Health Happening
The "No-Brainers" for Physical and Mental Health:
Vitamin K is well known as a blood clotting agent, without which, an injury could cause us to bleed to death. In fact, vitamin K was named after the German word "koagulation". However - there are two main types of K - K1 and K2 - and although most people get enough dietary K1 to maintain adequate blood clotting, they do NOT obtain enough K2, to perform its more recently discovered important functions / roles, including:
Fat-Soluble vitamin K exists in two basic natural forms, K1 and K2. Each now found to have quite DIFFERENT physiological functions:
(1) Vitamin K1 (PHYLLOQUINONE) - ~90% of vitamin K intake in typical Western diet
(2) Vitamin K2 (E.g. MENAQUINONE 4,7,8,9 thru 14). ~10% of vitamin K intake in typical Western diet found in primarily fermented foods and aged cheeses; also produced by gut bacteria;
K2 is preferentially used by vessel walls, bones, and tissues other than your liver
Spronk, H.M., Soute, B.A., Schurgers, L.J., Thijssen, H.H., De Mey, J.G., Vermeer, C., 2003. Tissue-specific utilization of menaquinone-4 results in the prevention of arterial calcification in warfarin-treated rats. J. Vasc. Res. 40(6), pp 531-537.
K2 has several subforms (with repeating 5-carbon units in the side chain of the molecule) -denoted as menaquinone-n or MK-n, where n is the number of 5-carbon units) :
Beneficial gut bacteria (called probiotics) produce several subforms of vitamin K2. These lactic acid bacteriapartially contribute to body's K-status as the K2 is absorbed in small amounts from the distal small intestine (ileum).
K2 subforms found in animal foods (especially organs and pastured dairy), curds and fermented foods. Many of them containing saturated fat:
Amount of K2 in fermented Foods is dependent on type of K2-producing bacteria used for fermentation:
Newborns are sometimes given K1 shots to prevent intracranial hemorrhage - to tide them over until at just over a week old, their intestinal bacteria produce K2 and the the infant has been ingesting K in colostrum, breastmilk or non-soy based formula (contains more K than breastmilk);
Under ideal circumstances, gut bacteria or enzymes in cell metabolism can convert K1 from food and convert it into K2 - maintaining an optimal balance between the K1 and K2 forms of this vitamin. The mammary glands are especially efficient at producing K2 from K1, presumeably to supply growing breast-fed infants.
Certain factors can interfere with the K1 to K2 conversion:
The body's K1 =>K2 conversion ratio is said to be about 10:1 and is enhanced by the presence of fat
Although animals can convert K1K2 , evidence suggests that the human diet needs to contain preformed K2 for optimal health:
The study showing vitamin K2′s dramatic role in treating prostate cancer, revealed that vitamin K1 had no effect. Study by European Prospective Investigation into Cancer and Nutrition (EPIC), Heidelburg, German
K2 is better absorbed than K1 and remains active much longer
Phylloquinones present in green leafy vegetables are tightly bound to the thylakoid membranes in plant chloroplasts, and are not well solubilized and absorbed without the concomitant intake of fat, which stimulates bile secretion. Gijsbers et al, 1996; Schurgers and Vermeer, 2000; Schurgers, 2002; Vermeer et al., 2004
K2 is carried in the lymph in mixed micelles composed of bile salts, and subsequently released into the circulation.
Absorption of vitamin K (as other fat-soluble vitamins E.g. A, D and E) depends on healthy liver, gallbladder and digestive function. Deficiency is more likely in people with digestive problems such as pancreatic disease, celiac disease, irritable bowel syndrome (IBS), ulcerative colitis, Crohn's disease or those who have had intestinal bypass surgery.
Binkley NC, Grueger DC, Kawahara TN, Engelke JA, Chappell RJ, Suttie JW. 2002. A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation. Am J Clin Nutr. 2002; 76: 1055-60.
Garber AK, Binkley NC, Krueger DC, Suttie JW. 1999. Comparison of Phylloquinone Bioavailability from Food Sources or a Supplement in Human Subjects. J Nutr. 1999; 129: 1201-1203.
Gijsbers BLMG, Jie K-SG, Vermeer C. 1996. Effect of food composition on vitamin K absorption in human volunteers. Br J Nutr. 1996; 76: 223-229.
McKeown NM, Jacques PF, Gundberg CM, Peterson JW, Tucker KL, Kiel KP, Wilson PWF, Booth SL.2002. Dietary and nondietary determinants of vitamin K biochemical measures in men and women.J Nutr. 2002; 132(6): 1329-1334.
Schurgers LJ, Vermeer C., 2000. Determination of Phylloquinone and Menaquinones in Food. Haemostasis. 2000; 30: 298-307
.Schurgers LJ, Teunissen KJF, Hamulyak K, Knapen MHJ, Hogne V, Vermeer C.2007. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2006; [Epub ahead of print].
Vermeer, C. 2003. Pharmacokinetics of vitamin K2 after ingestion of natto food and natto capsules. (Natto-1 Study). VitaK/University of Maastricht. Research Project, July 25, 2003.
Vermeer, C., Shearer, M.J., Zittermann, A., Bolton-Smith, C., Szulc, P., Hodges, S., Walter, P., Rambeck, W., Stocklin, E., Weber, P. 2004. Beyond deficiency: Potential benefits of increased intakes of vitamin K for bone and vascular health. Eur. J. Nutr. 43(6), 325-335.
OSTEOCALCIN and MGP (Matrix GLA Protein) put calcium in bones / teeth and not in soft tissue (E.g. arteries, cartilage)
"Impairment of the function of OSTEOCALCIN and MGP due to incomplete carboxylation results in an increased risk for developing osteoporosis and vascular calcification, respectively, and is an unexpected side effect of treatment with oral anticoagulants. . . In healthy individuals, substantial fractions of OSTEOCALCIN and MGP circulate as incompletely carboxylated species, indicating that the majority of these individuals is subclinically vitamin K-deficient. Potential new application areas for vitamin K are therefore its use in dietary supplements and functional foods for healthy individuals to prevent bone and vascular disease, as well as for patients on oral anticoagulant treatment to offer them protection against coumarin-induced side effects" Cranenburg EC, Schurgers LJ, Vermeer C. Vitamin K: The coagulation vitamin that became omnipotent. Thromb Haemost. 2007 Jul;98(1):120-5.
Vitamin K2-dependent OSTEOCALCIN activation seems to concurrently strengthen bones and inhibit (and possibly reverse) soft tissue calcification. Vitamin K2 functions as a cofactor for the enzyme (γ-glutamylcarboxylase) that activates (catalyzes the carboxylation of) a protein hormone called OSTEOCALCIN, (produced by bone-building osteoblasts), which is needed to bind calcium into hydroxyapatite crystals forming the bone matrix. OSTEOCALCIN also appears to help prevent calcium from depositing into your arteries.
|
Technically - the K-dependent enzyme catalyzes the carboxylation of the amino acid glutamic acid, resulting in gamma-carboxyglutamic acid (Gla); Gla's make it possible to bind calcium. E.g. (a) OSTEOCALCIN contains 3 residues of Gla, which can bind calcium into bone, and (b) K-dependent gamma-carboxylation of glutamic acid residues in clotting factor proteins makes it possible for themto bind calcium ions, which activates the blood clotting factors |
Animation showing how K2 (MK-7) builds bones
Vitamin K and vitamin D together increase Matrix GLA Protein (MGP), which protects soft tissue from calcification. By preventing calcium crystal formation E.g. in blood vessels, bone spurs and cartilage
|
Vitamin K in hydrogenated canola and soybean oils (typically found in processed foods) is changed to an unnatural form (dihydrophylloquinone), which is unable to activate OSTEOCALCIN and MGP - such that regularly eating processed / fast foods together with a diet low in leafy greens greatly increases risk of functional K-deficiency Booth SL, Lichtenstein AH, et al. Effects of a hydrogenated form of vitamin K on bone formation and resorption Am J Clin Nutr. 2001 Dec;74(6):783-90 Those consuming higher amounts of dihydrophylloquinone were found to have lower bone mineral density at the neck, hip and spine. Troy LM, Jacques PF, Hannan MT, Kiel DP, Lichtenstein AH, Kennedy ET, Booth SL. Dihydrophylloquinone intake is associated with low bone mineral density in men and women. Am J Clin Nutr. 2007 Aug;86(2):504-8. |
According to vitamin K researcher Professor Cees Vermeer: The only mechanism for arteries to protect themselves from calcification is via the vitamin K-dependent protein MGP. MPG is the most powerful inhibitor of soft tissue calcification presently known, but non-supplemented healthy adults are desufficient in vitamin K to a level that 30 per cent of their MGP is synthesized in an inactive form. So, protection against cardiovascular calcification is only 70% in the young, healthy population, and this figure decreases at increasing age."
Vitamin K and vitamin D increase MGP, which protects blood vessels from calcification - In healthy arteries, MGP functions as a powerful inhibitor of calcification in arteries (and cartilage). MGP congregates around the elastic fibers of the tunica media (arterial lining), guarding them against calcium crystal formation. Optimal vitamin K levels are needed to produce proper amounts of MGP to prevent arterial calcification. Shearer Role of vitamin K and Gla proteins in the pathophysiology of osteoporosis and vascular calcification. MJ.Curr Opin Clin Nutr Metab Care 2000 Nov;3(6):433-8; Dhore CR, Cleutjens JP, Lutgens E, et. al. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):1998-2003. Even a diet rich in leafy greens supplies less than half the vitamin K needed for its calcium-regulating activities. Cranenburg EC, Schurgers LJ. Thromb Haemost. 2007 Jul;98(1):120-5.
Evidence for K2 rather than K1 for heart benefits.
People with severe calcifications have high percentages of inactive OSTEOCALCIN - which indicates a general deficiency of vitamin K2.
|
Taking Calcium to prevent osteoporosis WITHOUT vitamin K increases risk of heart attack by an average 149% whilst decreasing risk of fracture by only 12% - According to 2008 randomized, controlled research published in British Medical 1471 postmenopausal women taking calcium supplements also increased their risk of stroke an average of 142% and sudden death 137%. Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ. 2008 Feb 2;336(7638):262-6. An editorial accompanying the study entitled "Cardiovascular risks of calcium supplements in women - Increased risk of myocardial infarction outweighs the reduction in fractures"points out: "Under certain stimuli, vascular smooth muscle cells may undergo a phenotypic switch to bone-like cells, and in the presence of high amounts of calcium these may be capable of producing vascular calcification." Jones G, Winzenberg T. BMJ. 2008 Feb 2;336(7638):226-7. A footnote refers to the "certain stimuli"as lack of sufficient vitamin K2, which can cause the cells lining blood vessel walls to absorb calcium, like bone cells. Wallin R, Wajih N, et al. Arterial calcification: a review of mechanisms, animal models, and the prospects for therapy. Med Res Rev. 2001 Jul;21(4):274-301 The long and short --- Don't take calcium supplements without concurrent intake of vitamin K1 (from eating such as dark green leafy and cruciferous vegetables, although older people seem to have a poor conversion of K1 to K2) and a K2 supplement. Also, taking vitamin D increases calcium absorption making vitamin K even more necessary |
High-dose K2 can not only increase bone mineral density in those with osteoporosis but also reduce fracture rates (according to human intervention studies). Emerging evidence also supports that low dose K1 when combined with vitamin D may also benefit bone health. Proposed K mechanisms are:
Supporting trials:
In the Prospect EPIC (European Prospective Investigation into Cancer and Nutrition) study, 16,057 women (aged 49-70) were followed for an average of 8.1 years. It was found that a high intake of vitamin K2, but not K1, leads to reduced cancer risk and a 30% lower risk of dying from cancer, in particular it lowered risk of prostate cancer, lung cancer and leukemia / MDS (study data suggests that vitamin K2+ vitamin D3 may be an effective combination for differentiation-based therapy for leukemia and MDS)
Daniells S. "Vitamin D may reduce cancer risk: EPIC study"Nutraingredients.com(March 30, 2010)
Nimptsch K, Rohrmann S, Kaaks R, and Linseisen J. "Dietary vitamin K intake in relation to cancer incidence and mortality: Results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg)"Am J Clin Nutr (March 24, 2010)
Yoshida T, Miyazawa K, Kasuga I, Yokoyama T, Minemura K, Ustumi K, Aoshima M, Ohyashiki K. Apoptosis induction of vitamin K2 in lung carcinoma cell lines: the possibility of vitamin K2 therapy for lung cancer. Int J Oncol. 2003 Sep;23(3):627-32. PMID: 12888897.
Iguchi T, Miyazawa K, Asada M, Gotoh A, Mizutani S, Ohyashiki K. Combined treatment of leukemia cells with vitamin K2 and 1alpha,25-dihydroxy vitamin D3 enhances monocytic differentiation along with becoming resistant to apoptosis by induction of cytoplasmic p21CIP1. Int J Oncol. 2005 Oct;27(4):893-900. PMID: 16142303.
New research shows that K2-dependently-activated MGP is needed to prevent the excessive proliferation and mineralization of muscle cells in the walls of the veins that ca uses varicose veins -Researchers compared healthy veins from 36 male patients (aged 30 - 83) with varicose veins from 50 male patients (aged40 - 81). High levels of uncarboxylated (inactive) MGP and increased calcification were seen only in the varicose veins. When vitamin K was added to cultures of small muscle cells from the varicose veins, MGP was activated, stopping the mineralization process.
Cario-Toumaniantz C, Boularan C, Schurgers LJ, Heymann MF, Le Cunff M, Léger J, Loirand G, Pacaud P. Identification of Differentially Expressed Genes in Human Varicose Veins: Involvement of Matrix Gla Protein in Extracellular Matrix Remodeling. J Vasc Res. 2007 Jul 20;44(6):444-459 [Epub ahead of print] Abstract
Vitamin K-activated OSTEOCALCIN ( a hormone secreted by bone-buildingosteoblast cells) is directly involved in the proliferation of INSULIN- producing pancreatic β-cells - thus improving glucose tolerance and INSULIN sensitivity.
Vitamin K2-dependent activation of MGP plays a key role in protecting skin elasticity by inhibiting calcium deposits in elastin fibers - smoothing out lines and wrinkles. Gheduzzi D, Boraldi F, et al. Matrix Gla protein is involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients. Lab Invest. 2007 Oct;87(10):998-1008.
Evidence suggests that vitamin K2 plays a role as an antioxidant within the cells that synthesize the myelin sheath - which forms the electrical insulation of nerves. Denisova NA, Booth SL. Vitamin K and Sphingolipid Metabolism: Evidence to Date. Nutr Rev. 2005; 63(4): 110-121.
Low fat diets are a bad idea if you want to obtain vitamin K - Eat vitamin K or take K2 supplements with fat such as olive olive oil and butter to enable effective K absorption
K2 works in synergy with:
The Institute of Medicine Recommended Dose of Vitamin K - was recently increasedto 90 microg/d for females and 120 microg/d for males (an increase of ~ 50% from previous recommendations). However, this dose is much lower than study doses that increased carboxylation of OSTEOCALCIN for bone mineralization and increased MGP to prevent calcium crystallization where it doesn't belong.
K1 is easily obtained in our diet - and is important for producing clotting factors, but did not seem to influence study results that helped CVD or cancer.
Some Foods High in Vitamin K1 (USDANutrient Base) |
|||
| Details | Portion | Vitamin K1 (mcg) | |
| Kale | Boiled, fresh, drained | ½C | 531 |
| Boiled, frozen, drained | ½C | 573 | |
| Spinach | Boiled, fresh, chopped | ½C | 444 |
| Boiled, frozen, chopped | ½C | 514 | |
| Brussel Sprouts | Boiled, fresh | 1C | 218 |
| Boiled, frozen | 1C | 300 | |
| Broccoli | Boiled, fresh, drained | 1C | 220 |
| Boiled, frozen, drained | 1C | 163 | |
| Cabbage | Boiled, fresh, drained | ½C | 81 |
| Asparagus | Boiled, fresh, drained | ½C (6 spears) | 45 |
| Boiled, frozen, drained | ½C (6 spears) | 44 | |
| Butterhead Lettuce | Raw; Incl. Boston, Bibb | ¼head | 42 |
| Kiwi | Raw | medium | 31 |
| UK -2003* | 68mcg/day@ | ||
| US -1996Young adults # | 60-110mcg/day@ | ||
| US -1996Adults> 55 yrs old # | 80-210mcg@ | ||
* EVM, 2003. Safe Upper Levels for Vitamins and Minerals. Risk Assessment: Vitamin K. Report of the Expert Group on Vitamins and Minerals; London, Engl., pp. 154-161. Available from: <http://www.food.gov.uk/multimedia/pdfs/vitmin2003.pdf>.
# Data from Several US studies @ Mean average intake from food
K2 form is many times more effective than K1
K2 effective aganst heart disease and cancer, but not K1 - A 2004 study published in the "Journal of Nutrition" studied the effects of vitamin K1 and K2 ingestion on heart disease. A high dietary intake of menaquinone, mostly in the form of cheese, was correlated with a lower risk of heart disease.
K2 content of Some Foods (in mcg)Good K2 sources are egg yolks, liver, some aged cheeses and fermented foods |
|||||
| K2 Type => | MK-4 | MK-7 | MK-8 | MK-9 | MK-10 |
| Natto (Fermented soybean) (½oz) | 142 | 12 | |||
| Sauerkraut | Purported to be high in K2 | ||||
| Hard Cheese (3.5oz) | 5 | ||||
Most table data calculated from ng/g values at:
Vermeer, C., Knapen, M.H., Schurgers, LJ., 1998. Vitamin K and metabolic bone disease. J Clin. Pathol. 51(6), 424-426.
Ikeda Y., Iki M., Morita A., Kajita E., Kagamimori S., Kagawa Y., Yoneshima H. (2006). Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study. J. Nutr. 2006 May; 136(5):1323-8.
Schurgers, L.J., Vermeer, C., 2000. Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis 30(6), 298-307.
"K-Sandwich"▲ Butter a piece of whole-grain bread (properly prepared to remove antinutrients) with organic butter from grass-fed cows▲ Add some grated fermented hard cheese, a slice of tomato and 2-3 tablespoons of sauerkraut ▲ Add white or black pepper and some Celtic Sea or Himalayan salt to taste |
Those with K-deficient symptoms / conditions:
Those with or who want to prevent:
Low-dose* Vitamin K supplementation has been shown to stabilize fluctuations in INR** of those taking warfarin
*Low-dose = 50-150 mcg/day; ** INR is a standard measuement for the time it takes for blood to clot;
Sconce E, Khan T, Mason J, et al. Patients with unstable control have a poorer dietary intake of vitamin K compared to patients with stable control of anticoagulation. Thromb Haemost. 2005 May;93(5):872-5.
However, If on cholesterol-lowering or blood-thinning medication, do not supplement K without seeking medical supervision
Supplement K2 not K1 -K1 is usually supplied in the diet and K2 is more effective against the health problems listed above;
MK-7 form extracted from natto is longer acting/better absorbed than MK-4 (synthetic supplemental form supposedly identical to natural MK-4),MK-8 or MK- 9 supplements -CHOOSE MK-7 EXTRACTS from NON-GMO SOY;
You don't need to take a K2 supplement if you can eat ½oz of relatively cheap natto daily -which provides ~154 mcg of K2. Unfortunately, most Westerners find natto unpalatable (not only slimy, it also smells pretty bad)
K2 supplement Dosage?- Vitamin K expert Dr. Vermeer recommends between 45 mcg and 185 mcg daily for adults. This author's suggested recommendation is:
Take 150 mcg K2 /day WITH FAT (to enable its absorption).
Although allergic reaction is possible, there is no known toxicity associated with high doses of vitamin K1 or K2 forms of vitamin K
Food and Nutrition Board, Institute of Medicine. Vitamin K. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, D.C.: National Academy Press; 2001:162-196. (National Academy Press). 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.
Synthetic menadione (vitamin K3) and its derivatives have resulted in several health problems - as such, it is no longer used.
Drug Interactions
Nutrient interactions. Large doses of vitamin A and vitamin E (~1000 IU or more) have been found to antagonize vitamin K. Olson RE. Vitamin K. In: Shils M, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore: Lippincott Williams & Wilkins; 1999:363-380.
The usual prothrombin test only tests for clotting activity - and does notindicate whether enough K is present to maintain vascular matrix-GLA protein or bone OSTEOCALCIN activity.
OSTEOCALCIN test - measures how much uncarboxylated OSTEOCALCIN is present in the blood.High levels indicate insufficient vitamin K present to promote optimal bone health.
Matrix-GLA protein ( MGP) test - High levels of undercarboxylated MGP indicate that insufficient vitamin K is present to protect against vascular calcification.
Linus Pauling Institute: http://lpi.oregonstate.edu/infocenter/vitamins/vitaminK/
Weston A.Price Foundation: http://www.westonaprice.org/fat-soluble-activators/x-factor-is-vitamin-k2
Vitamin K2 as source of vitamin K added for nutritional purposes to foodstuffs http://www.efsa.europa.eu/en/scdocs/doc/nda_op_ej822_vit_k2_en.pdf?ssbinary=true
