Differential effects of L- and D-phenylalanine on pancreatic and gastrointestinal hormone release in humans: a randomised crossover study.

AIM To investigate the effects of L-phenylalanine on gastroenteropancreatic hormone release, glucose levels, subjective appetite and energy intake in humans, and to determine whether these effects were stereoisomer-specific by comparing them with D-phenylalanine. MATERIALS AND METHODS A dose-finding, non-randomized, unblinded, crossover study was conducted during October-December 2017 at the NIHR Imperial Clinical Research Facility in five participants, in which the tolerability of escalating doses of oral L-phenylalanine was assessed (0, 3, 6 and 10 g). Also, an acute, randomized, double-blind, placebo-controlled crossover study was conducted during January-May 2018 at the NIHR Imperial Clinical Research Facility in 11 participants, in which the effects of oral 10 g L-phenylalanine relative to D-phenylalanine and placebo on gastroenteropancreatic hormone (insulin, glucagon, glucose-dependent insulinotropic polypeptide [GIP], peptide tyrosine tyrosine [PYY], glucagon-like peptide-1) and glucose concentrations, visual analogue scales for subjective appetite and energy intake at an ad libitum meal served 70 minutes postingestion, were investigated. RESULTS L-phenylalanine was well-tolerated and increased insulin and glucagon concentrations prior to meal ingestion at several time points relative to placebo and D-phenylalanine (P  .05). D-phenylalanine increased postprandial PYY AUC70-150mins concentrations relative to placebo (P = .0002). CONCLUSIONS Ingestion of L-phenylalanine, but not D-phenylalanine, increases insulin, glucagon and GIP concentrations without appearing to have a marked effect on appetite.