Vitamin K2 linked to better heart health

Study gives vitamin K anti-inflammation boost

By Stephen Daniells, 03-Dec-2007

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.

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.

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

Vitamin K linked to fewer varicose veins, better vascular health

By Stephen Daniells, 23-Aug-2007

The study, published in the Journal of Vascular Research, indicates that inadequate levels of vitamin K may reduce the activity of the matrix GLA protein (MGP) to reduce vascular proliferation and mineralisation, thereby stopping the development of varicosis.

The exact mechanisms behind varicose vein development are not clear, although several risk factors are known to be involved, including age, obesity, physical activity, standing occupations, genetic predispositions, multiple pregnancies and connective tissue abnormalities.

The new study reports that MGP activity may also play an important role in the development of these types of veins.

"Defects in the vein wall are indicated in varicosis, with a central role for the vitamin-K dependent protein MGP," explained study co-author Leon Schurgers from the University of Maastricht.

"MGP is important in relation to the health of the entire cardiovascular system. Previous studies from our group demonstrated the importance of MGP and vitamin K for the arterial vessel wall, and now we show that MGP and vitamin K could play a significant role in varicose veins," he added.

There are two main forms of vitamin K: phylloquinone, also known as phytonadione, (vitamin K1) which 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; and menaquinones (vitamins K2), which make 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 researchers, led by Chrystelle Cario-Toumaniantz from INSERM (U533) and the University of Nantes, compared healthy veins from 36 male patients (age range 30 to 83) and varicose veins from 50 male patients (age range 40 to 81).

Inactive MGP was identified by the researchers as a key player in the development of varicosis, and since vitamin K is necessary to activate MGP, they suggested that adequate dietary intake of vitamin K may be a necessary prerequisite in preventing the development of varicose veins.

"The increased calcification process in varicose veins could thus be due to incomplete MGP carboxylation as observed in other vascular diseases," wrote Cario-Toumaniantz.

"As vitamin K is an essential cofactor for MGP carboxylation, it might be expected that the local vascular vitamin K status is insufficient in varicose vein to mediate full carboxylation of all newly formed MGP.

"In varicose SMC cultures, our results showed that vitamin K supplementation inhibited the mineralization process, suggesting that in vitro, carboxylation of MGP could be partly induced and that the inhibitory effect of MGP could be restored," she added.

The researchers called for future studies to analyse vitamin K levels in the walls of both varicose and healthy veins in order to deepen the understanding the MGP under-carboxylation mechanism.

Source: Journal of Vascular Research

2007, Volume 44, Pages 444-459, doi: 10.1159/000106189

Authors: C. Cario-Toumaniantz, C. Boularan, L.J. Schurgers, M.-F. Heymann, M. Le Cunff, J. Léger, G. Loirand, P. Pacaud