일반의약품 비타민 K 의진면목 (1) 저자김성철영남대임상약학대학원겸임교수약학정보원학술자문위원 개요 현재약국임상에서지용성비타민의일종인비타민 K 제제는전부전문의약품으로인식되어있으며, 일부종합비타민제제에함유되어있어도비타민 K의효능과새로이연구되고있는적응증에대해서는관심도가떨어진

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1 일반의약품 비타민 K 의진면목 (1) 저자김성철영남대임상약학대학원겸임교수약학정보원학술자문위원 개요 현재약국임상에서지용성비타민의일종인비타민 K 제제는전부전문의약품으로인식되어있으며, 일부종합비타민제제에함유되어있어도비타민 K의효능과새로이연구되고있는적응증에대해서는관심도가떨어진것은주지의사실이다. 이번호에는지용성비타민 K의작용기전과새로이연구되고있는적응증및작용기전특히외용비타민 K 제제에대하여숙지하여약국경영에다소도움이되었으면한다. 키워드 비타민 K, 비타민 K 의종류, 비타민 K 가많이함유된음식 1. 비타민 K 의역사 비타민 K는 1929년덴마크의과학자인헨릭댐 (Henrik Dam) 이저콜레스테롤식을먹인닭에서의콜레스테롤의역할에대한연구중에발견하였다. 저콜레스톨식을시행한동물에서출혈경향이나타남을발견하고, 콜레스테롤식을시행하여도출혈이멈추지않음으로출혈에관여하는제2의물질이있음을확인하고이것을응고비타민이라고칭하였다. 이것을발표한독일학회에서본물질을독일어로응고즉 Koagulation 비타민이라하고비타민 K라고명명하였다. 이후미국세인트루이스대학의에드워드도이시가이물질의분자구조와화학적성질을발견하였다. 이것으로댐과도이시는 1943에노벨의학상을수상하였다. 이후비타민 K의연구가활발하게추진되어현재는천연비타민인 K 1 과 K 2 및합성비타민인 K 3, K 5, K 7 을발견하게되었다. 이후수십년동안비타민결핍모델닭을이용하여각종음식속에함유된비타민 K의함량을결정하는기준으로하게되었다. 전세계적으로본연구는덴마크의코펜하겐대학생물학과, 미국아이오와대학의병리학과및메이요크리닉에서활발하게연구를진행하였다. 1938년에프로트롬빈결핍증을수반한황달환자에있어서의생명을위협하는출혈경향에비타민 K를사용함으로써임상적성공을거두면서현재의료현장에널리사용하게되었다. 2. 비타민 K 의종류 비타민 K는분자구조적으로는모두유사하며혈액응고에관여하는특정단백질의후변환조절 (post-translational modification) 및뼈및타조직의대사경로에작용하는인체에필수적인지용성비타민이다. 비타민 K 1, 비타민 K 2 는 2-methyl-1,4-naphthoquinone 유도체인천연의비타민 K군이다. 1

2 (1) 비타민 K 1 비타민 K 1 은 phylloquinone, phytomenadione, 또는 phytonadione으로알려져있으며, 주로직접광합성이가능한짙은녹색잎을가진식물에서합성되어진다. 그러므로식물성비타민 K라고일컫는다. 비타민 K 1 은이것을섭취한동물에있어서도혈액응고작용을나타내게되며, 대부분의동물들에서비타민 K 1 은체내에서비타민 K 2 로전환된다. [ 그림 ] 비타민 K 1 및 K 2 (MK-4/MK-7) 구조식 (2) 비타민 K 2 비타민 K 2 는동물에있어서는저장형태로써 isoprenoid 측쇄의길이에따라몇개의아류로구분된다. 이것의동족체를 menaquinones라고일컫는다. 이것을줄여서 MK-n으로칭한다. M은 menaquinone을의미하며 K는비타민 K를뜻하며 n은 isoprenoid 측쇄의수를나타낸다. 즉 MK-4는측쇄에 4개의 isoprene 잔기가있는것임을의미한다. 통상 menatetrenone이라고일컬어지는 Menaquinone-4가동물에있어서는가장흔한비타민 K 2 의형태로써, 비타민 K 1 으로부터동맥벽, 췌장및고환에서합성되어지며, 이것은일종의효소기능을발휘하는것이비타민 K 1 과는상이한점이다. 동물의대장에존재하는세균의혐기성호흡과정을통하여비타민 K 1 은비타민 K 2 로변환된다. 이세균은 MK-7에서부터 MK-11까지더긴측쇄를형성할수있다. 현재까지알려진합성비타민 K는 K 3, K 4 와 K 5 이며이중 menadione이라고불리는비타민 K 3 의독성이임상에서보고되어지고있다. 3. 비타민 K 의섭취및흡수 비타민 K는소장또는대장의손상으로흡수불량이존재하거나광범위항생제의투여로장내정상세균총의살멸에의하여생성이저하되며, 연령에따라비타민 K의합성이저하되어혈중농도가낮아진다. 연구에의하면항생제를투여한쥐실험에서정상식사를한쥐보다약 74% 정도혈중농도가낮아졌음이보고되어있다. 최근연구에의하면와파린을계속투여한환자는동맥벽의석회화진행이되었다고보고하였다. 그러나비타민 K를투여한군에서는와파린유도성석회화는감소하였다. 2

3 4. 일일권장량및많이함유된음식 (1) 일일권장량 국내의 1일권장량은없지만미국의경우 1일권장량 (DRI : Dietary Reference Intake) 은다음과같다. - 남성 : 120 μg - 여성 : 90 μg - 유아 : μg - 소아및청소년 : μg - 1일최대량 : 1000 μg ( 비타민 K 1 ) osteocalcin의 carboxylation을최대화하기위함 (2) 많이함유된음식 요구르트, 알팔파, 노른자, 홍화유, 대두유, 물고기의간유, 해조류, 녹색잎야채, 민들레, 케일, 시금치, 브로컬리, 아스파라거스, 파슬리, 키위, 포도, 아보가도등에함유되어있다. 다음표는비타민 K 1 과 K 2 가많이함유된음식을표한다. ( 비타민 K 1 ) Food Serving Size Vit. K 1 Vit. K 1 Food Serving Size Kale, cooked 1/2 cup 531 Parsley, raw 1/4 cup 246 Spinach, cooked 1/2 cup 444 Spinach, raw 1 cup 145 Mustard greens, cooked 1/2 cup 210 Mustard greens, raw 1 cup 279 Broccoli, cooked 1 cup 220 Broccoli, raw 1 cup 89 Cabbage, cooked 1/2 cup 82 Green leaf lettuce 1 cup 71 Asparagus 4 spears 48 ( 비타민 K 2 ) Food 100 grams (3.5 oz) portion Vit. K 2 Proportion of vit. K 2 Food 100 grams (3.5 oz) portion Vit. K 2 Proportion of vit. K 2 Natto, cooked 1,103.4 (90% MK-7, 10% other MK) Chicken Leg 8.5 (100% MK-4) Goose liver pâté (100% MK-4) Ground beef (medium fat) 8.1 (100% MK-4) Hard cheeses (Dutch (6% MK-4, Chicken liver 76.3 Gouda style), raw 94% other MK) (braised) 6.7 (100% MK-4) Soft cheeses (French (6.5 MK-4, 56.5 Brie style) 93.5% other MK) Hot dog 5.7 (100% MK-4) Egg yolk, (98% MK-4, 32.1 (Netherlands) 2% other MK) Bacon 5.6 (100% MK-4) Goose leg 31.0 (100% MK-4) Calf s liver 6.0 (100% MK-4) Egg yolk (U.S.) 15.5 (100% MK-4) Sauerkraut 4.8 (100% MK-4) Butter 15.0 (100% MK-4) Whole milk 1.0 (100% MK-4) Chicken liver (raw) 14.1 (100% MK-4) Cow s liver 0.4 (100% MK-4) Chicken liver 12.6 (100% MK-4) Egg white 0.4 (100% MK-4) [ 출처 : Nutrition facts, calories in food, labels, nutritional information and analysis. Nutritiondata.com (13 February 2008). Retrieved on 21 April 2013.] 3

4 5. 독성 뚜렷이알려진독성은없다. 그러나알레르기가알려져있으며, 다만고용량 (1 일 135mg 이상 ) 투여시응 고성장애와용혈성빈혈, 간세포독성이보고되어있다. 약사 Point - 비타민 K는단순히혈액응고작용만있는것이아니라와파린또는아스피린의장기복용으로야기되는혈관석회화의예방에도도움이된다. - 비타민 K는항산화작용이있어서인슐린의저항성을낮춰줌으로당뇨병환자에게는비타민 K가함유된종합비타민제제를반드시추천하여야한다. - 비타민 K 외용제제는각종멍 ( 자반증 ) 에효과가입증되어있다. ( 멍소실의시간단축, 흉터최소화 ) - 아직연구중에있지만간암의예방, 전립선암에도효과가보고되어있다. 참고문헌 1. Dam, H. (1935). "The Antihæmorrhagic Vitamin of the Chick.: Occurrence And Chemical Nature". Nature 135 (3417): Will, BH; Usui Y, Suttie JW (1992). "Comparative Metabolism and Requirement of Vitamin K in Chicks and Rats". Journal of Nutrition 122 (12): Vermeer, C; Braam L (2001). "Role of K vitamins in the regulation of tissue calcification". Journal of bone and mineral metabolism 19 (4): Suttie, JW (1995). "The importance of menaquinones in human nutrition". Annual Review of Nutrition 15: Weber, P (2001). "Vitamin K and bone health". Nutrition17 (10): Sato, Y; Kanoko T, Satoh K, Iwamoto J (2005). "Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease". Bone36 (1): Inoue, T; Sugiyama T, Matsubara T, Kawai S, Furukawa S (2001). "Inverse correlation between the changes of lumbar bone mineral density and serum undercarboxylated osteocalcin after vitamin K 2(menatetrenone) treatment in children treated with glucocorticoid and alfacalcidol". Endocrine Journal 48 (1): Sasaki, N, Kusano E, Takahashi H, Ando Y, Yano K, Tsuda E, Asano Y; Kusano E, Takahashi H, Ando Y, Yano K, Tsuda E, Asano Y (2005). "Vitamin K 2 inhibits glucocorticoid-induced bone loss partly by preventing the reduction of osteoprotegerin(opg)". Journal of bone and mineral metabolism 23 (1): Yonemura, K; Fukasawa H, Fujigaki Y, Hishida A. (2004). "Protective effect of vitamins K 2 and D 3 on prednisolone-induced loss of bone mineral density in the lumbar spine". American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation 43 (1): Shiomi, S; Nishiguchi S, Kubo S (2002). "Vitamin K 2(menatetrenone) for bone loss in patients with cirrhosis of the liver". The American Journal of Gastroenterology 97 (4): Sato, Y; Kanoko T, Satoh K, Iwamoto J (2005). "Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease". Bone36 (1): Sato, Y; Honda Y, Kaji M (2002). "Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency". Bone31 (1): Nishiguchi, S; Shimoi S, Kurooka H (2001). "Randomized pilot trial of vitamin K 2 for bone loss in patients with primary biliary cirrhosis". Journal of Hepatology 35 (4):

5 14. Viegas, C. S. B.; Cavaco, S.; Neves, P. L.; Ferreira, A.; João, A.; Williamson, M. K.; Price, P. A.; Cancela, M. L.; Simes, D. C. (2009). "Gla-Rich Protein is a Novel Vitamin K-Dependent Protein Present in Serum That Accumulates at Sites of Pathological Calcifications". The American Journal of Pathology175 (6): Binkley NC, Krueger DC, Kawahara TN, angelke JA, Chappell RJ, Suttie JW (2002). "A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation". Am.J.Clin.Nutr.76 (5): Spronk, H. M. H.; Soute, B. A. M.; Schurgers, L. J.; Thijssen, H. H. W.; De Mey, J. G. R.; Vermeer, C. (2003). "Tissue-Specific Utilization of Menaquinone-4 Results in the Prevention of Arterial Calcification in Warfarin-Treated Rats". Journal of Vascular Research 40 (6): Nutrition Facts and Information for Parsley, raw. Nutritiondata.com. Retrieved on 21 April Nutrition facts, calories in food, labels, nutritional information and analysis. Nutritiondata.com (13 February 2008). Retrieved on 21 April Vitamin K. Vivo.colostate.edu (2 July 1999). Retrieved on 21 April Ikeda; 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". The Journal of nutrition 136 (5): Katsuyama; Ideguchi, S; Fukunaga, M; Saijoh, K; Sunami, S (2002). "Usual dietary intake of fermented soybeans (Natto) is associated with bone mineral density in premenopausal women". Journal of nutritional science and vitaminology 48 (3): Gast, G. C. M.; De Roos, N. M.; Sluijs, I.; Bots, M. L.; Beulens, J. W. J.; Geleijnse, J. M.; Witteman, J. C.; Grobbee, D. E.; Peeters, P. H. M.; Van Der Schouw, Y. T. (2009). "A high menaquinone intake reduces the incidence of coronary heart disease". Nutrition,Metabolism and Cardiovascular Diseases 19 (7): Geleijnse; Vermeer, C; Grobbee, DE; Schurgers, LJ; Knapen, MH; van der Meer, IM; Hofman, A; Witteman, JC (2004). "Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: The Rotterdam Study". The Journal of nutrition 134 (11): Allison AC (2001). "The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease". Medical hypotheses 57 (2): Cohen, JL; Bhatia, AC (November 2009). "The role of topical vitamin K oxide gel in the resolution of postprocedural purpura". Journal of drugs in dermatology :JDD8 (11): Leu, S; Havey, J; White, LE; Martin, N; Yoo, SS; Rademaker, AW; Alam, M (September 2010). "Accelerated resolution of laser-induced bruising with topical 20% arnica: a rater-blinded randomized controlled trial". The British journal of dermatology 163 (3): "Vitamin K Found to Protect Against Liver Cancer". utraingredients.com (21 July 2004) 28. Nimptsch K, Rohrmann S, Linseisen J (2008). "Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition. (EPIC-Heidelberg)". Am.J.Clin.Nutr.87 (4): American Cancer Society: Vitamin K. Cancer.org. Retrieved on 21 April Ibarrola-Jurado, N.; Salas-Salvado, J.; Martinez-Gonzalez, M. A.; Bullo, M. (2012). "Dietary phylloquinone intake and risk of type 2 diabetes in elderly subjects at high risk of cardiovascular disease". American Journal of Clinical Nutrition 96 (5):

일반의약품_비타민 K의 진면목 (2)_편집완료_최종.hwp

일반의약품_비타민 K의 진면목 (2)_편집완료_최종.hwp 일반의약품 비타민 K 의진면목 (2) 저자김성철영남대임상약학대학원겸임교수약학정보원학술자문위원 개요 현재약국임상에서지용성비타민의일종인비타민 K 제제는전부전문의약품으로인식되어있으며, 일부종합비타민제제에함유되어있어도비타민 K의효능과새로이연구되고있는적응증에대해서는관심도가떨어진것은주지의사실이다. 이번호에는지용성비타민 K의작용기전과새로이연구되고있는적응증및작용기전특히외용비타민