Vitamin K, discovered by Danish scientist Henrik Dam in 1929, is well known for its effects on the clotting cascade in blood.1 Also known as phylloquinone, vitamin K is important because it has been found to be involved in many metabolic processes in the body. As recently as 1974, researchers were able to isolate vitamin K’s role in blood coagulation in human beings.2 For such a prominent vitamin, however, its processes, impact, and methods of metabolism in humans remain poorly understood.

Background

Vitamin K is widely known as an antidote or antagonist of warfarin-induced bleeding. It is a key component in the body’s manufacture of prothrombin in the clotting cascade. It has also been a long-standing practice to give newborns an immediate injection of supplemental vitamin K to prevent potentially lethal hemorrhage. This is done because newborns have only 30% to 60% of recommended levels of vitamin K, making them more susceptible to bleeding.3 

Science 


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In addition to its role in hemostasis, vitamin K plays a pivotal role in the metabolism of calcium in the human body. In a cascade similar to that in hemostasis, phylloquinone is converted in the intestinal tract, the endothelium, and in other organs from the plant form, vitamin K1, into the more active form, K2, with subgroups of K4 (menaquinone-4) and K7 (menaquinone-7).4 These forms serve as essential coenzymes that facilitate the incorporation of calcium into hydroxyapatite crystals in the bone, thereby playing a key role in bone structure maintenance.5 A meta-analysis of studies researching vitamin K intake and the incidence of osteoporosis in postmenopausal women reviewed data from trials involving nearly 7000 participants.6 Overall results of pooled data revealed a relative risk reduction of 0.50 in favor of vitamin K supplementation.6 

In a study of more than 240 women with known osteoporosis, researchers randomly assigned the participants to either no change in management or diet (control group) or daily supplemental vitamin K27 At the end of the study, participants were examined for new compression fractures and lumbar bone mineral density. The control group, as expected, showed increased fractures and continued loss of lumbar bone density. Some fractures also occurred in the supplemented group; however, there were significantly fewer fractures than in the control group and the supplemented group had a much smaller loss of lumbar bone mineral density.7 

The role of vitamin K in bone maintenance is significant, but perhaps the more exciting possibility for vitamin K supplementation is the potential for reversal of atherosclerosis. The mechanism of action of vitamin K and calcium deposition in soft tissues involves the known action of a calcium inhibitory protein that requires vitamin K to function.8 This is seen especially in the arterial endothelium. Increased vitamin K intake has been shown to reduce arterial calcium deposition in humans and, in some animal studies, has been shown to reverse existing plaque.8 In a pivotal population study, researchers enrolled nearly 8000 men and women aged 55 years and older into a 10-year trial evaluating the relationship between reported dietary intake of vitamin K and aortic calcification.9 All-cause mortality and incident cardiovascular events showed a strong inverse relationship with vitamin K, specifically K4 intake, and especially in higher risk level participants.

Safety, interactions, side effects

Vitamin K has long been used as an antidote for warfarin overdose. This is important because, for those taking warfarin, a dietary habit such as enjoying fresh green leafy vegetables, can push a stable international normalized ratio into the danger zone. There is, however, increasing evidence that the K4 form and some other forms of vitamin K do not interact in the clotting cascade in the same way that K1 does and that some of the increased calcium maldistribution seen in those on long-term warfarin therapy can be mitigated by small daily doses of vitamin K. 

Other interactions tend to be those that cause vitamin deficiency by interfering with normal gut absorption. Broad-spectrum antibiotics reduce absorption by as much as 74%.10 Phenytoin and lipid-lowering medications in the bile acid sequestrant family also reduce absorption.11

How supplied, dose, cost 

Foods are the preferred source of vitamin K; however, supplements are widely available, although in a confusing array of subtypes. In a medical setting, vitamin K is usually administered as an injection, but for consumers purchasing over-the-counter supplemental vitamin K, capsules or tablets are the most common form. The cost is relatively modest, at about $20 per month’s supply. 

Summary

As a healthcare provider, it is not a simple task to decide whether to recommend vitamin K supplementation to patients. The decision must involve eliciting a detailed personal and family history to determine risk factors for osteoporosis and atherosclerosis as well as performing a comprehensive dietary evaluation. In addition, as with many supplements, patients must understand that if they are told to take supplemental vitamin K, it is likely to be a life-long therapy. 

References

  1. Dam H. The antihemorrhagic vitamin of the chick: Occurrence and chemical nature. Nature. 1935;135:652-653.
  2. Stenflo J, Fernlund P, Egan W, Roepstorff P. Vitamin-K-dependent modifications of glutamic acid residues in prothrombin. Proc Natl Acad Sci U.S.A. 1974;71:2730-2733.
  3. American Academy of Pediatrics Committee on Fetus and Newborn. Controversies concerning vitamin K and the newborn. Pediatrics. 2003;112:191-192.
  4. Shearer MJ, Newman P. Metabolism and cell biology of vitamin K. Thromb Haemost. 2008;100:530-547.
  5. Bügel S. Vitamin K and bone health in adult humans. Vitam Horm. 2008;78:393-416.
  6. Huang ZB, Wan SL, Lu YJ, Ning L, Liu C, Fan SW. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials. Osteoporosis Int. 2015;26:1175-1186. 
  7. Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res. 2000;15:515-521.
  8. O’Keefe JH, Bergman N, Carrera-Bastos P, Fontes-Villalba M, DiNicolantonio JJ, Cordain L. Nutritional strategies for skeletal and cardiovascular health: hard bones, soft arteries, rather than vice versa. Open Heart. 2016;3:e000325.
  9. Geleijnse JM, Vermeer C, Grobbee DE, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam study. J Nutr. 2004;134:3100-3105. 
  10. Conly J, Stein K. Reduction of vitamin K2 concentrations in human liver associated with the use of broad spectrum antimicrobials. Clin Invest Med. 1994;17:531-539.