Effects of Vitamin K Deficiency in Cystic Fibrosis

New research into vitamin K deficiency among cystic fibrosis patients may help explain why exocrine pancreatic insufficiency increases the risk of pathological shortages.

Cystic fibrosis patients in general face a greatly elevated risk of vitamin K shortfalls, but researchers from Poland studied 168 of them to determine what factors are associated with greater and lesser risk.

They first separated the 146 patients (86.9%) who took vitamin K supplements from the other 22 patients (13.1%), collected a wide variety of data on each patient and then looked for correlation between each data point and 2 measures of deficiency: prothrombin inducted by vitamin K absence (PIVKA-II) and undercarboxylated osteocalcin (u-OC).

Blood tests found a pathological PIVKA-II concentration (≥2 ng/ml) in 72 patients (42.8%) and an abnormal percentage of osteocalcin (≥20%) in 60 patients (35.7%). Analysis determined that that liver involvement, diabetes, and glucocorticoid therapy were potential risk factors for vitamin K deficiency.

“Pathological concentrations of PIVKA-II occurred more frequently in patients with pancreatic insufficiency and those who have two severe mutations in both alleles of the CFTR gene. Pathological percentage of u-OC was found more frequently in adult CF patients and those not receiving vitamin K,” the study authors wrote in Scientific Reports.

“However,” they continued, “it seems that there are no good predictive factors of vitamin K deficiency in cystic fibrosis patients in everyday clinical care.”

Previous research has established a strong link between cystic fibrosis and vitamin K. Indeed, the authors of the new paper noted that a 2014 study found shortages in 29% of juvenile cystic fibrosis patients while a 2005 study found that 10% to 35% of children with pancreatic insufficiency were deficient in fat-soluble vitamins.

The new study found pathological PIVKA-II concentrations in 38.4% of patients who received vitamin K supplements at recommended doses and 72.7% of patients who did not receive supplemental vitamin K. Results from u-OC tests were similar. An insufficiency (u-OC 20%-50%) or deficiency (u-OC > 50%) was found in 30.8% of supplement-taking patients and 76.2% of those who took no supplements.

Studies have yet to explain exactly why cystic fibrosis patients suffer vitamin K deficiencies. Possible causes include fat malabsorption, liver disease, bowel resection, increased mucous accumulation and frequent treatment with antibiotics.

Earlier studies have found that cystic fibrosis patients with pancreatic insufficiency are more prone to vitamin K deficiency than other cystic fibrosis patients. The current study may have explained that finding to some degree. It found a greater tendency to pathological PIVKA-II concentrations in patients with the genotype F508del/F508del or with two severe mutations in both alleles. This is potentially important because previous research indicates that such mutations are associated with a greater risk of pancreatic insufficiency and a more severe course of disease.

That said, the relationships the study team found between pancreatic insufficiency and vitamin K deficiency were not strong enough to warrant different testing regimes or different levels of vitamin K supplementation among cystic fibrosis patients with pancreatic insufficiency.

“To summarize, although we documented some statistical relationships and differences, there have been no strong predictive factors of vitamin K deficiency in cystic fibrosis patients in the present study,” the study authors wrote. “Early vitamin K supplementation in cystic fibrosis patients seems to be warranted. It is impossible to clearly determine the supplementation dose. Therefore, constant monitoring of vitamin K status seems to be justified.”