Low Vitamin K increases cancer risk; bone loss

Vitamin K is a fat-soluble vitamin (like vitamin A, D, and E). The best way to get the daily requirement of vitamin K is by eating following foods: green leafy vegetables (broccoli, kale, spinach, cauliflower, cabbage,…), fish, liver, meat, eggs, and cereals. Vitamin K deficiency is very rare. It usually occurs when the body can’t properly absorb the vitamin from the intestinal tract or as a result of long-term antibiotic treatment. [1]

Low vitamin K – Increased Cancer Risk?

Some studies have suggested the link between low blood levels of vitamin K and increased risk for some types of cancer [2]. The synthetic menadione (vitamin K₃) has been shown to inhibit carcinogenic cell growth, especially in combination with vitamin C [3]. A study published in 2008 found a higher risk of prostate cancer in men with a low intake of some forms of vitamin K [2]. It is noted on cancer.org that [4]: “In some cases, vitamin K may be given credit for benefits that are actually due to other compounds that appear in the same foods.”

Vitamin K and Bone Mass

Low vitamin K status was found to be associated with low bone mass, osteoporosis, and fracture risk [8,10]. However, studies have shown contradictory results with some studies reporting beneficial effects on bone health (measured by bone mineral density) while others show no effect [8]. It is argued that these discrepancies are because bone mineral density is not an appropriate endpoint to monitor effects of vitamin K on bone health.

A systematic review and meta-analysis [9] which included 13 trials assessed whether oral vitamin K (phytonadione and menaquinone) supplementation can reduce bone loss and prevent fractures. This review suggested that vitamin K reduces bone loss. Reduction of fracture incidence was particularly striking with an 80% reduction in hip fracture (notice: only 7 studies measured fracture incidence).

Low peak bone mass and rapid bone loss are often seen in relatively young female athletes who engage in vigorous exercise, which may cause hypoestrogenism (estrogen deficiency) and amenorrhoea (absence of a menstrual period). The paper by researchers from Maastricht University [5] reported that supplementing with 10 mg of vitamin K per day during one month increased calcium-binding capacity of osteocalcin (a protein found in bone). Vitamin K supplementation induced a 15 – 20 % increase in bone formation in the low-estrogen group. Furthermore, women who ingest at least 110 micrograms of vitamin K a day are 30 per cent less likely to break a hip than women with lower intake [10].

Vitamin K in Infancy

Vitamin K deficiency bleeding is a rare (0.25% to 1.7% incidence [16]) and potentially life-threatening bleeding disorder in an infant in the first hours to months of life [11]. In general, newborn infants have low vitamin K status because vitamin K transport across the placental barrier is limited, storage of vitamin K in the liver is low, not fully functional vitamin K cycle, human milk is low in vitamin K, and/or low colonic bacterial synthesis [7,15]. This low levels of vitamin K can cause bleeding in an infant in the first weeks of life also known as Hemorrhagic Disease of the Newborn (HDN) [11,12]. Early HDN occurs within 24 hours postpartum while late HDN occurs from week 2-12 [12,13]. Randomized clinical trials have shown that a single dose (1.0 mg) of intramuscular vitamin K after birth is effective in the prevention of classic HDN, either with intramuscular or oral administration [12,14]. However, the oral administration appears to be less effective (although not significant) [11].

Controversy Concerning Vitamin K Administration in Infancy

The recommendation that all newborn infants receive vitamin K at birth has been uniformly adopted, however, some controversies still persist [17] especially among conspiracy theorists. In early 1990, two retrospective studies were published by Golding et al. [18,19] attempting to show a possible association between vitamin K₁ (phylloquinone) injections in newborns and the increased incidence of childhood leukaemia and other forms of childhood cancer. Draper and Stiller [20] questioned the results of Golding et al. and failed to show a correlation between increased use of intramuscular vitamin K and the incidence of childhood leukaemia using data from the National Registry of Childhood Tumors. Draper and Stiller also believe the study by Golding et al. is seriously flawed in design and interpretation. Two large retrospective studies [20,21], which reviewed the medical records of 54,795 and 1,384,424 children found no association between exposure to vitamin K and an increased risk of any childhood cancer or of all childhood cancers combined. A better-designed study by Olsen and colleagues [22] compared 835,430 children born in Denmark from 1945 to 1954 were not exposed to vitamin K, 797,472 infants whose mothers were given oral vitamin K supplements during pregnancy, and 586,378 children who received vitamin K intramuscularly. Researchers reported no trend in risk of childhood leukaemia over the three defined birth cohorts. Furthermore, since 1961 there has been no increase in the annual incidence of childhood leukaemia in the US as well as Australia [23]. To date, only Golding et al. reported an association.

In the recent years, a rise in late-onset cases of Vitamin K deficiency bleeding has been reported due to an increasingly common parental refusal of newborn vitamin K prophylaxis [24].

Side Effects and Deficiency

While allergic reactions are possible, there is no known toxicity associated with high doses of vitamin K₁ (phylloquinone) or vitamin K₂ (menaquinone) [6]. Synthetic vitamin K₃ (menadione) and its derivates, on the other hand, can interfere with the function of glutathione, resulting in oxidative damage to cell membranes [7]. Menadione injections have been reported to cause liver toxicity, jaundice, and hemolytic anaemia in infants and are therefore no longer used for the treatment of vitamin K deficiency [7].

Vitamin K is also known as the clotting vitamin because it is necessary for normal blood clotting and without it, blood would not clot [1]. It is an essential nutrient needed by the liver in order to form proteins that promote blood clotting and prevent abnormal bleeding [4]. However uncommon in healthy adults, people with vitamin K deficiency are usually more likely to have bruising and bleeding [1]. It is therefore often thought that high intake of vitamin K may increase thrombosis risk but this is evidently not true as excess vitamin K intake cannot result in more clotting factor carboxylation [8].

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References

1. Alison Evert – K. Retrieved from Medline Plus at 5. May 2013
2. Nimptsch, Katharina, Sabine Rohrmann, and Jakob Linseisen. “Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg).” The American journal of clinical nutrition 87.4 (2008): 985-992.
3. Verrax, Julien, et al. “The association of vitamins C and K3 kills cancer cells mainly by autoschizis, a novel form of cell death. Basis for their potential use as coadjuvants in anticancer therapy.” European journal of medicinal chemistry 38.5 (2003): 451-457.
4. Vitamin K. Retrieved from www.cancer.org at 5. May 2013
5. Craciun, A. M., et al. “Improved bone metabolism in female elite athletes after vitamin K supplementation.” International journal of sports medicine 19.07 (2007): 479-484.
6. Trumbo, Paula, et al. “Dietary reference intakes: vitamin A, vita K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc.” Journal of the American Dietetic Association 101.3 (2001): 294-301.
7. http://lpi.oregonstate.edu/infocenter/vitamins/vitaminK/
8. Vermeer, Cees. “Vita K: the effect on health beyond coagulation–an overview.” Food & nutrition research 56 (2012).
9. Cockayne, Sarah, et al. “Vita K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials.” Archives of Internal Medicine 166.12 (2006): 1256-1261.
10. Feskanich, Diane, et al. “Vita K intake and hip fractures in women: a prospective study.” The American journal of clinical nutrition 69.1 (1999): 74-79.
11. Kries, Rüdiger, and Ulrich Göbel. “Vitamin K prophylaxis and vit K deficiency bleeding (VKDB) in early infancy.” Acta Paediatrica 81.9 (1992): 655-657.
12. Puckett, Renee M., and Martin Offringa. “Prophylactic vit K for vit K deficiency bleeding in neonates.” Cochrane Database Syst Rev 4 (2000).
13. Shearer, Martin J. “Vit K deficiency bleeding (VKDB) in early infancy.” Blood reviews 23.2 (2009): 49-59.
14. Hathaway, Wiliam E. “Vitamin K deficiency.” The Southeast Asian journal of tropical medicine and public health 24 (1992): 5-9.
15. http://emedicine.medscape.com/article/126354-overview
16. Force, Vitamin K. Ad Hoc Task. “Controversies concerning vita K and the newborn.” Pediatrics 91.5 (1993): 1001-1002.
17. Lane, Peter A., and Wm E. Hathaway. “Vitamin K in infancy.” The Journal of pediatrics 106.3 (1985): 351-359.
18. Golding, J., M. Paterson, and L. J. Kinlen. “Factors associated with childhood cancer in a national cohort study.” British Journal of Cancer 62.2 (1990): 304.
19. Golding, Jean, et al. “Childhood cancer, intramuscular vita K, and pethidine given during labour.” BMJ: British Medical Journal 305.6849 (1992): 341.
20. Klebanoff, Mark A., et al. “The risk of childhood cancer after neonatal exposure to vita K.” New England Journal of Medicine 329.13 (1993): 905-908.
21. Ekelund, Hans, et al. “Administration of vita K to newborn infants and childhood cancer.” BMJ: British Medical Journal 307.6896 (1993): 89.
22. Olsen, Jorgen H., et al. “Vit K regimens and incidence of childhood cancer in Denmark.” BMJ 308.6933 (1994): 895-896.
23. Rennie, Janet M., and A. W. Kelsall. “Vita K prophylaxis in the newborn–again.” Archives of disease in childhood 70.3 (1994): 248.
24. Schulte, Rachael, et al. “Rise in Late Onset Vita K Deficiency Bleeding in Young Infants Because of Omission or Refusal of Prophylaxis at Birth.” Pediatric neurology 50.6 (2014): 564-568.