Dietary Carbohydrate Manipulation and Energy Balance: RCT

Not Applicable

Completed

Conditions: Physical Activity
Diet Modification

Interventions: Other: Diet

Registration Number: NCT03574987

Lead Sponsor: University of Bath

Brief Summary: 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: 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:

1. CONTROL (moderate sugar) - reflecting the composition of a typical European diet

2. Low sugar - the same composition of a typical European diet but with \<5% energy intake from sugar

3. Low carbohydrate - low carbohydrate diet with \<5% energy intake from sugar, replacing carbohydrate energy with fat

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LOW CHO	Diet	Diet consisting of \<8% carbohydrate (\<5% sugar), 15% protein, \>77% fat
CONTROL	Diet	Diet consisting of 50% carbohydrate (20% sugar), 15% protein, 35% fat
LOW SUG	Diet	Diet consisting of 50% carbohydrate (\<5% sugar), 15% protein, 35% fat

Primary Outcome Measures

Name	Time	Method
Physical Activity Energy Expenditure (kJ/Day or kcal/Day)	7 days (across 12 weeks) - Primary outcome at week 4	24-hour physical activity energy expenditure (kJ/day or kcal/day)

Secondary Outcome Measures

Name	Time	Method
Step Count	12 weeks	Measured daily using pedometers
Body Mass	12 weeks	Measured weekly using electric scales
Bone Mineral Content	12 weeks	Bone mineral content measured using dual x-ray absorptiometry
Energy Intake and Dietary Macronutrient Composition	12 weeks	Estimated using food diaries, 7 days each time concurrently measured with PAEE and 3 days per week for the rest of the intervention
Energy Expended in Different Physical Activity Intensities (MET Categories) (kJ or kcal)	7 days (across 12 weeks)	Energy expended in different physical activity intensities (MET categories) (kJ or kcal)
Substrate Oxidation	12 weeks	Substrate oxidation will be measured using indirect calorimetry both at rest and during exercise
Blood Pressure	12 weeks	Measured using an automated sphygmomanometer
Time Spent in Different Physical Activity Intensities (MET Categories) (Minutes)	7 days (across 12 weeks)	Time spent in different physical activity intensities (MET categories) (minutes)
Android Fat Mass	12 weeks	Android fat mass measured using dual x-ray absorptiometry
Resting Metabolic Rate	12 weeks	Resting metabolic rate will be measured using indirect calorimetry
Subjective Appetite and Mood Ratings	12 weeks	Measured by 0-100 mm visual analogue scale
Bone Mineral Density	12 weeks	Bone mineral density measured using dual x-ray absorptiometry
Fat Mass	12 weeks	Fat mass measured using dual x-ray absorptiometry
Fat-free Mass	12 weeks	Fat-free mass measured using dual x-ray absorptiometry
Muscle Glycogen Concentrations	12 weeks	Glycogen concentrations measured from vastus lateralis muscle samples
Gynoid Fat Mass	12 weeks	Gynoid fat mass measured using dual x-ray absorptiometry
Food Preference Ratings	12 weeks	Food preference ratings determined by bespoke computer software
Adipose Tissue Gene Expression	12 weeks	Expression of a panel of genes related to glucose metabolism in adipose biopsies using real-time polymerase chain reaction
Muscle Tissue Gene Expression	12 weeks	Expression of a panel of genes related to glucose metabolism in muscle biopsies using real-time polymerase chain reaction
Waist and Hip Circumference	12 weeks	Waist and hip circumference will be measured using a tape measure
Fasting Metabolite/Hormone Profile	12 weeks	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)
Postprandial Metabolite/Hormone Profile	4 hours (across 12 weeks)	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)
Interstitial Glucose Concentrations	14 days (across 12 weeks)	Measured using research-grade freestyle libre glucose monitors. Measured pre-, during- and at the end of the intervention
Adipose Tissue Protein Expression	12 weeks	Expression of various proteins related to glucose metabolism in adipose biopsies via Western blot
Muscle Tissue Protein Expression	12 weeks	Expression of various proteins related to glucose metabolism in muscle biopsies via Western blot
Gut Microbiome Characterisation	12 weeks	Faecal sample DNA and water will be used to determine taxonomic and functional diversity of microbes using transcriptomic techniques
Urinary Acetoacetate Concentrations	12 weeks	Will be measured using handheld sticks
Urine Urea Nitrogen Excretion	12 weeks	Will be measured across trial days