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Study gives vitamin K anti-inflammation boost

By Stephen Daniells , 03-Dec-2007

Increased intake of vitamin K1, and to a lesser extend vitamin D, could protect against inflammation, and positively effect chronic disease risk, suggests a new observational study.

The study, published on-line in the American Journal of Epidemiology, adds to in vitro data supporting benefits for the vitamins against inflammation, brought about by an over-expression or lack of control of the normal protective mechanism. Chronic inflammation has been linked to range of conditions linked to heart disease, osteoporosis, cognitive decline and Alzheimer's, and type-2 diabetes. "Our findings provide one potential alternative mechanism for a putative protective effect of vitamin K in the progression of cardiovascular disease and osteoporosis, since both diseases are characterized by inflammation," wrote lead author Kyla Shea from the Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University. Using data from 1,381 participants in the Framingham Offspring Study (average age 59, 52 per cent women), the researchers analysed vitamin K status using blood concentrations and dietary intake of phylloquinone (vitamin K1), and vitamin D, and related this to markers of inflammation. Shea and co-workers report that both blood levels and dietary intakes of K1 were associated with decreased levels of 14 inflammatory markers. Secondary analysis, factoring in the exclusion of people with heart disease, also showed increased vitamin K intake was related to reductions in several specific biomarkers, such as CD40 ligand (15 per cent reduction), intracellular adhesion molecule-1 concentration (three per cent), interleukin-6 concentration (eight per cent), serum osteoprotegerin concentration (four per cent), tumor necrosis factor receptor-2 (four per cent). The inverse associations were statistically significant after adjusting for various confounding factors, such as age, sex, BMI, aspirin use, statins, season (for vitamin D status), and whether the female participants were post-menopausal and prescribed hormone replacement therapy. For vitamin D, Shea and co-workers report that increased levels of plasma 25-hydroxyvitamin D, the inactive storage form of the vitamin, were linked to lower levels of urinary isoprostane, reportedly a marker of oxidative stress. However, other association s between vitamin D status and levels of inflammation were described by the researchers as "inconsistent". "The current study expanded our knowledge of this putative role of vitamin K because our panel consisted of 14 biomarkers of inflammation, many of which have not been previously studied with respect to vitamin K," wrote the researchers. Concerning the potential mechanisms by which vitamin K influences inflammation biomarkers are not known, said the researchers. There is some suggestion, they added, that vitamin K's role is by decreasing the gene expression for individual cytokines, like interleukin-6 and osteoprotegerin. "Limited in vitro data support the inverse association between vitamin K and interleukin-6, and this may influence the association between vitamin K and other cytokines, such as osteoprotegerin," wrote the researchers. "Further research to better elucidate mechanisms underlying the associations between vitamin K and inflammatory cytokines is warranted," they concluded. The biomarkers of inflammation studied included: C-reactive protein (CRP), CD40 ligand, P-selectin, osteoprotegerin, tumor necrosis factor-a, tumor necrosis factor receptor-2, intercellular adhesion molecule-1, interleukin-6 (IL-6), monocyte chemo-attractant protein, myeloperoxidase, urinary isoprostanes, fibrinogen, and lipoprotein phospholipase A2. There are two main forms of vitamin K: phylloquinone, also known as phytonadione, (vitamin K1) and menaquinones (vitamins K2). K1 is found in green leafy vegetables such as lettuce, broccoli and spinach, and makes up about 90 per cent of the vitamin K in a typical Western diet; while K2, which makes up about 10 per cent of Western vitamin K consumption and can be synthesised in the gut by microflora. Menaquinones (MK-n: with the n determined by the number of prenyl side chains) can also be found in the diet; MK-4 can be found in animal meat, MK-7, MK-8, and MK-9 are found in fermented food products like cheese, and natto is a rich source of MK-7. MK-4 is distinct from other MKs because it is not a major constituent of the spectrum of MKs produced by gut microflora, but can be derived from K1 in vivo. A synthetic form of vitamin K, known as K3, does exist but is not recommended for human consumption. The vitamin is less well known than vitamins A to E, but this increasing body of research, as well as increased marketing and advertising from supplement makers, is raising public awareness of vitamin K. Source: American Journal of Epidemiology Published on-line ahead of print, doi:10.1093/aje/kwm306 "Vitamin K and Vitamin D Status: Associations with Inflammatory Markers in the Framingham Offspring Study" Authors: M.K. Shea, S.L. Booth, J.M. Massaro, P.F. Jacques, R.B. D'Agostino Sr, B. Dawson-Hughes, J.M. Ordovas, C.J. O'Donnell, S. Kathiresan, J.F. Keaney Jr, R.S. Vasan, and E.J. Benjamin

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