Vitamin K: The effect on health beyond coagulation - An overview

VitaK and Cardiovascular Research Institute CARIM, Maastricht University, Maastricht, The Netherlands.
Food & Nutrition Research (Impact Factor: 1.79). 04/2012; 56. DOI: 10.3402/fnr.v56i0.5329
Source: PubMed


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.

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    • "MGP needs to undergo posttranslational activation in order to become biologically active. MGP shares similarities with vitamin K-dependent clotting factors and thus also depends on the activity and integrity of the vitamin K system [1] [7]. Mutagenesis of the Glu-residues into aspartateresidues indeed resembled the warfarin induced calcification phenotype [8]. "
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    ABSTRACT: With the discovery that vitamin K-dependent matrix Gla-protein (MGP) is a strong and modifiable factor in the prevention of arterial calcification, vitamin K was put forward as novel treatment option in cardiovascular disease. The vasculoprotective properties of vitamin K are in part based on the ability to improve gamma-glutamylcarboxylation of MGP, which is a prerequisite for MGP as a calcification inhibitor. Data from experimental animal models reveal that high intake of vitamin K can prevent and even reverse vascular calcifications. In addition, clinical data demonstrate that prescription of vitamin K antagonists for long-term oral anticoagulant therapy accelerates vascular calcification. However, controlled data from randomized prospective vitamin K interventional trials are lacking, thereby weakening a general recommendation for supplementation. The present article summarizes our current knowledge on the association between vitamin K and cardiovascular health. Additionally, we focus on an outlook on important ongoing prospective vitamin K intervention studies. These studies address the issues whether vitamin K substitution helps modifying relevant cardiovascular surrogates such as vascular calcification and whether non-vitamin K oral anticoagulants provide an alternative to support cardiovascular health benefits. So research about cardiovascular protection by vitamin K is an evolving field in which we expect a boost of novel and relevant evidence shortly. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Feb 2015 · Atherosclerosis
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    • "For example, phylloquinone from fruit and vegetables is tightly bound to the plant cell membranes and is less bioavailable than phylloquinone from plant oils or phylloquinone supplements [8] [11]. Also, as the length of the side chain increases, the lipophylicity (fat solubility) of menaquinones increases [5]. Therefore, the bioavailability and intestinal uptake of different forms of vitamin K is partly dependent on the composition of the meal or the food matrix in which they are present. "
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    ABSTRACT: Aside from its important role in blood clotting, vitamin K is an important dietary factor in regulating bone and cartilage mineralization. The vitamin K requirements to maintain musculoskeletal health may be more than the current recommendations and subclinical vitamin K deficiency may be involved in the pathogenesis of osteoporosis and osteoarthritis. Observational studies suggest that diets low in vitamin K are associated with increased risk of fractures and osteoarthritis in older adults. However, so far randomized controlled trials of vitamin K supplementation in Caucasian populations have not shown clinically significant improvements in bone mineral density at major skeletal sites. Supplementation with vitamin K may reduce the risk of fractures, but this conclusion comes from clinical trials with methodological limitations. At this time, only one randomized controlled trial has examined the effect of vitamin K supplementation on radiographic hand osteoarthritis and found no overall effect. Large well-designed randomized controlled trials are needed to compare the efficacies of vitamin K1 and K2 on fractures and osteoarthritis among older adults. In summary, currently there is not enough evidence to recommend the use of vitamin K supplements for the prevention of bone loss, fractures, or osteoarthritis in postmenopausal women.
    Full-text · Article · Aug 2014 · Molecular Nutrition & Food Research
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    • "Our results emphasize that the involvement of this protein should be considered whenever conditions for correct carboxylation of VKDPs are affected. Furthermore, the measurement of carboxylation degree of Gla proteins, such as MGP, osteocalcin, and prothrombin, has been proposed as a marker for certain pathological conditions and vitamin K status [14, 40, 45, 46]. Further investigation aiming to correlate circulating levels and γ-carboxylation status of GRP with the degree of calcification and disease progression are currently in progress in our labs. "
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    ABSTRACT: Gla-rich protein (GRP) was described in sturgeon as a new vitamin-K-dependent protein (VKDP) with a high density of Gla residues and associated with ectopic calcifications in humans. Although VKDPs function has been related with γ-carboxylation, the Gla status of GRP in humans is still unknown. Here, we investigated the expression of recently identified GRP spliced transcripts, the γ-carboxylation status, and its association with ectopic calcifications, in skin basal cell and breast carcinomas. GRP-F1 was identified as the predominant splice variant expressed in healthy and cancer tissues. Patterns of γ-carboxylated GRP (cGRP)/undercarboxylated GRP (ucGRP) accumulation in healthy and cancer tissues were determined by immunohistochemistry, using newly developed conformation-specific antibodies. Both GRP protein forms were found colocalized in healthy tissues, while ucGRP was the predominant form associated with tumor cells. Both cGRP and ucGRP found at sites of microcalcifications were shown to have in vitro calcium mineral-binding capacity. The decreased levels of cGRP and predominance of ucGRP in tumor cells suggest that GRP may represent a new target for the anticancer potential of vitamin K. Also, the direct interaction of cGRP and ucGRP with BCP crystals provides a possible mechanism explaining GRP association with pathological mineralization.
    Full-text · Article · Apr 2014 · BioMed Research International
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