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Beyond calcium and magnesium—Vitamin K for bone health

It is well known that calcium is vital for bone health.  Scientist are now beginning to understand that calcium isn’t the only necessary nutrient. Several vitamins and minerals are essential for supporting healthy bone mass over one’s lifespan. For example, ample evidence shows that magnesium plays a critical role in converting vitamin D into its active form to activate calcium absorption.  Researchers are also beginning to understand the role of vitamin K for supporting the maintenance of bone quality.

runnerSince the support of healthy bones is a top priority for many populations, especially seniors, this discovery underscores the growing significance of vitamin K. A specific focus on vitamin K is now of increasing concern since analyses of NHANES data sets suggest that only one-third of the U.S. population has adequate intake.

What does vitamin K do?

Vitamin K is the generic name for a family of fat-soluble compounds with the chemical structure of 2-methyl-1,4-naphthoquinone. The most common forms are phylloquinone known as vitamin K1 and a series of menaquinones known as vitamin K2. These compounds function as a coenzyme for vitamin K dependent carboxylase, an enzyme that is needed for synthesis of proteins used in blood clotting, bone metabolism and various other physiological functions.,

As it relates to bone support, vitamin K dependent protein, such as matrix-GLA protein, is present in vascular smooth muscle, bone and cartilage and is of interest for its ability to reduce abnormal calcification. Another K-dependent protein, osteocalcin, is present in bone and may be involved in bone mineralization or turnover.

Beyond these protein dependent associations, less is known about how vitamin K is absorbed and transported in the body. However, research does suggest that there are large chain menaquinones in the large bowel. Though it is unclear how they are obtained, it is thought likely that they provide some of the body’s vitamin K requirements.,

Research on the role of vitamin K forms is just beginning. Still, as concerns over the risk of poor bone health and vascular calcification for health increase, emerging evidence shows its role in these functions.  

Vitamin K2 or menaquinone-7 is the more researched form of the vitamin.  A 2016 study examining the role of vitamin K2 in bones and blood vessels suggests that the vitamin may stimulate bone formation by promoting osteoblast differentiation and carboxylation of osteocalcin, as well as supporting other markers of health such as increasing alkaline phosphatase, insulin-like growth factor-1, growth differentiation factor-15 and stanniocalcin 2 levels. Researchers concluded that including vitamin K2 may be a worthwhile strategy for maintaining healthy bone and vascular function, especially in post-menopausal women.

Another 2016 study noted vitamin K2 as a valuable member of the vitamin K series thought to have significant effects for both maintenance of healthy bones and support of cardiovascular function.

Emerging evidence suggesting that, like magnesium, vitamin K may  have a synergistic effect with vitamin D. In particular, recent studies in Japan have shown a connection between vitamin K2, calcium and vitamin D. These findings stressed that good nutrition, with adequate intake of these nutrients starting at a young age, may be instrumental in supporting long-term bone health. Another study looking at the pharmacokinetics of active vitamin K2 and vitamin D and its derivatives found that menatetrenone (one of the nine forms of K2) is easily absorbed from the intestine and distributes to bone at higher rates than other natural vitamin K homologues.

Some studies, however, have shown mixed results in the effects of vitamin K for bone mineral density, but the authors of one review note caution in comparing studies in which both vitamin K and D (and/or calcium) are administered to those in which only vitamin K was used. The paper’s authors suggest that vitamin D and/or calcium along with K may explain the inconsistent results. This may be particularly true for vitamin K1, which was cited in a 2016 study where researchers noted the influence on bone mineral density with supplementation of vitamin D and vitamin K1.

Vitamin K deficiency

Although deficiency of vitamin K is rare, there is growing concern that many Americans may not be getting enough of the vitamin in their diet. Adequate intake of vitamin K as established by the Food Nutrition Board ranges from 2.0 mcg for infants to 90 mcg for adult women and 120 mcg for adult men.

vit-k-rich-foodsVitamin K is available in a number of food sources. Phylloquinone or vitamin K1 can be found in foods including dark green vegetables (spinach, broccoli) and fats and oils such as soybean and canola. The best food sources for vitamin K2 include meat, dairy, and eggs.  Because menaquinones are of bacterial origin, K2 is also present in fermented foods, like natto (a Japanese food made with fermented soybeans). The amount of the nutrient present in these foods varies by the bacterial strains used.

Studies on the bioavailability of vitamin K from food sources are limited, but evidence suggests it may be difficult to get enough from food alone.  Absorption of phylloquinone is relatively low at under 20 percent. This may be enhanced when vegetables are consumed with fats. Research suggests that menaquinones from oils may have higher bioavailability than phylloquinones from vegetable sources.

Supplements are the best option for those with less than optimal vitamin K dietary intake. The nutrient is present in small amounts in most multivitamins.  There are also specialty supplements that contain a combination of vitamin K with important partners, such as calcium, magnesium and vitamin D. Various forms of vitamin K are used in supplements, and while there is little research on their specific bioavailability, one study noted that phytonadione (a synthetic form of vitamin K1) and MK-7 are both well absorbed though MK-7 has a longer half life.

Vitamin K deficiency is not often assessed, but low levels can lead to less healthy bone mass. This may be important to monitor in some patients, especially populations at particular risk.  Newborns are especially susceptible  because vitamin K does not transfer well across the placenta.  Given this, the American Academy of Pediatrics recommends an administration of a single vitamin K dose at birth. Infants not treated at birth may show a vitamin inadequacy.

Other groups at risk for low vitamin K levels include patients with malabsorption disorders and gastrointestinal problems, such as cystic fibrosis and those with celiac disease and ulcerative colitis, because they may not absorb vitamin K properly. Nutritional disorders, like anorexia nervosa have also been linked to low vitamin K levels and patients with this issue may benefit from vitamin K supplementation to help maintain healthy bone mass. Use of particular medications, such as anticoagulants and antioxidants can also impact vitamin K levels and should be monitored, especially when the drug use is prolonged.

References

  1.       Fulgoni VL, 3rd et al. Foods, fortifications and supplements: Where do Americans get their nutrients? J Nutr 2011;141:1847-54.
  2.       Wallace TC et al. Multivitamin/mineral supplement contribution to micronutrient intakes in the United States, 2007-2010. J Am Coll Nutr 2014;33:94-102.   
  3.       Institute of medicine Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, maganese, molybdenum, nickel, silicon, vanadium and zine. Washington DC; National Academy Press; 2001.
  4.       NIH Vitamin K Fact Sheet for Health Professionals, accessed online at https://ods.od.nih.gov/factsheets/VitaminK-HealthProfessional/., In: Coates PM, Betz JM, Blackman MR et al., eds. Encyclopedia of Dietary Supplements. 2nd Ed. London and New York; Informa Healthcare;2010;851-60.
  5.       Schurgers LJ. Vitamin K; key vitamin in controlling vascular function in chronic kidney disease. Kidney Int. 2013;83:782-4.
  6.       Ibid. NIH Vitamin K Fact Sheet for Health Professionals.
  7.       Conly JM et al. The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitam K. Am J Gastroenterol 1994;89:915-23.
  8.       NIH Vitamin K Fact Sheet for Health Professionals, accessed online at https://ods.od.nih.gov/factsheets/VitaminK-HealthProfessional/., In: Ross AC et al. Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD; Lippincott Williams & Wilkins; 2014:305-16.
  9.       Villa JK et al. Effect of vitamin K in bone metabolism and vascular calcification: A review of mechanisms of action and evidences. Crit Rev Food Sci Nutr. 2016 Jul20:0 (Epub ahead of print).
  10.   Mahdinia E et al. Production and application of menaquinone-7 (vitamin K2): a new perspective. World J Microbiol Biotechnol 2017 Jan;33(1):2. Epub 2016 Nov. 10.
  11.   Ito M, Tanaka S. Bone disorder and nutrition. Clin Calcium 2016 Mar;26(3):375-83. Doi: CliCa1603375383.
  12.   Tsugawa N. Clinical pharmacokinetics of active vitamin D and its derivatives, and vitamin K2(menatetrenone). Clin Calcium 2016;26(11):1547-1558.
  13.   Binkley N et al. Vitamin K treatment reduces underbarbosylated osteocalcin, but does not alter bone turnover, density or geometry in healthy postmenopausal North American women. J Bone Miner Res 2009;24:983-91.
  14.   Hoffman MR, MSc, et al. Vitamin D status and bone mineral density is influenced by vitamin D and vitamin K1 intake in adults with Diabetes and Chronic Kidney Disease. Can J Diet Pract Res. 2016 Oct 25:1-9.
  15.   Ibid. Modern Nutrition in Health and Disease.
  16.   Schurgers LJ et al. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 2007;109:3279-83.
  17.   NIH Vitamin K Fact Sheet for Health Professionals from the American Academy of pediatric Committee on F, newborn. Controversies Concerning vitamin k and the newborn. American Academy of Pediatrics Committee on Fetus and Newborn. Pediatrics 2003;112:91-2.
  18.   Urano A et al. Vitamin K deficiency evaluated by serum levels of undercarboxylated osteocalcin in patients with anorexia nervosa with bone loss. Clin Nutr 2015 Jun;34(3):443-448.

 

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