Category Archives: MK-4

Low Dose MK-4 May Benefit Bones in Postmenopausal Japanese Women

Abstract

Effect of low dose vitamin K2 (MK-4) supplementation on bio-indices in postmenopausal Japanese women.

It has been reported that treatment with a pharmacological dose (45 mg/d) of menaquinone-4 (MK-4) prevents bone loss in postmenopausal women. However, it is not known whether supplementation with low dose MK-4 has beneficial effects on bone metabolism in healthy women. The aim of this study is to examine the effects of the supplementation of 1.5 mg/d MK-4 for 4 wk on bone and lipid metabolism in healthy postmenopausal Japanese women. The study was performed as a randomized double blind placebo-controlled trial. The participants aged 53-65 y were randomly assigned to 2 groups and supplemented with 1.5 mg/d of MK-4 or a placebo for 4 wk (n=20 for each group). The most marked effects of MK-4 intake were observed on serum osteocalcin (OC) concentrations. Serum undercarboxylated OC (ucOC) concentration decreased, and the gamma-carboxylated OC (GlaOC) and GlaOC/GlaOC+ucOC ratio that indicates the degree of OC gamma-carboxylation increased significantly at 2 and 4 wk compared with that at baseline in the MK-4 group. The serum ucOC and GlaOC concentrations in the MK-4 group were significantly different from those in the placebo group at 2 wk. These results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC gamma-carboxylation. The concentrations of serum lipids and other indices were not different between the groups at either intervention period. Thus, the additional intake of MK-4 might be beneficial in the maintenance of bone health in postmenopausal Japanese women.

Koitaya N, Ezaki J, Nishimuta M, Yamauchi J…
J. Nutr. Sci. Vitaminol. Feb 2009
PMID: 19352059 | Free Full Text

In conclusion, our study clearly shows that the vitamin K status of postmenopausal women taking an extra dose of 1.5 mg MK-4 daily substantially improved after 4 wk. This improved satus was evidenced by the more than 1 ng/mL of serum MK-4 concentration. This suggests that increasing MK-4 intake by 1.5 mg/d led to an increase in the degree of γ-carboxylation of OC. Thus, the supplementation of low doses of vitamin K2 may favorably affect bone health in healthy postmenopausal women. It is desirable that the required amount of vitamin K be taken with daily meals.

Review: Vitamin K1 and MK-4 Reduce Bone Loss

Abstract

Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials.

Observational and some experimental data suggest that low intake of vitamin K may be associated with an increased risk of fracture.
To assess whether oral vitamin K (phytonadione and menaquinone) supplementation can reduce bone loss and prevent fractures.
The search included the following electronic databases: MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), the Cochrane Library (issue 2, 2005), the ISI Web of Science (1945 to June 2005), the National Research Register (inception to the present), Current Controlled Trials, and the Medical Research Council Research Register.
Randomized controlled trials that gave adult participants oral phytonadione and menaquinone supplements for longer than 6 months were included in this review.
Four authors extracted data on changes in bone density and type of fracture. All articles were double screened and double data extracted.
Thirteen trials were identified with data on bone loss, and 7 reported fracture data. All studies but 1 showed an advantage of phytonadione and menaquinone in reducing bone loss. All 7 trials that reported fracture effects were Japanese and used menaquinone. Pooling the 7 trials with fracture data in a meta-analysis, we found an odds ratio (OR) favoring menaquinone of 0.40 (95% confidence interval [CI], 0.25-0.65) for vertebral fractures, an OR of 0.23 (95% CI, 0.12-0.47) for hip fractures, and an OR of 0.19 (95% CI, 0.11-0.35) for all nonvertebral fractures.
This systematic review suggests that supplementation with phytonadione and menaquinone-4 reduces bone loss. In the case of the latter, there is a strong effect on incident fractures among Japanese patients.

Cockayne S, Adamson J, Lanham-New S, Shearer MJ…
Arch. Intern. Med. Jun 2006
PMID: 16801507

Review: Vitamin K and Bone Health

Abstract

Chemistry, nutritional sources, tissue distribution and metabolism of vitamin K with special reference to bone health.

Vitamin K occurs in nature as a series of compounds with a common 2-methyl- 1,4 naphthoquinone nucleus and differing isoprenoid side chains at the 3 position. They comprise a single major plant form, phylloquinone with a phytyl side chain and a family of bacterially synthesized menaquinones (MKs) with multiprenyl side chains. The major dietary source to humans is phylloquinone for which the chief food contributors are green, leafy vegetables followed by certain vegetable oils (soybean, rapeseed and olive oils). Recent analyses by high pressure liquid chromatography are now providing a wide-ranging database of phylloquinone in foods. Menaquinones are found in moderate concentrations in only a few foods such as cheeses (MK-8 and MK-9). A wider spectrum of MKs is synthesized by the gut microflora, and their intestinal absorption probably accounts for most of the hepatic stores, particularly those with very long side chains (MKs-10-13) synthesized by members of the genus Bacteroides. The site of absorption of floral MKs is not known, but reasonable concentrations are found in the terminal ileum where bile salt-mediated absorption is possible. Both phylloquinone and menaquinones are bioactive in hepatic gamma-carboxylation but long-chain MKs are less well absorbed. Liver stores of vitamin K are relatively small and predominantly MKs-7-13. The hepatic reserves of phylloquinone (approximately 10% of the total) are labile and turn over at a faster rate than menaquinones. Trabecular and cortical bone appear to contain substantial concentrations of both phylloquinone and menaquinones. A majority (approximately 60-70%) of the daily dietary intake of phylloquinone is lost to the body by excretion, which emphasizes the need for a continuous dietary supply to maintain tissue reserves.

Shearer MJ, Bach A, Kohlmeier M
J. Nutr. Apr 1996
PMID: 8642453 | Free Full Text

At the present time the human requirements for vitamin K are based solely on its classical function in coagulation being listed as a Recommended Dietary Allowance (RDA) in the United States (Suttie 1992) and a Safe and Adequate Intake in the United Kingdom (Department of Health Report 1991). In both cases these requirements were set at a value of 1 mcg/kg/d. If, as argued by Vermeer et al. and Kohlmeier et al. in this volume, vitamin K is important to bone health and its requirements for this bone function are greater than for its hepatic function, a great challenge to researchers and future committees alike is to determine whether these putative extra demands can be quantified more precisely. Finally, it should be noted that the concept of reexamining the optimal intake of a vitamin with respect to the extra health benefits, which may be conferred by giving amounts over and above those required to protect against the originally discovered deficiency disease, is not new. There is already a recognition of the newer and often unexpected roles played by several other vitamins including in some cases the beneficial effects of extra intakes (Sauberlich and Machlin 1992).

Vitamin K2 MK-4 Improves Bone Strength, but Not Density, in Postmenopausal Women

Abstract

Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women.

Vitamin K mediates the synthesis of proteins regulating bone metabolism. We have tested whether high vitamin K(2) intake promotes bone mineral density and bone strength. Results showed that K(2) improved BMC and femoral neck width, but not DXA-BMD. Hence high vitamin K(2) intake may contribute to preventing postmenopausal bone loss.
Vitamin K is involved in the synthesis of several proteins in bone. The importance of K vitamins for optimal bone health has been suggested by population-based studies, but intervention studies with DXA-BMD as a clinical endpoint have shown contradicting results. Unlike BMC, DXA-BMD does not take into account the geometry (size, thickness) of bone, which has an independent contribution to bone strength and fracture risk. Here we have tested whether BMC and femoral neck width are affected by high vitamin K intake.
A randomized clinical intervention study among 325 postmenopausal women receiving either placebo or 45 mg/day of vitamin K(2) (MK-4, menatetrenone) during three years. BMC and hip geometry were assessed by DXA. Bone strength indices were calculated from DXA-BMD, femoral neck width (FNW) and hip axis length (HAL).
K(2) did not affect the DXA-BMD, but BMC and the FNW had increased relative to placebo. In the K(2)-treated group hip bone strength remained unchanged during the 3-year intervention period, whereas in the placebo group bone strength decreased significantly.
Vitamin K(2) helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW, whereas it has little effect on DXA-BMD.

Knapen MH, Schurgers LJ, Vermeer C
Osteoporos Int Jul 2007
PMID: 17287908 | Free Full Text