Emerging evidence suggests novel roles for vitamin K in health and disease. Apart from other crucial health beneficial rules vitamin K also plays protective rules against oxidative stress and inflammation the two leading factors in development of modern diseases and early aging. We have already enough evidence that vitamin K2 plays more crucial rule than K1. Sources of vitamin K2 are limited and for synthesis of vitamin K2 or menaquinone it needs bacterial presence except MK-4 form. On the other hand you can get phylloquinone or K1 from leafy greens. There is evidence that mammals can convert K1 to MK-4 but whether it is enough to fulfil the K2 requirement. Whether we can utilize bacterial derived meaquinones from our intestines? Or Should you supplement with vitamin K2? , the X factor.
Despite of lack of data I am trying to get the answer.
If you have not read the earlier articles you should read them.
Vitamin K2 food source database
Should you supplement with vitamin K2?
Vitamin K1 and K2
Vitamin K1 or phylloquinone participates in blood coagulation as major rule that means it has ability the ability to clot blood or prevent hemorrhage. It also serves as a cofactor for carboxylation of some protein.(1)
A series of enzymes or proteins exist in human body. Vitamin K2 plays major rule in activation of them. Together they are called vitamin K dependant proteins(VKDPs). One major function of vitamin K2 includes ensuring calcium absorption in right place such as bones, cartilage and not in wrong part. Calcium deposition at wrong place like artery, kidney can put your health in risk.
Vitamin K2 takes part in activation of enzymes by a process called Carboxylation. In the molecular chain of the vitamin K2 it contains carboxyl group. It helps in adding a carbon dioxide to enzyme making it negatively charged and thus that allow binding the enzyme with positively charged calcium.
Additionally vitamin K2 participates in metabolism of major lipid signaling molecules sphingolipid. Sphingolipids have a role in motor and cognitive behavior and viewed as key players in important cellular events such as proliferation, differentiation, senescence, cell–cell interaction, and transformation.(2)
Human body appears to convert K1 to K2, but how much?
In earlier animal studies researchers had found conversion of K1 to K2. (3,4)
In 2006 study published in The British Journal of Nutrition, researchers had found conversion of K1 to MK-4 in humans.(5) Lactating mother taking K1 or phylloquinone produces MK-4 in breast milk may have beneficial rules to the newborn infant. (6)
In 2008 study published in The Journal of Biological Chemistry suggests that the conversion of K1 to MK-4 appears in the intestine and tissues.(7)
Although the extent of conversion to MK-4 was estimated to range from 5% to 25% of the ingested phylloquinone, In 2013 study evidenced that the conversion is only to a small proportion through an intermediately molecule menadione or K3. They also found that gut microflora hadn’t converted K1 to MK-4. (8,9)
More discouragingly past study on human volunteers found K1 or phylloquinone from plant food is poorly absorbed than butter containing MK-4 and may depend on other food components, notably fat. (10) And even more negatively people are eating less greens today.
Gut bacteria can produce almost all menaquinones except MK-4 but can your body utilize them?
Some intestine bacteria synthesize almost all menaquinones including MK-7 but not MK-4.(11)But question is whether human body utilize those menaquinones from large intestine?
In 2017 published 8 week study in American Journal of Clinical Nutrition conducted on 80 men and postmenopausal women of age 40–65 y, J Philip Karl et. al found bacterially derived nenaquinone in faeces. However, the health implications remain unclear. (12) Despite of lack of information about the way of absorption and transportation some gut bacteria produces long chain K2 or menaquinones.
Animal experiments published in 1992 suggests that bacterially synthesized menaquinones particularly in ileum part of the small intestine do play a significant role in contributing to vitamin K requirements in humans. (13)
Another 1994 study evidenced absorption of bacterially synthesized vitamin K2 from the parts of small bowel and contributing to the human nutritional requirements. (14)
Bottom line:
These studies that evidenced utilization of bacterial derived menaquinone were from small intestine. There you need menaquinone-producing bacteria and bile salts for solubilization of menaquinones.
Major absorption take place in small intestine and also it shouldn’t hold excessive bacterial colonization. Large has largest bacterial colonization. But unlike the small intestine the colon does not play a major role in absorption of foods and nutrients. Therefore, although intestinal microflora synthesizes large amounts of menaquinones in large intestine, you have less chance to get benefits from that. And so diet plays the major source of functionally available vitamin K2. Recent studies also showed that a short-term decrease in dietary vitamin K intake is not compensated by intestinal menaquinones.(15) Is it possible to replenish a part of your vitamin K2 level through small intestine bacterial derived menaquinone?
Apart from that not only antibiotics wide range of more than 1000 marketed medicine or drugs including antipsychotics, acid suppressor like proton-pump inhibitors, hormones, nonsteroidal anti-inflammatory drug (NSAID), anti-cancer drugs affect gut microbes.(16,17)
What data says about vitamin K deficiency?
Consumption of vitamin K even is going lesser with change of time. A study on 4599 children born on 3-9 March 1946 and 307 children in the 1990s as published in the journal of Public Health Nutrition in 2005 concluded vitamin K1 intakes of children have decreased significantly since 1950.(18)
Study suggest intake of vitamin K above RDA due to identification of undercarboxylated extra-hepatic Gla-proteins in the circulation of non-supplemented individuals. Vitamin K’s recommended dietary allowance (RDA) is based on the requirement for blood clotting factor synthesis. They found children and adults above 40 years showed the largest tissue-specific the vitamin deficiency and may have benefits from supplementation of K2. (19)
Other studies also found elevation of undercarboxylated (i.e. inactive) osteocalcin (ucOC). As we discussed earlier vitamin K is needed for activation or carboxylation of osteocalcin, those studies indicate low vitamin K intake. (20, 21) You can’t directly measure vitamin K2 but measure through inactive osteocalcin.
Final Word
Study on vitamin K like begins to go. Vitamin K dependent proteins involve in wide range of activity including bone metabolism, inflammatory response, cancer progression, oxidative stress as well as pancreas exocrine activity. Activation of which is equally important and need vitamin K. Vitamin K have also crucial rules in blood coagulation, energy metabolism and prevention of arterial calcification. (22) But sad news is that we have limited source of most important part vitamin K2 in present environment.
With industrialization of food vitamin K2 are disappearing from diet. Modern day’s diet appears to have lack of vitamin K sources. I am not opposing industrialization but we need balance of life. Too much greediness can be destructive. Not eating of enough vegetables containing phylloquinone or having unhealthy gut can be another factor. Grass feed cattle, poultry converted to grain feed resulting to not having enough vitamin K2. Such meat sources even more lacking K2 content. More discouragingly many of such meat and dairy source comes along with other medications like use of antibiotics, hormones as well as other toxic inputs.
Plant sources
Generally nutrient from plant sources encased with fiber and that must be separated from fiber to be absorbed in intestine. People don’t having enough stomach acid may found difficulties in the separation process. And long term acid suppression can make it even harder along with development of other diseases. I have written numbers of articles about stomach acid, acid reflux or heartburn and other relevant conditions. You can read about this with below link:
How not having enough stomach acid can cause acid reflux or heartburn.
How weak stomach acid can lead to iron deficiency as well as vitamin B12 deficiency anemia.
We also need healthy fats in our diet. Over all if you look deeper in the situation we are lacking some balance here in present environment. I always prefer to get valuable nutrient through foods. However we are in such a stage supplementation of Vitamin K2 with D3 makes sense.
Disclaimer: Information provided here are generalized information for
educational purpose only, not intended to provide one to one health
consultation or replace practice of a qualified practitioner. Different
people may have different health condition and may have different reaction
to the same food. Hence it has been advised to consult with health care
provider before application of any of above guidelines.
Source and References:
1.Vitamins K1 and K2: The Emerging Group of Vitamins Required for Human
Health,Gerry Kurt Schwalfenberg,J Nutr Metab. 2017; 2017: 6254836
2.Vitamin K Dependent Proteins and the Role of Vitamin K2 in the Modulation
of Vascular Calcification: A Review,Margueritta S. El Asmar,Joseph J.
Naoum, and Elias J. Arbid, Oman Med J. 2014 May; 29(3): 172–177
3.Vitamin K distribution in rat tissues: dietary phylloquinone is a source
of tissue menaquinone-4,Thijssen HH, Drittij-Reijnders MJ.,
Br J Nutr. 1994 Sep;72(3):415-25
4.Conversion of Phylloquinone (Vitamin K1) into Menaquinone-4 (Vitamin K2)
in Mice TWO POSSIBLE ROUTES FOR MENAQUINONE-4 ACCUMULATION IN CEREBRA OF
MICE,Toshio Okano,Yuka Shimomura,Makiko Yamane,Yoshitomo Suhara, Maya
Kamao,Makiko Sugiura and Kimie Nakagawa,April 25, 2008, The Journal of
Biological Chemistry,283,11270-11279
5.Menadione is a metabolite of oral vitamin K,Thijssen HH, Vervoort LM,
Schurgers LJ, Shearer MJ.,Br J Nutr. 2006 Feb;95(2):260-6.
6.Menaquinone-4 in breast milk is derived from dietary phylloquinone,
Thijssen HH, Drittij MJ, Vermeer C, Schoffelen E., Br J Nutr. 2002 Mar;87(3):219-26.
7.Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2)
in mice: two possible routes for menaquinone-4 accumulation in cerebra of
mice,Okano T, Shimomura Y, Yamane M, Suhara Y, Kamao M, Sugiura M, Nakagawa
K.,J Biol Chem. 2008 Apr 25;283(17):11270-9. Epub 2007 Dec 14.
8.Vitamin K Nutrition, Metabolism, and Requirements: Current Concepts and
Future Research,Martin J. Shearer, Xueyan Fu,and Sarah L. Booth,
Adv Nutr. 2012 Mar; 3(2): 182–195
9.Menadione (Vitamin K3) Is a Catabolic Product of Oral Phylloquinone
(Vitamin K1) in the Intestine and a Circulating Precursor of Tissue
Menaquinone-4 (Vitamin K2) in Rats, Yoshihisa Hirota et. al.,
J Biol Chem. 2013 Nov 15; 288(46): 33071–33080
10.Effect of food composition on vitamin K absorption in human volunteers.
Gijsbers BL, Jie KS, Vermeer C., Br J Nutr. 1996 Aug;76(2):223-9
11.Recent trends in the metabolism and cell biology of vitamin K with
special reference to vitamin K cycling and MK-4 biosynthesis, Martin J.
Shearer and Paul Newman,J Lipid Res. 2014 Mar; 55(3): 345–362
12.J Philip Karl et. al.,Fecal concentrations of bacterially derived
vitamin K forms are associated with gut microbiota composition but not
plasma or fecal cytokine concentrations in healthy adults, Am J Clin Nutr.
2017 Oct; 106(4): 1052–1061
13.Conly JM, Stein K.,The production of menaquinones (vitamin K2) by
intestinal bacteria and their role in maintaining coagulation homeostasis.,
Prog Food Nutr Sci. 1992 Oct-Dec;16(4):307-43.
14. Conly JM, Stein K, Worobetz L, Rutledge-Harding S., The contribution of
vitamin K2 (menaquinones) produced by the intestinal microflora to human
nutritional requirements for vitamin K., Am J Gastroenterol. 1994 Jun;89(6):915-23
15.Barbara Walther and Magali Chollet (March 22nd 2017). Menaquinones,
Bacteria, and Foods: Vitamin K2 in the Diet, Vitamin K2 - Vital for Health
and Wellbeing, Jan Oxholm Gordeladze, IntechOpen, DOI: 10.5772/63712.
Available from: https://www.intechopen.com/books/vitamin-k2-vital-for-
health-and-wellbeing/menaquinones-bacteria-and-foods-vitamin-k2-in-the-diet
16.Lisa Maier et. al.,Extensive impact of non-antibiotic drugs on human gut
bacteria, Nature. 2018 Mar 29; 555(7698): 623–628.
17.Xue Liang, Kyle Bittinger, Xuanwen Li, Darrell R Abernethy, Frederic D
Bushman, Garret A FitzGerald. Bidirectional interactions between
indomethacin and the murine intestinal microbiota. eLife, 2015; 4
18.Prynne CJ, Thane CW, Prentice A, Wadsworth ME.,Intake and sources of
phylloquinone (vitamin K(1)) in 4-year-old British children: comparison
between 1950 and the 1990s,Public Health Nutr. 2005 Apr;8(2):171-80.
19.Theuwissen E, Magdeleyns EJ, Braam LA, Teunissen KJ, Knapen MH,
Binnekamp IA, van Summeren MJ, Vermeer C.,Vitamin K status in healthy
volunteers,Food Funct. 2014 Feb;5(2):229-34.
20.van Summeren M, Braam L, Noirt F, Kuis W, Vermeer C.,
Pronounced elevation of undercarboxylated osteocalcin in healthy children,
Pediatr Res. 2007 Mar;61(3):366-70
21.Kalkwarf HJ, Khoury JC, Bean J, Elliot JG., Vitamin K, bone turnover,
and bone mass in girls, Am J Clin Nutr. 2004 Oct;80(4):1075-80
22.Nolan Chatron, Abdessalem Hammed, Etienne Benoît and Virginie Lattard,
Structural Insights into Phylloquinone (Vitamin K1), Menaquinone (MK4,
MK7), and Menadione (Vitamin K3) Binding to VKORC1, Nutrients 2019, 11(1),
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3 Responses
Wish to see much more like this post !
It gives me pleasure, keep posting, thanks
Very informative post. For synthesis of vitamin K in the gut we would need proper diet. Unfortunately our food habits are changing as our propensity of disease are increasing.