The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification
"> Figure 1
<p>Molecular structure of the two main forms of Vitamin K. The upper structure represents Vitamin K1, also known as phylloquinone. The bottom structure is Vitamin K2, also known as menaquinone (MK).</p> "> Figure 2
<p>Mechanisms of action of VitK2 in “bone and vascular cross-talk”. At vascular level, VitK2, acting as cofactor for the enzyme GGCX, triggers the conversion of undercarboxylated MGP (ucMGP) in active carboxylated MGP (cMGP). The active cMGP could directly inhibit ectopic Ca2+ precipitation, but also VSMCst trans-differentiation through BMP-2. VitK2 can also inhibit VSMCs apoptosis through the Gas6/ AxL/Akt anti-apoptotic pathway. In bone tissue, VitK2 could promote osteoblasts proliferation and activity through MGP and Wnt/β-catenin pathway, control of oxidative stress (Ox-S) imbalance, via SXR receptor, and the well-established GGCX-dependent pathway. VitK2 may also exert a control of osteoclasts activities through the inhibition of NF-kB.</p> ">
Abstract
:1. Introduction
2. Vitamin K, a Family of Essential Fat-Soluble Compounds
3. Vitamin K2 and Its Biomolecular Mechanisms of Action
4. Vitamin K2 and Bone Health
5. Vitamin K2 and Vascular Health
Study | Type of the Study | Number of Patients Enrolled | Key Findings |
---|---|---|---|
[120] | Meta-analysis of Prospect-EPIC cohort study | Healthy 16,057 women (49–70 years) | Menaquinone’s intake reduces the incidence of coronary heart disease |
[121] | RCT | 564 post-menopausal women | Menaquinone’s intake decreased coronary calcification |
[122] | Prospective cohort | 35,476 healthy subjects | Menaquinone’s dietary intake was not associated with reduced stroke risk |
[106] | RCT | 244 post-menopausal women | Vitamin K2 (MK-7; 180 μg/day) supplementation improves arterial stiffness |
[123] | Prospective cohort study | 7216 participants (Mediterranean population at high cardiovascular disease risk) | Vitamin K2 dietary intake was associated with a reduced risk of cardiovascular events and mortality |
[124] | RCT | Patients with coronary artery disease (number not specified) | MK-7 (360 μg/day) supplementation arrested coronary artery calcification progression |
[125] | Prospective cohort study | 36,629 participants with PAD | Vitamin K2 intake was associated with a reduced risk of PAD |
[126] | Prospective cohort study | 2987 (Norwegian men and women) | Vitamin K2 intake was associated with a reduced risk of coronary artery disease |
[127] | Prospective cohort study | 33,289 participants from the EPIC-NL cohort | Higher intake Menaquinones was borderline significantly associated with lower CVD mortality |
[128] | RCT | 68 Type II diabetes and CVD patients | MK-7 (360 μg/day) was not associated with arterial calcification |
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study | Name of the Study | Number of Patients Enrolled | Key Findings |
---|---|---|---|
[21] | Framingham Heart Study | 364 women and 190 men (28–62 years old) | Bone loss was associated with progression of aortic calcification in women over 25 years |
[22] | Women’s Health Across the Nation Study | 90 women (45–58 years old) | Lower BMD was related to high aortic calcification |
[23] | MESA Study | 946 women (mean age 65.5 years old) and 963 men (mean age 64.1 years old) | Lower BMD was associated with greater coronary artery and abdominal aortic calcium score |
[24] | Rotterdam Study | 582 men and 694 women all >55 years old | BMD loss was significantly associated with higher follow-up coronary artery calcification |
Study | Type of the Study | Number of Patients Enrolled | Key Findings |
---|---|---|---|
[85] | RCT | 219 post-menopausal women | BMD increase following one year of vitamin K2 supplementation (100 μg/day) |
[86] | RCT | 244 healthy post-menopausal women | Decrease bone loss following three years MK-7 supplement (180 μg/day) |
[87] | Meta-analysis of 19 RCTs | 6759 participants (post-menopausal women) | BMD improvement and low incidence of fracture in osteoporotic subjects following K2 treatment |
[88] | Meta-analysis of 36 RCTs | 11,122 participants (post-menopausal women) | Vitamin K2 treatment (MK-4: 45 mg/day) reduce fracture, increase cOC and decrease ucOC serum concentration |
[89] | RCT | 55 healthy children | 8 weeks MK-7 supplementation increase cOC serum concentration |
[90] | Non-placebo-controlled dose-examination study | 55 healthy males | MK-4 supplementation (600 and 900 μg/day) decrease ucOC and increase cOC level respectively |
[91] | RCT | 48 healthy post-menopausal women | Serum ucOC concentrations were significantly lower following 6–12 months MK-4 treatment (1.5 mg/day) |
[92] | RCT | 60 postmenopausal women | MK-7 treatment (100 μg/day) significantly decrease ucOC and increase cOC/ucOC ratio |
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Mandatori, D.; Pelusi, L.; Schiavone, V.; Pipino, C.; Di Pietro, N.; Pandolfi, A. The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification. Nutrients 2021, 13, 1222. https://doi.org/10.3390/nu13041222
Mandatori D, Pelusi L, Schiavone V, Pipino C, Di Pietro N, Pandolfi A. The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification. Nutrients. 2021; 13(4):1222. https://doi.org/10.3390/nu13041222
Chicago/Turabian StyleMandatori, Domitilla, Letizia Pelusi, Valeria Schiavone, Caterina Pipino, Natalia Di Pietro, and Assunta Pandolfi. 2021. "The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification" Nutrients 13, no. 4: 1222. https://doi.org/10.3390/nu13041222