Treatment of vitamin K deficiency in cystic fibrosis: Effectiveness of a daily fat-soluble vitamin combination.

OBJECTIVE: Patients with cystic fibrosis (CF) and pancreatic insufficiency (PI) commonly have vitamin K deficiency, and those with CF-associated liver disease (CFLD) have universal vitamin K deficiency. We evaluated the effectiveness of an oral fat-soluble vitamin combination (ADEKs) to treat patients with vitamin K deficiency. STUDY DESIGN: Patients with PI and CF (mean age, 15 years; range, 0.6 to 46 years) including 6 with advanced CFLD were prospectively enrolled in a study of a fat-soluble vitamin combination taken on a daily basis. None had received vitamin K supplementation for at least 4 months before the study. Fat-soluble vitamin combination supplementation was given for a minimum of 4 months; the mean vitamin K intake was 0.18 mg/d (SD = 0.1, range, 0 to 0.3). The primary outcome was change in plasma PIVKA-II (prothrombin in vitamin K absence). RESULTS: Before supplementation 58 (81%) of 72 patients had abnormal PIVKA-II levels (>2.9 ng/mL). After supplementation 29 (40%) had abnormal PIVKA-II levels (P =.001). All 6 patients with advanced CFLD had abnormal PIVKA-II levels (median, range of 20.8, 5.5 to 55 ng/mL) before treatment, which corrected to normal in 50% (4.1, 2.1 to 65 ng/mL). Four patients, 2 with CFLD, had a prolonged prothrombin time (>13.5 seconds) at both time periods. CONCLUSIONS: An oral fat-soluble vitamin combination with a modest amount of vitamin K can, as a daily supplement, improve the PIVKA-II levels in patients with PI and CF.

Challenges in the dietary treatment of cystic fibrosis related diabetes mellitus.

Cystic fibrosis related diabetes mellitus is an increasingly recognized problem as survival in patients with cystic fibrosis improves. In a 5 year retrospective study of 627 children and adults attending Toronto cystic fibrosis clinics, we identified 57 (9%) patients with cystic fibrosis related diabetes mellitus; four (1.3%) of 301 children (<18 years) and 53 (16%) of 326 adults. The development of this complication of cystic fibrosis is associated with increased mortality, deteriorations in both respiratory and nutritional status, and the development of late microvascular, but not macrovascular, diabetic complications. Unfortunately, systematic review of the literature provides few well designed studies that provide sound evidence for clinical practice. Recommendations are therefore often based on anecdote, rather than physiological or outcomes research. Dietary therapy combines the principles of the dietary management of both cystic fibrosis and diabetes mellitus, but emphasizes the need for a high energy diet (> 100% of recommended daily intake) in patients with cystic fibrosis related diabetes mellitus. The importance of calories from fat is emphasized, with no restriction on total carbohydrate intake. Insulin intake mirrors carbohydrate intake. Routine dietary therapy is straightforward, but challenges occur due to both complications of cystic fibrosis and advancing disease. If a patient with cystic fibrosis related diabetes mellitus is malnourished, overnight enteral tube feeding is often used, with an adjusted insulin regimen. There is a great need for both physiological and outcomes research to provide sound scientific evidence for the dietary treatment of cystic fibrosis related diabetes mellitus.

Prevalence of vitamin K deficiency in cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) are at risk of developing vitamin K deficiency because of pancreatic insufficiency, hepatobiliary disease, or both. OBJECTIVE: Our objective was to determine the prevalence of vitamin K deficiency in unsupplemented patients with CF and to identify risk factors that might be associated with the deficiency. DESIGN: Ninety-eight patients with CF-83 who were pancreatic insufficient (age: 15.2 +/- 10.7 y; range: 0.6-45.8 y), 15 who were pancreatic sufficient (age: 26.2 +/- 11.6 y; range: 6.5-45.3 y), and 62 healthy individuals (age: 16.2 +/- 12. 8 y; range: 1-45 y)-were studied prospectively. None had taken vitamin K supplements. Eight pancreatic-insufficient patients had advanced CF-associated liver disease. Plasma prothrombin in vitamin K absence (PIVKA-II) was measured by immunoassay. All control subjects had PIVKA-II concentrations <3 microg/L. RESULTS: Seventy-eight percent of pancreatic-insufficient patients had PIVKA-II concentrations >/=3 microg/L (22.8 +/- 35.7 microg/L). All patients with CF-associated liver disease had abnormal PIVKA-II concentrations. The mean PIVKA-II concentration of pancreatic-insufficient patients with liver disease was greater than that of those without liver disease (46.6 +/- 65.3 compared with 15. 3 +/- 26.1 microg/L; P < 0.05). Five pancreatic-sufficient patients had mildly elevated PIVKA-II concentrations. Six (7%) pancreatic insufficient patients (3 with CF-associated liver disease) had mildly prolonged prothrombin time but no clinical bleeding. There was no correlation between PIVKA-II concentrations and severity of fat malabsorption or antibiotic use. CONCLUSIONS: Vitamin K deficiency is common in unsupplemented patients with CF and pancreatic insufficiency and routine supplementation should be considered in all of these patients.

Do infants with cystic fibrosis need a protein hydrolysate formula? A prospective, randomized, comparative study.

OBJECTIVES: We compared the nutritional benefits of a protein hydrolysate and a conventional infant formula in infants newly diagnosed with cystic fibrosis (CF). STUDY DESIGN: Twenty-three infants with CF (<6 months of age) and pancreatic insufficiency were randomized to receive a hydrolysate formula (Alimentum) or a cow's milk-based formula (Similac). Each patient was monitored at 1 month and then every 3 months for 1 year. RESULTS: Eighteen patients (8 Alimentum, 10 Similac) completed the study. At entry, the age distribution and clinical characteristics of each group were comparable. Energy intake with each formula was the same at 1 and 3 months, but at 6 and 12 months the hydrolysate-fed infants had higher age-adjusted energy intake. There were no differences in fecal energy or fecal fat at entry or throughout the study. Although the hydrolysate-fed infants were slightly more malnourished at diagnosis, growth velocity and nutritional status of infants with CF in each group were the same throughout the study. CONCLUSIONS: The results of this randomized study fail to support the use of a hydrolyzed formula for the routine care of infants newly diagnosed with CF.

Dietary intakes of young children with cystic fibrosis: is there a difference?

Caloric intakes of preadolescent and adolescent girls and boys with cystic fibrosis (CF) were compared in order to evaluate the possibility that poor caloric intake contributes to poor nutritional status and high mortality among girls with CF. Fifty-six CF patients (26 girls and 30 boys), 10-15 years old, completed a 3-day food record, answered a short questionnaire, and underwent anthropometric and pulmonary function assessment. The mean ages of the girls and boys were similar, but the height and weight percentiles of the girls were lower than those of the boys (p = 0.02). Mean caloric intakes were no different (116% and 112% of the recommended nutrient intake in the girls and boys, respectively). Nutritional status, as determined by weight as a percentage of ideal weight for height, mean triceps skinfold thickness, and midarm muscle circumference, was normal and similar in both sexes. Most girls and boys with CF in this study had an appropriate perception of their body weight. Pulmonary function tests suggested mild lung disease with no significant difference between girls and boys (forced expiratory volume in 1 s of 82.2% and 79.8% of predicted values, respectively). The similar nutritional and pulmonary status of the girls and boys with CF in this age group is in contrast to previous reports. This finding may be the result of our policy, introduced > 15 years ago, of expecting normal growth, by paying close attention to enzyme therapy and encouraging high energy intake from the time of diagnosis. It remains to be seen whether boys and girls continue to maintain similar nutritional and pulmonary status at a later age and whether both sexes experience a similar mortality rate as they age.