Vitamin D3, K2 & Calcium Homeostasis — References

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Parent Topic: Vitamin D3, K2 & Calcium Homeostasis | References Hub: 02 - Compounds & Molecules References MOC

Landmark Peer-Reviewed Studies

Citation: Knapen, M. H. J., Drummen, N. E., Smit, E., Vermeer, C., & Theuwissen, E. (2013). Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporosis International, 24(9), 2499–2507.
Identifiers: PMID: 23525894 (PubMed · Europe PMC) | DOI: 10.1007/s00198-013-2325-6 (DOI · SciDB · Scholar)
Study Design & Sample Size: 3-year randomized, double-blind, placebo-controlled trial in healthy postmenopausal women aged 55–65 years ( $N = 244$ ).
Key Quantitative Outcomes: Supplementation with $180 μ g/day$ menaquinone-7 (MK-7) reduced circulating uncarboxylated osteocalcin (ucOC) by $- 58%$ compared to $- 1%$ in placebo ( $p < 0.001$ ). MK-7 significantly attenuated loss of bone mineral content (BMC) and bone mineral density (BMD) at the lumbar spine and femoral neck ( $p < 0.05$ ) and preserved femoral neck compression strength index (CSI) over 36 months.

Citation: Knapen, M. H. J., Braam, L. A. J. L., Drummen, N. E., Bekers, O., Hoeks, A. P. G., & Vermeer, C. (2015). Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women: a double-blind randomised clinical trial. Thrombosis and Haemostasis, 113(5), 1135–1144.
Identifiers: PMID: 25694037 (PubMed · Europe PMC) | DOI: 10.1160/TH14-08-0675 (DOI · SciDB · Scholar)
Study Design & Sample Size: 3-year randomized, double-blind, placebo-controlled vascular sub-study ( $N = 244$ ).
Key Quantitative Outcomes: $180 μ g/day$ MK-7 decreased dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP) by $- 50%$ relative to placebo ( $p < 0.0001$ ). Carotid-femoral pulse wave velocity (cfPWV) decreased by $- 0.36 m/s$ in the MK-7 group versus $+ 0.02 m/s$ in placebo ( $p = 0.040$ ), and in women with elevated baseline arterial stiffness (Stiffness Index $β > 10.8$ ), MK-7 reduced the Stiffness Index $β$ by $- 0.67$ vs. $+ 0.15$ in placebo ( $p = 0.018$ ).

Citation: Heaney, R. P., Recker, R. R., Grote, J., Horst, R. L., & Armas, L. A. G. (2011). Vitamin D3 is more potent than vitamin D2 in humans. The Journal of Clinical Endocrinology & Metabolism, 96(3), E447–E452.
Identifiers: PMID: 21177785 (PubMed · Europe PMC) | DOI: 10.1210/jc.2010-2230 (DOI · SciDB · Scholar)
Study Design & Sample Size: 12-week randomized, single-blind pharmacokinetic and tissue-storage study in healthy adults ( $N = 33$ ) comparing equimolar weekly doses ( $50, 000 IU/week$ ) of cholecalciferol ( $D_{3}$ ) vs. ergocalciferol ( $D_{2}$ ) including subcutaneous adipose biopsies.
Key Quantitative Outcomes: Vitamin $D_{3}$ produced an $87%$ greater area under the curve ( $AUC$ ) for serum $25 (OH) D$ elevation ( $p < 0.001$ ) and resulted in a $2 - to 3 -fold$ greater storage of calciferol in subcutaneous adipose tissue compared to Vitamin $D_{2}$ .

Citation: van Ballegooijen, A. J., Pilz, S., Tomaschitz, A., Grübler, M. R., & Verheyen, N. (2017). The synergistic interplay between vitamins D and K for bone and cardiovascular health: a narrative review. International Journal of Endocrinology, 2017, 7454376.
Identifiers: PMID: 29138634 (PubMed · Europe PMC) | DOI: 10.1155/2017/7454376 (DOI · SciDB · Scholar)
Study Design & Sample Size: Mechanistic and clinical synthesis of human RCTs evaluating combined Vitamin D3 + Vitamin K2 administration vs. monotherapies.
Key Quantitative Outcomes: Synthesizes clinical trial data showing that combined D3 ( $400 - 4, 000 IU/day$ ) and K2 ( $90 - 180 μ g/day$ MK-7 or $45 mg/day$ MK-4) produces significantly greater lumbar spine BMD gains ( $+ 1.5 - 2.5%$ over 12–24 months) and blunts progression of coronary artery calcification (CAC) and carotid intima-media thickness compared to Vitamin D3 alone.