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Vitamin K2 for bone health Vitamin K2-A key factor for optimal bone health at all ages


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Vitamin K is important for optimal bone health throughout life as vitamin K is crucial for calcium regulation in the body. Osteocalcin, an important vitamin K-dependent protein, found in bone tissue binds calcium and ensures calcium is incorporated into bone. Vitamin K comprises a group of closely related fat-soluble vitamins. The most important naturally occurring forms of vitamin K are phylloquinone and menaquinones, also known as vitamin K1 and vitamin K2 (consisting of a group of menaquinones), respectively. Recent studies suggest that there is a vitamin K2 deficiency in the general population and that supplemental doses of menaquinone-7 (MK-7) (microgram doses), may result in improved bone health.
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Monographic special issue: DIETARY INGREDIENTS & SUPPLEMENTS - Agro FOOD Industry Hi Tech - vol 26(5) - July/August 2015
KEYWORDS: Vitamin K2, menaquinone-7, bone health, osteoporosis, osteocalcin, calcium.
Abstract Vitamin K is important for optimal bone health throughout life as vitamin K is crucial for calcium regulation
in the body. Osteocalcin, an important vitamin K-dependent protein, found in bone tissue binds calcium
and ensures calcium is incorporated into bone. Vitamin K comprises a group of closely related fat-soluble vitamins. The most
important naturally occurring forms of vitamin K are phylloquinone and menaquinones, also known as vitamin K1 and vitamin K2
(consisting of a group of menaquinones), respectively. Recent studies suggest that there is a vitamin K2 deficiency in the general
population and that supplemental doses of menaquinone-7 (MK-7) (microgram doses), may result in improved bone health.
Vitamin K2 for bone health
Vitamin K2 – A key factor for optimal bone health at all ages
Bone diseases present
large challenges for
Bone health is critically
important to overall
health and quality of
life. Healthy bones
provide the body with
the framework that
allows for mobility
and for protection
against injury. Bones
stores minerals such
as calcium which are
vital to the functioning
of for instance muscle
contraction, nerve
signaling and many
enzymatic reactions.
A major health challenge is the increasing number of people
with weak bones caused by osteopenia (lower than normal
bone mineral density (BMD)) and osteoporosis (a disease
state with low BMD). An estimated 75 million people in Europe,
USA and Japan have osteoporosis and three times as many
women are affected (1, 2) compared to men. TThere is a
clear, worldwide correlation between osteoporosis and
fractures, with lifetime risk of osteoporotic fractures in women
and men 30-50% and 15-30%, respectively (3). It has been
estimated that the fracture incidence is more than 2.3 million
cases annually in Europe and the US
alone (1).
Brittle bones and osteoporosis result in
a huge economic burden worldwide
with large implications for the individual
as well as for society.
The economic burden in the EU is
estimated to be € 37 billion, and this is
projected to increase, on an average,
by 25% in 2025 (4).
As such, just a small improvement in
bone health may have large positive
implications on public health budgets
and increase the longevity and quality
of life of individuals. The importance of
vitamin K for bone health, particularly
vitamin K1 and vitamin K2 (MK-4), has
been summarized in several review
papers (5-7). K2 MK-4 is approved
as a drug in Japan for treatment of
osteoporosis (dose; 45 mg/day, 3 X 15
mg/ day).This paper focuses speci cally on the documented
role of vitamin K2 MK-7, in supplement doses, in relation to
bone health and the bone building process.
The skeleton consists of bone (hydroxyapatite)
supplemented by ligaments, tendons, muscles and
Kappa Bioscience AS
Gaustadalléen 21, 0349 Oslo, Norway
Mona E. Møller
Figure 1. Osteopenia and osteoporosis are common in elderly
people. Bones are getting porous and brittle as we get older; the risk
of fractures increases with age (Zoaring 2014, © Kappa Bioscience).
Monographic special issue: DIETARY INGREDIENTS & SUPPLEMENTS - Agro FOOD Industry Hi Tech - vol 26(5) - July/August 2015
Japan is one of the
countries with ow
frequencies of bone-
and cardiovascular
diseases, especially
in certain regions
in the North (10). In
these Northern regions
the Japanese eat a
dish called natto -
fermented soybeans
which contain high
amounts of vitamin
K2, menaquinones-7
(MK-7). This food has
been used for hundreds of years and is approved as a
Health Food in Japan. Many Japanese epidemiological
studies have pointed to benecial effects of vitamin K2,
MK-7 for bone health (11, 12). In a large three-year study in
Japanese women it was demonstrated that intake of natto
resulted in increased BMD at the femoral neck (13). These
effects were attributed to intake of MK-7 in the natto food.
When the incidence of hip fractures in twelve regions in
Japan were an analysed and correlated to intake of the
key nutrients calcium, magnesium, vitamin D and vitamin
K, the strongest inverse correlation to fractures was found
to be intake of vitamin K, in particularly vitamin K2, MK-7,
both in men and women (10). Intake of natto food was
also inversely correlated with hip fractures in women (14).
Furthermore, natto intake was associated with improved
BMD in elderly men (15). Thus, several Japanese studies
demonstrate the benecial effects of MK-7 on bone
strength and for prevention of fractures. Furthermore, these
studies show that MK-7 is safe without any side effects.
The most widely
used supplements
to support bone
health are
calcium and
vitamin D3. Vitamin D3 increases the intestinal uptake of
calcium into the blood stream. To secure an optimal bone
building process, however, vitamin K is needed to activate
osteocalcin, allowing osteocalcin to bind calcium and
transport calcium from blood into the bone. Vitamin K,
vitamin D3 and calcium work in concert for building strong
bones: the “tri-essentials” for bone health (Figure 3).
The importance of vitamin K2 for bone health in healthy
subjects has been recently documented. In a large three
year placebo-controlled study of 244 postmenopausal
women with daily intake of 180 µg of MK-7, a statistically
signicant difference in bone quality parameters was
found between the MK-7 group and the control (16). It was
concluded that MK-7 preserves bone at Lumbar spine L1-L4
(both BMC and BMD).
cartilage. Calcium is an important building block in the
bone matrix. Bone building processes constantly ongoing
- in fact the entire skeleton is regenerated every seven
years. Bone build-up cells (osteoblasts) and break-
down cells (osteoclasts) regulate the strength of bones,
and when break-down cell activity dominates, the
skeleton becomes increasingly fragile. This may result in
development of osteoporosis.
In the cycle of bone remodeling, the osteoclasts remove
old or damaged bone (this removal is called bone
resorption. The removed bone constituents, including
calcium, are released into circulating blood. At the same
time the osteoblasts produce new bone (bone formation).
In this process, osteoblasts produce osteocalcin (OC), a
protein that, in its activated form, can bind calcium and
incorporate calcium into bones (8).
It is important throughout life to secure sufficient calcium
to maintain a healthy skeleton. Bone mass increases from
childhood until the early twenties, before beginning to
decline (Figure 2). From 30-40 years onwards, bone mass
gradually decreases in both men and women. This implies
that sufficient calcium intake is particularly important in
childhood/puberty and from age 35 onwards. Further,
the risk of broken bones increases with age and the
ability to recover decreases. Post-menopausal women
are particularly vulnerable for development of brittle
bones, leading to fractures.
Osteoporosis is to a large extent a preventable disease.
Several environmental factors, such as physical exercise
and diet (considered mainly to be attributed to sufficient
intake of calcium and vitamin D3), can strongly influence
our bone quality. Worldwide, the risk of osteoporotic
fracture can vary up to 10-fold, depending on country
of origin, with Caucasians having the greatest reported
risk (9). The fact that major risk factors for osteoporosis
are well known, but incidences are increasing worldwide,
suggests that important factor) for a good bone health
are being overlooked.
Figure 2. Bone mass as a function of age. During puberty: a large
increase in bone mass. From 50 years onwards: a strong decrease in
bone mass, particularly in females (© Kappa Bioscience).
Figure 3.
The “three
essentials” for
bone health:
vitamin D3 and
vitamin K. See
Knapen et al.
(© Kappa
Monographic special issue: DIETARY INGREDIENTS & SUPPLEMENTS - Agro FOOD Industry Hi Tech - vol 26(5) - July/August 2015
Vitamin K is a fat-soluble vitamin. Vitamin K comprises a
number of structurally related compounds including
phylloquinone (vitamin K1) and menaquinones (vitamin K2s).
Menaquinones are classied according to the length
of their side chains; menaquinone-4 (MK-4) and
menaquinone-7 (MK-7) being the most important.
Phylloquinone is found in green/leafy vegetables such
as green salads, broccoli and spinach. Vitamin K1 is
considered as the major dietary source of vitamin K,
accounting for approximately 90% of total vitamin K
intake (23). Based on different studies of content in food
worldwide, Suttie has estimated the intake of vitamin K in
the general population to be between 70 - 250 µg/day (24).
However, the bioavailability of vitamin K1 from food is low;
less than 20% is absorbed (25).
Vitamin K2, menaquinones, are found in animal products
such as meat, dairy, eggs (mainly MK-4) and fermented
food, e.g. cheese, yoghurt, and fermented soybean
products/natto (mainly MK-7).
( 23,26,27). In the Netherlands the
average intake of MK-4 and long-chain
menaquinones from eggs and cheese
has been reported to be in the range
of 7µg/day and 22µg/day, respectively
(28). Limited knowledge exists regarding
intake of longer menaquinones from
food in other European countries or the
US, though fermented cheeses may
be the most important source (23, 29).
However, the most efcacious vitamin
K, specically MK-7, is found to a very
low extent in these fermented products
(23). These factors likely lead to a
deciency of vitamin K2 intake in most
Several medical conditions and drug
treatments may result in vitamin K
deciency. For instance, treatment with
anti-coagulants (warfarin/coumarins)
that block the re-use of vitamin K in the so-called vitamin
K cycle result in low serum concentration of vitamin K. This
has been shown to affect bone health in both adults and
In young people aged 8.6 to 18.8 years that received
warfarin for more than 12 months, signicant reduction in
bone mineral density was observed. In another study, more
than 50% of pediatric patients on warfarin/coumarin were
reported to have osteopenia (30). Long–term treatment
with anti-inammatory drugs (corticosteroids) is another
example of drugs that have detrimental effects on bone
quality (31).
People with various diseases affecting intestinal absorption
of vitamin K (and other vitamins and minerals) such as
Furthermore, measured bone strength was preserved in the
treatment group.
This study demonstrates that benecial effects on bone
health can be obtained with supplement doses of vitamin
K2, MK-7 (180µg). Vitamin K1 and MK-4 are also used, but
this is documented to be sub-optimal, due to the very high
doses of vitamin K1 (1-5 mg) or MK-4 (45 mg) required.
(Reviews 5, 6, 7). Such dosages exceed the nutritional
vitamin guidelines, and the amount typically available in
dietary supplement tablets of 50 -100µg - far below what
is needed for vitamin K1 or MK-4 to have benecial effects
on bone parameters. Vitamins in high (mg) doses are often
classied as drugs; for example, MK-4 is registered as a drug
for treatment of osteoporosis in Japan and administered at
45mg/daily dose.
Osteocalcin (OC) is a non-collagenous protein primarily
expressed in osteoblasts involved in bone metabolism
and calcium binding. OC
is dependent on vitamin
K in order to carry out its
function of building calcium
into bone and is important
for bone mineralization and
calcium homeostasis (7).
Vitamin K is a co-factor for
the enzyme that activates
OC by carboxylation of the
protein at certain sites. In the
activated (carboxylated)
form, OC can bind calcium
and transport calcium into the
bone matrix (Figure 4). OC is a
so-called Gla-protein which is
dependent on vitamin K for its
function (all Gla-proteins use
vitamin K as cofactor for the
carboxylation step).
From bone, OC partly goes
into blood circulation and the
fraction of undercaboxylated-
osteocalcin (ucOC, inactive)
and carboxylated osteocalcin
(cOC) can be measured as
surrogate markers for vitamin
K status (17).
Individuals with low vitamin K2 intake have a larger fraction
of non-activated osteocalcin, resulting in reduced capacity
for calcium binding. High serum concentration of ucOC
is thus correlated with low BMD and is a predictor of hip
fracture risk (18-20). Since high ucOC concentration also is
a marker of vitamin K deciency, studies demonstrate the
pivotal role of sufcient intake of vitamin K for optimal bone
health. As may be expected, low serum concentration of
vitamin K, in particular vitamin K2, menaquinone-7 (MK-7), is
correlated with increased fracture incidence (21-22, 10).
In conclusion, ucOC is an important biomarker for bone
health; a high concentration of ucOC is a strong indicator
of vitamin K deciency and relates to low BMD and risk of
hip fractures.
Figure 4. Osteocalcin, OC, is activated by a vitamin
K-dependent step. After activation OC binds calcium
and brings it to bone
(© Kappa Bioscience).
Monographic special issue: DIETARY INGREDIENTS & SUPPLEMENTS - Agro FOOD Industry Hi Tech - vol 26(5) - July/August 2015
effect on bone health in young people with
cystic  brosis (34).
The major difference between vitamin K1 and
vitamin K2 as MK-7 are their respective half-
lives. All fat-soluble vitamins are absorbed well
in the presence of fat. Vitamin K1 however,
quickly disappears from circulation (half-life
approx. 1- 2 hours). MK-7 in contrast, has a
very long half-life (approx. 2- 3 days) (35). This
considerable difference in half-lives is due
to the MK-7 molecular structure, resulting in
a difference in uptake, transport in blood,
distribution and breakdown in the body. This
leads to the large difference in the steady
state concentration. Serum concentration of
MK-7 is substantially higher than for vitamin K1
when subjects are given equimolar amounts
(same number of molecules) (Figure 5). As a result, MK-7
remains in serum and is far more accessible for extra-
hepatic organs such as bone and vessel walls, resulting in
more ef cacious carboxylation of osteocalcin and MGP
(36). In the EU the recommended daily allowance (RDA)
celiac disease and cystic  brosis are reported to have
poor bone health (32, 33). The correlation of poor bone
health associated with cystic  brosis and vitamin K
de ciency (increased ucOC) is well established (32) and
supplementation with vitamin K is known to have bene cial
Figure 5. Concentration of vitamin K in serum after intake of vitamin K1 and vitamin K2
(MK-7), including natto food in various amounts. Only intake of MK-7 in dietary doses
gives a serum concentration above 1ng/ml. DS = dietary supplement (modi ed from ref
42, 29, 46, own data, unpublished), (© Kappa Bioscience).
Monographic special issue: DIETARY INGREDIENTS & SUPPLEMENTS - Agro FOOD Industry Hi Tech - vol 26(5) - July/August 2015
Osteoporosis Int, 2012, 23, 2239-56
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incidence and intake of calcium, magnesium, vitamin D, and
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11. Iwamoto J, Takeda T, Ichimura S; Treatment with vitamin D3 and/
or vitamin K2 for postmenopausal osteoporosis, Keio J Med. 2003;
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therapy with vitamin K(2) and vitamin D(3) on bone mineral
density and coagulofibrinolysis function in postmenopausal
women. Maturitas. 2002 25; 41:211-21
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Natto, Is Associated wiht Reduced Bone Loss in Postmenopausal
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soybean food as the major determinant of the large geographic
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osteocalcin correlates with hip bone mineral density in elderly
women, J Bone Miner Res. 1994; 9(10):1591-5
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vitamins K1 and K2 decreased in elderly women with hip
fracture. J Bone Miner Res, 1993;8:1241-5
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vitamin K concentrations. Haemostasis. 2000; 30(6):298-307
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25. Garber AK, Binkley NC, Krueger DC, et al., Comparison of
Phylloquinone Bioavailability from Food Sources or a Supplement
in Human Subjects, J Nutr , 1999, 129,1201-1203
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soybean food as the major determinant of the large geographic
difference in circulating levels of vitamin K2: possible implications
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Readers interested in a full list of references are invited to visit our
website at
of vitamin K is 75 µg/day and is based on requirements for
activation of clotting factors in the blood (37). In healthy
individuals the intake of vitamin K from food is sufcient
to fully activate clotting factors in the liver (meaning the
clotting factors are always 100% activated) (35, 38). In
contrast to the coagulation factors, several studies have
demonstrated that both OC and matrix Gla-protein in
serum are far from fully activated in the general population
(10-40%) and that supplementation with vitamin K increases
the degree of activation (38-43).
In a recent study of healthy volunteers it as documented
that the concentration of undercarboxylated OC (ucOC)
was high, pointing to an extra-hepatic vitamin K deciency
(44). Interestingly, both children and adults above age 40
year had high concentrations of circulating ucOC. The
authors concluded that by increasing the extra-hepatic
carboxylation of Gla-proteins (i.e. supplementation with
vitamin K2) one can contribute to better bone health (44).
Recent published data supports that doses of vitamin K2 in
the range of 90-120 µg/day (US RDA) can to a great extent
reduce circulating ucOC (40, 43).
Vitamin K2 deciencies seem to be quite common in
the general population, except for people eating natto.
Dietary supplement tablets typically contain 50 -100 µg
vitamin K . Based on data from the literature, only vitamin
K2, as MK-7, seems to be efcacious with respect to
benecial effects on bone health in supplement doses.
Vitamin K2 is also documented to be safe with no side
effects even in very high doses. Increased intake of vitamin
K2 in the general population to faciillitate healthy bones
may have substantial benecial effects for the individual
and huge positive implications on the public health and
health budgets worldwide.
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European Union: a compendium of country-specific reports ,
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supplementation reduces fracture incidence in postmenopausal
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6. Cockayne S, Adamson J, Lanham-New S, et al.; Vitamin K and
the prevention of fractures: systematic review and meta-analysis
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8. Crockett JC, Rogers MJ, Coxon FP, et al.; Bone remodelling at a
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ResearchGate has not been able to resolve any citations for this publication.
Full-text available
This report describes epidemiology, burden, and treatment of osteoporosis in each of the 27 countries of the European Union (EU27). In 2010, 22 million women and 5.5 million men were estimated to have osteoporosis in the EU; and 3.5 million new fragility fractures were sustained, comprising 620,000 hip fractures, 520,000 vertebral fractures, 560,000 forearm fractures and 1,800,000 other fractures. The economic burden of incident and prior fragility fractures was estimated at 37 billion. Previous and incident fractures also accounted for 1,180,000 quality-adjusted life years lost during 2010. The costs are expected to increase by 25 % in 2025. The majority of individuals who have sustained an osteoporosis-related fracture or who are at high risk of fracture are untreated and the number of patients on treatment is declining. The aim of this report was to characterize the burden of osteoporosis in each of the EU27 countries in 2010 and beyond. The data on fracture incidence and costs of fractures in the EU27 were taken from a concurrent publication in this journal (Osteoporosis in the European Union: Medical Management, Epidemiology and Economic Burden) and country specific information extracted. The clinical and economic burden of osteoporotic fractures in 2010 is given for each of the 27 countries of the EU. The costs are expected to increase on average by 25 % in 2025. The majority of individuals who have sustained an osteoporosis-related fracture or who are at high risk of fracture are untreated and the number of patients on treatment is declining. In spite of the high cost of osteoporosis, a substantial treatment gap and projected increase of the economic burden driven by aging populations, the use of pharmacological prevention of osteoporosis has decreased in recent years, suggesting that a change in healthcare policy concerning the disease is warranted.
Full-text available
We have investigated whether low-dose vitamin K2 supplements (menaquinone-7, MK-7) could beneficially affect bone health. Next to an improved vitamin K status, MK-7 supplementation significantly decreased the age-related decline in bone mineral density and bone strength. Low-dose MK-7 supplements may therefore help postmenopausal women prevent bone loss. Introduction Despite contradictory data on vitamin K supplementation and bone health, the European Food Safety Authorities (EFSA) accepted the health claim on vitamin K’s role in maintenance of normal bone. In line with EFSA’s opinion, we showed that 3-year high-dose vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation improved bone health after menopause. Because of the longer half-life and greater potency of the long-chain MK-7, we have extended these investigations by measuring the effect of low-dose MK-7 supplementation on bone health. Methods Healthy postmenopausal women (n = 244) received for 3 years placebo or MK-7 (180 μg MK-7/day) capsules. Bone mineral density of lumbar spine, total hip, and femoral neck was measured by DXA; bone strength indices of the femoral neck were calculated. Vertebral fracture assessment was performed by DXA and used as measure for vertebral fractures. Circulating uncarboxylated osteocalcin (ucOC) and carboxylated OC (cOC) were measured; the ucOC/cOC ratio served as marker of vitamin K status. Measurements occurred at baseline and after 1, 2, and 3 years of treatment. Results MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae. Conclusions MK-7 supplements may help postmenopausal women to prevent bone loss. Whether these results can be extrapolated to other populations, e.g., children and men, needs further investigation.
Full-text available
Vitamin K plays a key role in the hepatic synthesis of blood clotting factors. Recently, other tissues (bone, vessel wall) were shown to produce vitamin K-dependent proteins not involved in blood coagulation. Multiple forms of vitamin K have been found in human food: phylloquinone (K1) and various menaquinones. A recommended dietary allowance (RDA) has only been defined for K1, and its value is exclusively based on blood clotting data. We have prepared a provisional table of menaquinones in food, which has been used to calculate the total vitamin K intake in a well-defined cohort of the Dutch population. It is concluded that K1 is the major form of nutritional vitamin K, that total vitamin K intake is higher than in other populations described and that the correlation between vitamin K intake and serum concentration is poor. It is suggested that present RDA values be reconsidered and intakes comparable with those in the highest quartile of our study population are recommended.
Full-text available
The country-specific risk of hip fracture and the 10-year probability of a major osteoporotic fracture were determined on a worldwide basis from a systematic review of literature. There was a greater than 10-fold variation in hip fracture risk and fracture probability between countries. The present study aimed to update the available information base available on the heterogeneity in the risk of hip fracture on a worldwide basis. An additional aim was to document variations in major fracture probability as determined from the available FRAX models. Studies on hip fracture risk were identified from 1950 to November 2011 by a Medline OVID search. Evaluable studies in each country were reviewed for quality and representativeness and a study (studies) chosen to represent that country. Age-specific incidence rates were age-standardised to the world population in 2010 in men, women and both sexes combined. The 10-year probability of a major osteoporotic fracture for a specific clinical scenario was computed in those countries for which a FRAX model was available. Following quality evaluation, age-standardised rates of hip fracture were available for 63 countries and 45 FRAX models available in 40 countries to determine fracture probability. There was a greater than 10-fold variation in hip fracture risk and fracture probability between countries. Worldwide, there are marked variations in hip fracture rates and in the 10-year probability of major osteoporotic fractures. The variation is sufficiently large that these cannot be explained by the often multiple sources of error in the ascertainment of cases or the catchment population. Understanding the reasons for this heterogeneity may lead to global strategies for the prevention of fractures.
Full-text available
The bone remodelling cycle (see Poster panel “The bone remodelling cycle”) maintains the integrity of the skeleton through the balanced activities of its constituent cell types. These are the bone-forming osteoblast, a cell that produces the organic bone matrix and aids its mineralisation ([
Vitamin K: Past, Present, Future Essential for normal blood coagulation, possible roles in bone, vascular, and tumor metabolism, and a nutrient critical to the health of the newborn infant -- these are just some of the many health-promoting aspects of Vitamin K. Vitamin K in Health and Disease navigates the exciting research venues that have opened in the past few years surrounding this micro nutrient, particularly its role in skeletal and cardiovascular health. It also provides the historical timeline of vitamin K research and discovery that began in the 1930s. Comprehensive in scope, this book offers complete coverage of the chemistry of Vitamin K; deficiency signs and nutritional assessment; metabolism and biochemistry; and pharmacology. It also presents up-to-date scientific studies on the nutritional, metabolic, and medical aspects along with a review of current dietary requirements and the difficulty involved in establishing an appropriate dietary reference intake for Vitamin K. Extensive References, More than 45 Illustrations, Numerous Tables Based on John Suttie’s 35 years of experience directing a broad vitamin K research program, this work discusses plasma and non-plasma Vitamin K-dependent proteins. It also includes helpful tables on food sources, population intake of Vitamin K, and the impact of diet on the circulating levels of the vitamin – highlighting the role of vitamin K in health and disease. Vitamin K in Health and Disease provides a foundation for future innovations in research and in determining the best ways to implement current knowledge.
Phylloquinone (K) absorption was assessed in 22- to 30-y-old human subjects consuming a standard test meal [402 kcal (1682 kJ), 27% energy from fat]. The absorption of phylloquinone, measured over a 9-h period as the area under the curve (AUC), was higher (P < 0.01) after the consumption of a 500-μg phylloquinone tablet [27.55 ± 10.08 nmol/(L · h), n = 8] than after the ingestion of 495 μg phylloquinone as 150 g of raw spinach [4.79 ± 1.11 nmol/(L · h), n = 3]. Less phylloquinone (P < 0.05) was absorbed from 50 g of spinach (AUC = 2.49 ± 1.11 nmol/(L · h) than from 150 g of spinach. Absorption of phylloquinone from fresh spinach (165 μg K), fresh broccoli (184 μg K) and fresh romaine lettuce (179 μg K) did not differ. There was no difference in phylloquinone absorption from fresh or cooked broccoli or from fresh romaine lettuce consumed with a meal containing 30 or 45% energy as fat.
Guidance is provided in a European setting on the assessment and treatment of postmenopausal women with or at risk from osteoporosis. INTRODUCTION: The European Foundation for Osteoporosis and Bone disease (subsequently the International Osteoporosis Foundation) published guidelines for the diagnosis and management of osteoporosis in 1997. This manuscript updates these in a European setting. METHODS: The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; monitoring of treatment; assessment of fracture risk; case finding strategies; investigation of patients; health economics of treatment. RESULTS AND CONCLUSIONS: A platform is provided on which specific guidelines can be developed for national use.
Fluctuations in international normalized ratio values are often ascribed to dietary changes in vitamin K intake. Here we present a database with vitamin K1 and K2 contents of a wide variety of food items. K1 was mainly present in green vegetables and plant margarins, K2 in meat, liver, butter, egg yolk, natto, cheese and curd cheese. To investigate the effect of the food matrix on vitamin K bioavailability, 6 healthy male volunteers consumed either a detergent-solubilized K1 (3.5 µmol) or a meal consisting 400 g of spinach (3.5 µmol K1) and 200 g of natto (3.1 µmol K2). The absorption of pure K1 was faster than that of food-bound K vitamins (serum peak values at 4 h vs. 6 h after ingestion). Moreover, circulating K2 concentrations after the consumption of natto were about 10 times higher than those of K1 after eating spinach. It is concluded that the contribution of K2 vitamins (menaquinones) to the human vitamin K status is presently underestimated, and that their potential interference with oral anticoagulant treatment needs to be investigated.
A cross-sectional analysis of 1,662 community dwelling elderly Japanese men suggested that habitual natto intake was significantly associated with higher bone mineral density (BMD). When adjustment was made for undercarboxylated osteocalcin levels, this association was insignificant, showing the natto-bone association to be primarily mediated by vitamin K. Low vitamin K intake is associated with an increased risk of hip fracture, but reports have been inconsistent on its effect on BMD. Our first aim was to examine the association between BMD and intake of fermented soybeans, natto, which contain vitamin K1 (20 μg/pack) and K2 (380 μg/pack). Our second aim was to examine the association between undercarboxylated osteocalcin (ucOC), a biomarker of vitamin K intake, and BMD to evaluate the role of vitamin K in this association. Of the Japanese men aged ≥65 years who participated in the baseline survey of the Fujiwara-kyo Osteoporosis Risk in Men study, 1,662 men without diseases or medications known to affect bone metabolism were examined for associations between self-reported natto intake or serum ucOC levels with lumbar spine or hip BMD. The subjects with greater intake of natto showed significantly lower level of serum ucOC. Analysis after adjustment for confounding variables showed an association of greater intake of natto with both significantly higher BMD and lower risk of low BMD (T-score < -1 SD) at the total hip and femoral neck. This association became insignificant after further adjustment for ucOC level. Habitual intake of natto was associated with a beneficial effect on bone health in elderly men, and this association is primarily due to vitamin K content of natto, although the lack of information on dietary nutrient intake, including vitamin K1 and K2, prevented us from further examining the association.