Role of Vitamin K in Bone and Muscle Metabolism

Abstract

Vitamin K, a cofactor for the γ-glutamyl carboxylase enzyme, is required for the post-translational activation of osteocalcin and matrix Gla protein, which play a key role in bone and muscle homeostasis. In vivo and in vitro models for osteoporosis and sarcopenia suggest the vitamin K could exert a positive effect in both conditions. In bone, it increases osteoblastogenesis, whilst decreases osteoclast formation and function. In muscle, it is associated with increased satellite cell proliferation and migration and might play a role in energy metabolism. Observational trials suggest that high levels of vitamin K are associated with increased bone mineral density and reduced fracture risk. However, interventional studies for vitamin K supplementation yielded conflicting results. Clinical trials in sarcopenia suggest that vitamin K supplementation could improve muscle mass and function. One of the main limitations on the vitamin K studies are the technical challenges to measure its levels in serum. Thus, they are obtained from indirect sources like food questionnaires, or levels of undercarboxylated proteins, which can be affected by other environmental or biological processes. Although current research appoints to a beneficial effect of vitamin K in bone and muscle, further studies overcoming the current limitations are required in order to incorporate this supplementation in the clinical management of patients with osteosarcopenia.

The Pleiotropic Role of Vitamin K in Multimorbidity of Chronic Obstructive Pulmonary Disease

“…Reduced vitamin K intake and low plasma vitamin K1 levels were both associated with increased markers of inflammation in human cross-sectional studies [ 133 , 134 ], although clinical trials have not confirmed this association [ 132 , 134 , 135 ]. Oxidative stress and chronic inflammation are contributing mechanisms to the pathogenesis of COPD, cardiovascular disorders, osteoporosis, CKD, and sarcopenia [ 4 , 5 , 90 , 91 , 136 , 137 ] and vitamin K could form a possible link by counteracting these pathological processes. Future studies including animal models are, however, warranted to explore this.…”

“…Vitamin K has received less attention than vitamin D for its role in bone health, but a deficiency of vitamin K may also be a potential link between COPD and osteoporosis. Osteoblasts synthesize vitamin K-dependent osteocalcin, which is the most plentiful non-collagenous protein in bone tissue [ 90 , 91 ]. After vitamin K-dependent carboxylation, osteocalcin contributes to both formation of hydroxyapatite crystals in bone and the inhibition of bone mineralization, thereby preventing over-mineralization [ 91 ].…”

“…MGP is also involved in both processes of bone mineral regulation [ 91 ]. In addition, vitamin K directly affects bone metabolism, e.g., by protecting against reactive oxygen species (ROS) that are produced by osteoblasts [ 90 , 91 ].…”

Increasing Muscle Mass in Elders through Diet and Exercise: A Literature Review of Recent RCTs

“…More and better-designed studies are needed to accurately determine the effects on the human population. Additionally, the various forms of vitamin K appear to affect energy metabolism in skeletal muscle by increasing ATP production and maintaining the mitochondrial number and satellite cell proliferation in muscle [ 34 ].…”

Role of the Clinical Laboratory in the Assessment of Metabolic Musculoskeletal Diseases

“…In addition, they emphasised the importance of standardisation or harmonisation of commercial assays for optimal utilisation of these relevant biomarkers. Markus Herrmann and his colleagues have emphasised the significance of good analytical tools such as mass spectrometry coupled with liquid chromatography (LCMS/MS) and the emerging significance of 24,25-dihydroxy vitamin D [11] and the vitamin D metabolite ratio (VMR) to define vitamin D deficiency [12,13]. Vitamins D and K are known to play an important role in musculoskeletal health, despite the fact that different studies have given inconsistent results, as far as vitamin supplementation in vitamin D or K replete individuals.…”