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

Background: Pancreatic enzyme replacement therapy frequently fails to corre ct 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 triacylglyc erols 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 th ey ingested 1,3-distearoyl,2[1-C-13]octanoyl glycerol ([C-13]MTG). Intestin al uptake of long-chain fatty acids was determined by analyzing plasma [C-1 3]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 fa t absorption (r = 0.88, P < 0.001). Conclusion: Our results suggest that continuing fat malabsorption in CF pat ients receiving enzyme replacement therapy is not likely due to insufficien t lipolytic enzyme activity, but rather to incomplete intraluminal solubili zation of long-chain fatty acids, reduced mucosal uptake of long-chain fatt y acids, or both.