Vitamin K

Vitamin K is a significant but often underappreciated nutrient. Essential for various bodily functions, Vitamin K's role extends beyond its well-known contribution to blood clotting. 

Vitamin K, existing in two primary forms – K1 (phylloquinone) and K2 (menaquinones) – plays a pivotal role in health. K1 is predominantly found in green leafy vegetables and is the main form involved in clotting processes, while K2, derived from some animal-sourced foods and fermented products, is crucial for bone and cardiovascular health.

This article explores Vitamin K as a biomarker, delving into its functions, dietary sources, and daily requirements, and discussing the significance of lab testing for Vitamin K and related biomarkers.

Understanding Vitamin K

What is Vitamin K?

Vitamin K is a group of fat-soluble vitamins crucial for blood coagulation, bone metabolism, and regulating blood calcium levels. It exists mainly in two forms, and each has unique roles in the body:

• Vitamin K1 (Phylloquinone): Found predominantly in green leafy vegetables, K1 is primarily involved in blood clotting.  

• Vitamin K2 (Menaquinones): vitamin K2 is a group of compounds called menaquinones; they are found in fermented foods and some animal products; they are also synthesized by some gut bacteria.  They may play stronger role in bone and cardiovascular health.  

The various forms of vitamin K2 include:

Menaquinone-4 (MK-4)

Menaquinone-7 (MK-7)

Menaquinone-8 (MK-8)

Menaquinone-9 (MK-9)

Menaquinone-10 (MK-10)

Menaquinone-11 (MK-11)

Menaquinone-12 (MK-12)

While both forms contribute to overall health, their distinct functions underscore the importance of a balanced intake of vitamin K1 from plant sources and vitamin K2 from animal and fermented foods for optimal health outcomes.  

Both forms are available as supplements, although vitamin K1 is the predominant form used to treat deficiency.  [8.]

Another form of vitamin K exists, vitamin K3 or menadione.  VItamin K3 is the synthetic form of vitamin K which interferes with glutathione, and causes toxicity to animals. For this reason, vitamin K3 is no longer used as a treatment for vitamin K deficiency.  [6.]

What Does Vitamin K Do? [6., 8.]

• Blood Clotting: vitamin K is essential for the synthesis of clotting factors II (prothrombin), VII, IX, and X in the liver, which are crucial for normal blood coagulation.

• Bone Health: vitamin K2 contributes to bone health by regulating calcium deposition, aiding in the maintenance of strong bones, and reducing fracture risk.  Specifically, vitamin K facilitates the carboxylation of osteocalcin, a protein that regulates bone mineralization by binding to hydroxyapatite crystals in bone tissue, thus contributing to bone health and density.

• Cardiovascular Health: vitamin K2 may help prevent calcification of arteries, thus playing a protective role in cardiovascular health.  Vitamin K prevents calcium deposition in arteries and veins by activating matrix Gla protein (MGP), which inhibits vascular calcification and maintains cardiovascular health.

• Cellular Health: additionally, vitamin K is implicated in cell signaling pathways, inflammation regulation, and cell proliferation, although the mechanisms underlying these functions are still being elucidated.

• Metabolic and Immune Function: emerging research suggests potential roles for vitamin K in other physiological processes including insulin sensitivity, glucose metabolism, and immune function, highlighting its multifaceted impact on overall health and well-being.

• Neurological function: emerging research suggests a potential role for vitamin K in neurological health, including neuronal survival, synaptic plasticity, and cognitive function, although further studies are needed to elucidate its mechanisms fully.

What is the Difference Between Vitamin K1 and Vitamin K2?  [4.]

Vitamin K1 (phylloquinone) and vitamin K2 (menaquinones) serve distinct yet overlapping functions in the body. 

Vitamin K1 is primarily involved in blood clotting, as it acts as a cofactor for the enzyme gamma-glutamyl carboxylase, facilitating the carboxylation of clotting factors in the liver. 

In contrast, vitamin K2, particularly menaquinone-4 (MK-4) and menaquinone-7 (MK-7), plays a crucial role in extrahepatic tissues such as bones and blood vessels. 

MK-4 is synthesized in animal tissues and serves as a cofactor for gamma-carboxylation reactions, contributing to bone metabolism and the regulation of vascular calcification. 

MK-7, derived from fermented foods, has a longer half-life and is involved in preventing arterial calcification by activating matrix Gla protein (MGP), thereby regulating calcium deposition in blood vessel walls.

Sources of Vitamin K  [9.]

Green Leafy Vegetables: kale, spinach, parsley and broccoli are high in Vitamin K1.

Fermented Foods: natto, a fermented soybean product, is particularly rich in Vitamin K2.

Animal Products: certain cheeses and meats can also provide Vitamin K2.

Vitamin K Deficiency  [3.]

While Vitamin K deficiency is rare in adults, it can lead to increased bleeding time due to impaired blood clotting. Newborns are at a higher risk of Vitamin K deficiency, which is typically prevented through supplementation at birth.

Balancing Vitamin K1 Intake with Anticoagulant Therapies

Particularly for individuals on anticoagulant medications like warfarin, balancing Vitamin K1 intake is important to avoid interfering with the medication's effectiveness. Consistent dietary intake of Vitamin K1 helps in managing its levels.

Individuals on anticoagulant medications should speak with their healthcare provider regarding an appropriate intake of vitamin K, particularly vitamin K1 from vegetables.  

Recommended Vitamin K Intake and Supplementation

RDA of Vitamin K  [9.]

The Recommended Dietary Allowance (RDA) for vitamin K varies based on age and gender.

For adult men, the RDA is 120 micrograms (mcg) of vitamin K per day.  For adult women, the RDA is 90 mcg per day.  The RDA does not change in pregnancy or lactation. 

Indications for Vitamin K Supplementation  [3., 6., 8.]

Vitamin K Deficiency

Although rare, Vitamin K deficiency can lead to serious health issues.  Symptoms of deficiency can include easy bruising, excessive bleeding from wounds or punctures, and heavy menstrual bleeding in women.

Populations at increased risk of vitamin K deficiency include newborns, individuals with certain digestive disorders affecting nutrient absorption, and those on long-term antibiotics are more susceptible to Vitamin K deficiency.

Blood Clotting Disorders

Vitamin K is crucial for synthesizing clotting factors, which are proteins necessary for blood coagulation.

Bone Health

Vitamin K plays a key role in bone metabolism by aiding in the carboxylation of certain bone proteins; this contributes to bone formation and maintenance and reduces the risk of osteoporosis.

Cardiovascular Health

This benefit is particularly associated with Vitamin K2, which helps prevent the calcification of arteries and other soft tissues.

Prevention and Treatment of Bleeding Disorders

Adequate Vitamin K levels are essential for normal blood clotting, preventing conditions like hemorrhagic disease, particularly in newborns.

Lab Testing for Vitamin K

Measuring Vitamin K levels in the body is essential for assessing its sufficiency and for guiding dietary and medical interventions. 

Methods of Vitamin K Testing

Vitamin K levels are usually measured through blood tests in serum and plasma. [8.]

However, direct measurement of Vitamin K in the blood is controversial.  [1., 2.]

Instead, some experts recommend indirect testing that assess blood clotting:

Prothrombin Time (PT) Test and PTT Test: these tests measure how long it takes for blood to clot. Since Vitamin K is vital for clotting, prolonged clotting time can suggest a deficiency.

Some experts note that urinary metabolites of vitamin K may be an alternative method of testing.  [1.]

Interpreting Vitamin K Test Results

Reference ranges can vary depending on the lab used; therefore it is important to contact the laboratory used to determine reference ranges.  

Reference ranges for vitamin K testing in the serum are often given as 0.2-3.2 ng/mL, although  impaired blood clotting has been associated with levels below 0.5 ng/mL.  [10.]

Factors Influencing Vitamin K Levels

Several factors can affect Vitamin K levels and/or function in the body:

Dietary Intake: the amount and type of Vitamin K-rich foods consumed significantly influence blood levels.

Gut Health: conditions affecting gut health, such as celiac disease or Crohn’s disease, can impair Vitamin K absorption.

Medications: certain medications like antibiotics and anticoagulants, can affect Vitamin K metabolism.  Specifically, broad-spectrum antibiotics can deplete the bacteria that produce vitamin K, while cephalosporins can inhibit vitamin K function.  [6.]  Anticoagulants impair vitamin K function.  

The Clinical Importance of Vitamin K Testing

Regular testing of Vitamin K levels is important in certain situations:

Identifying Deficiencies: early detection of low Vitamin K levels is crucial, especially in populations at risk, like newborns and individuals with malabsorption disorders.

Guiding Treatment: in cases of bleeding disorders or osteoporosis, Vitamin K testing can inform treatment strategies.

Monitoring for Medication Interactions: for individuals on anticoagulant therapy, monitoring Vitamin K levels may be important.

Related Biomarkers and Their Testing

To fully understand the function of Vitamin K in the body, considering related biomarkers may provide insight.

Biomarkers Associated with Vitamin K

The effectiveness and activity of Vitamin K in the body are closely related to several other health markers:

• Vitamin D: vitamin D and Vitamin K work synergistically in bone health and calcium metabolism, making it important to assess Vitamin D levels when assessing bone health.

• Prothrombin time test with an INR (PT/INR): the prothrombin time test with an international normalized ratio (PT/INR) is a laboratory test used to assess the blood's ability to clot by measuring the time it takes for blood to clot, normalized to a standard scale, to monitor and evaluate coagulation status and the effectiveness of anticoagulant therapy.  PT monitors the extrinsic clotting pathway.  

• Partial Thromboplastin time (PTT): the partial thromboplastin time (PTT) test is a laboratory assay used to evaluate the intrinsic pathway of coagulation, measuring the time it takes for blood to clot when specific reagents are added. It is often employed to assess the function of factors involved in the clotting cascade and to monitor patients on heparin therapy.

Diet and Lifestyle Measures to Optimize Vitamin K Levels and Function

• Incorporate vitamin K-rich foods into your diet, such as leafy greens (e.g., kale, spinach, Swiss chard), broccoli, Brussels sprouts, and parsley.  [ 9.]  Individuals on anticoagulant medications should speak to their doctor before adjusting their dietary intake of these vegetables. 

• Consume fermented foods like natto, sauerkraut, and kefir, which contain vitamin K2-producing bacteria.  [9.]

• Include healthy fats in your diet, as vitamin K is fat-soluble and requires dietary fats for absorption. Examples include olive oil, avocado, nuts, and seeds.

• Avoid excessive alcohol consumption, as it may impair vitamin K absorption and utilization.  [5.]

• Engage in regular physical activity, which supports overall metabolic health and may indirectly enhance vitamin K function.

• Practice stress management techniques, as chronic stress can negatively impact nutrient absorption and utilization and affect vitamin K-dependent proteins and is associated with increased oxidative stress and depression.  [11.]

Order Vitamin K Testing

Click here to view and order vitamin K testing as part of a comprehensive nutrient panel.