Dietary Carbohydrate Manipulation and Energy Balance: RCT

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

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.

Study Overview

• Status: Completed
• Conditions: Physical Activity; Diet Modification
• Intervention / Treatment: Other: Diet

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

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Bath, United Kingdom, BA2 7AY
    • Department for Health, University of Bath

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Bath

Publications and helpful links

General Publications

• Bergwall S, Johansson A, Sonestedt E, Acosta S. High versus low-added sugar consumption for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2022 Jan 5;1(1):CD013320. doi: 10.1002/14651858.CD013320.pub2.
• Smith HA, Gonzalez JT, Thompson D, Betts JA. Dietary carbohydrates, components of energy balance, and associated health outcomes. Nutr Rev. 2017 Oct 1;75(10):783-797. doi: 10.1093/nutrit/nux045.
• Betts JA, Richardson JD, Chowdhury EA, Holman GD, Tsintzas K, Thompson D. The causal role of breakfast in energy balance and health: a randomized controlled trial in lean adults. Am J Clin Nutr. 2014 Aug;100(2):539-47. doi: 10.3945/ajcn.114.083402. Epub 2014 Jun 4.
• Erickson J, Sadeghirad B, Lytvyn L, Slavin J, Johnston BC. The Scientific Basis of Guideline Recommendations on Sugar Intake: A Systematic Review. Ann Intern Med. 2017 Feb 21;166(4):257-267. doi: 10.7326/M16-2020. Epub 2016 Dec 20.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2018
• Primary Completion (ACTUAL): February 11, 2022
• Study Completion (ACTUAL): March 30, 2022

Study Registration Dates

• First Submitted: June 20, 2018
• First Submitted That Met QC Criteria: June 20, 2018
• First Posted (ACTUAL): July 2, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 7, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Physical Activity; Nutrition; Carbohydrates; Sugar; Energy Balance
• Other Study ID Numbers: CHEB-Intervention

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No