Proceedings of The Physiological Society
University College Dublin (2009) Proc Physiol Soc 15, PC187
Colestyramine: a Novel Non-nutrient Tool in Human Gastric Emptying Studies
A. Psichas1, T. Little2, M. Case1, J. McLaughlin2
1. Faculty of Life Sciences, Manchester University, United Kingdom. 2. School of Translational Medicine, Manchester University, United Kingdom.
Two established physiological actions of the enteroendocrine peptide cholecystokinin (CCK) include inhibition of gastric emptying and mediation of satiation after a nutrient meal. There is evidence to suggest that the particulate resin colestyramine stimulates secretion of CCK in humans. It also directly stimulates the STC-1 enteroendocrine cell line. This preliminary study therefore examines the effect of colestyramine on gastric emptying and appetite in vivo in healthy humans in order to assess its potential use as a non-nutrient tool in gastric emptying studies. Nine healthy volunteers were given liquid test meals (500ml) containing 4g colestyramine, 12g colestyramine or water alone, on three occasions, in a randomised order. The effect of colestyramine on gastric emptying was determined non-invasively using the 13C-acetate breath test and the effect on appetite was assessed by visual analogue scales. Colestyramine significantly delayed gastric emptying (overall treatment effect, p < 0.001). The cumulative 13CO2:12CO2 expired over the 45-minute period after vehicle was 427.7 ± 28.1 mean/SEM), compared to 342 ± 26.7 after 4g, and 280.6 ± 14.3 after 12g colestyramine. Pairwise comparisons revealed that the significance of the emptying delay was greater in response to 12g (p<0.001) than 4g colestyramine (p = 0.048) compared to vehicle. The delay in gastric emptying in response to 4g was considerably variable between individuals, whereas the response to 12g was relatively consistent. Colestyramine also significantly reduced hunger (p=0.007), the amount of food participants felt able to eat (p=0.001) and bloating (p=0.01). It did not evoke nausea. After vehicle, it took subjects ~20 min to reach the average baseline hunger score, whereas the baseline score was not reached within the 45-min period with colestyramine. These data demonstrate that colestyramine significantly delays gastric emptying and reduces appetite in humans. Therefore, it has potential as a novel non-nutrient tool in gastric emptying studies in health and disease (eg diabetic gastroenteropathy). Colestyramine is particularly interesting in that it is not absorbed from the lumen and therefore cannot exert post-absorptive effects, which are problematic in interpreting the effects of absorbable nutrients. Furthermore, in light of its effects on gastric emptying and appetite, understanding the underlying mechanisms could lead to new therapeutic applications.
Where applicable, experiments conform with Society ethical requirements