The Miraculous Vitamin K (Part 1)

It's important to recognize that vitamin K's role in human physiology is multifaceted and intricate. I aim to shed light on some of the intriguing components that contribute to the complexity of this remarkable vitamin.

Vitamin K family consists of vitamin K1 (phylloquinone or phytomenadione) and comes as only one type; whereas vitamin K2 (menaquinones) happens to be fat-soluble and has fourteen types [MK1-14], and lastly vitamin K3 (menadione) is water soluble and also has only one type.[1] 

Vitamin K1 is acknowledged as a genuine essential vitamin crucial for the well-being of both humans and animals. Vitamins K2 and K3 can be produced as metabolites of vitamin K1 within various tissues or in the gastrointestinal (GI) tract of humans.

On average, it is estimated that approximately 85% of dietary vitamin K intake is typically derived from vitamin K1, with the rest coming from vitamin K2. [2]

Absorption of vitamin K1 varies considerably depending on its source. When we obtain vitamin K1 by eating various vegetable sources, its bioavailability is low (<10%) because it is trapped in the chloroplast.[3] Cooking or blending of the vegetables enables the oils to be pressed out of the vegetable/vegetable seeds and increases the vitamins bioavailability and absorption up to as much as 50% as compared with the raw vegetable.[4]

Vitamin K1 is absorbed by specific bacteria residing in our gastrointestinal tract (GI), which include beneficial organisms such as Bacteroides, Escherichia coli, and Propionibacterium. Within these bacteria, vitamin K1 can undergo processing to produce vitamin K2 or K3. Subsequently, the vitamin is absorbed and transported via chylomicrons, small fat particles, to the liver and other tissues for storage or utilization. Vitamin K2 seems to be preferentially transported by low density lipoproteins (LDL) and high-density lipoprotein (HDL).   Upon uptake by various tissues, vitamin K1 may be stored and utilized as is, while a portion may undergo conversion to K2 (MK-4), the most prevalent form of vitamin K in humans. For unknown reasons, each tissue will have a different ratio of vitamin K1/vitamin K2 (MK-4).[5] 

One study estimates that 5-25% of the absorbed vitamin K1, the same as various K2 forms, is converted to K3 in the intestinal cells. [6] Various cells in the body may take up vitamin K3 and convert it to vitamin K2 (MK-4) in each tissue.[7]

Numerous studies have demonstrated that different long-chain forms of vitamin K2 (MK 7-11) undergo conversion to vitamin K2 (MK-4) in all tissues except the liver. While a significant proportion (90%) of longer vitamin K2 (MK 7-11) remains unchanged in the liver, with 10% being vitamin K1, it's important to note that vitamin K1 remains pivotal as it serves as the catalyst for the various forms of vitamin K in the body. I wonder if there are any medications that may inhibit the conversion of vitamin K1 to vitamin K2?

There are numerous vitamin K dependent proteins (VKDs) in our body that vitamin K activates via a process of carboxylation (which uses CO2) which allows for these VKD proteins to function better. Why is this important? One of these functions is to bind calcium or to interact with cell membranes more efficiently.  A review by McCann and Ames brings to question whether there is a specific order that may influence which VKD proteins vitamin K will activate? Most likely, this is done in an order of physiologic priority.[8]  For instance, when daily vitamin K intake is approximately 100mcg (micrograms) or lower, clotting processes may take precedence in utilizing the majority of ingested vitamin K. Consequently, other vitamin K-dependent proteins (VKDs) throughout the body may not receive sufficient support, leading to diminished functionality. It's worth noting that manganese and vitamin B6 are crucial cofactors that influence the rate of carboxylation of VKDs.

Vitamin K serves as a crucial cofactor essential for the physiological process that prevents the abnormal calcification of soft tissues that typically remain uncalcified. These tissues include arterial and venous vessel walls, heart valves, skin (specifically elastin fibers), cartilage (excluding normal growth-related mineralization), and kidneys.[9] Vitamin K enhances the defensive actions of various vitamin K dependent proteins (such as MGP [matrix Gla protein] and GAS-6) which enhances their ability to bind calcium ions and prevent their inappropriate deposition in tissues.  GAS-6 is also involved in supporting adequate innate immune responses (Natural Killer [NK] cells) and reducing the risk or severity of autoimmune cellular events.[10] 

If you’re to consider supplementing with vitamin D, it would be crucial to also consider consuming vitamin K simultaneously as there is major synergism between these two powerful vitamins.

Significant Food Sources of Vitamin K1 and K2

Food Source	Vitamin K1 (mcg/100g)	Vitamin K2 (MK-4) (mcg/100g)	Vitamin K2 (MK-7) (mcg/100g)
Goose Liver Pate	10.9 mcg	369 mcg
Ground Beef (medium fat)	1.3 mcg	8.1 mcg
Chicken Liver	4.0 mcg	14 mcg
Chicken Thigh	-	27 mcg
Beef Chuck	0.6 mcg	15 mcg
Pork Thigh	-	6.0 mcg
Pork Steak	0.3 mcg	2.1 mcg	0.5 mcg
Salami	2.3 mcg	9.0
Sauerkraut	25 mcg	0.4 mcg
Boiled Cabbage	180 mcg	0.4
Natto	34 mcg		998 mcg
Whipping cream	5.1 mcg	5.4 mcg
Hard Cheese	10.4 mcg	4.7 mcg	1.3 mcg
Soft Cheese	2.6 mcg	3.7 mcg	1.0 mcg
Egg yolk	2.1 mcg	31.4 mcg
Egg white	-	0.9 mcg
Butter	2.0 mcg	21.0 mcg
Mayonnaise (with egg)	189 mcg	38 mcg

Significant sources of Vitamin K1 and K2 data is from Kamao M, Suhara Y, Tsugawa N, et al. Vitamin K content of foods and dietary vitamin K intake in Japanese young women. J Nutr Sci Vitaminol (Tokyo). 2007.

[1] Suttie JW. Vitamin K in health and disease. Boca Raton, FL: CRC Press; 2009.

[2] Elder SJ, Haytowitz DB, Howe J, et al. Vitamin K contents of meat, dairy, and fast food in the U.S. diet. J Agric Food Chem. 2006

[3] Novotny JA, Jurilick AC, Britz SJ, et al. Vitamin K absorption and kinetics in human subjects after consumption of 13C-labelled phylloquinone from kale. Br J Nutur. 2010.

[4] Garber AK, Binkley NC, Krueger DC, et al. Comparison of phylloquinone bioavailability from food sources or a supplement in human subjects. J Nutr. 1999.

[5] Thijssen HH, Drittij-Reijnders MJ. Vitamin K status in human tissues: tissue-specific accumulation of phylloquinone and menaquinone-4. Br J Nutr. 1996.

[6] Okano T, Shimomura Y, Yamane M, et al. Conversion of phylloquinone (vitamin K1) into menaquinone-4 (vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice. J Biol Chem. 2008

[7] Thijssen HH, Drittij-Reijnders MJ, Fischer MA. Phylloquinone and menaquinone-4 distribution in rats: synthesis rather than uptake determines menaquinone-4 organ concentrations. J Nutr. 1996.

[8] McCann JC, Ames BN. Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr. 2009.

[9] Berkner XL, Runge KW. The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis. J Thromb Haemost. 2004.

[10] Bellido-Martin L, de Frutos PG. Vitam Horm. Vitamin K-dependent actions of Gas6. 2008. Department of Cell Death and Proliferation, Institute for Biomedical Research of Barcelona.