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Vitamin K2 prevents prostate cancer, cardiovascular disease, and bone weakness

Introduction.

It has long been noticed geographical or national differences in prostate cancer susceptibility. These variations were mostly attributed to the specificity of the diet and culinary preferences of different cultures. And this, in turn, suggests that some foods or ingredients of food may have chemoprotective properties against cancer cells. Lycopene, selenium, vitamins C, D, E, and K, green tea, silymarin, pomegranate, and Resveratrol are well known dietary components that attracted considerable attention of scientists in terms of their anticancer potential. Here I’ll focus on vitamin K2 and its varieties as the natural food components capable of stopping the development of the prostate cancer or slowing down its progression.

Chemical structure, dietary recommendations, and absorption of vitamin K2.

Vitamin K structurally exists in two forms, Phylloquinone (Vitamin K1) and Menaquinones (Vitamin K2), which determines their functional specificity. Most of the people associate vitamin K with a clotting factor of the blood, vitamin K1, and have never heard about vitamin K2. It’s vitamin K2 that attracts the most intensive attention both scientists and dietitians lately. For millions of people suffering from cardiovascular disease (CVD) and osteoporosis, it may prove the only natural life-saving food alternative.

The chemical structure of both forms of vitamin K includes a naphthoquinone ring and a side chain of isoprene residues. It is the length, and the degree of saturation of the side chain, which determines the differences of various forms of Vitamine K. Vitamine K1 is a compound with a side chain of four residues, three of which are saturated (fig. 1). Menaquinones include side chains of varying length between 4 and 13 residues, most of which are unsaturated. The short-chain MK-4 and the long-chain MK-7, MK-8, MK-9, and MK-10 are the most abundant menaquinones in the human diet.

Structure of VitaminK 2
From “The role of menaquinones (vitamin K₂) in human health.” https://www.ncbi.nlm.nih.gov/pubmed/23590754

Dietary recommendations for vitamin K are developed only for phylloquinone and are in the range of 55-90 mg/d for adult women and 65–120 mg/d for adult men.

Green vegetables, such as spinach, broccoli, kale, and Brussels sprouts are rich with vitamin K1.

Significant sources of vitamin K2 are fermented foods such as cheese, curd, sauerkraut, and natto (a traditional Japanese food composed of fermented soya beans). Natto is an excellent source of vitamin K2 and contains more than 100 times as much menaquinones as various cheeses.

Fermentation is a process of converting sugars from the food to alcohol or organic acids. This process runs without oxygen and requires some specific microorganisms—yeasts or bacteria. Human’s colon contains from 1.5 to 4 lbs of microbiota and fermentation is a natural process for this environment. I particular, it’s in an intestinal system that a considerable amount of vitamin K1 is converted to vitamin K2.

Bioavailability of all forms of vitamin K is higher in the fat-rich diets.

Absorption of the vitamin K takes place in the small intestine, and this process requires the bile salts. The role of the menaquinones produced by the gut microbiota via fermentation of some foods is unclear since no bile salts are available in the colon, where most microbial strains exist.

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How much vitamin K2 required to prevent cardiovascular disease?

Investigating the physiological role of vitamin K2 in inhibiting prostate cancer, we cannot overlook its well-established functions in preventing cardiovascular disease and bone health. Both of these healing effects of vitamin K2 are due to its function of regulating calcium metabolism: vitamin K2 improves deposition of calcium in bones and prevents calcification of soft tissues, kidneys, and blood vessels. Calcium accumulation in the arteries is the leading risk factor for CVD.

The standard function of all forms of vitamin K is that they serve as an active center for the enzyme g-glutamate carboxylase, which converts specific glutamate residues into g-carboxyglutamate, known as Gla. Gla-protein family includes 17 members, seven of which are involved in blood clotting. However, only for blood coagulation factors, osteocalcin (OC; bone formation), and matrix Gla protein (MGP; an inhibitor of soft tissue calcification), the physiological role is well established and studied.
MGP may inhibit coronary calcification thus preventing CVD or significantly reducing its risk.

Studies show an inverse association of high vitamin K2 intake with reduced coronary calcification. More information you can find in these articles:

  • Geleijnse JM, Vermeer C, Grobbee DE, et al. (2004) Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr 134, 3100–3105.
  • Beulens JW, Bots ML, Atsma F, et al. (2009) High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis 203, 489–493.

In the Rotterdam Study, the hardness of aortic calcification correlated linearly with the dietary deficit of menaquinones (25·6 mg/d and 28·8 mg/d in severe and moderate cases respectively). People who consumed the largest amounts of vitamin K2 were 52% less prone to develop artery calcification and had a 57% lower risk of dying from heart disease.

In the second study, vitamin K2 intake over 48mg/d was linked with decreased coronary calcification among 600 women.

Vitamin K2 and bone health.

Osteoporosis or bone weakening is the most common reason for a broken bone among seniors, particularly in postmenopausal women.
Osteocalcin and MGP are vitamin K2 dependant proteins regulating calcium metabolism in bones. Calcium is the most abundant component in the skeleton which is in charge of its stiffness. MGP is tied to bone organic matrix formation and mobilization of calcium in bones. This protein has been found in blood vessels, cartilage, bone, and dentine. MGP significantly reduces bone fracture risk, promotes bone growth and development and prevents the calcification of soft tissue and blood vessels.

For example, two Japanese studies showed that the usual dietary
intake of natto was effective in maintaining bone stiffness. In Japan, vitamin K supplements are authorized for preventing and treating osteoporosis.

Even low-dose vitamin K2 supplementation (MK-7 180 μg MK-7/day) in postmenopausal women significantly decreased the age-related bone mineral loss and bone strength. These results suggest that the low-dose MK-7 supplements may, therefore, help senior women to maintain bone health.

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A meta-analysis of seven randomized controlled trials showed that
vitamin K2 decreased spinal fractures by 60%, hip fractures by 77% and all non-spinal fractures by 81%.

A vast majority of studies suggest that vitamin K2 is a proven alternative to prevent osteoporosis and fractures.

Can Vitamin K2 be used as a potential therapy for prostate cancer?

To answer the question, a group of scientists from the University of Illinois analyzed both the results of their own research and available literature data. According to their review, vitamin K inhibits the growth of cancer cells through apoptosis, cell cycle arrest, and autophagy and can potentially be explored as a therapy for prostate cancer. Apoptosis is a programmed cell death that takes place during normal organisms development.

Vitamin K is a group of naturally occurring fat-soluble chemicals characterized by a common naphthoquinone ring. This structural feature they share with some drugs used for cancer chemotherapy.
This partly explains why vitamin K has attracted interest in the prevention and treatment of cancer.

The anticancer effect of vitamin K was first reported about 60 years ago when the intravenous injection of the vitamin K3 (Menadione-synthetic form of vitamin K) extended the survival of inoperable bronchial carcinoma patients.

Vitamin K3 in combination with vitamin C enhances the suppression of cancer cell growth by activating oxidative stress. Oxidative stress refers to a disproportion between the production of reactive oxygen species in the cells and the ability of the organism to detoxify them or neutralize the resulting damage. Reactive oxygen species are intermediary products of many biological reactions. They contain oxygen and readily react with proteins, lipids, and DNA, often causing their damage. Examples of reactive oxygen species include peroxides, superoxide, hydroxyl radical and oxygen.

Both vitamin K1 and vitamin K2 have anticancer effects in various cancer cells including breast, stomach, liver, and prostate.

It has long been noticed that dietary vitamin K2 affects overall cancer risk. An inverse correlation was detected in males with cancers of the prostate, colorectum, and lung. Nimptsch et al. reported that the risk of advanced prostate cancer increases by 63% in patients with low levels of serum vitamin K2.

The long-term (one year ) vitamin K treatment reduced the risk of prostate cancer by 40% more than the short-term (three months) vitamin K treatment in another study (Taliani MR et al.).

By contrast, a few studies are reporting no apparent association between intake of vitamin K and total cancer risk (Pottegard et al., Hoyt M. et al.).
However, the treatment of vitamin K2 was shown to significantly inhibit the proliferation of both androgen-dependent and androgen-independent prostate cancer cells.

Menadione, combined with some other compounds such as vitamin C, plumbagin, and juglone has been shown to reduce the rate of prostate cancer growth in both in vitro and in vivo models. Plumbagin is a naphthoquinone containing and naturally occurring compound found in roots, leaves, bark, and wood of a walnut. Zhou et al. reported that plumbagin promotes the apoptosis and autophagy in prostate cancer cells.

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These studies suggest that vitamin K and its derivatives can effectively be used as a chemopreventive and therapeutic agent for prostate cancer.

Is it safe taking high vitamin K2 doses?

There is no evidence of toxicity for vitamin K1 or vitamin K2. The European Food Safety Authority concluded that low doses of menaquinones as a source of vitamin K presented no safety concerns.
Similarly, a single oral dose of 2g/kg or administration of 10 mg/kg per d for 90 days showed no toxicity in an animal study. Moreover, in humans, the thrombosis risk was not affected by MK-7 intakes as high as 360mg/d for six weeks.

Conclusion

Since nor any form of vitamin K has yet been tested for mutagenicity, it is advisable to use natural food sources of vitamin K. The most accessible sources of vitamin K2 are eggs, dairy foods of fermentation, cheese, curd, sauerkraut, liver, and natto. Natto would definitely be the best choice, but for some reason, it is not so popular on the American or European markets yet, and therefore the price is pretty high. If using animal products, remember, they must be from pastured cows or chickens.
If these foods are inaccessible to you, taking supplements is a proven alternative. Moreover, you can find some excellent combinations of vitamin K2 and vitamin D3 on Amazon. Vitamin D3 is another natural food component the anticancer properties of which has been proven scientifically.

Take care of your health, be aware before you put anything inside your body.

Literature.

  1. Hoyt M. et al. Vitamin K intake and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. Am J Clin Nutr. 2019 Feb 1;109(2):392-401
  2. Subramanyam D. et al. Vitamin K and its analogs: Potential avenues for prostate cancer management. Oncotarget. 2017 Aug 22; 8(34): 57782–57799.
  3. Nimptsch K, Rohrmann S, Kaaks R, Linseisen J. Dietary vitamin K intake in relation to cancer incidence and mortality: results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg) Am J Clin Nutr. 2010;91:1348–1358.
  4. Taliani MR, Agnelli G, Prandoni P, Becattini C, Moia M, Bazzan M, Ageno W, Tomasi C, Guazzaloca G, Ambrosio GB, Bertoldi A, Salvi R, Poggio R, et al. Incidence of cancer after a first episode of idiopathic venous thromboembolism treated with 3 months or 1 year of oral anticoagulation. J Thromb Haemost. 2003;1:1730–1733.
  5. Pottegard A, Friis S, Hallas J. Cancer risk in long-term users of vitamin K antagonists: a population-based case-control study. Int J Cancer. 2013;132:2606–2612.
  6. Cockayne S1, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Jun 26;166(12):1256-61.

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