An enteric-coated high-buffered pancrelipase reduces steatorrhea in patients with cystic fibrosis: a prospective, randomized study.

OBJECTIVE: Enteric-coated (EC) high-buffered (2.5 mEq [2.5 mmol] bicarbonate per capsule) pancrelipase microsphere enzymes were compared to EC-nonbuffered pancreatic enzymes for efficacy in reducing steatorrhea in patients with cystic fibrosis. DESIGN: Prospective, randomized, controlled trial using a crossover design with each subject as his/her own control. SUBJECTS/SETTING: Eighteen subjects with cystic fibrosis, who had pancreatic insufficiency and required large enzyme doses, were studied over two consecutive 7-day treatment periods. INTERVENTION: Each 7-day period consisted of 3 days at home followed by 4 days in a general clinical research center for careful control of diets, enzyme lipase doses (given at approximately 50% of the subject's usual lipase dose), and carmine red-labeled stool collections for 72-hour fecal fat balance studies. MAIN OUTCOME MEASURE: Fecal fat excretion. STATISTICAL ANALYSES PERFORMED: Differences in fat excretion, when each subject received EC-high-buffered pancrelipase vs EC-nonbuffered enzymes, were compared using linear modeling. RESULTS: Mean fat excretion decreased significantly in each subject during periods when given EC-high-buffered pancrelipase compared with periods when given EC-nonbuffered enzymes (fat excretion 18.2% vs 24.9% or fat absorption 81.8% vs 75.1%, respectively; P=0.01). Thirteen of 18 subjects (72%) excreted less fat when receiving EC-high-buffered pancrelipase whereas 10 (56%) decreased fat excretion by more than 5%, and five subjects did not respond. CONCLUSIONS: EC-high-buffered pancrelipase decreased fat excretion, symbolizing improved fat absorption, when compared with EC-nonbuffered pancreatic enzymes given at equivalent, reduced (approximately 50% of usual) lipase doses in nourished subjects with cystic fibrosis and mild pulmonary disease.

Does the pancreas really produce much more lipase than required for fat digestion?

Thirty years ago, it was reported that a linear relationship does not exist between the amounts of human pancreatic lipase secreted in chronic pancreatitis and the degree of steatorrhea, which was considered to appear only after more than 90% of the pancreatic secretory capacity had been lost. From these observations, it was generally thought that the lipolytic potential of the pancreas is much higher than required. In recent years, however, it has been noted that: 1) the level of inhibition of digestive lipases and gastrointestinal lipolysis by the lipase inhibitor orlistat were almost linearly correlated with the amount of excreted fat; 2) in minipigs with experimentally-induced pancreatic exocrine insufficiency, the amounts of enteric-coated pancreatic extracts needed for restoring fat digestion to normal levels were estimated to be much higher than those usually administered; 3) human pancreatic lipase specific activity on meal triglycerides is 3 orders of magnitude lower than the very high specific activity usually measured under experimental in vitro conditions which are far from physiological conditions; 4) in patients with reduced human pancreatic lipase secretion, gastric lipase plays a significant role in fat digestion. This last observation might explain the absence of a linear relationship between human pancreatic lipase secretion in chronic pancreatitis and steatorrhea. From the low specific activity displayed by human pancreatic lipase on meal triglycerides, one can better understand why more lipase than expected is needed, why fat digestion lasts for more than a few minutes and, finally, why there is not such an excess secretory capacity for lipase as had been previously thought.