Home  Vitamins Natto K2, the Unique Vitamin K - New Benefits for Bone & Cardiovascular Health
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Natto K2, the Unique Vitamin K - New Benefits for Bone & Cardiovascular Health |
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New Benefits for Bone
& Cardiovascular Health
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by Dallas Clouatre, Ph.D. and Sid Shastri, M.Sc. |
 Is vitamin K, that is derived from natto fermented soybean food,
another Japanese secret for avoiding osteoporosis? Perhaps.
Here in the United States, the rate of osteoporosis is expected to
increase sharply after menopause. However, in Japan women typically
only begin to suffer from osteoporosis starting about age 65,
that is, a decade later than is true of American women. This is
despite the fact that in Japan most women consume less than 600
mg calcium per day, the Japanese recommended daily allowance
for that mineral. In the U.S. women routinely consume much more
calcium and are strongly urged to take in 1,000 or even 1,500 mg of
calcium per day.
Although much has been made of the consumption of soybean
isoflavones in Japan, similarly protective effects of soy are not
nearly so strong in South China, where yet more soy is consumed.
Moreover, even in soy-consuming Japan the benefits of natto stand
out. Study after study has found that a higher consumption of natto
is associated with a lower rate of osteoporosis and greater bone
mineral density (BMD) in both pre- and postmenopausal women. In
other words, with regard to bone health, natto is more than just soy.
Furthermore, natto’s benefits are not limited to improved bone
health. It has been shown in postmenopausal women that vitamin
K is important for preventing the calcification of soft tissues, such
as the walls of arteries. K2, as will be explained below, differs from K1
in part of its structure and belongs to the menaquinone family of
vitamin K analogs. Menaquinone-4 has been shown to be much
superior to K1 in preventing arterial calcification when tested in an
animal model. In a study conducted in Rotterdam involving over
4,000 participants, menaquinone-7, the K2 form found in natto,
showed dramatic results. Individuals with the highest K2 consumption
had 50 percent fewer heart attacks, 50 percent fewer cardiovascular
related deaths and 25 percent fewer deaths over all. The
Rotterdam findings show that humans supplementing with vitamin
K2 enjoy the benefits to bone and vascular health that continue to
be explored with recent animal model and cell culture research.
Different Forms of Vitamin K
Discovered in 1935, vitamin K was initially characterized by its role
as a clotting factor in blood. Little progress was made in further
determining the nature of this vitamin’s mechanisms of action until the mid-1960s. Today, vitamin K has
come a long way from its initial discovery
as a clotting factor and enjoys a renewed
interest in exploring its other biological
functions.
Vitamin K is a fat-soluble vitamin
found naturally in two primary forms,
both of which contain the 2-methyl-1,4-
napthoquinone moiety. This vitamin is
best known for its role in blood clotting
because it is essential for the formation
of prothrombin and at least five other
proteins that regulate clotting. In plants,
the vitamin appears as vitamin K1, also
called phylloquinone. This form is found
chiefly in green leafy vegetables, such as
spinach, salad greens and kale. The other
form, K2, is created by bacteria, such as
Bacillus subtilis in the case of natto, as
well as by the flora in the digestive tracts
of humans. It is found in meat, liver,
butter, egg yolk, natto, cheese and curd
cheese. This form is actually a family of
related compounds known as
menaquinones. One well-researched
menaquinone is menaquinone-4. (The
numeral following menaquinone indicates
the number of isoprenoid units.)
The K2 found in natto is menaquinone-7,
also written as MK7. Vitamin K is
absorbed from foods mostly in the
jejunum and ileum of the small intestine,
and only poorly from the colon. Current
opinion is that humans can convert phylloquinone
directly to menaquinone,
albeit inefficiently, without the intermediary
of gut bacteria.
The extent of absorption has been the
subject of debate, especially inasmuch as
assimilation is highly dependent upon
the normal flow of bile and pancreatic
juice. As is true of vitamin E and coenzyme
Q10, vitamin K is far better absorbed
when taken at meals containing fat. In
the case of vitamin K2, which is better
absorbed than K1, maximal absorption
requires that there be approximately 35
grams fat in the meal. A trial with K1 indicated
that there is little difference in
availability between different green vegetable
sources or between meals with
either 30 percent or 45 percent of their
energy derived from fat. However, supplemental
K1 in tablet form was more
available than the same amount derived
from food. It is thought that vegetable
sources of vitamin K exhibit inferior
bioavailability because of interactions of
the vitamin with chloroplast membranes.
Of considerable significance is the fact
that circulating K2 concentrations after
the consumption of natto are about 10
times higher than those of K1 after the
consumption of spinach.
Osteocalcin and Matrix Gla-Protein (MGP)
Much of the current excitement in
vitamin K research stems from findings
regarding two related proteins, osteocalcin
and matrix-Gla protein (MGP). The
importance of osteocalcin arises from its
link to the bone-forming cells known as
osteoblasts. Osteoblasts produce osteocalcin
in the process of forming bone.
Osteocalcin, however, has both active
and non- or non-fully-active forms.
Activation requires the process of carboxylation
(the introduction of a carboxyl
group, COOH), and vitamin K functions as
a cofactor for the enzyme that catalyzes
this carboxylation. Past research has
shown that natto K2 is effective in
increasing circulating carboxylated
osteocalcin.
According to a study reported earlier
this year, circulating under-carboxylated
osteocalcin (a marker for hip fracture
risk) was decreased much more by K2
(from natto) than by K1. The ratio
between carboxylated and under-carboxylated
osteocalcin was improved similarly
by both forms of vitamin K after six
weeks of supplementation, but whereas
no further improvements were appearing
with K1, K2 continued to reduce the
amount of under-carboxylated osteocalcin
in circulation. Researchers inferred
from their data that K2 not only supports
the bone-building actions of osteoblasts,
but also, and unlike K1, has a more substantial
impact in reducing the rate of
bone turnover. One possible reason for
the greater success of K2 is that K1
appears to collect in the liver, whereas K2
is more active in peripheral tissues. The
difference can be impressive. In a clinical
setting, K2 has been used to successfully
prevent bone loss, even when hormone
replace therapy had failed. K2 appears to
be quite successful in preventing new
fractures without necessarily increasing
bone mineral density.
Whereas osteocalcin is a regulator of
the use of calcium in the hard tissues,
matrix-Gla protein is largely active in the
soft tissues. It is a strong inhibitor of vascular
calcification. Just as osteocalcin
requires vitamin K-dependent carboxylation,
MGP contains .ve components that
are similarly vitamin K-dependent in formation
and function. Thus, peripheral
vitamin K deficiency will result in undercarboxylated,
inactive MGP and an increased risk of vascular calcification.
Researchers now argue that extrahepatic
tissues such as bone and vessel wall
require higher dietary intakes and have a
preference for menaquinone [i.e., K2]
rather than for phylloquinone. Moreover,
undercarboxylation of MGP is a risk factor
for vascular calci.cation and the present
RDA values are too low to ensure full carboxylation
of MGP. Indeed, K2, as long ago
as 1996, was shown to suppress soft
tissue calcification in animals and was
suggested as a treatment for arteriosclerosis
with calcification.
Other Benefits, Safety and Dosage Considerations
Curiously, although vitamin K is associated
with clotting, it is also a component
in anticoagulant proteins. Early animal
experiments with K2 demonstrated not
only its anticoagulant properties but also
reductions in total cholesterol and lipid
peroxidation. Japanese researchers, likewise,
have indicated that vitamin K may
play a role in blood sugar regulation.
Experiments utilizing vitamin K deficient
animals have shown striking differences
in the tissue uptake of K1 and K2.
For example, whereas K1 has been found
to accumulate in the heart and liver, K2
has been found in higher concentrations
in the pancreas, testis and blood vessel
walls. These findings suggest that K2 has
a regulatory function in the prevention of
vascular mineralization. Vascular mineralization
is a critical component in the
pathogenesis atherosclerotic calcification.
This point is corroborated by a
population-based study that showed a
strong inverse correlation between K2
intake and atherosclerotic calcification.
In other words, vitamin K2 showed
cardiovascular protective benefits.
The natural forms of vitamin K have
not been demonstrated to have toxicity
even when ingested at large dosages for
very extended periods of time. Expert
opinion is that chronic intakes of 10 to 45
mg/day are safe.
References available upon request. Send a SASE to totalhealth.
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