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Vitamin K2
VITAMIN K2
Vitamin K2 plays a vital role in ensuring that calcium stays in the bones and out of the arteries. It may also protect the heart and inhibit cancer. Vitamin K1 is most effective at supporting healthy insulin levels.

Vitamin K was first recognized in 1929 for its vital role in the blood-clotting process. Research now shows that the different forms of vitamin K have distinct benefits and are found in very different foods. Studies have shown that vitamin K2 is particularly effective for the treatment of osteoporosis, heart disease and various forms of cancer.

AN INTRODUCTION TO VITAMIN K
There are two main forms of vitamin K. Vitamin K1 (phylloquinone) is found in green leafy vegetables and makes up about 90 per cent of the vitamin K in a typical western diet. Vitamin K2 (menaquinones) makes up about 10 per cent of western vitamin K consumption and can be synthesized in the gut by microflora.

Vitamin K2 is actually a group of compounds known as menaquinones or MK-n. MK-7, MK-8, and MK-9 are found in fermented food products like cheese and natto-a popular fermented soy product found in Japan. Natto is a particularly rich source of MK-7.

MK-4 is distinct from other MKs because it is not produced in significant amounts by bacteria but appears to be synthesized by animals and humans from the phylloquinone in plants and also from menadione- a synthetic form of vitamin K present in animal feed. MK-4 may be found in animal meat. It has also been an approved medication for osteoporosis since 1995 in Japan.

VITAMIN K2 SUPPLEMENTS
Vitamin supplements of both MK-4 and MK-7 are readily available throughout North America. An MK-4 supplement (45 mcg) can cost as little as 4 cents a tablet, while an MK-7 tablet of 50 mcg will cost about 25 cents for a softgel.

Is MK-7 worth the extra money? Here is what the research says.

VITAMIN K2 (MK-4)
In Japan, studies with osteoporotic women using 45mg/day of MK-4 have reported significant reductions in the rate of bone loss. (J Orthop Sci. 2001;6(6):487-492. and Annu Rev Nutr. 1995;15:1-22) A meta-analysis of seven Japanese randomized controlled trials indicated that MK-4 supplements increased bone mineral density and reduced fracture incidence. The studies indicated lowered risk for vertebral fractures by 60%, hip fractures by 77%, and nonvertebral fractures by 81%. (Arch Intern Med. 2006;166(12):1256-1261) A 45 mg/day dose of MK-4 supplements used in a 3-year placebo-controlled study of 325 postmenopausal women also found improved measures of bone strength compared to a placebo.(Osteoporos Int. 2007;18(7):963-972) In Japan, MK4 has been an approved medication for osteoporosis since 1995.

VITAMIN K2 (MK-7)
Vitamin K supplements in the form of MK-7  are derived from fermented soy (natto) and are generally more expensive than MK-4 supplements.

Research conducted in Japan has been very encouraging regarding the contribution of MK-7 to improved bone health. A study of 944 women (20-79 years old) over three years found that dietary natto intake helped to increase bone mineral density (BMD) in the hips of the postmenopausal women and slowed the loss of BMD in the femoral neck and the forearm. (2006 American Society for Nutrition J. Nutr. 136:1323-1328, May 2006)

Supplement manufactures argue that MK-7 remains in the blood longer than MK-4 but there are no published studies demonstrating that this claim has been clinically proven or that a longer plasma half-life is beneficial to bone health.

It is clear from the above studies that both MK-4 and MK-7 are excellent for bone health. However, the research does not clearly demonstrate that MK-7 produces superior results and therefore warrants the additional cost of the supplements. This lack of clinical proof has not prevented many people who are taking an MK-7 supplement from reporting outstanding health benefits.

MK4 versus MK7 for Bone Health
There are primarily two forms of vitamin K2 commercially available. These are MK4 and MK7. MK4 used in dietary supplements is created through chemical synthesis. MK7 is produced by bacterial fermentation of soy, appears to have a longer half life then MK4, and can also decrease serum ucOC.8

However, only MK4 has demonstrated the ability to decrease fractures, the most relevant end point in randomized, controlled clinical trials.
9,10,11 Additionally, people with an allergy to soy can react to MK7, since it is produced from soy fermentation. People with celiac disease and gluten intolerance frequently have allergies to other foods, such as soy. MK4 is hypoallergenic.

Vitamin K2 exerts a powerful influence on bone building, especially in osteoporosis, and in Japan has been accepted as an osteoporosis treatment.
12 It is a fat-soluble vitamin that is a coenzyme for a vitamin K-dependent carboxylase enzyme that catalyzes carboxylation of the amino acid glutamic acid, resulting in its conversion to gamma-carboxyglutamic acid (Gla). This carboxylation reaction is essential for formation of bone collagen, which allows bone to deform upon impact, for example during a fall, without fracturing. Although vitamin K-dependent gamma-carboxylation occurs only on specific glutamic acid residues in a small number of proteins, it is critical to the calcium-binding function of those proteins. Three vitamin K-dependent proteins have been isolated in bone—osteocalcin, matrix Gla protein (MGP) and protein S. Osteocalcin is a protein that is synthesized by osteoblasts and is regulated by the active form of vitamin D, 1,25-(OH)2D3, also called calcitriol. The mineral-binding capacity of osteocalcin requires vitamin K-dependent gamma-carboxylation of 3 glutamic acid residues. Multiple randomized, double-blind, placebo-controlled clinical trials have shown significant decreases in undercarboxylated osteocalcin (ucOC) in volunteers supplemented with 45 mg of vitamin K2 with and without the addition of calcium and vitamin D3 compared to controls

A 2006 meta-analysis published in the
Archives of Internal Medicine by Sarah Cockayne, MSc, Joy Adams, PhD, Susan Lanham-New, PhD, and colleagues, at the University of York in England, evaluated clinical trials on vitamin K2 and fracture risk.16  They identified 13 randomized, controlled trials of the effect of vitamin K2 on osteoporosis. Of those, 7 had fracture risk as an end point and so were included in their meta-analysis. They concluded that 45 mg of vitamin K2 as menaquinone-4 (MK-4) could decrease vertebral fracture by 60%, hip fracture by 73%, and all nonvertebral fractures by 81%.

A randomized, controlled, open-label study of 241 osteoporotic women (avg. age approximately 67 yrs.) evaluated the fracture prevention effects of MK4.
17 A control group of 121 women took  150 mg of calcium daily, while 120 women (the treatment group) received 150 mg of calcium daily plus 45 mg per day of MK4. The study lasted 24 months (two years) and evaluated lumbar BMD and fractures. Over the two year period there were 30 new fractures (30.3%) in the women who did not take the MK4, and only 13 fractures (10.9%) in the women who did supplement with 45 mg/day of MK4. That’s a 200% decrease in risk.

A second randomized, controlled clinical trial evaluated the risk of fractures in women with Alzheimer’s disease.
18 In this study, 200 women with Alzheimer disease (average age 78 years) received 45 mg MK4, 1000 IU vitamin D3 and 600 mg calcium per day. These women were followed on this regimen for two years, and evaluated for bone mineral density and fractures. After two years those in the control group, who did not receive the MK4, experienced twenty-two new fractures (fifteen hip fractures, two distal forearm fractures, two proximal femur fractures, and one each at the proximal humerous, ribs and pelvis). In contrast, those who received the MK4 experienced three fractures total (two hip fractures and one proximal femur fracture). Those in the treatment group who took the MK4 experienced 86% fewer nonvertebral fractures compared to the control group. Additionally, there were 87% fewer hip fractures in treatment group compared to controls. Interestingly, there was no difference in the number of falls sustained in each group. Therefore, MK4 protected these women against fractures even when they did fall.

An excellent review of vitamin K2 by Stephen Plaza, ND, and Davis Lamson, ND, was published in 2005 in the journal
Alternative Medicine Review.19In this article they reviewed clinical trials using vitamin K2 that showed increases in BMD and/or reduction in fracture risk in volunteers who had bone loss from anorexia nervosa, Parkinson’s disease, biliary cirrhosis, and stroke and in volunteers who were taking prednisone and leuprolide; in other volunteers, it increased the efficacy of bisphosphonate medications.

Food

Vitamin K1

Vitamin K2

MK-4

MK-5

MK-6

MK-7

MK-8

Fats & Oils

Margarine

0.509

0.09

-

-

-

-

Salad Oil

1.479

-

-

-

-

-

Olive Oil

0.421

-

-

-

-

-

Pulses

Roasted soybean

0.386

-

-

-

-

-

Soymilk

0.051

-

-

-

-

-

Natto

0.100

0.013

0.079

0.330

8.636

0.096

Vegetables

Spinach

4.785

-

-

-

-

-

Broccoli

2.050

-

-

-

-

-

Meats

Beef

0.003

0.034

-

0.0003

-

-

Chicken

0.002

0.090

-

-

-

-

 
There are three forms of vitamin K supplements available today, including synthetic vitamin K1 (phylloquinone), synthetic vitamin K2 as MK-4 (menaquinone), and natural vitamin K2 as MK-7 (menaquinone-7).

Both vitamin K2 supplements are nearly completely absorbed, with peak serum concentration at 2 hours for MK-4 and 4 hours for MK-7 after intake. However, MK-4 quickly disappears from the circulation (after approx. 8 hours), whereas MK-7 is capable of accumulating in the bloodstream (remains in the body for approx. 72 hours). Supplementation with MK-7 only needs to be taken once a day and is therefore more convenient.
57

The long half-life of MK-7 results in significantly better accumulation compared to MK-4. Research shows that in only 8 days MK-7 has 6 times better absorption. Hence, smaller quantities and less frequent intakes of MK-7 is sufficient in order to supply all of the tissues.58
 
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