Vitamin K2, but not Vitamin K1, is Helpful for bone Density

Vitamin K's effectiveness in the prevention and treatment of osteopenia/osteoporosis has just been discounted in a WebMD review1 ("Vitamin K: No Help for Bone Density") of research published Oct. 14, 2008, in PLOS Medicine (Cheung A, et al.)2

In this two-year study, which involved 440 post-menopausal women diagnosed with osteopenia, Canadian researchers, not surprisingly, found that taking 5 mg per day of vitamin K1 did not prevent further age-related declines in bone density, even if the women had adequate levels of vitamin D. What is surprising is that the researchers, despite noting that vitamin K is a family of compounds, and that vitamin K2 is the form which is an approved treatment for osteoporosis in Japan, chose to use vitamin K1 in their clinical trial.

It is well known that vitamin K1 (phylloquinone) is involved in blood coagulation. It is also well documented that vitamin K2 (menaquinone) is the essential cofactor for the carboxylation (activation) of the (gamma-carboxyglutamic acid) Gla-containing proteins involved in calcium regulation.3

Numerous peer-reviewed studies have shown that vitamin K2—given either in its MK-4 form (a short-chain version called menatetrenone) at a dosage of 45 mg/day, or as MK-7 (a long-chain version called menaquinone derived from natto) at a dosage of 45 mcg/day—is a highly effective activator of osteocalcin, the Gla-containing protein essential to calcium deposition in bone.4 This body of research conclusively demonstrates that vitamin K2 not only lessens fracture incidence and improves bone density but also, via the carboxylation of another Gla protein (matrix Gla protein), inhibits arterial calcification.5

Furthermore, even though they did not receive the appropriate form of vitamin K, women in the treatment group had significantly fewer fractures—only 9 women given vitamin K1 vs. 20 given placebo had fractures (the reason we treat to promote higher bone density!). In addition, surrogate markers of bone production were up, and the trends were toward higher density at several points during the intervention.

Cheung said she cannot account for these highly beneficial findings. We propose that recently published research indicating that vitamin K, both as K1 and K2, significantly lowers cytokine production and overall inflammation, may provide one reason. It is well known that inflammation increases as estrogen levels decline with menopause, and that increased production of pro-inflammatory cytokines is associated with increased differentiation and activation of osteoclasts.6 Vitamin K lessens oxidative stress and down-regulates expression of pro-inflammatory cytokines. In the Framingham Offspring Study, vitamin K status, measured by plasma phylloquinone concentration and phylloquinone intake, was inversely associated with lower concentrations of circulating inflammatory markers.7 K2 also provides anti-inflammatory effects via carboxylation of Gas6 (growth arrest specific gene 6), which then speeds the phagocytosis of apoptotic cells (an essential process for normal tissue development and maintenance), and promotes cell survival in a wide range of cell types.8 9

What possible reason could Cheung et al. have had for not using K2, clearly the optimal form of vitamin D for bone health?

Some vitamin K1 undergoes intestinal conversion to K2

True, but only 5-25% of ingested vitamin K1 is catabolized, first to menadione, even less of which is further converted via prenylation, to K2. What is most important to note here, however, is that the form of K2 into which menadione is converted is the MK-4 form. Many studies have shown specific clinical benefits of MK-4 at pharmacological doses for osteoporosis and cancer, but the dosage required is 45 mg/ day.10 Even, given the best case scenario, in which 25% of the 5 mg daily dose of K1 is converted into 1,250 mcg of mendadione, 25% of which is further prenylated into 312.5 mcg of MK-4, the result is nowhere near the 45 mg of MK-4 necessary to carboxylate osteocalcin in amounts sufficient to increase bone mineralization.11

Vitamin K1 is the primary form in the diet

It is true that vitamin K1 is, far and away, the primary form ingested in the Western diet. As noted above, it is also true that some K1 is converted into K2 in the intestines (if the pro-biotic bacteria necessary are present, which in any individual with gastrointestinal dysfunction may be an issue). Animal products, such as dairy and eggs, and fermented foods also provide a tiny amount of K2. Natto, the only significant food source of K2, is infrequently consumed, even in Japan, due to its taste.

So, perhaps Cheung et al. chose K1 in deference to "real life" conditions? This cannot be the case given the amount of leafy greens one would need to consume to provide 5 mg/day of K1. As the tables below indicate, it would be impossible to achieve anything remotely close to this dosage via diet, a fact reflected by public health recommendations for vitamin K intake (i.e., K1). In 2000, the National Academy of Sciences established the following Adequate Intake (AI) levels for vitamin K12:

Adequate Intake Levels for Vitamin K
Sex and Age Vitamin K (mcg)
Males and females, 0-6 months 2
Males and females, 7-12 months 2.5
Males and females, 1-3 years 30
Males and females, 4-8 years 55
Males and females, 9-13 years 60
Males and females, 14-18 years 75
Males, 19 years and older 120
Females, 19 years and older 90
Pregnant or lactating females, 18 years and younger 75
Pregnant or lactating females, 19 years and older 90
Food Sources of Vitamin K113
Food Serving Micrograms of Vitamin K1
Kale, raw 1 cup, chopped 547
Swiss chard, raw 1 cup 299
Parsley, raw ¼ cup 246
Broccoli, cooked 1 cup, chopped 220
Spinach, raw 1 cup 145
Watercress 1 cup, chopped 85
Green leaf lettuce, raw 1 cup, shredded 62.5
Soybean oil 1 tablespoon 25
Canola oil 1 tablespoon 16.6
Olive oil 1 tablespoon 8.1
Mayonnaise 1 tablespoon 3.7

So, the choice of K1 for this trial remains a mystery, as does the lack of critical analysis and incomplete conclusion provided by the WebMD review. Hopefully, the outcome of this misleading information will not be an increased incidence of osteopenia/osteoporosis in women at risk of these conditions whose physicians are dissuaded from prescribing vitamin K2.

ReferencesClick to Show/Hide References

  1. Cheung A, Tile L, Lee Y, et al. Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial. PLOS Medicine. Oct. 14, 2008; Vol 5: p. e196.

  2. http://www.webmd.com/osteoporosis/news/20081013/vitamin-k-no-help-for-bone-density

  3. Pizzorno L, Pizzorno J. Vitamin K: Beyond Coagulation to uses in Bone, Vascular, and Anti-Cancer Metabolism. IMCJ. Apr/May 2008, Vol 7:No. 2, p.24-30.

  4. Schurgers LJ, Teunissen KJ, Hamulyák K. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007 Apr 15;109(8):3279-83.

  5. Schurgers LJ. Vitamin K2 as MenaQ7, Improve bone health and inhibit arterial calcification. NattoPharma.
    http://www.menaq7.com/index.php?s=Research

  6. Mundy GR. Osteoporosis and inflammation. Nutr Rev. 2007 Dec;65(12 Pt 2):S147-51.

  7. Shea MK, Booth SL, Massaro JM, et al. Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study. Am J Epidemiol. 2008 Feb 1;167(3):313-20.

  8. Grommes C, Lee CY, Wilkinson BL, et al. Regulation of microglial phagocytosis and inflammatory gene expression by Gas6 acting on the Axl/Mer family of tyrosine kinases. J Neuroimmune Pharmacol. 2008 Jun;3(2):130-40.

  9. Bellido-Martín L, de Frutos PG. Vitamin K-dependent actions of Gas6. Vitam Horm. 2008;78:185-209.

  10. Thijssen HH, Vervoort LM, Schurgers LJ, et al. Menadione is a metabolite of oral vitamin K. Br J Nutr. 2006 Feb;95(2):260-6.

  11. Shearer MJ, Newman P. Metabolism and cell biology of vitamin K. Thromb Haemost. 2008 Oct;100(4):530-47.

  12. The National Academies. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. The National Academy Press. Washington DC, 2001.

  13. Food Processor Version 7.60, ESHA Research,Salem, OR, December 2000.

 

7 Comments

1. June 23, 2010
5:45am

By whey protein isolate

daily intake of 180 micrograms of vitamin K2 increases the bone mass of the lower back vertebrae.

2. June 23, 2010
5:58am

By Catholic drug rehab

It is very important that things needs to be cleared as it can mislead many people including some physicians as well. I am sure that these doubts will be cleared as some more research is still going on over it.

3. June 24, 2010
5:12am

By vitamin D

vitamin K regulates calcium in the bones and arteries promoting heart health and bone health at the same time Vitamin K seems to do the impossible accommodating the needs of both bones and arteries.

4. August 9, 2010
4:12am

By dietary supplements

Doctors have discovered that my sister has moderate/severe calcification of the heart. I’ve read several articles on the internet regarding clinical studies that have shown vitamin K2 will stop and reverse the calcification process. What I need to know is; If you are taking Warfarin, a medicine that helps to prevent blood clots, are you able to take a daily supplement of vitamin K2, without an adverse reaction occurring?

5. December 14, 2010
1:19pm

By excessive sweating

Vitamin K is used to reduce bleeding in liver disease, jaundice, malabsorption, or long-term use of aspirin or antibiotics. gastrointestinal disturbances, which reduce the absorption of vitamin K as obstacles biliary fibrosis, cystic, celiac disease, Crohns disease, colitis, and drugs that reduce the absorption of this vitamin, such as antibiotics. Vitamin K deficiency in cystic fibrosis is aggravated by the need for antibiotics applicant.

6. March 12, 2011
3:47pm

By Annie L. Williams

Thank you for this invaluable information!

7. March 12, 2011
3:51pm

By Annie L. Williams

Would you please show the date that this article was written (posted)? I would appreciate it very much.

Thank You

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Lara Pizzorno is a member of the American Medical Writers Association with 25+ years of experience writing for physicians and the public, Lara is Editor for Longevity Medicine Review as well as Senior Medical Editor for SaluGenecists, Inc. Read more...

Lara Pizzorno, MDiv, MA, LMT

Lara Pizzorno, MDiv, MA, LMT

John Morgenthaler has been active in the field of nutritional medicine since 1986. Today, John travels the world looking for breakthrough nutraceuticals and anti-aging therapies.  He also continues to publish cutting-edge nutrition and medical science books and periodicals. Read more...

John Morgenthaler, Publisher

John Morgenthaler, Publisher