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Vitamin K, circulating cytokines, and bone mineral density in older men and women^1,2,3,4

¹ From the US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA (MKS, GED, BD-H, JMO, JWP, and SLB); the NIH National Heart, Lung, and Blood Institute, Framingham Heart Study, Framingham, MA (CJO); and the Department of Orthopaedics, Yale University School of Medicine, New Haven, CT (CMG)

Background: Vitamin K modulates cytokines involved in bone turnover, including interleukin-6 (IL-6) and osteoprotegerin in vitro.

Objective: The objective of this study was to assess 1) associations between measures of vitamin K status [plasma phylloquinone and serum percentage of undercarboxylated osteocalcin (%ucOC)] and IL-6, osteoprotegerin, and C-reactive protein (CRP) concentrations and 2) the effect of daily 500 µg phylloquinone supplementation for 3 y on cytokine concentrations.

Design: Concentrations of IL-6, osteoprotegerin, and CRP and bone mineral density (BMD) were measured at baseline and after 3 y of follow-up in 379 healthy men and women (60–81 y; 58.5% women) 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, whereas serum %ucOC was inversely associated with IL-6. Osteoprotegerin was associated positively with plasma phylloquinone and inversely with %ucOC. No differences were observed in the 3-y change in IL-6, osteoprotegerin, and CRP concentrations between participants who received phylloquinone supplementation and those who did not. Overall, no association was observed between the 3-y 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. The healthy status of this cohort may explain a lack of effect of vitamin K supplementation on cytokine concentrations. This trial was registered with www.clinicaltrials.gov as NCT00183001.