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

Members: Log in to see your data below.
Not a member? Join here. Membership lets you see your data right in each article and also gives you access to the member’s only information in the Lifehacks sections.

 

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 .

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 .


Lifehacks:

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:

The rest of this article is for Genetic Lifehacks members only.  Consider joining today to see the rest of this article.

Member Content:

An active subscription is required to access this content.

Join Here for full access to this article, genotype reports, and much more!


Already a member? Log in below.


Related Articles and Genes:

Detoxification: Phase I and Phase II Metabolism
Our body has an amazing capacity to rid itself of harmful substances. We take in toxins daily through eating natural plant toxins. We are exposed to toxicants (man-made toxins) through pesticide residue, air pollution, skin care products, and medications. Plus, our bodies all break down and eliminate substances made and used within ourselves.

Ancestral Diet: Omega-3 and Omega-6 Fatty Acids Impact the FADS1 gene
At one point, researchers thought that butter will give you a heart attack. Therefore, we should only cook with Crisco, vegetable oil, canola oil, olive oil. Wait, everyone is now switching back to butter now… while eating flax seeds for their omega-3s.

Blood clots, platelets, and adenoviruses
Take a look into the role of platelets, their connection to blood clots, and a discussion of the research on adenovirus-vector therapy, thrombocytopenia, and platelet reactions.

Nutrigenomics: How Genes Impact Your Dietary Needs
Learn more from this collection of articles on nutrigenomics that focus on the underlying science, current research, and relevant genetic variations.

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

References:

Berkner, Kathleen L. “The Vitamin K-Dependent Carboxylase.” Annual Review of Nutrition, vol. 25, 2005, pp. 127–49. PubMed, https://doi.org/10.1146/annurev.nutr.25.050304.092713.

Borgiani, Paola, et al. “CYP4F2 Genetic Variant (Rs2108622) Significantly Contributes to Warfarin Dosing Variability in the Italian Population.” Pharmacogenomics, vol. 10, no. 2, Feb. 2009, pp. 261–66. PubMed, https://doi.org/10.2217/14622416.10.2.261.

Chiba, Tsuyoshi, et al. “Trans-Resveratrol Enhances the Anticoagulant Activity of Warfarin in a Mouse Model.” Journal of Atherosclerosis and Thrombosis, vol. 23, no. 9, Sept. 2016, pp. 1099–110. PubMed Central, https://doi.org/10.5551/jat.31765.

Danziger, John. “Vitamin K-Dependent Proteins, Warfarin, and Vascular Calcification.” Clinical Journal of the American Society of Nephrology : CJASN, vol. 3, no. 5, Sept. 2008, pp. 1504–10. PubMed Central, https://doi.org/10.2215/CJN.00770208.

Dubovyk, Yevhen I., et al. “G-1639A but Not C1173T VKORC1 Gene Polymorphism Is Related to Ischemic Stroke and Its Various Risk Factors in Ukrainian Population.” BioMed Research International, vol. 2016, 2016, p. 1298198. PubMed Central, https://doi.org/10.1155/2016/1298198.

Edson, Katheryne Z., et al. “Cytochrome P450-Dependent Catabolism of Vitamin K: ω-Hydroxylation Catalyzed by Human CYP4F2 and CYP4F11.” Biochemistry, vol. 52, no. 46, Nov. 2013, pp. 8276–85. DOI.org (Crossref), https://doi.org/10.1021/bi401208m.

Geng, Huixia, et al. “Association Between the CYP4F2 Gene Rs1558139 and Rs2108622 Polymorphisms and Hypertension: A Meta-Analysis.” Genetic Testing and Molecular Biomarkers, vol. 23, no. 5, May 2019, pp. 342–47. PubMed, https://doi.org/10.1089/gtmb.2018.0202.

Halder, Maurice, et al. “Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease.” International Journal of Molecular Sciences, vol. 20, no. 4, Feb. 2019, p. 896. PubMed Central, https://doi.org/10.3390/ijms20040896.

Iwamoto, Jun. “Vitamin K2 Therapy for Postmenopausal Osteoporosis.” Nutrients, vol. 6, no. 5, May 2014, pp. 1971–80. PubMed Central, https://doi.org/10.3390/nu6051971.

Kaiser, Rachel, et al. “SNPs in VKORC1 Are Risk Factors for Systemic Lupus Erythematosus in Asians.” Arthritis and Rheumatism, vol. 65, no. 1, Jan. 2013, pp. 211–15. PubMed Central, https://doi.org/10.1002/art.37751.

Knapen, M. H. J., et al. “Vitamin K2 Supplementation Improves Hip Bone Geometry and Bone Strength Indices in Postmenopausal Women.” Osteoporosis International, vol. 18, no. 7, July 2007, pp. 963–72. PubMed Central, https://doi.org/10.1007/s00198-007-0337-9.

Kurnatowska, Ilona, et al. “Effect of Vitamin K2 on Progression of Atherosclerosis and Vascular Calcification in Nondialyzed Patients with Chronic Kidney Disease Stages 3-5.” Polskie Archiwum Medycyny Wewnetrznej, vol. 125, no. 9, 2015, pp. 631–40. PubMed, https://doi.org/10.20452/pamw.3041.

Liao, Duanxiu, et al. “Interaction Between CYP4F2 Rs2108622 and CPY4A11 Rs9333025 Variants Is Significantly Correlated with Susceptibility to Ischemic Stroke and 20-Hydroxyeicosatetraenoic Acid Level.” Genetic Testing and Molecular Biomarkers, vol. 20, no. 5, May 2016, pp. 223–28. PubMed, https://doi.org/10.1089/gtmb.2015.0205.

Meng, Chong, et al. “Correlation between CYP4F2 Gene Rs2108622 Polymorphism and Susceptibility to Ischemic Stroke.” International Journal of Clinical and Experimental Medicine, vol. 8, no. 9, 2015, pp. 16122–26.

Nimptsch, Katharina, et al. “The Association between Dietary Vitamin K Intake and Serum Undercarboxylated Osteocalcin Is Modulated by Vitamin K Epoxide Reductase Genotype.” The British Journal of Nutrition, vol. 101, no. 12, June 2009, pp. 1812–20. PubMed, https://doi.org/10.1017/S0007114508131750.

Patillon, Blandine, et al. “Positive Selection in the Chromosome 16 VKORC1 Genomic Region Has Contributed to the Variability of Anticoagulant Response in Humans.” PLoS ONE, vol. 7, no. 12, Dec. 2012, p. e53049. PubMed Central, https://doi.org/10.1371/journal.pone.0053049.

Schelleman, Hedi, et al. “Dosing Algorithms to Predict Warfarin Maintenance Dose in Caucasians and African Americans.” Clinical Pharmacology and Therapeutics, vol. 84, no. 3, Sept. 2008, pp. 332–39. PubMed Central, https://doi.org/10.1038/clpt.2008.101.

Simes, Dina C., et al. “Vitamin K as a Powerful Micronutrient in Aging and Age-Related Diseases: Pros and Cons from Clinical Studies.” International Journal of Molecular Sciences, vol. 20, no. 17, Aug. 2019, p. 4150. PubMed Central, https://doi.org/10.3390/ijms20174150.

Singh, Onkar, et al. “Influence of CYP4F2 Rs2108622 (V433M) on Warfarin Dose Requirement in Asian Patients.” Drug Metabolism and Pharmacokinetics, vol. 26, no. 2, 2011, pp. 130–36. PubMed, https://doi.org/10.2133/dmpk.dmpk-10-rg-080.

Sun, Xue, et al. “Impact of the CYP4F2 Gene Polymorphisms on the Warfarin Maintenance Dose: A Systematic Review and Meta-Analysis.” Biomedical Reports, vol. 4, no. 4, Apr. 2016, pp. 498–506. PubMed, https://doi.org/10.3892/br.2016.599.

Teichert, M., et al. “Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1) Polymorphism and Aortic Calcification: The Rotterdam Study.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 4, Apr. 2008, pp. 771–76. PubMed, https://doi.org/10.1161/ATVBAHA.107.159913.

Vitamin K: MedlinePlus Medical Encyclopedia. https://medlineplus.gov/ency/article/002407.htm. Accessed 1 July 2022.

VKORC1 Gene: MedlinePlus Genetics. https://medlineplus.gov/genetics/gene/vkorc1/. Accessed 1 July 2022.

Vos, Melissa, et al. “Vitamin K2 Is a Mitochondrial Electron Carrier That Rescues Pink1 Deficiency.” Science (New York, N.Y.), vol. 336, no. 6086, June 2012, pp. 1306–10. PubMed, https://doi.org/10.1126/science.1218632.


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.