Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7

Toxicology Mechanisms and Methods

Volumn 21, Issue 7, 2011, Pages 520-532

  Pucaj, Kresimir ^a   Rasmussen, Henrik ^b   Møller, Mona ^c   Preston, Tom ^a  

^a Nucro Technics   (Canada)

^b NORWEGIAN INSTITUTE OF PUBLIC HEALTH   (Norway)

^c Kappa Bioscience AS   (Norway)

Author keywords

90 day oral subchronic toxicity study; Acute oral toxicity; Histopathology; Menaquinone 7

Indexed keywords

MENAQUINONE; MENAQUINONE 7; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; FEMALE; LETHAL DOSE; MALE; MOUSE; MOUSE STRAIN; NONHUMAN; PRIORITY JOURNAL; RAT; SINGLE DRUG DOSE; SPRAGUE DAWLEY RAT; TOXICITY TESTING; TREATMENT DURATION;

ANIMALS; ANTIFIBRINOLYTIC AGENTS; BIOMARKERS, PHARMACOLOGICAL; BODY WEIGHT; EATING; FEMALE; LETHAL DOSE 50; MALE; MICE; MICE, INBRED STRAINS; NO-OBSERVED-ADVERSE-EFFECT LEVEL; ORGAN SIZE; ORGAN SPECIFICITY; RATS; RATS, SPRAGUE-DAWLEY; TOXICITY TESTS, ACUTE; TOXICITY TESTS, SUBCHRONIC; VITAMIN K 2;

ANIMALIA; MUS; RATTUS; ZEA MAYS;

EID: 80051740908     PISSN: 15376516     EISSN: 15376524     Source Type: Journal    
DOI: 10.3109/15376516.2011.568983     Document Type: Article

References (30)

1. Beulens JW, Bots ML, Atsma F, Bartelink ML, Prokop M, Geleijnse JM, Witteman JC, Grobbee DE, van der Schouw YT. 2009. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis 203:489-493.
2. Binkley NC, Krueger 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 76:1055-1060. (Pubitemid 35244677)
3. Booth SL, Suttie JW. 1998. Dietary intake and adequacy of vitamin K. J Nutr 128:785-788. (Pubitemid 28225505)
4. Bügel S. 2008. Vitamin K and bone health in adult humans. Vitam Horm 78:393-416.
5. Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, Hu H, Vieth R, Thompson L, Jamal S, Josse R. 2008. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med 5:e196.
6. Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ. 2006. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 166:1256-1261. (Pubitemid 43967576)
7. Cranenburg EC, Schurgers LJ, Vermeer C. 2007. Vitamin K: the coagulation vitamin that became omnipotent. Thromb Haemost 98:120-125. (Pubitemid 47074186)
8. Doi T, Shirotsuka Y, Yoshioka M, Yamamoto S, Tsukuda R, Suzuki T. 1995. Thirteen-week oral toxicity study of ipriflavone (TC-80) administered to rats concurrently with menatetrenone (vitamin K2). Jpn Pharmacol Ther 23:205-215.
9. EFSA. 2008. Vitamin K2 added for nutritional purposes in foods for particular nutritional uses, food supplements and foods intended for the general population and vitamin K2 as a source of vitamin K added for nutritional purposes to foodstuffs, in the context of Regulation (EC) No. 258/971, Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies. EFSA J 822:1-31.
10. Gast GC, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT. 2009. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis 19:504-510.
11. Geleijnse JM, 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. J Nutr 134:3100-3105. (Pubitemid 39470091)
12. Goldsmith LA, Keller JG, Noguchi M, Matsubara Y, Sagami F. 1995. 3-Month oral (capsule) toxicity study with 1-month reversibility period in dogs with menatetrenone. Jpn Pharmacol Ther 23:157-170. (Pubitemid 26012787)
13. Hosokawa S, Nakanowatari J, Ogura K., Okada F, Sagami F. 1995. 52-Week toxicity study of menatetrenone in rats by oral administration. Jpn Pharmacol Ther 23:171-184. [English Summary & Tables from Japanese Article] (Pubitemid 26012788)
14. 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 136:1323-1328.
15. Iwamoto J, Sato Y, Takeda T, Matsumoto H. 2009. High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature. Nutr Res 29:221-228.
16. Iwamoto J, Takeda T, Sato Y. 2006. Menatetrenone (vitamin K2) and bone quality in the treatment of postmenopausal osteoporosis. Nutr Rev 64:509-517. (Pubitemid 46057718)
17. Knapen MH, Schurgers LJ, Vermeer C. 2007. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 18:963-972. (Pubitemid 46889558)
18. Physicians Desk Reference for Nutritional Supplements, 2nd Edition. 2008. Vitamin K, Hendler SS, Rorvik D, eds. Physicians Desk Reference Inc., NJ, pp. 708-713.
19. Rishavy MA, Pudota BN, Hallgren KW, Qian W, Yakubenko AV, Song JH, Runge KW, Berkner KL. 2004. A new model for vitamin K-dependent carboxylation: the catalytic base that deprotonates vitamin K hydroquinone is not Cys but an activated amine. Proc Natl Acad Sci USA 101:13732-13737. (Pubitemid 39298476)
20. Sato T, Yamada Y, Ohtani Y, Mitsui N, Murasawa H, Araki S. 2001. Production of menaquinone (vitamin K2)-7 by Bacillus subtilis. J Biosci Bioeng 91:16-20. (Pubitemid 32163401)
21. Schurgers LJ, Teunissen KJ, Hamuly K, Knapen MH, Vik H, Vermeer C. 2007. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 109:3279-3283. (Pubitemid 46572513)
22. Schurgers LJ, Vermeer C. 2000. Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis 30:298-307. (Pubitemid 32453662)
23. Schurgers LJ, Vermeer C. 2002. Differential lipoprotein transport pathways of K-vitamins in healthy subjects. Biochim Biophys Acta 1570:27-32. (Pubitemid 34311890)
24. Shea MK, Booth SL. 2008. Update on the role of vitamin K in skeletal health. Nutr Rev 66:549-557.
25. Shearer MJ, Newman P. 2008. Metabolism and cell biology of vitamin K. Thromb Haemost 100:530-547.
26. Sumi H. 1999. Accumulation of vitamin K (menaquinone-7) in plasma after ingestion of natto and natto bacilli (B. subtilis natto). Food Sci Technol Res 5:48-50. (Pubitemid 129605370)
27. van Summeren MJ, Braam LA, Lilien MR, Schurgers LJ, Kuis W, Vermeer C. 2009. The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children. Br J Nutr 102:1171-1178.
28. Vanatta PM, Keller JG, Steinberg M, Noguchi M, Matsubara Y, Sagami F. 1995. 12-Month oral (capsule) toxicity study with 3-month reversibility period in dogs with menatetrenone. Jpn Pharmacol Ther 23:191-206. (Pubitemid 26018446)
29. Yamaguchi M, Kakuda H, Gao YH, Tsukamoto Y. 2000. Prolonged intake of fermented soybean (natto) diets containing vitamin K2 (menaquinone-7) prevents bone loss in ovariectomized rats. J Bone Miner Metab 18:71-76. (Pubitemid 30133663)
30. Yamaguchi M, Taguchi H, Gao YH, Igarashi A, Tsukamoto Y. 1999. Effect of vitamin K2 (menaquinone-7) in fermented soybean (natto) on bone loss in ovariectomized rats. J Bone Miner Metab 17:23-29. (Pubitemid 29117748)