Vitamin K Snapshot Monograph

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1 vitamins minerals nutrients Vitamin K Snapshot Monograph Vitamin K1 and Vitamin K2 Most Frequent Reported Uses: Blood clotting Anticoagulant reversal; bleeding disorders Osteoporosis prevention Arthritis, including oste- and rheumatoid Prevention of Nutrient name(s): Vitamin K1 (Phytonadione) Vitamin K2 (Menaquinone) Menaquinone 3 (Menadione or MK3) Menaquinone 4 (menantrenone or MK4) Introduction: Vitamin K refers to a group of three fat-soluble compounds called naphthoquinones. Phytonadione (K 1 ) is the natural form of vitamin k and occurs in green plants, and menaquinone (K 2 ) and menantrenone (MK4) are synthesized by the intestinal microflora ( probiotic flora). Menadione (MK 3 ) is a water-soluble form of vitamin K and is manufactured synthetically.

2 Vitamin K2 is used in formulations when increased absorption is needed. Although K2 vitamins comprise only some 10-25% of the total dietary vitamin K intake, menaquinones produce much of the therapeutic effects of vitamin K (Beulens et al, 2013). Functions: Blood Clotting: Vitamin K is an enzymatic cofactor that is necessary for the production of a number of blood clotting factors, including prothrombin, and factors VII, IX, and X. A deficiency in vitamin K may lead to deficiencies in clotting factors and bleeding can occur. Cardiovascular: Animal and human studies have reported that vitamin K2 may decrease the calcification of arterial plaque, thereby reducing the risk of developing cardiovascular diseases such as atherosclerosis and stroke (Rees et al, 2010). Vitamin K2 is reported to help decrease the cardio-metabolic problems including cardiovascular disease, insulin resistance/type 2 diabetes and metabolic syndrome (MetS) (Rees et al, 2010). Osteoporosis Prevention: Necessary for the synthesis of osteocalcin, a unique protein in bone, which attracts calcium to bone tissue. Osteocalcin modulates the deposition of calcium into bone matrix. Therefore, vitamin K may play a role in the prevention and treatment of osteoporosis. Vitamin K2 has been reported to be beneficial in improving bone quality in type 2 diabetics (Iwamoto et al, 2011). A 2009 systematic review reported that vitamin K1 has similar efficacy to the bisphosphonates in bone fracture prevention, but further research is necessary (Stevenson et al, 2009). A 2009 meta-analysis reported that use of vitamin K2 helped decrease the incidence of non-vertebral and hip fractures in patients with neurological conditions, including Alzheimer s disease, stroke and Parkinson s disease (Iwamoto et al, 2009). A 2009 meta-analysis reported that high dose vitamin K2 helped to decrease the incidence of bone fracture in postmenopausal women (Iwamoto et al, 2009). Arthritis/Inflammatory Conditions: Vitamin K may have multiple effects on articular cartilage and subchondral bone that can modulate the pathogenesis of osteoarthritis (OA) (Ishii et al, 2012). A clinical study reported that vitamin K2 administration helped improve the inflammatory C-reactive protein (CRP) levels and reduce disease progression of rheumatoid arthritis (Ebina et al, 2012). Cancer: Studies report vitamin K2 use may decrease the rate of recurrence in patients with hepatocellular cancer (Riaz et al, 2012). Dosage: DRI* Women: 65mcg daily Men: 80mcg daily ODA** (Adults) Vitamin K mg daily

3 Vitamin K2 45 mg daily * The Dietary Reference Intakes (DRI) are the most recent set of dietary recommendations established by the Food and Nutrition Board of the Institute of Medicine, They replace previous RDAs, and may be the basis for eventually updating the RDIs. **The Optimum Daily Allowance (ODA) represents a reference level beyond the RDI, and is often many times higher than the RDI to prevent diseases such as aging or cancer. These numbers are based on clinical use. Symptoms of Deficiency: Those with an increased need for vitamin K include: o Alzheimer s Disease o Atherosclerosis o Alcoholics o Gastrointestinal conditions that may limit vitamin K absorption, including ulcerative colitis, celiac disease, biliary obstruction, IBS and IBD. o Malnutrition o Those with blood clotting disorders o Aging population The following drugs can cause a depletion of vitamin K, which may increase an individual s need for vitamin K: o Antibiotics o Anticoagulants, including warfarin (Coumadin) o Anticonvulsants (barbiturates and phenytoin) o Cholestyramine (Questran) o Mineral oil Side Effects and Warnings: There are no known toxic effects from taking vitamin K; however large doses of vitamin K2 can lead to hemolytic anemia and possible hepatic damage. Food Sources: Best sources of vitamin K1 are liver, green leafy vegetables, and members of the cabbage family. Some fermented foods, such as natto (soybean curd), contains high levels of vitamin K2 (menaquinone). Since vitamin K is also synthesized by intestinal bacteria, humans are not dependent upon food for this nutrient. However, imbalances in microflora can lead to vitamin K deficiencies.

4 Vitamin K (K1 and K2) Patient Snapshot Uses: Vitamin K is important for normal blood clotting. Vitamin K is important for bone health, decreasing the risks of developing osteoporosis. Dosage: DRI* Women: 65mcg (micrograms) daily Men: 80mcg daily ODA** (Adults) Vitamin K1 Vitamin K mg daily 45 mg daily * The Dietary Reference Intakes (DRI) are the most recent set of dietary recommendations established by the Food and Nutrition Board of the Institute of Medicine, They replace previous RDAs, and may be the basis for eventually updating the RDIs. **The Optimum Daily Allowance (ODA) represents a reference level beyond the RDI, and is often many times higher than the RDI to prevent diseases such as aging or cancer. These numbers are based on clinical use. Special Concerns: If you are taking prescription or non-prescription medications, have a pre-existing medical condition, or are pregnant and/or breastfeeding, talk with your healthcare provider before taking any dietary supplement. Large doses of vitamin K2 can lead to anemia and/or liver damage. Do not take if there is an allergy to any component of this dietary supplement. Those with an increased need for vitamin K include: o Alzheimer s Disease o Atherosclerosis o Alcoholics o Gastrointestinal conditions that may limit vitamin K absorption, including ulcerative colitis, celiac disease, biliary obstruction, irritable bowel syndrome (IBS) o Malnutrition o Those with blood clotting disorders The following medications may deplete vitamin K from the body. When taking these medications, it is best to supplement your diet with vitamin K: o Antibiotics o Anticonvulsants DISCLAIMER: Statements made are for educational purposes and have not been evaluated by the US Food and Drug Administration. They are not intended to diagnose, treat, cure, or prevent any disease. If you have a medical condition or disease, please talk to your doctor prior to using the recommendations given.

5 References: Allison AC. The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease. Med Hypotheses. Aug2001;57(2): Beulens JW, Booth SL, van den Heuvel EG, et al,. The role of menaquinones (Vitamin K2) in human health. Br J Nutr. 2013;[Epub ahead of print]. Burnier JP, Borowski M, Furie BC, Furie B. Gamma-carboxyglutamic acid. Mol Cell Biochem. Sep1981;39: Byrd DC, Stephens MA, Hamann GL, Dorko C. Subcutaneous phytonadione for reversal of warfarininduced elevation of the International Normalized Ratio. Am J Health Syst Pharm. Nov1999;56(22): Ebina K, Shi K, Hirao M, et al. Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis. Mod Rheumatol. 2012;[Epub ahead of print]. Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr. Jan1999;69(1):74-9. Igarashi O. Vitamin K. Nippon Rinsho. Apr1993;51(4): Iwamoto I, Kosha S, Noguchi S, Murakami M, Fujino T, Douchi T, Nagata Y. A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapy. Maturitas. Jan1999;31(2): Iwamoto J, Matsumoto H, Takeda. Efficacy of menatetrenone (Vitamin K2) against non-vertebral and hip fractures in patients with neurological diseases: meta-analysis of three randomized, controlled trials. Clin Drug Investig. 2009;29(7): Iwamoto J, Sato Y, Takeda T, et al. High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature. Nutr Res. 2009;29(4): Iwamoto J, Sato Y, Takeda T, et al. Bone quality and vitamin k2 in type 2 diabetes: a review. Nutr Rev. 2011;69(3): Iwamoto J, Sato Y. Menatetrenone for the treatment of osteoporosis. Expert Opin Pharmacother. 2013;14(4): Jie KS, Bots ML, Vermeer C, Witteman JC, Grobbee DE. Vitamin K intake and osteocalcin levels in women with and without aortic atherosclerosis: a population-based study. Atherosclerosis. Jul1995;116(1): Kawashima H, Nakajima Y, Matubara Y, Nakanowatari J, Fukuta T, Mizuno S, et al. Effects of vitamin K2 (menatetrenone) on atherosclerosis and blood coagulation in hypercholesterolemic rabbits. Jpn J Pharmacol. Oct1997;75(2): Patel RJ, Witt DM, Saseen JJ, Tillman DJ, Wilkinson DS. Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation. Pharmacotherapy. Oct2000;20(10): Rees K, Guraewal S, Wong YL, et al. Is vitamin K consumption associated with cardio-metabolic disorders? A systematic review. Maturitas. 2010;67(2):121-8.

6 Riaz IB, Riaz H, Riaz T, et al. Role of vitamin K2 in preventing the recurrence of hepatocellular carcinoma after curative treatment: a meta-analysis of randomized controlled trials. BMC Gastroenterol. 2012;12:170. Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res. Mar2000;15(3): Stevenson M, Lloyd-Jones M, Papaioannou D. Vitamin K to prevent fractures in older women: systematic review and economic evaluation. Health Technol Assess. 2009;13(45):iii-xi, Weber P. Vitamin K and bone health. Nutrition. Oct2001;17(10): Zhong JH, Mo XS, Xiang BD, et al. Postoperative use of the chomopreventive vitamin K2 analog in patient with hepatocellular carcinoma. PLoS One. 2013;8(3):e DISCLAIMER: Statements made are for educational purposes and have not been evaluated by the US Food and Drug Administration. They are not intended to diagnose, treat, cure, or prevent any disease. If you have a medical condition or disease, please talk to your doctor prior to using the recommendations given.

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