Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women

Toshiro Sato, Leon J Schurgers, Kazuhiro Uenishi, Toshiro Sato, Leon J Schurgers, Kazuhiro Uenishi

Abstract

Background: Vitamin K₂ contributes to bone and cardiovascular health. Therefore, two vitamin K₂ homologues, menaquinone-4 (MK-4) and menaquinone-7 (MK-7), have been used as nutrients by the food industry and as nutritional supplements to support bone and cardiovascular health. However, little is known about the bioavailability of nutritional MK-4. To investigate MK-4 and MK-7 bioavailability, nutritional doses were administered to healthy Japanese women.

Findings: Single dose administration of MK-4 (420 μg; 945 nmol) or MK-7 (420 μg; 647 nmol) was given in the morning together with standardized breakfast. MK-7 was well absorbed and reached maximal serum level at 6 h after intake and was detected up to 48 h after intake. MK-4 was not detectable in the serum of all subjects at any time point. Consecutive administration of MK-4 (60 μg; 135 nmol) or MK-7 (60 μg; 92 nmol) for 7 days demonstrated that MK-4 supplementation did not increase serum MK-4 levels. However, consecutive administration of MK-7 increased serum MK-7 levels significantly in all subjects.

Conclusions: We conclude that MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels. MK-7, however significantly increases serum MK-7 levels and therefore may be of particular importance for extrahepatic tissues.

Figures

Figure 1
Figure 1
Change in serum vitamin K2 levels following a single oral dose (420 μg) of MK-4 or MK-7. Each point represents the mean ± SEM of 5 subjects at 0, 2, 4, 6, 10, 24, 48 and 72 h. ■=MK-4; ○=MK-7
Figure 2
Figure 2
Increased serum vitamin K2 levels in subjects after 7 days of consecutive administration (60 μg/day). Each value is expressed as the mean ± SEM of 5 subjects. ■=MK-4;□=MK-7

References

    1. Cranenburg EC, Schurgers LJ, Vermeer C. Vitamin K: The coagulation vitamin that became omnipotent. Thromb Haemost. 2007;98:120–125.
    1. Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in food. Haemostasis. 2000;30:298–307.
    1. Groenen-van Dooren MM, Ronden JE, Soute BA, Vermeer C. Bioavailability of phylloquinone and menaquinones after oral and colorectal administration in vitamin K-deficient rats. Biochem Pharmacol. 1995;50:797–801. doi: 10.1016/0006-2952(95)00202-B.
    1. Sato T, Ohtani Y, Yamada Y, Saitoh S, Harada H. Difference in the metabolism of vitamin K between liver and bone in vitamin K-deficient rats. Br J Nutr. 2002;87:307–314.
    1. Schurgers LJ, Teunissen KJ, Hamulyák K, Knapen MH, Vik H, Vermeer C. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007;109:3279–3283. doi: 10.1182/blood-2006-08-040709.
    1. Fang Y, Hu C, Tao X, Wan Y, Tao F. Effect of vitamin K on bone mineral density: a meta-analysis of randomized controlled trials. J Bone Miner Metab. 2012;30:60–68. doi: 10.1007/s00774-011-0287-3.
    1. Shearer MJ, Newman P. Metabolism and cell biology of vitamin K. Thromb Haemost. 2008;100:530–547.
    1. Chatrou ML, Reutelingsperger CP, Schurgers LJ. Role of vitamin K-dependent proteins in the arterial vessel wall. Hämostaseologie. 2012;31:251–257.
    1. Kimura S, Satoh H, Komai M. The roles of intestinal flora and intestinal function on vitamin K metabolism. J Nutr Sci Vitaminol (Tokyo) 1992;38(suppl):425–428.
    1. Thijssen HH, Vervoort LM, Schurgers LJ, Shearer MJ. Menadione is a metabolite of oral vitamin K. Br J Nutr. 2006;95:260–6. doi: 10.1079/BJN20051630.
    1. Nakagawa K, Hirota Y, Sawada N, Yuge N, Watanabe M, Uchino Y, Okuda N, Shimomura Y, Suhara Y, Okano T. Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature. 2010;468:117–121. doi: 10.1038/nature09464.
    1. Ichikawa T, Horie-Inoue K, Ikeda K, Blumberg B, Inoue S. Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. J Biol Chem. 2006;281:16927–16934. doi: 10.1074/jbc.M600896200.
    1. Ito A, Shirakawa H, Takumi N, Minegishi Y, Ohashi A, Howlader ZH, Ohsaki Y, Sato T, Goto T, Komai M. Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells. Lipids Health Dis. 2011;10:158. doi: 10.1186/1476-511X-10-158.
    1. Schurgers LJ, Vermeer C. Differential lipoprotein transport pathways of K-vitamins in healthy subjects. Biochim Biophys Acta. 2002;1570:27–32. doi: 10.1016/S0304-4165(02)00147-2.
    1. Takeuchi A, Masuda Y, Kimura M, Marushima R, Matsuoka R, Hasegawa M, Takahama M, Onuki M. Minimal effective dose of vitamin K2 (menaquinone-4) on serum osteocalcin concentration in Japanese subjects and safety evaluation of vitamin K2 supplemented in calcium tablet. J Jpn Soc Clin Nutr. 2005;26:254–260.
    1. van Summeren MJ, Braam LA, Lilien MR, Schurgers LJ, Kuis W, Vermeer C. The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children. Br J Nutr. 2009;102:1171–1178. doi: 10.1017/S0007114509382100.
    1. Brugè F, Bacchetti T, Principi F, Littarru GP, Tiano L. Olive oil supplemented with menaquinone-7 significantly affects osteocalcin carboxylation. Br J Nutr. 2011;106:1058–1062. doi: 10.1017/S0007114511001425.
    1. Sato T, Kawahara R, Kamo S, Saito S. Comparison of menaquinone-4 and menaquinone-7 in rats. Vitamins (Japan) 2007;81:377–381.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj