Reducing undercarboxylated osteocalcin with vitamin K supplementation does not promote lean tissue loss or fat gain over three years in older women and men: a randomized controlled trial

Authors: SHEA, KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GUNBERG, CAREN - Yale University; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Bone and Mineral Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/2/2016
Publication Date: 2/1/2017
Citation: Shea, K., Dawson-Hughes, B., Gunberg, C., Booth, S.L. 2017. Reducing undercarboxylated osteocalcin with vitamin K supplementation does not promote lean tissue loss or fat gain over three years in older women and men: a randomized controlled trial. Journal of Bone and Mineral Research. 32(2):243-249. doi: 10.1002/jbmr.2989.

Interpretive Summary: Osteocalcin is a protein made by bone cells. After it is made, it undergoes an enzymatic modification called carboxylation. This requires vitamin K. When vitamin K nutritional status is low, the carboxylated form of osteocalcin (cOC) in blood decreases, and the undercarboxylated form of osteocalcin (ucOC) increases. Experiments conducted in mice reported that ucOC influences energy metabolism because mice injected with ucOC lost fat and gained skeletal muscle. We tested this theory in humans by comparing the change in body fat mass and the change in skeletal muscle mass between older adults whose serum ucOC was reduced by vitamin K supplementation for 3 years to older adults whose serum ucOC did not change because they did not receive vitamin K supplementation. After 3 years, the changes in body fat mass and skeletal muscle mass did not differ between the two groups. These findings indicate reducing ucOC through vitamin K supplementation does not affect fat or muscle mass in older community-dwelling adults.

Technical Abstract: Osteocalcin (OC) is a vitamin K-dependent protein synthesized during bone formation. Mice injected with the undercarboxylated form of OC (ucOC) had more skeletal muscle mass and less fat mass than sham-treated controls, suggesting a unique metabolic role for ucOC. UcOC decreases in response to vitamin K supplementation. Our objective was to determine the effect of reducing ucOC on change in lean tissue and fat mass in older community-dwelling adults (n=401, mean +/- SD 69 +/- 6 years) using data from a randomized controlled trial of vitamin K supplementation. Over 3 years, serum ucOC was reduced by 58% in women and by 61% in men randomized to vitamin K, whereas in the control group, ucOC decreased by 1% in women and 4% in men (supplementation*time p<0.001 in men and women). However, there were no differences in the change in appendicular lean mass (calculated as arm lean mass + leg lean mass) or total body fat mass between women randomized to vitamin K and control over 3 years (supplementation*time p-values all >/=0.18) or between men randomized to vitamin K and control (supplementation*time p-values all >/=0.54). Consistent with these findings, ucOC was not associated cross-sectionally with appendicular lean mass or fat mass in men or women after adjustment for total OC at baseline (all p >/=0.12). These findings indicate the undercarboxylated form of OC is not implicated in age-related changes in skeletal muscle or adipose tissue mass in older community-dwelling adults.