The Effect of Artificial Sweeteners (AFS) on Sweetness Sensitivity, Preference and Brain Response in Adolescents

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of dietary exposure to artificial sweeteners on taste sensitivity, preference and brain response in adolescents using fMRI, psychophysical measures, and questionnaires. The investigators hypothesize that dietary exposure to artificial sweeteners (sucralose) will decrease sensitivity to taste, shift preference of sweet and savory taste to a higher dose, and reduce brain response in amygdala to sweet taste compared to sucrose.

Detailed Description
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We aim to identify neural factors that contribute to taste intensity perception in humans and to determine environmental mechanisms that contribute to variation in taste sensitivity. Significant controversy surrounds the possibility that consumption of artificial sweeteners (AFS) leads to weight gain. Given that the five FDA approved AFSs are found in thousands of foods (Yang 2010) this marks a clear and significant gap in knowledge. Our preliminary data demonstrate a 3-fold decrease in sweet taste sensitivity following consumption of a beverage sweetened with two packets of Splenda for just 10 days. These data provide strong evidence that repeated exposure to sucralose reduces perception of sweet taste intensity, most likely by down-regulation of the sweet taste receptor. Adolescents may be more sensitive to exposure to AFS because of changes in metabolism during this period of development. Physiologic insulin resistance occurs during adolescence (Moran, Jacobs et al. 1999); this change in insulin sensitivity may predispose adolescents to greater impairments in sweet taste intensity by altering the relationship between sweet taste and post-ingestive reward, as suggested by the Davidson and Swithers model (Davidson and Swithers 2004). Therefore, it is imperative that we gain a greater understanding of the physiological consequences of AFS use in adolescents, since alterations in sweet taste perception, metabolism and brain reward that occur in response to AFS exposure may promote weight gain.

Official Title
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The Effect of Artificial Sweeteners (AFS) on Sweetness Sensitivity, Preference and Brain Response in Adolescents

Conditions
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Insulin Resistance, Obesity

Intervention / Treatment
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* Dietary Supplement: Sucralose
* Dietary Supplement: Sucrose
* Dietary Supplement: Sucralose + maltodextrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Fluent in English Right handed 13-17 years old Exclusion Criteria: History of oral nerve damage, presence of known taste or smell disorder, food allergies or sensitivities (for example nuts, lactose, artificial sweeteners), history of CNS disease, diabetes, history of DSM-IV major psychiatric disorder, including alcohol and substance abuse, chronic use of medication that may affect taste, conditions that may interefere with gustatory or olfactory perception (colds, seasonal allergies, recent smoking history), aberrant stimulus ratings, contra-indication for fMRI, uncomfortable swallowing in supine position, discomfort or anxiety associated with insertion an intravenous catheter, regular artificial sweetener use.

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sucralose<br>Flavored beverage with sucralose. | Dietary Supplement: Sucralose<br>* 2 packets<br>|
| Experimental: Sucrose<br>Flavored beverage with sucrose. | Dietary Supplement: Sucrose<br>* equisweet to sucralose<br>|
| Experimental: Sucralose + maltodextrin<br>Flavored beverage with Splenda + maltodextrin . | Dietary Supplement: Sucralose + maltodextrin<br>* sucralose plus equicaloric (to sucrose) maltodextrin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratings of taste sensitivity | At baseline and after on average 2 weeks, subjects will rate intensity of sucrose, sucralose, mono potassium glutamate, sodium chloride and citric acid using the General Labeled Magnitude Scale (gLMS). It is a vertical line with quasi-logarithmic spaced labels that start at the bottom with 'barely detectable' to 'strongest imaginable' at the top, recoded to 0-100. | on average 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance and GLP-1 | We will draw a blood sample to assess glucose, insulin and GLP-1 | on average 2 weeks | 
| Ad libitum food intake | Subject is offered milk and cereal and asked to consume as much as they want. The amount consumed is measured in weight and converted to calories. | on average 2 weeks | 
| percent signal change of brain response in reward and gustatory areas to taste stimuli | brain response in reward and gustatory areas to sucrose, mono potassium glutamate, sodium chloride and citric acid (in percent signal change). | on average 2 weeks |