Vitamin K2

This is an excerpt from the book, "Power Of Vitamin D."  Copyright © All rights reserved.         

Vitamin K2 may play an imprtant role in the cardiovascular health. Diabetics are at high risk for cardiovascular diseases. Therefore, vitamin K2 may be beneficial for the health of the diabetics. In addition, vitamin K2 seems to play a significant role in keeping our bones and teeth strong.

Vitamin K is a fat-soluble vitamin that was first identified by Henrik Dam in 1929 for its anti-hemorrhagic activities (1). It was later called vitamin K after the Danish word Koagulation. Vitamin K is an essential nutrient for the normal functioning of our body.

There are three forms of vitamin K:

K1 (phylloquinone)

K2 (menaquinones, MK) with several sub-types; MK4 through MK10. Currently MK4 and MK7 appear to be the most important forms of vitamin K2.

K3 (synthetic menadione).

While Vitamin K1 and K2 occur naturally and are nontoxic, vitamin K3 is man-made and can be toxic. Therefore, vitamin K3 should not be used to treat vitamin K deficiency.

Effects of Vitamin K

Vitamin K is an essential cofactor for the conversion of glutamate into gamma-carboxyglutamate (carboxylation). In this way, it activates a number of proteins in our body.

Role of Vitamin K in Blood Clotting

            Vitamin K1 is primarily involved with the clotting process. It activates a number of proteins called clotting factors (Factors II, VII, IX, X) inside the liver. Therefore, vitamin K deficiency can lead to excessive bleeding which sometime can be fatal. A commonly used blood thinner, Warfarin (Coumadin) acts by interfering with vitamin K. Patients on Warfarin have to be closely monitored in order to prevent excessive thinning of blood, which can be fatal.

Role Of Vitamin K2 In Preventing Fractures

            In the recent years medical science has discovered many other health benefits of Vitamin K in addition to its role in blood clotting.

            Vitamin K, especially Vitamin K2 has been found to be important for the health of bones and teeth. Vitamin K2 helps to incorporate calcium and phosphorus into the bones via a complex mechanism: There is a special protein in the bone, termed as osteocalcin, which is involved in maintaining the strength of the bone. Normally, osteocalcin undergoes a chemical change, termed gamma-carboxylation for it to be active and carry out its function. Vitamin K is essential for gamma-carboxylation of osteocalcin. In this way, vitamin K is intimately involved in keeping our bones strong.

            If you are low in vitamin K2, there is a decrease in the gamma-carboxylation  of osteocalcin. In other words, there is under-carboxylation of osteocalcin. Think of under-carboxylated osteocalcin (ucOC) as inactive (abnormal) form of osteocalcin. When you are low in vitamin K2, blood level of under-carboxylated osteocalcin (ucOC) rises. Therefore, the blood level of under-carboxylated osteocalcin (ucOC) has been considered a sensitive marker of vitamin K2 status in the bone. A high level of under-carboxylated osteocalcin (ucOC) indicates vitamin K2 deficiency and is found to be associated with weak bones and a greater risk of fracture.

Can Vitamin K2 Supplementation Can Prevent Fractures?

          Is there clinical evidence to show that vitamin K supplementation can reduce the risk of fracture in individuals suffering from osteoporosis? The answer is yes!

            In a study (2) from the Research Institute and Practice for Involutional Diseases, Japan, researchers recruited a total of 241 patients with osteoporosis. Fifty percent of these patients received placebo and fifty percent of patients received vitamin K2. These patients were followed for 2 years. The incidence of clinical fractures during the 2 years of treatment in the placebo group was higher than the vitamin K2-treated group. The blood levels of under-carboxylated osteocalcin (ucOC) at the end of the 2 years in the placebo and the treated group were 3.0 ng/ml and 1.6 ng/ml, respectively. In addition, the serum level of normal osteocalcin showed a significant rise (42% from the basal value) in the treated group at 2 years, compared to 18% for the placebo group. There was no significant change in the bone density at the lumbar spine. The researchers concluded that their findings suggest that vitamin K2 treatment effectively prevents the occurrence of new fractures, although the vitamin K2-treated group did not show any increase in lumbar bone density. Furthermore, vitamin K2 treatment enhances gamma-carboxylation of osteocalcin.

            In another analytical study (3), researchers from the Institute for Integrated Sports Medicine, Keio University School of Medicine, Japan evaluated the effect of vitamin K supplementation on the bones of postmenopausal women. They analyzed seven clinical trials. Their findings showed that high dose vitamin K(1) and vitamin K(2) supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures. Vitamin K1 and vitamin K2 supplementation reduced serum undercarboxylated osteocalcin (ucOC) levels regardless of dose. But vitamin K had inconsistent effects on serum total osteocalcin levels and no effect on bone resorption. Vitamin K treatment did not cause a significant increase in the bone density. They concluded the beneficial effect of vitamin K(1) and vitamin K(2) supplementation on the bones of postmenopausal women is mediated by mechanisms other than bone mineral density and bone turnover.

            In  another analytical study (4) from Hangzhou Xiasha Hospital ,China, researchers analyzed the data from nineteen randomized controlled trials. There were a total of 6759 participants. Researchers found that postmenopausal women with osteoporosis, who took vitamin K2, had a significant improvement of bone density at the lumbar spine. In addition, vitamin K2 significantly decreased the incidence of vertebral fractures. The level of undercarboxylated osteocalcin ((ucOC) ) came down and the level of normal osteocalcin increased in women who took vitamin K2.

            In conclusion, there is a mounting clinical evidence to clearly show the beneficial effects of vitamin K in preventing fractures in postmenopausal women with osteoporosis. Vitamin K exerts its beneficial effect on the bone through osteocalcin, a protein in the bone that seems to play an important role in the process of mineralization of the bone. Calcium and Phosphorus  are important ingredient for the mineralization of the bone. That is where vitamin D is crucial. Vitamin D increase absorption of Calcium and Phosphorus from the intestines. In this way, Vitamin D and Vitamin K appear to act in concert in keeping our bones strong.

Vitamin K2 and Cardiovascular System

            Vitamin K2 also activates (carboxylates) another protein, called Matrix Gla Protein (MGP), which is present in the LDL cholesterol in your blood. Activated MGP exerts important beneficial effects on your arteries: It may prevent calcification of the arteries, including coronary arteries and aorta.

Some individuals are at high risk for the calcification of arteries. These are patients with diabetes, chronic kidney failure, hyperparathyroidism and atherosclerosis. A number of factors place these patients at increased risk of calcification of the arteries. These are stress, high blood pressure, high calcium and high phosphate in the blood ( high Ca x P product). These factors can initiate a process in which smooth muscle cells in the blood vessels transform into bone-like cells, which then start to deposit bone-crystals ( hydroxyapatite)  in the cell wall. Hydroxyapatite bone crystals are made up of calcium and Phosphate.  MGP can inhibit the formation of  hydroxyapatite crystals. In this way, MGP may play a crucial role in preventing calcification in the arterial walls. 

            As mentioned earlier, vitamin K2 is essential to activate (carboxylase) MGP. The levels of dephosphorylated, un-carboxylated MPG (dp-ucMGP) are used as a marker for vitamin K deficiency in the blood vessels and have been found to correlate with cardiovascular morbidity.

Can Vitamin K2 Prevent Heart Disease?

          Is there clinical evidence to show that vitamin K supplementation can reduce the risk of heart disease ? The answer is yes!

In an excellent study  (5) from Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands, the researchers evaluated the effects of dietary intake of Vitamin K1 and Vitamin K2 on coronary heart disease, aortic atherosclerosis and overall mortality in 4807 men and women over the age of 55, who lived in a defined district of Rotterdam in the Netherlands. The study had a mean duration of follow-up of 7.2 years. Intake of vitamin K2 but not vitamin K1 was found to be associated with a decrease in the  risk of coronary heart disease, aortic atherosclerosis and overall mortality.

Main dietary sources of Vitamin K1 in this study were green leafy vegetables and vegetable oils. Vitamin K2 was present in meats and eggs (MK4 only), fish, sauerkraut, cheese, and other dairy produce (MK5 through MK10). The authors made an interesting observation that cheese has not been established as a dietary risk factor for cardiovascular disease in epidemiological studies, despite its high levels of saturated fat and salt.  They hypothesized that Vitamin K2 in cheese could exert a beneficial effect in the cardiovascular system and that the high cheese consumption in France and the Mediterranean countries may possibly account for lower prevalence of CHD.

In another study (6) from University Medical Center Utrecht, The Netherlands, the researchers investigated if there was a link between dietary intake of vitamin K1 and vitamin K2 with calcification of coronary arteries in a cross-sectional study among 564 post-menopausal women. They found that sixty-two percent of the women had coronary calcification. Vitamin K2 intake was associated with decreased coronary calcification. They concluded that high dietary vitamin K2 intake, but probably not vitamin K1, is associated with reduced coronary calcification. Adequate vitamin K2 intakes could therefore be important to prevent cardiovascular disease.

 Natural Sources Of Vitamin K

            Vitamin K naturally exists in 2 forms, namely phylloquinone (K1) and a group called vitamin K2, also called menaquinones or MK , with several sub-types. MK4 and MK7 have been clinically studied. While K1 is widely distributed in green and leafy vegetables, menaquinones exist preferentially in meats [menaquinone (MK)-4], eggs (MK-4), curd (MK-7), fermented cheese (MK-7), and fermented soy, called natto (MK-7).

Menaquinone is also produced by the intestinal flora, but the absorption seems to be limited.

Vitamin K2 Supplements: MK7 Versus MK4

Most people cannot get adequate amounts of Vitamin K2 from their diet. Therefore, they need to take vitamin K2 supplement.

Vitamin K2 in supplements: Vitamin K2 as MK4 in supplements is synthetic. It is made from the extract of the tobacco plant. To get it from meats and eggs would be very expensive.

On the other hand, MK7 in supplements usually comes from natto, which is fermented soy and is part of the Japanese cuisine. Natto, however, is highly unpalatable for most non-Japanese. But MK7 from natto in the supplement form does not have a bad taste.

Another advantage of MK7 over MK4: MK7 in supplements stays in your body longer than MK4 in supplements. Therefore, you can take MK7 supplement as once a day, but you will have to take MK4 supplement three to four times a day, to maintain a good level of vitamin K2 in your body.

How Much Vitamin K2 Supplement?

            The optimal dose of vitamin K2 is not established yet. In the clinical studies, researchers have used  a wide range of the daily dose of vitamin K2, as is obvious from some of the studies I discuss in the next paragraph. In addition, researchers have shown beneficial effects of MK4 as well as MK7.

In Japan, vitamin K2 as Menaquinone4 (MK4) is the standard medical treatment of osteoporosis. They use it as a daily dose of 45 mg. However, in a recent study (7), researchers from the National Institute of Health and Nutrition, Tokyo, Japan, researchers used a low-dose of MK-4 supplementation as 1.5 mg per day for 6-12 months in postmenopausal women, and showed there was an improvement in bone health. In another recent study (8), researchers from Maastricht University, Maastricht, The Netherlands used a low dose of MK7 as 180 microgram per day in postmenopausal women for 3 years. MK7 at this small dose prevented age-related decline in bone mineral density.

            Kidney dialysis patients are particularly prone to arterial calcification. In a study (9) from the University Hospital Düsseldorf, Germany, researchers assessed the status of vitamin K2 in their hemodialysis patients by measuring their dephosphorylated-uncarboxylated MGP and uncarboxylated osteocalcin levels. They found their patients were quite low in vitamin K2 as demonstrated by a 4.5-fold higher dephosphorylated-uncarboxylated MGP and 8.4-fold higher uncarboxylated osteocalcin levels compared with controls. Vitamin K2 supplementation was given as  135 microgram per day to one group of patients and  360 microgram per day to another group. They found the response rates in the reduction in dephosphorylated-uncarboxylated MGP levels were 77% and 93% in the groups receiving a daily dose of 135 microgram and 360 microgram of MK7, respectively.

 

References:

1. Dam H. The antihaemorrhagic vitamin of the chick. Biochem J 1935. Jun;29(6):1273-1285

2. Shiraki M1, Shiraki Y, Aoki C, Miura M. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res. 2000 Mar;15(3):515-21.

3.Iwamoto J, Sato Y, Takeda T, Matsumoto H. High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature. Nutr Res. 2009 Apr;29(4):221-8.

4. Huang ZB1, Wan SL, Lu YJ, Ning L, Liu C, Fan SW. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials. Osteoporos Int. 2014 Dec 17

5. Geleijnse JM1, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5.

6. Beulens JW1, Bots ML, Atsma F, Bartelink ML, Prokop M, Geleijnse JM, Witteman JC, Grobbee DE, van der Schouw YT. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2009 Apr;203(2):489-93

7. Koitaya N, Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, Gando Y, Miyachi M, Aoki M, Komatsu M, Watanabe F, Morishita K, Ishim Y.Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. J Bone Miner Metab. 2013 May 24.

8. Knapen MH, Drummen NE, Smit E, Vermeer C, Theuwissen E. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013 Mar 23

9. Westenfeld R1, Krueger T, Schlieper G, Cranenburg EC, Magdeleyns EJ, Heidenreich S, Holzmann S, Vermeer C, Jahnen-Dechent W, Ketteler M, Floege J, Schurgers LJ. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis. 2012 Feb;59(2):186-95.

  

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Each bottle contains 60 tablets

Each tablet contains 100 mcg of Vitamin K2

Regular Price = $ 34.95 per bottle

Sale Price = $ 19.95 per bottle

 
Warnings – Disclaimer: This website is for educational purposes only. The information as well dietary supplements in this website are not intended to diagnose, treat, cure or prevent any disease. These statements have not been evaluated by the Food and Drug Administration. Dietary supplements are Not intended for use by pregnant or nursing women. If you are taking any medications, planning any medical or surgical procedure or have any medical condition, consult your doctor before using any of the supplements. Discontinue use and consult your doctor if any adverse reactions occur. Keep out of reach of children. Do not use if outer wrap is missing or torn. Store at room temperature.

 

This article was written by Sarfraz Zaidi, MD, FACE. Dr. Zaidi specializes in Diabetes, photoEndocrinology and Metabolism.

Dr. Zaidi is a former assistant Clinical Professor of Medicine at UCLA and Director of the Jamila Diabetes and Endocrine Medical Center in Thousand Oaks, California.

 

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