and one in twelve men aged >55 years will suffer from osteoporosis in their lifetime and at a cost in the UK of >£1·7×109 per year. The pathogenesis of osteoporosis is multifactorial. Both the development of peak bone mass and the rate of bone loss are determined by key endogenous and exogenous factors. Ca supplements appear to be effective in reducing bone loss in women late post menopause (>5 years post menopause), particularly in those with low habitual Ca intake (<400 mg/d). In women early post menopause (<5 years post menopause) who are not vitamin D deficient, Ca supplementation has little effect on bone mineral density. However, supplementation with vitamin D and Ca has been shown to reduce fracture rates in the institutionalised elderly, but there remains controversy as to whether supplementation is effective in reducing fracture in free-living populations. Re-defining vitamin D requirements in the UK is needed since there is evidence of extensive hypovitaminosis D in the UK. Low vitamin D status is associated with an increased risk of falling and a variety of other health outcomes and is an area that requires urgent attention. The role of other micronutrients on bone remains to be fully defined, although there are promising data in the literature for a clear link between vitamin K nutrition and skeletal integrity, including fracture reduction.

The UK Food Standards Agency convened an international group of expert scientists to review the Agency-funded projects on diet and bone health in the context of developments in the field as a whole. The potential benefits of fruit and vegetables, vitamin K, early-life nutrition and vitamin D on bone health were presented and reviewed. The workshop reached two conclusions which have public health implications. First, that promoting a diet rich in fruit and vegetable intakes might be beneficial to bone health and would be very unlikely to produce adverse consequences on bone health. The mechanism(s) for any effect of fruit and vegetables remains unknown, but the results from these projects did not support the postulated acid–base balance hypothesis. Secondly, increased dietary consumption of vitamin K may contribute to bone health, possibly through its ability to increase the γ-carboxylation status of bone proteins such as osteocalcin. A supplementation trial comparing vitamin K supplementation with Ca and vitamin D showed an additional effect of vitamin K against baseline levels of bone mineral density, but the benefit was only seen at one bone site. The major research gap identified was the need to investigate vitamin D status to define deficiency, insufficiency and depletion across age and ethnic groups in relation to bone health.

Recent cross-sectional data suggest that better vitamin K status in young girls (aged 3–16 years) is associated with decreased bone turnover, even though it is not associated with bone mineral content (BMC). The objective of the present study was to investigate the relationship between serum percentage of undercarboxylated osteocalcin (%ucOC), as an index of vitamin K status, and BMC and biochemical indices of bone turnover in peri-pubertal Danish girls. This peri-pubertal stage is a dynamic period of bone development, and as such, may represent an important window of opportunity for vitamin K status to modulate childhood bone health. Serum %ucOC and serum 25-hydroxyvitamin D (25 (OH) D) were measured at baseline in a study of 223 healthy girls aged 11–12 years. Urinary pyridinium crosslinks of collagen and serum total osteocalcin as markers of bone resorption and formation, respectively, as well as BMC (total body and lumbar spine) were also measured. Serum %ucOC (median 21·9 %) was not associated with markers of bone resorption or with total osteocalcin. Serum %ucOC was inversely correlated with serum 25 (OH) D (r − 0·143; P < 0·05). Serum %ucOC was negatively associated with BMC of the total body (β − 0·045; P < 0·001) and lumbar spine (β − 0·055; P < 0·05), after adjustment for potential confounders including vitamin D status. Better vitamin K status was associated with increased BMC, but not bone turnover, in healthy peri-pubertal Danish girls. There is a need for well-designed, randomized phylloquinone supplementation trials in children and adolescents to confirm epidemiological findings of an association between vitamin K status and bone health.

Vitamin K, originally recognised as a factor required for normal blood coagulation, is now receiving more attention in relation to its role in bone metabolism. Vitamin K is a coenzyme for glutamate carboxylase, which mediates the conversion of glutamate to γ-carboxyglutamate (Gla). Gla residues attract Ca2+ and incorporate these ions into the hydroxyapatite crystals. There are at least three Gla proteins associated with bone tissue, of which osteocalcin is the most abundant and best known. Osteocalcin is the major non-collagenous protein incorporated in bone matrix during bone formation. However, approximately 30% of the newly-produced osteocalcin stays in the circulation where it may be used as an indicator of bone formation. Vitamin K deficiency results in an increase in undercarboxylated osteocalcin, a protein with low biological activity. Several studies have demonstrated that low dietary vitamin K intake is associated with low bone mineral density or increased fractures. Additionally, vitamin K supplementation has been shown to reduce undercarboxylated osteocalcin and improve the bone turnover profile. Some studies have indicated that high levels of undercarboxylated osteocalcin (as a result of low vitamin K intake?) are associated with low bone mineral density and increased hip fracture. The current dietary recommendation for vitamin K is 1 μ/kg body weight per d, based on saturation of the coagulation system. The daily dietary vitamin K intake is estimated to be in the range 124–375 μg/d in a European population. Thus, a deficiency based on the hepatic coagulation system would be unusual, but recent data suggest that the requirement in relation to bone health might be higher.