Vitamin K2 plays an important role in the production of collagen and in the synthesis of osteocalcin, the protein which is the main substance in bone. But, if you are not getting enough vitamin K2, you could be at risk for osteoporosis and other related conditions. Its metabolites, phylloquinone and menaquinone, are the most important ones for maintaining and improving bone health.
Menaquinone forms are most important for improving bone health
Menaquinones are vitamin K compounds produced by various bacteria. These compounds are the vitamin K of the gut, and are known to contribute to the microbiota’s role in bone metabolism.
The nitty gritty of menaquinone production involves two steps. First, the precursor is synthesized in the liver. Next, these molecules are released into the colon. Although it is not a common practice in the West, in Japan menaquinone is commonly ingested. Interestingly, these ingredients are not detected in the blood stream. However, they are present in many fermented foods.
For example, the best-known source of menaquinones is cheese. In Europe, dairy products are the biggest source of menaquinones. Other sources include fermented soybeans such as natto. Natto is a typical Japanese food and is extremely rich in menaquinone.
However, the main reason behind the popularity of menaquinones is their ability to help prevent osteoporosis. Studies have shown that natto can help prevent postmenopausal bone loss. Some of these studies have even suggested that natto can help boost bone density.
Menaquinone has been shown to do the following: stimulate protein synthesis in osteoblastic cells, inhibit osteoclastic bone resorption, and stimulate posteoblastic bone formation. However, the most effective form is long-chain menaquinones, which are not only better for absorption, but also better at promoting efficiency.
Despite the popularity of calcium, there are still new players in the bone health game. More research into the benefits of a wide variety of ingredients is driving innovation in the industry. With the latest ingredient innovations, the bone health market is set for an exciting future. As the industry evolves, more botanicals and herbs will enter the mix for a competitive edge.
Phylloquinone (vitamin K1)
Vitamin K is an essential bioactive compound that plays a critical role in the regulation of blood clotting. It is also an important bioactive compound for maintaining bone health.
The two main dietary forms of vitamin K are menaquinones and phylloquinone. Menaquinones are long-chain derivatives that stay in the blood for a longer period of time, and are more bioavailable. They are found in foods like meat, eggs, cheese, milk, green leafy vegetables, and fermented dairy products. Some of them are also available as supplements.
Dietary menaquinones are generally taken up by enterocytes in the small intestine. Long-chain menaquinones are more efficient and better at promoting absorption.
Intake of menaquinones is associated with an inverse association with ischemic stroke and peripheral arterial disease. However, higher intakes did not decrease the risk of cardiovascular disease or all-cause mortality.
Plasma concentrations of phylloquinone were associated with an increased risk of knee osteoarthritis. There was a trend towards an inverse relationship between plasma phylloquinone and the incidence of vertebral fractures. Phylloquinone supplementation may also improve bone health in high-risk individuals.
Both vitamin Ks have important roles in the liver, with production of coagulation factors and VKDPs. However, the two vitamin Ks have different tissue distributions, absorption rates, and metabolism.
The pharmacological properties of vitamin K2 have been studied in rats with anxiety, and in humans with depression. These studies suggest that it may have a positive impact on bone and brain health.
However, more research is needed to determine the effects of phylloquinone on bone health. For now, randomized controlled trials are the only way to assess the benefits of phylloquinone on bones.
Vitamin K is required for a variety of protein functions. One of these is the carboxylation of coagulation factors.
Bacterial overgrowth affects vitamin K2 metabolism
Small intestinal bacterial overgrowth (SIBO) is a condition associated with decreased vitamin K2 synthesis in the intestine, leading to increased plasma levels of the inactive matrix Gla-protein (MGP). An increase in MGP correlates with early markers of atherosclerosis and arterial stiffening. This study evaluated if SIBO and increased circulating MGP are related.
One of the best markers for low vitamin K2 status is dephosphorylated-uncarboxylated MGP, or dp-ucMGP. A small sample of 27 patients without SIBO was used to investigate the relationship between plasma dp-ucMGP and dietary vitamin K2 intake.
The daily median dp-ucMGP level of these patients was 9.5 mg/L, compared to a mere 4.5 mg/L in the control group. Despite the differences in plasma dp-ucMGP levels, there was no correlation between dp-ucMGP and diet-related vitamin K2 intake.
In addition to measuring dp-ucMGP, a blood sample was collected for ultrasound examination of the noncoronary artery system. Moreover, a food frequency questionnaire was completed to gauge vitamin K2 intake.
In conclusion, a small intestinal bacterial overgrowth is associated with a decrease in the vitamin K2 production attributed to the increased circulating MGP. However, the dp-ucMGP may not be the ostensive signification of SIBO. Nonetheless, it has been linked to an increase in cardiovascular morbidity, so a dose of caution should be applied. Also, a reduction in dietary vitamin K2 intake should be considered. If this is not possible, additional preventive measures such as intestinal decontamination may be a prudent step.
Hopefully, the results of this study will be useful to physicians and researchers in future studies. For now, SIBO should not be ignored, and further research should be conducted to determine the true role of bacteria in the human body.
Induces apoptosis
Vitamin K2 is a ubiquitously produced vitamin that inhibits the growth of various cancer cells. It has also been associated with reduced risk of hepatocellular carcinoma, prostate cancer, and leukemia. However, its precise mechanism of action remains unknown.
In addition to reducing the growth of cancer cells, vitamin K2 has been proven to induce apoptosis in cancer cells. This apoptosis is achieved via mitochondria-mediated pathways. The apoptotic effect of vitamin K2 is attributed to its inhibition of NF-kB signaling.
As a part of a study on the anticancer activity of vitamin K2, researchers treated the rat astroglioma C6 cell with 0-10 uM vitamin K2. Cells were subjected to TUNEL staining to detect apoptotic cells. These cells were then rinsed with PBS.
To further evaluate the effects of vitamin K2, the promoter of cyclin D1 was used. Cyclin D1 is an important component of the G1-S transition and is regulated by NF-kB. Overexpression of cyclin D1 has been shown to enhance contact-independent growth of HCC.
A 12-week randomized, double-blind, placebo-controlled study was conducted to evaluate the therapeutic effectiveness of vitamin K2-7. Sixty patients were given a dose of 180 or 360 ug of the compound. After the treatment, the dp-cMGP, an indicator of cell proliferation, decreased. Moreover, serum levels increased significantly.
The protective role of vitamin K2 was confirmed by its antioxidant properties. Furthermore, its ability to inhibit apoptosis by blocking NF-kB signaling and activating protein Bad, a protein involved in the apoptosis pathway, was also demonstrated.
Vitamin K2 has been reported to inhibit NF-kB and PI3K/Akt signaling, two major cellular mechanisms that promote cancer cell proliferation and apoptosis. Interestingly, it does not affect IKKa/b, the major inhibitor of NF-kB, which has led to speculation that its anticancer effects may not be mediated through this pathway.
Inhibits cyclin D1 promoter activity
Inhibition of cyclin D1 promoter activity is a critical factor in the development of hormone therapy resistance in breast cancer. However, the regulation of cyclin D1 levels in cellular systems is not well understood. Several factors have been shown to modulate cyclin D1 phosphorylation, degradation, expression, and stability. A better understanding of these processes will help determine whether they can be targeted as potential therapies for cancer.
Cyclin D1 is a cyclic peptide that is a major regulator of cell cycle progression. This protein is required for the maintenance of the G1 phase and arrests DNA synthesis in the S phase. Several studies have shown that cyclin D1 is degraded in many different cancers. These studies have focused on the ubiquitin and proteasomal pathways of cyclin D1 degradation. However, some cancers may be able to utilize a novel mechanism for regulating cyclin D1 activity.
A cyclin D1 mutant containing a single lysine substitution from the N-terminus, T286A, retained nuclear localization throughout the cell cycle and was unable to undergo polyubiquitylation. The effect of a cyclin D1 mutation on cellular proliferation has not been reported.
In the SK-UT-1B cell line, cyclin D1 levels did not decline during the S phase. However, cyclin D1 degradation was abolished when the p38SAPK2 activity was inhibited. Interestingly, the SK-UT-1B cell line did not show polyubiquitylation of cyclin D1.
Several studies have shown that ubiquitin and proteasomal inhibition can inhibit cyclin D1 expression and degradation. In addition, ionizing radiation and environmental stress can induce cyclin D1 degradation. There are several different mechanisms by which cyclin D1 is degraded, but the role of the ubiquitin pathway is not entirely clear.
