In cultured media, menaquinone-7 (0.01-10 μM; 7 days) inhibits osteoclast-like cells [1]. In the presence of the phytoestrogen genistein (1, 10 μM), menaquinone-7 (10 μM) dramatically increases phosphorylated Menaquinone-7 (1, 10 μM) in MC3T3E1 cells and enhances the anabolic effect on femoral calcium levels [3].

Depigmented bone loss is halted by menaquinone-7 (18.1 mg/100 g diet; in animal feed; 24 days) [5].

Cell viability assay [1]
Cell Types: Bone marrow cells (from 3-week-old male Wistar rats; stimulated by PTH/PGE2)
Tested Concentrations: 0.01-10 µM
Incubation Duration: 7 days
Experimental Results: The number of TRACP-positive MNCs stimulated by PTH or PGE2 was significant. Dramatically reduces prostaglandin E2.

Animal/Disease Models: Female Wistar rat (5 weeks old; ovariectomized (OVX) rat model)) [5].
Doses: 18.1 mg/100 g Dietary
Route of Administration: animal feed; 24-day
Experimental Results: Preventive effect on bone loss caused by OVX.

Absorption, Distribution and Excretion
Vitamin K, mainly in the form of vitamin K1, is principally absorbed from the jejunum and ileum. ... Vitamin K is delivered to the enterocytes in micelles formed from bile salts and other substances. Vitamin K is secreted by enterocytes into the lymphatics in the form of chylomicrons. It enters the circulation via the thoracic duct and is carried in the circulation to various tissues including hepatic, bone and spleen, in the form of chylomicron remnants. In the liver, some vitamin K is stored, some is oxidized to inactive end products and some is secreted with VLDL (very low density lipoprotein). Approximately 50% of vitamin K is carried in the plasma in the form of VLDL, about 25% in LDL (low-density lopoprotein) and about 25% in HDL (high-density lipoprotein). /Vitamin K/
Excretion of vitamin K and its metabolites is mainly via the feces. Some urinary excretion of vitamin K also occurs. /Vitamin K/
...Menaquinones are adequately absorbed from the GI tract only if bile salts are present. Menaquinones and its water-soluble derivatives, however, are absorbed even in the absence of bile. ... Menaquinones are absorbed almost entirely by way of the lymph. /Menaquinones/
Menaquinone forms of vitamin K are produced by bacteria in the lower bowel, where the forms appear in large amounts. However, their contributuion to the maintenance of vitamin K status has been difficult to assess. Although the content is extremely variable, the human liver contains about 10 times as much vitamin K as a mixture of menaquinones than as phylloquinone. /Menaquinones/

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Metabolism / Metabolites
A major pathway of vitamin K metabolism is that which is involved in the reduction and recycling of the epoxide formed by the carboxylase. /Vitamin K/
Vitamin K undergoes some oxidative metabolism. /Vitamin K/

Interactions
... MK-7 induced more complete carboxylation of osteocalcin, and hematologists should be aware that preparations supplying 50 ug/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way.
Broad specturm antibiotics may sterilize the bowel and decrease the vitamin K contribution to the body by the intestinal microflora. /Vitamin K/
Cephalosporins containing side chains of N-methylthiotetrazole (cefmenoxime, cefoperazone, cefotetan, cefamandole, latamoxef) or methylthiadiazole (cefazolin) can cause vitamin K deficiency and hypoprothombinemia. These cephalosporins are inhibitors of hepatic vitamin K epoxide reductase. /Vitamin K/
Concomitant intake of cholestyramine and vitamin K may reduce the absorption of vitamin K. /Vitamin K/
For more Interactions (Complete) data for Vitamin K2 (16 total), please visit the HSDB record page.

[1]. Inhibitory effect of menaquinone-7 (vitamin K2) on osteoclast-like cell formation and osteoclastic bone resorption in rat bone tissues in vitro. Mol Cell Biochem. 2001 Dec;228(1-2):39-47.

[2]. Menaquinone-7 regulates gene expression in osteoblastic MC3T3E1 cells. Int J Mol Med. 2007 Feb;19(2):279-84.

[3]. Stimulatory effect of menaquinone-7 on bone formation in elderly female rat femoral tissues in vitro: prevention of bone deterioration with aging. Int J Mol Med. 2002 Dec;10(6):729-33.

[4]. Bicuspid Aortic Valve Stenosis and the Effect of Vitamin K2 on Calcification Using 18F-Sodium Fluoride Positron Emission Tomography/Magnetic Resonance: The BASIK2 Rationale and Trial Design. Nutrients. 2018 Mar 21;10(4):386.

[5]. Yamaguchi M, Taguchi H, Gao YH, Igarashi A, Tsukamoto Y. Effect of vitamin K2 (menaquinone-7) in fermented soybean (natto) on bone loss in ovariectomized rats. J Bone Miner Metab. 1999;17(1):23-9.

Menaquinone-7 is a menaquinone whose side-chain contains seven isoprene units in an all-trans-configutation. It has a role as a Mycoplasma genitalium metabolite, a bone density conservation agent, an Escherichia coli metabolite, a human blood serum metabolite and a cofactor.
Menaquinone 7 is under investigation in clinical trial NCT00402974 (The Effect of Vitamin K Supplementation on Osteocalcin Carboxylation in Healthy Children).
Menaquinone-7 has been reported in Brevibacillus brevis with data available.

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Mechanism of Action
In vivo and in vitro studies have shown that vitamin K may directly act on bone metabolism. In vitro studies have demonstrated that vitamin K2 inhibits bone resorption by, in part, inhibiting the production of bone resorbing substances such as prostaglandin E2 and interleukin-6. Vitamin K2 has been reported to enhance human osteoblast-induced mineralization in vitro and to inhibit bone loss in steroid-treated rats and ovariectomized rats.
Certain naphthoquinones, in particular the synthetic vitamin K menadione, have been found to have antitumor activity in vitro and in vivo. Vitamin K2 has been found to induce the in vitro differentiation of myeloid leukemic cell lines. The mechanism of the possible anticarcinogenic activity of vitamin K is not well understood. Menadione is an oxidative stress inducer and its possible anticarcinogenic activity may, in part, be explained by induction of apoptotic cell death. One study suggested that the induction of apoptosis by menadione is mediated by the Fas/Fas ligand system. Another study reported that menadione induces cell cycle arrest and cell death by inhibiting Cda 25 phosphatase.
Vitamin K is involved as a cofactor in the posttranslational gamma-carboxylation of glutamic acid residues of certain proteins in the body. These proteins include the vitamin K-dependent coagulation factors II (prothrombin), VII (proconvertin), IX (Christmas factor), X (Stuart factor), protein C, protein S, protein Zv and a growth-arrest-specific factor (Gas6). In contrast to the other vitamin K-dependent proteins in the blood coagulation cascade, protein C and protein X serve anticoagulant roles. The two vitamin K-dependent proteins found in bone are osteocalcin, also known as bone G1a (gamma-carboxyglutamate) protein or BGP, and the matrix G1a protein or MGP. Gamma-carboxylation is catalyzed by the vitamin K-dependent gamma-carboxylases. /Vitamin K/
The primary gene product of the vitamin K-dependent proteins contains a very homologous domain between the amino terminus of the mature protein and the signal sequence that targets the polypeptide for the secretory pathway. This "propeptide" region appears to be both a "docking" or "recognition " site for the enzyme and a modulator of the activity of the enzyme by decreasing the apparent Km of the Glu site substrate. ... A key finding essential to a complete understanding of the detailed mechanism of action of this enzyme has been the identification of an intermediate chemical form of vitamin K, which could be sufficiently basic to abstract the gamma-hydrogen of the glutamyl residue. It has been proposed that the initial attack of O(2) at the naphthoquinone carbonyl carbon adjacent to the methyl group results in the formation of a dioxetane ring, which generates an alkoxide intermediate. /Vitamin K/
For more Mechanism of Action (Complete) data for Vitamin K2 (8 total), please visit the HSDB record page.

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Therapeutic Uses
There is no typical dosage for vitamin K. Some multivitamin preparations contain vitamin K as vitamin K1 (phylloquinone or phytonadione) or vitamin K2 (menaquinones) at doses of 25 to 100 ug.
Vitamin K is used to treat anticoagulant-induced prothrombin deficiency caused by warfarin, hyporprothrombinemia secondary to antibiotic therapy and hypoprothrombinemia secondary to vitamin C deficiency from various causes, including malabsorption syndromes. /Vitamin K/
Because hemorrhagic disease of the newborn can be effectively prevented by administrating vitamin K, infants born in the US and Canada routinely receive 0.5-1 mg pf phylloquinone intramuscularly or 2.0 mg orally within 6 hours of birth. This practice is supported by both US and Canadian pediatric societies. /Phylloquinone/
The current recommendations of the American Academy of Pediatrics advise that "vitamin K (phylloquinone) should be given to all newborns as a single, intramuscular dose of 0.5-1 mg" and if this advice is followed, the disease /Vitamin K deficiency bleeding/ is effectively prevented. /Vitamin K/
For more Therapeutic Uses (Complete) data for Vitamin K2 (8 total), please visit the HSDB record page.

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Drug Warnings
... MK-7 induced more complete carboxylation of osteocalcin, and hematologists should be aware that preparations supplying 50 ug/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way.
It has been suggested that vitamin K may have roles in osteoporosis and vascular health. However, this is difficult to establish on the basis of the studies performed thus far. /Vitamin K/
Pregnant women and nursing mothers should avoid supplemental intakes of vitamin K greater than RDA amounts (65 ug daily) unless higher amounts are prescribed by their physicians. /Vitamin K/
Individuals on chronic warfarin therapy may require dietary counseling on how to maintain steady vitamin K intake levels. Because habitual vitamin K intake may modulate warfarin dosage in patients using this anticoagulant, these individuals should maintain their normal dietary and supplementation patterns once an effective dose of warfarin has been established. /Vitamin K/
For more Drug Warnings (Complete) data for Vitamin K2 (6 total), please visit the HSDB record page.

C46H64O2

649.00

648.49

2124-57-4

Menaquinone-7-13C6;Menaquinone-7-d7;1233937-31-9

5287554

Light yellow to yellow solid powder

0.961

720.1±60.0 °C at 760 mmHg

54ºC

254.9±29.9 °C

0.0±2.3 mmHg at 25°C

1.532

17.05

0

2

20

48

1310

0

CC1=C(C(=O)C2=CC=CC=C2C1=O)C/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CCC=C(C)C

RAKQPZMEYJZGPI-LJWNYQGCSA-N

InChI=1S/C46H64O2/c1-34(2)18-12-19-35(3)20-13-21-36(4)22-14-23-37(5)24-15-25-38(6)26-16-27-39(7)28-17-29-40(8)32-33-42-41(9)45(47)43-30-10-11-31-44(43)46(42)48/h10-11,18,20,22,24,26,28,30-32H,12-17,19,21,23,25,27,29,33H2,1-9H3/b35-20+,36-22+,37-24+,38-26+,39-28+,40-32+

2-[(2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaenyl]-3-methylnaphthalene-1,4-dione

Vitamin K2-7; Vitamin K2(35); Vitamin MK-7

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~5 mg/mL (~7.70 mM)

Solubility in Formulation 1: 0.54 mg/mL (0.83 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.4 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 0.54 mg/mL (0.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.4 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)