Dietary Carbohydrate Manipulation and Energy Balance: RCT

Study Overview
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Brief Summary
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This study will investigate how dietary sugar and carbohydrates influence metabolism and health across a 12-week period, with a focus on physical activity. One third of participants will eat a diet with typical amounts of sugar and carbohydrate, one third of participants will eat a diet with sugar intake restricted, and the final third of participants will eat a diet where both sugar and total carbohydrates are restricted and replaced with fat.

Detailed Description
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Sugar is perceived negatively, leading to government taxation and targets to reduce consumption. These actions have been taken based on the limited evidence that high-sugar diets are associated with greater total energy intake. However, energy intake is only one half of the energy balance equation (energy in vs energy out). Without considering energy expenditure, it is impossible to fully understand the effects of sugar on health. Removing dietary sugar or carbohydrates from the diet may influence energy balance through mechanisms other than energy intake - for example by reducing levels of physical activity. Understanding dietary regulators of energy balance is more important than ever because diseases like obesity are a consequence of energy surplus (i.e. energy in > energy out). No studies have investigated a causal role of dietary sugar or carbohydrate on energy balance. The proposed research will seek to understand the responses to manipulating dietary carbohydrate and sugar content on energy balance and health. This research will enable the public to make informed dietary choices about carbohydrate and sugar consumption. To achieve this, healthy non-obese adults, aged 18-65 years will be recruited to take part in an intervention study with measures of energy intake, energy expenditure, metabolic health, gut microbiota, and appetite. All laboratory trials will take place at the University of Bath. Participants will be randomised to consume one of three diets for a period of 12 weeks, with laboratory visits at baseline, at week 4, and at week 12: CONTROL (moderate sugar) - reflecting the composition of a typical European diet Low sugar - the same composition of a typical European diet but with <5% energy intake from sugar Low carbohydrate - low carbohydrate diet with <5% energy intake from sugar, replacing carbohydrate energy with fat

Official Title
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The Effect of Dietary Carbohydrate Manipulation on All Major Aspects of Energy Balance: A 12-week Randomised Controlled Trial

Conditions
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Physical Activity, Diet Modification

Intervention / Treatment
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* Other: Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index 18.5-29.9 kg∙m-2 Age 18-65 years Able and willing to provide informed consent and safely comply with study procedures Females to maintain record of regular menstrual cycle phase/contraceptive use No anticipated changes in physical activity during the first 4 weeks of the study (e.g. holidays or training programmes) Exclusion Criteria: Any reported condition or behaviour deemed either to pose undue personal risk to the participant or introduce bias Any diagnosed metabolic disease (e.g. type 1 or type 2 diabetes) Any reported use of substances which may pose undue personal risk to the participants or introduce bias into the experiment Lifestyle not conforming to standard sleep-wake cycle (e.g. shift worker) Any reported recent (<6 months) change in body mass (± 3%) Use of antibiotic medication in the last 3 months Use of prebiotic or probiotic products in the last month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Interventional Model Description: Randomised controlled trial with 3 arms. One arm is a typical diet (50% CHO, 20% SUG), one arm is low sugar (50% CHO, <5% SUG), one arm is low carbohydrate (<8% CHO, <5% SUG). Stratified by sex and physical activity level (PAL).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CONTROL<br>Diet consisting of 50% carbohydrate (20% sugar), 15% protein, 35% fat | Other: Diet<br>* Macronutrient composition (specifically type and/or amount of carbohydrate) is manipulated<br>|
| Experimental: LOW SUG<br>Diet consisting of 50% carbohydrate (<5% sugar), 15% protein, 35% fat | Other: Diet<br>* Macronutrient composition (specifically type and/or amount of carbohydrate) is manipulated<br>|
| Experimental: LOW CHO<br>Diet consisting of <8% carbohydrate (<5% sugar), 15% protein, >77% fat | Other: Diet<br>* Macronutrient composition (specifically type and/or amount of carbohydrate) is manipulated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical activity energy expenditure (kJ/day or kcal/day) | 24-hour physical activity energy expenditure (kJ/day or kcal/day) | 7 days (across 12 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time spent in different physical activity intensities (MET categories) (minutes) | Time spent in different physical activity intensities (MET categories) (minutes) | 7 days (across 12 weeks) | 
| Energy expended in different physical activity intensities (MET categories) (kJ or kcal) | Energy expended in different physical activity intensities (MET categories) (kJ or kcal) | 7 days (across 12 weeks) | 
| Energy intake and dietary macronutrient composition | Estimated using food diaries, 7 days each time concurrently measured with PAEE and 3 days per week for the rest of the intervention | 12 weeks | 
| Body mass | Measured weekly using electric scales | 12 weeks | 
| Bone mineral density | Bone mineral density measured using dual x-ray absorptiometry | 12 weeks | 
| Bone mineral content | Bone mineral content measured using dual x-ray absorptiometry | 12 weeks | 
| Fat mass | Fat mass measured using dual x-ray absorptiometry | 12 weeks | 
| Fat-free mass | Fat-free mass measured using dual x-ray absorptiometry | 12 weeks | 
| Android fat mass | Android fat mass measured using dual x-ray absorptiometry | 12 weeks | 
| Gynoid fat mass | Gynoid fat mass measured using dual x-ray absorptiometry | 12 weeks | 
| Resting metabolic rate | Resting metabolic rate will be measured using indirect calorimetry | 12 weeks | 
| Substrate oxidation | Substrate oxidation will be measured using indirect calorimetry both at rest and during exercise | 12 weeks | 
| Waist and hip circumference | Waist and hip circumference will be measured using a tape measure | 12 weeks | 
| Step count | Measured daily using pedometers | 12 weeks | 
| Fasting metabolite/hormone profile | Assessment of blood glucose, insulin, triglycerides, non-esterified fatty acids, lactate, beta-hydroxybutyrate, leptin, fibroblast growth factor-21, total cholesterol, high density lipoprotein, and low density lipoprotein concentrations, appetite hormone concentrations (including PYY, GLP-1, ghrelin) | 12 weeks | 
| Postprandial metabolite/hormone profile | Assessment of blood glucose, insulin, triglycerides, non-esterified fatty acids, lactate, beta-hydroxybutyrate, leptin, fibroblast growth factor-21, total cholesterol, high density lipoprotein, and low density lipoprotein concentrations, appetite hormone concentrations (including PYY, GLP-1, ghrelin) | 4 hours (across 12 weeks) | 
| Blood pressure | Measured using an automated sphygmomanometer | 12 weeks | 
| Food preference ratings | Food preference ratings determined by bespoke computer software | 12 weeks | 
| Subjective appetite and mood ratings | Measured by 0-100 mm visual analogue scale | 12 weeks | 
| Interstitial glucose concentrations | Measured using research-grade freestyle libre glucose monitors. Measured pre-, during- and at the end of the intervention | 14 days (across 12 weeks) | 
| Adipose tissue gene expression | Expression of a panel of genes related to glucose metabolism in adipose biopsies using real-time polymerase chain reaction | 12 weeks | 
| Adipose tissue protein expression | Expression of various proteins related to glucose metabolism in adipose biopsies via Western blot | 12 weeks | 
| Muscle tissue gene expression | Expression of a panel of genes related to glucose metabolism in muscle biopsies using real-time polymerase chain reaction | 12 weeks | 
| Muscle tissue protein expression | Expression of various proteins related to glucose metabolism in muscle biopsies via Western blot | 12 weeks | 
| Muscle glycogen concentrations | Glycogen concentrations measured from vastus lateralis muscle samples | 12 weeks | 
| Gut microbiome characterisation | Faecal sample DNA and water will be used to determine taxonomic and functional diversity of microbes using transcriptomic techniques | 12 weeks | 
| Urinary acetoacetate concentrations | Will be measured using handheld sticks | 12 weeks | 
| Urine urea nitrogen excretion | Will be measured across trial days | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Physical Activity, Nutrition, Carbohydrates, Energy Balance, Sugar