What is Vitamin K?
This post was written with Consensus AI Academic Search Engine – please read our Disclaimer at the end of this article. Vitamin K is a fat-soluble vitamin that plays a crucial role in various physiological processes, including blood clotting, bone health, and cardiovascular function. Discovered in 1935 by Danish biochemist Henrik Dam, vitamin K was initially identified for its essential role in blood coagulation, hence the name “Koagulation Vitamin” or vitamin K1. Other names include: 2-methyl-1,4-naphthoquinone, 2-methyl-3-phytyl-1,4-naphthoquinone, 4-Amino-2-Methyl-1-Naphthol, Fat-Soluble Vitamin, Menadiol, Menadiol Acetate, Menadiol Diacetate, Menadiol Sodium Diphosphate, Menadiol Sodium Phosphate, Menadiolum Solubile Methynaphthohydroquinone, Menadione, Ménadione, Menadione Sodium Bisulfite, Menaquinone, Ménaquinone, Menatetrenone, Menatétrenone, Phytonadione, Methylphytyl Naphthoquinone, Phylloquinone, Phytomenadione, Vitamina K, Vitamine K, Vitamine Liposoluble, Vitamine Soluble dans les Graisses.
Types of Vitamin K
Vitamin K exists in two primary forms: phylloquinone (K1) and menaquinones (MK-n). Phylloquinone is predominantly found in green leafy vegetables and certain plant oils, while menaquinones are present in fermented foods and synthesized by gut bacteria1. The different forms of menaquinones vary in the length and saturation of their isoprenyl side chains, which influence their biological activity and tissue distribution3.
Biological Functions of Vitamin K
Blood Clotting
Vitamin K is essential for the synthesis of clotting factors in the liver. It acts as a cofactor for the enzyme gamma-glutamyl carboxylase, which modifies specific glutamate residues in clotting factors to gamma-carboxyglutamate (Gla) residues. This modification is crucial for the binding of calcium ions, which is necessary for the clotting cascade1.
Bone Health
Vitamin K is also vital for bone health. It is involved in the carboxylation of osteocalcin, a protein that binds calcium in the bone matrix, thereby contributing to bone mineralization and strength. Suboptimal vitamin K status has been linked to lower bone mineral density (BMD) and an increased risk of fractures1 2. Clinical trials have shown that vitamin K supplementation can reduce the levels of undercarboxylated osteocalcin, a marker of vitamin K deficiency, and may help in maintaining bone health in postmenopausal women2 10.
Cardiovascular Health
Vitamin K plays a role in preventing vascular calcification, a risk factor for cardiovascular disease. Matrix Gla protein (MGP), a vitamin K-dependent protein, inhibits arterial calcification. Studies have shown that vitamin K supplementation can improve the carboxylation status of MGP, potentially reducing the progression of vascular calcification5 6 8.
Vitamin K Metabolism
Dietary vitamin K is absorbed in the small intestine and transported to the liver, where it is incorporated into lipoproteins and distributed to various tissues. Both phylloquinone and menaquinones can be converted to menaquinone-4 (MK-4) in tissues, which is the most biologically active form of vitamin K in extrahepatic tissues3 9.
Health Implications of Vitamin K
Bone Health
Several studies have investigated the role of vitamin K in bone health. For instance, the ECKO trial found that high-dose vitamin K1 supplementation did not significantly affect BMD but may reduce the risk of fractures in postmenopausal women with osteopenia2. Another study demonstrated that vitamin K supplementation, along with vitamin D and calcium, increased BMD and reduced undercarboxylated osteocalcin levels in postmenopausal women10.
Cardiovascular Health
The InterVitaminK trial aims to investigate the effects of vitamin K supplementation on cardiovascular health, particularly in preventing the progression of vascular calcification in an aging population5. However, the RenaKvit trial found no significant effect of vitamin K supplementation on arterial calcification in dialysis patients, despite improved vitamin K status6.
Insulin Resistance
Vitamin K may also have a beneficial role in insulin resistance. A study found that vitamin K supplementation for 36 months reduced the progression of insulin resistance in older men, although no significant effects were observed in women4.
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Adverse Effects of Vitamin K
No Procoagulant Effects in Dialysis Patients
One year of vitamin K (MK-7) supplementation in dialysis patients showed no detectable effects on biomarkers of coagulation activation, clot activities of vitamin K-dependent coagulation factors, or vascular events, indicating no procoagulant effects1.
Bone Mineral Density (BMD) Effects
In dialysis patients, MK-7 supplementation resulted in an accelerated BMD loss at the distal radius but prevented a decline in lumbar spine BMD, suggesting site-specific effects on bone density5.
In postmenopausal women with osteopenia, high-dose vitamin K1 supplementation did not protect against age-related decline in BMD but may reduce fractures and cancers8.
Interaction with Vitamin E
High vitamin E intake can lower tissue concentrations of vitamin K, indicating a nutrient-nutrient interaction that may affect vitamin K status adversely7.
Potential Protective Effects Against Vascular Calcification
Vitamin K1 supplementation in hemodialysis patients showed a reduction in the progression of thoracic aortic and coronary artery calcifications, suggesting a protective effect against vascular calcification9.
However, in another study, withdrawal of vitamin K antagonists and high-dose vitamin K2 did not significantly affect vascular calcification progression in hemodialysis patients10.
No Severe Adverse Events in General Population
In a general aging population, MK-7 supplementation was considered safe with no severe adverse events reported3.
Effects on Coagulation and Bone Health
Vitamin K antagonists, commonly used to reduce thromboembolic risk, may accelerate vascular calcification in hemodialysis patients, potentially due to functional vitamin K deficiency4.
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How has Vitamin K Improved Patient Outcomes?
Anticoagulation Stability in Warfarin-Treated Patients
Increasing dietary Vitamin K intake or supplementation improves anticoagulation stability in patients treated with warfarin, leading to more time within the therapeutic range and fewer bleeding and thrombotic complications2 3.
Patients receiving dietary Vitamin K had a greater proportion achieving stable anticoagulation compared to those receiving general dietary advice2.
Vascular Health in Hemodialysis Patients
Vitamin K supplementation reduces levels of inactive matrix Gla protein (MGP), a marker of vascular calcification, in hemodialysis patients, indicating improved Vitamin K status5 8.
Despite improved Vitamin K status, there was no significant effect on the progression of vascular calcification or vascular stiffness in hemodialysis patients5 6 9.
Vascular Health in Kidney Transplant Recipients
Vitamin K supplementation did not significantly reduce vascular stiffness or calcification in kidney transplant recipients over one year7 10.
General Vascular Health in Older Adults with Vascular Disease
Six months of Vitamin K2 supplementation did not improve markers of vascular health or physical function in older patients with established vascular disease1.
Quality of Life in Anticoagulated Patients
Both conventional dose adjustment and dietary Vitamin K strategies improved health-related quality of life (HRQoL) in anticoagulated patients, with no significant difference between the two approaches4.
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Vitamin K Mechanisms of Action
Blood Clotting and Carboxylation
Vitamin K is essential for the carboxylation of specific glutamate residues in proteins, converting them into gamma-carboxyglutamate (Gla) residues, which are necessary for the biological activity of these proteins, particularly in blood clotting2.
Bone Health and Osteocalcin
Vitamin K is crucial for the carboxylation of osteocalcin, a protein secreted by osteoblasts that is involved in bone mineralization. Carboxylated osteocalcin (cOC) is necessary for binding calcium in the bone matrix, thereby enhancing bone strength and reducing fracture risk2 8.
Low dietary intake of Vitamin K is associated with increased levels of uncarboxylated osteocalcin (ucOC), which is a marker of poor bone health2 8.
Glucose Metabolism and Insulin Sensitivity
Vitamin K2 (menaquinone) has been shown to improve insulin sensitivity and glucose metabolism by modulating osteocalcin levels. Increased carboxylation of osteocalcin enhances its endocrine functions, which include promoting insulin secretion and sensitivity1 5 6.
Vitamin K2 supplementation in diabetic rats led to improved glycemic control and increased expression of genes related to insulin production and beta-cell function1.
Vascular Health and Calcification
Vitamin K2 inhibits vascular calcification by downregulating the expression of bone morphogenetic proteins (BMPs) and other osteoblast markers in vascular smooth muscle cells, thereby preventing the calcification process3.
Vitamin K status is inversely associated with inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP), which are involved in vascular health and bone turnover8.
Metabolism and Tissue Distribution
Different forms of dietary Vitamin K (phylloquinone and menaquinones) are converted to menaquinone-4 (MK4) in tissues, indicating a common metabolic pathway for these forms of Vitamin K4.
Tissue concentrations of Vitamin K and the expression of key enzymes involved in its metabolism are influenced by factors such as diet and sex, but not housing conditions in animal models10.
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Common Complaints Associated with Vitamin K Use
Cognitive Impairment and Survival Rates
Low vitamin K intake is associated with cognitive deficits, such as impaired learning and memory, and reduced survival rates in animal models1.
Vascular Health and Calcification
Vitamin K deficiency is linked to increased vascular stiffness and calcification, which are markers of cardiovascular disease. However, supplementation did not significantly reduce these issues in kidney transplant recipients or hemodialysis patients2 3 5.
Bone Health
Suboptimal vitamin K status can adversely affect bone mineral density (BMD) and increase the risk of bone fractures. This is particularly evident in postmenopausal women and individuals with low dietary intake of vitamin K4.
Anticoagulation Stability
Variations in dietary vitamin K intake can significantly impact the stability of anticoagulation therapy, leading to either overcoagulation or undercoagulation in patients on vitamin K antagonists6.
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