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The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized, double-blind, placebo-controlled trial.
Am J Clin Nutr 2019; 110(4):883-890AJ

Abstract

BACKGROUND

Vitamin K occurs in the diet as phylloquinone and menaquinones. Observational studies have shown that both phylloquinone and menaquinone intake might reduce cardiovascular disease (CVD) risk. However, the effect of vitamin K on vascular calcification is unknown.

OBJECTIVES

The aim of this study was to assess if menaquinone supplementation, compared to placebo, decreases vascular calcification in people with type 2 diabetes and known CVD.

METHODS

In this double-blind, randomized, placebo-controlled trial, we randomly assigned men and women with type 2 diabetes and CVD to 360 µg/d menaquinone-7 (MK-7) or placebo for 6 mo. Femoral arterial calcification at baseline and 6 mo was measured with 18sodium fluoride positron emission tomography (18F-NaF PET) scans as target-to-background ratios (TBRs), a promising technique to detect active calcification. Calcification mass on conventional computed tomography (CT) scan was measured as secondary outcome. Dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) concentrations were measured to assess compliance. Linear regression analyses were performed with either TBR or CT calcification at follow-up as the dependent variable, and treatment and baseline TBR or CT calcification as independent variables.

RESULTS

We randomly assigned 35 patients to the MK-7 group (33 completed follow-up) and 33 to the placebo group (27 completed follow-up). After the 6-mo intervention, TBR tended to increase in the MK-7 group compared with placebo (0.25; 95% CI: -0.02, 0.51; P = 0.06), although this was not significant. Log-transformed CT calcification mass did not increase in the intervention group compared with placebo (0.50; 95% CI: -0.23, 1.36; P = 0.18). MK-7 supplementation significantly reduced dp-ucMGP compared with placebo (-205.6 pmol/L; 95% CI: -255.8, -155.3 pmol/L). No adverse events were reported.

CONCLUSION

MK-7 supplementation tended to increase active calcification measured with 18F-NaF PET activity compared with placebo, but no effect was found on conventional CT. Additional research investigating the interpretation of 18F-NaF PET activity is necessary. This trial was registered at clinicaltrials.gov as NCT02839044.

Authors+Show Affiliations

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.Department of Endocrinology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.Image Sciences Institute, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.Department of Vascular Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.Department of Vascular Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.Department of Internal Medicine, Diakonessenhuis, Utrecht, Netherlands.Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. Department of Epidemiology & Biostatistics, Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, Amsterdam, Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31387121

Citation

Zwakenberg, S R., et al. "The Effect of Menaquinone-7 Supplementation On Vascular Calcification in Patients With Diabetes: a Randomized, Double-blind, Placebo-controlled Trial." The American Journal of Clinical Nutrition, vol. 110, no. 4, 2019, pp. 883-890.
Zwakenberg SR, de Jong PA, Bartstra JW, et al. The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2019;110(4):883-890.
Zwakenberg, S. R., de Jong, P. A., Bartstra, J. W., van Asperen, R., Westerink, J., de Valk, H., ... Beulens, J. W. J. (2019). The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized, double-blind, placebo-controlled trial. The American Journal of Clinical Nutrition, 110(4), pp. 883-890. doi:10.1093/ajcn/nqz147.
Zwakenberg SR, et al. The Effect of Menaquinone-7 Supplementation On Vascular Calcification in Patients With Diabetes: a Randomized, Double-blind, Placebo-controlled Trial. Am J Clin Nutr. 2019 Oct 1;110(4):883-890. PubMed PMID: 31387121.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized, double-blind, placebo-controlled trial. AU - Zwakenberg,S R, AU - de Jong,P A, AU - Bartstra,J W, AU - van Asperen,R, AU - Westerink,J, AU - de Valk,H, AU - Slart,R H J A, AU - Luurtsema,G, AU - Wolterink,J M, AU - de Borst,G J, AU - van Herwaarden,J A, AU - van de Ree,M A, AU - Schurgers,L J, AU - van der Schouw,Y T, AU - Beulens,J W J, PY - 2019/03/05/received PY - 2019/06/24/accepted PY - 2019/8/7/pubmed PY - 2019/8/7/medline PY - 2019/8/7/entrez KW - cardiovascular disease KW - diabetes KW - menaquinone-7 KW - vascular calcification KW - vitamin K SP - 883 EP - 890 JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 110 IS - 4 N2 - BACKGROUND: Vitamin K occurs in the diet as phylloquinone and menaquinones. Observational studies have shown that both phylloquinone and menaquinone intake might reduce cardiovascular disease (CVD) risk. However, the effect of vitamin K on vascular calcification is unknown. OBJECTIVES: The aim of this study was to assess if menaquinone supplementation, compared to placebo, decreases vascular calcification in people with type 2 diabetes and known CVD. METHODS: In this double-blind, randomized, placebo-controlled trial, we randomly assigned men and women with type 2 diabetes and CVD to 360 µg/d menaquinone-7 (MK-7) or placebo for 6 mo. Femoral arterial calcification at baseline and 6 mo was measured with 18sodium fluoride positron emission tomography (18F-NaF PET) scans as target-to-background ratios (TBRs), a promising technique to detect active calcification. Calcification mass on conventional computed tomography (CT) scan was measured as secondary outcome. Dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) concentrations were measured to assess compliance. Linear regression analyses were performed with either TBR or CT calcification at follow-up as the dependent variable, and treatment and baseline TBR or CT calcification as independent variables. RESULTS: We randomly assigned 35 patients to the MK-7 group (33 completed follow-up) and 33 to the placebo group (27 completed follow-up). After the 6-mo intervention, TBR tended to increase in the MK-7 group compared with placebo (0.25; 95% CI: -0.02, 0.51; P = 0.06), although this was not significant. Log-transformed CT calcification mass did not increase in the intervention group compared with placebo (0.50; 95% CI: -0.23, 1.36; P = 0.18). MK-7 supplementation significantly reduced dp-ucMGP compared with placebo (-205.6 pmol/L; 95% CI: -255.8, -155.3 pmol/L). No adverse events were reported. CONCLUSION: MK-7 supplementation tended to increase active calcification measured with 18F-NaF PET activity compared with placebo, but no effect was found on conventional CT. Additional research investigating the interpretation of 18F-NaF PET activity is necessary. This trial was registered at clinicaltrials.gov as NCT02839044. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/31387121/The_effect_of_menaquinone-7_supplementation_on_vascular_calcification_in_patients_with_diabetes:_a_randomized,_double-blind,_placebo-controlled_trial L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.1093/ajcn/nqz147 DB - PRIME DP - Unbound Medicine ER -