Dietary Carbohydrate and Internal Body Fat (CARBFUNC)

Dietary Carbohydrate and Internal Body Fat Mass in Women and Men With Obesity

This is a 2-year randomized controlled trial to test the effect of dietary carbohydrates, both quality and quantity, on changes in internal body fat mass. Up to 250 women and men with obesity are recruited in Bergen, Norway, and randomized to one of the following normo- and isocaloric dietary patterns (same amount of protein, polyunsaturated fatty acids and moderate energy, 2,000 - 2,500 kcal per day): 1) a low-fat high-carbohydrate diet primarily with refined (e.g., flour-based) carbohydrate sources, 2) a low-fat high-carbohydrate diet based on minimally refined (e.g., cellular) carbohydrate sources, and 3) a very-high-fat low-carbohydrate diet.

Study Overview

• Status: Completed
• Conditions: Adiposity
• Intervention / Treatment: Behavioral: Acellular carbohydrate diet; Behavioral: Cellular carbohydrate diet; Behavioral: Low-carbohydrate high-fat diet

Detailed Description

Obesity, and high internal fat storage in particular, represents a tremendous and increasing health challenge across the world, and is linked to the recent introduction and globalization of an ultra-processed food supply largely based on refined carbohydrates. However, more high-quality studies are needed to directly assess the role of carbohydrate quality in abdominal adiposity. We also need studies with greater long-term adherence to prescribed food profiles, which may be achievied with the help of new electronic tools such as meal planning applications.

The participants select and plan all meals among a list of carefully designed options, using an application/recipe booklet developed for the study. Each recipe/meal/snack is designed to fully comply with the overall macronutrient- and dietary profile for the respective groups. We will further instruct the participants to record their meal choices during three days every 14 days, and to record all deviations throughout the intervention.

Enrolled participants are invited to study visits at baseline and after 3, 6, 9, 12 and 24 months. At all or some of these time points, the participants provide biological samples (blood, urine and feces, and for some, adipose and/or muscle tissue) and undergo phenotyping, e.g., measurement of body weight and fat mass by bioelectrical impedance analysis and low-radiation CT imaging, and a standardized meal test with blood sample collection up to 4 hours postprandially. In addition, participants will be asked to fill out a collection of questionnaires that assess quality of life, motivation, fatigue, gastrointestinal health, appetite and physical activity. We ask the participants to maintain the same level of physical activity throughout the study.

The primary outcome measure is change in internal body fat mass (visceral adipose tissue) measured by CT imaging. Secondary outcome measures include change in 2-hour postprandial serum concentrations of insulin, change in 4-hour postprandial serum concentrations of triacylglycerols, and change in fecal microbiota composition measured by 16S sequencing.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway, 5021
    • Forskningsenhet for helseundersøkelser (research unit for clinical trials), Department of Clinical Science, University of Bergen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body-mass index (BMI) equal to or above 30 kg/m2 and/or waist circumference equal to or above 102 cm for men and 88 cm for women
• Weight stable during the last 2 months before start of the study (less than 5 % change in body weight up or down)
• No known diabetes or consumption of diabetes medication
• Desire to follow a specified dietary pattern using specific recipes throughout the time of the study period
• Ability to periodically record food intake using a specially designed app for the study

Exclusion Criteria:

• Use of statins and/or diabetes medication
• Recent surgical or antibiotics treatment during the last 2 months before start of the study
• Chronic inflammatory bowel disease
• Serious disease
• Smoking
• Pregnancy or breast feeding
• Alcohol consumption during the study of more than 2 alcohol units per day (1 unit = 15 ml (12.8 g) pure alcohol)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Acellular carbohydrate diet; Prescribed dietary pattern. Carbohydrates from acellular sources, e.g., refined flour/bakery products, at least 500 grams of fruits/vegetables per day, and a macronutrient composition within typical nutritional recommendations for the general population.	Behavioral: Acellular carbohydrate diet; Participants will be asked to consume 2,000 - 2,500 kcals, thereof 45 energy percent (E%) carbohydrate (up to 5 E% added sugar), 30 E% fat (10-12 E% saturated fatty acids and 7-10 E% polyunsaturated fatty acids) and 17 E% protein. They will use an original online/smartphone application that provides choices of meals/food combinations/recipes corresponding to their prescribed macronutrient profile and dietary pattern. Participants are asked to complete 3-day dietary records every 14 days throughout the study, and to report any deviations from the planned interventions.
EXPERIMENTAL: Cellular carbohydrate diet; Prescribed dietary pattern. Carbohydrates from cellular sources, e.g., root vegetables, fruits, whole-grain rice, non-flour grain products, at least 500 grams of fruits/vegetables per day, and a macronutrient composition within typical nutritional recommendations for the general population similar to the acellular carbohydrate diet.	Behavioral: Cellular carbohydrate diet; Participants will be asked to consume 2,000 - 2,500 kcals, thereof 45 energy percent (E%) carbohydrate (up to 1 E% added sugar), 38 E% fat (10-12 E% saturated fatty acids and 7-10 E% polyunsaturated fatty acids) and 17 E% protein. They will use an original online/smartphone application that provides choices of meals/food combinations/recipes corresponding to their prescribed macronutrient profile and dietary pattern. Participants are asked to complete 3-day dietary records every 14 days throughout the study, and to report any deviations from the planned interventions.
EXPERIMENTAL: Low-carbohydrate high-fat diet; Prescribed dietary pattern. Energy largely from fat, cellular carbohydrate sources, and otherwise similar food types as in the acellular/cellular carbohydrate diets including at least 500 grams of fruits/vegetables per day.	Behavioral: Low-carbohydrate high-fat diet; Participants will be asked to consume 2,000 - 2,500 kcals, thereof 10 energy percent (E%) carbohydrate (up to 1 E% added sugar), 73 E% fat (30 E% saturated fatty acids and 7-10 E% polyunsaturated fatty acids) and 17 E% protein. They will use an original online/smartphone application that provides choices of meals/food combinations/recipes corresponding to their prescribed macronutrient profile and dietary pattern. Participants are asked to complete 3-day dietary records every 14 days throughout the study, and to report any deviations from the planned interventions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in internal body fat	Visceral fat mass (cm3) measured by computed tomography (CT) imaging	Baseline and 6, 12 and 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in postprandial insulin	Circulating insulin concentrations measured before and 2 hours after intake of a standardized mixed meal	Baseline and 3, 6, 9, 12 and 24 months
Change in postprandial C-peptide	Circulating C-peptide concentrations measured before and 2 hours after intake of a standardized mixed meal	Baseline and 3, 6, 9, 12 and 24 months
Change in postprandial triacylglycerol	Triacylglycerol concentrations measured before and 4 hours after intake of a mixed meal	Baseline and 3, 6, 9, 12 and 24 months
Change in postprandial area under the curve (AUC) glucose	Circulating glucose measured before and after 30, 60, 90, 120 and 240 minutes after intake of a standardized mixed meal	Baseline and 3, 6, 9, 12 and 24 months
Change in postprandial non-esterified fatty acids	Circulating non-esterified fatty acid concentrations before and after 60, 120 and 240 minutes after intake of a standardized mixed meal	Baseline and 3, 6, 9, 12 and 24 months
Change in fecal microbiome composition	Microbiome composition measured by 16S sequencing	Baseline and 3, 6, 9, 12 and 24 months
Change in liver density	Calculated as liver/spleen attenuation index (Hounsfield units) based on quantification by computed tomography (CT) imaging	Baseline and 6, 12 and 24 months
Change in pericardial fat mass	Pericardial fat mass (cm3) measured by computed tomography (CT) imaging	Baseline and 6, 12 and 24 months
Change in abdominal subcutaneous fat mass	Abdominal subcutaneous fat mass (cm3) measured by computed tomography (CT) imaging	Baseline and 6, 12 and 24 months
Change in coronary artery calcification (CAC)	CAC score calculated based on computed tomography (CT) imaging	Baseline and 6, 12 and 24 months
Change in waist circumference	Waist circumference (cm) measured by a measuring tape	Baseline and 3, 6, 9, 12 and 24 months
Change in body-mass index	Body-mass index measured as body weight (kg) divided by height (m) squared	Baseline and 3, 6, 9, 12 and 24 months
Change in fasting insulin	Circulating fasting insulin concentrations	Baseline and 3, 6, 9, 12 and 24 months
Change in fasting C-peptide	Circulating fasting C-peptide concentrations	Baseline and 3, 6, 9, 12 and 24 months
Change in fasting TAG	Circulating fasting triacylglycerol concentrations	Baseline and 3, 6, 9, 12 and 24 months
Change in fasting HDL cholesterol	Circulating fasting high-density lipoprotein cholesterol (HDL-C)	Baseline and 3, 6, 9, 12 and 24 months
Change in TAG/HDL-C ratio	The ratio of circulating fasting triacylglycerol (TAG) and high-density lipoprotein cholesterol (HDL-C)	Baseline and 3, 6, 9, 12 and 24 months
Change in fasting LDL cholesterol	Circulating fasting low-density lipoprotein cholesterol (LDL-C)	Baseline and 3, 6, 9, 12 and 24 months
Change in apolipoprotein profile	Circulating fasting apolipoprotein profile measured by multiplex ELISA	Baseline and 3, 6, 9, 12 and 24 months
Change in circulating and urine metabolites associated with one-carbon metabolism	Circulating metabolites in the serine, glycine and histidine pathways measured in the fasted state by GC-MS/MS	Baseline and 3, 6, 9, 12 and 24 months
Change in total fat mass	Total fat mass measured by bioimpedance analysis (BIA)	Baseline and 3, 6, 9, 12 and 24 months
Change in lean mass	Lean mass will be measured by bioimpedance analysis (BIA)	Baseline and 3, 6, 9, 12 and 24 months
Change in appetite/fullness	Subjective appetite and fullness assessed and quantified by the VAS questionnaire	Baseline and 3, 6, 9, 12 and 24 months
Change in gastrointestinal symptoms by the Roma III questionnaire	Gastrointestinal health will be surveyed and quantified by a questionnaire (Rome III Diagnostic Criteria for Irritable Bowel Syndrome (IBS)). The questionnaire surveys criteria for diagnosis of IBS within a 12-week period. The criteria for IBS are based on recurrent abdominal pain or discomfort, 3 days per month in the last 3 months (12 weeks), associated with ≥2 of the following criteria: 1.Improvement with defecation; 2. Onset associated with a change in stool frequency; 3. Onset associated with a change in stool form (appearance). The criteria are fulfilled with symptoms onset 6 months prior to diagnosis.	Baseline and 3, 6, 9, 12 and 24 months
Change in gastrointestinal symptoms by the IBS-SSS questionnaire	Gastrointestinal health will be surveyed by the IBS-SSS questionnaire. Scores on the IBS-SSS range from 0 to 500 with higher scores indicating more severe symptoms. Subjects can be categorized as having mild (75-175), moderate (175-300), or severe (>300) IBS. A decrease of 50 points is associated with a clinically meaningful improvement. Each question on the VAS ranges from 0-100mm, where higher score indicates more severe symptoms. The categorization based on scores (total possible score = 500) are as follows: 0-75 = not IBS 75-175= mild IBS 175-300 = moderate IBS 300-500 = severe IBS	Baseline and 3, 6, 9, 12 and 24 months
Change in fatigue	The Fatigue Impact Scale will be used to compute a total score for fatigue by summing up the scores for subclasses as follows: cognitive functioning (10 items, subscale range: 0-40), physical functioning (10 items, subscale range: 0-40), and psychosocial functioning (20 items, subscale range: 0-80). The statements are ranged on a five-level scale (0 = no problem to 4 = extreme problems), giving a maximum total FIS score of 160 (total scale range: 0-160) where low scores indicate less fatigue-related issues.	Baseline and 3, 6, 9, 12 and 24 months
Change in perception of health / quality of life	Obesity-specific quality of life is measured with "Patient-Reported Outcomes in Obesity" (PROS), which consists of 8 items tapping how different life domains are affected by obesity. PROS have one overall score, ranging from 0 (optimal) to 3 (poorest). Generic health-related quality of life is measured with RAND-36, which consists of dimensions ranging from 0 (poorest) to 100 (optimal). There are 8 subscales; physical functioning, physical role functioning, bodily pain, general health, vitality, social functioning, emotional role functioning and mental health. In addition, RAND-36 also have 2 summary scores: the physical component summary (PCS) (tapping from physical functioning, physical role functioning, bodily pain and general health) and mental component summary (MCS) (tapping from vitality, social functioning, emotional role functioning and mental health).	Baseline and 3, 6, 9, 12 and 24 months
Change in quality of life related to gastrointestinal symptoms	The SF-NDI (Short-Form Nepean Dyspepsia Index (SF-NDI)) questionnaire will be used to assess quality of life / psychological wellbeing related to gastrointestinal symptoms. The 10-item SF-NDI was constructed and validated in patients with functional gastrointestinal disorders for measuring health-related quality of life. The 10-item short form includes five subscales: tension, interference with daily activities, eating/drinking, knowledge/control, and work/study, and each subscale contains two items. The items were measured by a 5-point graded Likert scale from 1 to 5. A total sum score for quality of life and a sum score for each of the five subscales were calculated by adding up scores for each item (range of total quality of life, 10-50; range of each subscale, 2-10). Higher scores indicate worse functioning or symptoms.	Baseline and 3, 6, 9, 12 and 24 months

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Collaborators: University of Bergen
• Investigators: Principal Investigator: Simon N Dankel, PhD, University of Bergen; Study Director: Gunnar Mellgren, MD PhD, Haukeland University Hospital

Publications and helpful links

General Publications

• Sommersten CH, Laupsa-Borge J, Andersen AIO, Fasmer KE, Holmefjord MA, Revheim I, Johannessen KK, Naesheim NT, Storas I, Leikanger T, Amundsen K, Skjerve KL, Lawrence-Archer L, Spjelkavik C, Haldorsen I, Lindseth I, Dierkes J, Mellgren G, Dankel SN. Diets differing in carbohydrate cellularity and amount similarly reduced visceral fat in people with obesity - a randomized controlled trial (CARBFUNC). Clin Nutr. 2022 Oct;41(10):2345-2355. doi: 10.1016/j.clnu.2022.08.028. Epub 2022 Sep 5.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 3, 2018
• Primary Completion (ACTUAL): May 20, 2020
• Study Completion (ACTUAL): March 24, 2021

Study Registration Dates

• First Submitted: August 23, 2017
• First Submitted That Met QC Criteria: January 9, 2018
• First Posted (ACTUAL): January 17, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 26, 2021
• Last Update Submitted That Met QC Criteria: April 23, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Body composition; Dietary pattern; Internal body fat; Dietary carbohydrate
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: 2017/621

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