The synergistic interaction between Vit D3 and Vit K2.

The synergistic interaction between cholecalciferol (vitamin D3) and menaquinone (vitamin K2) encompasses remarkable biochemical and physiological complexity, influencing bone, cardiovascular and other health through specific cellular and molecular mechanisms. This article delves into the technical details of the metabolic pathways involved, the receptors activated and the resulting biological effects, based on evidence from recent scientific studies.

Cholecalciferol and its metabolism

Cholecalciferol, after conversion in the liver to 25-hydroxyvitamin D3 [25(OH)D3], is subsequently hydroxylated in the kidney by 1α-hydroxylase (CYP27B1) generating its active form, 1,25-dihydroxyvitamin D3 (calcitriol, 1,25(OH)2D3). This active metabolite exerts its effects through binding to the vitamin D receptor (VDR), a member of the nuclear receptor family that regulates the transcription of more than 200 genes.

Activation of the VDR influences calcium and phosphorus homeostasis, promoting intestinal absorption of these minerals, renal reabsorption of calcium, and release of calcium from the bones into the circulation.

Menaquinone and its Role in Carboxylation

Menaquinone acts as a cofactor for the enzyme γ-glutamyl carboxylase, which catalyzes the carboxylation of glutamic acid residues in vitamin K-dependent proteins (VKDPs), such as osteocalcin in bone and matrix Gla protein (MGP) in blood vessels.

Carboxylated osteocalcin binds calcium and facilitates its incorporation into bone. Carboxylated MGP prevents pathological calcification of soft tissues, including blood vessels.

Synergistic Interaction in Metabolic Pathways

The synergy between these two vitamins is manifested in their combined ability to optimize bone and cardiovascular health. Cholecalciferol facilitates the absorption of calcium, essential for bone mineralization and muscle function. At the same time, menaquinone ensures the proper use of this calcium, promoting its incorporation into the bone and preventing its deposit in the blood vessels.

Effects on Receptors and Biological Consequences

• VDR (Vitamin D Receptor): Calcitriol activates the VDR, which binds to the vitamin D response element (VDRE) in DNA, modulating gene expression related to calcium and phosphorus metabolism, cell differentiation, immune response and inhibition of cell proliferation.
• γ-Glutamyl Carboxylase: Activated by vitamin K2, this enzyme is crucial for the activation of VKDPs, facilitating bone mineralization and inhibiting vascular calcification.

Recent studies have delineated these mechanisms in detail. For example, research shows that co-supplementation with vitamin D3 and K2 significantly improves bone health and reduces the risk of cardiovascular disease by enhancing bone mineralization and preventing vascular calcification (Maresz, 2015; Flore et al., 2013). These studies underscore the importance of both vitamins in regulating bone mineralization and cardiovascular health, providing a rationale for co-supplementation in preventing diseases related to deficiency of these vitamins.

References

• Maresz, K. (2015). Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health. Integrative Medicine: A Clinician's Journal, 14(1), 34-39.
• Flore, R., Ponziani, FR, Di Rienzo, TA, Zocco, MA, Flex, A., Gerardino, L., ... & Gasbarrini, A. (2013). Something more to say about calcium homeostasis: the role of vitamin K2 in vascular calcification and osteoporosis. European Review for Medical and Pharmacological Sciences, 17(18), 2433-2440.