An interventional study of Acellular carbohydrate diet and Cellular carbohydrate diet in Adiposity, sponsored by Haukeland University Hospital. Completed at 1 site in Norway. Open to participants aged 20 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-04-26.
Sponsored by Haukeland University Hospital · Not applicable, Interventional, and Treatment
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.
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.
Exclusion Criteria:
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
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
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 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.
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.
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.
Change in internal body fat
Visceral fat mass (cm3) measured by computed tomography (CT) imaging
Time frame: Baseline and 6, 12 and 24 months
Change in postprandial insulin
Circulating insulin concentrations measured before and 2 hours after intake of a standardized mixed meal
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline and 3, 6, 9, 12 and 24 months
Change in fecal microbiome composition
Microbiome composition measured by 16S sequencing
Time frame: 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
Time frame: Baseline and 6, 12 and 24 months
Change in pericardial fat mass
Pericardial fat mass (cm3) measured by computed tomography (CT) imaging
Time frame: Baseline and 6, 12 and 24 months
Change in abdominal subcutaneous fat mass
Abdominal subcutaneous fat mass (cm3) measured by computed tomography (CT) imaging
Time frame: Baseline and 6, 12 and 24 months
Change in coronary artery calcification (CAC)
CAC score calculated based on computed tomography (CT) imaging
Time frame: Baseline and 6, 12 and 24 months
Change in waist circumference
Waist circumference (cm) measured by a measuring tape
Time frame: 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
Time frame: Baseline and 3, 6, 9, 12 and 24 months
Change in fasting insulin
Circulating fasting insulin concentrations
Time frame: Baseline and 3, 6, 9, 12 and 24 months
Change in fasting C-peptide
Circulating fasting C-peptide concentrations
Time frame: Baseline and 3, 6, 9, 12 and 24 months
Change in fasting TAG
Circulating fasting triacylglycerol concentrations
Time frame: Baseline and 3, 6, 9, 12 and 24 months
Change in fasting HDL cholesterol
Circulating fasting high-density lipoprotein cholesterol (HDL-C)
Time frame: 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)
Time frame: Baseline and 3, 6, 9, 12 and 24 months
Change in fasting LDL cholesterol
Circulating fasting low-density lipoprotein cholesterol (LDL-C)
Time frame: Baseline and 3, 6, 9, 12 and 24 months
Change in apolipoprotein profile
Circulating fasting apolipoprotein profile measured by multiplex ELISA
Time frame: 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
Time frame: Baseline and 3, 6, 9, 12 and 24 months
Change in total fat mass
Total fat mass measured by bioimpedance analysis (BIA)
Time frame: Baseline and 3, 6, 9, 12 and 24 months
Change in lean mass
Lean mass will be measured by bioimpedance analysis (BIA)
Time frame: Baseline and 3, 6, 9, 12 and 24 months
Change in appetite/fullness
Subjective appetite and fullness assessed and quantified by the VAS questionnaire
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: Baseline and 3, 6, 9, 12 and 24 months
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Haukeland University Hospital