Differential effects of L‐ and D‐phenylalanine on pancreatic and gastrointestinal hormone release in humans: A randomized crossover study

Abstract 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). L‐phenylalanine also increased GIP concentrations relative to D‐phenylalanine ( P = .0420) and placebo ( P = .0249) 70 minutes following ingestion. L‐phenylalanine reduced postprandial glucose area under the curve (AUC) 70‐150mins relative to placebo ( P = .0317) but did not affect subjective appetite or energy intake ( P > .05). D‐phenylalanine increased postprandial PYY AUC 70‐150mins 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.