The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite regulation in males: a randomized controlled study.

An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight-loss treatment. Metabolic responses to acute exercise are, however, dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon-like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, -48.8 pmol/L; exercise: -22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1 H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. KEY POINTS: Carbohydrate and exercise independently influence key appetite-regulating hormones. Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY. Postexercise energy intake is associated with glucagon-like peptide 1 and succinate levels.

Differential effects of L- and D-phenylalanine on pancreatic and gastrointestinal hormone release in humans: A randomized 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). 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 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.

A study protocol for a randomised crossover study evaluating the effect of diets differing in carbohydrate quality on ileal content and appetite regulation in healthy humans.

Introduction: A major component of the digesta reaching the colon from the distal ileum is carbohydrate. This carbohydrate is subject to microbial fermentation and can radically change bacterial populations in the colon and the metabolites they produce, particularly short-chain fatty acids (SCFA). However, very little is currently known about the forms and levels of carbohydrate in the ileum and the composition of the ileal microbiota in humans. Most of our current understanding of carbohydrate that is not absorbed by the small intestine comes from ileostomy models, which may not reflect the physiology of an intact gastrointestinal tract. Methods: We will investigate how ileal content changes depending on diet using a randomised crossover study in healthy humans. Participants will be inpatients at the research facility for three separate 4-day visits. During each visit, participants will consume one of three diets, which differ in carbohydrate quality: 1) low-fibre refined diet; 2) high-fibre diet with intact cellular structures; 3) high-fibre diet where the cellular structures have been disrupted (e.g. milling, blending). On day 1, a nasoenteric tube will be placed into the distal ileum and its position confirmed under fluoroscopy. Ileal samples will be collected via the nasoenteric tube and metabolically profiled, which will determine the amount and type of carbohydrate present, and the composition of the ileal microbiota will be measured. Blood samples will be collected to assess circulating hormones and metabolites. Stool samples will be collected to assess faecal microbiota composition. Subjective appetite measures will be collected using visual analogue scales. Breath hydrogen will be measured in real-time as a marker of intestinal fermentation. Finally, an in vitro continuous fermentation model will be inoculated with ileal fluid in order to understand the shift in microbial composition and SCFA produced in the colon following the different diets. Registration: ISRCTN11327221.