Diet Modification, Physical Activity
Conditions
Keywords
Physical Activity, Nutrition, Carbohydrates, Sugar, Energy Balance
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
Interventions
OTHERDiet
Macronutrient composition (specifically type and/or amount of carbohydrate) is manipulated
Sponsors
University of Bath
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention 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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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) |
| 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 |
| Body Mass | 12 weeks | Measured weekly using electric scales |
| Bone Mineral Density | 12 weeks | Bone mineral density measured using dual x-ray absorptiometry |
| Bone Mineral Content | 12 weeks | Bone mineral content 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 |
| Android Fat Mass | 12 weeks | Android fat mass measured using dual x-ray absorptiometry |
| Gynoid Fat Mass | 12 weeks | Gynoid fat mass measured using dual x-ray absorptiometry |
| Resting Metabolic Rate | 12 weeks | Resting metabolic rate will be measured using indirect calorimetry |
| Substrate Oxidation | 12 weeks | Substrate oxidation will be measured using indirect calorimetry both at rest and during exercise |
| Waist and Hip Circumference | 12 weeks | Waist and hip circumference will be measured using a tape measure |
| Urine Urea Nitrogen Excretion | 12 weeks | Will be measured across trial days |
| 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) |
| Blood Pressure | 12 weeks | Measured using an automated sphygmomanometer |
| Food Preference Ratings | 12 weeks | Food preference ratings determined by bespoke computer software |
| Subjective Appetite and Mood Ratings | 12 weeks | Measured by 0-100 mm visual analogue scale |
| 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 Gene Expression | 12 weeks | Expression of a panel of genes related to glucose metabolism in adipose biopsies using real-time polymerase chain reaction |
| Adipose Tissue Protein Expression | 12 weeks | Expression of various proteins related to glucose metabolism in adipose biopsies via Western blot |
| 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 |
| Muscle Tissue Protein Expression | 12 weeks | Expression of various proteins related to glucose metabolism in muscle biopsies via Western blot |
| Muscle Glycogen Concentrations | 12 weeks | Glycogen concentrations measured from vastus lateralis muscle samples |
| 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 |
| Step Count | 12 weeks | Measured daily using pedometers |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CONTROL Diet consisting of 50% carbohydrate (20% sugar), 15% protein, 35% fat
Diet: Macronutrient composition (specifically type and/or amount of carbohydrate) is manipulated | 18 |
| LOW SUG Diet consisting of 50% carbohydrate (\<5% sugar), 15% protein, 35% fat
Diet: Macronutrient composition (specifically type and/or amount of carbohydrate) is manipulated | 17 |
| LOW CHO Diet consisting of \<8% carbohydrate (\<5% sugar), 15% protein, \>77% fat
Diet: Macronutrient composition (specifically type and/or amount of carbohydrate) is manipulated | 18 |
| Total | 53 |
Baseline characteristics
| Characteristic | LOW SUG | LOW CHO | Total | CONTROL |
|---|---|---|---|---|
| Age, Continuous | 32 years STANDARD_DEVIATION 16 | 34 years STANDARD_DEVIATION 14 | 35 years STANDARD_DEVIATION 16 | 40 years STANDARD_DEVIATION 18 |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment United Kingdom | 17 participants | 18 participants | 53 participants | 18 participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 30 Participants | 11 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 23 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 17 | 0 / 18 |
| other Total, other adverse events | 0 / 18 | 0 / 17 | 1 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 | 0 / 18 |
Outcome results
Primary
Physical Activity Energy Expenditure (kJ/Day or kcal/Day)
24-hour physical activity energy expenditure (kJ/day or kcal/day)
Time frame: 7 days (across 12 weeks) - Primary outcome at week 4
Population: Dropout and/or missing data (device malfunction) between weeks 4 and 12.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CONTROL | Physical Activity Energy Expenditure (kJ/Day or kcal/Day) | Week 4 | 1229 kcal/d |
| CONTROL | Physical Activity Energy Expenditure (kJ/Day or kcal/Day) | Week 12 | 1142 kcal/d |
| LOW SUG | Physical Activity Energy Expenditure (kJ/Day or kcal/Day) | Week 4 | 1096 kcal/d |
| LOW SUG | Physical Activity Energy Expenditure (kJ/Day or kcal/Day) | Week 12 | 1077 kcal/d |
| LOW CHO | Physical Activity Energy Expenditure (kJ/Day or kcal/Day) | Week 4 | 1275 kcal/d |
| LOW CHO | Physical Activity Energy Expenditure (kJ/Day or kcal/Day) | Week 12 | 1136 kcal/d |
Secondary
Adipose Tissue Gene Expression
Expression of a panel of genes related to glucose metabolism in adipose biopsies using real-time polymerase chain reaction
Time frame: 12 weeks
Secondary
Adipose Tissue Protein Expression
Expression of various proteins related to glucose metabolism in adipose biopsies via Western blot
Time frame: 12 weeks
Secondary
Android Fat Mass
Android fat mass measured using dual x-ray absorptiometry
Time frame: 12 weeks
Secondary
Blood Pressure
Measured using an automated sphygmomanometer
Time frame: 12 weeks
Secondary
Body Mass
Measured weekly using electric scales
Time frame: 12 weeks
Secondary
Bone Mineral Content
Bone mineral content measured using dual x-ray absorptiometry
Time frame: 12 weeks
Secondary
Bone Mineral Density
Bone mineral density measured using dual x-ray absorptiometry
Time frame: 12 weeks
Secondary
Energy Expended in Different Physical Activity Intensities (MET Categories) (kJ or kcal)
Energy expended in different physical activity intensities (MET categories) (kJ or kcal)
Time frame: 7 days (across 12 weeks)
Secondary
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
Time frame: 12 weeks
Secondary
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)
Time frame: 12 weeks
Secondary
Fat-free Mass
Fat-free mass measured using dual x-ray absorptiometry
Time frame: 12 weeks
Secondary
Fat Mass
Fat mass measured using dual x-ray absorptiometry
Time frame: 12 weeks
Secondary
Food Preference Ratings
Food preference ratings determined by bespoke computer software
Time frame: 12 weeks
Secondary
Gut Microbiome Characterisation
Faecal sample DNA and water will be used to determine taxonomic and functional diversity of microbes using transcriptomic techniques
Time frame: 12 weeks
Secondary
Gynoid Fat Mass
Gynoid fat mass measured using dual x-ray absorptiometry
Time frame: 12 weeks
Secondary
Interstitial Glucose Concentrations
Measured using research-grade freestyle libre glucose monitors. Measured pre-, during- and at the end of the intervention
Time frame: 14 days (across 12 weeks)
Secondary
Muscle Glycogen Concentrations
Glycogen concentrations measured from vastus lateralis muscle samples
Time frame: 12 weeks
Secondary
Muscle Tissue Gene Expression
Expression of a panel of genes related to glucose metabolism in muscle biopsies using real-time polymerase chain reaction
Time frame: 12 weeks
Secondary
Muscle Tissue Protein Expression
Expression of various proteins related to glucose metabolism in muscle biopsies via Western blot
Time frame: 12 weeks
Secondary
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)
Time frame: 4 hours (across 12 weeks)
Secondary
Resting Metabolic Rate
Resting metabolic rate will be measured using indirect calorimetry
Time frame: 12 weeks
Secondary
Step Count
Measured daily using pedometers
Time frame: 12 weeks
Secondary
Subjective Appetite and Mood Ratings
Measured by 0-100 mm visual analogue scale
Time frame: 12 weeks
Secondary
Substrate Oxidation
Substrate oxidation will be measured using indirect calorimetry both at rest and during exercise
Time frame: 12 weeks
Secondary
Time Spent in Different Physical Activity Intensities (MET Categories) (Minutes)
Time spent in different physical activity intensities (MET categories) (minutes)
Time frame: 7 days (across 12 weeks)
Secondary
Urinary Acetoacetate Concentrations
Will be measured using handheld sticks
Time frame: 12 weeks
Secondary
Urine Urea Nitrogen Excretion
Will be measured across trial days
Time frame: 12 weeks
Secondary
Waist and Hip Circumference
Waist and hip circumference will be measured using a tape measure
Time frame: 12 weeks