A review investigated whether there is a potential link between vitamin K deficiency and mechanisms associated with the development of pulmonary disease.
Inflammation of the lungs in chronic obstructive pulmonary disease (COPD) is characterized by breathlessness due to restricted air flow. Studies have shown that this inflammation may not be limited to the lungs, but may also impact other organs such as the heart and result in diseases like coronary artery disease.
The associated high frequency of COPD and cardiovascular diseases means that COPD patients are being required to take anticoagulation medication such as vitamin K antagonists, which help prevent blood clots but leads to significant vitamin K deficiency. The reliance on the long-term use of anticoagulation medication can be a consequence of acute exacerbations which may be caused by pulmonary embolisms (a blockage in the lung typically caused by a blood clot).
Vitamin K antagonists reduce blood clotting by inhibiting vitamin K, an essential cofactor required for the activation of the coagulation, or blood clotting pathway. However, a major side effect associated with the use of vitamin K antagonists is vascular calcification, a significant cardiovascular morbidity, and mortality risk factor. Vitamin K is required for the activation of a protein which is a potent inhibitor of calcification of the arteries. Alternatively, increasing vitamin K intake has been shown to have a protective effect against arterial calcification.
Furthermore, a shared mechanism between vascular calcification and disease progression in COPD patients is elastin degradation. Elastin is present in both the lungs and arterial walls, providing elasticity and resilience to these tissues. The breakdown and calcification of elastin are two pathogenic mechanisms which have been shown to stimulate each other and may be the pathogenic mechanism behind the observed link between COPD and cardiovascular diseases.
In a recent article published in Respiratory Research, researchers in the Netherlands hypothesized that vitamin K deficiency is a key determinant of the rate of elastin degradation and calcification and therefore associated with pathogenic mechanisms of COPD. The researchers reviewed current literature, including observational and human studies, along with animal intervention studies.
There are various reasons why an individual may have vitamin K deficiency, including but not limited to low vitamin K consumption. Interestingly, in a large observational study, it was reported that a large consumption of cheese (which is rich in vitamin K2) in many countries was associated with better lung function and less emphysema. However, observations indicate individuals with higher rates of elastin degradation also have a higher expenditure of vitamin K. As higher levels of elastin degradation stimulates elastin calcification, this can lead also to vitamin K deficiency. This vicious cycle can, therefore, have a significant impact on survival rates of COPD patients given their increased risk of cardiovascular diseases.
Overall, there is an abundance of circumstantial evidence which supports the hypothesis that there is, in fact, a link between vitamin K deficiency and the degradation of elastin with the pathogenic mechanisms of cardiovascular diseases in chronic obstructive pulmonary disease patients. This raises concerns surrounding the efficacy and safety of the still widely used vitamin K antagonists in COPD patients. Future studies are necessary to investigate the role vitamin K supplementation could potentially have on reducing elastin degradation and subsequently vascular calcification. Also, human cohort studies that assess the relationship between vitamin k deficiency and its impact on the progression of diseases such as emphysema in COPD patients are essential.
Written by Lacey Hizartzidis, PhD
Piscaer I, Wouters EFM, Vermeer C, Franssen FME, Janssen R. Vitamin K deficiency: the linking pin between COPD and cardiovascular diseases? Respiratory Research Nov 13 2017; 18:189. Doi: 10.1186/s12931-017-0673-z.
Chatrou ML, Winckers K, Hackeng TM, Reutelingsperger CP, Schurgers LJ. Vascular calcification: the price to pay for anticoagulation therapy with vitamin K-antagonists. Blood Rev. 2012 Jul;26(4):155-66. doi: 10.1016/j.blre.2012.03.002.