Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7
Open Access
- 21 March 2011
- journal article
- Published by Taylor & Francis Ltd in Toxicology Mechanisms and Methods
- Vol. 21 (7), 520-532
- https://doi.org/10.3109/15376516.2011.568983
Abstract
Menaquinone-7 (MK-7) is part of a family of vitamin K that are essential co-factors for the enzyme γ-glutamyl carboxylase, which is involved in the activation of γ-carboxy glutamate (Gla) proteins in the body. Gla proteins are important for normal blood coagulation and normality of bones and arteries. The objective of this study was to examine the potential toxicity of synthetic MK-7 in BomTac:NMRI mice and in Sprague-Dawley rats. In an acute oral toxicity test, mice were administered a single oral dose of 2000 mg/kg body weight (limit dose) and no toxicity was observed during the 14-day observation period. In the subchronic oral toxicity test in rats, animals were administered MK-7 for 90 days by gavage at the following doses: 0 (vehicle control, corn oil), 2.5, 5, and 10 mg/kg body weight/day. All generated data, including clinical observations, ophthalmology, clinical pathology, gross necropsy, and histopathology, revealed no compound-related toxicity in rats. Any statistically significant findings in clinical pathology parameters and/or organ weights noted were considered to be within normal biological variability. Therefore, under the conditions of this experiment, the median lethal dose (LD50) of MK-7 after a single oral administration in mice was determined to be greater than the limit dose level of 2000 mg/kg body weight. The no observed adverse effect level (NOAEL) of MK-7, when administered orally to rats for 90 days, was considered to be equal to 10 mg/kg body weight/day, the highest dose tested, based on lack of toxicity during the 90-day study period.Keywords
This publication has 28 references indexed in Scilit:
- The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal childrenBritish Journal of Nutrition, 2009
- Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled TrialPLoS Medicine, 2008
- Update on the role of vitamin K in skeletal healthNutrition Reviews, 2008
- Metabolism and cell biology of vitamin KThrombosis and Haemostasis, 2008
- Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal womenOsteoporosis International, 2007
- Vitamin K: The coagulation vitamin that became omnipotentThrombosis and Haemostasis, 2007
- Vitamin K–containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7Blood, 2006
- Menatetrenone (Vitamin K2) and Bone Quality in the Treatment of Postmenopausal OsteoporosisNutrition Reviews, 2006
- Determination of Phylloquinone and Menaquinones in FoodPathophysiology of Haemostasis and Thrombosis, 2000
- Accumulation of Vitamin K(Menaquinone-7) in Plasma after Ingestion of Natto and Natto Bacilli(B. subtilis natto).Food Science and Technology Research, 1999