Assessment of Reward Responses to Erythritol Using Flavor Preference Learning

University Hospital, Basel, Switzerland20 enrolled

Overview

The aim of this project is to investigate the reward responses to oral erythritol compared to sucrose and sucralose using flavor preference learning in healthy participants. In addition, the release of GI hormones, glycemic control, appetite-related sensations, and emotional state in response to erythritol will be investigated.

This trial is a randomized, double-blind, cross-over study; the project set-up will be single-centre, national. The study is composed of six visits: one screening visit, one pre-test visit, three conditioning visits, and one post-test visit. The screening and pre-test will last about two hours, the conditioning days and the post-test day about 4 hours each. During the screening participants take part in a 6-n-propylthiouracil (PROP) sensitivity test to exclude potential supertasters. Moreover, the participants will rate explicit liking and explicit wanting of 10 non-caloric flavored and colored beverages in a randomized order (flavor preference learning). The pre-test visit consists of two parts. First, a chemosensory sweetness matching will be performed, during which we will establish dose-response relationships for perceived sweetness of sucrose, erythritol, and sucralose using equisweet watery solutions across a range of concentrations. Second, the participants will perform a triangle test to ensure that they cannot distinguish the matched erythritol and sucralose solutions from a 10% sucrose solution. During the 3 conditioning visits, participants will be presented with three conditioning trials (at t = 0, 45, and 90min), each consisting of drinking 100mL of the flavored drink (CS) paired with one of the sweet substances (US = erythritol, sucrose, or sucralose). In post-test visit, preference for each of the 3 flavored CS drinks will be assessed and a computerized forced choice task will be completed by the participants.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy normal weight participants with a body-mass index (BMI) of 19.0-24.9 kg/m2 * Age 18-55 years * Stable body weight (±5%) for at least three months * Able to give informed consent as documented by signature * 3 drinks rated as neutral and novel (from the flavor preference learning) Exclusion Criteria: * Non-taster (deficits of taste and smell) or supertaster * Fructose intolerance * Shift worker * Pre-existing regular consumption of erythritol and/or sucralose and/or aspartame (\>1/week) * Substance abuse (more than 1 glass wine/beer per day; consumption of cannabis, cocaine, heroin, etc.) * Regular intake of medications, except contraceptives * Chronic or clinically relevant acute infections * Pregnancy: although no contraindication, pregnancy might influence metabolic state. * Participation in another study with investigational drug within the 30 days preceding and during the present study * Pre-existing diet (vegetarian, vegan, sugar free) * Inability to follow procedures due to psychological disorders or insufficient knowledge of project language (German) * Calculated dose of erythritol outside the range of 30-60g (per 300mL) (from the sweetness matching)

Outcomes

Primary Outcomes

Assessment of the change of explicit wanting (reward response) to oral erythritol versus sucrose and sucralose as change from baseline to post-test visit.

Beverages are consumed during the screening visit, conditioning visits and the post-test visit. The beverages will be consumed at t = 0min, t = 45min and t = 90min and afterwards explicit wanting will be assessed. Explicit wanting of the consumed beverages is assessed by Visual Analogue Scale (VAS) as "How much do you want to drink of the drink". The Visual Analogue Scale consists of a horizontal, unstructured, 10 cm line representing the minimum (0.0 points) labeled with "not much at all" to the maximum rating (10.0 points) labeled with "very much". Participants are instructed to draw a dash in the answer line to indicate the magnitude of their subjective sensation at the present time point.

Time frame: from baseline to post-test visit (at t = 0min, t = 45min and t = 90min)

Secondary Outcomes

Effects on reward response - explicit liking

Beverages are consumed at the screening visit (during the flavor preference learning), conditioning visits and the post-test visit. Explicit liking of the consumed beverages during the screening visit, the conditioning visits and post-test visit is rated from -100 to 100 using the Global Hedonic Intensity Scale (GHIS). The Global Hedonic Intensity Scale ranges from -100 "the most intensive disliking ever experienced" to 100 "most intensive liking ever experienced" and has no anchors and in the middle is 0 as a neutral point. Participants are instructed to draw a dash in the answer line to indicate the magnitude of their subjective liking at the present time point.

Time frame: The beverages will be consumed at t = 0min, t = 45min and t = 90min and afterwards explicit liking will be rated.

Effects on reward response - desire to drink

Beverages are consumed at the screening visit (during the flavor preference learning), conditioning visits and the post-test visit. During the post-test visit, the desire to drink will be recorded with a 10 cm Visual Analogue Scale (VAS) as "How strong is your desire to drink, that is, to taste and swallow, the rest of the drink RIGHT NOW? (Take a sip of the drink first)". The Visual Analogue Scale consists of a horizontal, unstructured, 10 cm line representing the minimum (0.0 points) labeled with "not strong at all" to the maximum rating (10.0 points) labeled with "very strong". Participants are instructed to draw a dash in the answer line to indicate the magnitude of their subjective sensation at the present time point.

Time frame: The beverages will be consumed at t = 0min, t = 45min and t = 90min and afterwards desire to drink will be rated.

Effects on reward response - implicit wanting

Implicit wanting will be measured at the end of the post-test visit by using a computerized forced choice task. Participants will be shown a paired presentation of three drinks where they have to select their most wanted drink ("select the drink which you would most want to drink right now"). In the four presentation parts, participants will have to choose between e.g. red bull drink vs. diet coke vs. fanta, or between diet coke vs. orange juice vs. ice tea. During the fifth presentation, pictures of the previous conditioned drinks will be shown and participants have to choose the drink which they would most want to drink right now. During the choice task, the chosen drink and the reaction time with which this drink was chosen (implicit wanting) will be measured.

Time frame: The computerized forced choice task will be performed at t = 135 min during the post-test visit.

Effects on GI hormone response - GLP-1

Plasma GLP-1 will be quantified using a non-radioactive high sensitive sandwich ELISA (Millipore - # EZGLPHS-35K) in the presence of a chemiluminescent substrate.