La Vitamina K2 - Proprietà e benefici

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Vitam Horm. 2008;78:393-416. doi: 10.1016/S0083-6729(07)00016-7. Vitamin K and bone health in adult humans. 
Bügel S1.
Author information 
Vitamin K is receiving more attention in relation to its role in bone metabolism. Vitamin K is a coenzyme for glutamate carboxylase, which mediates the conversion of glutamate to gamma- carboxyglutamate (Gla). The gamma-carboxylation of the Gla proteins is essential for the proteins to attract Ca2+ and to incorporate these into hydroxyapatite crystals. The best known of the three known bone-related Gla proteins is osteocalcin (OC). Even though the exact role of OC is not known, a number of studies have shown that vitamin K insufficiency or high levels of undercarboxylated osteocalcin (ucOC) is associated with an increase in the concentration of circulating ucOC. Furthermore, several studies have demonstrated that vitamin K insufficiency is associated with low bone mineral density (BMD) and increased fractures. Vitamin K supplementation, on the other hand, has been shown to improve the bone turnover profile and decrease the level of circulating ucOC. Dietary recommendations are based on saturation of the coagulation system, and in most countries the dietary intake is sufficient to obtain the amount recommended. In relation to bone, requirements might be higher. The aim of this chapter is to give an overview of the importance of vitamin K in relation to bone health in adult humans and thereby in the prevention of osteoporosis. Furthermore, I will shortly discuss the interaction with vitamin D and the paradox in relation to warfarin treatment. 
PMID: 18374202 [PubMed - indexed for MEDLINE] 
J Nutr. 1996 Apr;126(4 Suppl):1187S-91S.
Effects of vitamin K on bone mass and bone metabolism. 
Vermeer C1, Gijsbers BL, Crāciun AM, Groenen-van Dooren MM, Knapen MH. Author information 
Vitamin K is involved in blood coagulation and in bone metabolism via the carboxylation of glutamate residues in (hepatic) blood coagulation factors and (osteoblastic) bone proteins. The bioavailability of nutritional vitamin K depends on the type of food, the dietary fat content, the length of the aliphatic side chain in the K-vitamer and probably also the genetically determined polymorphism of apolipoprotein E. Although undercarboxylation of blood coagulation factors is very rare, undercarboxylated osteocalcin (bone Gla-protein) is frequently found in postmenopausal women. Supplementation of these women with extra vitamin K causes the markers for bone formation to increase. In parallel, a decrease of the markers for bone resorption is frequently seen. Insufficient data are available to conclude that the regular administration of vitamin K concentrates will reduce the loss of bone mass in white women at risk for developing postmenopausal osteoporosis. 
PMID: 8642454 [PubMed - indexed for MEDLINE] 
Clin Calcium. 2010 Sep;20(9):1334-40. doi: CliCa100913341340.
 [Vitamin K and fracture]. 
[Article in Japanese] Tsugawa N1, Okano T. 
Author information 
Vitamin K is well known for its role in the synthesis of a number of blood coagulation factors. Vitamin K is also an important factor for bone metabolism via gamma-carboxylation of vitamin K- dependent proteins such as osteocalcin, matrix Gla protein, and protein S. Recent studies suggest that there is potential vitamin K insufficiency in bone, even in sufficient vitamin K status for blood coagulation. In the present review, the studies concerning relationship between vitamin K status and fracture are reviewed. 
PMID: 20808041 [PubMed - indexed for MEDLINE] 
Nutr Clin Pract. 2007 Oct;22(5):517-44.
Bone health and osteoporosis: the role of vitamin K and potential 
antagonism by anticoagulants. 
Pearson DA1.
Author information 
BACKGROUND: Vitamin K's effects extend beyond blood clotting to include a role in bone metabolism and potential protection against osteoporosis. Vitamin K is required for the gamma- carboxylation of osteocalcin. Likewise, this gamma-carboxylation also occurs in the liver for several coagulation proteins. This mechanism is interrupted by coumarin-based anticoagulants in both the liver and bone. 
METHODS: A thorough review of the literature on vitamin K, osteocalcin and their role in bone metabolism and osteoporosis, as well as the potential bone effects of anticoagulant therapy was conducted. 
CONCLUSIONS: Epidemiological studies and clinical trials consistently indicate that vitamin K has a positive effect on bone mineral density and decreases fracture risk. Typical dietary intakes of vitamin K are below the levels associated with better BMD and reduced fracture risk; thus issues of increasing dietary intakes, supplementation, and/or fortification arise. To effectively address these issues, large-scale, intervention trials of vitamin K are needed. The effects of coumarin- based anticoagulants on bone health are more ambiguous, with retrospective studies suggesting that long-term therapy adversely affects vertebral BMD and fracture risk. Anticoagulants that do not affect vitamin K metabolism are now available and make clinical trials feasible to answer the question of whether coumarins adversely affect bone. The research suggests that at a minimum, clinicians should carefully assess anticoagulated patients for osteoporosis risk, monitor BMD, and refer them to dietitians for dietary and supplement advice on bone health. Further research is needed to make more efficacious decisions about vitamin K intake, anticoagulant therapy, and bone health. 
PMID: 17906277 [PubMed - indexed for MEDLINE] 


Biofactors. 2012 Mar-Apr;38(2):151-7. doi: 10.1002/biof.1004. Epub 2012 Mar 15. Vitamin K, an emerging nutrient in brain function. 
Ferland G1.
Author information 
Historically discovered for its role in blood coagulation, there is now convincing evidence that vitamin K has important actions in the nervous system. As a unique cofactor to the γ-glutamyl carboxylase enzyme, vitamin K contributes to the biological activation of proteins Gas6 and protein S, ligands for the receptor tyrosine kinases of the TAM family (Tyro3, Axl, and Mer). Functionally, Gas6 has been involved in a wide range of cellular processes that include cell growth, survival, and apoptosis. In brain, vitamin K also participates in the synthesis of sphingolipids, an important class of lipids present in high concentrations in brain cell membranes. In addition to their structural role, sphingolipids are now known to partake in important cellular events such as proliferation, differentiation, senescence and cell-cell interactions. In recent years, studies have linked alterations in sphingolipid metabolism to age-related cognitive decline and neurodegenerative diseases such as Alzheimer's disease (AD). Emerging data also point to unique actions of the K vitamer menaquinone-4 (MK-4) against oxidative stress and inflammation. Finally, there is now data to suggest that vitamin K has the potential to influence psychomotor behavior and cognition. This review presents an overview of what is known of the role of vitamin K in brain function. 
Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc. 
PMID: 22419547 [PubMed - indexed for MEDLINE] 
Vitamin K and the Nervous System: An Overview of its Actions1,2 Guylaine Ferland* 
Department of Nutrition, Université de Montréal, Montreal, Quebec, Canada
*To whom correspondence should be addressed: E-mail: Questo indirizzo email è protetto dagli spambots. E' necessario abilitare JavaScript per vederlo.
Copyright © 2012 American Society for Nutrition
This article has been cited by other articles in PMC. 
The role of vitamin K in the nervous system has been somewhat neglected compared with other physiological systems despite the fact that this nutrient was identified some 40 y ago as essential for the synthesis of sphingolipids. Present in high concentrations in brain cell membranes, sphingolipids are now known to possess important cell signaling functions in addition to their structural role. In the past 20 y, additional support for vitamin K functions in the nervous system has come from the discovery and characterization of vitamin K– dependent proteins that are now known to play key roles in the central and peripheral nervous systems. Notably, protein Gas6 has been shown to be actively involved in cell survival, chemotaxis, mitogenesis, and cell growth of neurons and glial cells. Although limited in number, studies focusing on the relationship between vitamin K nutritional status and behavior and cognition have also become available, pointing to diet and certain drug treatments (i.e., warfarin derivatives) as potential modulators of the action of vitamin K in the nervous system. This review presents an overview of the research that first identified vitamin K as an important nutrient for the nervous system and summarizes recent findings that support this notion. 


Vitamin K Status and Vascular Calcification: Evidence from Observational and Clinical Studies
M. Kyla Shea3,* and Rachel M. Holden4 
3Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem NC; and 4Department of Medicine, Queen's University, Kingston, Ontario, Canada
*To whom correspondence should be addressed. E-mail: Questo indirizzo email è protetto dagli spambots. E' necessario abilitare JavaScript per vederlo.
Copyright © 2012 American Society for Nutrition
This article has been cited by other articles in PMC. 
Vascular calcification occurs when calcium accumulates in the intima (associated with atherosclerosis) and/or media layers of the vessel wall. Coronary artery calcification (CAC) reflects the calcium burden within the intima and media of the coronary arteries. In population-based studies, CAC independently predicts cardiovascular disease (CVD) and mortality. A preventive role for vitamin K in vascular calcification has been proposed based on its role in activating matrix Gla protein (MGP), a calcification inhibitor that is expressed in vascular tissue. Although animal and in vitro data support this role of vitamin K, overall data from human studies are inconsistent. The majority of population-based studies have relied on vitamin K intake to measure status. Phylloquinone is the primary dietary form of vitamin K and available supplementation trials, albeit limited, suggest phylloquinone supplementation is relevant to CAC. Yet observational studies have found higher dietary menaquinone, but not phylloquinone, to be associated with less calcification. Vascular calcification is highly prevalent in certain patient populations, especially in those with chronic kidney disease (CKD), and it is plausible vitamin K may contribute to reducing vascular calcification in patients at higher risk. Subclinical vitamin K deficiency has been reported in CKD patients, but studies linking vitamin K status to calcification outcomes in CKD are needed to clarify whether or not improving vitamin K status is associated with improved vascular health in CKD. This review summarizes the available evidence of vitamin K and vascular calcification in population-based studies and clinic-based studies, with a specific focus on CKD patients. 
Hematol Oncol Clin North Am. 2000 Apr;14(2):339-53.
A comprehensive review of vitamin K and vitamin K antagonists. 
Vermeer C1, Schurgers LJ. Author information 
For more than 60 years, vitamin K-dependent proteins have been known to play an important role in regulating blood coagulation. During recent years it has become clear, however, that vitamin K is also involved in other physiologic processes, including bone metabolism and vascular biology. Because the vitamin K requirement of bone and vessel wall is higher than that of the liver (where the clotting factors are produced) recommended daily allowance (RDA) values for K vitamins must be redefined. According to the new definition, a substantial part of the population is mildly deficient in vitamin K, and at later ages this deficiency may contribute to increased bone fracture risk, arterial calcification, and cardiovascular disease. 
PMID: 10806559 [PubMed - indexed for MEDLINE] Food Nutr Res. 2012; 56: 10.3402/fnr.v56i0.5329.
Published online 2012 Apr 2. doi:  10.3402/fnr.v56i0.5329
Vitamin K: the effect on health beyond coagulation – an overview
Cees Vermeer*
This article has been cited by other articles in PMC.
Vitamin K is essential for the synthesis of proteins belonging to the Gla-protein family. To the members of this family belong four blood coagulation factors, which all are exclusively formed in the liver. The importance of vitamin K for hemostasis is demonstrated from the fact that vitamin K-deficiency is an acute, life-threatening condition due to excessive bleeding. Other members of the Gla-protein family are osteocalcin, matrix Gla-protein (MGP), and Gas6 that play key functions in maintaining bone strength, arterial calcification inhibition, and cell growth regulation, respectively. In total 17 Gla-proteins have been discovered at this time. Recently, it was observed that the dietary vitamin K requirement for the synthesis of the coagulation factors is much lower than for that of the extra-hepatic Gla-proteins. This forms the basis of the triage theory stating that during poor dietary supply, vitamins are preferentially utilized for functions that are important for immediate survival. This explains why in the healthy population all clotting factors are synthesized in their active form, whereas the synthesis of other Gla-proteins is sub-optimal in non-supplemented subjects. Prolonged sub-clinical vitamin K deficiency is a risk factor for osteoporosis, atherosclerosis, and cancer. Present recommendations for dietary intake are based on the daily dose required to prevent bleeding. Accumulating scientific data suggests that new, higher recommendations for vitamin K intake should be formulated.