Scot Sweet Study (Interaction of a Non-nutritive Sweetener With a High-fibre Weight Loss Diet)

Study Overview
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Brief Summary
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The investigators present a weight loss diet intervention study, to be conducted as a within-subject design, with all food and beverages provided, to assess interaction of non-nutritive sweetener (sucralose) with a high-fibre weight loss diet, on markers of gut health in humans. This study will allow assessment of the effects of a non-nutritive sweetener (sucralose) with a high-fibre (soluble fibre, fructo-oligosaccharides, FOS) diet on metabolic health and activity and composition of gut microbiota, by a controlled human diet intervention study. The investigators propose to recruit participants living with obesity, with a poor diet quality (moderate habitual fibre intake) to additionally address diet inequalities in the research approach, and this will also allow examine the time-course of adaptation of the gut microbiome (measured in faecal samples). The investigators will also assess changes in free-living glycaemic control with addition of dietary fibre and bio-markers of health.

Official Title
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Healthy Diets for a Healthy Weight: Exploring Physiological Mechanisms Related to Dietary Fibre and Non-Nutritive Sweeteners

Conditions
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Appetitive Behavior

Intervention / Treatment
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* Other: Phase 1 Control
* Other: Phase 2 High Fibre Weight Loss
* Other: Phase 3 High Fibre and Non-Nutritive Sweetener Weight Loss


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy but overweight/obese (BMI 28-40kg/m2) males and females (postmenopausal, using the oral contraceptive pill or some form of hormonal contraceptive) moderate habitual fibre intake (18-23g/day) Exclusion Criteria: Medication exclusion criteria: antibiotic use (within the past 3 months due to impact on gut microbiota) anti-depressants (current) smoking or vaping weight loss medication Medical exclusion criteria: Females who are planning to be pregnant, are pregnant or are breastfeeding Anyone with food allergies, self-reported food sensitivity or intolerance Anyone with coeliac disease or gluten intolerance Anyone taking medication which may affect their appetite Anyone with an eating disorder Anyone with diabetes Anyone with a gastrointestinal disorder, kidney disease, liver disease or gout Anyone suffering from a psychiatric disorder or any type of substance abuse Anyone suffering from unregulated thyroid disease Other exclusion criteria: Anyone following a vegetarian or vegan diet Anyone following a current weight loss programme (that may be affecting lifestyle, physical activity & diet) or undergone gastric band/reduction surgery Anyone with unsuitable veins for blood sampling Anyone who is unable to fluently speak, read and understand English Anyone who is unable to comply to an alcohol-free diet for 6 weeks Current sweetener consumption will not be an exclusion criteria as the Phase 1 - CTRL and Phase 2 - HF WL diets will provide enough of a washout (4 weeks) before the Phase 3 diets containing sucralose are consumed. Participants who do habitually consume sweeteners will be asked not to use them during the study.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control-High Fibre Weight Loss-High Fibre Non-Nutritive Sweetener Weight Loss: CTRL-HF WL-HF-NNS WL<br>Phase 1 CTRL: Control diet with moderate fibre consumption for 14days. Phase 2 HF WL: High Fibre Weight Loss meal consumption for 14days. Phase 3 HF-NNS WL: High Fibre and Non-Nutritive Sweetener Weight Loss meal consumption for 14days. | Other: Phase 1 Control<br>* Control diet (30% Fat, 15% Protein, 55% Carbohydrate, Fibre rising from 10 to 16g/d). Fed to energy balance (1.5 x Resting Metabolic Rate, RMR).<br>* Other names: CTRL;Other: Phase 2 High Fibre Weight Loss<br>* High Fibre Weight Loss diet (30% Fat, 15% Protein, 55% Carbohydrate). Fed to energy deficit (100% RMR). The quantity of fructo-oligosaccharides (FOS) will be fixed at 20g/day for all kcal levels with additional fibre coming from the diet provided. The FOS will be split over breakfast, lunch and dinner in drinks/yoghurts which will be compulsory to consume.<br>* Other names: HF WL;Other: Phase 3 High Fibre and Non-Nutritive Sweetener Weight Loss<br>* High Fibre and Non-Nutritive Sweetener Weight Loss diet (30% Fat, 15% Protein, 55% Carbohydrate). Fed to energy deficit (100% RMR). The quantity of fructo-oligosaccharides (FOS) and non-nutritive sweetener (sucralose) will be fixed at 20g/day and 30mg/day respectively for all kcal levels with additional fibre coming from the diet provided. The FOS and sucralose will be split over breakfast, lunch and dinner in drinks/yoghurts which will be compulsory to consume.<br>* Other names: HF-NNS WL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gut metabolites (from faecal samples) in response to dietary fibre and non-nutritive sweetener | Measured by changes in faecal short chain fatty acids concentrations | At baseline and end of each arm (study days 1, 15, 29 and 43) | 
| Change in gut microbiome composition (from faecal samples) in response to dietary fibre and non-nutritive sweetener | Measured by changes in bacterial 16S ribosomal ribonucleic acid gene sequencing; 16S rRNA | At baseline and end of each arm (study days 1, 15, 29 and 43) | 
| Change in gut metabolite production (from faecal samples) in response to dietary fibre and non-nutritive sweetener | Measured by changes in calprotectin concentrations | At baseline and end of each arm (study days 1, 15, 29 and 43) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in free-living glycaemic control in response to dietary fibre and non-nutritive sweetener | measured using continuous glucose monitoring (CGM) | every day of study diets (42days) | 
| Change in glycaemic control in response to dietary fibre and non-nutritive sweetener | measured by changes in fasted plasma glucose and insulin | At baseline and end of each arm (study days 1, 15, 29 and 43) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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weight loss, gut microbiome, glycaemic control, fibre, non-nutritive sweetener