Vitamin K, circulating cytokines, and bone mineral density in older men and women

US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 09/2008; 88(2):356-63.
Source: PubMed


Vitamin K modulates cytokines involved in bone turnover, including interleukin-6 (IL-6) and osteoprotegerin in vitro.
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 mug phylloquinone supplementation for 3 y on cytokine concentrations.
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.
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.
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 as NCT00183001.

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Available from: Jose M Ordovas, Feb 27, 2014
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    • "Elderly people [74] living in institutions [75] showed a higher susceptibility to vitamin K deficiency. These subjects may be good candidates to evaluate the anti-fracture efficacy of vitamin K [76]. Children, who have very high bone turnover Table 2 Determinants of g-carboxylation of osteocalcin. "
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    ABSTRACT: Vitamin K is a multi-functional nutrient and various tissues modify their function in response to vitamin K bioavailability mainly through post-translational modification of vitamin K-dependent (VKD) proteins. In this review, we discuss five clinical topics of vitamin K nutrition and vitamin K-dependent Gla-containing proteins. Although the physiological roles of these VKD proteins need further elucidation, study of these proteins may open new avenues for therapy in the clinical field. The topics discussed in the review are focused on des-gamma-carboxyprothrombin (DCP) in relation to the pathogenesis of hepatocellular carcinoma, osteocalcin (OC) and undercarboxylated OC (ucOC) in relation to bone fractures and insulin sensitivity, matrix Gla protein (MGP) in relation to vascular calcification, and growth arrest-specific protein-6 (Gas6) in relation to inflammation and platelet aggregation. Finally, interaction among vitamins were discussed.
    Full-text · Article · Oct 2015
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    • "In a subsample of 1,321 subjects from the Framingham Offspring Study, both plasma phylloquinone and dietary phylloquinone intake were inversely associated with peripheral concentrations of some inflammatory markers [9]. However, in a 3-year randomized clinical trial designed to assess the effect of vitamin K supplementation on bone loss, no differences were found in the plasma IL-6, C-reactive protein or osteoprotegerin concentrations of participants receiving or not a phylloquinone supplement [10]. "
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    ABSTRACT: Vitamin K has been related to glucose metabolism, insulin sensitivity and diabetes. Because inflammation underlies all these metabolic conditions, it is plausible that the potential role of vitamin K in glucose metabolism occurs through the modulation of cytokines and related molecules. The purpose of the study was to assess the associations between dietary intake of vitamin K and peripheral adipokines and other metabolic risk markers related to insulin resistance and type 2 diabetes mellitus. Cross-sectional and longitudinal assessments of these associations in 510 elderly participants recruited in the PREDIMED centers of Reus and Barcelona (Spain). We determined 1-year changes in dietary phylloquinone intake estimated by food frequency questionnaires, serum inflammatory cytokines and other metabolic risk markers. In the cross-sectional analysis at baseline no significant associations were found between dietary phylloquinone intake and the rest of metabolic risk markers evaluated, with exception of a negative association with plasminogen activator inhibitor-1. After 1-year of follow-up, subjects in the upper tertile of changes in dietary phylloquinone intake showed a greater reduction in ghrelin (−15.0%), glucose-dependent insulinotropic peptide (−12.9%), glucagon-like peptide-1 (−17.6%), IL-6 (−27.9%), leptin (−10.3%), TNF (−26.9%) and visfatin (−24.9%) plasma concentrations than those in the lowest tertile (all p<0.05). These results show that dietary phylloquinone intake is associated with an improvement of cytokines and other markers related to insulin resistance and diabetes, thus extending the potential protection by dietary phylloquinone on chronic inflammatory diseases. Trial registration as ISRCTN35739639
    Full-text · Article · Jan 2013 · Cardiovascular Diabetology
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    • "According to the Framingham Offspring Cohort cross-sectional study, following the measurement of vitamin K levels in subjects in a community-based setting, proinflammatory cytokines such as IL-6, intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor receptor 2 (TNFR2) were found to be negatively correlated with vitamin K [21]. Furthermore, according to Shea et al. [22], the concentration of serum high sensitivity C-reactive protein (hs-CRP), a sensitive inflammatory marker, had a negative correlation with serum vitamin K concentration. Moreover, according to a cross-sectional study conducted in elderly individuals, there was a positive correlation between osteoprotegerin, an inflammatory marker suppressing bone loss reactions, and vitamin K. "
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    ABSTRACT: Vitamin K intake has been reported as an essential factor for bone formation. The current study was conducted under the hypothesis that insufficient vitamin K intake would affect inflammatory markers and bone mineral density in young adult women. The study was a cross-sectional design that included 75 women in their 20s. Physical assessments, bone mineral density measurements, 24-hr dietary recalls, and biochemical assessments for high sensitivity C-reactive protein (hs-CRP) and percentages of undercarboxylated osteocalcin (%ucOC) were performed. An analysis of vitamin K nutritional status was performed comparing first, second, and third tertiles of intake based on %ucOC in plasma. Vitamin K intake levels in the first, second, and third tertiles were 94.88 ± 51.48 µg, 73.85 ± 45.15 µg, and 62.58 ± 39.92 µg, respectively (P < 0.05). The T-scores of the first and third tertiles were 1.06 and -0.03, respectively, indicating that bone mineral density was significantly lower in the group with lower vitamin K intake (P < 0.05). There was a tendency for different serum hs-CRP concentrations between the first (0.04 ± 0.02) and third tertiles (0.11 ± 0.18), however this was not statistically significant. Regression analysis was performed to identify the correlations between vitamin K nutritional status, inflammatory markers, and bone mineral density after adjusting for age and BMI. Serum hs-CRP concentrations were positively correlated with vitamin K deficiency status (P < 0.05). And bone mineral density, which was represented by speed, was negatively correlated with vitamin K deficiency status (P < 0.05). In conclusion, status of vitamin K affects inflammatory status and bone formation. Therefore, sufficient intake of vitamin K is required to secure peak bone mass in young adult women.
    Full-text · Article · Dec 2010 · Nutrition research and practice
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