Effects of quinine, alone and combined with dietary nutrients before a highly palatable milkshake, on gut function and blood glucose in healthy volunteers

INTERVENTION: Participants will receive in randomised, double‐blind fashion, a 10‐ml bolus of either(i) 600 mg quinine (ii) 300 mg quinine, (iii) water (control) intraduodenally on 3 separate visits. Each visit will be 5 hours in duration and separated by 3‐7 days. In females, the study visits will be arranged in the 7‐10 days from the start of their period cycle. Studies will be performed at the Clinical Research Facility, Adelaide Medical School, University of Adelaide, by staff and students trained in the required clinical research techniques. Participants will consume a standardised dinner meal, (400g McCain's beef lasagne), the night before each study visit by no later than 7pm. After fasting for 13.5 hours overnight and refraining from alcohol and exercise for 24 hours, participants will arrive at the Clinical Research Facility by 8:15 am. Upon arrival, participants will be given a standardised light breakfast (1 slice (30 g) white bread, 10 g jam and a cup (200 ml) black tea; 100 kcal), after which they will be intubated with a 17‐channel manometric catheter (Dentsleeve, Mui Scientific) that will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The infusion port will be positioned 14 cm distal to the pylorus. The correct positioning of the catheter will be monitored continuously by measurement of the transmucosal potential difference in the stomach ( ‐40 mV) and the duodenum ( 0 mV). Once the catheter has been positioned correctly, an intravenous cannula will be placed into a forearm vein for regular blood sampling. At 11.30 am, t = ‐30 min, a baseline blood sample (10 ml) will be taken, the participant will complete a validated 100‐ml visual analogue scale (VAS) questionnaire, to assess a CONDITION: increased energy intake; ; increased energy intake Metabolic and Endocrine ‐ Normal metabolism and endocrine development and function PRIMARY OUTCOME: Energy intake from palatable milkshake will be measured using the computer software program FoodWorks.[A palatable milkshake will be presented during each study visit (t = 0‐30 min). The cups will be refilled at irregular intervals e.g., t=0, 2, 5, 9, 14, 19, 24.] INCLUSION CRITERIA: Healthy SECONDARY OUTCOME: Amount of food desired to eat measured using VAS questionnaires.[VAS questionnaires will be completed at t = ‐31, ‐20, ‐10, 0, 30, 60 and 90 min, where t = ‐30 is just prior to the time of quinine administration and t = 0 is immediately before milkshake.] Desire to eat will be measured using VAS questionnaires.[VAS questionnaires will be completed at t = ‐31, ‐20, ‐10, 0, 30, 60 and 90 min, where t = ‐30 is just prior to the time of quinine administration and t = 0 is immediately before milkshake.] Fullness will be measured using VAS questionnaires.[VAS questionnaires will be completed at t = ‐31, ‐20, ‐10, 0, 30, 60 and 90 min, where t = ‐30 is just prior to the time of quinine administration and t = 0 is immediately before milkshake.] Hunger will be measured using VAS questionnaire.[VAS questionnaires will be completed at t = ‐31, ‐20, ‐10, 0, 30, 60 and 90 min, where t = ‐30 is just prior to the time of quinine administration and t = 0 is immediately before milkshake.] Plasma concentrations of cholecystokinin, other gastrointestinal hormones e.g., peptide yy (PYY), ghrelin and blood glucose will be measured. This outcome is of an exploratory nature so that the specific parameters to be measured may be decided upon based on the effect of the intervention on this and other outcomes, therefore, this is a composite outcome.[Plasma gut hormone concentration and blood glucose levels will be assessed from blood samples taken at t= ‐30, ‐20, ‐10, 0, 30, 60, and 90 min, where t = ‐30 is just prior to the time of quinine administration and t = 0 is immediately before milkshake.] The 'liking' and 'wanting' components of food preference and food reward will be measured using the Leeds Food Preference Questionnaire. This is a composite secondary outcome.[The 'liking' and 'wanting' components of food preference and food reward will be measured once immediately before treatment administration (t=‐30) and once 30 minutes later, immediately before milkshake (t=‐1). ]