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

Abstract

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 13 CO 2 recovery in 10 CF patients receiving pancreatic enzyme replacement therapy after they ingested 1,3-distearoyl,2[1- 13 Results: Fecal fat excretion ranged from 5.1 to 27.8 g/d (x -± SD: 11.1 ± 7.0 g/d) and fat absorption ranged from 79% to 93% (89 ± 5%). There was no relation between breath 13 CO 2 recovery and dietary fat absorption (r = 0.04) after ingestion of [ 13 C]MTG. In contrast, there was a strong relation between 8-h plasma [ 13 C]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. Am J Clin Nutr 1999;69:127-34. KEY WORDSBreath test, mixed triacylglycerol, [13 C]linoleic acid, fat malabsorption, fat balance, lipolysis, stable isotopes, cystic fibrosis, recommended dietary allowance, children, long-chain fatty acids INTRODUCTIONIn humans, triacylglycerols composed of long-chain fatty acids constitute 92-96% of dietary fats (1). Absorption of these fats is by 2 main processes. Lipolysis, by lipolytic enzymes originating predominantly in the pancreas, leads to hydrolysis of triacylglycerols into fatty acids and 2-monoacylglycerols. Second, intestinal uptake involves the formation of mixed micelles composed of bile components and lipolytic products, followed by the disintegration of the mixed micelles in the unstirred water layer and the translocation of the lipolytic products across the intestinal epithelium (1-4).Most cystic fibrosis (CF) patients malabsorb dietary fats because of pancreatic insufficiency, which leads to impaired lipolysis (5, 6). The symptoms of pancreatic insufficiency, such as steatorrhea and poor growth, can be alleviated by oral supplementation with pancreatic enzymes. However, despite recent improvements in the pharmacokinetics of these supplements, many patients continue to experience a certain degree of steatorrhea (7-9), with 10-20% of the dietary fat they consume being malabsorbed. It has not been elucidated whether this malabsorption is due to insufficient pancreatic enzyme replacement therapy. This possibility is likely because decreased pancreatic bicarbonate secretion may negatively affect enzyme activity by sustaining a low pH in the duodenum (10, 11). At a low duodenal pH, the release of enzymes from the microcapsules is inhibited and denaturation of the enzymes is stimul...

Functional Development of Fat Absorption in Term and Preterm Neonates Strongly Correlates with Ability to Absorb Long-Chain Fatty Acids from Intestinal Lumen

“…13 C]linoleic acid absorption study in children with cystic fibrosis (31). We do realize that the observations in the rat cannot be directly extrapolated to the human situation and that results obtained for [ 13 C]linoleic acid absorption may not be similar for 13 C-PA or 13 C-SA.…”

“…Resulting fatty acid methyl esters were analyzed both by gas chromatography and by gas chromatography-combustion isotope ratio mass 58 RINGS ET AL. spectrometry, as detailed previously (31). Quantification of the resulting fatty acid methyl esters was performed with the use of heptadecanoic acid (C 17:0 ) as an internal standard.…”

Diagnosis and Treatment of Intestinal Malabsorption in Cystic Fibrosis

“…11 Impaired mucosal uptake and transport of long-chain fatty acids may occur. 12,13 There is also altered motility, with an increased small bowel transit time. 14,15 Structural abnormalities from previous gastrointestinal surgery for meconium ileus (e.g., shortened bowel, strictures, malrotations, and adhesions) and an excess of mucus may also be relevant.…”

Fibrose cística: uma abordagem clínica e nutricional

“…As proteínas requeridas para o crescimento e reparo de tecidos do corpo não são totalmente utilizadas. A gordura, o nutriente mais energético não é absorvido; assim, o crescimento é atrasado e as deficiências de vitaminas lipossolúveis podem ocorrer 28 .…”

“…Para tanto, o cuidado nutricional adequado deve incluir: terapia de reposição enzimática, dietas hiperenergéticas e hiperlipídicas, e suplementação de micronutrientes 28 .…”