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 Our Vitamin K Complex delivers: Vitamin K1, Vitamin K2, Vitamin Mk7 and Mk4.  It offers 3 different types of vitamin K at doses high enough to be therapeutic.  It gives you enough vitamin K for your body’s basic needs, with additional vitamin K to be distributed to the rest of the tissues in your body that need it.Why Take Koncentrated K?

Below are some highlights of the many reasons why you want to take Koncentrated K.  It offers 3 different types of vitamin K at doses high enough to be therapeutic.  It gives you enough vitamin K for your body’s basic needs, with additional vitamin K to be distributed to the rest of the tissues in your body that need it.  It is the only product on the market offering a therapeutic dose, and it is the only product with a value price.  The different vitamin K’s clear from your body at different lengths, and the Koncentrated K formula ensures that you always have enough vitamin K available.  Plus, the astaxanthin in the formula is the most powerful antioxidant available.

* Vitamin K is known for clotting your blood, but research indicates that it is vital to the health functioning of many tissues in your body.

* Research shows that a prolonged vitamin K deficiency is a risk factor for osteoporosis, atherosclerosis, Alzheimer’s and cancer. Present recommendations for daily intake are based on what your body needs to prevent bleeding. The current recommendations for daily intake do not take into account what the rest of your body needs.

* Research indicates that the vitamin K intake of the general population is too low, and that most people test as being deficient in vitamin K.

* Vitamin K is not toxic at any level.  Some folks have taken doses as high as 45 mg a day, with no adverse effects.  It appears that your body uses all that it gets.  There are no recommended daily allowances, as there are no upper limits, meaning you can take high doses without worry.

* Vitamin K is associated with many health benefits.  Research has greatly expanded in the last decade, and vitamin K is associated with reversing cardiovascular disease, with strengthening bones, with interfering with the growth of cancer cells, with benefitting those with chronic kidney disease, as helping regulating insulin in diabetics, improving cognitive functioning and much more. Vitamin K is naturally occurring, and can be a non-toxic intervention to treat these diseases  

* Phylloquinone and menaquinones differ in source, absorption rates, tissue distribution, bioavailability, and target activity.  Early research suggested that certain menaquinones may be the predominant form of vitamin K found in extra-hepatic tissues and may be affected by diet, gender, and age (Huber et al, 1999).  There is ongoing research to highlight and summarizes differences between vitamin K1 and K2 in intake and function, beyond coagulation (Wen et al, 2018; Halder et al, 2019; Simes et al, 2020).  This new information will contribute to foster the use of vitamin K as a health-promoting supplement, which may prevent a wide range of disabling diseases (Wei et al, 2019), and which could meet the increasing consumer demand.

* In humans, at least 17 different VKDPs, which are also known as Gla proteins, have been identified to date, and are generally referred to as hepatic and extra-hepatic VKDPs, according to the synthesis location (Willems, Vermeer et al, 2014). The hepatic group of VKDPs synthesized in the liver are essential for regulating blood coagulation and comprise the coagulation factors II, VII, IX, and X, and the anti-coagulation proteins C, S, and Z. Extra-hepatic VKDPs include matrix Gla protein (MGP), osteocalcin (OC), Gla-rich protein (GRP), growth arrest-specific protein 6 (Gas6), proline-rich Gla proteins (PRGP1 and 2), transmembrane Gla proteins (TMG3 and 4), periostin, and the GGCX enzyme. These extra-hepatic VKDPs, which are mostly known for their protective role in the bone and cardiovascular system, exhibit a broad tissue distribution and are involved in a wide range of biological functions such as bone homeostasis, ectopic calcification, cell differentiation and proliferation, inflammation, and signal transduction (Parker et al, 2009; Calvo et al 1996; Schurgers, 2005).  The widespread expression of MGP points to its role in maintaining microvascular integrity and preserving the structure and function of vital organs, including the retina (Wei et al, 2018), kidney (Wei et al, 2016; Puzantian et al, 2018) and heart (Willems et al, 2014; Andrews et al, 2018) and bone (Ducy et al, 1996; Levinger et al, 2017).

* Vitamin K2, or menaquinones, have been found to improve mitochondria functioning in cells.  Mitochondria are unique structures in the cells of people.  They serve as batteries, generating energy and powering the cell and the body.  They also synthesize and package proteins for transport to different parts of the cell and beyond, and contribute to neurological functioning.  Damaged mitochondria have been implicated in such diseases as Parkinson's Disease, cancer, Alzheimer's Disease, and ALS, a progressive neurological disease that impairs nerve functioning to the muscles.  (Schapira, 2006; Alam, et al 2016, Seyfried, 2015; Anandatheerthavarada et al 2003; Devi et al 2006; Manczak et al 2006; Reddy & Beal 2008; Martin et al 2007; Martin et al 2009). 

* Research indicates that MK4, a menaquinone, improves the functioning of mitochondria and can alleviate defects that impair mitochondria function.  Studies showed that vitamin K2 'rescued' mitochondrial dysfunction, and restored normal function (Vos, et al 2012).

* Koncentrated K is formulated to give you high doses of three types of K = vitamin K1, MK7 and MK4, along with Astaxanthin, a powerful antioxidant which helps fight inflammation. Koncentrated K can be taken once or twice a day, so that you always have adequate amounts of vitamin K in your body at all times.

* There is a vitamin K family, including vitamin K1 also known as phylloquinone, and vitamin K2s, also known as menaquinones.  In the K2 family, MK7 and MK4 are the most widely researched.

* Research has highlighted the vitamin K family as being key regulators of calcium in the body.  Research has identified proteins in most body tissues that are dependent on vitamin K, in order to be effective.  Without vitamin K being available, calcium is misplaced and becomes part of a disease process.

* Vitamin K triggers a modification in some proteins in your body, making them carboxylated and involved in disease prevention.  Carboxylation is a good thing.

* Vitamin K1 can be found in green leafy foods, though in very small quantities, and is poorly absorbed.  It is impossible to eat enough fresh vegetables on a daily basis to get the same amount of vitamin K as Koncentrated K provides.  The photo above is an attempt to illustrate how much food one would have to eat daily, in order to get the same amount of vitamin K that comes in the Koncentrated K capsule.

* In humans, gut bacteria also synthesize vitamin K (Ichihashi et al, 1992; LeBlanc et al, 2013).  Antibiotics impairs the synthesis of vitamin K by the gut flora (Wei et al, 2016).

* Most physicians focus on prescription medications and are not familiar with nutritional supplements that aid in disease prevention and disease reversal.  It is not part of their medical education typically, hence they rarely suggest it or recommend it for your health.

*In addition, vitamin K deficiency has been linked to several pathological conditions such as cardiovascular diseases (CVD), chronic kidney disease (CKD), osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis, cancer, dementia, certain skin pathologies, functional decline, and disability. Most of these chronic health conditions are associated with pathological calcification and inflammation, where the role of VKDPs and vitamin K is being highlighted.  The number of in vitro, in vivo, and clinical data showing the beneficial effects of vitamin K without adverse effects or documented toxicity raised increasing interest on the use of vitamin K as a health promoting supplement (Cranenburg et al, 2012; Misra et al, 2013; Simes et al, 2019).

*The data is so compelling that some believe that vitamin K supplementation early on, may prevent a wide range of disabling diseases (Wei et al, 2019).

Vitamin K and Cardiovascular Disease

Cardiovascular disease affects millions of people around the world. It is the leading cause of mortality in the western world.  The major underlying disease is atherosclerosis.  Current medical treatments are often invasive and surgical, and medications can have toxic side effects.  Vitamin K is not known to be toxic.

* A key vitamin K dependent protein is matrix Gla protein (MGP), and is the most important inhibitor of arterial calcification – or of plaque build up in arteries.  Mice who have been genetically bred without MGP die within weeks due to rupture of their arteries.

* Full activation of MGP (matrix Gla protein) requires 2 posttranslational modifications, that is, vitamin K–dependent carboxylation of glutamate at positions 2, 37, 41, 48, and 52 and serine phosphorylation at positions 3, 6, and 9 by a Golgi-casein kinase. MGP therefore occurs in 4 conformations: dp-ucMGP (desphospho-uncarboxylated MGP), dp-cMGP (desphospho-carboxylated MGP), p-ucMGP (phosphorylated-uncarboxylated MGP), and p-cMGP (phosphorylated-carboxylated MGP) (Hacking et al, 2001).

* Gla needs an adequate amount of vitamin K available in order to function effectively and inhibit calcium.  If Gla has enough vitamin K available to it, it becomes ‘carboxylated’.  This is desirable, as it means that your body has enough vitamin K for health. 

* Supplementation with vitamin K might upregulate the function of MGP, reduce calcification, and protect against mortality and cardiovascular disease (Roumeliotis et al, 2019).

* Research has measured Matrix Gla Protein in the body and low amounts of Gla are correlated with high arterial calcification scores – a key measure of the extent of heart disease, meaning most folks with heart disease are also vitamin K deficient.

* It is now understood that atherosclerosis and heart disease are part of the vascular-bone axis, and can result from dysregulation of calcium in the body – rather than going to bones and teeth, etc, it ends up in veins and arteries.

* Peer reviewed scientific research indicates that adequate amounts of vitamin K can reverse heart disease.

Research has identified several ways that carboxylation can be disrupted, meaning that heart disease can begin. People with these events should take vitamin K.

1. antibiotics can affect the bacteria in your gut, interfering with the metabolism of vitamin K from food.

2. vaccinations can have the same effect.

3. a diet which is low in green leafy vegetables, meaning your diet doesn’t give you enough vitamin K

4. medications such as warfarin, or coumarin, which is prescribed for blood clots.  Warfarin interferes with vitamin K and people taking warfarin often develop heart disease as a result.


Vitamin K and Bone Health

Globally it is estimated that one in three women and one in twelve men over the age of 50 will suffer from osteoporosis in their lifetime.  In the United States, 10 million people have osteoporosis and 18 million have osteopenia, a milder condition that precedes osteoporosis.

* Bone is a living tissue, continuously recycling and reforming and about every three to five years your bones are newly reformed.  both osteoporosis and osteopenia, the bone cycle has been disrupted, by something like a reduction in vitamin K in the body, or other disease processes.

* The vitamin K family play an important role in bone metabolism and bone health.  Matrix Gla Protein (Gla), depends on vitamin K in order to be effective, and at least three bone proteins containing Gla have been identified, including osteocalcin, matrix Gla protein and protein S.

* Research shows that adequate amounts of vitamin K are needed in order to activate osteocalcin, a protein in the body responsible for making bones stronger.

* Research shows that bone fractures are reduced when vitamin K levels are higher.  And that brittle bones and low bone mineral density are caused by what is called under-carboxylated osteocalcin, meaning the osteocalcin did not have enough vitamin K.

* Research shows that warfarin, taking to prevent blood clots, is associated with brittle bones, due to its interference with vitamin K.

* High doses of vitamin K2, specifically MK4, are an approved treatment for osteopososis in Japan. Research shows that when taking a supplement of vitamin K, bone loss is reduced.

 

Ichihashi T, Takagishi Y, Uchida K, Yamada H. Colonic absorption of menaquinone-4 and menaquinone-9 in rats. J Nutr. 1992;122:506–512.
In contrast to dietary vitamins, which are absorbed in the proximal tract of the small intestine, the predominant uptake of microbiotically synthesized vitamins occurs in the colon.

Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A, Karsenty G. Increased bone formation in osteocalcin-deficient mice. Nature. 1996;382:448–452. 

Huber AM, Davidson KW, O’Brien-Morse ME, Sadowski JA.  Tissue phylloquinone and menaquinones in rats are affected by age and gender.  Nutrient Metab.  1999 Feb;129(5):1039-44.

Hackeng TM, Rosing J, Spronk HM, Vermeer C. Total chemical synthesis of human matrix Gla protein. Protein Sci. 2001;10:864–870.

Anandatheerthavarada HK, Biswas G, Robin MA, Avadhani NG.  Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial functionin neuronal cells.  J Cell Biol.  2003;161:41-54.
Their results showed that APP (amyloid precursor protein) is targeted to neuronal mitochondria under some physiological and pathological conditions.

Schurgers LJ, Teunissen KJ, Knapen MH, Kwaijtaal M, van Diest R, Appels A, Reutelingsperger CP, Cleutjens JP, Vermeer C. Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification. Arterioscler Thromb Vasc Biol. 2005;25:1629–1633.
These data show that impaired carboxylation of MGP is associated with intimal and medial vascular calcification and suggest the essentiality of the vitamin K modification to the function of MGP as an inhibitor of ectopic calcification.

Devi L, Prabhu BM, Galati DF, Avadhani NG, Anantheerthavarada HK.  Accumulationof amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction.  J Neurosci.  2006;26:9057-68.
Mitochondria are the major source of energy for the brain.  Oxidative damage, induced by amyloid beta is associated with mitochondria early in Alzheimer's disease progression.  There is increasing evidence suggesting that synaptic damage from the import of AB into mitochondria play a significant role in aging and AD development.

Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH.  Mitochondria are a direct site of Aβ accumulation in Alzheimer's disease neurons:  implications for free radical generation and oxidative damage in disease progression.  Hum Mol Genet.  2006;15:1437-49.
Alzheimer's is a complex, neurodegenerative disease characterized by the impairment of cognitive function in elderly individuals.  Their findings suggest that early therapeutic interventions targeted to mitochondria may be effective in delaying AD progress in elderly individuals and as a treatment for folks with Alzheimers.

Schapira AHV.  Etiology of Parkinson's disease.  Neurology.  2006;66(Suppl. 4):S10-23.

Martin LJ, Liu Z, Chen , Price AC, Pan Y, Swaby JA, et al.  Motor neuron degeneration in amyotrophic lateral sclerosis mutant superoxide dismutase-1 transgenic mice:  mechanisms of mitochondriopathy and cell death.  J Comp Neurol.  2007;500-20-46.
Their study identified novel mechanisms for mitochondriopathy and motor neuron degeneration in ayotrophic lateral sclerosis mice. 

Reddy PH, Beal MF>  Amyloid Beta, mitochondrial dysfunction and synaptic damage:  implications for cognitive decline in aging and Alzheimer's disease.  Trends Mol Med.  2008;14:45-53.
Mitochondria are the major source of energy for the brain.  Oxidative damage, induced by amyloid beta is associated with mitochondria early in Alzheimer's disease progression.  There is increasing evidence suggesting that synaptic damage from the import of AB into mitochondria membranes play a significant role in aging and AD development.

Martin LJ, Gertz B, Pan Y, Price AC, Molkentin JD, Chang Q.  The mitochondrial permeability transition pore in motor neurons:  involvement in the pathobiology of ALS mice.  Exp Neurol.  2009;218:333-46.
Amytrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons that causes paralysis.  Mitochondria in motor neurons might be key sites for ALS pathogenesis.  This study tested that hypothesis and their results demonstrated that mitochondria have causal roles in the disease mechanisms in MNS in ALS mice.

Cranenburg E.C.M., Schurgers L.J., Uiterwijk H.H., Beulens J.W.J., Dalmeijer G.W., Westerhuis R., Magdeleyns E.J., Herfs M., Vermeer C., Laverman G.D. Vitamin K intake and status are low in hemodialysis patients. Kidney Int. 2012;82:605–610.

Vos M, Esposito G, Edirisinghe JN, Vilain S, Haada DM, Slabbaert JR, Van Meensel S, et al.  Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency.  Science. 2012 Jun;336(6086):1306-10.

LeBlanc JG, Milani C, de Giori GS, Sesma F, van Sinderen D, Ventura M. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotechnol. 2013;24:160–168.

Misra D., Booth S.L., Tolstykh I., Felson D.T., Nevitt M.C., Lewis C.E., Torner J., Neogi T. Vitamin K Deficiency Is Associated with Incident Knee Osteoarthritis. Am. J. Med. 2013;126:243–248.

Willems BA, Vermeer C, Reutelingsperger CP, Schurgers LJ. The realm of vitamin K dependent proteins: shifting from coagulation toward calcification. Mol Nutr Food Res. 2014;58:1620–1635.
In the past few decades vitamin K has emerged from a single-function "haemostasis vitamin" to a "multi-function vitamin." The use of vitamin K antagonists (VKA) inevitably showed that the inhibition was not restricted to vitamin K dependent coagulation factors but also synthesis of functional extrahepatic vitamin K dependent proteins (VKDPs), thereby eliciting undesired side effects. Vascular calcification is one of the recently revealed detrimental effects of VKA. The discovery that VKDPs are involved in vascular calcification has propelled our mechanistic understanding of this process and has opened novel avenues for diagnosis and treatment. This review addresses mechanisms of VKDPs and their significance for physiological and pathological calcification.

Seyfried TN.  Cancer as a mitochondrial metabolic disease.  Front Cell Dev Biol.  2015;3:43.

Alam MM, Lal S, FitzGerald KE, Zhang L.  A holistic view of cancer bioenergetics:  mitochondrial function and respiration play fundamental roles in the development and progression of diverse tumors.  Clin Transl Med.  2016 Mar;5(1):3.

Wei FF, Drummen NE, Schutte AE, et al Vitamin K dependent protection of renal function in multi-ethnic population studies. EBioMedicine. 2016;4:162–169.  
We assessed the association of renal microvascular function as exemplified by eGFR with both circulating dp-ucMGP and t-ucMGP in a multi-ethnic population study. In white Flemish and black South Africans recruited from the general population, eGFR decreased and the risk of renal impairment increased with higher dp-ucMGP, a marker of vitamin K deficiency. These epidemiological findings support the concept that active MGP might not only inhibit calcification in large arteries, as was well known before, but might also protect renal function.  

Levinger I, Brennan-Speranza TC, Zulli A, Parker L, Lin X, Lewis JR, Yeap BB. Multifaceted interaction of bone, muscle, lifestyle interventions and metabolic and cardiovascular disease: role of osteocalcin. Osteoporos Int2017;28:2265–2273. 
Undercarboxylated osteocalcin (ucOC) may play a role in glucose homeostasis and cardiometabolic health. This review examines the epidemiological and interventional evidence associating osteocalcin (OC) and ucOC with metabolic risk and cardiovascular disease.  Current observational and indirect interventional evidence appears to support a relationship between ucOC with metabolic and cardiovascular disease. There is also emerging evidence to suggest a direct role of ucOC in human metabolism.

Andrews J, Psaltis PJ, Bayturan O, Shao M, Stegman B, Elshazly M.  Warfarin use is associated with progressive coronary arterial calcification: insights from serial intravascular ultrasound. JACC Cardiovasc Imaging. 2018;11:1315–1323. 

Puzantian H, Akers SR, Oldland G, Javaid K, Miller R, Ge Y, et al.  Circulating dephospho-uncarboxylated matrix Gla-protein is associated with kidney dysfunction and arterial stiffness. Am J Hypertens. 2018;31:988–994. 
Large artery stiffening is increased in advanced chronic kidney disease (CKD) but likely develops progressively in earlier stages of CKD. Active matrix Gla-protein (MGP) is a potent vitamin K-dependent inhibitor of vascular calcification. A recent animal model demonstrated intrinsic abnormalities in vitamin K metabolism even in early CKD.  They found that CKD is associated with increased inactive dp-ucMGP with correlates with large artery stiffness.  

Wei FF, Huang QF, Zhang ZY, Van Keer K, Thijs L, Trenson S, et al.  Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans. Sci Rep2018;8:15088. 
Active matrix Gla protein (MGP), a potent inhibitor of calcification in large arteries, protects against macrovascular complications. Recent studies suggested that active MGP helps maintaining the integrity of the renal and myocardial microcirculation, but its role in preserving the retinal microcirculation remains unknown.  This study recruited Flemish participants where they measured dp-ucMGP in blood levels which is a measure of poor vitamin K status.  They found that dp-ucMGP was a long term predictor of smaller retinal arteriolar diameter in the general population.  They concluded that vitamin K supplementation may promote retinal health.

Wen L, Chen J, Duan L, Li S. Vitamin K-dependent proteins involved in bone and cardiovascular health (Review). Mol Med Rep. 2018;18:3–15.
This review describes and briefly discusses several important vitamin K-dependent proteins that serve an important role in bone and the cardiovascular system.

Halder M, Petsophonsakul P, Akbulut AC, Pavlic A, Bohan F, Anderson E, et al.  Vitamin K:  Double bonds beyond coagulation insights into differences between Vitamin K1 and K2 in health and disease.  Int J Mol Sci. 2019 Feb;20(4):896.
The discovery of different isoforms of vitamin K is beginning to elucidate a significant role for vitamin K outside of coagulation.  Functions of K2 are proving to be beneficial with regard to cardiovascular disease and bone.  There is a growing body of evidence suggesting vitamin K2 is involved in multiple cellular processes and might have a protective role in various organs throughout the body.

Roumeliotis S, Dounousi E, Eleftheriadis T, Liakopoulos V.  Association of the inactive circulating Matrix Gla Protein with vitamin K intake calcification, mortality, and cardiovascular disease:  A review.  Int J Mol Sci.  2019 Feb;20(3):DOI: 10.3390/ijms20030628.
Vascular calcification is not a passive, degenerative, untreatable disease, but an active process in which proteins and molecules are involved. MGP is the most powerful natural calcification inhibitor found in the human body, and is tightly associated with all types of calcification, mortality, and cardiovascular disease. Exogenous supplementation of vitamin K might upregulate its function, reduce calcification, and protect against mortality and cardiovascular disease.

Wei FF, Trenson S, Verhamme P, Vermeer C, Staessen JA.  Vitamin K-dependent matrix Gla protein as multifaceted protector of vascular and tissue integrity. Hypertension. 2019 Jun; 73(6):1160-1169.
Aging is one of the greatest social and economic challenges worldwide.  Vitamin K supplementation before irreversible organ damage sets in may help prevent a wide range of disabling diseases.  In aged people, and people with CKD, diabetes, and cardiovascular disease, circulating dp-ucMGP levels might be measured over time to track the risk of vascular complications, which increasingly challenge health care systems in the second millennium. 

Simes DC, Viegas CSB, Araujo N, Marreiros C.  Vitamin K as a diet supplement with impact on human health:  Current evidence in age-related diseases.  Nutrients.  2020 Jan;12(a):138.
Vitamin K health benefits has been  implicated in chronic low-grade inflammatory diseases such as cardiovascular disease, osteoarthritis, dementia, cognitive impairment, mobility disability, and frailty. Novel and more efficient nutritional and therapeutic options are urgently needed to lower the burden and the associated health care costs of these age-related diseases. Naturally occurring vitamin K comprise the phylloquinone (vitamin K1), and a series of menaquinones broadly designated as vitamin K2 that differ in source, absorption rates, tissue distribution, bioavailability, and target activity. The aim of this review is to update the reader regarding the specific contribution and effect of each K1 and K2 vitamers in human health, and novel natural sources of vitamin K and formulations to improve absorption and bioavailability. This new information will contribute to foster the use of vitamin K as a health-promoting supplement, which meets the increasing consumer demand.

 

Written by RPT 1/2/13

"In life, in any given situation, one can either be a winner, a loser, or a victim. If you keep your nose clean, work hard, work smart, and pay attention, you will win far more than you lose - - - but every now and then you will lose - - - no worries - - - but what is unacceptable is being a victim. I chose not be a victim.” - Pat

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