Menaquinone-4

Menaquinone-4, also known as MK-4, is a form of vitamin K2 that plays an essential role in blood clotting and bone metabolism. It is found naturally in some foods, such as animal products and fermented foods, or can be synthesized in the body from vitamin K1, which is primarily found in leafy green vegetables. MK-4 has been shown to have various health benefits, including the ability to improve bone health, reduce the risk of fractures, and prevent arterial calcification. It has also been studied for its potential to support cardiovascular health and improve cognitive function. MK-4 supplements are available and are often used in conjunction with other nutrients to support overall health and wellbeing.

Menaquinone-4 for Bone Health:

Menaquinone-4 has been shown to support bone health by activating proteins involved in bone formation and reducing the risk of fractures. In a clinical study, supplementation with menaquinone-4 was found to reduce the incidence of vertebral fractures in postmenopausal women with osteoporosis.

Menaquinone-4 for Cardiovascular Health:

Menaquinone-4 has been linked to cardiovascular health by inhibiting the buildup of calcium in arterial walls, which can lead to atherosclerosis (hardening of the arteries). A study found that supplementing with menaquinone-4 reduced arterial stiffness in healthy postmenopausal women.

Menaquinone-4 for Dental Health:

Menaquinone-4 has also been shown to promote dental health by enhancing the production of osteocalcin, a protein involved in tooth development and maintenance. In a study, menaquinone-4 supplementation improved dental health and reduced gum bleeding in patients with periodontal disease.  It is important to note that while menaquinone-4 is generally considered safe for most people when taken in recommended doses, it may interact with certain medications and should be used with caution in people with certain medical conditions. As with any supplement, it is important to talk to your healthcare provider before taking menaquinone-4.

Additional Studies

1. Identification of UBIAD1 as a novel human menaquinone–4 biosynthetic enzyme
2. Comparison of menaquinone–4 and menaquinone-7 bioavailability in healthy women
3. Conversion of phylloquinone (Vitamin K1) into menaquinone–4 (Vitamin K2) in mice: two possible routes for menaquinone–4 accumulation in cerebra of mice
4. Intestinal flora is not an intermediate in the phylloquinone-menaquinone–4 conversion in the rat
5. Phylloquinone and menaquinone–4 distribution in rats: synthesis rather than uptake determines menaquinone–4 organ concentrations
6. Vitamin K status in human tissues: tissue-specific accumulation of phylloquinone and menaquinone–4
7. Conversion of dietary phylloquinone to tissue menaquinone–4 in rats is not dependent on gut bacteria
8. Tissue-specific utilization of menaquinone–4 results in the prevention of arterial calcification in warfarin-treated rats
9. Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone–4
10. menaquinone–4 concentration is correlated with sphingolipid concentrations in rat brain
11. Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone–4: in vitro and in vivo experiments
12. Neuroprotective effect of menaquinone–4 (MK-4) on transient global cerebral ischemia/reperfusion injury in rat
13. Multiple dietary vitamin K forms are converted to tissue menaquinone–4 in mice
14. Colonic absorption of menaquinone–4 and menaquinone-9 in rats
15. menaquinone–4 in breast milk is derived from dietary phylloquinone
16. menaquinone–4 accumulation in various tissues after and oral administration of phylloquinone in Wistar rats
17. menaquinone–4 enhances testosterone production in rats and testis-derived tumor cells
18. Combinatorial engineering for improved menaquinone–4 biosynthesis in Bacillus subtilis
19. Effects of long-term vitamin K1 (phylloquinone) or vitamin K2 (menaquinone–4) supplementation on body composition and serum parameters in rats
20. … (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone–4 (vitamin K2) in rats
21. Vitamin K metabolism. menaquinone–4 (MK-4) formation from ingested VK analogues and its potent relation to bone function
22. Deuterium-labeled phylloquinone has tissue-specific conversion to menaquinone–4 among Fischer 344 male rats
23. Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice
24. Possible effects of one week vitamin K (menaquinone–4) tablets intake on glucose tolerance in healthy young male volunteers with different descarboxy prothrombin …
25. Identification of menaquinone–4 metabolites in the rat
26. Vitamin K2 (menaquinone 4) reduces serum undercarboxylated osteocalcin level as early as 2 weeks in elderly women with established osteoporosis
27. Anti‐arthritis effects of vitamin K2 (menaquinone‐4) − a new potential therapeutic strategy for rheumatoid arthritis
28. Comparative uptake, metabolism, and utilization of menaquinone–4 and phylloquinone in human cultured cell lines
29. Impact of menaquinone–4 supplementation on coronary artery calcification and arterial stiffness: an open label single arm study
30. Elucidation of the mechanism producing menaquinone–4 in osteoblastic cells
31. Engineering a ComA Quorum-Sensing circuit to dynamically control the production of menaquinone–4 in Bacillus subtilis
32. Vitamin K in milk and infant formulas: determination and distribution of phylloquinone and menaquinone–4
33. Vitamin K1 (phylloquinone) and K2 (menaquinone–4) supplementation improves bone formation in a high-fat diet-induced obese mice
34. LC–MS/MS quantitative analysis of phylloquinone, menaquinone–4 and menaquinone-7 in the human serum of a healthy population
35. menaquinone–4 suppresses lipopolysaccharide-induced inflammation in MG6 mouse microglia-derived cells by inhibiting the NF-κB signaling pathway
36. Age and dietary form of vitamin K affect menaquinone–4 concentrations in male Fischer 344 rats
37. Atorvastatin decreases renal menaquinone–4 formation in C57BL/6 male mice
38. menaquinone–4 Production by a Mutant of Flavobacterium sp. 238-7
39. Structure–Activity Relationship of Novel menaquinone–4 Analogues: Modification of the Side Chain Affects their Biological Activities
40. Rapid, high performance method for the determination of vitamin K1, menaquinone–4 and vitamin K1 2, 3-epoxide in human serum and plasma using liquid …
41. Daily intake and serum concentration of menaquinone–4 (MK-4) in haemodialysis patients with chronic kidney disease
42. menaquinone‐4 enhances osteogenic potential of human amniotic fluid mesenchymal stem cells cultured in 2D and 3D dynamic culture systems
43. Vitamin K1 (phylloquinone) or vitamin K2 (menaquinone–4) induces intestinal alkaline phosphatase gene expression
44. Tissue distribution of phylloquinone and menaquinone–4 in sardine, Sardinops melanostictus
45. Enhancement effects of vitamin K1 (phylloquinone) or vitamin K2 (menaquinone–4) on intestinal alkaline phosphatase activity in rats
46. Extracellular production of menaquinone–4 by a mutant of Flavobacterium sp. 238-7 with a detergent-supplemented culture
47. Vitamin E decreases extra‐hepatic menaquinone‐4 concentrations in rats fed menadione or phylloquinone
48. Isolation and characterization of menaquinone–4 as a product of menadione metabolism in chicks and rats.
49. menaquinone–4 (vitamin K2) up-regulates expression of human intestinal alkaline phosphatase in Caco-2 cells
50. … –activity relationships in the conversion of vitamin K analogues into menaquinone–4. Substrates essential to the synthesis of menaquinone–4 in cultured human cell …
51. Low-dose menaquinone–4 improves γ-carboxylation of osteocalcin in young males: a non-placebo-controlled dose–response study
52. menaquinone–4 (vitamin K2) induces proliferation responses in bovine peripheral blood mononuclear cells
53. Osteogenic transdifferentiation of vascular smooth muscle cells isolated from spontaneously hypertensive rats and potential menaquinone‐4 inhibiting effect
54. A comparatively study of menaquinone-7 isolated from Cheonggukjang with vitamin K1 and menaquinone–4 on osteoblastic cells differentiation and mineralization
55. Menaquinone 4 Reduces Bone Loss in Ovariectomized Mice through Dual Regulation of Bone Remodeling
56. Circulating levels of vitamin K1, menaquinone–4, and menaquinone-7 in healthy elderly Japanese women and patients with vertebral fractures and patients with hip …
57. The formation of menaquinone–4 (vitamin K) and its oxide in some marine invertebrates
58. Effects of dietary vitamin K on survival, growth, and tissue concentrations of phylloquinone (PK) and menaquinone–4 (MK-4) for juvenile abalone, Haliotis discus …
59. The relative effects of phylloquinone and menaquinone–4 on the blood coagulation factor synthesis in vitamin K-deficient rats
60. menaquinone–4 amplified glucose-stimulated insulin secretion in isolated mouse pancreatic islets and INS-1 rat insulinoma cells
61. Phylloquinone and menaquinone–4 tissue distribution at different life stages in male and female Sprague–Dawley rats fed different VK levels since weaning or …
62. … -phase HPLC determination of chlorophyll a′ and naphthoquinones in photosystem I of red algae: existence of two menaquinone–4 molecules in photosystem I of …
63. menaquinone–4 Production by a Sulfonamide-resistant Mutant of Flavobacterium sp. 238–7
64. Changes of phylloquinone and menaquinone–4 concentrations in rat liver after oral, intravenous and intraperitoneal administration.
65. Enhanced antitumor effects of novel intracellular delivery of an active form of menaquinone–4, menahydroquinone-4, into hepatocellular carcinoma
66. menaquinone–4 accelerates calcification of human aortic valve interstitial cells in high-phosphate medium through PXR
67. Concentrations of circulating phylloquinone, but not cerebral menaquinone–4, are positively correlated with a wide range of cognitive measures: exploratory findings in …
68. Deuterium‐labeled phylloquinone fed to α‐tocopherol‐injected rats demonstrates sensitivity of low phylloquinone‐containing tissues to menaquinone‐4 depletion
69. Distribution of menaquinone–4, a therapeutic agent for osteoporosis, in bone and other tissues of rats
70. Determination of vitamin K1 in canola oils by high performance liquid chromatography with menaquinone–4 as an internal standard
71. Effects of combined menaquinone–4 and PTH1–34 treatment on osetogenesis and angiogenesis in calvarial defect in osteopenic rats
72. The Biosynthesis of menaquinone–4: How a Historic Biochemical Pathway Is Changing Our Understanding of Vitamin K Nutrition
73. Plasma phylloquinone, menaquinone–4 and menaquinone-7 levels and coronary artery calcification
74. Excess α‐tocopherol decreases extrahepatic phylloquinone in phylloquinone‐fed rats but not menaquinone‐4 in menaquinone‐4‐fed rats
75. menaquinone‑4 modulates the expression levels of calcification‑associated factors to inhibit calcification of rat aortic vascular smooth muscle cells in a dose …
76. Exocrine pancreatic secretion of phospholipid, menaquinone–4, and caveolin-1 in vivo
77. menaquinone–4 and-5 in a bacterium.
78. Pharmacokinetic characterization of menaquinone–4 in dogs by sensitive HPLC determination
79. Simultaneous determination of vitamin K1, vitamin K1 2, 3-epoxide and menaquinone–4 in human plasma by high-performance liquid chromatography with fluorimetric …
80. Maximal dose-response of vitamin-K2 (menaquinone–4) on undercarboxylated osteocalcin in women with osteoporosis
81. Excretion of menaquinone–4 by a Mutant of Flavobacterium sp. 238-7 in a Detergent-supplemented Culture
82. Reversed phase uplc/apci-ms determination of vitamin k1 and menaquinone–4 in human plasma: Application to a clinical study
83. Genistein and menaquinone–4 treatment-induced alterations in the expression of mRNAs and their products are beneficial to osteoblastic MC3T3-E1 cell …
84. Development of a liquid chromatography mass spectrometry method for the determination of vitamin K1, menaquinone–4, menaquinone-7 and vitamin K1-2, 3 epoxide …
85. The placental and mammary transport of [14C] menaquinone–4 in rats
86. Effect of solubilizer on the metabolic fate of menaquinone–4 in rats
87. Selective Release of menaquinone–4 from Cells of a Mutant of Flavobacterium sp. 238–7 with a Detergent
88. Stereobiochemical aspects of warfarin isomers for inhibition of enzymatic alkylation of menaquinone-0 to menaquinone–4 in chick liver.
89. The secondary electron acceptor of photosystem I in Gloeobacter violaceus PCC 7421 is menaquinone–4 that is synthesized by a unique but unknown …
90. Interactions and structure—organizations of menaquinone–4 and egg yolk phosphatidylcholine mixtures: Formation of bilayer and nonbilayer structures in an aqueous …
91. Enzymatic Alteration in the Shikimate Pathway during Derivation of menaquinone–4-producing Mutants of Flavobacterium sp. 238-7
92. Simultaneous determination of menaquinone–4 and its metabolite in human osteoblasts by high-performance liquid chromatography/atmospheric pressure chemical …
93. Upregulation of thrombomodulin antigen levels in u937 cells by combined stimulation with estradiol-17β and vitamin K2 (menaquinone 4)
94. Supplementation of rats with a lutein mixture preserved with vitamin E reduces tissue phylloquinone and menaquinone–4
95. Changes of K vitamins in portal and femoral venous plasma of rats after oral administration of phylloquinone and menaquinone–4.
96. The effect of menaquinone–4 administration on the expression of proinflammatory factors following transient global cerebral ischemia/reperfusion in the hippocampus …
97. … of isoprenoid quinones. I. Separation of homologues, geometrical isomers and decomposition products of phylloquinone, menaquinone–4 and ubiquinone-10
98. Dietary intake of menaquinone–4 may determine hepatic and pancreatic menaquinone–4 in chickens
99. Vitamin K (menaquinone–4) metabolism in liver disease
100. Metabolic fate of menaquinone–4 in dogs (I): Absorption, distribution, metabolism and excretion after a single oral administration
101. Effects of combined human parathyroid hormone (1–34) and menaquinone–4 treatment on the interface of hydroxyapatite-coated titanium implants in the femur of …
102. Synthetic studies on isoprenoidquinones. II. Syntheses of Ubiquinone-10, phylloquinone, and menaquinone–4 by a chain-extending method utilizing terminally …
103. The Interaction of menaquinone–4 with Phopholipid Membranes
104. Simultaneous Determination of Vitamins D3 (Calcitriol, Cholecalciferol) and K2 (menaquinone–4 and menaquinone-7) in Dietary Supplements by UHPLC
105. Atorvastatin Decreases menaquinone‐4 Formation in C57Bl6 Male Mice
106. New Development of Vitamin K Research: Identification of Human menaquinone–4 Biosynthetic Enzyme.
107. Synthesis of all trans [3′‐14C]menaquinone‐4
108. 2. DELTA.-Stereocontrolled Entry to (E)-or (Z)-Prenyl Aromatics and Quinones. Synthesis of menaquinone–4
109. Enhanced Intracellular Delivery and Improved Antitumor Efficacy of menaquinone–4
110. An UFLC-DAD Method for the Quantification of menaquinone–4 in Spiked Rabbit Plasma
111. Simultaneous Determination of menaquinone–4 and Its Metabolite in Human Osteoblasts by High-Performance Liquid Chromatography/Atmospheric Pressure …
112. Menaquinone 4 Alters Plasma Lipid Profile In Hypercholesterolemic Mice
113. Metabolic Fate of menaquinone–4 in Dogs (II): Absorption, Distribution, Metabolism and Excretion after Repeated Oral Administration
114. Effect of vitamin K2 (menaquinone–4) and vitamin D3 on bone mineralization in young and adult female rats
115. The effect of menaquinone–4 administration on the expression of pro-inflammatory factors following transient global cerebral ischemia/reperfusion in the hippocampus …
116. Vitamin K Tissue Distribution Is Modified by Large-Dose Warfarin and menaquinone–4 Content of the Diet
117. Synthesis Vitamin K Derivatives with High Conversion Rates to menaquinone–4
118. The Enzymatic Conversion of Phylloquinone to menaquinone–4
119. Menadione is an Intermediate in the Phylloquinone to menaquinone‐4 Conversion
120. … Develop and Validate a UPLC-QToFMS Method for Simultaneous Estimation of Ergocalciferol, Cholecalciferol, Phylloquinone, menaquinone–4, menaquinone-7, and …
121. Conversion of phylloquinone to menaquinone–4 in chickens, rats and cultured cells
122. Mode of Action of menaquinone–4 on Blood Coagulation
123. menaquinone–4 effects on working memory impairment and anxiety behavior after transient cerebral ischemia/reperfusion in male wistar rat
124. Correlation between serum concentrations of menaquinone–4 and developmental quotients in children with autism spectrum disorder
125. The effect of vitamin K2 (menaquinone–4) on the cognitive impairments and anxiety in transient cerebral global Ischemia
126. Reduction of ovariectomy-induced bone loss in rats by menaquinone–4, cholecalciferol, and (n-3) polyunsaturated fats
127. Tissue‐Specific Proportions of Phylloquinone to menaquinone‐4 Concentrations Differ in Response to Dietary Phylloquinone Manipulation in Lean Male Zucker Rats
128. Oral Administration of Cal K2 Containing menaquinone–4 (Vitamin K2) Enhances Serum r-Carboxylated Osteocalcin and Biochemical Components in the Femoral …
129. A Rationale for an Approach to Preventing and Treating Bisphosphonate-related Osteonecrosis of the Jaw With Vitamin K2 menaquinone–4
130. Changes in analgesia and hyperalgesia induced by intraperitoneal administration of morphine in the formalin test during intrathecal administration of menaquinone–4 …
131. UBIAD1 combined with menaquinone–4 induce aPoPtosis in human bladder carcinoma T24 cell line via c-Jun N-terminal Kinase/P53 Pathways
132. 5.2. 3 Tissue-specific proportions of phylloquinone to menaquinone–4 concentrations differ in response to dietary phylloquinone manipulation in lean male Zucker rats
133. A methyl 4-oxo-4-phenylbut-2-enoate with in vivo activity against MRSA that inhibits MenB in the bacterial menaquinone biosynthesis pathway
134. Bioconversion of farnesol and 1, 4-dihydroxy-2-naphthoate to menaquinone by an immobilized whole-cell biocatalyst using engineered Elizabethkingia …
135. The acid–base and redox properties of menaquinone MK-4, MK-7, and MK-9 (vitamin K2) in DMPC monolayers on mercury
136. Aerobic culture of Propionibacterium freudenreichii ET-3 can increase production ratio of 1, 4-dihydroxy-2-naphthoic acid to menaquinone
137. PROGRESS TOWARDS THE SYNTHESIS OF THE SUBSTRATE FOR THE BACTERIAL menaquinone BIOSYNTHETIC ENZYME, 1, 4-DIHYDROXY-6 …
138. Design, synthesis and antitumor activity of phthalazine-1, 4-dione-based menaquinone analogs