Vitamin K: CYP4F2 and VKOR Genetic Variants

VitaminK1 is a fat-soluble vitamin that is needed by our bodies to synthesize the proteins responsible for blood coagulation.  Without vitaminK1, also known as phylloquinone, bleeding is hard to control.  We get vitaminK1 from eating green plants, as phylloquinone is a part of the photosynthesis process.

Vitamin K2 comes in several different forms (MK-4, MK-7, MK-8, MK-10) and helps maintain bone strength.  Additionally, higher levels of K2 has been shown to reduce calcification in the arteries [ref], as well as possibly playing a role in mitochondrial function.[ref]

We get the highest amounts of vitaminK2 from pasture-raised eggs, dairy, and organ meat as well as from fermented soy (natto). We can also convertK1 toK2 in some organs of our bodies, and certain residents of our gut microbiome (E. coli especially) convert K1 to K2 for us.

CYP4F2 Gene:

Our body breaks down or metabolizes a lot of medications through the CYP 450 family of genes.  One of those genes, CYP4F2, codes for the enzyme that is involved in converting vitaminK1 and vitaminK2 (MK-4) to oxidized forms, thus regulating the amount available.[ref]

Genetic variation in the CYP4F2 gene causes people to naturally have higher or lower levels of vitamin K, 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.

Quick note of caution on Warfarin dosages: While the information provided here is based on good research studies,  you should always talk with your doctor about questions on medications.  Everyone is different and there can be more than one genetic variant affecting the metabolism of a drug. So while the genetic variants listed below may be tied to increased or decreased dosages for most people, it may not hold true for you specifically.


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 that they have eaten.[ref] Thus Warfarin dosages may need to be higher for someone with an impaired CYP4F2.  (If you are wondering why there are so many studies on Warfarin, there are about 30 million people in the US prescribed the drug each year![ref])

CYP4F2 is also involved in the break down of certain omega 6 fatty acids as well as vitamin E, so it plays an important role in our body’s inflammatory response.

Check your 23andMe results for rs2108622  (v4, v5) — also known as  Val433Met or CYP4F2*3

  • TT: reduced CYP4F2 function, possibly need higher Warfarin dosages[ref][ref][ref], somewhat increased risk of stroke[ref][ref]
  • CT: reduced CYP4F2 function, possibly need higher Warfarin dosages[ref][ref], somewhat increased risk of stroke[ref][ref]
  • CC: normal

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 23andMe results for rs9923231 (v4, v5)

CC: normal VKORC1 activity, increased risk of lupus (Asian population)[ref]

CT: decreased VKORC1 activity, increased Warfarin sensitivity (lower dose)[ref], increased stroke risk [ref]

TT: decreased VKORC1 activity, increased Warfarin sensitivity (lower dose)[ref],  increased stroke risk [ref]


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.

The role of K2 in mitochondrial function is still being determined, but the more recent research shows some promising results.  [ref]

Resveratrol, in high doses, may increase Warfarin’s anticoagulation activity.  This was a mouse study, though, so it may not hold true for humans.[ref]

Osteoporosis studies have shown that doses of 45mg/day of MK-4 were effective in preventing bone loss in postmenopausal women.[ref] This is a really high dose of vitamin K, but there have been multiple studies using this dose of MK-4 (mostly in Japanese women). [ref]

If you aren’t getting enough vitamin K through food sources — specifically enough vitaminK2 through pastured eggs and dairy or from natto — you may want to look into a vitamin K supplement.

While there is no known upper limit or toxicity set for vitamin K1 orK2  supplementation, there are user reviews showing that some people react poorly to too much MK-7. So just a word of warning to pay attention to how you feel if you start taking higher doses of MK-7.

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

More to read: 
Chris Masterjohn’s Ultimate Vitamin K2 Resource

Warfarin Dosage Calculator:
If you are comfortable with uploading your genome to Stanford, there is a nifty little calculator that gives an estimate (for informational purposes only) of warfarin dosage.

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