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Vitamin K shows potential in the fight against wrinkles

By Katie Bird, 19-Oct-2007

Related topics: Research, Vitamins & premixes, Skin health

Research suggests that vitamin K plays a role in protecting skin elasticity and may help protect against skin aging and the development of wrinkles.

Recent studies have linked vitamin K to the elasticity of skin in patients suffering from pseudoxanthoma elasticum (PXE), an inherited condition resulting in severe wrinkling of the skin on the face and body.

Although the link between vitamin K and normal levels of skin wrinkling seen in healthy populations is unknown, scientists suggest that these studies illustrate that the vitamin is involved, in some capacity, in the skin's elastic qualities.

The findings add to an increasing body of research illustrating the effects of nutritional intake and supplements of skin health, tapping in to the ever trend for beauty from within.

This severe loss of elastic qualities is due to the calcification of the elastic fibers. The high concentrations of calcium and phosphate in the extracellular space would lead to calcification if it wasn't inhibited by families of proteins.

The recent study published online in the journal Laboratory Investigation illustrates the involvement of Matrix ?-carboxyglutamic acid protein (MGP) in the inhibition of calcium precipitation in sufferers of PXE. However this protein must be activated by a vitamin K dependent enzyme.

Furthermore, prior research has shown that individuals who are unable to metabolise vitamin K also exhibit the PXE symptoms, thereby confirming the role of the vitamin in the skin wrinkling seen in sufferers.

"For the moment the link between vitamin K and skin elastin in the population that does not have PXE is unknown" Leon Schurgers, from the University of Maastricht, the Netherlands, and co-author of the report told NutraIngredients.com's sister site, CosmeticsDesign.

However, the fact that the research has identified a strong link between vitamin K and the PXE phenotype, leads Schurgers to speculate that the vitamin may be linked to signs of wrinkling and loss of skin elastin in aging individuals in healthy populations.



"It is often easier to investigate the diseased form, in order to reveal a protein's function, as in healthy populations the differences are too subtle" Schurgers explained.

Similarly, the effect of vitamin K supplements on the skin in healthy individuals is not yet known, although Schurgers imagined that the findings might be of particular interest to those working in the supplements market.

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 (a Japanese fermented soy food) is a rich source of MK-7.

Source: Laboratory Investigation

2007 doi: 10.1038/labinvest.3700667



"Matrix Gla protein is involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients"

Dealba Gheduzzi, Frederica Boraldi, Guilia Annovi, Chiara Paolinelli DeVincenzi, Leon Schurgers, Cees Vermeer, Daniela Quaglino and Ivonne Pasquali Ronchetti


Vitamin K help for diabetes?

By Alex McNally, 21-Aug-2007

Related topics: Research, Vitamins & premixes, Bone & joint health, Cardiovascular health

The vitamin K dependant protein osteocalcin may have a positive effect on reducing obesity and diabetes, suggests a new study with mice.

Researchers writing in the journal Cells studied the effect bone cells have in energy regulation, and found that osteocalcin plays a key role in regulating insulin activity.

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 (vitamin K2), which make up about 10 per cent of Western vitamin K consumption and can be synthesised in the gut by microflora.

The study points to another potential avenue for vitamin K - a vitamin which is less known than vitamins A to E - and could help diversify its health benefits, which have previously been linked to cardiovascular health and bone health.

Previous animal studies have thrown up interesting results at high dose supplementation of vitamin K and its effect on arterial calcification.

Both K1 and K2 have been shown to play a role in bone health, influencing the secondary modification of osteocalcin, a protein needed to bind calcium to the bone matrix. Some large human studies have tested the bone health benefits of calcium alone, calcium plus vitamin D and calcium plus vitamin D plus vitamin K. The latter has been reported to show the best effect on osteoporosis.

In this animal study, researchers from America, Canada and Britain identified the genes that operate primarily in the bone cells that are linked to glucose metabolism. By "knocking out" these genes in mice so that they could not function, the animals lacking a functional osteocalcin gene gained fat, showing that osteocalcin helps regulate the cells that produce insulin in the pancreas and release it into the bloodstream.

These osteocalcin deficient mice also became glucose intolerant. Both conditions are considered "pre-diabetic."

Osteocalcin was also shown to signal fat cells to release a hormone called adiponectin that increases insulin sensitivity.

"We show here that mice lacking the protein tyrosine phosphatase OST-PTP are hypoglycemic and are protected from obesity and glucose intolerance because of an increase in b-cell proliferation, insulin secretion, and insulin sensitivity. In contrast, mice lacking the osteoblast-secreted molecule osteocalcin display decreased b-cell proliferation, glucose intolerance, and insulin resistance," the researchers wrote.

They added: "Ex vivo, osteocalcin can stimulate CyclinD1 and Insulin expression in b-cells and Adiponectin, an insulin-sensitizing adipokine, in adipocytes; in vivo osteocalcin can improve glucose tolerance.

"By revealing that the skeleton exerts an endocrine regulation of sugar homeostasis this study expands the biological importance of this organ and our understanding of energy metabolism."

American based firm PL Thomas, which markets a vitamin supplement for K2 as menaquinone-7 under the tradename MenaQ7 in alliance with Natto Pharma, Norway, welcomed the study which it says could help reinforce further potential health benefits of the vitamin.

A spokesperson said: "Obviously this is a very early observation and these results would need to be confirmed in humans. The authors and experts in the field find the link very interesting, particularly if it yields new therapeutic benefits for diabetes.

"The vitamin K market is rapidly expanding as the benefits beyond coagulation become better known… it is only in the last year or so that industry has recognized vitamin K's role in activating osteocalcin for bone health and activating another k-dependent protein called matrix GLA protein (MGP) for cardiovascular health."

Source: Cells

Published on-line, doi:10.1016/j.cell.2007.05.047.

"Endocrine Regulation of Energy Metabolism by the Skeleton"

Authors: Na Kyung Lee, Hideaki Sowa, Eiichi Hinoi, Mathieu Ferron, Jong Deok Ahn, Cyrille Confavreux, Romain Dacquin, Patrick Mee, Marc McKee, Dae Young Jung, Zhiyou Zhang, Jason Kim, Franck Mauvais-Jarvis, Patricia Ducy, and Gerard Karsenty

Vitamin K2 linked to lower prostate cancer risk

By Stephen Daniells, 09-Apr-2008

Related topics: Research, Vitamins & premixes, Cancer risk reduction

An increased intake of vitamin K2 may reduce the risk of prostate cancer by 35 per cent, suggest results from the European Prospective Investigation into Cancer and Nutrition (EPIC).

The potential benefits of K2 were more pronounced for advanced prostate cancer, while vitamin K1 intake did not offer any prostate benefits, report the researchers from the German Cancer Research Centre in Heidelberg.

The findings, based on data from the 11,319 men taking part in the EPIC Heidelberg cohort, are published in this month's issue of the American Journal of Clinical Nutrition.

The study, by Katharina Nimptsch, Sabine Rohrmann and Jakob Linseisen, adds to a small but ever-growing body of science supporting the potential health benefits of vitamin K, most notable for bone and blood health, but also recently linked to improved skin health.

The study has been welcomed by leading vitamin K researcher Cees Vermeer, PhD, from the VitaK and Cardiovascular Research Institute CARIM at the University of Maastricht, who told NutraIngredients.com that the study was "high quality."

"The anti-tumor effect of K2 vitamins has been suggested in several other (mainly Japanese) papers; in most cases these papers were based on smaller numbers, however. Also, in Japan it is usual to provide very high doses of the short-chain menaquinone-4 (45 mg/day or higher)," said Dr. Vermeer.

"The elegance of the Nimptsch paper is that the effect is found at nutritional doses of vitamin K," he added.



Study details

Nimptsch, Rohrmann and Linseisen from the Division of Cancer Epidemiology at the German Cancer Research Centre state that epidemiologic studies of dietary vitamin K intakes have not been conducted in relation to prostate cancer risk.

According to the European School of Oncology, over half a million news cases of prostate cancer are diagnosed every year world wide, and the cancer is the direct cause of over 200,000 deaths. More worryingly, the incidence of the disease is increasing with a rise of 1.7 per cent over 15 years.

A food frequency questionnaire was used to assess habitual dietary intakes at the start of the study, with vitamin K intakes divided into phylloquinone (vitamin K1) and menaquinones (vitamin K2) and total and advanced prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition.

The researchers documented 268 incident cases of prostate cancer during the 8.6 years of follow-up. Of these, 113 cases were classified as advanced prostate cancer. While no reduction in the risk of prostate cancer was observed for vitamin K1 (phylloquinone), an increased intake of all menaquinones (vitamin K2) was associated with a 35 per cent reduction in risk. However, the researchers stated that this association was "non-significant".

Furthermore, a strong association was documented when they considered only advanced prostate cancer, with increased intake of menaquinones linked to a 63 per cent reduction in risk.

While dietary sources of menaquinones include meat and fermented food products like cheese, and natto, Nimptsch and co-workers report that menaquinones from dairy had a stronger inverse association with advanced prostate cancer than did menaquinones from meat.

"Our results suggest an inverse association between the intake of menaquinones, but not that of phylloquinone, and prostate cancer," concluded the researchers. "Further studies of dietary vitamin K and prostate cancer are warranted."

Independent expert comment

Commenting on the research, Dr. Vermeer told this website that the data, in addition to being consistent with other reports in the literature, "the beneficial effect of the long-chain menaquinones has previously been reported for cardiovascular disease; this specific form of vitamin K2 is characterized by preferential transport (via LDL) to extra-hepatic tissues (such as prostate and arterial vessel wall), and by very long half-life times (three days versus 1.5 hours) as compared to vitamin K1 and the short-chain menaquinone-4.



"I am highly pleased by this paper, which underpins the (widely underestimated) importance of long chain menaquinones for disease prevention," Dr. Vermeer told this website.

"It also supports my opinion that intake of vitamin K2 supplements may have a significant contribution to public health."

K definitions

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 Clinical Nutrition

April 2008, Volume 87, Number 4, Pages 985-992



"Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg)"

Authors: K. Nimptsch, S. Rohrmann, J. Linseisen


Vitamin K may have anti-diabetes benefits: Study

By Stephen Daniells, 27-Nov-2008

Related topics: Research, Vitamins & premixes, Diabetes

Supplements of vitamin K1 may reduce the development of insulin resistance in older men, and thereby offer protection against diabetes, suggests a new study.

Insulin resistance, whereby insufficient insulin is released to produce a normal glucose response from fat, muscle and liver cells, was significantly lower in men following a daily vitamin K1 supplement, according to results of a 36-month, randomised, double-blind, controlled trial.

No effects were observed in women, report the researchers, led by Sarah Booth from the Jean Mayer USDA Human Nutrition Research Center at Tufts University, in this month’s issue of Diabetes Care.

The authors speculated that weight might be influencing the effects of vitamin K in men and women. "In our study, there was a higher prevalence of obese or overweight women in the vitamin K supplementation group compared to the male supplementation group," said Booth. "Vitamin K is stored in fat tissue. If there is excess fat, vitamin K may not be readily available to cells that require it to process glucose."

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.

Study details

The researchers recruited 355 non-diabetic men and women between the ages of 60 and 80. Sixty per cent of the participants were women. The participants were randomly assigned to receive a daily vitamin K1 supplement (500 micrograms per day of phylloquinone) or placebo for 36 months. The vitamin K doses is approximately five times the adequate intake, said the researchers. All of the participants also received a calcium and vitamin D supplement.

Booth and her co-workers report that insulin resistance, assessed using the homeostasis model (HOMA-IR), improved in men consuming the vitamin K supplements. On the other hand, progression of insulin resistance continued in all women, and in the men in the placebo group.

What’s happening?

Previously, researchers from America, Canada and Britain reported in the journal Cell that vitamin K may have an effect on diabetes development via the vitamin K-dependant protein osteocalcin. The study with mice looked at genes that operate primarily in the bone cells that are linked to glucose metabolism.

By "knocking out" these genes in mice so that they could not function, the animals lacking a functional osteocalcin gene gained fat, showing that osteocalcin helps regulate the cells that produce insulin in the pancreas and release it into the bloodstream.

Booth and co-workers dismiss this as the mechanism, however, noting that men in vitamin K group actually had less of the functional osteocalcin than men in the placebo group.

It is plausible,” they stated, “That vitamin K may improve insulin sensitivity through suppression of inflammation. In vivo and in vitro studies have shown that vitamin K reduced lipopolysaccharide-induced inflammation.

More recently, it was reported that biochemical and dietary measures of vitamin K status were inversely associated with inflammatory markers in an observational study,” they said.

Booth and her co-workers note that the study was limited to Caucasian adults and that generalization of the results may not be possible. Additional studies are recommended.

The study was funded by the United States Department of Agriculture Agricultural Research Service, the National Institutes of Health, the American Heart Association, the Ministry of Education, Culture Sports and Technology in Japan and the American Diabetes Association.



Worrying statistics

An estimated 19 million people are affected by diabetes in the EU 25, equal to four per cent of the total population. This figure is projected to increase to 26 million by 2030.

In the US, there are almost 24 million people with diabetes, equal to seven per cent of the population. The total costs are thought to be as much as $174 billion, with $116 billion being direct costs from medical expenditures, according to 2007 American Diabetes Association figures.

Source: Diabetes Care


November 2008, Volume 31, Pages 2092-2096, doi: 10.2337/dc08-1204
"Effect of Vitamin K Supplementation on Insulin Resistance in Older Men and Women”
Authors: M. Yoshida, P.F. Jacques, J.B. Meigs, E. Saltzman, M.K. Shea, C. Gundberg, B. Dawson-Hughes, G. Dallal, S.L. Booth




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