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There is strong new evidence supporting
Vitamin K2, making it an ingredient with
untapped potential with applications in bone and cardivascular
Also supporting evidence of its antioxidant properties:
Vitamin K2 provides major protection from osteoporosis, cardiovascular
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
of soft tissues.
Vitamin K: Its Relationship to the Optimal Tissue
Distribution and Function of
It has been shown that calcium has a ubiquitous
role in health, impacting on
essentially all the Syndrome X conditions and diseases, which
blood pressure disorders, cardiovascular disease, diabetes, and
of cell signaling. Calcification of the arteries is a major known
of aging, as is the calcification of soft tissues and the accumulation
calcium intracellularly (within the cells).
Optimum calcium nutrition depends on the interplay
of a number of related
compounds, such as magnesium, vitamin D3, and vitamin K. Just
importance of vitamin K in regulating the healthy function of
calcium has been
recognized. It has been shown that vitamin K2 can be supplemented
in very high
doses, as used in Japan. It has been found to be safe even at
45 mg or more per
day - up to a thousand times greater than generally occurring
in the daily diet.
Even small amounts of vitamins K1 & K2, as we will see, can
have a great impact
on overall health.
Vitamin K1 and more importantly, vitamin K2,
play critical roles in preventing
arterial calcification, which is a risk factor in coronary artery
well as other calcification conditions associated with aging.
Vitamin K is actually a group name for related
compounds, which all have a
similar molecular structure (methylated naphthoquinone ring structure).
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
bacteria, aka "good bacteria," from the GI tract. The
body can store about a
one-month supply of the vitamin. Antibiotics interfere with the
healthy intestinal bacteria and as a result, impair vitamin K
prescription anticoagulant Warfarin also interferes with the
function of vitamin K by inhibiting critical enzymes that are
involved with the
production of coagulation factors. Without these coagulation
bleeding can occur.
How this vitamin is involved in blood coagulation
eluded scientists until 1974,
when a requirement for vitamin K was shown for the formation
proteins in the body known as gamma-carboxy glutamic acid (GCGA)
These proteins, when modified, specifically bind to calcium which
for blood coagulation, as well as other critical processes, and
calcium regulation affects cartilage, bone, protein in blood,
importantly, regulates the calcium in the cardiovascular system.
that the extra carboxyl group binds calcium so that it can be
What Are GCGA Proteins?
Vitamin K works by acting as a cofactor in the
carboxylation (adding of a
carboxyl group C02) via an enzyme (gamma glutamyl carboxylase),
acid (a specific amino acid) to form a modification of that amino
carboxyglutamic acid) in a variety of critical plasma proteins.
step, these plasma proteins will not function in their role of
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
the GCGA protein containing blood coagulation factors are synthesized
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
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.
uptake from the liver is much greater for K1 than for other tissues.
important recent findings indicate that vitamin K2, and not K1
Warfarin-induced arterial calcification. This research is important
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
for bone, and the special requirements for the cardiovascular
cartilage may not be met even though normal clotting factor production
as this occurs in the liver. Therefore, the requirement to keep
clear of accumulating calcium and to keep the bones well supplied
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
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
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 under-carboxylated osteocalcin
It was found that this occurs in the majority of the healthy
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
The results of a vitamin K intervention study
have been examined in which both
bone mineral density and vascular elasticity were shown to increase.
studies have demonstrated consistent findings adding to the conclusion
vitamin K1, and preferably, a good amount of vitamin K2, may
be some of the
best protection for preventing calcification of the arteries,
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.
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,
Brouns, Hamulyak, Gerichhausen, and Vermeer, epub 2003. See below
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
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
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
vitamin K intake almost doubled that in the higher quintile.
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
vitamin K intake had a significantly lower hip fracture risk.
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
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
transiently. In the group with vitamin K, bone loss at the femoral
retarded by 35%-40% compared to the other mineral vitamin D group.
It is stated
that if these effects continued over decades, lifelong supplementation
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.
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
and that the equivalent supplementation in high osteoporotic
risk groups may be
beneficial. Extremely high doses 45-90 mg/day of vitamin K2 are
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
arterosclerotic aorta calcification. 21 Only vitamin K1 (phylloquinone)
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.
was stronger for K2 than for K1. This is consistent with the
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
vascular plaque, thickening in the vessels, and pulmonary atherosclerosis.
In a study of rats on arterial calcification, vitamin K2 completely
calcification, whereas vitamin K1 had little effect. 24 A three
involving postmenopausal women (a group which is generally known
to be at risk
for vascular illness), the elastic properties of the carotid
recorded using ultrasound. A supplement of 1 mg/day of vitamin
abolished age-related arterial stiffening, whereas the placebo
group showed a
decrease of 13% of elastic properties of the vasculature during
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
available scientific data to formulate an opinion on the amount
dietary vitamin K and the use of vitamin K-containing supplements,
bone and vascular health. Some of the conclusions from this meeting
Daily intake of between 200 and 500 mcg/day of vitamin K through
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
to interference with oral anticoagulant medications such as Warfarin
Coumadin, which are antagonists of vitamin K. Patients on oral
treatment should not use vitamin K supplements and avoid strong
their daily dietary vitamin K intake. However, in a systematic
study of patients on oral anticoagulant therapy, it was demonstrated
stability of anticoagulation was not significantly affected by
supplementation at doses below 150 mcg/day. 30 Patients on anticoagulant
medications should consult with their physician or healthcare
regarding vitamin K.
Other Benefits of Vitamin K
We have discussed the beneficial effects of vitamin K on bone
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
increase. Once IL-6 becomes out of ba lance with the other cytokines,
inflammation accelerates. It has been observed that people with
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
with the highest levels of IL-6 were almost twice as likely to
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.
studies, Japanese researchers found that when they induced vitamin
deficiency, the test animals developed Type II diabetes. 31
Research has indicated that vitamin K has antioxidant activity
vitamin E and CoQ10. 32,33 Animal studies have demonstrated complete
(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
Alzheimer's disease - they carry the E4 form of the lipoprotein
Interestingly, people who carry this gene have been found to
have low levels of
vitamin K. Calcification and the development of lesions in blood
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,
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,
by delaying the onset of the cancer. 34 For over seven years,
progress was closely followed. The proportion of patients who
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
of liver cancer in the treated group was 1.6%, compared to the
group, which was 8.8%. The researchers believe that a substance
geranyl-geraniol (a by-product of vitamin K2), induces cell death
cells suggesting that it may play an important role in cell growth
The researchers wrote, "The study indicates that vitamin
K2 decreases the risk
of liver cancer to about 20% compared to the control group." The
also commented that these are only preliminary results and further
needs to be done through clinical trials.
Vitamin K2 References:
1. Schurgers LJ, Vermeer C. Differential lipoprotein transport
K-vitamins in healthy subjects. Biochim Biophys Acta. 2002 Feb
2. Kelleys Textbook of Internal Medicine, Fourth Edition, 2000,
Williams and Wilkins, Philadelphia, PA.
3. Knapen MH, Jie KS, Hamulyak K, Vermeer C. Vitamin K-induced
markers for osteoblast activity and urinary calcium loss. Calcif
4. Booth SL, Sokoll LJ, O'Brien ME, Tucker K, Dawson-Hughes
B, Sadowski JA.
Assessment of dietary phylloquinone intake and vitamin K status
postmenopausal women. Eur J Clin Nutr. 1995 Nov;49(11):832-41.
5. Vermeer C, Braam L, Schurgers L, Brouns F. Agro-Food Industry
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
RA, Bitensky L, Chayen J. Electrochemical detection of depressed
levels of vitamin K1 in osteoporosis. J Clin Endocrinol Metab.
8. Hodges SJ, Pilkington MJ, Stamp TC, Catterall A, Shearer
MJ, Bitensky L,
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osteoporotic fractures of the spine and femoral neck. Bone. 1991;12(6):387-9.
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vitamins K1 and K2 decreased in elderly women with hip fracture.
J Bone Miner
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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
lifestyle factors in a national sample of British elderly people.
Br J Nutr.
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GA. Vitamin K
intake and hip fractures in women: a prospective study. Am J
Clin Nutr. 1999
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B, Wilson PW, Cupples LA, Kiel DP. Vitamin K intake and bone
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LA, Wilson PW,
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K intakes are
associated with hip fracture but not with bone mineral density
in elderly men
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Vermeer C. Vitamin K1 supplementation retards bone loss in postmenopausal
between 50 and 60 years of age. Calcif. Tissue Int. 72, epub
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Metab. 45 Suppl. 1 246 (2001).
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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
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
osteoporosis: a comparison with the effect of etidronate. J Orthop
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K intake and
osteocalcin levels in women with and without aortic atherosclerosis:
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HAP, Witteman JCM.
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T, Mizuno S,
Takahashi S, Tajima T, Nakamura T. Effects of vitamin K2 (menatetrenone)
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24. Spronk HM, Soute BA, Schurgers LJ, Thijssen HH, De Mey JG,
Tissue-specific utilization of menaquinone-4 results in the prevention
arterial calcification in warfarin-treated rats. J Vasc Res.
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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.
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simple way to improve vascular health. Agr Food Industry hi Tech
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P, Hodges S,
Walter P, Rambeck W, Stocklin E, Weber P. Beyond deficiency:
of increased intakes of vitamin K for bone and vascular health.
Eur J Nutr. 2004
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30. Schurgers LJ. Thesis, Maastricht ISBN 90-5681-138-X, 2002.
31. Sakamoto N, Wakabayashi I, Sakamoto K. Low vitamin K intake
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
ubiquinone, vitamin K, and tocopherolquinone) in solution. J
Biol Chem. 1992
33. Mukai K, Morimoto H, Kikuchi S, Nagaoka S. Kinetic study
free-radical-scavenging action of biological hydroquinones (reduced
ubiquinone, vitamin K and tocopherol quinone) in solution. Biochim
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.