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Overview Vitamin K and Vitamin D

Vitamin K2 is similar to D3 in many ways

  1. Both vitamins were initially confused with its lesser form (D2 ==> D3, K1 ==> K2)
  2. Both vitamins appear to influence health in large number of ways
  3. Both vitamins in the body are about 1/10 that of a century ago
    Example: Grass fed beef has a lot more K2, D3, and Magnesium
  4. Need very little of both vitamins <1 milligram)
  5. When Vitamin D is increased, it appears that Vitamin K2 should also be increased
  6. Vitamin K2 understanding and research is about 20 years behind that of Vitamin D3
    One of the reasons: No simple blood test for K2 as of Dec 2014

Importance of K2

  • Makes for harder bones and softer arteries
  • Appears to increase the effectiveness (Bioavailability?) of Vitamin D by 10%

Overview of K1 vs K2 controversy

K1K2 M-4K2 M-7
Supplement Synthetic/Natural SyntheticSyntheticNatural
Food SourceGreen leafy vegetables Cheese, animal fat, egg yoke,
natto, free-range lard
BoneSlight ability to activate osteocalcinStrong ability to build strong bones
Duration in bodyDaysHoursdays
Recycled in bodyYes - so not need much
deficiency is uncommon
Not recycled
Ability to activate MGP and reduced arterial plaqueSlightStrong
Amount needed for health90 ug not specified 90 -300 -1000ug
Japanese have 45,000 ug

Vitamin K1 = phylloquinone = phytomenadione = phytonadione

(memory aid: K1 = P = Plant)
Vitamin K2 = menaquinone = menatetrenone

Both K1 and K2 promote blood clotting (Koagulations vitamin, from German)

Controversy, but appears that

  • K2 better than K1 at building bones
  • Coumadin (warfarin) blocks all forms of vitamin K
  • 2007 – vitamin K2 is the most bioavailable, bioactive and longest lasting form of vitamin K
  • Extensive interaction between Vitamin K, Vitamin D, and Calcium (bones, prostate, arteries, . . . )

Vitamin K emerging issues – Jan 2011 (click to see PDF)

  • In Japan, a common therapy for osteoporosis is vitamin K supplementation in the form of menaquinone-4.
  • The standard dose of menaquinone-4 that is employed is 45,000ug/d, and it is used as a drug therapy rather than as a nutritional supplement.
  • This dosage is 450-fold higher than the current US dietary

Vitamin K2 and the Calcium Paradox - 2012 book

Some suppliers of large amounts of K2

  • Thorne liquid 10 drops = 1000 mcg K2 (MK4) and 5,000 IU vitamin D3
    125 servings (of 10 drops) per $22 bottle
  • Bone restore with K2 Life Extension (improved)
    4 capsules: Vitamin D3 1000 IU (low) ; MK-7 200 mcg, Ca 700 mg, Magnesium (citrate) 300 mg, Zinc 2 mg, Manganese 1 mg, Silicon 5 mg, Boron 3 mg
  • Natures Life Vitamin K-2 Menatetrenone — 5000 mcg - 60 Tablets $17
    Comment by admin of VitaminDWiki: taking this about once every 4 days with vitamin D, and hoping that the half life of K2 is long enough

Medical Publications

PubMed 18,900 hits Dec 2014

  • "vitamin k" OR "vitamin k1" OR "vitamin k2" OR "Vitamin K(2)" OR phylloquinone OR phytomenadione OR phytonadione OR menaquinone OR menatetrenone
  • 2014 K2 reduces Osteoporosis for postmenopausal women: a meta-analysis]
  • 2012 Vitamin k and the nervous system: an overview of its actions -full text on-line
  • 2012 Vitamin K-antagonists create arterial plaque. Vermeer full text on-line
  • 2012 The role of vitamin k in soft-tissue calcification. -full text on-line Vermeer
  • 2012 Vitamin k status and vascular calcification: evidence from observational and clinical studies -full text on-line
  • 2012 Vitamin K, an emerging nutrient in brain function
  • 2012 Vitamin K: the effect on health beyond coagulation - an overview -PDF at bottom of this page (Vermeer)
  • 2011 Conclusion: A low intake of vitamin K1, but not K2, was associated with an increased risk of hip fractures.
    This is the opposite of current belief
  • 2011 Bone quality in diabetics improved with vitamin K2
  • 2010 Vitamin K2: a novel therapy for osteoporosis
  • 2011 Vitamin K, bone fractures, and vascular calcifications in chronic kidney disease: an important but poorly studied relationship.

Clinical Trials for "vitamin K" 433 as Dec 2014

Effect of Vitamin K Supplementation on Markers of Diabetes Risk in Overweight Children
The Efficacy of Vitamin K2 n Human Osteoporosis, Blood-vessel Calcification and Sclerosis
Vitamin K-absorption From Dairy
The Effects of Vitamin K2 Supplementation on the Progression of Coronary Artery Calcification (VitaK-CAC)
Beneficial Effects of Long Term Menaquinone-7: 180 µg menaquinone-7 daily for three years; Bone Loss & Arteriosclerosis
Comparison of Absorption of Vitamin K2: softgel capsules containing 180 µg MK-7 and 750 IU vitamin D3 + 120 µg MK-4
The Effect of Vitamin K2 on Bone Turnover


Green Medical Info has many medical references for Vitamin K1 and K2

  • Menaquinone-7, a form of vitamin K2, may prevent age-related bone loss.
  • Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease, cardiac mortality, aortic calcification and all-cause mortality.
  • Vitamin K may reduce the risk for artherosclerosis.
  • Vitamin K may be effective in preventing and treating osteoporosis and arterial calcification.
  • Evidence shows that deficiency of Vit. K may contribute to the development of cardiovascular plaque (increased intima media thickness)
    and supplementation may reverse or forestall the process of calcification.
  • Vitamin K supplementation inhibits the progression of coronary artery calcification in older men and women.
  • High dietary menaquinone (Vitamin K2) intake is associated with reduced coronary calcification.
  • Vitamin K(2) may represent a new agent for the treatment of rheumatoid arthritis.
  • Vitamin K supplementation in postmenopausal women wih osteopenia appears to protect against bone fractures and cancers.
  • Vitamin K1 and K2 exhibit anti-fracture activity.
  • The intake of natto, an excellent source of vitamin K2, may reduce bone fracture risk.
  • Menaquinone-7 (vitamin K2) supplementation increases osteocalcin carboxylation associated
  • High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women.
  • Vitamin K2 (MK-4) may be beneficial in the maintenance of bone health in postmenopausal women.
  • Supplementation with phytonadione (Vitamin K1) and menaquinone (Vitamin K2) , particularly menaquinone-4, is associated with increased BMD and reduced fracture incidence.
  • vitamin Vitamin (2) works synergistically with alendronate on improving both osteocalcin carboxylation and BMD of femoral neck in postmenopausal women with osteoporosis.
  • Low vitamin K status is associated with abnormal cartilage, bone mineralizations and osteoarthritis in the hand and knee.
  • Vitamin K3 induces programmed cell death in breast cancer cells.
  • Vitamin K2 inhibits cell growth in cholangiocellular carcinoma cell lines.
  • Pharmacological Actions : Apoptotic, Cell cycle arrest
  • Supplementation of vitamin K antagonists with 100 mcg of vitamin K improves stability of anticoagulant therapy and reduces side effects.
  • High dietary intake of vitamin K rich foods is associated with a lower risk of coronary artery disease.
  • Research indicates that vitamin K2 intake reduces coronary heart disease events.
  • A high vitamin K2 (menaquinone) intake reduces the incidence of coronary heart disease.
  • Vitamins K2 and D3 have a protective effect on prednisolone-induced loss of bone mineral density in the lumbar spine.
  • High dose vitamin K is efficacious in correcting vitamin K deficiency in cystic fibrosis.
  • Vitamin K2 may improve bone quality in type 2 diabetes.
  • Low levels of vitamin D and K are highly prevalent and independent of overall malnutrition in the institutionalized elderly.
  • Vitamin K2 induces cell cycle arrest and programmed cell death in gastric cancer cell lines.
  • Levels of menaquinone-7 and vitamin D are lower in those wtih hip fracture, indicating they may have a role in fracture prevention.

Vitamins D and K as pleiotropic nutrients - 2010

Clinical importance to the skeletal and cardiovascular systems and preliminary evidence for synergy.
Altern Med Rev. 2010 Sep;15(3):199-222. Kidd PM. University of California, Berkeley, USA. dockidd at dockidd.com
CLICK HERE for excellent full text and PDF


See also VitaminDWiki

See on web

Benefits of vitamin D: from http://tinyurl.com/mercola311

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Cardiovascular Mortality much worse if lacking Vitamin K2 from MenaQ7.com

Image

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The above is their advertisement

Make your own Vitamin K2 / Natto at home from a starter kit

Called Natto in Japan and Thau-nao in Thailand this cultured whole bean soy food has a strong, somewhat persistent, unique flavor.
The bacteria, Bacillus subtilis var natto, that culture the cooked soybeans make a sticky, viscous polymer during the 6-12 hours of incubation.
This creates wispy threads evident when the cultured soybeans are pulled apart.

A good source of protein, this robust soyfood adds zest to any grain or noodle dish, soup or sandwich.
A little goes a long way, so what is not intended for use in a day or two may be easily frozen.
Our Natto starter, imported from Japan, has a 6 month or more shelf life.

Natto Starter Kit:
This 11gm packet contains culture directions, recipes, and enough spore to start 3 batches of natto, each making 5 cups or 1.5 pounds.
$3.00 + $3.00 shipping in the US. As of July 2011 the supplier only accepts check of money order, no on-line sales
- - - - - - - - - - - - - -
Cees Vermeer (64) is Associate Professor of Biochemistry at the Maastricht University and since 10 years also CEO of VitaK, a spin-off company focusing on research on vitamin K and vitamin K-dependent proteins. VitaK employs 14 researchers (PhD, MSc, and BSc) who are all working on a) clinical trials to demonstrate health effects of vitamin K, b) development of new biomarkers based on vitamin K-dependent proteins and c) analysis of K-vitamins in foods and body fluids. Cees Vermeer has been the supervisor of 16 PhD students and is an author in over 300 papers in the international scientific press. VitaK is specialized in bone and cardiovascular health and has a long-standing R&D collaboration with NattoPharma; we have demonstrated the quality and health effects of MenaQ7 in several independent clinical trials and also act as consultant for scientific and regulatory affairs as well as for designing and defending IPR.

Dr. Vermeer studied Biochemistry at Leiden, where he also presented his PhD thesis (1974) on the initiation of protein biosynthesis in E coli. In 1975 Dr. Vermeer was appointed at the Department of Biochemistry of the Universiteit Maastricht, where he has founded the Division on Vitamin K In 1984 he was appointed as an Associate Professor of Biochemistry and Principal Investigator at CARIM. In 1994 Dr. Vermeer was appointed as a temporary adviser of the World Health Organization and in 2001 he received the honorary title of Doctor honoris causa at the University of Medicine and Pharmacy "Iuliu Hatieganu" of the city of Cluj-Napoca, Romania. Moreover, in 2001 Dr. Vermeer founded the company VitaK BV, where he became the first CEO of the company.

Slide show for VitaK from Dec 2010 is attached at the bottom of this page

The following are some of the slides


Image Image Image


Cees Vermeer, PhD; Associate Professor of Biochemistry; BioPartner Center Maastricht; c.vermeer at bioch.unimaas.nl


WikiPedia on Vitamin K Deficiency Oct 2011

Average diets are usually not lacking in vitamin K and primary vitamin K deficiency is rare in healthy adults.
Newborn infants are at an increased risk of deficiency.
Other populations with an increased prevalence of vitamin K deficiency include individuals who suffer from liver damage or disease (e.g. alcoholics), people with cystic fibrosis, inflammatory bowel diseases or those who have recently had abdominal surgeries.
Groups that may suffer from secondary vitamin K deficiency include bulimics, those on stringent diets, and those taking anticoagulants.
Other drugs that have been associated with vitamin K deficiency include salicylates, barbiturates, and cefamandole, although the mechanism is still unknown.
There is no difference between the sexes as both males and females are affected equally.
Symptoms of deficiency include heavy menstrual bleeding in women, anemia, bruising, and bleeding of the gums or nose.
They could also have disorders such as coagulopathy.[59]
Osteoporosis[60][61] and coronary heart disease[62][63] are strongly associated with lower levels of K2 (menaquinone).
Menaquinone is not inhibited by salicylates as happens with K1, so menaquinone supplementation can alleviate the chronic vitamin K deficiency
caused by long term aspirin use.[citation needed]
Wikipedia snip
Vitamin K2 (MK4, but not MK7 or vitamin K1) has also been shown to prevent bone loss and/or fractures in the following circumstances:

  • caused by corticosteroids (e.g., prednisone, dexamethasone, prednisolone), [17][18][19][20]
  • anorexia nervosa, [21]
  • cirrhosis of the liver, [22]
  • postmenopausal osteoporosis, [16][23][24][25][26][27]
  • disuse from stroke, [28]
  • Alzheimer's disease, [29]
  • Parkinson disease, [30]
  • primary biliary cirrhosis [31]
  • and leuprolide treatment (for prostate cancer).32

Vitamin K2: The Missing Nutrient

2008 long excellent article has the following points

  • The authors point out that the benefits of K2 were most pronounced for advanced prostate cancer, and, importantly, that vitamin K1 did not offer any prostate benefits.
  • It has been commonly believed that the benefits of vitamin K are limited to its role in blood clotting. Another popular misconception is that vitamins K1 and K2 are simply different forms of the same vitamin – with the same physiological functions.
  • However, intake of vitamin K1 had no effect on cardiovascular disease outcomes.
  • Foods high in vitamin K2
    • Natto
    • Hard cheese, Soft cheese (if grass fed, not grain fed)
    • Egg yolk, Butter (grass fed, not grain) , Chicken liver, Salami, Chicken breast, Ground beef

See also Vitamin D council

  • Dr. Cannell authored a book, The Athletes Edge
    in which he recommends 1,000 micrograms of K2 daily (probably if taking > 5,000 IU of vitamin D
  • Dr. Cannell on vitamin K2 Nov 2013, behind a $5/month paywall
    ''One cup of cooked kale has more than 1,000 mcg of vitamin K1. A cup of cooked spinach has more than 800 mcg. And a cup of turnip greens has more than 500 mcg. But that is all vitamin K1.""
    There appears to be two sites of conversion of K1 to K2, one in the intestine and another in peripheral tissues.
    In Nov 2013 the mechanism by which the body turns vitamin K1 into vitamin K2 was clarified.
       It occurs through an intermediary molecule, vitamin K3, which is made in the intestine from vitamin K1.

RCT 1500 micrograms daily K2 preserves bone - 2013

Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women May 2013
6 month Random Controlled Trial: Control group with no K-2 had decreased forearm BMD, 1.5-mg K-2 MK-4 has no decrease


Appears that Vitamin K is needed to prevent bone loss - Booth 2012

Vitamin K-Dependent Carboxylation of Osteocalcin: Friend or Foe?
Caren M. Gundberg3, caren.gundberg at yale.edu, Jane B. Lian4, and Sarah L. Booth (see also below) 5
3Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT
4Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA; and
5Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA
Adv Nutr March 2012 Adv Nutr vol. 3: 149-157, 2012

Osteocalcin originates from osteoblastic synthesis and is deposited into bone or released into circulation, where it correlates with histological measures of bone formation. The presence of 3 vitamin K-dependent ? carboxyglutamic acid residues is critical for osteocalcin’s structure, which appears to regulate the maturation of bone mineral. In humans, the percentage of the circulating osteocalcin that is not ?-carboxylated (percent ucOC) is used as a biomarker of vitamin K status. In contrast, when ucOC is not corrected for total osteocalcin, the interpretation of this measure is confounded by osteoblastic activity, independent of vitamin K. Observational studies using percent ucOC have led to the conclusion that vitamin K insufficiency leads to age-related bone loss. However, clinical trials do not provide overall support for the suggestion that vitamin K supplementation of the general population will reduce bone loss or fracture risk. More recently, results from in vitro and in vivo studies using animal models indicate that ucOC is an active hormone with a positive role in glucose metabolism. By inference, vitamin K, which decreases ucOC, would have a detrimental effect. However, in humans this hypothesis is not supported by the limited data available, nor is it supported by what has been established regarding osteocalcin chemistry. In summary, the specific function of osteocalcin in bone and glucose metabolism has yet to be elucidated.


Dr. Sarah Booth Jan 2014

Video from Grassroots
PDF including all images is attached at the bottom of this page

__here are some of the images


Image Image Image

Her 2008 PDF is attached at the bottom of this page


Vitamin K1 is Inversely Associated with Mortality Risk, K2 is also good - March 2014

Dietary Intake of Vitamin K Is Inversely Associated with Mortality Risk.
J Nutr. 2014 Mar 19. [Epub ahead of print]
Juanola-Falgarona M1, Salas-Salvadó J, Martínez-González MA, Corella D, Estruch R, Ros E, Fitó M, Arós F, Gómez-Gracia E, Fiol M, Lapetra J, Basora J, Lamuela-Raventós RM, Serra-Majem L, Pintó X, Muñoz MA, Ruiz-Gutiérrez V, Fernández-Ballart J, Bulló M.

Vitamin K has been related to cardiovascular disease and cancer risk. However, data on total mortality are scarce. The aim of the present study was to assess the association between the dietary intake of different types of vitamin K and mortality in a Mediterranean population at high cardiovascular disease risk. A prospective cohort analysis was conducted in 7216 participants from the PREDIMED (Prevención con Dieta Mediterránea) study (median follow-up of 4.8 y). Energy and nutrient intakes were evaluated using a validated 137-item food frequency questionnaire. Dietary vitamin K intake was calculated annually using the USDA food composition database and other published sources. Deaths were ascertained by an end-point adjudication committee unaware of the dietary habits of participants after they had reviewed medical records and linked up to the National Death Index. Cox proportional hazard models were fitted to assess the RR of mortality.
Energy-adjusted baseline dietary phylloquinone intake was inversely associated with a significantly reduced risk of cancer and all-cause mortality after controlling for potential confounders (HR: 0.54; 95% CI: 0.30, 0.96; and HR: 0.64; 95% CI: 0.45, 0.90, respectively).

In longitudinal assessments, individuals who increased their intake of phylloquinone or menaquinone during follow-up had a lower risk of

  • cancer (HR: 0.64; 95% CI: 0.43, 0.95; and HR: 0.41; 95% CI: 0.26, 0.64, respectively) and
  • all-cause mortality (HR: 0.57; 95% CI: 0.44, 0.73; and HR: 0.55; 95% CI: 0.42, 0.73, respectively)

than individuals who decreased or did not change their intake.
Also, individuals who increased their intake of dietary phylloquinone had a lower risk of cardiovascular mortality risk (HR: 0.52; 95% CI: 0.31, 0.86).
However, no association between changes in menaquinone intake and cardiovascular mortality was observed (HR: 0.76; 95% CI: 0.44, 1.29).
An increase in dietary intake of vitamin K is associated with a reduced risk of cardiovascular, cancer, or all-cause mortality in a Mediterranean population at high cardiovascular disease risk.
This trial was registered at http://www.controlled-trials.com as ISRCTN35739639.
PMID: 24647393


MK7 is a natural form and is more effective in the body

Accumulation in the serum
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The long half-life of MK-7 results in significantly better accumulation compared to MK-4. Research shows that in only 8 days MK-7 has 6 times better absorption. Hence, smaller quantities and less frequent intakes of MK-7 is sufficient in order to supply all of the tissues.

MK7 more effective
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MK-7 is much more effective than MK-4 at doses that do not exceed the present recommended intake for vitamin K. MK-4 has to be applied in very high pharmacological doses (milligrams) to demonstrate benefits for bone and heart health. In case of MK-7, doses in micrograms – 1000x less - are sufficient for significant bioactive effect.



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