Intermittent Carbohydrate Restriction in Cardiometabolic Health

The Effects of Intermittent Carbohydrate Restriction on Metabolic Health and Energy Balance in Adults with Abdominal Overweight and Obesity

Metabolic conditions, such as heart disease, type 2 diabetes, and metabolic syndrome, are among the leading causes of disability and mortality worldwide. Identifying innovative lifestyle strategies to reduce metabolic risk remains a public health priority. Further research is essential to understand how low carbohydrate intake influences human metabolism and how intermittent carbohydrate restriction impacts weight loss and metabolic health markers.

This study will investigate two interventions that restrict dietary carbohydrate intake on different schedules, examining their effects on metabolic health and energy balance in adults with abdominal overweight or obesity. The physiological mechanisms potentially underlying these effects will be explored by measuring a range of lifestyle and metabolic health parameters in both free-living and laboratory settings. A digital behaviour-change intervention will be incorporated after the dietary intervention to assess whether any metabolic effects can be sustained over time.

The study employs a three-arm parallel-group design consisting of a two-week lifestyle monitoring phase, a four-week dietary intervention, and a four-week digital intervention, with four laboratory visits throughout each phase. During the dietary intervention, participants will be allocated to one of three groups: (i) carbohydrate restriction (<8% of energy intake) on two consecutive days per week, (ii) carbohydrate restriction after 4 pm each day, or (iii) no dietary changes.

Dietary intake, physical activity, and glucose levels will be monitored through wearable devices in free-living conditions. The digital intervention will use a mobile health application that provides individualised lifestyle recommendations and education based on data collected in free-living conditions. Laboratory-based measures will include anthropometry, body composition scans, indirect calorimetry, blood pressure monitoring, fat biopsies, and postprandial sampling of blood and expired air.

Study Overview

• Status: Recruiting
• Conditions: Obesity and Overweight
• Intervention / Treatment: Other: 5:2 carbohydrate restriction; Other: Early time-restricted carbohydrate intake

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guoda Karoblyte; Phone Number: +44 (0) 1225 386478; Email: gk678@bath.ac.uk

Study Locations

• United Kingdom
  • Somerset
    • Bath, Somerset, United Kingdom, BA2 7AY
      • Recruiting
      • University of Bath
      • Contact: Guoda Karoblyte; Phone Number: +44 (0) 1225 386478; Email: gk678@bath.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Waist circumference of ≥94 cm (37 inches) if male and ≥80 cm (31.5 inches) if female, or BMI above 25 kg/m2
2. Fat mass index (FMI) of >6 kg/m2 for males, and >9 kg/m2 for females
3. Aged between 18-65 years
4. Has maintained a stable weight in the last three months (<3% change in body mass)
5. Keeps track of menstrual cycle regularity or oral contraceptive use (females only)

Exclusion Criteria:

1. Has a body weight of ≥120kg
2. Plans to undertake other lifestyle modifications during the study to manage weight (e.g. changes in dietary intake or activity levels)
3. Current or previous eating disorder
4. Diagnosed with major chronic conditions (e.g. type 2 diabetes, coronary heart disease, cancer, chronic kidney disease, etc.)
5. Use of medication that may interfere with study outcomes (e.g. glucose or lipid lowering medications)
6. Currently or recently pregnant (within last 6 months), planning to get pregnant or currently lactating
7. Has donated more than 500ml of blood in the last 3 months prior to the initial laboratory visit
8. Insufficient mental capacity or language skills to independently understand and follow the study protocol
9. Dietary restrictions to ingredients in test meals (e.g. gluten and lactose)
10. Has an irregular sleeping pattern (e.g. due to undertaking night-shift work)
11. Any condition, concurrent intervention or behaviour deemed either to pose undue personal risk to the participant or to introduce bias into the experiment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5:2 carbohydrate restriction (5:2CR); Laboratory measurements will be obtained before and after the intervention. Physical activity, dietary intake and interstitial glucose concentrations will be monitored in free-living conditions throughout the intervention.	Other: 5:2 carbohydrate restriction; Carbohydrate ingestion restricted to <8% of energy intake on 2 self-selected consecutive days each week over 28-30 days. Ad libitum dietary amount, type and pattern followed on the remaining 5 days each week.
Experimental: Early time-restricted carbohydrate intake (eTRC); Laboratory measurements will be obtained before and after the intervention. Physical activity, dietary intake and interstitial glucose concentrations will be monitored in free-living conditions throughout the intervention.	Other: Early time-restricted carbohydrate intake; Carbohydrate intake restricted to <8% of energy intake after 4pm each day for 28 days. Ad libitum dietary amount, type and pattern followed before 4pm.
No Intervention: Lifestyle maintenance (control); Laboratory measurements will be obtained before and after the intervention. Physical activity, dietary intake and interstitial glucose concentrations will be monitored in free-living conditions throughout the intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post Prandial Triglyceride Area Under the Curve (AUC)	Plasma triglyceride concentrations assessed postprandially for 5 hours after a mixed meal test	Pre and post intervention (4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fat Mass	Measured in kilogrammes using Dual Energy X-ray Absorptiometry	Pre and post intervention (4 weeks)
Lean Body Mass	Measured in kilogrammes using Dual Energy X-ray Absorptiometry	Pre and post intervention (4 weeks)
Fasting and Post Prandial Glucose Concentration	Plasma glucose concentrations assessed after an overnight fast, postprandially for 5 hours after a mixed meal test	Pre and post intervention (4 weeks)
Fasting and Post Prandial Insulin Concentration	Plasma insulin concentrations assessed after an overnight fast, postprandially for 5 hours after a mixed meal test	Pre and post intervention (4 weeks)
Fasting and Post Prandial NEFA Concentration	Plasma NEFA concentrations assessed after an overnight fast, postprandially for 5 hours after a mixed meal test	Pre and post intervention (4 weeks)
Fasting Triglyceride Concentration	Plasma triglyceride concentrations assessed after an overnight fast	Pre and post intervention (4 weeks)
Fasting Total Cholesterol Concentration	Assessed after an overnight fast	Pre and post intervention (4 weeks)
Fasting LDL-C Concentration	Assessed after an overnight fast	Pre and post intervention (4 weeks)
Fasting HDL-C Concentration	Assessed after an overnight fast	Pre and post intervention (4 weeks)
Substrate Oxidation	Carbohydrate and fat oxidation rates will be measured using indirect calorimetry at rest and every hour postprandially	Pre and post intervention (4 weeks)
Adipose Tissue Gene Expression	Expression of several genes related to energy metabolism in adipose biopsies using real-time polymerase chain reaction (RT-PCR)	Pre and post intervention (4 weeks)
Adipose Tissue Protein Expression	Expression of several proteins related to energy metabolism in adipose biopsies using Western blot	Pre and post intervention (4 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Activity Energy Expenditure (kJ or kcal)	Assessed using combined heart rate and accelerometery wearable monitor (Actiheart™) in free-living conditions.	1 week during baseline monitoring, and weeks 1 and 4 of the intervention
Time Spent in Different Physical Activity Intensities (minutes)	Assessed using combined heart rate and accelerometery wearable monitor (Actiheart™) in free-living conditions	1 week during baseline monitoring, and weeks 1 and 4 of the intervention
Dietary Intake	Dietary records manually kept by study participants	1 week during baseline monitoring, and weeks 1 and 4 of intervention
Interstitial Glucose	Continuous glucose records will be used to capture interstitial glucose before and during the intervention	2 weeks during baseline monitoring, 2 weeks during weeks 3-4 of intervention
Sleep Quality	Self-reported sleep quality will be assessed via the Pittsburgh Sleep Quality Index (PSQI) questionnaire, consisting of 9 questions. Seven component scores are derived, scored from 0 (no difficulty) to 3 (severe difficulty)	Pre and post intervention (10 weeks)
Diet Satisfaction	Diet satisfaction will be assessed via the 28-item Diet Satisfaction Questionnaire (28-DSQ), scored on a five-point Likert scale with 1 being 'Disagree Strongly' and 5 being 'Agree Strongly'	Pre and post intervention (10 weeks)
Engagement with Mobile Application	Data on number of sessions, session length, session interval and session frequency will be obtained through the Salus Metabolism mobile health application	4 weeks post intervention
Usability of Mobile Application	Assessed via the mHealth App Usability Questionnaire, consisting of 16 statements scored on a seven-point Likert scale with 1 being 'Disagree' and 7 being 'Agree'	4 weeks post intervention
Subjective App Usability and Engagement	Participants will be asked to provide feedback on the Salus Metabolism mHealth application through a semi-structured interview. Thematic analysis will be used to analyse interview data.	4 weeks post intervention

Collaborators and Investigators

• Sponsor: University of Bath

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2036

Study Registration Dates

• First Submitted: October 24, 2024
• First Submitted That Met QC Criteria: November 9, 2024
• First Posted (Estimated): November 12, 2024

Study Record Updates

• Last Update Posted (Estimated): November 12, 2024
• Last Update Submitted That Met QC Criteria: November 9, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: carbohydrate restriction; intermittent energy restriction; carbohydrate periodisation; carbohydrate timing; intermittent carbohydrate restriction; evening carbohydrate restriction
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Obesity
• Other Study ID Numbers: 323721

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
• product manufactured in and exported from the U.S.: No