Jessie King

Vitamin K and serum osteocalcin

October 7, 2014

Vitamin K is a fat soluble vitamin that has several known roles in the body, and several
that are just beginning to be understood and researched in the scientific community. Vitamin K is
found in many food sources, like leafy greens, but is also synthesized by a variety of microbes,
many of whom commonly dwell in the human intestines, contributing to circulating levels.
Vitamin Ks role in blood clotting has been widely known for quite some time, but the vitamins
role in carboxylating glutamic acid, and what carboxylated proteins role, or lack thereof, in the
body is still an area in need of research and understanding. Vitamin Ks relationship to bone
density and vascular calcification is an area of research that is currently very popular.
The main purpose of the research, Effect of Phylloquinone (Vitamin K1) Supplementation
for 12 Months on the Indices of Vitamin K Status and Bone Health in Adult Patients with Crohns
Disease, was to assess the results of supplementation of phylloquinone or vitamin K1, along with
calcium and vitamin D, on carboxylated osteocalcin in serum as well as effects on bone mineral
density in patients with Crohns Disease compared to control. It has been widely known that
inflammatory bowel diseases can affect vitamin and mineral absorption in the intestines,
resulting in deficiency, even when dietary intake is adequate. Other studies have looked at
vitamin K deficiencies in inflammatory bowel diseases in pediatrics (Nowak et al., 2013) as well
as assessed anemia and iron deficiency in patients with inflammatory bowel disease (Alves,
Miszputen, & Figueiredo, 2014). It is also known that vitamin K works in the body to
carboxylate glutamic acid, and one measure of this in serum uncarboxylated osteocalcin.
Carboxylated osteocalcin is thought to bind calcium more easily making it available for bone
matrix growth (Cristiani et al. 2014). Growing interest in how vitamin K relates to bone health as
well as vascular calcification makes this study important to the scientific community.

This study utilized an experiment method of research, specifically a double-blind,

placebo-controlled study. This is generally considered the top model for studies. Researchers and
participants were both unaware of their status as a placebo member or active ingredient member
of the study. This allows for unbiased data from the investigators and from the participants.
Many other studies use a blinded, placebo controlled study to study a response to something, like
a vitamin supplement (Lalla, et al. 2012). The study gave 43 participants a supplement of
phylloquinone, vitamin K1, and 43 participants a placebo. Both parties received an additional
and identical calcium and vitamin D supplement to aid treatment. Serum measurements were
taken baseline, before the study began, at a 6 month midpoint and 12 month end point of the
trial. Bone density was measured baseline and at the 12 month end point.
Parts of the studys hypothesis were rejected, and parts were accepted. They predicted
that participants given the supplementation would have increased serum phylloquinone levels,
increasing serum carboxylated osteocalcin. This would in turn decrease bone turnover and
increase bone density. The supplementation of the vitamin K did increase serum phylloquinone
levels as well as significantly increasing carboxylated osteocalcin levels by 76% at the 12 month
endpoint in the trial compared to baseline as well as to the placebo control group (OConnor et
al. 2014). However, in opposition to their hypothesis, there was no statistically significant
increase in bone density in either the control group or supplement group. These findings are
consistent wither other similar research done (Binkley et al. 2009). The study was conducted on a
relatively small scale, and a larger trial with more participants could yield more conclusive
results. Although a year is a modest time, a longer supplementation time may yield different
results. The study participants all had healthy bone density as osteoporosis was an exclusion

criterion for the trial. People with further progression of bone demineralization may react more
significantly to increased vitamin K and carboxylated osteocalcin.
While this study looked at decreased serum phylloquinone levels and uncarboxylated
osteocalcin in patients with inflammatory bowel disease, many other populations are being
researched for similar phenomenon. Postmenopausal women, a known population at risk for low
bone density, is also a current area of similar studies (Je, H. S. 2011). Those with conditions that
can alter normal vitamin and mineral absorption in the intestines, like inflammatory bowel
disease, are also an area of research for many of the vitamins and minerals, but specifically the
fat soluble ones like vitamin D (Veit, Maranda, Fong & Nwosu 2014). As science uses research
studies to better understand vitamin absorption, and the role it plays in the body, the knowledge
of how to prevent and treat conditions and disease becomes more apparent and allows for
different therapies and complementary therapies to maximize health for all populations. This
research on vitamin K and bone health and other similar studies (Nakajima et al. 2011) should
lead the way for further research on the matter. A related area to be researched is the role vitamin
K plays in vascular calcification. Matrix gla protein is thought to inhibit arterial calcification;
when uncarboxylated, its ability to do so are diminished. Vitamin K status may affect vascular
calcification (Shea et al. 2011)
While the role of vitamin K in carboxylating proteins in the body is moderately
understood, the full role that those proteins play in the body is not, and needs to be researched
further. Emerging studies suggest that many disease states could be helped by increased vitamin
K levels, however results from studies are mixed. More research needs to be done in the area of
vitamin K and the affect it has on bone as well as the role it plays with calcium.

Works Cited
OConnor, E. M., Grealy, G., McCarthy, J., Desmond, A., Craig, O., Shanahan, F., & Cashman,
K., D., (2014). Effects of phylloquinone (Vitamin K1) supplementation for 12 months on
the indices of vitamin K status and bone health in adult patients Crohns disease. British
Journal of Nutrition. Sept 2: 1-12. doi: 10.1017/S0007114514001913
Nowak, J. K., Grzybowska-Chlebowczyk, U., Landowski, P., Szaflarska, A., Klincewicz, B.,
Adamczak, D., Walkowiak, J. (2014). Prevalence and correlates of vitamin K
deficiency in children with inflammatory bowel disease. Scientific Reports. Published
online doi:10.1038/srep04768
Alves, R. A., Miszputen, S. J. & Figueiredo, M. S. (2014) Anemia in inflammatory bowel
disease: prevalence, differential diagnosis and association with clinical and laboratory
variables. S o PauloMedical Journal. 132(3): 140-6.
Cristiani, A., Maset, F., De Toni, L., Guidolin, D., Sabbadin D., Strapazzon, G., Foresta, C.
(2014). Carboxylation-dependent conformational changes of human osteocalcin. Front
Biosci. 1;19:1105-16.
Lalla, R., V., Choquette, L. E., Feinn, R., S., Zawistowski, H., Latortue, M. C., Kelly, E. T. &
Baccaglini, L. (2012) Multivitamin therapy for recurrent aphthous stomatitis: a
randomized, double-masked, placebo-controlled trial. Journal of the American Dental
Association. 143(4): 370-376.
Binkley, N., Harke, J., Krueger. D., Engelke, J., Vallarta-Ast, N., Gemar, D., Suttie, J. (2009)
Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone

turnover, density or geometry in healthy postmenopausal North American women.

Journal of Bone and Mineral Research. 24(6):983-991. doi:10.1359/JBMR.081254
Je, S. H., Joo, N., Choi, B., Kim, K-M., Kim, B., Park, S., Lee, D. (2011) Vitamin K
supplement along with vitamin D and calcium reduced serum concentrations of
undercarboxylated ostocalcin while increasing bone mineral density in Korean
postmenopausal women over sixty-years-old. Journal of Korean Medical Science. 26:
1093-1098. doi: 10.3346/jkms2011.26.8.1093
Viet, L., Maranda, L., Fong, J. & Nwosu, B. U. (2014) The vitamin D status in inflammatory
bowel disease. PLoS One. 9(7):e101583. doi: 10.1371/journal.pone.0101583
Nakajima, S., Iijima, H., Egawa, S., Shinzaki, S., Kondo, J., Inoue, T., Hayashi, N. (2011)
Association of vitamin K deficiency with bone metabolism and clinical disease activity in
inflammatory bowel disease. Nutrition. 27(10):1023-8. doi: 10.1016/j.nut.2010.10.021
Shea, M. K., ODonnell, C. J., Vermeer, C., Magdeleyns, E. J., Crosier, M. D., Gundberg, C. M.,
Booth, S. L. (2011) Circulating uncarboxylated matrix gla protein is associated with
vitamin K nutritional status, but not coronary artery calcium, in older adults. Journal of
Nutrition. 141(8):1529-1534. doi: 10.3945/jn.111.139634