Vitamin K2 and the calcium connection

Vitamin K2 and the calcium connection.

Inadequate calcium intake can lead to decreased bone
mineral density, which can increase the risk of bone fractures.
Supplemental calcium promotes bone mineral density and
strength and can prevent osteoporosis (i.e., porous bones),
particularly in elderly and postmenopausal women.1, 2 However,
recent scientific evidence suggests that elevated calcium
consumption accelerates calcium deposits in blood vessel
walls and soft tissues, which may raise the risk for heart
disease3-8 (see Table 1-2 and Figure 1).
In contrast, vitamin K2 has been shown to prevent arterial
calcification and arterial stiffening9, 10, which means increased
vitamin K2 amounts in the body could be a means of lowering
calcium-associated health risks. With the human diet lacking
vitamin K2, taking vitamin K2 supplements is one way to secure
adequate intake. By striking the right balance between calcium
and vitamin K2 intake, it may be possible to fight osteoporosis
and at the same time prevent the calcification and stiffening of
the arteries. A new clinical study pending publication with vitamin
K2 supplementation showed an improvement in arterial elasticity
and regression in age-related arterial stiffening (data pending
publication).50 Most important, vitamin K2 could optimize calcium
utilization in the body preventing any potential negative health
impacts associated with increased calcium intake.
Approximately 43% of the U.S. population and 70% of older
women regularly take calcium supplements.11, 12 Calcium
supplementation is supported by several studies backing its
benefits for bone health and osteoporosis prevention, as well as for
overall health (see Table 1).
Eighty-four years ago while investigating the effects of a low-fat diet
fed to chickens, Danish scientist Henrik Dam discovered vitamin K.
He found that bleeding tendencies in chickens could be prevented
when a regular fat diet was restored and vitamin K was added to
their diet. From this point forward, vitamin K became known as
Vitamin K2 and the calcium connection


the coagulation vitamin – the “K” coming from the German word
“Koagulation” (see Table 3).29
Later it was found that this fat-soluble compound needed for
blood clotting exists in two forms: phylloquinone (vitamin K1) and
menaquinone (vitamin K2) (see Figure 2).30 Vitamin K1 is made in
plants and algae – green leafy vegetables are a particularly rich
source of it. On the other hand, bacteria generate vitamin K2,
which can also be found in meat, dairy, eggs and fermented foods
such as cheese, yogurt and natto (a Japanese dish of fermented
soybeans).31, 32
Even though the side chains of isoprenoid units of vitamin K differ
in length from 1 to 14 repeats, they are all used by the enzyme
γ-glutamate carboxylase to activate a specific set of proteins,
including proteins involved in blood coagulation, bone formation
and inhibition of soft tissue calcification. Vitamin K (K1 and K2)
is essential in maintaining blood homeostasis and optimal bone
and heart health through the role it plays in inducing calcium use
by proteins. Vitamin K, particularly vitamin K2, is essential for
calcium utilization, helping build strong bones and inhibit arterial
Bone structure is secured by two type of cells – osteoblasts
which build bones and osteoclasts which remodel bones (see
Figure 2). Osteoblasts produce the protein osteocalcin, which
needs to be activated by vitamin K2 to bind calcium to the
bone’s mineral matrix, thereby strengthening the skeleton

If there is a lack of vitamin K2 over a long period of time, then
calcium will not be integrated into the bone and poor bone quality
will result. Populations that consume enough vitamin K2 have
stronger, healthier bones. The Western diet, however, does not
contain sufficient vitamin K2 leaving many people vitamin K2-
deficient.34, 35
Children in particular need more vitamin K2 since they have a
much higher bone metabolism than adults. From the late 20s to
mid-30s peak bone mass is reached, after which bone mineral
content slowly diminishes. Thus, the higher the peak bone mass
attained at a younger age, the longer the bone mass can be
preserved (see Figure 3).
Population-based studies and clinical trials have linked higher
blood vitamin K2 concentrations to stronger bones. Further,
studies in adults have revealed that vitamin K2 supplementation
helps promote bone health and maintain bone mineral density.36-38
A study in children also showed that improving vitamin K2 intake
over a two-year period led to stronger and denser bones.39
The recent double-blind, randomized clinical trial
investigated the effect of supplemental MK-7 (MenaQ7®)
over three years in a group of 244 post-menopausal Dutch
women.49 Researchers found that a daily dose of 180 mcg
was enough to improve bone mineral density, bone strength
and cardiovascular health. They also showed that achieving a
clinically relevant improvement required at least two years of
Adequate intake of vitamin K2 has been shown to lower
the risk of vascular damage because it activates Matrix Gla
Protein (MGP), which inhibits calcium from depositing in the
vessel walls (arterial calcification).
Hence, calcium is available for other multiple roles in the body,
leaving the arteries healthy and flexible.43 However, vitamin K
deficiency results in inadequate activation of MGP, which
greatly impairs the calcium removal process and increases the
risk of blood vessel calcification.44 Since this process occurs in
the vessel wall, it leads to the wall thickening via calcified plaques
(i.e., typical atherosclerosis progression), which is associated with
higher risk of cardiovascular events.
The population-based Rotterdam study evaluated 4807 healthy
men and women over age 55 and the relationship between dietary
intake of vitamin K and aortic calcification, heart disease and allcause
mortality.10 The study revealed that high dietary intake of
vitamin K2 (at least 32 mcg per day) and not vitamin K1, reduced
arterial calcification by 50%, cardiovascular death by 50%, and
all-cause mortality by 25% (see Figure 4).
These findings were supported by another population-based
study with 16,000 healthy women (aged 49-70) from the Prospect-
EPIC cohort population.45
After eight years, the data showed that high intake of
natural vitamin K2, but not vitamin K1, helps protect against
cardiovascular events; for every 10 mcg of vitamin K2 (in the forms
of MK-7, MK-8 and MK-9) consumed, the risk of coronary heart
disease was reduced by 9%. A study on 564 post-menopausal
women also revealed that vitamin K2 intake decreases coronary
calcification, whereas vitamin K1 does not.9
A study pending publication on 244 postmenopausal women
supplemented with 180 mcg of vitamin K2 as MK-7 actually
showed a significant improvement in cardiovascular health as
measured by ultra-sound and pulse-wave velocity, which are
recognized standard measurements for cardiovascular health. In
this trial, carotid artery distensibility (i.e., elasticity) – the ability for
a blood vessel to stretch or dilate – was significantly improved
over a three- year period as compared to the placebo group. Also,
pulse-wave velocity was significantly decreased in the vitamin
K2 (MK-7) group, but not the placebo group, demonstrating an
increase in the elasticity and reduction in age-related arterial
The studies presented in Table 3 illustrate that high calcium
consumption helps strengthen the skeleton but at the same
time may increase the risk of heart disease due to arterial
calcification.3-8, 16
Dysfunctional calcium-regulatory proteins such as MGP
correlate with the development of arterial calcification. To render
these proteins active, a sufficient amount of vitamin K2 has to be
present in the body.46 If at least 32 mcg of vitamin K2 is present
in the diet, then the risk for blood vessel calcification and heart
problems is significantly lowered10 and elasticity of the vessel wall
is increased.47 On the contrary, if less vitamin K2 is present in the
diet, then cardiovascular problems may arise.
In general, the typical Western diet contains insufficient amounts
of vitamin K2 to adequately activate MGP, which means about
30% of vitamin K2-activated proteins remain inactive. This amount
only increases with age.
Vitamin K, especially as vitamin K2, is nearly non-existent in

“junk” food, and even in a healthy Western diet. The only exception
seems to be the Japanese diet, particularly in the portion of the
population consuming high quantities of vitamin k-rich foods, such
as natto (see Figure 5).
It appears that suboptimal vitamin K2 levels in the body may
disadvantage the vitamin K2-dependent activation of specific
proteins. If these proteins cannot perform their function by keeping
calcium in the bones and preventing calcium deposits in soft
tissues (e.g. arterial walls) during situations of increased calcium
intake, then general health – and in particular cardiovascular health
– may suffer due to an inefficient and misdirected utilization of
calcium in the body.
Dietary calcium is linked to many benefits, especially bone health.
This is why recommended daily intakes for calcium have been
established. Because diets often fall short of these guidelines, in
particular in individuals with higher needs (e.g. children, the elderly
and postmenopausal women), dietary supplementation can help
address the body’s demands. Although the study outcomes of high
calcium consumption are controversial, several studies do suggest

caution when it comes to over supplementing, especially since
some evidence points to health problems at elevated levels.3-8
This issue could be remedied, however, if the right amount
of vitamin K2 is added to a high calcium regimen. Vitamin
K2 promotes arterial flexibility by preventing arterial calcium
10, 43, 48, 50 which could correct the imbalance of calcium in
the body. Thus, calcium in tandem with vitamin K2 may well
be the solution for bringing necessary bone benefits while
circumventing an increased risk for heart disease.