Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities

Abstract

Vitamin K2-7, also known as menaquinone-7 (MK-7) is a form of vitamin K that has health-beneficial effects in osteoporosis, cardiovascular disease, inflammation, cancer, Alzheimer’s disease, diabetes and peripheral neuropathy. Compared to vitamin K1 (phylloquinone), K2-7 is absorbed more readily and is more bioavailable. Clinical studies have unequivocally demonstrated the utility of vitamin K2-7 supplementation in ameliorating peripheral neuropathy, reducing bone fracture risk and improving cardiovascular health. We examine how undercarboxylated osteocalcin (ucOC) and matrix Gla protein (ucMGP) are converted to carboxylated forms (cOC and cMGP respectively) by K2-7 acting as a cofactor, thus facilitating the deposition of calcium in bones and preventing vascular calcification. K2-7 is beneficial in managing bone loss because it upregulates osteoprotegerin which is a decoy receptor for RANK ligand (RANKL) thus inhibiting bone resorption. We also review the evidence for the health-beneficial outcomes of K2-7 in diabetes, peripheral neuropathy and Alzheimer’s disease. In addition, we discuss the K2-7-mediated suppression of growth in cancer cells via cell-cycle arrest, autophagy and apoptosis. The mechanistic basis for the disease-modulating effects of K2-7 is mediated through various signal transduction pathways such as PI3K/AKT, MAP Kinase, JAK/STAT, NF-κB, etc. Interestingly, K2-7 is also responsible for suppression of proinflammatory mediators such as IL-1α, IL-1β and TNF-α. We elucidate various genes modulated by K2-7 as well as the clinical pharmacometrics of vitamin K2-7 including K2-7-mediated pharmacokinetics/pharmacodynamics (PK/PD). Further, we discuss the current status of clinical trials on K2-7 that shed light on dosing strategies for maximum health benefits. Taken together, this is a synthetic review that delineates the health-beneficial effects of K2-7 in a clinical setting, highlights the molecular basis for these effects, elucidates the clinical pharmacokinetics of K2-7, and underscores the need for K2-7 supplementation in the global diet.

The biological responses of vitamin K2: A comprehensive review

“…The association of VitK2 involvement in the repression of pathological vascular calcification and the upregulation of Gas6 expression has been shown (Jadhav et al, 2022;Jiang et al, 2016). In a study conducted by Qiu et al (2017) Western blotting detected that substantial aortic smooth muscle Gas6 expression was restored after VitK2 treatment and that a significant decrease of VSMC calcification and apoptosis induced by CaCl 2 and β-sodium glycerophosphate was also observed.…”

Vitamins in neuropathy: pathophysiological and therapeutic roles

“…Clinical evidence demonstrates that K2-7 dietary supplementation can ameliorate peripheral neuropathy, reduce bone fracture risk, and improve cardiovascular health [53 ▪ ]. The mechanistic basis for K2-7 might be mediated through signal transduction pathways including PI3K/AKT, MAP kinase, JAK/STAT, NF-κB, and through suppression of proinflammatory mediators IL-1α, IL-1β, and TNF-α [58 ▪ ]. A case report showed that vitamin K deficiency can result in permanent peripheral neuropathy in infants with biliary atresia [59].…”

Nutrición animal: Texto de formación universitaria

“…La vitamina K2 contribuye a la salud ósea y cardiovascular, siendo la menaquinona-7 (MK-7) la que se absorbe de manera más eficiente y exhibe la mayor biodisponibilidad, volviéndose popular como suplemento para la salud ósea y vascular (Sato et al, 2012). La vitamina K2-7, también conocida como menaquinona-7 (MK-7) es una forma de vitamina K que tiene efectos beneficiosos para la salud en la osteoporosis, las enfermedades cardiovasculares, la inflamación, el cáncer, la enfermedad de Alzheimer, la diabetes y la neuropatía periférica en humanos (Jadhav et al, 2022). MK-7 sirve como cofactor en el proceso de carboxilación de ciertos residuos de glutamato unidos a proteínas, donde estos se convierten en residuos de -carboxiglutamato (Gla).…”