Efficacy of high dose phylloquinone in correcting vitamin K deficiency in cystic fibrosis. Effect of vitamin K1 supplementation on vitamin K status in cystic fibrosis patients.
Subclinical deficiencies of vitamin K are universally present in unsupplemented cystic fibrosis (CF) patients. The dose required to prevent deficiencies cannot be estimated from the existing literature. The aim of this study is determine if a supplemental dose of 1 mg/day or 5 mg/day vitamin K1 per day would normalize vitamin K status in a population of children with cystic fibrosis.
                Fourteen pancreatic insufficient CF children, between the ages of 8 to 18 years old, were randomized to receive either 1 mg/day or 5 mg/day vitamin K1 per day, for one month. Fasting blood tests were done at baseline and after one month of the intervention. The degree of undercarboxylation of osteocalcin (%Glu-OC), and serum vitamin K1, were evaluated by descriptive statistics and nonparametric Wilcoxon matched-pair test and Mann-Whitney U test.
                Of the 50% of subjects who were below the optimal serum vitamin K1 at baseline, all rose into the normal range with supplementation. Supplementation also significantly reduced the overall %Glu-OC from a median of 46.8 to 29.1% (p<0.0003).
                Our results suggest that both 1 mg and 5 mg of vitamin K1, given over a one-month period in pancreatic insufficient pediatric cystic fibrosis patients improve vitamin K status. Patients with cystic fibrosis are at risk for impaired vitamin K status due to fat malabsorption from pancreatic insufficiency. This study was designed to assess vitamin K status and measure the effect of vitamin K1 supplementation in cystic fibrosis patients.
                Eighteen outpatients participated in a crossover study to determine the effect of vitamin K1 (phylloquinone) supplementation. After obtaining initial data, each subject was randomly assigned to either a 4-week study treatment of 5 mg oral vitamin K1 supplementation per week, or no supplementation and then crossed over to the other treatment for a second 4 week period. Plasma, serum and urine samples were collected and analyzed pre-study and at the end of each study period.
                The mean concentration of plasma vitamin K1 for the supplemented group was significantly higher than the unsupplemented group, [0.34 nmol/L and 0.21 nmol/L, respectively (p < 0.05)]. The percent of undercarboxylated osteocalcin increased on supplementation from 17% to 31%, (p < 0.005). Prothrombin induced in vitamin K absence (PIVKA-II) increased on supplementation from 5 ng/mL to 22 ng/mL, (p < 0.005). The ratio of urinary gamma-carboxyglutamic acid/creatinine was similar for both study periods.
                In contrast to other studies in cystic fibrosis, this study demonstrated a need for vitamin K1 supplementation. The carboxylation state of osteocalcin and PIVKA-II were the most sensitive indices of changes in vitamin K1 status. Although the 5 mg vitamin K1/week dose improved these vitamin K parameters, normal levels were not achieved.
Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.