scholarly journals Vitamin K2 Needs an RDI Separate from Vitamin K1

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1852 ◽  
Author(s):  
Asim Cengiz Akbulut ◽  
Angelina Pavlic ◽  
Ploingarm Petsophonsakul ◽  
Maurice Halder ◽  
Katarzyna Maresz ◽  
...  

Vitamin K and its essential role in coagulation (vitamin K [Koagulation]) have been well established and accepted the world over. Many countries have a Recommended Daily Intake (RDI) for vitamin K based on early research, and its necessary role in the activation of vitamin K-dependent coagulation proteins is known. In the past few decades, the role of vitamin K-dependent proteins in processes beyond coagulation has been discovered. Various isoforms of vitamin K have been identified, and vitamin K2 specifically has been highlighted for its long half-life and extrahepatic activity, whereas the dietary form vitamin K1 has a shorter half-life. In this review, we highlight the specific activity of vitamin K2 based upon proposed frameworks necessary for a bioactive substance to be recommended for an RDI. Vitamin K2 meets all these criteria and should be considered for a specific dietary recommendation intake.

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 965 ◽  
Author(s):  
Toshiro Sato ◽  
Naoko Inaba ◽  
Takatoshi Yamashita

Vitamin K acts as a cofactor and is required for post-translational γ-carboxylation of vitamin K-dependent proteins (VKDP). The current recommended daily intake (RDI) of vitamin K in most countries has been established based on normal coagulation requirements. Vitamin K1 and menaquinone (MK)-4 has been shown to decrease osteocalcin (OC) γ-carboxylation at RDI levels. Among the several vitamin K homologs, only MK-7 (vitamin K2) can promote γ-carboxylation of extrahepatic VKDPs, OC, and the matrix Gla protein at a nutritional dose around RDI. MK-7 has higher efficacy due to its higher bioavailability and longer half-life than other vitamin K homologs. As vitamin K1, MK-4, and MK-7 have distinct bioactivities, their RDIs should be established based on their relative activities. MK-7 increases bone mineral density and promotes bone quality and strength. Collagen production, and thus, bone quality may be affected by MK-7 or MK-4 converted from MK-7. In this review, we comprehensively discuss the various properties of MK-7.


2014 ◽  
Vol 29 (3) ◽  
pp. 172-177 ◽  
Author(s):  
Margueritta El Asmar ◽  
Joseph Naoum ◽  
Elias Arbid

2009 ◽  
Vol 297 (6) ◽  
pp. C1358-C1367 ◽  
Author(s):  
Gerald J. Atkins ◽  
Katie J. Welldon ◽  
Asiri R. Wijenayaka ◽  
Lynda F. Bonewald ◽  
David M. Findlay

The vitamin K family members phylloquinone (vitamin K1) and the menaquinones (vitamin K2) are under study for their roles in bone metabolism and as potential therapeutic agents for skeletal diseases. We have investigated the effects of two naturally occurring homologs, phytonadione (vitamin K1) and menatetrenone (vitamin K2), and those of the synthetic vitamin K, menadione (vitamin K3), on human primary osteoblasts. All homologs promoted in vitro mineralization by these cells. Vitamin K1-induced mineralization was highly sensitive to warfarin, whereas that induced by vitamins K2 and K3 was less sensitive, implying that γ-carboxylation and other mechanisms, possibly genomic actions through activation of the steroid xenobiotic receptor, are involved in the effect. The positive effect on mineralization was associated with decreased matrix synthesis, evidenced by a decrease from control in expression of type I collagen mRNA, implying a maturational effect. Incubation in the presence of vitamin K2 or K3 in a three-dimensional type I collagen gel culture system resulted in increased numbers of cells with elongated cytoplasmic processes resembling osteocytes. This effect was not warfarin sensitive. Addition of calcein to vitamin K-treated cells revealed vitamin K-dependent deposition of mineral associated with cell processes. These effects are consistent with vitamin K promoting the osteoblast-to-osteocyte transition in humans. To test whether vitamin K may also act on mature osteocytes, we tested the effects of vitamin K on MLO-Y4 cells. Vitamin K reduced receptor activator of NF-κB ligand expression relative to osteoprotegerin by MLO-Y4 cells, an effect also seen in human cultures. Together, our findings suggest that vitamin K promotes the osteoblast-to-osteocyte transition, at the same time decreasing the osteoclastogenic potential of these cells. These may be mechanisms by which vitamin K optimizes bone formation and integrity in vivo and may help explain the net positive effect of vitamin K on bone formation.


BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e035953
Author(s):  
Teresa R Haugsgjerd ◽  
Grace M Egeland ◽  
Ottar K Nygård ◽  
Kathrine J Vinknes ◽  
Gerhard Sulo ◽  
...  

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 inconclusive.DesignProspective cohort study.SettingWe followed participants in the community-based Hordaland Health Study from 1997 - 1999 through 2009 to evaluate associations between intake of vitamin K and incident (new onset) CHD. Baseline diet was assessed by a past-year food frequency questionnaire. Energy-adjusted residuals of vitamin K1 and vitamin K2 intakes were categorised into quartiles.Participants2987 Norwegian men and women, age 46–49 years.MethodsInformation on incident CHD events was obtained from the nationwide Cardiovascular Disease in Norway (CVDNOR) Project. Multivariable Cox regression estimated HRs and 95% CIs with test for linear trends across quartiles. Analyses were adjusted for age, sex, total energy intake, physical activity, smoking and education. A third model further adjusted K1 intake for energy-adjusted fibre and folate, while K2 intake was adjusted for energy-adjusted saturated fatty acids and calcium.ResultsDuring a median follow-up time of 11 years, we documented 112 incident CHD cases. In the adjusted analyses, there was no association between intake of vitamin K1 and CHD (HRQ4vsQ1 = 0.92 (95% CI 0.54 to 1.57), p for trend 0.64), while there was a lower risk of CHD associated with higher intake of energy-adjusted vitamin K2 (HRQ4vsQ1 = 0.52 (0.29 to 0.94), p for trend 0.03). Further adjustment for potential dietary confounders did not materially change the association for K1, while the association for K2 was slightly attenuated (HRQ4vsQ1 = 0.58 (0.28 to 1.19)).ConclusionsA higher intake of vitamin K2 was associated with lower risk of CHD, while there was no association between intake of vitamin K1 and CHD.Trial registration numberNCT03013725


2018 ◽  
Vol 9 (1) ◽  
pp. 450-462 ◽  
Author(s):  
Anjum Dihingia ◽  
Dibyajyoti Ozah ◽  
Pranab Kumar Baruah ◽  
Jatin Kalita ◽  
Prasenjit Manna

There is no previous study that has examined the relationship between circulating vitamin K1 (VK1) and vascular inflammation in type 2 diabetes (T2D).


1988 ◽  
Vol 08 (01) ◽  
pp. 8-17 ◽  
Author(s):  
K. Andrassy ◽  
H. Bechtold
Keyword(s):  

ZusammenfassungAus den vorliegenden Untersuchungen und aus den Mitteilungen der Literatur läßt sich auf die Bedeutung folgender zwei Faktoren für die Genese der Cephalosporin-induzierten HP schlieβen:1. Latenter Vitamin-K-Mangelzustand des Organismus durch fehlende oder reduzierte exogene Vitamin-K-Zufuhr (z.B. bei ausschlieβlich parenteraler Ernährung) und möglicherweise durch Unterdrückung der Vitamin-K2-produzie-renden (Dünn-)Darmflora.2. Kumarinartige Hemmung des Vit-amin-K1Stoffwechsels in der Leber durch bestimmte Cephalosporine (z.B. NMTT-Cephalosporine).Das Zusammenwirken dieser Faktoren führt funktionell zu einem manifesten Vitamin-K-Mangelzustand, erkenntlich an einem Abfall der Vitamin-K-abhängigen Gerinnungsfaktoren. Aufgrund dieses Mechanismus ist es verständlich, daß die Cephalosporin-induzierte HP durch prophylaktische Vitamin-K1Gaben verhindert (ca. 10 mg Vitamin K1 pro Woche) bzw. eine manifeste HP korrigiert werden kann.Der Vollständigkeit halber sei auf die hier nicht näher erläuterten Anta-bus®-ähnlichen Reaktionen nach Alkoholzufuhr hingewiesen, die - in Analogie zu der kumarinartigen Hemmung des Vitamin-K1Stoffwechsels -ebenfalls die Gruppe der NMTT- und MTD-Cephalosporine betreffen und durch entsprechende Alkoholkarenz vermeidbar sind (60).


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4425-4425
Author(s):  
Abhinav B. Chandra ◽  
Nanda K. Methuku ◽  
Yiwu Huang

Abstract Abstract 4425 Case description– A 47 year old man presented to emergency room due to back pain, hematuria and persistent gum bleed for more than one week after dental procedure. He had also noted easy bruisability for the last two months. He was found to have elevated PT and PTT. On admission, his PT was >120 sec with INR > 9.9 and his PTT > 100 sec. The abnormal PT and PTT were completed corrected by the addition of normal plasma on mixing study. Factor assay showed factor II level 19%, factor VII 1.5%, factor IX 7.4%, factor × 15%, factor V 87%, factor VIII 140%, factor XI 96%, and factor XII 49%. Since he had no other medical conditions and no history of hepatic dysfunction that would cause his coagulopathy, superwarfarin toxicity was suspected. Blood toxicology screen was positive for superwarfarin compound brodifacoum. He received few units of FFP and was given a loading dose of 50 mg phytonadione (vitamin K) followed by 20 mg three times daily. His PT and INR normalized and gum bleeding and hematuria resolved. The patient was discharged from hospital. Patient denied any intentional ingestion of rat poison, any suicidal ideation or any conflicts within family. He was exposed to rodenticide at his workplace. During outpatient follow up, patient was again found to have elevated PT/INR and on questioning informed that he was taking Chinese herbal medications provided by his friends to facilitate excretion of the rat poison. Patient was advised to stop taking any alternative therapies. His phytonadione was increased to 240 mg/day for more than two months which have normalized his coagulopathy. Discussion– Human toxicity from ingestion of older rodenticides that contain warfarin is uncommon because these products contain less warfarin and the drug is rapidly metabolized. Newer derivates of warfarin (superwarfarins) brodifacoum, difethialone and difenicoum have been developed to overcome warfarin resistance. These compounds are more toxic to humans than warfarin because of their more avid binding to hepatic microsomes and longer duration of action. Brodifacoum and difenicoum are far more potent and have a much longer half-life than warfarin. The half-life of brodifacoum has been described as long as 30 days. Superwarfarins produce their anticoagulation effect by inhibiting the conversion of vitamin K1 2,3 epoxide to vitamin K1. This reaction is coupled to the carboxylation reaction required to produce the active form of prothrombin and the other vitamin K dependent clotting factors. There is increase in the vitamin K epoxide to vitamin K ratio and severely decreased activity of vitamin K dependent clotting factors. The duration of coagulation disturbance can be from few weeks to as long as few months. As illustrated by our patient, the treatment of superwarfarin posioning requires large doses of phytonadione, ranging from 50 – 800 mg/day administered for several months. Our patient has required daily 240 mg of phytonadione over two months to normalize his coagulopathy. Disclosures: No relevant conflicts of interest to declare.


1956 ◽  
Vol 34 (6) ◽  
pp. 1143-1152 ◽  
Author(s):  
J. D. Taylor ◽  
G. J. Millar ◽  
L. B. Jaques ◽  
J. W. T. Spinks

Radioactive vitamin K1-C14 was administered orally, intramuscularly, and intravenously to albino rats and the distribution of radioactive C14 determined. Isotope dilution studies were performed to ascertain the degree to which the vitamin K1-C14 was present in unchanged form in some tissues. Regardless of the route of administration, radioactivity was deposited in all the tissues. The liver accumulated the largest amounts of radioactivity but the spleen had a much higher specific activity following intravenous administration of the vitamin. Radioactivity could be detected in the liver for as long as 12 days after administration. When the log of the dose of vitamin K1-C14 (5.6–82 mgm./kgm.) was plotted against the log of the vitamin K1 equivalent in the various tissues a straight line relationship was obtained. The per cent of the injected dose present in the tissues 24 hr. after injection was as follows: liver 2.8, skeletal muscle 12.2, small intestine and contents 2.5, bile 26, feces 6.2, urine 0.98. The per cent of such activity present as unchanged vitamin K1-C14, as judged by isotope dilution tests, was liver 78, skeletal muscle 74, small intestine and contents 15, bile 1.5, feces 6.5, and urine 0.0.


Blood ◽  
2015 ◽  
Vol 125 (3) ◽  
pp. 438-442 ◽  
Author(s):  
Sol Schulman ◽  
Bruce Furie

Abstract Severe deficiency of vitamin K–dependent proteins in patients not maintained on vitamin K antagonists is most commonly associated with poisoning by or surreptitious ingestion of warfarin, warfarin-like anticoagulants, or potent rodenticides (“superwarfarins”), such as brodifacoum. Serious bleeding manifestations are common. Superwarfarins are 2 orders of magnitude more potent than warfarin and have a half-life measured in weeks. These rodenticides are readily available household environmental hazards and are sometimes consumed accidentally or as manifestations of psychiatric disease. Immediate diagnosis and proper therapy is critically important to minimize morbidity and mortality because this condition, affecting thousands of patients annually, is reversible. Treatment with large doses of oral vitamin K1, often over months to years, to maintain a near-normal prothrombin time can reverse the coagulopathy associated with superwarfarins. Although these patients initially present to various medical specialties, the hematologist is often consulted to offer the definitive diagnosis and proper therapy.


1995 ◽  
Vol 74 (06) ◽  
pp. 1486-1490 ◽  
Author(s):  
J Nathan Hagstrom ◽  
Edwin G Bovill ◽  
Roger F Soll ◽  
Kenneth W Davidson ◽  
James A Sadowski

SummaryPrenatal maternal vitamin K1 supplementation to improve the hemostatic status of the fetus may depend upon the route of administration and subsequent presentation at the placental barrier. We investigated intramuscular (IM) vs oral (PO) vitamin K1 supplementation in eight healthy, nonpregnant women of childbearing age. Pharmacokinetics were studied in each subject after a 5 mg IM dose and after a 5 mg oral dose of vitamin K1 approximately one month later. Plasma collected at the peak vitamin K level for each treatment was separated into very low density lipoproteins (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) and lipoprotein-free fractions by density gradient ultracentrifugation. Vitamin K1 was measured in the plasma and lipoprotein fractions using HPLC. The concentration of vitamin K1, in plasma reached a peak 2 h after an IM dose and remained high throughout the 30 h course of the study. In contrast, the oral dose of vitamin K1 peaked at 4 h and rapidly decreased to near baseline by 18 to 30 h. The distribution of vitamin K1 in the lipid fractions was different for IM compared to PO. The percentage of vitamin K1 in the VLDL fraction at the peak for an oral dose was significantly higher than for an IM dose (80.8% ± 3.5 vs 10.8% ± 6.5, p <0.0001). After the oral absorption stage, the subjects took 5 mg of vitamin K1 orally, once a day, for 12 days. No significant differences were observed for the following coagulation proteins and hemostatic markers measured immediately before and after long-term oral vitamin K supplementation: factor II, factor VII, protein C, and thrombin-antithrombin III complex. In conclusion, physiological processing of supplemented vitamin K1 differs in the IM vs PO routes of administration and 12 days of oral vitamin K1does not alter the concentration of selected vitamin Independent coagulation proteins or thrombin-antithrombin complex generation


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