Vitamin K2 added for nutritional purposes in foods for particular nutritional uses, food supplements and foods intended for the general population

SUMMARY Following a request from the Commission, the European Food Safety Authority has been asked to carry out the safety assessment for “vitamin K2 as source of vitamin K added for nutritional purposes to foodstuffs, in the context of Regulation (EC) N° 258/97”, and to provide a scientific opinion, based on its consideration of “the safety and bioavailability of vitamin K2 added for nutritional purposes in foods for particular nutritional uses and foods (including food supplements) intended for the general population”. The collective term “vitamin K”, encompasses several lipid-soluble 2-methyl-1,4naphthoquinone derivatives. Naturally occurring forms of vitamin K include vitamin K1 (phylloquinones) and vitamin K2 (menaquinones).

[1]  A. Zuckerman,et al.  IARC Monographs on the Evaluation of Carcinogenic Risks to Humans , 1995, IARC monographs on the evaluation of carcinogenic risks to humans.

[2]  VITAMIN K SUBSTANCES , 2008 .

[3]  M. Iki,et al.  Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study. , 2006, The Journal of nutrition.

[4]  A. Hofman,et al.  Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. , 2004, The Journal of nutrition.

[5]  L. Schurgers,et al.  Tissue-Specific Utilization of Menaquinone-4 Results in the Prevention of Arterial Calcification in Warfarin-Treated Rats , 2003, Journal of Vascular Research.

[6]  Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Vitamin K , 2003 .

[7]  T. Terao,et al.  Improvement of vitamin K status of breastfeeding infants with maternal supplement of vitamin K2 (MK40). , 2002, Seminars in thrombosis and hemostasis.

[8]  A. Tamori,et al.  Vitamin K2 (menatetrenone) for bone loss in patients with cirrhosis of the liver , 2002, American Journal of Gastroenterology.

[9]  L. Schurgers,et al.  Differential lipoprotein transport pathways of K-vitamins in healthy subjects. , 2002, Biochimica et biophysica acta.

[10]  L. Schurgers.  Studies on the role of vitamin K1 and K2 in bone metabolism and cardiovascular disease : structural differences determine different metabolic pathways , 2002 .

[11]  S. Myou,et al.  Vitamin K Administration to Elderly Patients with Osteoporosis Induces No Hemostatic Activation, Even in Those with Suspected Vitamin K Deficiency , 2001, Osteoporosis International.

[12]  N. Bunyaratavej,et al.  Efficacy and safety of Menatetrenone-4 postmenopausal Thai women. , 2001, Journal of the Medical Association of Thailand = Chotmaihet thangphaet.

[13]  Y. Ouchi,et al.  Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. , 2001, Nutrition.

[14]  Opinion of the Scientific Committee on Food , 2001 .

[15]  M. Shiraki,et al.  Vitamin K2 (Menatetrenone) Effectively Prevents Fractures and Sustains Lumbar Bone Mineral Density in Osteoporosis , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[16]  L. Schurgers,et al.  Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. , 2000, Haemostasis.

[17]  Y. Hayashi,et al.  Absorption of Vitamin K2 by Dogs after Oral Administration of a Soft Gelatin Capsule Formulation Containing a New Emulsion‐type Vehicle , 1999, The Journal of pharmacy and pharmacology.

[18]  D. Jukes.  Foodstuffs intended for particular nutritional uses , 1999 .

[19]  H. Sumi.  Accumulation of Vitamin K (Menaquinone-7) in Plasma after Ingestion of Natto and Natto Bacilli (B. subtilis natto) , 1999 .

[20]  T. Fujita,et al.  Effects of menatetrenone on the bone and calcium metabolism in osteoporosis: A double-blind placebo-controlled study , 1998, Journal of Bone and Mineral Metabolism.

[21]  L. Schurgers,et al.  Vitamin K and metabolic bone disease. , 1998, Journal of clinical pathology.

[22]  G. Sturniolo,et al.  Quinone-induced DNA single strand breaks in a human colon carcinoma cell line. , 1997, Carcinogenesis.

[23]  C. Vermeer,et al.  Effect of food composition on vitamin K absorption in human volunteers , 1996, British Journal of Nutrition.

[24]  T. Kameda,et al.  Vitamin K2 inhibits osteoclastic bone resorption by inducing osteoclast apoptosis. , 1996, Biochemical and biophysical research communications.

[25]  J. Castaǹer,et al.  MENATETRENONE : TREATMENT FOR OSTEOPOROSIS , 1996 .

[26]  K. Kikuchi,et al.  Distribution of menaquinone-4, a therapeutic agent for osteoporosis, in bone and other tissues of rats. , 1995, Journal of nutritional science and vitaminology.

[27]  S. Takahashi,et al.  Comparison of intestinal absorption of vitamin K2 (menaquinone) homologues and their effects on blood coagulation in rats with hypoprothrombinaemia. , 1995, Biochemical pharmacology.

[28]  I. Morita,et al.  The inhibitory effect of vitamin K2 (menatetrenone) on bone resorption may be related to its side chain. , 1995, Bone.

[29]  P. Davies,et al.  National Diet and Nutrition Survey: children aged 1.5 to 4.5 years , 1995 .

[30]  L. A. Goldsmith.  3-Month oral (capsule) toxicity study with 1-month reversibility period in dogs with Menatetrenone. , 1995 .

[31]  J. Conly,et al.  Reduction of vitamin K2 concentrations in human liver associated with the use of broad spectrum antimicrobials. , 1994, Clinical and investigative medicine. Medecine clinique et experimentale.

[32]  H. Thijssen,et al.  Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4 , 1994, British Journal of Nutrition.

[33]  J. Conly,et al.  The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K. , 1994, The American journal of gastroenterology.

[34]  J. Conly,et al.  The production of menaquinones (vitamin K2) by intestinal bacteria and their role in maintaining coagulation homeostasis. , 1992, Progress in food & nutrition science.

[35]  A. D'odorico,et al.  Menaquinone mediated free radical generation: a possible mutagenic mechanism. , 1991, Biochemical Society transactions.

[36]  Dietary reference values for food energy and nutrients for the United Kingdom. Report of the Panel on Dietary Reference Values of the Committee on Medical Aspects of Food Policy. , 1991, Reports on health and social subjects.

[37]  K. Nakanishi,et al.  Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. , 1990, Acta Haematologica.

[38]  T. Fujita,et al.  Identification of menaquinone-4 metabolites in the rat. , 1989, Journal of pharmacobio-dynamics.

[39]  K. Shiraki,et al.  Vitamin K absorption capacity and its association with vitamin K deficiency. , 1989, American journal of diseases of children.

[40]  P. Powers,et al.  Development of the human coagulation system in the full-term infant. , 1987, Blood.

[41]  M. Shearer,et al.  Preparative isolation and characterization of the urinary aglycones of vitamin K1 (phylloquinone in man. , 1980, Biochemical medicine.

[42]  D. Hollander,et al.  Vitamin K2 colonic and ileal in vivo absorption: bile, fatty acids, and pH effects on transport. , 1977, The American journal of physiology.

[43]  D. Hollander,et al.  Vitamin K2 absorption by rat everted small intestinal sacs. , 1976, The American journal of physiology.

[44]  D. Hollander,et al.  Colonic absorption of bacterially synthesized vitamin K2 in the rat. , 1976, The American journal of physiology.

[45]  J. Higginson,et al.  International Agency for Research on Cancer. , 1968, WHO chronicle.