Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/18/2008
Publication Date: 8/8/2008
Citation: Shea, K., Dallal, G., Dawson-Hughes, B., Ordovas, J.M., O'Donnell, C., Gundberg, C., Peterson, J., Booth, S.L. 2008. Vitamin K circulating cytokines and bone mineral density in older men and women. American Journal of Clinical Nutrition. 88:356-63. Interpretive Summary: Limited data from cell studies suggest that vitamin K can modulate inflammation, and the results from one population study support this. To better understand the influence of vitamin K on inflammation in older adults, 379 men and women (60-80y) were randomized to receive a multi-vitamin with vitamin K or a multi-vitamin without vitamin K for 3 years. Measures of inflammation, as well as bone mineral density, were done at baseline and after 3 years of follow-up. Although vitamin K status, as measured by blood concentrations of vitamin K, was inversely associated with inflammation at baseline, there was no difference in the change in inflammation between those who received the vitamin K supplement and those who did not. The change in inflammation over 3 years was also not associated with the change in bone loss in these older adults. In summary, vitamin K status may be associated with lower inflammation, but supplementation with vitamin K for 3 years did not influence change in inflammation in generally healthy older men and women.
Technical Abstract: Background: Vitamin K has been shown in vitro to modulate cytokines involved in bone turnover, including interleukin-6 (IL-6) and osteoprotegerin (OPG). Objective: To assess: (1) associations between measures of vitamin K status [plasma phylloquinone and serum percent undercarboxylated osteocalcin (percent ucOC)] and IL-6, OPG, and C-reactive protein (CRP) concentrations; and (2) the effect of 3-years of daily 500ug phylloquinone (vitamin K1) supplementation on cytokine concentrations in older men and women. Design: IL-6, OPG, CRP concentrations, and bone mineral density (BMD), were measured at baseline and after 3-years of follow-up in 379 men and women (60-80y; 59percent F) participating in a randomized trial that studied the effect of vitamin K supplementation on bone loss. Results: Cross-sectionally, plasma phylloquinone was inversely associated with IL-6 and CRP while serum percentucOC, which is elevated when vitamin K status is reduced, was positively associated with IL-6. Contrary to expectation, OPG was associated positively with plasma phylloquinone and inversely with percentucOC. There were no differences in 3-year IL-6, OPG, and CRP concentrations between individuals who received phylloquinone supplementation and those who did not. Overall, there was no association between the 3-year changes in circulating cytokines and BMD. Conclusions: Poor vitamin K status was associated with high concentrations of cytokines involved in bone turnover, but vitamin K supplementation did not confer a decrease in cytokine concentrations. Poor vitamin K status may be a marker for overall poor health. Alternatively, the health status of this cohort may explain a lack of effect of vitamin K supplementation on cytokine concentration.