Observed genes

Polygenic score

Influential genes: ZPR1,CYP4F2

The activity of the CYP4F2 gene is crucial for the transformation of vitamin K into its active form, which plays a vital role in the synthesis of clotting factors within the liver.

ZPR1 gene encodes a protein that is believed to play a critical role in cell signaling and is important for the growth and proliferation of cells.

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Summary

Vitamin K is a fat-soluble vitamin required for the production of certain proteins involved in blood clotting and bone metabolism. Vitamin K deficiency can lead to blood clotting issues, like bruising and nosebleeds, weak bones, and an increased risk of cardiovascular disease.

Overview 

Vitamin K is a vital fat-soluble nutrient (together with vitamin A, D and E), essential for blood clotting and bone health. It plays a pivotal role in producing proteins necessary for preventing excessive bleeding from wounds as well as maintaining strong bones by producing osteocalcin. There are various forms of vitamin K, such as K1 found in leafy greens and K2 from gut bacteria and certain foods.

Vitamin K deficiency can lead to blood clotting issues, like bruising and nosebleeds, weak bones, and an increased risk of cardiovascular disease.

While vitamin K deficiency is rare in healthy adults, it can occur with some severe underlying conditions, gastrointestinal problems or prolonged antibiotic use. Newborns are susceptible to vitamin K deficiency, which can lead to bleeding, so they receive a vitamin K injection after birth.

Excessive vitamin K intake typically doesn't cause problems in the general population due to rapid breakdown and excretion.

What is Vitamin K and its function?

Vitamin K is a fat-soluble vitamin responsible for several functions in our body. 

Vitamin K is required for the production of certain proteins involved in blood clotting and bone metabolism. 

Blood clotting is a process that prevents excessive bleeding from wounds. 4 out of 13 proteins involved in this process are vitamin K dependent. 

In bones, vitamin K is required to produce osteocalcin, a protein needed to prevent bone weakness. Some studies also researched vitamin K's role in heart health. It takes part in making proteins that help prevent calcification and hardening of arteries.^[1]

Types and sources

Vitamin K refers to a group of compounds with the same chemical structure. These compounds are phylloquinone (vitamin K1) and menoquinones (vitamin K2). They are naturally found in a variety of foods and are also available as supplements. 

Phylloquinone can be obtained from green leafy vegetables, like spinach, kale, or Brussels sprouts, and it is the predominant dietary form. 

Our gut bacteria is the primary source of menaquinones, but it is also present in smaller amounts in some animal-based and fermented foods, such as meat, cheese, eggs, and fermented soybeans.^[2,3]

Requirements 

Recommended Vitamin K intake varies based on age and gender. Most individuals can meet the required amount by maintaining a well-balanced diet. 

The recommended daily intake is listed in the table below^[1]:

Vitamin K deficiency 

A deficiency in Vitamin K can give rise to some adverse health effects. When your Vitamin K levels are low, it can compromise your blood clotting ability, potentially resulting in the following symptoms:

• Bruising (bleeding into the skin)
• Epistaxis (nosebleeds)
• Gastrointestinal bleeding, which may manifest as vomiting with blood or blood in the stool
• Hematuria (presence of blood in urine)

Furthermore, vitamin K deficiency can also result in decreased bone mineralization and the development of osteoporosis, a condition characterized by weak bone, increasing the risk of fractures.^[2,5]

A new study has also shown that vitamin K insufficiency is significantly higher in people with cardiovascular disease and is also strongly linked to an increased risk of cardiovascular mortality.^[4]

Vitamin K deficiency in a healthy adult is rare and typically manifests in the presence of underlying severe medical conditions, such as cystic fibrosis, bile duct obstruction, or celiac disease. Additionally, prolonged antibiotic therapy can disrupt the balance of beneficial bacteria responsible for synthesizing vitamin K, thereby reducing its levels in the body.

On the other hand, newborns are naturally prone to vitamin K deficiency. Their intestinal flora has not developed yet, so they lack vitamin K-producing bacteria. Furthermore, breast milk contains really low amounts of this nutrient. During the first few weeks of life, vitamin K deficiency can cause vitamin K deficiency bleeding (VKDB), a condition associated with bleeding in the umbilicus, gastrointestinal tract, skin, nose, or other sites.  For this reason, all newborns are recommended to get a single intramuscular injection of vitamin K.^[5]

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Vitamin K excess 

Vitamin K is broken down very quickly and excreted in urine or stool. Because of that, there have been no reported adverse effects from vitamin K excess in any amount from food or supplements in the general population. 

However, people taking warfarin must be careful about their vitamin K levels, maintaining a consistent intake. Warfarin is an anticoagulant (a blood-thinning medication) that works by antagonizing the activity of vitamin K. This leads to the depletion of vitamin K-dependent coagulation factors, thus preventing thrombosis. Sudden changes in vitamin K intake can increase or decrease the activity of the drug, leading to adverse health effects like bleeding or thrombosis.^[2]

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Genetics 

In general, there are two well-known genes associated with the vitamin K molecular processes. The first gene, VKORC1, plays a key role in activating vitamin K. The second gene is GGCX, which is involved in the modification of vitamin K-dependent proteins that are essential for blood clotting. Genetic changes in these genes may lead to several health problems.

The VKORC1 gene has a significant role in the vitamin K activation. Vitamin K is needed for coagulation, energy metabolism, or arterial calcification prevention. There are multiple steps leading to its activation, such as conversion to vitamin K-epoxide followed by its reduction by VKORC1 enzyme. A number of polymorphisms and mutations connected to VKORC1 have been reported. ^[6]

The GGCX gene is another participant in the vitamin K cycle, it produces the enzyme Gamma-glutamyl carboxylase, which modifies vitamin K-dependent proteins. Changes affecting this gene can lead to vitamin K-dependent coagulation factor deficiency type 1 (VKCFD1). ^[7]

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Warfarin is known to interfere with the conversion step by inhibiting the reduction of VKORC1, and also negatively affects GGCX activity. Several studies addressing this issue have reported an association between identified single nucleotide polymorphisms (SNPs) and warfarin doses. Such studies and a more detailed understanding of pharmacogenomics are important for healthcare providers as they can guide drug dosing according to the respective needs of each patient. ^[8,9]

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Recommendations

• Ensure a well-balanced diet that includes foods rich in vitamin K. This includes green leafy vegetables like spinach and kale for vitamin K1 and animal-based or fermented foods for vitamin K2.
• If you have a newborn, ensure they receive the recommended vitamin K injection shortly after birth to prevent vitamin K deficiency bleeding (VKDB).
• If you are taking warfarin, be vigilant about your vitamin K levels. Maintain a consistent intake and consult your healthcare provider to manage your medication effectively.
• Heart Health: Given the potential role of vitamin K in heart health, consider incorporating vitamin K-rich foods into your diet as part of a broader heart-healthy lifestyle.
• To support strong bones and reduce the risk of osteoporosis, ensure you're meeting your vitamin K requirements, especially as you age.
• If you have underlying medical conditions affecting vitamin K absorption or metabolism, such as cystic fibrosis or celiac disease, discuss your nutritional needs with a healthcare provider and schedule regular check-ups to monitor your vitamin K levels.
• If you struggle to meet your vitamin K requirements through diet alone, consider vitamin K supplements under the guidance of a healthcare professional.

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