Vitamin K Genes: Bone strength, blood clots

Vitamin K is one of those vitamins that doesn’t get a lot of press. You may have heard of it in relation to preventing osteoporosis, but it turns out this little-known vitamin impacts overall health as we age.

In this article, I’ll explain what vitamin K does in the body and how your genes affect the conversion of vitamin K. If you are struggling with Warfarin dosing, your genes may hold the answers. Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today 

Vitamin K Genes: Bleeding and Bones

There are two different forms of Vitamin K:

  • Vitamin K1, is a fat-soluble vitamin needed by our bodies to synthesize the proteins responsible for blood coagulation. Without vitamin K1, also known as phylloquinone, bleeding is hard to control.
  • Vitamin K2, also known as menaquinone, comes in several different forms (MK-4, MK-7, MK-8, MK-10). It helps maintain bone strength. Additionally, higher levels of K2 have been shown to reduce calcification in the arteries[ref], as well as possibly play a role in mitochondrial function.[ref]

Vitamin K levels have links to osteoporosis (low bone density). Lower vitamin K levels are associated with a higher risk of osteoporosis.[ref]

Beyond coagulation and bone health:

Recent studies show vitamin K plays an important role in preventing several age-related diseases.

Vitamin K interacts with vitamin D and calcium. It is vital in the interplay between calcification and inflammation.

Vitamin K is also an essential co-factor for reactions involving the enzyme vitamin K carboxylase. These enzyme-catalyzed reactions activate VKD (vitamin-K dependent) proteins.[ref] While the most well-known VKD proteins are involved in blood clotting, recent research has shed a lot of light on VDK proteins that contribute to vascular calcification and apoptosis.[ref]

The role of K2 in mitochondrial function is still being determined, but more recent research shows some promising results. It acts as an intercellular antioxidant, and it also acts as an electron carrier in the mitochondria.[ref][ref]

What sources do we have for vitamin K?

We get vitamin K1 from eating green plants, as phylloquinone is a part of the photosynthesis process.

Pasture-raised eggs, dairy, organ meat, and fermented soy (natto) contain the highest amounts of vitaminK2. We can also convert K1 to K2 in some organs of our bodies, and certain residents of our gut microbiome (E. coli especially) convert K1 to K2 for us.

Vitamin K Genotype Report

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CYP4F2 gene:

The CYP4F2 codes for the enzyme involved in converting both vitaminK1 and vitaminK2 (MK-4) to oxidized forms, thus regulating the amount of vitamin K available.[ref]

Genetic variation in the CYP4F2 gene causes people to naturally have higher or lower levels of vitamin K available, which can affect blood clotting. Warfarin, a commonly prescribed blood thinner, works by acting on vitamin K, and CYP4F2 variants can affect Warfarin dosage levels.

A quick note of caution on Warfarin dosages: While the information provided here is based on research studies, always talk with your doctor about medication questions. There are multiple genetic variants affecting the metabolism of a drug.

Because the body regulates the amount of vitamin K via CYP4F2, someone with a genetic variant that slows down their CYP4F2 production could have higher circulating levels of vitamin K, depending on the foods they have eaten.[ref] Thus, Warfarin dosages may need to be higher for someone with an impaired CYP4F2. (If you are wondering why so many studies on Warfarin exist… about 30 million people in the US are prescribed the drug each year.[ref])

CYP4F2 also helps break down certain omega 6 fatty acids and vitamin E, so it plays an important role in our body’s inflammatory response.

Check your genetic data for rs2108622 (23andMe v4, v5 ; AncestryDNA):

  • T/T: reduced CYP4F2 function, possibly need higher Warfarin dosages[ref][ref][ref], somewhat increased risk of stroke[ref][ref] CYP4F2*3
  • C/T: reduced CYP4F2 function, possibly need higher Warfarin dosages[ref][ref], somewhat increased risk of stroke[ref][ref]
  • C/C: typical

Members: Your genotype for rs2108622 is .

Check your genetic data for rs1558139 (23andMe v4; AncestryDNA):

  • A/A: lower risk of stroke[ref] possibly increase CYP4F2 function
  • A/G: slightly lower risk of stroke
  • G/G: typical

Members: Your genotype for rs1558139 is .

VKORC1 Gene:

VKORC1 is the gene that codes for vitamin K epoxide reductase complex subunit 1. Basically, VKORC1 is responsible for recycling vitamin K back to the active form, which is then involved in activating clotting factors.[ref][ref]

The anticoagulant Warfarin acts on VKORC1, preventing it from activating clotting proteins. Variants in VKORC1, then, can play a big role in the amount of Warfarin that is needed.

Check your genetic data for rs9923231 1639G/A (23andMe v4, v5):

  • C/C: typical VKORC1 activity, increased risk of lupus (Asian population)[ref]
  • C/T: decreased VKORC1 activity, increased Warfarin sensitivity (lower dose)[ref], increased stroke risk[ref]
  • T/T: decreased VKORC1 activity, increased Warfarin sensitivity (lower dose)[ref], increased stroke risk[ref]

Members: Your genotype for rs9923231 is .

Check your genetic data for rs9934438 1173C>T(23andMe v4, v5):

  • G/G: typical VKORC1 activity,
  • A/G: decreased VKORC1 activity, increased Warfarin sensitivity (lower dose)[ref], somewhat increased risk of aortic calcification[ref]
  • A/A: decreased VKORC1 activity, increased Warfarin sensitivity (lower dose)[ref], increased risk of aortic calcification[ref]

Members: Your genotype for rs9934438 is .


Dietary Sources:

Vitamin K is a fat-soluble vitamin, and including fat while eating green veggies will increase your absorption. Most animal sources of vitamin K2 are naturally found with fat.

Conversion of vitamin K2 in the gut microbiome is dependent on having a good gut microbiome — so if you have been on a broad-spectrum antibiotic recently, your vitamin K conversion may be impaired.

Vitamin K Supplements:

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Originally published: June 2018. Revised and updated: Jan. 2021


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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.