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In humans, phenylalanine stimulates plasma cholecystokinin (CCK) and pyloric pressures, both of which are important in the regulation of energy intake and gastric emptying. Gastric emptying is a key determinant of postprandial blood glucose. We evaluated the effects of intragastric phenylalanine on appetite perceptions and subsequent energy intake, and the glycaemic response to, and gastric emptying of, a mixed-nutrient drink. The study consisted of two parts, each including 16 healthy, lean males (age: 23 ± 1 years). In each part, participants received on three separate occasions, in randomised, double-blind fashion, 5 g (Phe-5 g) or 10g ('Phe-10 g) L-phenylalanine, or control, intragastrically, 30 min before a standardised buffet-meal (part A), or a standardised mixed-nutrient drink (part B). In part A, plasma CCK and peptide-YY (PYY), and appetite perceptions, were measured at baseline, after phenylalanine alone, and following the buffet-meal, from which energy intake was assessed. In part B, plasma glucose, glucagon-like peptide-1 (GLP-1), insulin and glucagon were measured at baseline, after phenylalanine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured by 13 C-acetate breath-test. Phe-10 g, but not Phe-5 g, stimulated plasma CCK ( p = 0.01) and suppressed energy intake ( p = 0.012); energy intake was correlated with stimulation of CCK (r = -0.4, p = 0.027), and tended to be associated with stimulation of PYY (r = -0.31, p = 0.082). Both Phe-10 g and Phe-5 g stimulated insulin and glucagon (all p &lt; 0.05), but not GLP-1. Phe-10 g, but not Phe-5 g, reduced overall plasma glucose ( p = 0.043) and peak plasma glucose ( p = 0.017) in response to the mixed-nutrient drink. Phenylalanine had no effect on gastric emptying of the drink. In conclusion, our observations indicate that the energy intake-suppressant effect of phenylalanine is related to the stimulation of CCK and PYY, while the glucoregulatory effect may be independent of stimulation of plasma GLP-1 or slowing of gastric emptying.

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Effects of L-Phenylalanine on Energy Intake and Glycaemia—Impacts on Appetite Perceptions, Gastrointestinal Hormones and Gastric Emptying in Healthy Males