Archives ofDisease in Childhood 1990; 65: 589-593 Excessive faecal losses of vitamin A (retinol) in cystic fibrosis F Ahmed, J Ellis, J Murphy, S Wootton, A A Jackson Abstract Vitamin A (retinol) deficiency is a recognised complication of cystic fibrosis and is pre- sumed to be a consequence of an impairment in the digestion and absorption of dietary fats. The dietary intake of fat and retinol was assessed from a seven day weighed food intake in 11 subjects with cystic fibrosis and 12 matched controls. Faecal excretion of retinol and fat were measured from three day stool coliections. There was little difference between the two groups in the intake of fat or retinol equivalents. When studied the subjects with cystic fibrosis were cfinicaily stable and the apparent absorption of fat was not signifi- cantly different to that in the controls. There was a significant increase in the faecal losses of retinol in cystic fibrosis, which was unre- lated to the degree of fat in the stool. In cystic fibrosis the median retinol recovered in the stool was 40% of the intake, compared with 1-8% in the controls. It is concluded that there is a specific defect in the handling of retinol by the gastrointestinal tract in cystic fibrosis, which may be unrelated to the digestion and absorption of dietary fat. Department of Human Nutrition, University of Southampton, Bassett Crescent East, Southampton S09 3TU F Ahmed J Ellis J Murphy S Wootton AA Jackson Correspondence to: Professor Jackson. Accepted 8 February 1990 Children with cystic fibrosis experience com- plex nutritional problems caused by a combina- tion of the underlying disease process and the effects of pancreatic exocrine insufficiency upon digestion and absorption. There is clinical evi- dence for deficiencies of the fat soluble vita- mins, and xerophthalmia has been attributed to vitamin A (retinol) deficiency.' 2 A recognised feature of cystic fibrosis is steatorrhoea caused by a failure of fat digestion and absorption. In earlier studies it was thought most likely that a deficiency of retinol was a consequence of fat malabsorption. Postmortem studies have shown that the retinol concentra- tion in the liver might be three to four times that seen in a control group, however, even though serum concentrations of vitamin A might be low.3 Supplementation with retinol failed to bring the serum concentrations within the normal range, despite normal concentrations in the liver.4 These observations gave rise to the suggestion that the primary disorder of retinol metabolism in cystic fibrosis might be an inabil- ity to mobilise retinol from storage in the liver.4 Under normal circumstances retinol is carried in the circulation bound to retinol binding pro- tein, which is synthesised in the liver. There is evidence to show that factors which influence the synthesis or mobilisation of retinol binding protein may contribute to a clinical deficiency of retinol. Among the possible factors that could contribute to a deficiency are hepatic damage,4 zinc deficiency,5 and protein inanition.6 Notwithstanding these observations, little work has been carried out to explore the original suggestion by Andersen that deranged gastroin- testinal handling of retinol is of importance.' As the intestinal esterification of retinol appears to be normal,7 it has been presumed that any fat maldigestion and malabsorption due to pancrea- tic insufficiency would automatically be associ- ated with increased faecal loss of the vitamin. To our knowledge no attempt has been made to quantitate faecal losses. Animal experiments suggest that under normal circumstances retinol is excreted in urine or stool as a series of com- plex degradation products, but mainly as the glucuronide.8 Therefore, it is reasonable to assume that any retinol found in the stool approximates malabsorbed losses, rather than endogenous wastage or excretion. In this study we have developed a method for measuring retinol in the stool by high perform- ance liquid chromatography (HPLC). Using this method we have been able to demonstrate an apparent excess faecal loss of retinol relative to fat in children with cystic fibrosis compared with a control group. Subjects and methods SUBJECTS The study was carried out in 11 subjects who were participating in a larger study of nutri- tional state in cystic fibrosis. They were compared with a group of age matched local children and young adults, who were willing to participate and had no relevant medical history. The study had the approval of the joint ethical subcommittee of the Southampton and South West Hampshire district health authority and the University of Southampton. Consent was given by the subjects or the parents of the chil- dren in the full knowledge that they could with- draw at any time without prejudice. All the subjects showed some degree of failure to thrive, but were generally well at the time of study. They all had regular access to dietary support and had regular supplements of vita- mins and replacement pancreatic enzymes (Creon, Duphar) prescribed. Only three of the 11 subjects with cystic fibrosis were taking a multivitamin supplement that contained vita- min A at the time of study. Each participant completed a record of a seven day weighed food intake. During the final days of this period a three day stool collection was completed between carmine markers. The 589 group.bmj.com on July 10, 2011 - Published by adc.bmj.com Downloaded from