Vitamin K acts as an essential cofactor for the enzyme γ-glutamate carboxylase (GGCX), which catalyzes the posttranslational conversion of protein-bound glutamate residues into γ-carboxyglutamate (Gla) residues in vitamin K-dependent proteins (e.g., osteocalcin, matrix Gla protein). [1]
Vitamin K acts as an essential cofactor for the endoplasmic enzyme γ-glutamyl carboxylase (GGCX), which catalyzes the posttranslational conversion of glutamic acid (Glu) residues to γ-carboxyglutamic acid (Gla) residues in vitamin K-dependent proteins (VKDPs).
The vitamin K-dependent proteins Gas6 (growth arrest-specific gene 6 protein) and protein S are ligands for the receptor tyrosine kinases of the TAM family (Tyro3, Axl, and Mer). [3]

The two naturally occurring forms of vitamin K are menaquinone (vitamin K2) and phylloquinone (vitamin K1). The primary dietary supply of vitamin K is phylloquinone, which is mostly found in green leafy vegetables [1]. Menaquinone, or vitamin K2, can be found in trace levels in cheese, egg yolks, poultry, butter, and fermented soybeans. For all vitamin K-dependent proteins to be γ-glutamyl carboxylated, vitamins K1 and K2 are necessary [2]. An essential function of vitamin K is in the neurological system. Proteins Gas6 and S, which bind to TAM family receptor tyrosine kinases (Tyro3, Axl, and Mer), are bioactivated in part by vitamin K. Vitamin K plays a role in the brain's production of sphingolipids, a significant family of lipids found in high concentrations in the membranes of brain cells [3].

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Vitamin K was shown to promote nerve growth factor (NGF)-mediated neurite outgrowth from PC12D cells. This action was mediated by the protein kinase A and mitogen-activated protein kinase (MAPK) signaling pathways. [3]
Vitamin K (specifically phylloquinone and menaquinone-4) has survival-promoting effects on different neuronal cell types (cortex, hippocampus, and striatum) in the later stages of embryogenesis. [3]
Menaquinone-4 (MK-4), and to a lesser extent phylloquinone (K1), prevented glutathione depletion-mediated oxidative injury (defined by free radical accumulation and cell death) in primary cultures of oligodendrocyte precursors and immature fetal cortical neurons. Treating cell cultures with warfarin did not affect this protective role of MK-4, indicating an action independent of VKDPs. This protective effect was shown to be mediated, at least in part, through inhibition of the enzyme 12-lipoxygenase. [3]
MK-4 was shown to limit the production of interleukin-6 (IL-6) in cultured human fibroblasts and prostaglandins in cultured cells. [3]
The anti-inflammatory activity of vitamin K, notably MK-4, is mediated via inhibition of the nuclear factor κB (NF-κB) signaling pathway. [3]
Gas6 (a VKDP) prevents apoptosis of gonadotropin-releasing hormone (GnRH) neurons via recruitment of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway and stimulation of extracellular signal-regulated kinase (ERK) and Akt. [3]
Gas6 rescues cortical neurons from amyloid β protein (Aβ)-induced apoptosis by inhibiting Ca2+ influx. [3]
Gas6 promotes the survival of human oligodendrocytes in vitro and protects them from tumor necrosis factor alpha (TNFα)-induced apoptosis through activation of the Axl receptor and the PI3-K/Akt pathway. [3]
In a murine microglia cell line, Gas6 treatment reduced expression of proinflammatory mediators inducible nitric oxide synthase (iNOS) and interleukin-1β (IL-1β) following a lipopolysaccharide (LPS) challenge. [3]
Gas6 stimulates myelin synthesis by oligodendrocytes in vitro. [3]
Protein S offers neuronal protection during ischemic/hypoxic injury in cultured neurons and protects neurons from NMDA-induced toxicity and apoptosis through the Tyro3-PI3-K-Akt pathway. [3]

The ability of vitamin K to coagulate blood is well established. Vitamin K supplementation has been shown in numerous human trials to have positive effects on insulin sensitivity and glucose tolerance, as well as to prevent insulin resistance and lower the incidence of type 2 diabetes [1]. For women, 90 μg per day and for men, 120 μg per day is the recommended appropriate intake of vitamin K [2]. A lower level of biological activity protein called carboxylated osteocalcin is elevated in cases of vitamin K insufficiency. Low dietary vitamin K consumption has been linked to lower bone mineral density or more fractures, according to numerous research. Furthermore, it has been demonstrated that vitamin K administration enhances bone turnover and lessens the deficit of carboxylated osteocalcin [4].

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1. Phylloquinone (Vitamin K1) in Humans: In a study of older men and postmenopausal women (n=355, 60-80 y), supplementation with phylloquinone (500 µg/day for 36 months) resulted in a significantly lower homeostasis model assessment of insulin resistance (HOMA-IR) among men, and a beneficial effect on fasting plasma glucose levels in the older male population, compared to the control group. No significant effects were observed in the female population. [1]
2. Phylloquinone (Vitamin K1) in Humans: In a study of prediabetic premenopausal women (aged 22-45 y), supplementation with vitamin K1 (1000 µg/day for 4 weeks) caused a significant decrease in fasting glucose, 2-hour post-oral glucose tolerance test (OGTT) glucose and insulin concentrations, and an increase in the insulin sensitivity index, compared to placebo. However, it did not affect HOMA-IR. [1]
3. Menaquinone (Vitamin K2) in Humans: In a study of healthy young men (n=18, aged ~25.5-31.5 y), supplementation with menaquinone (30 mg/day for 4 weeks) significantly increased the insulin sensitivity index and disposition index compared to placebo. [1]
4. Phylloquinone (Vitamin K1) in Animal Model: In streptozotocin (STZ)-induced diabetic Wistar rats, subcutaneous administration of phylloquinone (5 mg/kg body weight, twice a week) reduced cataract formation, potentially by regulating blood glucose homeostasis and minimizing oxidative and osmotic stress. [1]
5. Menaquinone (Vitamin K2) in Animal Model: In STZ-induced diabetic male Sprague-Dawley rats, oral administration of menatrenone (a form of vitamin K2, 30 mg/kg body weight, five times a week for 12 weeks) prevented the development of hyperglycemia. [1]
6. Menaquinone (Vitamin K2) in Animal Model: In ovariectomized rats (both exercised and non-exercised), supplementation with menaquinone-7 (0.0009 mg/kg body weight/day for 9 weeks) decreased glucose levels and increased insulin, lipocalcin-2, and adiponectin levels compared to only ovariectomized rats. [1]
7. Epidemiological Studies: Higher dietary intake of both phylloquinone and menaquinone was associated with a reduced risk of developing type 2 diabetes in several large cohort studies. For example, in a Dutch cohort, the highest versus lowest quartile of phylloquinone intake had a hazard ratio of 0.81 for type 2 diabetes. Each 10-µg increment in menaquinone intake was associated with a hazard ratio of 0.93. [1]
8. Adipokine Modulation: A 1-year follow-up study within the PREDIMED trial showed that elderly subjects who increased their dietary phylloquinone intake had significant reductions in inflammatory cytokines (leptin, TNF-α, IL-6) and other metabolic risk markers compared to those who decreased or did not change intake. [1]
Administration of a vitamin K-deficient diet or warfarin treatment in rats was associated with hypoactivity (25% lower locomotor activity) and a shift from more to less exploratory behavior, but did not alter cognitive abilities assessed with a radial arm maze. [3]
Lifetime consumption of a low-phylloquinone diet (80 µg kg⁻¹ diet since weaning) resulted in cognitive deficits in 20-month-old rats. These rats acquired spatial learning more slowly (longer latencies) in the Morris water maze test compared to rats fed adequate (500 µg kg⁻¹) or high (2000 µg kg⁻¹) phylloquinone diets. Motor activity, exploratory behavior, and anxiety were not affected by diet. This cognitive impairment was associated with higher concentrations of ceramides in the hippocampus and lower gangliosides in the pons medulla and midbrain. No impact was observed in rats aged 6 and 12 months. [3]
In a murine in vivo model of stroke, protein S treatment significantly reduced brain infarction and edema volumes, improved post-ischemic cerebral blood flow, reduced fibrin deposition and neutrophil infiltration, and resulted in fewer apoptotic neurons and improved motor performance. [3]
MK-4 was shown to limit inflammation in animal models of encephalomyelitis. [3]
Phylloquinone suppressed lipopolysaccharide-induced inflammation in rats. [3]
In cuprizone-treated C57B16 mice, direct administration of Gas6 into the brain increased maturation of oligodendrocyte progenitor cells and enhanced remyelination. [3]
In knockout mice (Gas6⁻/⁻), the absence of Gas6 signaling was associated with decreased oligodendrocyte survival, greater cell loss, reduced overall myelination, and a delay in remyelination after cuprizone-induced demyelination. [3]
Fetal exposure to warfarin derivatives during the first trimester of pregnancy results in central nervous system anomalies (warfarin embryopathy), including dilatation of cerebral ventricles, microcephaly, mental retardation, optic atrophy, and blindness. [3]
In an analysis of patients in the early stages of Alzheimer's disease (AD), mean phylloquinone intakes were significantly lower (63 ± 90 µg day⁻¹) compared to cognitively intact controls (139 ± 233 µg day⁻¹), even after adjusting for energy intake. Lower consumption of green vegetables (the main vitamin K source) explained the lower intakes in AD patients. [3]
In a study of 100 women with AD and 100 controls, plasma phylloquinone levels were significantly lower in AD patients and correlated positively with cognitive abilities (assessed by mini-mental state examination) and negatively with undercarboxylated osteocalcin (a marker of low vitamin K status). [3]

1. STZ-induced Diabetic Wistar Rat Model (Vitamin K1): Streptozotocin (STZ)-induced diabetic Wistar rats were treated with phylloquinone via subcutaneous injection at a dose of 5 mg per kg body weight, administered twice a week. The treatment was evaluated for its effects on cataract formation and glucose homeostasis. [1]
2. STZ-induced Diabetic Sprague-Dawley Rat Model (Vitamin K2): Streptozotocin (STZ)-induced diabetic male Sprague-Dawley rats were treated with menatrenone (a form of vitamin K2) via oral gavage at a dose of 30 mg per kg body weight, administered five times per week for a duration of 12 weeks. The effect on hyperglycemia and bone mass was assessed. [1]
3. Ovariectomized Rat Model (Vitamin K2): Ovariectomized rats (both subjected to exercise and sedentary) were supplemented with menaquinone-7 at a dose of 0.0009 mg per kg body weight per day for 9 weeks. The impact on glucose homeostasis, insulin, lipocalin-2, and adiponectin levels was examined. [1]
Rats were fed diets containing different levels of phylloquinone (Vitamin K1) from weaning: a low (L) diet containing 80 µg kg⁻¹ diet, an adequate (A) diet containing 500 µg kg⁻¹ diet, and a high (H) diet containing 2000 µg kg⁻¹ diet. The animals were maintained on these diets for extended periods, up to 20 months of age. Behavioral and cognitive tests (Morris water maze, open field test, elevated plus maze) were performed at various ages (e.g., 6, 12, 20 months) to assess spatial learning, motor activity, exploratory behavior, and anxiety. Brain tissues were subsequently analyzed for sphingolipid concentrations. [3]
In a study on warfarin-induced effects, rats were administered a vitamin K-deficient diet or treated with warfarin. Their psychomotor functions were then assessed using an open field paradigm to measure locomotor and exploratory activity, and cognitive abilities were tested using a radial arm maze. [3]
In a murine model of stroke, protein S was administered to mice. Brain infarction, edema volumes, cerebral blood flow, fibrin deposition, neutrophil infiltration, apoptosis, and motor performance were evaluated to assess neuroprotection. [3]
In a model of cuprizone-induced demyelination in C57B16 mice, Gas6 was directly administered into the brain. The effects on oligodendrocyte progenitor cell maturation and remyelination were assessed in the weeks following treatment cessation. [3]

The literature indicates that there is currently no recommended dietary intake (RDA) for vitamin K. Adequate intake (AI) has been determined: according to US data, the ADA for phylloquinone (vitamin K1) is 120 μg/day for men and 90 μg/day for women; according to UK data, the ADA for menadione (vitamin K2) is estimated to be 54 μg/day for men and 36 μg/day for women. [1] In rats, regardless of age, vitamin K in the brain is mainly (>98%) in the form of menadione-4 (MK-4). MK-4 concentrations are highest in the midbrain and pons medulla oblongata, and lowest in the cerebellum, olfactory bulb, thalamus, hippocampus, and striatum. MK-4 concentrations in the brains of female rats are higher than those in male rats, decrease with age, and increase with phylloquinone intake. [3] Phloquinone (K1) is converted to menadione-4 (MK-4) in tissues including brain tissue. The human UBIAD1 enzyme is responsible for this biosynthesis. [3]

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
Vitamin K is naturally present in breast milk. Lactating women typically do not require additional vitamin K supplementation to meet the recommended daily intake of 75 micrograms. Daily supplementation with 5 mg of vitamin K can increase the vitamin K content in breast milk and improve the vitamin K status of breastfed infants who receive intramuscular vitamin K injections shortly after birth. While exclusively breastfed infants have a higher risk of vitamin K deficiency bleeding (VKDB), which can lead to intracranial hemorrhage and sometimes even infant death, maternal vitamin K supplementation alone is not a sufficient or safe alternative to direct vitamin K supplementation after birth to prevent VKDB, especially in premature infants.
◉ Impact on Breastfed Infants
Exclusive breastfeeding without prophylactic vitamin K administration at birth resulted in the deaths of three previously healthy male siblings due to intracranial hemorrhage. A fourth male sibling was found to have abnormal coagulation function 17 days after birth. Upon examination, no genetic diseases that could cause abnormal blood clotting were found in the infant or his parents. Within 24 hours, the infant's blood clotting function returned to normal after an injection of 1 mg of vitamin K. According to the literature reviewed, there are currently no records of toxicity in humans or animals caused by consuming chloroquinone or menadione in food or supplements. The Institute of Medicine in the United States also states that there are currently no known toxicities. [1]

[1]. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: A review. Nutrition. 2016 Jul-Aug;32(7-8):732-9.

[2]. The health benefits of vitamin K. Open Heart. 2015 Oct 6;2(1):e000300.

[3]. Vitamin K, an emerging nutrient in brain function. Biofactors. 2012 Mar-Apr;38(2):151-7.

[4]. Vitamin K and bone health. Proc Nutr Soc. 2003 Nov;62(4):839-43.

2-Methyl-3-(3,7,11,15-tetramethylhexadec-2-enyl)naphthyl-1,4-dione is a type of 1,4-naphthoquinone compound. It has been reported that soybeans (Glycine max), black chokeberry (Aronia melanocarpa), and other organisms with relevant data contain vitamin K. The term "vitamin K" refers to a group of chemically similar, fat-soluble compounds called naphthoquinones: Vitamin K1 (menaquinone) is found in plants and is the main source of vitamin K for humans through diet; vitamin K2 (menaquinone) is synthesized by intestinal bacteria; vitamin K3 (menaquinone) is a water-soluble preparation suitable only for adults. Vitamin K is essential for the liver to synthesize clotting factors II, VII, IX, and X, as well as clotting factor proteins C, S, and Z. Vitamin K deficiency can lead to insufficient clotting factors and excessive bleeding. Newborns are often given vitamin K injections to prevent vitamin K deficiency bleeding, also known as neonatal hemorrhagic disease. Vitamin K deficiency is rare in adults but can be caused by chronic malnutrition or malabsorption of dietary vitamins. Phloroquinone is a metabolite found or produced in Saccharomyces cerevisiae. It is a lipid cofactor essential for normal blood clotting. Several forms of vitamin K have been identified: plant-derived vitamin K1 (phyto-menadione), bacterial-derived vitamin K2 (menadione), and the synthetic pro-naphthoquinone vitamin K3 (menadione). Pro-menadione exhibits antifibrinolytic activity after alkylation in vivo. Green leafy vegetables, liver, cheese, butter, and egg yolks are good sources of vitamin K. See also: phyto-menadione (note moved to). Vitamin K is a fat-soluble vitamin, primarily existing in two natural forms: phylloquinone (vitamin K1, found in leafy green vegetables and some oils) and menadione (vitamin K2, found in meat, fermented foods, and produced by intestinal bacteria). [1] This review suggests that the beneficial effects of vitamin K on insulin sensitivity and glucose metabolism may be mediated through several mechanisms: 1) carboxylation of vitamin K-dependent proteins, particularly osteocalcin (OC), which is associated with β-cell function and insulin sensitivity. 2) regulation of circulating adipokines levels (e.g., reducing inflammatory cytokines such as IL-6 and TNF-α). 3) anti-inflammatory properties, possibly achieved by inhibiting NF-κB activation. 4) lipid-lowering effects (e.g., reducing total cholesterol and triglycerides in animal models). [1] Literature suggests that menadione (vitamin K2) may be more effective than phylloquinone (vitamin K1) in activating extrahepatic vitamin K-dependent proteins, thereby reducing the risk of type 2 diabetes. [1] Vitamin K plays a crucial role in blood clotting, a fact widely recognized. [1] Vitamin K is a fat-soluble vitamin. Phloquinone (vitamin K1) is synthesized from plants and is a major dietary source. Menadione (vitamin K2, MK-n) is derived from bacteria; MK-4 is synthesized from K1 in tissues. [3]
Vitamin K is essential for the bioactivation (γ-carboxylation) of vitamin K-dependent proteins (VKDPs), such as Gas6 and protein S, which are ligands of TAM family receptor tyrosine kinases (Tyro3, Axl, Mer). [3]
Vitamin K plays a key role in brain sphingolipid metabolism. Warfarin treatment reduces the levels of thiolipins, sphingomyelins, and cerebrosides in the brain and decreases the activity of sulfotransferases. Vitamin K supplementation can reverse these changes. Vitamin K intake can regulate the concentration of thiolipins and gangliosides in specific brain regions. Altered sphingolipid profiles (e.g., increased ceramide levels in the hippocampus) are associated with cognitive impairment in aging animals with low vitamin K intake. [3]
Vitamin K, especially MK-4, has a protective effect against oxidative stress and inflammation, and its mechanism may be independent of VKDP carboxylation, for example, by inhibiting 12-lipoxygenase and NF-κB signaling pathways. [3]
Decreased vitamin K intake and levels are associated with Alzheimer's disease (AD). The ApoE4 genotype (a risk factor for AD) is also associated with decreased circulating phylloquinone concentrations, suggesting a possible link between chronically low vitamin K levels and AD risk. [3]
Vitamin K levels may affect behavior and cognition. Vitamin K deficiency is associated with psychomotor abnormalities and cognitive deficits in older animals. In humans, low vitamin K intake is observed in early-stage AD patients. [3]

C31H46O2

450.69574

450.35

12001-79-5

Vitamin K1;84-80-0

5280483

Light yellow to yellow liquid（Density：0.984 g/cm3）

0.963g/cm3

546.4ºC at 760mmHg

112-114ºC

200.4ºC

5.37E-12mmHg at 25°C

n20/D 1.527(lit.)

9.157

0

2

14

33

696

0

[Vitamin K]

MBWXNTAXLNYFJB-LKUDQCMESA-N

InChI=1S/C31H46O2/c1-22(2)12-9-13-23(3)14-10-15-24(4)16-11-17-25(5)20-21-27-26(6)30(32)28-18-7-8-19-29(28)31(27)33/h7-8,18-20,22-24H,9-17,21H2,1-6H3/b25-20+

2-methyl-3-[(E)-3,7,11,15-tetramethylhexadec-2-enyl]naphthalene-1,4-dione

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 : ~50 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (Infinity mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (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 25.0 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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 (Please use freshly prepared in vivo formulations for optimal results.)