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

Abstract

Although defined by the presence of airflow obstruction and respiratory symptoms, patients with chronic obstructive pulmonary disease (COPD) are characterized by multimorbidity. Numerous co-occurring conditions and systemic manifestations contribute to the clinical presentation and progression of COPD; however, underlying mechanisms for multimorbidity are currently not fully elucidated. Vitamin A and vitamin D have been related to COPD pathogenesis. Another fat-soluble vitamin, vitamin K, has been put forward to exert protective roles in COPD. Vitamin K is an unequivocal cofactor for the carboxylation of coagulation factors, but also for extra-hepatic proteins including the soft tissue calcification inhibitor matrix Gla-protein and the bone protein osteocalcin. Additionally, vitamin K has been shown to have anti-oxidant and anti-ferroptosis properties. In this review, we discuss the potential role of vitamin K in the systemic manifestations of COPD. We will elaborate on the effect of vitamin K on prevalent co-occurring chronic conditions in COPD including cardiovascular disorders, chronic kidney disease, osteoporosis, and sarcopenia. Finally, we link these conditions to COPD with vitamin K as a connecting factor and provide recommendations for future clinical studies.

Zinc, Magnesium and Vitamin K Supplementation in Vitamin D Deficiency: Pathophysiological Background and Implications for Clinical Practice

“…In the Western diet, the majority of the VitK intake occurs in the form of VK1. However, VK2 has a higher bioavailability than VK1 and may therefore be at least as important for its bioactivity [ 54 ].…”

“…VK1 is mostly taken up by the liver, where it is used to activate coagulation factors. Long-chain VK2 is more lipophilic and, due to the long plasma half-life, more efficaciously penetrates extra-hepatic tissues (e.g., blood vessels and bones) and activates specific proteins there [ 54 ].…”

“…Via the process of the γ-carboxylation of vitamin K-dependent proteins (VKDPs), catalyzed by GGCX, VitK hydroquinone is oxidized into VitK epoxide. Subsequently, in a two-step reduction catalyzed by vitamin K epoxide reductase and vitamin K reductase, VitK epoxide is converted back into VitK hydroquinone [ 54 ]. There are 17 VKDPs that regulate blood coagulation, bone metabolism, and arterial calcification [ 53 ].…”

“…Firstly, VitK helps to bind Ca in bones by the formation of GLA residues on osteocalcin (OC). OC, the predominate non-collagenous protein in bone, is a VitK-dependent protein and is synthesized only in osteoblasts [ 54 , 58 , 59 ]. It is well known that the carboxylation of GLA domains helps the proteins (containing GLA domains) in Ca binding, and OC also has GLA domains [ 59 ].…”

Effects of Bacillus subtilis Natto NB205 and Its Mutant NBMK308 on Egg Quality in Aging Laying Hens

“…B. subtilis natto has the potential to naturally improve livestock production by promoting the growth of beneficial bacteria and reducing harmful bacteria. B. subtilis natto is rich in vitamin K2 (VK2), which confers beneficial effects in osteoporosis [ 16 , 17 ], cardiovascular calcification [ 18 ], cognitive disease [ 19 ], inflammation [ 20 ], and diabetes [ 21 ]. Studies have shown that vitamin K-dependent proteins (VKDPs) play a critical role in bone health and aging in laying hens [ 22 ], with dietary interventions with VK and calcium improving bone and eggshell quality [ 22 ].…”