Determining the Potential of Wholegrain Wheat and Rye to Improve Gut HealTh

Study Overview
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Brief Summary
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A dietary intervention study designed as a randomized, controlled, parallel intervention of 6-weeks duration. A total of 75 participants will be included in the study and randomly allocated to one of three interventions (refined wheat, whoelgrain wheat or wholegrain rye). Clinincal examinations including anthropometric assessment, fecal, urine and fastign blood sampling, dietary assessment and a meal challenge will be done before (week 0) and after (week 6) the intervention. At timepoints week 0, 2, 4 and 6 questionnaires will be filled in concerning satisfaction with diet and gastrointestinal symptoms.

Detailed Description
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A dietary intervention study designed as a randomized, controlled, parallel intervention of 6-weeks duration. A total of 75 participants will be included in the study and randomly allocated to one of three interventions (refined wheat, whoelgrain wheat or wholegrain rye). The randomization will be stratified according to sex and sex-specific median habitual cereal dietary fibre intake (16g/d for men and 13g/d for women). The randomization will be done by means of a randomization generator of the webpage (http://www.randomization.com). Recruitment and randomization will take place continuously during the study period, and therefore randomization will be done as mixed block randomization. During the intervention study, participants are instructed to substitute all cereal products (e.g. bread, breakfast cereals, pasta) of their diet with the provided study products. The amount of provided study products will match the average intake of carbohydrate-rich products of the Danish population, which corresponds to  200g of bread and cereal products per day. The participants will eat the study products in an ad libitum manner and b instructed to avoid other cereals in their diet including cake, biscuits, ready made meals and fast foods with the exception of White rice whis is allowed 1-2 times per week. Clinincal examinations including anthropometric assessment, fecal, urine and fastign blood sampling, dietary assessment and a meal challenge will be done before (week 0) and after (week 6) the intervention. At timepoints week 0, 2, 4 and 6 questionnaires will be filled in concerning satisfaction with diet and gastrointestinal symptoms.

Official Title
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Determining the Potential of Wholegrain Wheat and Rye to Improve Gut HealTh

Conditions
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Obesity, Gastrointestinal Diseases, Cardiovascular Diseases

Intervention / Treatment
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* Other: Wholegrain rye
* Other: Wholegrain wheat
* Other: Refined wheat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Age: 30 - 65 years Body mass index (BMI): 25 - 32 kg/m2 Weight stable (<3 kg weight change during the last 6 months) Apparently healthy Informed consent signed Freezer capacity for 2 weeks bread provision Can attend all visits required for the study Exclusion Criteria: • Smoking on a daily basis Lactating (or lactating within 6 weeks prior to study start), pregnant (or pregnant within 3 months prior to study start) or wish to become pregnant during the study Diagnosed with any form of diabetes or CVD Reported chronic GI disorders Antibiotic treatment 3 month before study start and during the study Use of pre- or probiotic 1 month before study start and during the study Lack of cooperation and adherence to the protocol Use of prescription medication will be evaluated on an individual basis

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Refined wheat<br>Refined wheat grain, a variety of cereal foods providing no wholegrain | Other: Refined wheat<br>* A variety of cereal foods providing 0g/day wholegrain<br>|
| Experimental: Wholegrain wheat<br>Wholegrain wheat grain, a variety of cereal foods providing >100g wheat wholegrain/day | Other: Wholegrain wheat<br>* A variety of cereal foods providing >100g/day wholegrain from wheat<br>|
| Experimental: Wholegrain rye<br>Wholegrain rye grain, a variety of cereal foods providing >100g rye wholegrain/day | Other: Wholegrain rye<br>* A variety of cereal foods providing >100g/day wholegrain from rye<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal symptoms evaluated by questionnaires (100mm visual analogue scales) | Subjective sensations of gastrointestinal symptoms evaluated by questionnaires (100mm visual analogue scales) | Change from 0 to 6 weeks | 
| Gut microbiota composition assessed using 16S in a single fecal sample | Gut microbiota compostion assessed using 16S in a single fecal sample | Change from 0 to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anthropometric masures | Body weight and waist circumference, saggital abdominal diameter and body composition (fat mass and fat free mass assessed using DEXA) | Change from 0 to 6 weeks | 
| Blood pressure | Diastolic and systolic blood pressure and heart rate assessed twice using an automated apparatus | Change from 0 to 6 weeks | 
| Blood lipids, fasting concentrations of total, LDL and HDL cholesterol and triglyerides | Fasting concentrations of total, LDL and HDL cholesterol and triglyerides | Change from 0 to 6 weeks | 
| Glucose metabolism, fasting concentrations of glucose, insulin and HbA1C as calculation of HOMA-IR | Fasting concentrations of glucose, insulin and HbA1C as calculation of HOMA-IR | Change from 0 to 6 weeks | 
| Low-grade inflammation, fasting concentrations of hsCRP, IL-6, IL-10, and TNF-a | Fasting concentrations of hsCRP, IL-6, IL-10, and TNF-a | Change from 0 to 6 weeks | 
| Appetite sensation | Fasting and postprandial (every 30 minutes for 240 minutes) sensation of hunger, satiety, fullness, prospective food intake, thirst and well being | Change from 0 to 6 weeks | 
| Breath hydrogen assessed using a Hydrolyzer | Fasting and postprandial (every 30 minutes for 240 minutes) concentrations of H2 in exhaled breath assessed using a Hydrolyzer | Change from 0 to 6 weeks | 
| Short chain fatty acids, fecal concentrations of short chain fatty acids | Fecal concentrations of short chain fatty acids | Change from 0 to 6 weeks | 
| Fecal pH | Fecal pH assessed in homogenized fecal sample | Change from 0 to 6 weeks | 
| Intestinal permeability, assessed by urinary excretion of lactulose and mannitol | Intestinal permeability is assessed by urinary excretion of lactulose and mannitol for 4 hours and 24 hours following an oral load of 10g lactulose and 2 g mannitol | Change from 0 to 6 weeks | 
| Zonulin, fasting concentrations in plasma | Fasting concentrations of zonulin in plasma | Change from 0 to 6 weeks | 
| Dietary intake, a weighted 4-day food record | a weighted 4-day food record will be used to assess energy intake and macronutrient (protein, fat, carbohydrates and dietaru fiber) composition | Change from 0 to 6 weeks | 
| Compliance, measured by fasting plasma alkylresorcinol concentrations will be used as a biomarker of wholegrain wheat and rye intake | Fasting plasma alkylresorcinol concentrations will be used as a biomarker of wholegrain wheat and rye intake | Change from 0 to 6 weeks |