The effects of the amino acid, L-tryptophan, alone or with the fatty acid, lauric acid, on energy intake and postprandial glycaemia in health, obesity and type 2 diabetes

Abstract

The studies reported in this thesis investigated whether specific dietary nutrients, including amino acids and fatty acids, when administered intraduodenally or intragastrically, reduce energy intake and/or blood glucose in healthy people and those with obesity and type 2 diabetes. These studies also investigated whether the effects are associated with modulation in GI functions, i.e. gut hormones, gut motility and gastric emptying. Moreover, they quantified extra-intestinal factors, including circulating amino acid concentrations, that may be surrogate markers for activity in central pathways in the brain. The key findings of the studies are: 1. Intragastric L-tryptophan, in a dose of 3 g, increased the plasma tryptophan/large neutral amino acids ratio more in lean participants than those with obesity, and in the lean the suppression of energy intake in response to tryptophan was related to the plasma tryptophan/LNAA ratio in the lean (Chapter 2). 2. Intragastric L-tryptophan, in a dose of 3 g, potently reduced energy intake, in both lean individuals and those with obesity. Suppression of energy intake was related to circulating tryptophan and the plasma tryptophan/LNAA ratio. L-tryptophan also suppressed appetite for 2 hours after the meal, despite the reduced energy intake. In the lean, appetite suppression was related to circulating tryptophan and the plasma tryptophan/LNAA ratio in lean participants (Chapter 3). 3. In individuals with type 2 diabetes, intragastric administration of L-tryptophan, in a dose of 3 g, before a carbohydrate-containing drink delayed the rise in plasma glucose, probably as a result of slowing of gastric emptying, but did not affect the overall blood glucose response (Chapter 4). 4. Intraduodenal infusion of lauric acid in combination with L-tryptophan, and lauric acid alone delayed the rise in postprandial plasma glucose in healthy men, probably by slowing of gastric emptying and GLP-1 stimulation, while L-tryptophan was ineffective (Chapter 5). In conclusion, the research presented in this thesis has established that while L-tryptophan potently suppresses energy intake in lean people and those with obesity, its effect on postprandial blood glucose differs between health, obesity and type 2 diabetes. GI factors, including gastric emptying and gut and pancreatic hormones, contribute to these effects, but apparently to varying extents, and other post-absorptive factors also play a role. Finally, the combination of lauric acid and L-tryptophan, each in doses that individually do not reduce postprandial glycaemia, has a potent effect to delay the early rise in postprandial glucose, reflecting slowing of gastric emptying. Further research is indicated to investigate the sustained effects of L-tryptophan on appetite, energy intake and body weight. Moreover, studies to assess the effect of the combination of lauric acid and L-tryptophan on postprandial glycaemia in obesity and/or type 2 diabetes are also indicated. Broadly, the purpose of these studies would be to determine whether these nutrients have the potential to offer a novel, nutrient-based treatment option for the management of obesity and/or type 2 diabetes.