Vitamin K3 inhibits the conversion of benzo(a)pyrene to its more polar metabolites in an in vitro rat liver microsomal system. Vitamin K3 also inhibits benzo(a)pyrene metabolism in rat liver fragments and reduces its mutagenicity in the Ames test. Higher concentrations of vitamin K3 are required to comparably reduce benzo(a)pyrene metabolism when the microsomal system has been induced with 3-methylcholanthrene. High pressure liquid chromatography analysis of the products of benzo(a)pyrene metabolism shows a uniform reduction of all the metabolic products. When tumors were induced in ICR/Ha female mice by the intraperitoneal injection of benzo(a)pyrene, those mice given vitamin K3 before or both before and after benzo(a)pyrene had a slower rate of tumor appearance and tumor death rate as compared with those receiving benzo(a)pyrene alone. However, vitamin K1 increased the rate of tumor death while vitaminK deprivation and warfarin decreased the rate of tumor appearance and death in benzo(a)pyrene-injected mice. These studies indicate that vitamin K3 is an inhibitor of aryl hydrocarbon hydroxylase and reduces the carcinogenic and mutagenic metabolites in vitro, and inhibits benzo(a)pyrene tumorigenesis in vivo. That vitamin K1 enhances the benzo(a)pyrene effect while warfarin and vitaminK deficiency inhibit benzo(a)pyrene tumorigenesis indicates that vitamin K1, vitaminK deprivation, or possibly blockade of its metabolic cycle also modulates benzo(a)pyrene metabolism in vivo but by a mechanism or at a […]
There was no direct association between vitaminK levels and bone turnover or bone density. This may reflect several confounding factors, such as the im- pact of the dietary intake in the previous 24 hours on serum vitaminK levels. Another limitation was the fact that many children (33%) had undetectable cir- culating vitaminK 1 levels, which reduced the statis- tical power of finding an association. An intervention study is required to show definitively whether there is a correlation between serum vitaminK levels and bone turnover. VitaminK levels showed a significant negative correlation with levels of Glu-OC, the pre- cursor and presumed inactive form of OC. The latter was correlated significantly with levels of bone turn- over markers, as were levels of total OC (71% of which was in the undercarboxylated form). In- creased skeletal turnover is associated with rapid bone loss. 29 Through its role in the carboxylation of
BACKGROUND AND OBJECTIVES: Based on a high incidence of VitaminK deficiency bleeding (VKDB) in breastfed infants with thus far unrecognized cholestasis, such as biliary atresia (BA), the Dutch regimen to prevent VKDB in breastfed infants was changed from a daily oral dosage of 25 μg to 150 μg vitaminK. Infants continued to receive 1 mg of vitaminK orally at birth. We compared the efficacy of the 150-μg regimen with the 25-μg regimen and with the Danish regimen of a single intramuscular (IM) dose of 2 mg vitaminK at birth.
The mechanism of warfarin helps us see clearly how it inhibits further coagulation of blood but it also shows its interference in the mechanism of vitaminK. VitaminK antagonists, also known as oralanticoagulants (OACs), are widely used for the treatment and prophylaxis of thromboebolic diseases. Short- term OAC treatment is applied often after deep venous thrombosis, while atrialfibrillation or after prosthetic heart valve implantation require long term treatment (Block, 2001). The below Figure 1 indicated; VitaminK is decarboxylated in the process and needs to be recycled. The enzyme VitaminK- epoxide reductase (VKORC) is essential in this cycle. It is this re-carboxylation by VKORC that is inhibited by Warfarin. Carboxylation of glutamate residues to γ-carboxyglutamates (Gla) on the N-terminal regions of vitaminK–dependent proteins requires vitaminK as a cofactor (Whitlon et al., 1978). Formation of coagulation factors II, VII, IX, and X is hence blocked by blocking this process. When the vitaminK conversion cycle is inhibited, warfarin will influence hepatic production of partially decarboxylated proteins with greatly decreased coagulant activity (Friedman et al., 1977; Malhotra et al., 1985). Carboxylation promotes the binding of phospholipid surfaces to the vitaminK–dependent coagulation factors, thereby accelerating blood coagulation (Nelsestuen, 1976).
patient-driven end of the spectrum, the physician presents factual information and available options, leaving parents to decide. This would be appropriate when there is more than one option with comparable effectiveness, not the case in our vitaminK scenario. At the physician- driven end of the spectrum, care is provided without discussion, as in life-threatening situations. Our vitaminK scenario falls somewhere in the middle, which leads to the next question: When a family declines the recommended care, how far can a clinician ethically go to promote a low-risk option with clear health beneﬁt?
The purpose of clinical records is to document patient care, and variation in recording practices by policy type, especially if vitaminK was not given, reflects this. There have been changes over the years, but, for all time periods, if no written record was made the most likely reason is that vitaminK was not given. Table 4 Implementation practices of official policies on vitaminK administration in midwives’ previous jobs (jobs held before 1990). Values are percentages (numbers)
In conclusion, this systematic review as well as meta-analysis suggests a lack of effect of vitaminK supplementation on insulin sensitivity. Given the limited evidence available and the heterogeneity in the study results, further well-designed, large sample size randomized controlled trials are warranted. Different forms and doses of vitaminK should be explored in various populations, and other surrogate markers for insulin sensitivity should be measured to better establish any ben- eficial effects and their clinical relevance.
Danish study found that AF patients with non-end-stage CKD or end-stage CKD had an increased risk of stroke/ TE of 50 and 83%, respectively, compared to patients without renal disease . Furthermore, the presence of both disorders increases the risk of bleeding , causing treatment for such patients to be complicated. Oral anticoagulation (OAC) reduces risk of stroke/TE and all- cause mortality in the general AF population , and AF patients at high stroke risk are recommended lifelong therapy with a vitamin-K antagonist (VKA) or non-VKA OAC (NOAC). NOACs have proven superior or nonin- ferior to VKA in AF patients in regards of stroke and TE
MK-4 is primarily formed from dietary phylloquinone, independent of intestinal bacteria, although the extent of this conversion varies among different tissues . We found MK-4 concentrations to be lowest in the testis, kid- ney, and brain of vitamin E-supplemented rats. For rea- sons for which we currently do not have an explanation, the ratio of phylloquinone to MK-4 in the brain of rats in our study, regardless of their diet group, was higher com- pared to other studies in which the MK-4 is the predomi- nant form [24,28]. However, the amounts and ratios of phylloquinone to MK-4 appear to vary with age and gen- der , which may in part explain the differences. MK-4 was very low and/or non-detectable in plasma and liver in all three diet groups, with no measurable differences in response to vitamin E status. This observation is consist- ent with the report by Davidson et al.  that hepatic cell lines are less active in converting phylloquinone to MK-4 than renal cell lines. In contrast to phylloquinone, there were no differences in MK-4 content of the spleen between the three vitamin E diet groups. As the mecha- nism by which phylloquinone is converted to MK-4 is unknown, we cannot readily speculate how vitamin E supplementation influences the concentrations of these forms of vitaminK in extrahepatic tissue. While it is plau- sible that less MK-4 is produced because vitamin E supple- mentation reduces phylloquinone as a substrate in the extrahepatic tissue, vitamin E may also decrease MK-4 concentrations independently of phylloquinone.
One of the most important potential ef- fects of VKORC1 regulation by miRNAs may be the consequences on oral antico- agulant therapies that target this protein. Our results show that miR-133a inversely correlates with VKORC1 mRNA in liver samples, regardless of the VKORC1 geno- type considered. Although VKORC1 mRNA levels are crucial to vitaminK an- tagonist dose (1), the potential role of the VKORC1 regulation by miRNAs on anti- coagulant therapy should be further con- firmed. Moreover, the relevance that inter-individual variations of miRNA lev- els may have for anticoagulant drug re- quirement is another aspect that deserves further research. Finally, VKORC1 is not only expressed in liver but also in other tissues such as endothelium and heart. The involvement of the VKORC1 γ-car-
with available four-factor PCCs) in combination with 10 mg of vitaminK [9,10]. Use of the recommended single- regimen dose has not yet become routine practice, as shown by the fact that only 205 patients (25%) received a dose of 25 IU/kg in our study. Guidelines also strongly recommend measuring the INR after reversal to control the degree of reversal and further normalize the coagula- tion 30 minutes after the first administration if the PCC dose was insufficient . Unfortunately, post-reversal INR was obtained within less than one hour in only 7% of our patients, underscoring the need for improved guideline adherence. In our study, bedside INR monitor- ing was never used. Adoption of this technique might help increase the rate of post-reversal INR measurement within one hour after treatment administration.
The systems involved in vitaminK-dependent carboxylation and vitaminK metabolism have been extensively studied in rat liver. To determine how clinically applicable this information is, similar in vitro studies were completed using human liver. One major difference exists in the pathways that provide reduced vitamin K1 cofactor for the carboxylation reaction. The coumarin-sensitive DT-diaphorase (EC.126.96.36.199) in human liver appears to play a relatively minor role in the dehydrogenase pathway. However, similar to rat liver, the human liver contains a warfarin-insensitive enzyme in this dehydrogenase pathway. The data suggest that this enzyme is responsible for the antidotic effect of vitamin K1 in cases of coumarin intoxication. Human vitaminK epoxide reductase, which constitutes the other pathway for vitamin K1 reduction, has kinetic and enzymological characteristics that are very similar to the rat enzyme. This enzyme exhibited similar activity in rat and human microsomes. Initial velocities for vitamin K1 epoxide reduction in rat and human microsomes were 20 and 32 pmol/mg X min, respectively. The human enzyme is highly sensitive to warfarin inhibition. The mechanism for this inhibition appears to be similar to what has been proposed for the rat enzyme. Also, a vitaminK-dependent carboxylation system is described that allows both pathways to support the carboxylation reaction with reduced vitamin K1 cofactor. The effect of warfarin on this in vitro […]
Low vitaminK status (indicated by undercarboxylated MGP) is associated with increased vascular calci ﬁ cations, and these levels can be improved by effective vitaminK supplementation 28–32 It was long believed that vitaminK was only involved in forming coagulation factors (ie, maintaining haemostasis). However, other vitamin-K dependent proteins (containing γ -carboxyglutamate or Gla) are dependent on vitamin-K carboxylation for func- tionality. 33 VitaminK acts as a cofactor in the conversion of glutamate into Gla. Gla-containing proteins (MGP and osteocalcin) regulate many anticalci ﬁ cation and bone-forming processes in the body, which are depend- ent on vitaminK in order to be produced. Low levels of vitaminK impair activation of osteocalcin and decrease the activity of osteoblasts (cells important for building bone). 33 34 Thus, vitaminK is vital to the functionality of proteins such as osteocalcin (important for building bone), (MGP, the most potent arterial calci ﬁ cation inhibitor known) and the growth-arrest sequence-6 protein (Gas6, involved in cell growth regulation 35