Although Vitamin K is best known for
its role in normal blood clotting function, recent research has revealed
Vitamin K's beneficial effects on bone and cardiovascular health. In bone
tissue, Vitamin K is critical for the formation of healthy, strong bone matrix.
In fact, bone quality is dependent on the presence of adequate Vitamin K.
Vitamin K's role in arterial health revolves around its ability to support
proper calcium metabolism in vascular structures. Vitamin K2 is the most biologically
active form of vitamin K. It is also the most beneficial for bone integrity, as
well as for the support of arterial health.
Vitamin K2 is involved in bone metabolism. Vitamin K2 homologs (menaquinones)
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. No known toxicity exists for vitamins K1 and K2.*
Vitamin K2 provides major protection from osteoporosis, cardiovascular
blockages, and pathological calcification.
Vitamin K's job is to put calcium in the right places and keep it from being
deposited in the wrong places. The right places are bones and blood, and the
wrong places include calcification of the vessels, bone spurs, and calcification
of soft tissues.
Vitamin K was discovered in the
1920's as a fat-soluble factor important in blood coagulation ("K"
for koagulation). Vitamin K1 is found in plants and vitamin K2 is found in
animals and bacteria, including beneficial probiotic bacteria, aka "good
bacteria," from the GI tract. The body can store about a one-month supply
of the vitamin. Antibiotics interfere with the growth of healthy intestinal bacteria
and as a result, impair vitamin K production. The prescription anticoagulant
Warfarin also interferes with the metabolism and function of vitamin K by
inhibiting critical enzymes that are involved with the production of
coagulation factors. Without these coagulation factors, excessive bleeding can
Vitamin K works by acting as a cofactor in the carboxylation (adding of a
carboxyl group C02) via an enzyme (gamma-glutamyl carboxylase), of glutamic
acid (a specific amino acid) to form a modification of that amino acid (gamma
carboxyglutamic acid) in a variety of critical plasma proteins. Without this
step, these plasma proteins will not function in their role of the regulation
of calcium concentrations in various tissues.
There are several different types of
GCGA proteins including osteocalcin (OC), which is the most abundant GCGA
protein in humans and is synthesized in bone; the GCGA protein-containing blood
coagulation factors are synthesized in the liver; the matrix GCGA proteins
(MGP) are synthesized in the cartilage and in the vessel walls of arteries. 1
According to the Food and Nutrition Board of the National Academy of Sciences
National Research Council, the requirements of vitamin K in micrograms (mcg)
ranges from 5 micrograms for infants and up to 80 mcg for adult males and 65
mcg for adult females. 2
When vitamin K is in short supply in the body, these proteins are formed
without the GCGA component and are inactive for their intended functions -
which play important roles in four different tissue types including: 1) liver;
2) bone; 3) cartilage; and 4) arterial vessel walls.
These four tissues are all able to pull vitamin K from the blood. However, the
uptake from the liver is much greater for K1 than for other tissues. Very
important recent findings indicate that vitamin K2, and not K1 inhibits
Warfarin-induced arterial calcification. This research is important for those
on Warfarin, and has implications for the majority of us who are unaware that
we are deficient in this lifesaving nutrient.
Because the liver needs so much
vitamin K, this can leave the cartilage and bone GCGA proteins with inadequate
levels. Hence the dietary vitamin K requirement for bone, and the special
requirements for the cardiovascular system and cartilage may not be met even
though normal clotting factor production occurs, as this occurs in the liver.
Therefore, the requirement to keep the vasculature clear of accumulating
calcium and to keep the bones well supplied with calcium may not be adequately
supplied. This is why the recent discoveries on the value of vitamin K2 and its
recent commercial availability can make a great difference in the lives of
millions - probably a majority of the population would benefit.
The FDA's current recommendations for vitamin K dosage is based solely on the
liver's requirements alone. It has been identified that a large percentage of
the enzymes that do not receive GCGA because of a vitamin K1 or K2 deficiency,
become unable to mobilize calcium and place it into the bone where it belongs.
This GCGA-deficient enzyme is known as undercarboxylated osteocalcin (ucOC).
It was found that this occurs in the majority of the healthy adult population
indicating subclinical vitamin deficiency in a large portion of the population.
3,4 Though this is subclinical in terms of obvious symptoms, the first symptoms
may be osteoporosis or acute coronary disease... the first symptom may even be
LifeSource Vitamins Vitamin K Products, Articles, and Studies: Click
The results of a vitamin K intervention study have been examined in which both
bone mineral density and vascular elasticity were shown to increase. 5 Other
studies have demonstrated consistent findings adding to the conclusion that
vitamin K1, and preferably, a good amount of vitamin K2, may just be some of the
best protection for preventing calcification of the arteries, and for
protection against osteoporosis.
Oral anticoagulant medications such
as Warfarin or Coumadin, etc., which are the most commonly used anticoagulants,
are vitamin K antagonists. Vitamin K may lessen the concentration of the anticoagulants.
Vitamin K: the overlooked bone builder and heart
by Dr. Susan E. Brown, PhD
At the Center for Better Bones, we
have long noted the trend towards increased arterial calcification with the use
of high-dose calcium supplementation when given without other key bone
nutrients. We propose that these trends are strongly related to vitamin K
status, particularly to the inadequacy of the menaquinone-7 (MK-7) form of vitamin
Vitamin K is essential for the
proper formation and full activation of the Gla proteins. The Gla protein osteocalcin,
when fully carboxylated by vitamin K, allows for the binding of calcium to the
bone matrix. The Gla protein known as matrix-Gla protein is found in
vascular smooth muscles. Matrix Gla protein is a key inhibitor of soft tissue
calcification that binds calcium, preventing it from depositing in the vessel
walls. Both GLA proteins are essential for proper calcium metabolism, and
neither can be fully activated without adequate vitamin K.
These assertions are supported by a
wide range of clinical data; for example:
- It is well known that vitamin K antagonists such as
warfarin double arterial calcification in humans.
- The decade-long, 4800-person Rotterdam study documented
that people who consumed the most vitamin K2 have a 50% reduced risk of arterial calcification. They also exhibited a 50% reduced risk for cardiovascular events during this 10 year period.
- In 2009, a 16,000-person study by Gast and colleagues
showed that a high intake of natural vitamin K2, but not vitamin K1,
protected from cardiovascular disease. This study reported that for every
10 mcg vitamin K2 consumed, the risk of coronary heart disease was reduced by 9%.
- A recent animal study by Schurgers and colleagues
(2006) showed regression of warfarin-induced arterial calcification when
given adequate supplemental doses of vitamin K2.
As it appears vitamin K, and vitamin
K2 as MK-7, in particular, plays an important role in keeping calcium in the
bones and out of the arteries. Hopefully, as we cast a broader net of
understanding, clinical bone trials will include analysis of vitamin K status
along with calcium intake evaluation.
LifeSource Vitamins - Vitamin K2, 90 chewable tablets, Most
Biologically Active Form of K-2, Supports Bone Health, Has Been shown to
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An excellent history and review of Vitamin K is offered in a number of
scientific papers - one being Vitamin K1 supplementation retards bone loss in
postmenopausal women between 50 and 60 years of age by Braam, Knapen, Geusens,
Brouns, Hamulyak, Gerichhausen, and Vermeer, epub 2003. See below for more
In 1984 it was found that patients with osteoporotic fractures had circulating
vitamin K levels which were over 70% lower than those in the control group. 6
The data was consistent with other studies show ing that low serum vitamin K is
associated with low mineral density, which is a high risk factor for bone
In analyzing British and American populations, it was found that they did not
meet the RDA levels of 1.5 micrograms per day per kg of body weight (10-12) and
that low intake is associated with low bone mineral density which is associated
with risk of bone fracture.
In the Nurses Health Study, over 72,000 women between 38 and 63 years of age
were followed for 10 years. The risk of fracture in the lower quintile for
vitamin K intake almost doubled that in the higher quintile. 13
In the Framingham study of an older group of patients, with an average age of
75 years, the results were more dramatic. 14 Subjects in the highest quartile
for vitamin K intake had a significantly lower hip fracture risk. 15
Hence the critical involvement of vitamin K in bone health and its general
deficiency in our population is firmly established.
Vitamin K Supplementation Retards Postmenopausal Bone Loss
In the Maastricht osteo study, 188 postmenopausal women between 50 and 60 years
old were treated for 3 years with daily supplements. 16 There was a placebo
group which received only maltodextrin and the second group received minerals,
500 mg/day of calcium, 150 mg/day of magnesium, 10 mg/day of zinc and 320
IU/day of vitamin D3. The third group received these minerals plus the vitamin
D3 and l mg/day of vitamin K1. The group without vitamin K benefited only
transiently. In the group with vitamin K, bone loss at the femoral neck was
retarded by 35%-40% compared to the other mineral vitamin D group. It is stated
that if these effects continued over decades, lifelong supplementation could
postpone fractures by up to 10 years.
Further research of the D-Bavis study using calcium (1000 mg), vitamin D (10
ug) and vitamin K (200 mcg) per day, supported the previous findings. They also
found a significant increase in bone mineral content and density in the vitamin
K group. 17
The authors concluded that combined supplementation with vitamin K1 and D3 at
dietary relevant levels improved bone mass density at the trabecular bone site
and that the equivalent supplementation in high osteoporotic risk groups may be
beneficial. Extremely high doses 45-90 mg/day of vitamin K2 are successfully
used in the treatment of osteoporosis in Japan. 18-20 These doses of K2 exceed
RDA levels by 1000 fold and no side effects were noted.
Low Vitamin K Intake as a Risk Factor for Cardiovascular Disease
256 postmenopausal women were studied by Jie, et. al. in the EPOZ study. They
found an inverse correlation between long term vitamin K intake and
arterosclerotic aorta calcification. 21 Only vitamin K1 (phylloquinone) was
included in the study.
A subsequent study of 4500 participants of the Rotterdam study by Gelejinse,
et. al. reports a much stronger negative correlation between long term, lower
than adequate intake of vitamin K2 (menaquinone) and aortic calcification. The
data was stronger for K2 than for K1. This is consistent with the suggestion of
preferential uptake of K2 by the vessel wall. 22
Vitamin K Supplementation Prevents Age Related Vascular Stiffening
In an animal study in rabbits with high cholesterol, vitamin K2 was shown to
decrease circulating cholesterol concentrations, suppress progression of
vascular plaque, thickening in the vessels, and pulmonary atherosclerosis. 23
In a study of rats on arterial calcification, vitamin K2 completely prevented
calcification, whereas vitamin K1 had little effect. 24 A three year study
involving postmenopausal women (a group which is generally known to be at risk
for vascular illness), the elastic properties of the carotid artery were
recorded using ultrasound. A supplement of 1 mg/day of vitamin K1 completely
abolished age-related arterial stiffening, whereas the placebo group showed a
decrease of 13% of elastic properties of the vasculature during the test
Dietary & Supplemental Forms of Vitamin K1 & K2
Most of our dietary vitamin K1 comes from vegetables - about 80%. Vitamin K2 is
obtained mainly from the "good" bacteria produced in the digestive
tract and is also found in certain fermented foods. 26 The absorbability of the
vitamin K2 from the GI tract bacteria is uncertain. 27 The absorption of
vitamin K1 from vegetables is about 10%.
"However, both K1 and K2 are well absorbed from supplements as long as
they are taken with some dietary fat to stimulate bile secretion." 28
Recommendations of a European Expert Group
In November 2002, a number of European experts in the fields of vitamin K
research, bone metabolism and cardiovascular disease met to review all the
available scientific data to formulate an opinion on the amount of recommended
dietary vitamin K and the use of vitamin K-containing supplements, for optimal
bone and vascular health. Some of the conclusions from this meeting are
Daily intake of between 200 and 500 mcg/day of vitamin K through food sources
may be required for optimal health.
Accumulating evidence suggests there is a synergistic effect between vitamins
K, D and calcium (and of course, magnesium). Optimal health effects may be
obtained from combined supplementation of vitamins K, D and minerals.
Any risks associated with high consumption of either vitamin K1 or K2 appear
minimal, with intakes up to 1 mg/day of vitamin K1 and 45 mg/day of vitamin K2,
often having been used with no observed side effects.
The only potential problem with high levels of vitamin K supplementation
relates to interference with oral anticoagulant medications such as Warfarin
and Coumadin, which are antagonists of vitamin K. Patients on oral
anticoagulant treatment should not use vitamin K supplements and avoid strong
fluctuations in their daily dietary vitamin K intake. However, in a systematic
dose-response study of patients on oral anticoagulant therapy, it was
demonstrated that the stability of anticoagulation was not significantly
affected by vitamin K supplementation at doses below 150 mcg/day. 30 Patients
on anticoagulant medications should consult with their physician or healthcare
practitioner regarding vitamin K.
Other Benefits of Vitamin K
We have discussed the beneficial effects of vitamin K on bone density,
cardiovascular health, and the Syndrome X diseases, however, there are even
more benefits to vitamin K supplementation.
Further research has demonstrated vitamin K's anti-inflammatory action. As the
body ages, levels of the inflammation-promoting cytokine interleukin-6 (IL-6)
increase. Once IL-6 becomes out of ba lance with the other cytokines,
inflammation accelerates. It has been observed that people with arthritis,
Alzheimer's disease, and atherosclerosis have higher levels of IL-6. In a study
done by the National Research Institute in Italy, it was shown that subjects
with the highest levels of IL-6 were almost twice as likely to develop
The second highest concentration of vitamin K in the body is in the pancreas,
which plays a major role in blood sugar and insulin regulation. In animal
studies, Japanese researchers found that when they induced vitamin K
deficiency, the test animals developed Type II diabetes. 31
Research has indicated that vitamin K has antioxidant activity comparable to
vitamin E and CoQ10. 32,33 Animal studies have demonstrated complete hepatic
(liver) protection from induced oxida tive stress using vitamin K, and was
found to be 80% as effective as vitamin E in preventing oxidation.
About 25% of the population have a genetic predisposition for developing
Alzheimer's disease - they carry the E4 form of the lipoprotein apoE.
Interestingly, people who carry this gene have been found to have low levels of
vitamin K. Calcification and the development of lesions in blood vessels that
feed the brain tissues are believed to be a component of Alzheimer's
development. Further research may reveal high-dose vitamin K therapy to be
Japanese Study on Vitamin K2 & Viral Cirrhosis-Related Liver Cancer
Japanese researchers have recently discovered that vitamin K2 may play a
significant role in prevention of liver cancer caused by viral cirrhosis. In a
2004 study published in the Journal of the American Medical Association, 40
women diagnosed with viral liver cirrhosis were studied, in which 21 were given
45 mg vitamin K2 per day. Vitamin K2 was found to decrease the risk of the
development of liver cancer in female patients with viral cirrhosis, possibly
by delaying the onset of the cancer. 34 For over seven years, the patient's
progress was closely followed. The proportion of patients who developed liver
cancer was significantly smaller in the group of women treated with the vitamin
K2 (2 of 21), compared to the non-treated group (9 of 19). The annual incidence
of liver cancer in the treated group was 1.6%, compared to the non-treated
group, which was 8.8%. The researchers believe that a substance called
geranyl-geraniol (a by-product of vitamin K2), induces cell death in tumor
cells suggesting that it may play an important role in cell growth inhibition.
The researchers wrote, "The study indicates that vitamin K2 decreases the
risk of liver cancer to about 20% compared to the control group." The
researchers also commented that these are only preliminary results and further
research needs to be done through clinical trials.
Vitamin K2 References:
1. Schurgers LJ, Vermeer C. Differential lipoprotein transport pathways of
K-vitamins in healthy subjects. Biochim Biophys Acta. 2002 Feb
2. Kelleys Textbook of Internal Medicine, Fourth Edition, 2000, Lippincott,
Williams and Wilkins, Philadelphia, PA.
3. Knapen MH, Jie KS, Hamulyak K, Vermeer C. Vitamin K-induced changes in
markers for osteoblast activity and urinary calcium loss. Calcif Tissue Int.
4. Booth SL, Sokoll LJ, O'Brien ME, Tucker K, Dawson-Hughes B, Sadowski JA.
Assessment of dietary phylloquinone intake and vitamin K status in
postmenopausal women. Eur J Clin Nutr. 1995 Nov;49(11):832-41.
5. Vermeer C, Braam L, Schurgers L, Brouns F. Agro-Food Industry Hi-Tech 2002,
6. Hart JP, Catterall A, Dodds RA, Klenerman L, Shearer MJ, Bitensky L, Chayen
J. Lancet ii 283 (1984).
7. Hart JP, Shearer MJ, Klenerman L, Catterall A, Reeve J, Sambrook PN, Dodds
RA, Bitensky L, Chayen J. Electrochemical detection of depressed circulating
levels of vitamin K1 in osteoporosis. J Clin Endocrinol Metab. 1985
8. Hodges SJ, Pilkington MJ, Stamp TC, Catterall A, Shearer MJ, Bitensky L,
Chayen J. Depressed levels of circulating menaquinones in patients with
osteoporotic fractures of the spine and femoral neck. Bone. 1991;12(6):387-9.
9. Hodges SJ, Akesson K, Vergnaud P, Obrant K, Delmas PD. Circulating levels of
vitamins K1 and K2 decreased in elderly women with hip fracture. J Bone Miner
Res. 1993 Oct;8(10):1241-5.
10. Booth SL, Pennington JA, Sadowski JA. Food sources and dietary intakes of
vitamin K-1 (phylloquinone) in the American diet: data from the FDA Total Diet
Study. J Am Diet Assoc. 1996 Feb;96(2):149-54.
11. Booth SL, Suttie JW. Dietary intake and adequacy of vitamin K. J Nutr. 1998
12. Thane CW, Paul AA, Bates CJ, Bolton-Smith C, Prentice A, Shearer MJ. Intake
and sources of phylloquinone (vitamin K1): variation with socio-demographic and
lifestyle factors in a national sample of British elderly people. Br J Nutr.
13. 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
14. Booth SL, Broe KE, Gagnon DR, Tucker KL, Hannan MT, McLean RR,
Dawson-Hughes B, Wilson PW, Cupples LA, Kiel DP. Vitamin K intake and bone
mineral density in women and men. Am J Clin Nutr. 2003 Feb;77(2):512-6.
15. Booth SL, Tucker KL, Chen H, Hannan MT, Gagnon DR, Cupples LA, Wilson PW,
Ordovas J, Schaefer EJ, Dawson-Hughes B, Kiel DP. 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 May;71(5):1201-8.
16. Braam LAJLM, Knapen MHJ, Geusens P, Brouns F, Hamulyak K, Gerichhausen MJW,
Vermeer C. Vitamin K1 supplementation retards bone loss in postmenopausal women
between 50 and 60 years of age. Calcif. Tissue Int. 72, epub (2003).
17. Bolton-Smith C, Mole PA, McMurdo MET, Paterson CR, Shearer MJ. Ann. Nutr.
Metab. 45 Suppl. 1 246 (2001).
18. Orimo H, Shiraki M, Tomita A, Morii H, Fujita T, Ohata M. J. Bone Miner.
Metab. 16:106-112, 1998.
19. Shiraki M, 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.
20. Iwamoto J, Takeda T, Ichimura S. Effect of menatetrenone on bone mineral
density and incidence of vertebral fractures in postmenopausal women with
osteoporosis: a comparison with the effect of etidronate. J Orthop Sci.
21. Jie KS, Bots ML, Vermeer C, Witteman JC, Grobbee DE. Vitamin K intake and
osteocalcin levels in women with and without aortic atherosclerosis: a
population-based study. Atherosclerosis. 1995 Jul;116(1):117-23.
22. Geleijnse JM, Vermeer C, Schurgers LJ, Grobbee DE, Pols HAP, Witteman JCM.
Thromb. Haemostas. (Suppl July) P473, 2001.
23. Kawashima H, Nakajima Y, Matubara Y, Nakanowatari J, Fukuta T, Mizuno S,
Takahashi S, Tajima T, Nakamura T. Effects of vitamin K2 (menatetrenone) on
atherosclerosis and blood coagulation in hypercholesterolemic rabbits. Jpn J
Pharmacol. 1997 Oct;75(2):135-43.
24. 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.
25. Braam LAJLM. Thesis, Maastricht ISBN 90-5681-145-2, 2002.
26. Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in
food. Effect of food matrix on circulating vitamin K concentrations.
Haemostasis. 2000 Nov-Dec;30(6):298-307.
27. Ronden JE, Drittij-Reijnders MJ, Vermeer C, Thijssen HH. Intestinal flora
is not an intermediate in the phylloquinone-menaquinone-4 conversion in the
rat. Biochim Biophys Acta. 1998 Jan 8;1379(1):69-75.
28. Vermeer C, Braam L, Knapen M and Schurgers L; Vitamin K supplementation: a
simple way to improve vascular health. Agr Food Industry hi Tech Nov 2003.
29. Vermeer C, Shearer MJ, Zittermann A, Bolton-Smith C, Szulc P, Hodges S,
Walter P, Rambeck W, Stocklin E, Weber P. Beyond deficiency: potential benefits
of increased intakes of vitamin K for bone and vascular health. Eur J Nutr.
2004 Dec;43(6):325-35. Epub 2004 Feb 5.
30. Schurgers LJ. Thesis, Maastricht ISBN 90-5681-138-X, 2002.
31. Sakamoto N, Wakabayashi I, Sakamoto K. Low vitamin K intake effects on
glucose tolerance in rats. Int J Vitam Nutr Res. 1999 Jan;69(1):27-31.
32. Mukai K, Itoh S, Morimoto H. Stopped-flow kinetic study of vitamin E
regeneration reaction with biological hydroquinones (reduced forms of
ubiquinone, vitamin K, and tocopherolquinone) in solution. J Biol Chem. 1992
33. Mukai K, Morimoto H, Kikuchi S, Nagaoka S. Kinetic study of
free-radical-scavenging action of biological hydroquinones (reduced forms of
ubiquinone, vitamin K and tocopherol quinone) in solution. Biochim Biophys
Acta. 1993 Jul 11;1157(3):313-7.
34. Habu D, Shiomi S, Tamori A, Takeda T, Tanaka T, Kubo S, Nishiguchi S. Role
of vitamin K2 in the development of hepatocellular carcinoma in women with
viral cirrhosis of the liver. JAMA, 2004 Jul 21;292(3):358-61.
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Vitamin K2, 90 VCaps, Most Biologically Active Form of K-2, Supports Bone Health, Healthy Cardiovascular System, Heart Health, Skin Health, and Anti-Aging, Tooth Remineralization, Reduces Varicose Veins, Brain Health, Helps to Synthesis other Nutrients, Vegetarian Formula.