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Vitamin K2
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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
health.
Also supporting evidence of its antioxidant properties:
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: Its Relationship to the Optimal Tissue
Distribution and Function of
Calcium
It has been shown that calcium has a ubiquitous
role in health, impacting on
essentially all the Syndrome X conditions and diseases, which
include obesity,
blood pressure disorders, cardiovascular disease, diabetes, and
malfunctioning
of cell signaling. Calcification of the arteries is a major known
consequence
of aging, as is the calcification of soft tissues and the accumulation
of
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
recently, the
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
disease, as
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
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 occur.
How this vitamin is involved in blood coagulation
eluded scientists until 1974,
when a requirement for vitamin K was shown for the formation
of numerous
proteins in the body known as gamma-carboxy glutamic acid (GCGA)
proteins.
These proteins, when modified, specifically bind to calcium which
is important
for blood coagulation, as well as other critical processes, and
through which
calcium regulation affects cartilage, bone, protein in blood,
and very
importantly, regulates the calcium in the cardiovascular system.
It appears
that the extra carboxyl group binds calcium so that it can be
moved around.
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),
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 under-carboxylated 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
death.
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
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.
Scientific Studies
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
study results:
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
fracture. 7-9
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
period. 25
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
summarized below:
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.
Anti-Inflammatory
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
mobility-related disabilities.
Diabetes
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
Antioxidant
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.
Alzheimer's
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
preventive.
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:
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pathways of
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2. Kelleys Textbook of Internal Medicine, Fourth Edition, 2000,
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23. Kawashima H, Nakajima Y, Matubara Y, Nakanowatari J, Fukuta
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in the rat.
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32. Mukai K, Itoh S, Morimoto H. Stopped-flow kinetic study
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regeneration reaction with biological hydroquinones (reduced
forms of
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