CORONARY DISEASE REVERSAL

CAD and vitamin K2

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CAD AND VITAMIN K2

"It has been hypothesized that insufficient intake of vitamin K may increase soft-tissue calcification owing to impaired gamma-carboxylation of the vitamin K-dependent protein matrix gamma-carboxyglutamic acid."

"In animal models, multiple forms of vitamin K have been shown to reverse the arterial calcification created by vitamin K antagonists. The human data, however, are less consistent. Phylloquinone, the primary dietary form, has not been associated consistently with the risk of cardiovascular diseases. High menaquinone intake may be associated with lower risk of coronary heart disease mortality, but this needs to be confirmed".1

1. Erkkilä AT, Booth SL.

Vitamin K intake and atherosclerosis.Curr Opin Lipidol. 2008 Feb;19(1):39-42.

 

 
HISTORY
 
1929: Vitamin K was discovered by Henrik Dam of Denmark. He noted that chickens started bleeding after several weeks on a cholesterol-depleted diet.
Bleeding could only be stoppped when an essential compound from food added with the cholesterol. This new compound received the letter "K" as the report was published as Koagulationsvitamin.
 
Dam H: Biochem Z, 215, 475,1929,
Dam, H. (1935). "The Antihęmorrhagic Vitamin of the Chick.: Occurrence And Chemical Nature". Nature 135 (3417): 652–653. doi:10.1038/135652b0
 
 
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Chronological history obtained from:
MENAQ7. HISTORY:
 

"1929 – Dam discovers that young birds fed a fat-deficient diet experience lengthened blood clotting time, anemia and hemorrhage. He postulates that there had to be a missing fat-soluble factor not previously known2

1934 – Dam and Schųnheyder identify a factor in hempseed that prevents bleeding. Dam called it vitamin K from "Koagulations-Vitamin" in German3. He also found vitamin K in other vegetables and in animal liver

1938 – Almquist et al show that vitamin K is formed also in bacteria in the intestinal canal4

1939 – Doisy et al succeed in determining the chemical structure of vitamin K as well as to synthesize vitamin K

1943 – Dam and Doisy shared the Nobel Prize in medicine for their discovery of vitamin K

1974 – Stenflo and Nelsestuen discover that prothrombin – one of the important coagulation factors- contains the unusual amino acid γ-carboxy glutamic acid (Gla) in the vitamin K-dependent region of the molecule. This led to the understanding of how vitamin K could contribute to the activation of coagulation factors5, 6

1975 – Esmon et al discover a vitamin K-dependent protein carboxylation reaction in the liver7

1983 – Price et al describe Matrix Gla-protein (MGP); the strongest vitamin K-dependent inhibitor of tissue calcification presently known8 GLA= gamma-carboxyglutamate

Price PA, Williamson MK.. Primary structure of bovine matrix Gla protein, a new vitamin K-dependent bone protein. J Biol Chem. 1985 Dec 5;260(28):14971-5.

The complete amino acid sequence of bovine bone matrix Gla protein (MGP) was determined by automatic sequence analysis of the intact protein and of peptides isolated from tryptic and BNPS-skatole digests. 

 There is sufficient sequence homology between MGP and bone Gla protein (BGP) to indicate that these two bovine bone proteins arose by gene duplication and subsequent divergent evolution. 

 MGP is the first vitamin K-dependent protein to be discovered which has several non-gamma-carboxylated residues to the NH2-terminal side of its Gla residues.

1997 – Lou et al demonstrate the importance of MGP for vascular health by using MGP-deficient animals9

Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature. 1997 Mar 6;386(6620):78-81.
 
Calcification of the extracellular matrix (ECM) can be physiological as in bones or pathological.as occurs in arteries and cartilage and other soft tissues.
What causes this pathological extracellular matrix calcification is not known. This paper identified a molecule, matrix GLA protein (Mgp), a mineral-binding ECM protein synthesized by vascular smooth-muscle cells and chondrocytes, that produce an uncalcified ECM. Mice that lacked Mgp,, though develop to term but die within months due to arterial calcification resulting blood-vessel rupture. Mgp-deficient mice also developed pathological calcification of various cartilages leading to short stature, osteopenia and fractures. This study indicted that ECM calcification must be actively inhibited in soft tissues by Mgp to prevent calcification of arteries and cartilage..

2004 – Geleijnse et al publish a population-based study demonstrating that high dietary intake of vitamin K2 influences cardiovascular health and reduced cardiovascular mortality. In this study dietary vitamin K2 appeared to be superior to vitamin K1

2007 – Schurgers et al show that natural vitamin K2 as Menaquinone-7 (MK-7) is the most bioavailable, bioactive and longest lasting form of vitamin K10

2008 – Gast el al publish another large population study confirming that natural dietary vitamin K2 is correlated to improved cardiovascular health. Intake of vitamin K1 has no effect, while the benefits are specifically associated with the longer menaquinones MK-7, MK-8 and MK-9"

 
 
 
2003:

H.M.H. Spronkb, B.A.M. Soutea, L.J. Schurgersa, H.H.W. Thijssenc, J.G.R. De Meyc, C. Vermeera.Tissue-Specific Utilization of Menaquinone-4 Results in the Prevention of Arterial Calcification in Warfarin-Treated Rats. J Vasc Res 2003;40:531-537 (DOI: 10.1159/000075344)

The warfarin-treated rat model were fed diets containing K1, MK-4, or both.

MK-4 and not K1 inhibited  warfarin-induced arterial calcification.

The total hepatic K1 accumulation was threefold higher than that of MK-4, whereas aortic MK-4 was three times that of K1.

 K1 and MK-4 were both equally utilized in the liver, but the aorta showed a more efficient utilization of MK-4.  

2004: The Rotterdam study:

Johanna M. Geleijnse*,†, Cees Vermeer**, Diederick E. Grobbee, Leon J. Schurgers**, Marjo H. J. Knapen**, Irene M. van der Meer*, Albert Hofman* and Jacqueline C. M. Witteman*.Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study. 2004 The American Society for Nutritional Sciences J. Nutr. 134:3100-3105, November 2004http://jn.nutrition.org/content/134/11/3100.full

The effects of dietary intake of Vitamin K1 and K2 (mainly MK-4 from eggs and meat, and MK-8 and MK-9 from cheese) were studied on following conditions:

1. The incidence of coronary heart disease (CHD)

2.  All-cause mortality.

3. Aortic calcification.

4,800 healthy men and women werestudied and followed for over a 10 year period. It was shown that the highest vitamin K2 intake, 45mcg daily, resulted in 50% less arterial calcification and a 50% reduction CAD related death compared to the lowest consumption group with intake of of K2, 12 mcg daily.

Findings from the study indicate that eating foods rich in natural vitamin K2 (at least 32 mcg per day) results in 50% reduction of arterial calcification, 50% reduction of cardiovascular death and 25% reduction of all cause mortality.
Geleijnse JM., et al. Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study, Nutritional Epidemiology, 2004 134: 3100-3105.
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Table from original study

Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study


TABLE 3Association of coronary events and all-cause mortality with intake of menaquinone in 4807 Dutch men and women aged 55 y and over1

Energy-adjusted menaquinone intake (µg/d)

P for trend
<21.6 21.6–32.7 >32.7

n 1578 1605 1624
Median intake, µg/d 15.1 26.9 40.9
Nonfatal MI
    Person-years 11181 11549 11915
    Events, n 51 57 36
    RR, model 12 1 1.15 (0.79, 1.69) 0.74 (0.48, 1.14) 0.18
    RR, model 23 1 1.08 (0.73, 1.62) 0.67 (0.41, 1.09) 0.12
Incident CHD4
    Person-years 11323 11556 11766
    Events, n 86 89 58
    RR, model 1 1 1.05 (0.78, 1.42) 0.71 (0.51, 1.00) 0.048
    RR, model 2 1 0.96 (0.70, 1.31) 0.59 (0.40, 0.86) 0.007
CHD mortality5
    Person-years 11356 11747 12043
    Events, n 41 35 23
    RR, model 1 1 0.84 (0.54, 1.33) 0.59 (0.35, 0.99) 0.045
    RR, model 2 1 0.73 (0.45, 1.17) 0.43 (0.24, 0.77) 0.005
All-cause mortality
    Person-years 11356 11747 12043
    Events, n 258 248 195
    RR, model 1 1 0.97 (0.82, 1.16) 0.81 (0.67, 0.98) 0.030
    RR, model 2 1 0.91 (0.75, 1.09) 0.74 (0.59, 0.92) 0.007

1 RR obtained by Cox proportional hazard analysis, with 95% CI in parentheses and P for linear trend across the tertiles.

2 Model includes age, gender, and total energy intake.

3 Model includes age, gender, total energy intake, BMI, smoking status, pack-years of cigarette smoking, diabetes, education (3 categories), and intake of alcohol, SFA, PUFA, flavonols (quercetin, myricetin, and kaempferol), and calcium.

4 CHD comprises fatal and nonfatal MI, sudden cardiac death, and other forms of acute and chronic ischemic heart disease (ICD-10 codes I20–I25 and I46).

5 CHD events followed by death within 28 d after the onset of symptoms.

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"Menaquinone intake was lower in subjects with severe aortic calcification (25.6 µg/d) than in subjects with moderate or mild calcification (28.6 and 28.8 µg/d, respectively; P = 0.001).................
Menaquinone intake showed no significant association with moderate calcification (Table 4). For severe calcification, however, a strong inverse relationship with menaquinone intake persisted after adjustment for BMI, smoking, education, diabetes, and intake of alcohol, PUFA, SFA, flavonols, and calcium (Table 4). Additional adjustment for intake of fiber, vitamin C, vitamin E, and ß-carotene did not change these results."

Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study


TABLE 4Association of aortic calcification with intake of menaquinone in 4473 Dutch men and women aged 55 y and over,1, 2

Energy-adjusted menaquinone intake (µg/d)

P for trend
<21.6 21.6–32.7 >32.7

n 1468 1493 1512
Median intake, µg/d 15.1 26.9 40.9
Moderate calcification
    Controls, n 916 958 1000
    Cases, n 454 452 453
    OR, model 13 1 0.93 (0.79, 1.10) 0.94 (0.80, 1.11) 0.49
    OR, model 24 1 0.91 (0.77, 1.09) 0.93 (0.76, 1.12) 0.45
Severe calcification
    Controls, n 916 958 1000
    Cases, n 98 83 59
    OR, model 1 1 0.75 (0.54, 1.03) 0.56 (0.39, 0.80) 0.001
    OR, model 2 1 0.71 (0.50, 1.00) 0.48 (0.32, 0.71) <0.001

1 Aortic calcification was graded according to the length of the calcified area, i.e., no/mild (reference), ≤1 cm; moderate, >1 and <5 cm; severe, ≥5 cm.

2 OR obtained by multivariate logistic regression, with 95% CI in parentheses and P for linear trend across the tertiles.

3 Model includes age, gender, and total energy intake.

4 Model includes age, gender, total energy intake, BMI, smoking status, pack-years of cigarette smoking, diabetes, education (3 categories), and intake of alcohol, SFA, PUFA, flavonols (quercetin, myricetin, and kaempferol), and calcium.

"For menaquinone (MK-n), dietary data are scanty in the literature. We therefore analyzed foods and beverages frequently consumed in the Netherlands for MK-4 through MK-10 and linked these data to the dietary database of the Rotterdam Study (19). Intake of menaquinone comprised 10% of the total vitamin K intake, but its bioavailability is probably higher than for phylloquinone that is strongly bound to vegetable fiber (14). Menaquinone in our Dutch population was mainly derived from dairy products, especially cheese (19). Interestingly, in this respect, 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. We hypothesize that menaquinones in cheese (MK-8 and MK-9) 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 prevalences of CHD. Menaquinone is also produced by the intestinal flora, but the absorption seems to be limited (27). In our study, however, it was not possible to quantify endogenous menaquinone synthesis. Dietary intake of menaquinone is reflected in serum levels. In healthy Japanese subjects who consumed fermented soybean (natto) high in menaquinone (especially MK-7), serum concentrations of MK-7 and carboxylated osteocalcin were significantly increased (28).

Vascular tissue and calcified plaques contain MGP, a vitamin K–dependent protein known to prevent excessive calcium deposition in bone (14,7,8).

Lack of vascular MGP resulted in excessive aortic and coronary calcification in knockout mice (9). The inverse association of menaquinone with aortic calcification and CHD in our study may be explained by undercarboxylation of vascular MGP and consequently enhanced calcification of atherosclerotic lesions. Calcified plaques are more prone to rupture, which will elicit a thrombotic response, thereby increasing the risk of a coronary event (29).

Another vitamin K–dependent protein found in the vessel wall is protein S (30). Together with activated protein C, this anticoagulant plays an important role in preventing clot formation at the inner surface of the vessel wall. However, the quantitative contribution of extrahepatic protein S synthesis to hemostasis is probably small.

There is evidence for a differential effect of vitamin K subtypes in the cardiovascular system. Rats at our laboratory were fed diets containing phylloquinone, menaquinone, or both after treatment with high doses of warfarin. Despite similar in vitro cofactor activity for γ-carboxylase, menaquinone but not phylloquinone supplementation prevented warfarin-induced arterial calcification (31). The tissue-specific use of phylloquinone and menaquinone in rats was assessed by measuring the ratios of quinone over epoxide (K:KO ratios) during warfarin treatment. In the arterial vessel wall, K:KO ratios were substantially lower for phylloquinone than for menaquinone whereas the reverse was observed for the liver, suggesting a tissue-specific utilization of vitamin K subtypes (31). In a recent trial in humans, phylloquinone was almost exclusively incorporated into the triacylglycerol-rich lipoprotein (TGRLP) fraction after intestinal absorption, whereas a substantial part of the menaquinones was recovered from the LDL fraction (32). The TGRLP fraction is mainly cleared by the liver, whereas LDL forms a transport system to extrahepatic tissues. Menaquinone supplementation lowered serum cholesterol levels in a study of 17 dialysis patients (33). In our population of healthy older subjects, we confirmed the favorable effect of menaquinone on blood lipids but effects were small and could not explain the inverse relation that we observed between dietary menaquinone and CHD.

In conclusion, our findings suggest a protective effect of menaquinone intake against CHD, which could be mediated by inhibition of arterial calcification. Adequate intake of foods rich in menaquinones, such as curds and (low-fat) cheese, may contribute to CHD prevention."

 
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"This information proves that Vitamin K2 is a critical nutrient for patients with arteriosclerosis as it has the potential to prevent and remove calcium from arteriosclerotic plaques thus making plaques easier to dissolve and less dangerous."1

VITAMIN K

Vitamin K is found in plants as phylloquinone K1 and in animals as menaquinone K2 and synthetic form K3.

Functions:

1. Helps blood coaguation (K1)

2. Influences bone formation and tissue calcification and atherosclerosis (K2).

 Vitamin D3, calcium, and magnesium are important for maintaining and promoting bone health. Vitamin K plays a vital role in bone metabolism and healthy bone formation and density.

Vitamin K helps osteoblastic cell that generates or lays down bone and osteocalcin production. Osteocalcin, a protein, acts as the structural framework holding calcium in place in bones. Vitamin K converts osteocalcin to an active bone-building form before it can perform its bone building function.

Vitamin K is also important for transportation of calcium in bloodstream into bones.

Osteoclasts as opposed to osteoblast, breaks down bone and remove bone tissue.

Vitamin K2 has also been shown to inhibit osteoclasts and help maintain bones.

 Vitamin K2-7 stimulates carboxylation (gamma-carboxylated osteocalcin), which plays an important role in bone formation.

 

References:

Y. Koshihara and K Hoshi. shows that vitamin K2 increased Gla-containing osteocalcin, which accumulated osteocalcin in the extracellular matrix, and facilitated mineralization in vitro.Journal of Bone and Mineral Research, 1997.

 ZJ Ma and M Yamaguchi.These results suggested that MK-7 (K2-7) has a suppressive effect on osteoclasts. Molecular and Cellular Biochemistry. 2001

 M Yamaguchi et al1. This study demonstrates that MK-7 (K2-7) has an anabolic effect on bone tissue and osteoblastic (MC3T3-E1) cells in vitro, suggesting that the compound can stimulate osteoblastic bone formation. Molecular and Cellular Biochemistry, 2001.

 

3. Supports hearts

4. Support skin

5. An antioxidant and helps cells against oxidative damage

6. Supports immune system

7. Supports normal blood sugar levels

K1(phylloquinone, or phytomenadione or phytonadione)

K2 ( (MK-n, menaquinone)

There is no good vitamin K2 test.

Three synthetic vitamin K are known: vitamins K3, K4, and K5.

The natural K1 and K2 forms are nontoxic.

 The synthetic form K3 (menadione) has shown toxicity.[1]

Vitamin K is heat-stable and water soluble. It is destroyed by strong acids or alkalis and gamma-irradiation of foods.

Vitamin K.

http://www.springboard4health.com/notebook/v_k.html

Fat absorbable vitamins are A D E K.

Sources:

K1 in plants mainly in green leafy vegetables but only 10-15% gets absorbed even if consumed with dietary fat.  

K2 in animals from meat, eggs, and dairy products and made by bacteria in the human gut.16

Japanese natto: A fermented soybea containing a good bacteria called bacillus subtilus that may also be a probiotic.

Low fat Dutch gouda

Edam cheese

Curd cheese is lower in animal fat than regular cheese, in equal portions, natto contains over 27 times more vitamin K2 than curd cheese.

http://products.mercola.com/vitamin-k/?e_cid=20120303_DNL_ban_HL&source=nl

Antibiotics and the non-steroidal anti-inflammatory drugs kill many of these good intestinal bacteria.

Vitamin K1 was less effective than Vitamin K2 in preventing bone loss.

Vitamin K2 (MK-7) is absorbed better and is 6 times more potent than Vitamin K1.

There is a lower incidence of calcification of the aorta if on long term K2 therapy.

High K2 level is associated with number of lower plaque in the arteries and more elastic are the arteries.

K2 lack causes calcium to deposit in arteries, aorta, soft tissues including muscle, breast, kidneys and in heel spurs instead of bones.

In Japan, osteoporosis is treated by K2.

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From
The secret to avoiding calcium-related osteoporosis and atherosclerosis by Dr. Kate Rheaume-Bleue.
 
 
Calcium and Vitamin D supplementation without the addition of Vitamin K2 could be dangerous.

Benefits of vitamin K2

The vitamin K2 activates its dependent proteins: Osteocalcin and MGP

a) Osteocalcin in bone building cells needs to be activated in order to bind calcium to the surface of bones.

b) Matrix Gla (gamma-carboxyglutamate) Protein (MGP) in the vasculature to get activated in and inhibit calcium deposition in the arteries.

MGP is the most powerful inhibitor of soft tissue calcification.

Americans as a society, consume far more calcium than most other populations, but suffer from far more osteoporosis ("calcium paradox").

The american diets are often very low in K2MK7.

 
Without Vitamin K2 , calcium is not transported to the bones  for depostion instead, the calcium get deposited in soft tissue and arteries resulting to a combination of osteoporosis and atherosclerosis.
 
If calcium isn’t absorbed properly, instead of going to bones, it accumulates in arteries and soft tissues leading to high blood pressure, atherosclerosis, heart attack, strokes, and arthritis.

Megumi Natto. You Need More MK7-type Vitamin K2

 

There are other health benefits of Vitamin K2:

Reduction of dental cavities, heart disease, prostate cancer, liver cancer, diabetes, wrinkles, obesity, varicose veins, and other ailments.

K2 and the Calcium Paradox: How a Little-Known Vitamin Could Save Your Life

References:James Howenstine. ARTERIOSCLEROSIS CAN BE REVERSED.PART 1 of 2 July 24, 2008

NewsWithViews.com

http://www.newswithviews.com/Howenstine/james67.htm

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Vitamin K1 had no effect on vascular health, and is primarily taken-up by the liver. K2 is transported to extra-hepatic tissues, such as vessel wall and bones-tissue, especially sub types MK7, MK8 and MK9 and are important for cardiovascular health.3, 4.

VITAMIN K2 REDUCES WOMEN'S RISK OF CORONARY HEART DISEASE.

 The Prospect-EPIC cohort Study:

16,057 women, aged 49 - 70 years and free of cardiovascular disease at baseline were followed over a period of more than 8 years. 

 The data confirmed that higher consumption of natural vitamin K2 (especially subtypes menaquinone-7, 8 & 9) - but not vitamin K1 - was associated with significantly reduced prevalence of CHD.

The study confirmed findings in the Rotterdam study[2].
 
The Gast et al.1 showed that a 9% reduction in risk of developing CHD for every 10 mcg of natural vitamin K2 consumed.
The researchers (Gast et.al) found that for every 10mcg vitamin K2 (MK-7, MK-8 and MK-9) consumed, the risk of coronary heart disease was reduced by 9%.
 
 
Vitamin K2 and prevention of calcification discussed by Schurgers LJ., et al.[3] in the Rotterdam study.
====
 
==
How vitamin K2 prevents blood vessels calcification?
Matrix Gla-protein (MGP), is the most potent inhibitor of vascular calcification known. MGP has a high affinity for calcium. MGP is vitamin K dependent, and without adequate vitamin K, MGP is inactive. Inactive MGP may lead to increased calcium-deposition on the blood vessels and atherosclerosis. 

---

. Cardiovascular Disease and Vitamin K2. http://wholehealthsource.blogspot.com/2008/11/cardiovascular-disease-and-vitamin-k2.html

MGP is secreted in cartilage, lung, heart, kidney and arteries.  Mice lacks MGP and develop extensive arterial and soft tissue calcification.
Humans with naturally occurring mutations in MGP (Keutel syndrome).
Rats treated with warfarin, which inhibits vitamin K recycling.
There seems to be no effective alternative mechanism to MGP for calcification inhibition in the vasculature.
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Spronk HM, Soute BA, Schurgers LJ, Thijssen HH, De Mey JG, Vermeer C.Tissue-specific utilization of menaquinone-4 results in the prevention of arterial calcification in warfarin-treated rats.J Vasc Res. 2003 Nov-Dec;40(6):531-7. Epub 2003 Dec 3.

MGP prefers the MK-4 form of vitamin K2.

The effects of vitamin K1 and K4 (MK4) on vascular calcification and their utilization in the arterial vessel wall were compared in the warfarin-treated rat model for arterial calcification.

Warfarin-treated rats were fed diets containing K1, MK-4, or both.

MK-4 and not K1 inhibits warfarin-induced arterial calcification.

The total hepatic K1 accumulation was threefold higher than that of MK-4, whereas aortic MK-4 was three times that of K1.

 K1 and MK-4 were both equally utilized in the liver, but the aorta showed a more efficient utilization of MK-4.

"K2 can be produced by bacterial fermentation, but an argument can be made that K2 MK-4, the animal form, is the most natural for humans and the most effective.

MK-4 is the type that mammals synthesize for themselves, whereas the MK-7 in natto and other bacterial menaquinones are different.

The form of K2 that Weston Price described in Nutrition and Physical Degeneration was almost certainly MK-4."

http://www.menaq7.com/index.php?s=Links

"Interesting. They suggest that MK-7 is superior because it stays in bloodstream 20 times longer (100h vs 5h). I am not sure about the interpretation of this fact - is it positive or negative? If it stays longer in the blood stream perhaps because it is not being readily absorbed by bone and other tissue then is is not so good (thus MK-4 should be better). If on the other hand MK-4 stays so short because it is getting destroyed too quickly then MK-7 should be more benefitial in smaller doses!

On the other hand the natural animal form of K2 is MK-4 thus, I suspect but have no proof, that we should probably stick to the natural MK-4 rather than fungal MK-7 from natto. We just had cooked pork tongues last week, added benefit was that it has lots of fat and cholesterol. Very cheap too. 8-:)"

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[1] Gast G.C.M., et al. A high menaquinone reduces the incidence of coronary heart disease in women, Nutrition, Metabolism and Cardiovascular Diseases, Available online 28 January 2009. doi:10.1016/j.numecd.2008.10.004   
[2] Geleijnse JM., et al. Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study, Nutritional Epidemiology, 2004 134: 3100-3105.
[3] Schurgers LJ., et al., Regression of Warfarin-Induced Medial Elastocalcinosis by High Intake of Vitamin K in Rats, Blood, 2007. 109(7): 2823-2831
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Cardiovascular health

22. Schurgers, LJ. Cranenburg, ECM and Vermeer, C. Matrix Gla –protein: The calcification inhibitor in need of vitamin K. Theme issue article. Thromb Haemost 2008; 100: 593-603
23. Geleijnse JM, 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;134(11):3100-5.
24. Beulens et al: High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2008 Jul 19.
25. Beulens JW, 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. 2008
26. Gast G.C.M., et al. A high menaquinone reduces the incidence of coronary heart disease in women, Nutrition, Metabolism and Cardiovascular Diseases, Available online 28 January 2009. doi:10.1016/j.numecd.2008.10.004
27. Bolland MJ, Barber PA, Doughty RN, Mason B, Horne A, Ames R, Gamble GD, Grey A, Reid IR. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial.BMJ. 2008;336(7638):262-6.
28. Schurgers, LJ: Unpublished data
29. Iribarren C, Sidney S, Sternfeld B, Browner WS. Calcification of the aortic arch: risk factors and association with coronary heart disease, stroke, and peripheral vascular disease. JAMA. 2000;283(21):2810-5
30. Shaw LJ, Raggi P, Berman DS, Callister TQ. Coronary artery calcium as a measure of biologic age. Atherosclerosis. 2006;188(1):112-9

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http://www.menaq7.com/index.php?page=cardiovascular-health

 

Another study24  which looked at the relation between vitamin K1 and vitamin K2 intake and coronary calcification among 564 post-menopausal women showed decreased calcification associated with vitamin K2 intake (specifically MK-7, MK-8 & MK-9) but not with vitamin K1 intake.25

An interesting double blind placebo-controlled bone health study from New Zealand where 1471 postmenopausal women received 1000 mg calcium daily reported a high frequency of cardiovascular events. Judged from the information given, it seems that the daily intake of vitamin K2 was very low in these women. Inadequate vitamin K2 supplementation seems to be a contributing factor to this cardiovascular problem27.

Unfortunately, the western diet does not contain sufficient vitamin K2 and supplementing with MenaQ7, the natural vitamin K2, is therefore recommended by experts.

Arterial calcification

Calcification was once believed to be an irreversible process and a result of aging. However, it is now known that calcium accumulation is an actively regulated process also involving vitamin K2-dependent MGP. Healthy arterial tissues have shown to contain 20-50 times more vitamin K2 than unhealthy arteries28. The amount of calcium in the arteries is a risk factor for cardiovascular health29. Significant calcification makes one older than what the birth certificate states; while with little or no calcification one can deduct up to 10 years from one's chronological age.30
In short, you are as old as your arteries.

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The Calcium Paradox

Impaired calcium metabolism results in simultaneous bone tissue degradation and excessive calcium accumulation in the vessel walls. This is known as the Calcium Paradox. While bones are in need of calcium, excessive calcification may occur in arteries and soft tissues including skin. Vitamin K2 is an essential co-factor involved in calcium utilization by activating proteins responsible for removing circulating mineral from the arteries and binding it to the bone matrix.

Matrix Gla Protein’s role

Matrix Gla Protein (MGP) is a key inhibitor of soft vascular tissue calcification – it can be measured in blood, but exerts its effect in tissues where it binds calcium, preventing it from depositing in the vessel walls. In collaboration with other soluble factors and cells MGP thus helps remove calcium from the arteries, and thereby keep them elastic and flexible.

In order to properly perform its inhibitory function, MGP must be activated by vitamin K during a process called carboxylation. Vitamin K2 deficiency results in undercarboxylation of MGP (ucMGP) and impairs their biological function. Without adequate vitamin K2 in the vessel walls ucMGP accumulates at the sites of calcium deposition but is basically inert as it cannot inhibit calcification, which in turn increases the risk of fatal cardiovascular events.

 

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Vitamin K

From Wikipedia, the free encyclopedia.

http://en.wikipedia.org/wiki/Vitamin_K

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http://www.vitamink2.org/?znfAction=referencesKeyStudies

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1939:

Discovery of K2.

Almquist H J: Early history of vitamin K. Am. J.Clin.  Nutrition. 28, 656-659, 1975

http://www.ajcn.org/content/28/6/656.full.pdf

 

The first crystalline antihemorrhagic vitamin K was discovered  from rottting (inoculated with bacteria) fish meal by E.A. Doisy and his group by and named as K2.

Dam and Doisy shared the 1943 Nobel Prize for medicine for their work on vitamin K (K1 and K2) published in 1939.

========

Average diets have enough vitamin K.

Primary vitamin K deficiency is rare in healthy adults.

Newborns are at an increased risk of deficiency.

Risk factors:

1.Liver damage or disease (e.g. alcoholics).

2. Cystic fibrosis.

3. Inflammatory bowel diseases.

4. Recent abdominal surgeries.

Secondary reasons:

5. Bulimics

6.Dieting.

DRUGS

7. Anticoagulants.

8. Salicylates. Vitamin K2 is not affected.

9. Barbiturates.

10. Cefamandole and other broad spectrum antibiotics

11. Malabsorption causes.

12. Reduced production among elderly.

Symptoms of deficiency:

Heavy menstrual bleeding in women, anemia, bruising, and bleeding of the gums or nose.

Osteoporosis[60][61] and coronary heart disease[62][63] are strongly associated with lower levels of K2 (menaquinone).

 As Menaquinone is not inhibited by salicylates, its supplementation may alleviate the chronic vitamin K deficiency caused by long term aspirin use.[citation needed]

===

WHICH MK2 IS NEED TO BE SUPPLEMENTED?

MK4 or MK7

Vitamin K2 (Menaquinone-4) is synthesized by animal tissues and is found in meat, eggs, and dairy products.[57] Menaquinone-7 is synthesized by bacteria during fermentation and is found in fermented soybeans (natto).[58] In natto 0% of vitamin K is from MK-4 and in cheese 2–7%.[59]

Vitamin K2 (MK4) and bone health

In contrast, MK4 has been shown in numerous studies to reduce fracture risk, stop and reverse bone loss. In Japan, MK4 in the dose of 45 mg daily is recognized as a treatment for osteoporosis[85][88] under the trade name Glakay.[89] MK4 has been shown to decrease fractures up to 87%.[13] In the amount of 45 mg daily MK4 has been approved by the Ministry of Health in Japan since 1995 for the prevention and treatment of osteoporosis.[14]

MK4 (but not MK7 or vitamin K1) prevented bone loss and/or fractures in the following circumstances:

[edit] Vitamin K2 (MK7) and bone health

Menaquinone-7 (MK7), which is abundant in fermented soybeans (natto), has been demonstrated to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption.[90] In another study, use of MK-7 caused significant elevations of serum Y-carboxylated osteocalcin concentration, a biomarker of bone formation. MK-7 also completely inhibited a decrease in the calcium content of bone tissue by inhibiting the bone-resorbing factors parathyroid hormone and prostaglandin E2.[91] On 19 February 2011, HSA (Singapore) approved a health supplement that contains vitamin K2 (MK7) and vitamin D3 for increasing bone mineral density.[92]

==

Vitamin K and cancer

While researchers in Japan were studying the role of vitamin K2 as the menaquinone-4 (MK-4) form in the prevention of bone loss in females with liver disease, they discovered another possible effect. This two-year study that involved 21 women with viral liver cirrhosis found that women in the supplement group were 90% less likely to develop liver cancer.[94][95] A German study performed on men with prostate cancer found a significant inverse relationship between vitamin K2 consumption and advanced prostate cancer.[96]

===

Toxicity

Although allergic reaction from supplementation is possible, there is no known toxicity associated with high doses of the phylloquinone (vitamin K1) or menaquinone (vitamin K2) forms of vitamin K and therefore no tolerable upper intake level (UL) has been set.[49]

Blood clotting (coagulation) studies in humans using 45 mg per day of vitamin K2 (as MK4)[25] and even up to 135 mg/day (45 mg three times daily) of K2 (as MK4),[50] showed no increase in blood clot risk. Even doses in rats as high as 250 mg/kg body weight did not alter the tendency for blood-clot formation to occur.[51]

However, a synthetic form of vitamin K, vitamin K3 (menadione), is demonstrably toxic. In fact, the FDA has banned this synthetic form of the vitamin from over-the-counter supplements because large doses have been shown to cause allergic reactions, hemolytic anemia, and cytotoxicity in liver cells.[1]

[edit] Drug interactions

Phylloquinone (K1)[52][53] or menaquinone (K2) are capable of blocking the blood thinning action of anticoagulants like warfarin, which work by interfering with the action of vitamin K. They also reverse the tendency of these drugs to cause arterial calcification in the long term.

==

There are three synthetic forms of vitamin K, vitamins K3, K4, and K5, which are used in many areas including the pet food industry (vitamin K3) and to inhibit fungal growth (vitamin K5).[41]

==

And in an animal model MK4 was shown to prevent arterial calcifications, pointing to its potential role in cardiovascular disease prevention.[40] I

--

Subtypes of vitamin K2

Vitamin K2 (menaquinone) includes several subtypes. The two subtypes of vitamin K2 that have been most studied are menaquinone-4 (menatetrenone, MK4) and menaquinone-7 (MK7).

MK4 is produced via conversion of vitamin K1 in the body, in the testes, pancreas and arterial walls.[3] While major questions still surround the biochemical pathway for the transformation of vitamin K1 to MK4, studies demonstrate that the conversion is not dependent on gut bacteria, occurring in germ-free rats[4][5] and in parenterally-administered K1 in rats.[6][7] In fact, tissues that accumulate high amounts of MK4 have a remarkable capacity to convert up to 90% of the available K1 into MK4.[8][9]

In contrast to MK4, menaquinone-7 (MK7) is not produced by humans but is converted from phylloquinone in the intestines by gut bacteria.[10] However, bacteria-derived menaquinones (MK7) appear to contribute minimally to overall vitamin K status.[11][12] MK4 and MK7 are both found in the United States in dietary supplements for bone health.

The US FDA has not approved any form of vitamin K for the prevention or treatment of osteoporosis; however, MK4 has been shown to decrease fractures up to 87%.[13] In the amount of 45 mg daily MK4 has been approved by the Ministry of Health in Japan since 1995 for the prevention and treatment of osteoporosis.[14]

Vitamin K2 (MK4, but not MK7 or vitamin K1) has also been shown to prevent bone loss and/or fractures in the following circumstances:

  • caused by corticosteroids (e.g., prednisone, dexamethasone, prednisolone),[15][16][17][18]
  • anorexia nervosa,[19]
  • cirrhosis of the liver,[20]
  • postmenopausal osteoporosis,[14][21][22][23][24][25]
  • disuse from stroke,[26]
  • Alzheimer's disease,[27]
  • Parkinson disease,[28]
  • primary biliary cirrhosis[29]
  • and leuprolide treatment (for prostate cancer).[30]
  • ==
  • Vitamin K2 is involved in bone metabolism.

  •  Vitamin K2  are characterized by the number of isoprenoid residues comprising the side chain. Menaquinones are abbreviated MK-n, where n represents the number of isoprenoid side chains. Thus, menaquinone-4 abbreviated MK-4, has 4 isoprene residues in the side chain. Bacteria can produce a range of vitamin K2 forms, including the conversion of K1 to K2 (MK-7) by bacteria in the small intestines.

  •  

  • ---------------

  • http://www.genoprice.com/vitamin_k2.htm

  •  

  • The Special Effects of Vitamin K2

    1.     Treatment of haemorrhage caused by VK2 deficiency;

  • promotes  thrombin formation,

  •  accelerates blood clotting,

  • maintains clotting time;

  •  a quick coagulant in surgeries or first aids

    2.      Treatment of  osteoporosis;

  • VK2 produces osteocalcin which can bind calcium, deposits on bone increasing  bones density and to prevent fracture. 

    3.      Prevention of hepatocellular carcinoma in women with viral cirrhosis.

    4.      Diuresis, detoxifcation of liver and lowering the blood pressure. 

  • ==

  • Vitamin K is a stronger antioxidant than vitamin E or coenzyme Q10

  •  Vitamin K2 deficiency can have effects similar to diabetes.And n

  • Vitamin K2 may be helpful in treating certain cancers and Alzheimer's disease.

  • ---

  • THROMBIN DEFICIENCY

  • 1. Newborn. At 1-2 weeks age, newborns often have low thrombin. The placenta is a difficult barrier to transport fat. It takes several weeks for newborn to have normallevel of thrombin. If the thrombin rate is lower than normal level by 10%, infant can have hemorrhagic disease.

  • Some senior citizens may lack of vitamin K2.

  • Drugs such as dicarboxylic coumarin.

  • ------

 

Vitamin K2

Benefits of vitamin K2

The vitamin K2 activates its dependent proteins: Osteocalcin and MGP

a) Osteocalcin in bone building cells needs to be activated in order to bind calcium to the surface of bones

b) Matrix Gla (glutamic acid) Protein (MGP) in the vasculature to get activated in and inhibit calcium deposition in the arteries.

MGP is the most powerful inhibitor of soft tissue calcification.

Healthy adults are insufficient in vitamin K as 30% of their MGP is synthesized in an inactive form. This figure increases at increasing age.

Protection against cardiovascular calcification is 70% in the young healthy person and diminishes as ages, unless K2 is suplemented.

Best references:

http://www.lef.org/Vitamins-Supplements/Item01224/Super-K-with-Advanced-K2-Complex.html

http://www.lef.org/Vitamins-Supplements/References/2011/Vitamins.htm

Vitamins

=====

http://www.westonaprice.org/fat-soluble-activators/x-factor-is-vitamin-k2#fig4

http://www.westonaprice.org/fat-soluble-activators/x-factor-is-vitamin-k2

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http://www.thorne.com/Products/Vitamins/prd~K170.jsp

Vitamin K2 Liquid

concentrated vitamin K2 in a convenient liquid form

  • effective in maintaining bone health*
  • supports a healthy cardiovascular system*
  • provides nutritional support for oncology patients*

Item Product Size Price
K170 Vitamin K2 Liquid 1 fl oz (30 mL) $61.20

Product Information

Vitamin K2 exerts a more powerful influence on bone than does vitamin K1.* Vitamin K2 is a series of molecules known as menaquinones. The most common and well studied of the menaquinones is MK-4. Thorne's vitamin K2 is MK-4.

Vitamin K2 appears to offer significant benefit for supporting bone health.* Although much of the vitamin K2 research has been conducted on postmenopausal support for bones, because vitamin K2 does not have any estrogenic effects, vitamin K2 also offers bone support for other populations, including anorexics, dialysis patients, individuals with Parkinson's disease, those who have cirrhosis of the liver, individuals who have had a bone marrow transplant, those immobilized after a stroke, and individuals on chronic steroid therapy.*

Thorne's Vitamin K2 Liquid supplies 1 mg of vitamin K2 per drop. Research shows doses up to 15 mg three times daily may be used.*
===

http://thorne.com/Products/Circulatory-Support/Cardiovascular_Health/prd~KD500.jsp

Vitamin D / K2 Liquid

liquid vitamins D3 and K2 in a balanced formula

  • 10 drops contain 5,000 IU vitamin D3 and 1 mg vitamin K2
  • vitamins K and D for support of healthy bones*
  • in liquid for ease of dosing and titration
  • both vitamins support a healthy cardiovascular system*
  • provides nutritional support for oncology patients*

Item Product Size Price
KD500 Vitamin D / K2 Liquid 1 fl oz (30 mL) $21.50

Product Information

Vitamin K2 exerts a more powerful influence on bone than does vitamin K1.* Vitamin K2 is a series of molecules known as menaquinones. The most common and well studied of the menaquinones is MK-4. Thorne's vitamin K2 is MK-4 and is derived from bacterial fermentation; thus, there is no soy in the product. Vitamin K is also essential for normal cell formation and maintenance of a healthy cardiovascular system.*

It is essential to maintain healthy vitamin D levels throughout all stages of life, from fetal development to old age.* Vitamin D helps protect a number of important systems in the body, including healthy bones, immunity, and cardiovascular function.*

Combining vitamins D and K may provide even better protection of these systems.* One study in postmenopausal women found a combination of minerals with vitamins D and K maintained healthy artery elasticity, compared to two other groups of women who received either minerals with vitamin D but not K, or placebo.*

Thorne's Vitamin D / K2 Liquid is in medium chain triglyceride oil, preserved with mixed tocopherols.

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Criteria
MK4
MK7
Comments

Nature

Synthetic

Natural

Add your content here

Source

 
Vitamin K2 MK4 is only found in animal products.
The best sources: Grass-fed butter from cows eating rapidly growing grass, and foie gras.
 
 K2 MK7 is found abundantly in natto, a type of fermented soybean, and it may be partially converted to MK-4.
 
 
Oil, butter,eggs, meats and dairy.


"Perigord, France is the world's capital of foie gras, or fatty goose liver. Good news for the bon vivants: foie gras turns out to be the richest known source of K2. Perigord also has the lowest rate of cardiovascular mortality in France, a country already noted for its low CVD mortality."

 

Healthy colon bacteria

Japanese natto

Low fat Dutch gouda

Edam cheese

Bacteria in the colon

Add your content here

Converson of Vitamin K1 to K2 subtype MK4.
The vitamin K in plants is K1. It's made into K2 subtype MK4 by some animals.
Bacteria can convert K1 to K2 by bacteria in the small intestines.
Bacteria can convert of K1 to K2(MK7) by bacteria in the small intestines
 
Humans are not good at making this conversion.
Add your content here

K2 in Europe

x

MK7 is the only approved as food supplement and fortified food.
 
 
 

Add your content here

The number of isoprene units attached to the molecules ring structure.

 MK4, has 4 isoprene residues in the side chain.
 

MK7, has 7 isoprene residues in the side chain.

Add your content here

Add your content here

 MK4 is synthesized by animals for their own use from K1 (and from MK7 in rats). 
Animals concentrate MK4 (with smaller amounts of K1) in the brain, pancreas and salivary gland.

MK4 is produced via conversion of vitamin K1 in the body, in the testes, pancreas and arterial walls.[3] While major questions still surround the biochemical pathway for the transformation of vitamin K1 to MK4, studies demonstrate that the conversion is not dependent on gut bacteria, occurring in germ-free rats[4][5] and in parenterally-administered K1 in rats.[6][7] In fact, tissues that accumulate high amounts of MK4 have a remarkable capacity to convert up to 90% of the available K1 into MK4.[8][9]

 

 

 


It appears that MK4 is capable of performing all the functions of vitamin K including activating blood clotting factors (function of Vitamin K1).
Newborns are often born clotting deficient, so, vitamin K1 injections is given to them after birth in the U.S. to prevent hemorrhaging.
 In Japan, they children receives MK4 to prevent hemorrhage.
Japan has half the infant mortality rate of the U.S.
 
 
Some countries utilize predominanantly MK4 over other forms of vitamin K in the diet ( dairy such as Masai)
Infants receive most of  vitamin K from MK4. Colostrum, the first milk to come out, is rich in MK4.

Vitamin K is required to activate Gla proteins (gamma-carboxyglutamic acid), a modified amino acid that's synthesized using vitamin K (by gamma-carboxylation reaction).
Gla proteins are important: the class includes:
 MGP, ( to keep arteries clean)
osteocalcin ( bones strong) and
blood clotting factors( to keep blood clotting correctly). 

Vitamin K2:
It acts like hormone, activating a nuclear receptor called the steroid and xenobiotic receptor (SXR) and influencing the expression of a number of genes.
It also acts as an antioxidant, a cofactor for sphingolipid synthesis in the brain, and an activator of protein kinase A signaling.
 
These  functions have been studied in the context of MK4 not yet with MK7 has equivalent effects.



SXR-independent effects of vitamin K2 on gene expression.
MK4 activates transcription of two specific genes in osteoblast cells (create bone tissue).
The genes are GDF15 and STC2 and they're involved in bone and cartilage formation.
They tested K1, MK-7, and MK-4.
Only MK4 has effects on gene expression in bone tissue.

Vitamin K2 MK4 seems to be able to perform all the functions of vitamin K:
1. Activates Gla proteins
2. Participates in sphingomyelin synthesis.
3. Binds SXR.
4. Activates transcription through protein kinase A.
 
No investigations with MK7 is  done yet in these respects.
 
MK4 is the only form of vitamin K2 that's been shown to reduce fracture risk in clinical trials. 

MK7  is made in large amounts by the bacterium Bacillus subtilis that ferments the Japanese condiment natto.
 
MK7 can activate clotting factors and osteocalcin. It can function as a cofactor for gamma-carboxylation.
 
MK7 stays in the blood for longer than MK4 in humans.
These findings were conducted by MK7 supplement vendors and the results have not been published.
 
MK4 and MK7 have the exact same plasma half-life in rats. The human experiment should be done.
 
 

MK5 through MK14 are synthesized by bacteria.
 
The liver, in some animals, including humans, concentrates longer menaquinones to a greater extent than MK4, if they're present in the diet.
Newborns are often born clotting deficient, and in USA they received Vitamin K1 injections after birth to prevent hemorrhaging.
In Japan, newborns receive MK4 to prevent.
Japan has half the infant mortality rate of the U.S.

Fracture prevention

 "all the studies showing lowered fracture risk with K2 supplementation used MK-4, not MK-7. MK-7 has never been directly shown to reduce fracture risk in humans."

Add your content here

Add your content here

Coronary artery disease

x

Data from the Prospect-EPIC cohort study:
16,057 women studied between 1993 and 1997aged 49-70 years. After adjustment for traditional risk and dietary factors, an inverse association between vitamin K2 and risk of CHD was observed with per 10mug/d vitamin K2 intake and mainly due to vitamin K2 subtypes MK-7, MK-8 and MK-9 and not Vitamin K1.
Reference:

Gast GC, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT.
A high menaquinone reduces the incidence of coronary heart disease in women. Nutr Metab Cardiovasc Dis. 2009 Jan 27.

Add your content here

Prevention of fractures

MK4 supplements can reduce fracture risk.
 
 

 MK7 hasn't been tested yet.

Add your content here

Calcification nreversal.

MK-4 reverses arterial calcification in rats?

Add your content here

Add your content here

Half life duration.

The reason MK-4 has a shorter half-life:
It is less lipid-soluble due to its shorter tail and resides more towards the surface of the lipoprotein and is therefore more easily absorbed into cells.
 
 
 

The reason MK7 has a longer half-life:
 This may be  due to that it has a longer side-chain, so more fat-soluble, and thus is located more in the core of the lipoproteins thus having less interaction with enzymes that would bring it into the cells.
.

Add your content here

Cost and dose.

MK4 is cheaper than MK-7!
 

 MK7s are being sold comes in much lower doses.
 

Add your content here

Add your content here

x

whereas vitamin K2 has an unsaturated side chain [1].

Add your content here

References:
 

Vitamin K2: MK-4 versus MK-7

 

"Wednesday, March 11, 2009

Are the MK-4 and MK-7 Forms of Vitamin K2 Equivalent?

The vitamin K found in food can be divided into two categories: phylloquinone
(K1) and menaquinone (K2). K1 is concentrated in leafy greens and other green vegetables. K2 can be further subdivided into menaquinone-4 through -14. The number represents the length of the side chain attached to the napthoquinone ring.
chain attached to the napthoquinone ring.
 
 
 

VITAMIN K

CAD & VITAMIN K

"This study shows that high dietary menaquinone intake, but probably not phylloquinone, is associated with reduced coronary calcification. Adequate menaquinone intakes could therefore be important to prevent cardiovascular disease."1

1. Beulens JW, 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. Epub 2008 Jul 19.
http://www.ncbi.nlm.nih.gov/pubmed/18722618

There are three forms of vitamin K.

K1 (phylloquinone or phytonadione)

K2 (menaquinone or or MKs).

K3 (menadione) is a potent synthetic (man-made) form and not used in humans.

K2 is thought to prevent and reduce coronary calcification but K1 does not, noted in a studies.1, 2

------
Vitamin K activates proteins such as matrix Gla-protein (MGP) via carboxylation . These proteins have been shown to inhibit vascular calcification.
The researchers here examined whether dietary intake of phylloquinone (K1) and menaquinone (K2) were related to aortic calcification and coronary heart or artery disease (CHD or CAD).
Their finding suggest a protective effect of menaquinone (K2) intake against CHD. K2 inhibited arterial calcification and contributed to CHD prevention.
The study also showed that people who consume 45 mcg of K2 daily lived seven years longer than people getting 12 mcg per day. 2
Johanna M. Geleijnse, Cees Vermeer et al. Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study. The American Society for Nutritional Sciences J. Nutr. 134:3100-3105, November 2004
http://jn.nutrition.org/content/134/11/3100.full
---------------
Vitamin K1:

Source: in green vegetables such as kale, spinach, collard greens, broccoli, and Brussels sprouts.and Vegetable oils: Soybean oil, olive oil, and canola oil, contain smaller amounts.

K1 is found in dark green leafy vegetables, and makes up about 90 percent of the vitamin K in a typical Western diet. The following table lists some vegetable sources of K1 that you should consider eating frequently:

Food Vitamin K*
Raw parsely 9113mcg
Raw chard swiss 8738mcg
Cooked or frozen Kale 5880mcg

Watercress

raw

4545mcg
Spinach cooked or raw

4292mcg

4190mcg

Mustard green raw or cooked 3900mcg+/-

Foods highest in Vitamin K (based on levels per 200-Calorie serving) http://nutritiondata.self.com/foods-000104000000000000000.html#ixzz1l5jP1gXT

http://nutritiondata.self.com/facts/vegetables-and-vegetable-products/2704/2

The best natural source of vitamin K2 is derived from an ancient Japanese food called Natto. Natto is made from fermented soybeans and significant amounts of vitamin K2 are produced during the fermentation process.

K1 goes directly to liver and helps in body's coagulation process.

Functions:

Maintains a healthy blood clotting system,

keeps blood vessels from calcifying, and

helps bones retain calcium and develop the right crystalline structure.

K1 is often given to new born, especially premature babies to prevent any bleeding problems.

Vitamin K2

Sources:

Intestinal bacterias produce this. and passes in stool.

Present in fermented foods: Cheese, curds and the Japanese food natto, a very rich source.

The fermented foods contains lactococci and proprionic acids bacteria which both produce K2.

One can also obtain daily need for K2 (about 200 micrograms) by eating 15 grams of natto daily ( half an ounce and inexpensive.

The best natural source of vitamin K2:

Ancient Japanese food Natto, made from fermented soybeans.

A significant amounts of K2 are produced during the fermentation.

Alternative to natto is curd, though is not as rich as natto.

Cooking does not affect the vitamin contents of the foods.

K2 goes straight to vessel walls, bones, and tissues other than liver.

High dietary intake of vitamin K2 is associated with reduced coronary artery calcification.

The Prospect Study:

Here 16,057 women were followed for 10 years. Researchers found that each additional 10 mcg of K2, resulted 9% fewer cardiac events and significant heart benefit. This association was noted mainly especially due to vitamin K2, subtypes MK-7, MK-8 and MK-9.

Vitamin K1 intake was in the diet results did not had cardiac beneficial effect.

How Vitamin K2 helps Heart?

Vitamin K2 is necessay for vitamin D to provide bone development by helping absorb calcium.

K2 directs the calcium to skeleton, and preventing it from being deposited in the organs, joint spaces, and arteries.

Arterial plaque contains a large part of calcium deposits leading to atherosclerosis or hardening of the arteries.

K2 activates hormone called osteocalcin, a protein produced by osteoblasts, which is needed to bind calcium into the bone matrix. Osteocalcin also to prevent calcium from depositing into arteries.

Vitamin K2 helps to produce Matrix GLA Protein (or MGP). MGP prevents blood vessels and soft tissue calcification following inflammatory reaction.

"According to Professor Cees Vermeer:

"The only mechanism for arteries to protect themselves from calcification is via the vitamin K-dependent protein MGP. MPG is the most powerful inhibitor of soft tissue calcification presently known, but non-supplemented healthy adults are insufficient in vitamin K to a level that 30 percent of their MGP is synthesized in an inactive form. So, protection against cardiovascular calcification is only 70 percent in the young, healthy population, and this figure decreases at increasing age."

.http://www.nutraingredients.com/Research/NattoPharma-says-calcium-research-highlights-vitamin-K-role

------

Other benefits of Vitamin K:

1. Fight cancers:

People who have the highest intakes of vitamin K2, not vitamin K1, may significantly lower their risk of cancer and cancer mortality, according to results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

After analyzing data from over 24,000 participants who were followed for over 10 years, those who had the highest intakes of vitamin K2 were 14 percent less likely to develop cancer and 28 percent less likely to die of cancer compared to those with the lowest intakes.

A separate study by researchers at the Mayo Clinic also revealed impressive anti-cancer effects from vitamin K. Those with the highest dietary vitamin K intakes had a 45 percent lower risk of developing Non-Hodgkin lymphoma, a cancer of the immune system, than those with the lowest.

Prostate: reduce risk of prostate cancer by 35 percent.

Nimptsch K, Rohrmann S, Linseisen

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).
Am J Clin Nutr. 2008 Apr;87(4):985-92.

---

Could This ‘Humble’ Vitamin Hinder Future Cancers?

Dr. Mercola | April 29 2010 |

http://articles.mercola.com/sites/articles/archive/2010/04/29/which-type-of-vitamin-k-decreases-cancer.aspx

---

Lung cancer

Yoshida T, Miyazawa K, Kasuga I, Yokoyama T, Minemura K, Ustumi K, Aoshima M, Ohyashiki K.

Apoptosis induction of vitamin K2 in lung carcinoma cell lines: the possibility of vitamin K2 therapy for lung cancer.

Int J Oncol. 2003 Sep;23(3):627-32.

http://www.ncbi.nlm.nih.gov/pubmed/12888897?dopt=Abstract

Studies have linked vitamin K2 with a nearly 30 percent reduction in your risk of cancer mortality and a 14 percent lowered risk of cancer altogether.
Non Hodgkins Lymphoma.
Liver, colon, stomach, nasopharynx, and oral cancers, lung and leukemia.

--

2. Prevent varicose

J.Vas. Res.: 2007, 44, 444-459.

veins.http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=000106189&Ausgabe=233319&ProduktNr=224160&filename=000106189.pdf

3. Prevents type 2 Diabetes

Among 38,000 adults followed for a decade, those who got the most vitamin K in their diets were about 20 percent less likely to be diagnosed with type 2 diabetes.

Both vitamins K1 and K2 were related to a lower diabetes risk, but the relationship was stronger with vitamin K2.

Foods Rich in This Vitamin Reduce Your Diabetes Risk by 20%

Posted By href="http://articles.mercola.com/members/Dr.-Mercola/default.aspx" this.s_oc?this.s_oc(e):true? articles.mercola.com http: default.aspx_1?;return Dr.-Mercola members>Dr. Mercola | June 19 2010 | 70,253 views

Plenty of vitamin-K-rich foods in your diet could lower diabetes risk by 20 percent by reducing systemic inflammation, thus improves ability to use insulin.

Vitamin K deficiency may interfere with insulin release and blood sugar regulation.

From Medscape Medical News. Vitamin K Supplementation May Reduce Progression of Insulin Resistance in Older Men. August 15, 2008

http://www.medscape.org/viewarticle/579145

----------------------------------------------------

4 . Helps bone density

Osteoporosis Drug Fosamax is Bad for Your Heart

Posted By
Dr. Mercola | May 20 2008 |

http://articles.mercola.com/sites/articles/archive/2008/05/20/osteoporosis-drug-fosamax-is-bad-for-your-heart.aspx

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How many people have adequate vitamin K2?

Just about zero, according to Dr. Vermeer and other experts in the field.

Circulating MGP: An indirect reliable test for measuring vitamin K, developed by Dr. Vermeer and his team will be avaiable soon.

The test should be helpfu to assess the risk for arterial calcification.

Improve Bone Density …
  • Lower Your Risk of Diabetes …

    People with the highest intakes of vitamin K from their diet had a 20 percent lower risk of diabetes compared with those with the lowest intakes, according to the latest research from University Medical Center Utrecht in the Netherlands. Past studies have also shown vitamin K to help href="http://cme.medscape.com/viewarticle/579145" target=_blank this.s_oc?this.s_oc(e):true? http: 579145_1?;return viewarticle cme.medscape.com>reduce the progression of insulin resistance.

    For comparison's sake, in the diabetes study from the University Medical Center Utrecht in the Netherlands those who had the highest vitamin K intakes -- and therefore experienced the greatest protection against diabetes -- were consuming between 250 and 360 mcg of vitamin K daily from their diets.

    The best natural source of vitamin K2 is derived from an ancient Japanese food called Natto. Natto is made from fermented soybeans and significant amounts of vitamin K2 are produced during the fermentation process. You can find natto at some health food stores and Asian grocery stores.

    Since most Americans do not eat traditionally fermented foods like natto, adding them to your diet is a must as the health benefits are tremendous. Keep in mind you can also get vitamin K2 from other fermented food aside from natto, such as certain types of cheese, like raw curd.

    If you find yourself not consuming enough fermented foods, you will certainly want to consider taking a supplement, especially if you have osteoporosis, heart disease or risk factors for diabetes.

Dose:
"Dr. Cees Vermeer, one of the world's top researchers in the field of vitamin K, nearly everyone is deficient in vitamin K -- just like most are deficient in vitamin D.

Most people get enough vitamin K from their diets to maintain adequate blood clotting, but NOT enough to offer protection against health problems like arterial calcification and cardiovascular disease."

Many people are not getting the currently recommended intakes of vitamin K, which are likely already too low to begin with. In fact, according to What We Eat In America NHANES 2001–2002, only one in four Americans are meeting the recommended levels of dietary vitamin K"

http://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/vitamin-k/index.html" target=_blank this.s_oc?this.s_oc(e):true? http: index.html_1?;return vitamin-k what-should-you-eat nutritionsource www.hsph.harvard.edu>meeting the recommended levels of dietary vitamin K.

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What We Eat In America NHANES 2001–2002:

Usual nutrient intakes from food compared to dietary nutrient intakes.

Vitamin K makes four of the 13 proteins factors needed for blood clotting cascade.

Vitamin K and building bone:

Low vitamin K have been linked with low bone density.

Supplementation with vitamin K shows improvements of bone health. (1)

Nurses' Health Study:

Women who got at least 110 micrograms of vitamin K a day had 30 percent less broke a hip than women who g0t less than that. (2)

Eating a serving of lettuce or green, leafy vegetable daily cut the risk of hip fracture in half when compared with one serving a week eating.2

The Framingham Heart Study:

A igh vitamin K intake and reduced risk of hip fracture in men and women and increased bone mineral density in women. (3, 4)

National data suggests that only about one in four Americans meets the goal for vitamin K intake from food. (5)

5. Moshfegh A, Goldman, J., Cleveland, L. . What We Eat In America. NHANES 2001–2002: Usual Nutrient Intakes from Food Compared to Dietary Intakes. U.S. Dept. of Agriculture, Agricultural Research Service. 2005.

The Nutrition Source

Vitamin K

http://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/vitamin-k/index.html

References

1. Weber P. Vitamin K and bone health. Nutrition. 2001; 17:880–7.

2. Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr. 1999; 69:74–9.

3. Booth SL, Tucker KL, Chen H, et al. Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr. 2000; 71:1201–8.

4. Booth SL, Broe KE, Gagnon DR, et al. Vitamin K intake and bone mineral density in women and men. Am J Clin Nutr. 2003; 77:512–6.

5. Moshfegh A, Goldman, J., Cleveland, L. . What We Eat In America. NHANES 2001–2002: Usual Nutrient Intakes from Food Compared to Dietary Reference Intakes. U.S. Dept. of Agriculture, Agricultural Research Service. 2005.

http://www.ars.usda.gov/SP2UserFiles/Place/12355000/pdf/0102/usualintaketables2001-02.pdf

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Further, the Institute of Medicine's recommended daily intake of 120 micrograms for men and 90 for women are based on levels that will ensure adequate blood coagulation. But vitamin K is important for more than just blood clotting; it impacts the health of your bones, arteries and immune system as well.

Now emerging research, including the "triage theory" from Joyce McCann, PhD and Bruce Ames, PhD, suggests that these other non-clotting functions that depend on vitamin K may need higher levels than are currently recommended.

Vitamin K is a fat-soluble vitamin.in order for body to absorb it, one needs to eat some fat along with it.

Dose:

The exact dosing is yet to be determined.

The Institute of Medicine's daily recommendation:

Men: 120 micrograms. for men.

Women: 90 microgram for women.

Vitamin K expert, Dr. Cees Vermeer daily recommendation: 45 mcg to 185 mcg for adults.

Dr. Mercola: Unless on anticoagulant therapy, dose could be 100 mcg

Above recommendation are for vitamin K , not as K1 and K2.

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"This information proves that Vitamin K2 is a critical nutrient for patients with arteriosclerosis as it has the potential to prevent and remove calcium from arteriosclerotic plaques thus making plaques easier to dissolve and less dangerous."1

TYPES:

K1 & K (2menaquinone-7)

Fat absorbable also A D E

Sources: K1 in plants

K2 in animals and bacterias

Healthy colon bacteria,

Japanese natto,

Low fat Dutch gouda and

Edam cheese

Bacteria in the colon

Antibiotics and the non-steroidal anti-inflammatory drugs kill many of these good intestinal bacteria.

Vitamin K1 was less effective than Vitamin K2 in preventing bone loss.

Vitamin K2(MK-7) is absorbed better and is 6 times more potent than Vitamin K1.

There is a lower incidence of calcification of the aorta if on long term K2 therapy.

High K2 level is associated with number of lower plaque in the arteries and more elastic are the arteries.

K2 lack causes calcium to deposit in arteries, aorta, soft tissues including muscle, breast, kidneys and in heel spurs instead of bones.

In Japan, osteoporosis is treated by K2.

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"The secret to avoiding calcium-related osteoporosis and atherosclerosis

While millions of people take calcium and Vitamin D supplements thinking they're helping their bones, the truth is, without the addition of Vitamin K2, such a health regimen could prove dangerous. Without Vitamin K2, the body cannot direct calcium to the bones where it's needed; instead, the calcium resides in soft tissue (like the arteries)—leading to a combination of osteoporosis and atherosclerosis, or the dreaded "calcium paradox." This is the first book to reveal how universal a Vitamin K2 deficiency is, and the risk (in the form of cancer and diabetes, among other ailments) the absence of Vitamin K2 poses.

Written by Dr. Kate Rheaume-Bleue, a popular health expert on Canadian television and radio, Vitamin K2 and the Calcium Paradox sounds a warning about the popularity of the calcium and Vitamin D craze, while illustrating the enormous health benefits of Vitamin K2 in making the body less susceptible to dental cavities, heart disease, prostate cancer, liver cancer, diabetes, wrinkles, obesity, varicose veins, and other ailments.

  • The book demystifies this obscure supernutrient—a fat soluble vitamin that humans once thrived on, ignored by scientists for almost seventy years
  • Details how the consumption of grass-fed animals led to adequate Vitamin K2 intake—while grain-based animal feed helped eradicate Vitamin K2 from our diets
  • Describes how doctors are raising recommended doses of calcium and Vitamin D—without prescribing Vitamin K2
  • Details more damning facts about transfats—and how the creation of a synthetic Vitamin K interfered with the body's Vitamin K metabolism

An essential book for anyone interested in bone health, or maintaining their overall health, Vitamin K2 and the Calcium Paradox is the guide to taking the right combination of supplements—and adding Vitamin K2 to a daily regimen.

Vitamin K2 and the Calcium Paradox: How a Little-Known Vitamin Could Save Your Life

References:

James Howenstine. ARTERIOSCLEROSIS CAN BE REVERSED.PART 1 of 2 July 24, 2008

NewsWithViews.com

http://www.newswithviews.com/Howenstine/james67.htm

And just a note: I had some measure of difficulty with the sound control on this video (and there’s not much I can do about it).  So if you have trouble listening, make sure to download the full transcript.

video: vitamin K2 and the calcium paradox