Fat malabsorption in cystic fibrosis patients receiving enzyme replacement therapy is due to impaired intestinal uptake of long-chain fatty acids

Background: Pancreatic enzyme replacement therapy frequently fails to correct intestinal fat malabsorption completely in cystic fibrosis (CF) patients. The reason for this failure is unknown. Objective: We investigated whether fat malabsorption in CF patients treated with pancreatic enzymes is caused by insufficient lipolysis of triacylglycerols or by defective intestinal uptake of long-chain fatty acids. Design: Lipolysis was determined on the basis of breath (CO2)-C-13 recovery in 10 CF patients receiving pancreatic enzyme replacement therapy after they ingested 1,3-distearoyl,2[1-C-13]octanoyl glycerol ([C-13]MTG). Intestinal uptake of long-chain fatty acids was determined by analyzing plasma [C-13]linoleic acid ([C-13]LA) concentrations after patients ingested [C-13]LA. For 3 d, dietary intakes were recorded and feces were collected. Results: Fecal fat excretion ranged from 5.1 to 27.8 g/d ((x) over bar +/- SD: 11.1 +/- 7.0 g/d) and fat absorption ranged from 79% to 93% (89 +/- 5%). There was no relation between breath (CO2)-C-13 recovery and dietary fat absorption (r = 0.04) after ingestion of [C-13]MTG. In contrast, there was a strong relation between 8-h plasma [C-13]LA concentrations and dietary fat absorption (r = 0.88, P <0.001). Conclusion: Our results suggest that continuing fat malabsorption in CF patients receiving enzyme replacement therapy is not likely due to insufficient lipolytic enzyme activity, but rather to incomplete intraluminal solubilization of long-chain fatty acids, reduced mucosal uptake of long-chain fatty acids, or both