Genetic Impact on Vitamin K Absorption

Vitamin K is a fat-soluble vitamin that plays an essential role in blood clotting and bone metabolism.

It exists in two natural forms: Vitamin K1 (phylloquinone) found in plants, and Vitamin K2 (menaquinones) found in animal products and fermented foods.

History of Vitamin K

Vitamin K was discovered in 1929 by Danish scientist Henrik Dam.

During his research on cholesterol, he observed that chickens fed a cholesterol-free diet developed hemorrhages and started bleeding.

This condition was attributed to a deficiency of a then-unknown factor, which was later identified as Vitamin K (the “K” coming from the Danish word “koagulation”).

Main functions of Vitamin K

Vitamin K is an essential fat-soluble vitamin known for its critical role in several biological processes.

It is integral to coagulation (blood clotting), bone metabolism, and the regulation of certain cellular functions.

Here are the main functions of Vitamin K:

Blood Clotting (Coagulation)

This is the most well-known function of Vitamin K. It is crucial in the production of several proteins that contribute to the coagulation cascade, a series of reactions that ultimately results in the formation of a blood clot. Without sufficient Vitamin K, the body’s ability to form blood clots is impaired, increasing the risk of excessive bleeding.

Bone Health

Vitamin K is involved in bone metabolism by activating osteocalcin, a protein that binds calcium ions and incorporates them into the bone to maintain bone density and strength. Several studies have linked higher Vitamin K intake to a lower risk of fractures, suggesting that Vitamin K can contribute to bone health.

Cellular Functions

Vitamin K is also involved in the regulation of cellular functions, including cell growth, apoptosis (programmed cell death), and cell differentiation. In particular, it has been implicated in the regulation of certain genes involved in cell growth and survival.

Vascular Health

Beyond its role in coagulation, Vitamin K-dependent proteins are also involved in maintaining the health of our blood vessels. Specifically, Matrix Gla protein (MGP), a Vitamin K-dependent protein, inhibits vascular calcification (hardening of the arteries), a major risk factor for heart disease.

Anti-inflammatory Properties

Some research suggests that Vitamin K has anti-inflammatory properties.

It may help reduce inflammation by inhibiting the production of pro-inflammatory cytokines, substances released by cells of the immune system that can cause inflammation.

Brain Health

Recent studies have indicated that Vitamin K might play a role in brain health, particularly in areas related to cognition and behavior.

The specific mechanisms of how Vitamin K may influence brain function are still under investigation.

These functions underline the importance of maintaining adequate Vitamin K levels.

Both Vitamin K1 (found mainly in leafy green vegetables) and Vitamin K2 (found in animal products and fermented foods) contribute to these functions, though they may have slightly different biological roles.

RDA of Vitamin K

The Recommended Dietary Allowance (RDA) for Vitamin K varies by age, sex, and life stage. For adult men, the RDA is 120 micrograms per day, and for adult women, it’s 90 micrograms per day.

Food Sources of Vitamin K

Vegan/vegetarian sources

Vitamin K1 is predominantly found in green leafy vegetables such as kale, spinach, broccoli, and Brussels sprouts. Other sources include certain fruits, such as kiwi and avocado, and some vegetable oils, especially soybean oil.

Animal sources

Vitamin K2 is found in animal products such as meat, eggs, and dairy, as well as in fermented foods like natto, a traditional Japanese dish made from fermented soybeans.

Factors that Affect Vitamin K Absorption

Non-genetic factors

The absorption of Vitamin K can be influenced by several non-genetic factors.

Diet

Dietary fat enhances the absorption of Vitamin K as it is a fat-soluble vitamin.

Medication

Certain medications, such as broad-spectrum antibiotics, bile acid sequestrants, and certain cholesterol-lowering medications, can interfere with Vitamin K absorption.

Underlying conditions

Furthermore, disorders that impair fat absorption, such as celiac disease, cystic fibrosis, and liver disease, can lead to Vitamin K deficiency.

Genetic Factors

Several genes play a role in the absorption, metabolism, and function of Vitamin K in the body.

Variations in these genes, known as single nucleotide polymorphisms (SNPs), can influence an individual’s Vitamin K status. Here are some of these key genes:

VKORC1 (Vitamin K epoxide reductase complex subunit 1):

This gene plays a key role in the Vitamin K cycle, a process by which Vitamin K is recycled in the body for repeated use. Variations in this gene can affect the efficiency of the Vitamin K cycle, impacting the body’s Vitamin K status.

Check your AncestryDNA, 23andMe raw data for the VKORC1 gene variants

GGCX (Gamma-glutamyl carboxylase):

This gene codes for a protein that activates certain Vitamin K-dependent proteins involved in blood clotting and bone metabolism. Variations in this gene can affect the function of these proteins, influencing the body’s Vitamin K needs.

Check your AncestryDNA, 23andMe raw data for the GGCX gene variants

CYP4F2 (Cytochrome P450 Family 4 Subfamily F Member 2):

This gene is involved in the metabolism of Vitamin K. Variations in this gene can affect the way the body processes and uses Vitamin K.

Check your AncestryDNA, 23andMe raw data for the CYP4F2 gene variants

Below is a table of some SNPs in these genes that might influence Vitamin K metabolism:

Gene	SNP	Possible Implication
VKORC1	rs9923231	Altered Vitamin K cycle efficiency
GGCX	rs699664	Impact on Vitamin K-dependent proteins
CYP4F2	rs2108622	Changes in Vitamin K metabolism

Keep in mind that the presence of these SNPs doesn’t necessarily mean an individual will have problems with Vitamin K absorption or metabolism.

Many factors, including dietary intake and overall health, can influence Vitamin K status.

DISCLAIMER: While genetic testing can provide insights into these SNPs, it is not a diagnostic tool and should not replace medical advice or guidance. It’s always best to consult with a healthcare provider or a genetic counselor when interpreting genetic testing results.

Causes of Vitamin K Deficiency

Vitamin K deficiency is relatively rare in adults but can occur in individuals with conditions that impair fat absorption, as Vitamin K is a fat-soluble vitamin.

Newborns are also at risk of Vitamin K deficiency. Low Vitamin K content in breast milk, limited storage in the body, and a sterile gut at birth prevent the production of Vitamin K2 by gut bacteria.

Effects of Vitamin K Deficiency

Vitamin K deficiency can lead to bleeding problems, as this vitamin is crucial for the blood clotting process.

In severe cases, it may cause hemorrhages.

Additionally, a deficiency might contribute to the weakening of the bones and the development of osteoporosis.

In newborns, a severe deficiency can lead to a condition known as ‘vitamin K deficiency bleeding’ or ‘hemorrhagic disease of the newborn,’ which can be life.

Takeaway

Understanding the impact of genetics on Vitamin K metabolism and function is a growing field of research.

With increasing knowledge about the intricate relationships between our genes and nutrients, personalized nutritional recommendations could become a reality in the future.

This would ensure that individuals are able to optimize their Vitamin K status and fully benefit from its crucial roles in blood clotting and bone health.

References

Interested in geeking out? Here are some interesting research papers you can review for further reading:

Rieder MJ, Reiner AP, Gage BF, Nickerson DA, Eby CS, McLeod HL, Blough DK, Thummel KE, Veenstra DL, Rettie AE. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med. 2005 Jun 2;352(22):2285-93. doi: 10.1056/NEJMoa044503. PMID: 15930419.
Wajih N, Sane DC, Hutson SM, Wallin R. The inhibitory effect of calumenin on the vitamin K-dependent gamma-carboxylation system. Characterization of the system in normal and warfarin-resistant rats. J Biol Chem. 2004 Feb 27;279(9):25276-83. doi: 10.1074/jbc.M313236200. Epub 2003 Dec 2. PMID: 14660577.
Caldwell MD, Awad T, Johnson JA, Gage BF, Falkowski M, Gardina P, Hubbard J, Turpaz Y, Langaee TY, Eby C, King CR, Brower A, Schmelzer JR, Glurich I, Vidaillet HJ, Yale SH, Qi Zhang K, Berg RL, Burmester JK. CYP4F2 genetic variant alters the required warfarin dose. Blood. 2008 Apr 15;111(8):4106-12. doi: 10.1182/blood-2007-11-122010