Vitamin K2

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. 

The group of vitamins that comprise vitamin K2 are called menaquinones, and they hold diverse roles in human health.  Unlike its counterpart, vitamin K1 which primarily aids in blood clotting, vitamin K2 plays multifaceted roles in bone metabolism, cardiovascular health, and emerging evidence points to its many other beneficial roles in human health. 

This article explores the functions of vitamin K2 more specifically as a biomarker by delving into its functions, dietary sources, and daily requirements, and discussing the significance of lab testing for Vitamin K and related biomarkers.

Definition and Function of Vitamin K2 

Definition of Vitamin K2: What is Vitamin K2?  [5., 7., 11.]

Structurally, both vitamins K1 and K2 have a methylated ring with an attached side chain. Vitamin K2 differs from vitamin K1 in its side chain length, which affects its bioactivity and bioavailability. 

Both vitamin K1 and K2 are absorbed similarly in the small intestine, but while vitamin K1 travels to the liver for blood clotting factor synthesis and conversion to vitamin K2, dietary vitamin K2 is preferentially transported to extrahepatic tissues like bones and arteries.  [5.]

Vitamin K2 refers to a group of compounds known as menaquinones (MQ), which are produced by bacteria in the gastrointestinal tract and also found in fermented foods. 

The distinct nature of Vitamin K2 lies in the different menaquinones, which are categorized by the length of their side chain (MK-4, MK-7, MK-9, etc.). 

These various forms have different biological activities and absorption rates, as well as different sources.

A list of all known menaquinones includes:

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)

These different forms of vitamin K2 have varying clinical significance, with MK-4 having a shorter half-life and MK-7 demonstrating greater bioavailability and persistence in the circulation. 

Menaquinone-4 (MK-4) is synthesized in animal tissues, particularly in the liver from dietary vitamin K1. Additionally, it can be found in some animal-based foods such as meat, liver, and eggs.

Menaquinone-7 (MK-7) is primarily produced by bacteria in the gastrointestinal tract, specifically in the colon. It is also found in certain fermented foods.

While vitamin K1 is primarily involved in blood clotting, vitamin K2 is more closely associated with bone and cardiovascular health due to its role in regulating calcium metabolism and preventing arterial calcification. Also, vitamin K2 may have additional roles in human health and wellness, as emerging research indicates.  

Functions of Vitamin K2  [5., 7., 9., 13.]

Regulation of Calcium Metabolism: vitamin K2 plays a crucial role in regulating calcium metabolism, particularly by facilitating the carboxylation of certain proteins involved in calcium utilization, such as osteocalcin and matrix Gla protein (MGP). 

This function helps in the proper deposition of calcium in bones and teeth, promoting skeletal health while preventing ectopic calcification in soft tissues.

Bone Health: by promoting bone mineralization and maintaining bone density, vitamin K2 contributes significantly to bone health and reduces the risk of osteoporosis and fractures.

By activating proteins that bind calcium to bones, vitamin K2 enhancing bone density and reduces the risk of fractures. Studies have shown that adequate Vitamin K2 intake is vital for bone metabolism and may be particularly beneficial in preventing osteoporosis, especially in postmenopausal women.  [9.]

Cardiovascular Health: vitamin K2 aids in preventing arterial calcification by activating matrix Gla protein (MGP), which inhibits the deposition of calcium in arterial walls. This function helps maintain the elasticity and integrity of blood vessels, reducing the risk of cardiovascular diseases like heart attacks and strokes.

Anti-Inflammatory Properties: vitamin K2 exhibits anti-inflammatory effects by modulating the expression of inflammatory mediators and cytokines, thereby contributing to overall immune health and reducing the risk of chronic inflammatory conditions.

Dental Health: low vitamin K2 levels are associated with the development of periodontal diseases.  [13.]

Cancer Prevention: some studies suggest that vitamin K2 may play a role in cancer prevention, particularly in reducing the risk of certain types of cancer such as breast and liver cancers, as well as leukemia and possibly other cancer types.  Further research is needed to elucidate its mechanisms and efficacy in this regard.  [8.]

Neurological Health: emerging evidence indicates that vitamin K2 may have neuroprotective effects and contribute to neurological health by supporting myelination, nerve function, and protecting against neurodegenerative diseases like Alzheimer's disease.  [2.]

Gut Health: Vitamin K2 may also influence gut health by modulating gut microbiota composition and function, although the exact mechanisms and implications require further investigation.  [2.]

Dietary Sources of Vitamin K2  [12.]

Unlike its counterpart, Vitamin K1, which is abundant in leafy green vegetables, Vitamin K2 is found in a different array of food sources, primarily in animal products and fermented foods.

Animal-Based Sources of K2

Egg Yolks: eggs, especially those from free-range chickens, can provide a good amount of Vitamin K2.

Meat: certain meats, particularly liver and other organ meats, are rich in Vitamin K2. The content can vary based on the animal's diet.  Chicken also contains vitamin K2.

Fatty Fish: some fatty fish including salmon and mackerel contain vitamin K2. 

Fermented Foods with Vitamin K2

Natto: a traditional Japanese food made from fermented soybeans, natto is one of the richest sources of Vitamin K2.

Sauerkraut: fermented cabbage, or sauerkraut, also contains Vitamin K2, although in lower amounts than natto.

Dairy and Fermented Dairy Products with Vitamin K2

Dairy Products including Butter and Cheese: these products can be good sources of Vitamin K2, especially when derived from grass-fed animals.

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Fermented Dairy including Yogurt and Fermented Cheeses: fermented dairy products like yogurt and fermented cheeses such as gouda and brie contain varying levels of Vitamin K2.

Vitamin K2 Supplements

For individuals who struggle to get enough Vitamin K2 from their diet, supplements can be a viable option. 

Supplements containing vitamin K2 often come in two forms: MK-4 and MK-7. MK-4 supplements are synthetic and have a shorter half-life, while MK-7, derived from natto, is natural and remains active in the body longer.

Vitamin K2 from Dietary Sources vs. Supplements

For those who can maintain a diet rich in Vitamin K2 (through cheese, natto, egg yolks, and meat), supplementation may not be necessary. Individuals who have dietary restrictions, such as vegans or those who have allergies to dairy or eggs, might find it challenging to get enough Vitamin K2 from diet alone and may consider supplements.

Vitamin K2 Absorption and Dietary Considerations

The absorption of Vitamin K2 from food can be influenced by several factors including the presence of dietary fat, as Vitamin K2 is fat-soluble. Hence, consuming Vitamin K2-rich foods as part of a meal that includes healthy fats can enhance absorption.

Vitamin K Deficiency  [4.]

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.

Recommended Vitamin K Intake

RDA of Vitamin K: How Much K2 Should I Get Per Day?  [12.]

The Recommended Dietary Allowance (RDA) for vitamin K varies based on age and gender.  There is no recommendation regarding vitamin K1 vs K2 intake. 

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. 

Gender-Specific Recommendations: How Much Vitamin K2 Should A Woman Get Per Day?

When considering "how much Vitamin K2 per day for a woman," it's important to note that the requirements may not significantly differ from men. The general RDA for adult women in 90 mcg a day.

However, women, especially postmenopausal women, might benefit more from Vitamin K2 due to its role in bone health.  [9.]

Individuals concerned about their vitamin K2 intake requirements should consult their healthcare provider and consider testing for vitamin K levels.

Indications for Vitamin K Supplementation  [4., 7., 11.]

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.

Balancing Vitamin K Intake with Anticoagulant Therapies

Particularly for individuals on anticoagulant medications like warfarin, balancing Vitamin K intake is important to avoid interfering with the medication's effectiveness. Consistent dietary intake of Vitamin K2 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.  

Lab Testing for Vitamin K2

Measuring Vitamin K2 levels in the body requires testing vitamin K levels, generally.  Alternatively, assessing clotting function may be appropriate.  

Methods of Vitamin K Testing

Vitamin K levels are usually measured through blood tests in serum and plasma. [11.]

However, direct measurement of Vitamin K in the blood is controversial.  [1., 3.]

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.  [14.]

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.  [10.]  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.  [12.]

• 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.  [6.]

• 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.  [15.]

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