Small Interfering Rna Transfection
The specific small interfering RNA against HSD17B4 , containing 5-GUACCUUUGUAUUUGAGGAdTdT-3 and 5-UCCUCAAAUACAAAGGUACdTdT-3, and the non-specific siRNA , containing 5-UUCUCCGAACGUGUCACGUTT-3 and 5-ACGUGACACGUUCGGAGAATT-3, all were purchased from Sigma . Transfection was performed using the Lipofectamine reagent following the manufacturers instructions. Transfection was conducted after 24 h, and the cells were treated with 50 M of VK2 for the indicated times, harvested and lysed for tests.
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Researchers for the European Prospective Investigation into Cancer and Nutrition have also found that increasing ones intake of vitamin K2 may lower the risk of getting prostate cancer dramatically by up to 35 percent. With a one in seven risk of developing prostate cancer within their lifetime, this is an encouraging discovery! But because were talking about a vitamin, Im sure you wont see commercials about it. And K2 is not something you have to buy, its commonly found in foods that most of us already enjoy like salads, green vegetables, green superfoods, as well as some meat and cheese. There are also supplements that are sold without prescription, at health food stores, however I encourage you to ask your physician if these are right for you, as K2 can interfere with blood-thinning medications.
For people on the healing process with cancer, their number one goal is to stop the spread of cancer to other organs and tissues, termed metastasis. When prostate cancer is caught early on, before it has spread to many other organs, the interventions are more useful.
Vitamin K2 has also proven to have neuroprotective effects upon the brain, preventing Alzheimers and dementia, to shuttle calcium out of the arteries and to the bones, where it hardens and strengthens them, helps wounds and bones to heal faster, improves the skin, and now hear this, reverses wrinkles as well.
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Fermented Foods Are A Good Source Of K2
Fermented foods, however, such as sauerkraut, cheese, and natto, contain substantial amounts of vitamin K2. Natto contains the highest concentration of K2 of any food measured nearly all of it is present as MK-7, which research has shown to be a highly effective form. One study demonstrated that MK-7 increased the percentage of osteocalcin in humans three times more powerfully than did vitamin K1.
How Much Vitamin K2 Is Required To Prevent Cardiovascular Disease
Investigating the physiological role of vitamin K2 in inhibiting prostate cancer, we cannot overlook its well-established functions in preventing cardiovascular disease and bone health. Both of these healing effects of vitamin K2 are due to its function of regulating calcium metabolism: vitamin K2 improves the deposition of calcium in bones and prevents calcification of soft tissues, kidneys, and blood vessels. Calcium accumulation in the arteries is the leading risk factor for CVD.
The standard function of all forms of vitamin K is that they serve as an active center for the enzyme g-glutamate carboxylase, which converts specific glutamate residues into g-carboxyglutamate, known as Gla. Gla-protein family includes 17 members, seven of which are involved in blood clotting. However, only for blood coagulation factors, osteocalcin , and matrix Gla protein , the physiological role is well established and studied. MGP may inhibit coronary calcification thus preventing CVD or significantly reducing its risk.
Studies show an inverse association between high vitamin K2 intake with reduced coronary calcification. More information you can find in these articles:
In the Rotterdam Study, the hardness of aortic calcification correlated linearly with the dietary deficit of menaquinones . People who consumed the largest amounts of vitamin K2 were 52% less prone to develop artery calcification and had a 57% lower risk of dying from heart disease.
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Vk2 Downregulated The Hsd17b4
Our recent studies have found that upregulation of HSD17B4 promoted HepG2 cell proliferation by enhancing cyclin D1 and proliferating cell nuclear antigen expression . To determine whether VK2 could reduce the HSD17B4-induced overexpression of proliferation genes, we investigated the expression of cyclin D1 and PCNA on the cells that were transfected with HSD17B4 expression plasmids or siHSD17B4. As shown in Figure 3, HSD17B4 overexpression increased the protein levels of cyclin D1 and PCNA, and VK2 not only suppressed the expression of cyclin D1 and PCNA on cells that were transfected with empty plasmids but also suppressed their increased expression induced by HSD17B4 overexpression . However, there was no significant decrease in the expression of cyclin D1 and PCNA on the HepG2 cells that were transfected with siHSD17B4 to knockdown HSD17B4 expression . These results indicated that VK2 inhibited the proliferation genes expression of HSD17B4-increased protein of cyclin D1 and PCNA in HepG2 cells.
Figure 3 VK2 downregulated the HSD17B4-induced expression of phosphorylated STAT3 gene and proliferation in HepG2 cells. HepG2 cells were treated with vitamin K2 for 48 h after transfection with HSD17B4-overexpression or control plasmids, and with specific or non-specific siRNA sequences against HSD17B4. The proteins of cyclinD1, PCNA, STAT3, and p-STAT3 were assayed by Western blot.
Cell Culture And Treatment
The human hepatocellular carcinoma cell line HepG2 was cultured with RPMI-1640 medium containing 10% fetal bovine serum , 100 U/ml penicillin and streptomycin. The cells were cultured in a cell incubator at 37°C, 5% CO2, and saturated humidity. The cell seeding density was 3 × 104 cells/cm2. After 24 h of culture, the cells were cultured in RPMI-1640 medium without FBS for another 24 h. The HSD17B4 expression plasmid was transfected 24 h before VK2 administration.
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Vitamin K2 And Bone Health
Osteoporosis or bone weakening is the most common reason for a broken bone among seniors, particularly in postmenopausal women. Osteocalcin and MGP are vitamin K2-dependent proteins regulating calcium metabolism in bones. Calcium is the most abundant component in the skeleton which is in charge of its stiffness. MGP is tied to bone organic matrix formation and mobilization of calcium in bones. This protein has been found in blood vessels, cartilage, bone, and dentine. MGP significantly reduces bone fracture risk, promotes bone growth and development, and prevents the calcification of soft tissue and blood vessels.
For example, two Japanese studies showed that the usual dietaryintake of natto was effective in maintaining bone stiffness. In Japan, vitamin K supplements are authorized for preventing and treating osteoporosis.
Even low-dose vitamin K2 supplementation in postmenopausal women significantly decreased the age-related bone mineral loss and bone strength. These results suggest that the low-dose MK-7 supplements may help senior women maintain bone health.
A meta-analysis of seven randomized controlled trials showed that vitamin K2 decreased spinal fractures by 60%, hip fractures by 77%, and all non-spinal fractures by 81%.
A vast majority of studies suggest that vitamin K2 is a proven alternative to prevent osteoporosis and fractures.
Higher Vitamin K Intake Tied To Lower Cancer Risks
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NEW YORK – People with higher intakes of vitamin K from food may be less likely to develop or die of cancer, particularly lung or prostate cancers, than those who eat relatively few vitamin-K- containing foods, a new study suggests.
The study, reported in the American Journal of Clinical Nutrition, appears to be the first to look at the association between vitamin K intake and the risk of developing or dying from cancer in general. A previous report had linked it to lower prostate cancer risk.
The findings do not prove that consuming more vitamin K helps lower the risks of certain cancers. But they lay the foundation for future studies to try to answer that question, according to Dr. Jakob Linseisin and colleagues at the German Cancer Research Center in Heidelberg.
Vitamin K exists in two natural forms: vitamin K1, or phylloquinone, found largely in green leafy vegetables, as well as some vegetable oils, such as canola and soybean oils and vitamin K2, or menaquinone, for which meat and cheese are the primary dietary sources.
In the current study, vitamin K2 — which study participants most frequently got through cheese — was linked to the odds of developing or dying from cancer, whereas vitamin K1 was not.
The findings are based on data from 24,340 German adults who were between the ages of 35 and 64, and cancer-free at the outset. The researchers estimated the participants usual vitamin K intake based on a detailed dietary questionnaire.
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Ascertainment Of Prostate Cancer
Men in the intervention arm were offered annual prostate-specific antigen blood test and digital rectal examinations for screening prostate cancer during their first 6 y of participation in the trial, and follow-up continued for 7 additional years. The diagnosis of prostate cancer was confirmed primarily through the review of medical records of men who were suspected of having prostate cancer because of the following reasons: 1) a self-report of prostate cancer on annual study update, 2) abnormal prostate-specific antigen value or digital rectal examination, or 3) indication of prostate cancer on the death certificate. Advanced prostate cancer was defined as disease with clinical stage III or IV tumors or tumors with a Gleason score 8 .
What Are The Benefits
Unfortunately, many people are not aware of the health benefits of the K2 vitamin. The K vitamins have been underrated and misunderstood up until very recently in both the scientific community and the general public.
Vitamin K2 can help you maintain cardiovascular health, improve your skin, strengthen bones, and promote brain function. Find out more about this powerful nutrient.
It has been commonly believed that the benefits of vitamin K are limited to its role in blood clotting. Another popular misconception is that vitamins K1 and K2 are simply different forms of the same vitaminwith the same physiological functions.
New evidence, however, has confirmed that the K2 vitamins role in the body extends far beyond blood clotting. It may help stave off chronic disease by:
K2 isn’t the only vitamin you need for healthy skin
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Vitamin K2 Triggers Ampk
Vitamin K2 induces AMPK-dependent autophagic cell death in bladder cancer cells. Western blot showed the effect of 50M Vitamin K2 on activation of AMPK and mTORC1 pathway in T24 cells. Western blot showed the effect of AMPK siRNA on the activation of AMPK, mTORC1, autophagy and apoptosis in Vitamin K2-treated T24 cells. Western blot showed the effect of 40M Compound C on the activation of AMPK, mTORC1, autophagy and apoptosis in Vitamin K2-treated EJ cells. MTS assays demonstrated the effect of Compound C and 10mM glucose supplementation on the cell viability in Vitamin K2-treated EJ or T24 cells. Flow cytometry demonstrated the effect of Compound C and glucose supplementation on apoptosis in Vitamin K2-treated EJ or T24 cells. Western blot showed the effect of glucose supplementation on c-MYC expression and activation of AMPK, autophagy and apoptosis in T24 cells treated with or without Vitamin K2. Data are presented as the mean ± SD of at least three independent experiments. *P< 0.05, **P< 0.01 and ***P< 0.001.
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Our guiding principles encompass total care for each and every one of our patients. This means that we provide only expert, professional, and compassionate treatment for our patients and their families. Our Tal Center for Integrative Medicine reflects this commitment as the first facility in the country to offer a truly holistic approach to cancer treatment in Israel. While all of our therapies are rooted in scientifically verified facts, we have made available complementary treatments in addition to the latest, cutting-edge Western medicine.These complementary treatments include physiotherapy, support from nutritionists, as well as professional and caring nursing staff. Psychological services are also provided as we understand that state of mind and mental health has a profound impact on physical health.For our patients, cancer is not a sentence or fate. We firmly believe that, with integrative medicine combining the latest in technology and medical research with compassion and experience, our patients can combat even the most serious diagnosis and enjoy a good quality of life.Other important aspects of our philosophy of cancer treatment include:
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Vitamin K And Cognition
The essential role of vitamin K in the synthesis of sphingolipids in the brain has been known for more than 40 years . More recently, vitamin K dependent proteins such as Protein Gas6 have been shown to play a key role in the peripheral and central nervous system . Vitamin K may have a role in the pathogenesis of Alzheimer’s disease because of its regulatory role in sulfotransferase activity and growth factor/tyrosine kinase receptor activity in the brain . There is evidence that vitamin K1 intake in the elderly with Alzheimer’s disease is significantly lower than in controls in the community . Intake of vitamin K may improve cognitive function in healthy older adults. One such study showed that vitamin K1 was associated with better verbal episodic memory performances especially on recall tasks . The use of vitamin K antagonists has been associated with more frequent cognitive impairment .
So What Causes Varicocele And Varicose Veins
The role of vitamin K2 in vein/arterial health has been studied as we saw with K2 deficiency associated with atherosclerosis. With K2 insufficiency, the artery and vein walls can become calcified, setting the stage for varicosities to form.
So is poor prostate health due to a vitamin K2 deficiency that ultimately leads to hyperplasia?
Evidence shows us that the protein MGP that we discussed in our first K2 blog post is seen to be over-expressed in varicose vein tissue, compared to normal vein samples. , and Gas6. MGP is the strongest inhibitor of soft tissue calcification presently known. But for these proteins to do their job and get the calcium into the correct parts of the body, they need Vitamin K2 to activate them.)
The form of MGP found in the varicose veins was the inactive form, i.e., it hadnt been activated by K2. In contrast, MGP found in the normal veins was mainly the activated form. The level of varicosity seems to also be dose-dependent on vitamin K levels. This suggests that vitamin K2 deficiency might be associated with varicose veins and might also be a factor in varicocele.
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Vitamin K May Help Prostate Health
Some researchers speculate that vitamin K may help reduce prostate cancer risk by promoting vein health. How? Varicose veins can cause backwards blood flow from the testes to the prostate gland. This can greatly increase the amount of testosterone near the prostate gland, causing it to enlarge.
An enlarged prostate, or benign prostate hyperplasia , increases the risk of prostate cancer. Vitamin K deficiency is linked to the formation of varicose veins. These researchers suggest that vitamin K can help prevent them near the testes.
Vitamin K2 For Prostate Health: The Missing Link
The research on K2 and prostate health is summarized in an interesting Medical Hypothesis article authored by Michael Donaldson.
He hypothesizes that the evidence today suggests that poor prostate health is essentially a vitamin K2 insufficiency disorder. The insufficiency leads to calcification of the vein walls through the presence of inactivated MGP, leading to the formation of a varicocele. Blood then does not flow normally rather it goes directly to the prostate resulting in high levels of testosterone in and around the prostate which can result in BPH and increase the risk of prostate cancer.
Sufficiency of vitamin K2 might be a key factor. Yes, further studies are needed to confirm these findings. But because supplementation with K2 is low risk with good potential benefits, supplementation with K2 might be warranted for you if you are suffering from prostate issues. Talk to your urologist or health care practitioner about it. Remember, K2 is just one factortheres also vitamin D, calcium, magnesium, vitamin A, a healthy diet, exercise
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Vitamin K And Diabetes
Even though it is known that there are high levels of vitamin K in the pancreas, deficiency in vitamin K results in excessive insulin release and reduces clearance of glucose from the blood in rats . Recently, a placebo controlled trial showed that using 30mg of vitamin K2 supplementation increased insulin sensitivity in healthy young men via osteocalcin metabolism . Vitamin K1 500gm/day for 36 months improved insulin resistance in men but not in women . Increased vitamin K1 intake in a cohort study was shown to decrease risk of developing diabetes by 51%. A recent review suggests that vitamin K supplementation may be used as a novel adjuvant therapy to improve glycemic control and quality of life .
Activation Of Pi3k/akt And Hif
We next investigate whether activation of PI3K/AKT and HIF-1 is implicated in Vitamin K2-upregulated glycolysis in bladder cancer cells. As shown in Fig. , Vitamin K2 significantly induced the phosphorylation of PI3K/AKT, and increased HIF-1 expression in bladder cancer T24 cells in a time-dependent manner. Moreover, both YC-1 and HIF-1 siRNA significantly attenuated Vitamin K2-elevated glucose consumption and lactate production in T24 cells . To validate the involvement of PI3K/AKT activation in Vitamin K2-induced glycolysis promotion, MK2206 and LY294002 were respectively utilized. Our data showed that both MK2206 and LY294002 markedly alleviated Vitamin K2-increased glucose consumption and lactate production in T24 and EJ cells . Additionally, Vitamin K2-upregulated glucose consumption and lactate production were significantly inhibited by respective treatment with AKT siRNA and PI3K siRNA . Collectively, these results indicate that Vitamin K2 promotes PI3K/AKT and HIF-1-mediated glycolysis in bladder cancer cells.
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