Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women

Knapen, Marjo H. J.; Drummen, Nadja E.A.; Smit, Eline Suzanne; Vermeer, Cees; Theuwissen, Elke

doi:10.1007/s00198-013-2325-6

Cited by 155 publications

(158 citation statements)

References 33 publications

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“…Only a few studies have investigated the bioavailability and single-dose kinetics of MK-7 [9,15,29,30]. In a recent study, Knapen and colleagues compared the bioavailability of MK-7 in four clinical trials using different formulations of capsules and tablets [28].…”

Section: Discussionmentioning

confidence: 99%

“…The uptake of vitamin K 1 from capsules was previously observed to be dependent on the food matrix [34]. However, recent studies suggest that for bioavailability of MK-7 as a nutritional supplement, the carrier material may not play an important role [15]. Sunflower oil was chosen as the carrier in the present studies because it is an edible oil often used as a carrier in pharmacological studies.…”

Section: Discussionmentioning

confidence: 99%

“…Vitamin K 2 is generally considered safe [38]. In a previous study, no side effects related to MK-7 were reported after daily intake of 180 µg for 3 years [15]. We previously conducted a 90-day toxicology study in rats [24].…”

Section: Discussionmentioning

confidence: 99%

“…Daily intake of 180 µg of MK-7 significantly reduced the age-related decline in bone mineral content and bone mineral density (BMD) in the lumbar spine and femoral neck [15]. Furthermore, MK-7 preserved bone strength as compared to placebo treatment.…”

Section: Introductionmentioning

confidence: 99%

“…Vitamin K 2 is documented to be safe, with no side effects reported in humans [15,23] or when tested at very high doses in rats [24].…”

Section: Introductionmentioning

confidence: 99%

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Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs Fermentation-Derived MK-7 in Randomised Controlled Trials

Møller

Gjelstad

Baksaas³

et al. 2017

International Journal for Vitamin and Nutrition Research

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Abstract:We investigated the bioavailability of a synthetic form of the vitamin K 2 molecule menaquinone-7 (MK-7) in a randomised single-blinded two-way cross-over study. Healthy subjects (20 -66 years of age) took a single 180 µg dose of synthetic MK-7 or fermentation-derived MK-7, and serum MK-7 concentrations were monitored for 72 hours to calculate AUC(0 -72 h) and C max . We also compared the biological effects of placebo, fermentation-derived MK-7 (90 µg) and 3 doses of synthetic MK-7 (45, 90 and 180 µg) in a randomised double-blinded parallel study. Healthy subjects (20 -60 years of age) took one of the supplements daily for 43 days, and the fraction of carboxylated osteocalcin (OC) was compared between day 1 and day 43 as a marker for vitamin K activity. In the bioavailability study, the 90 % confidence interval for the ratio of the AUC(0-72 h) values for synthetic and fermentationderived MK-7 was 83 -111, indicating bioequivalence. The 90 % confidence interval for the Cmax ratio was 83 -131. The serum concentrations of carboxylated OC and undercarboxylated OC were increased (p = 0.01) and reduced (p = 0.02), respectively, after daily intake of 180 µg of synthetic MK-7 for 43 days, indicating increased vitamin K activity. Across both studies, only 1 participant reported an adverse event (dry mouth; 180 µg synthetic MK-7 group, functional study) that was considered possibly related to synthetic MK-7 supplementation. Our findings provide evidence that the tested synthetic form of MK-7 is bioequivalent to fermentation-derived MK-7, exhibits vitamin K activity and is well tolerated in healthy subjects.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Vitamin K 2 is documented to be safe, with no side effects reported in humans [15,23] or when tested at very high doses in rats [24].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs Fermentation-Derived MK-7 in Randomised Controlled Trials

Møller

Gjelstad

Baksaas³

et al. 2017

International Journal for Vitamin and Nutrition Research

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Metabolic engineering of Bacillus subtilis for high‐titer production of menaquinone‐7

et al. 2019

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Menaquinone-7 (MK-7) is a member of vitamin K 2 used for prevention from osteoporosis and cardiovascular calcification. This study constructed Bacillus subtilis strains for hightiter production of MK-7 through metabolic engineering approaches. In B. subtilis, MK-7 biosynthesis was categorized into five modules: glycerol dissociation pathway, shikimate pathway, pyrimidine metabolic pathway, methylerythritol phosphate pathway, and MK-7 pathway. Overexpression of GlpK and GlpD (glycerol dissociation pathway) led to ã 10% increase in the MK-7 titer. Deletion of the genes mgsA and araM increased the MK-7 production by 15%. Furthermore, overexpression of AroG D146N (shikimate pathway), PyrG E156K (pyrimidine metabolic pathway), HepS (methylerythritol phosphate pathway), and VHb could also increase the MK-7 titer. Finally, we obtained a recombinant strain BSMK_11 with simultaneous overexpressing the genes glpK, glpD, aroG fbr , pyrG fbr , hepS, vgb, and knockouting the genes mgsA and araM, and the MK-7 titer reached 281.4 ± 5.0 mg/L (i.e., 12.0 mg/g DCW) in a 5 L fermenter.

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Carboxylative efficacy of trans and cisMK7 and comparison with other vitamin K isomers

et al. 2022

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Carboxylative enzymes are involved in many pathways and their regulation plays a crucial role in many of these pathways. In particular, γ‐glutamylcarboxylase (GGCX) converts glutamate residues (Glu) into γ‐carboxyglutamate (Gla) of the vitamin K‐dependent proteins (VKDPs) activating them. VKDPs include at least 17 proteins involved in processes such as blood coagulation, blood vessels calcification, and bone mineralization. VKDPs are activated by the reduced form of vitamin K, naturally occurring as vitamin K1 (phylloquinone) and K2 (menaquinones, MKs). Among these, MK7 is the most efficient in terms of bioavailability and biological effect. Similarly to other trans isomers, it is produced by natural fermentation or chemically in both trans and cis. However, the efficacy of the biological effect of the different isomers and the impact on humans are unknown. Our study assessed carboxylative efficacy of trans and cis MK7 and compared it with other vitamin K isomers, evaluating both the expression of residues of carboxylated Gla‐protein by western blot analysis and using a cell‐free system to determine the GGCX activity by HPLC. Trans MK7H2 showed a higher ability to carboxylate the 70 KDa GLA‐protein, previously inhibited in vitro by warfarin treatment. However, cis MK7 also induced a carboxylation activity albeit of a small extent. The data were confirmed chromatographically, in which a slight carboxylative activity of cis MK7H2 was demonstrated, comparable with both K1H2 and oxidized trans MK7 but less than trans MK7H2. For the first time, a difference of biological activity between cis and trans configuration of menaquinone‐7 has been reported.

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Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women

Abstract: MK-7 supplements may help postmenopausal women to prevent bone loss. Whether these results can be extrapolated to other populations, e.g., children and men, needs further investigation.

Cited by 155 publications

References 33 publications

Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs Fermentation-Derived MK-7 in Randomised Controlled Trials

Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs Fermentation-Derived MK-7 in Randomised Controlled Trials

Metabolic engineering of Bacillus subtilis for high‐titer production of menaquinone‐7

Carboxylative efficacy of trans and cisMK7 and comparison with other vitamin K isomers

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