Improving Resilience With Whole Grain Wheat

Study Overview
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Brief Summary
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This study investigates the health benefits of whole grain wheat on cardiovascular/ cardio-metabolic health, including glucose metabolism, by means of applying a mixed meal challenge. This study also investigates the health benefits of whole grain wheat (WGW) on liver- and adipose tissue health and evaluates the potential of do-it-yourself (DIY) devices in quantifying health effects in a nutritional intervention study.

Detailed Description
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The study is a randomized controlled, double blind, parallel trial. A 4-week run-in period with refined wheat (RW) products will be included prior to the intervention for all subjects. Thereafter, two different treatments will be evaluated e.g. a 12-week intervention with whole grain wheat (WGW) products (98g of WGW per day) and a 12-week control intervention with RW products. Two experimental visits will be planned before and two experimental visits will be planned after the 12-week intervention period. In the first experimental visit the investigators will determine liver fat and abdominal fat distribution by magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI). In the second experimental visit the investigators will comprehensively phenotype the participants which will include the response to a mixed meal challenge test.

Official Title
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Improving Resilience With Whole Grain Wheat

Conditions
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Healthy, Metabolism

Intervention / Treatment
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* Other: whole grain wheat
* Other: refined wheat


Participation Criteria
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Eligibility Criteria
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The inclusion of subjects with mildly impaired cardio-metabolic risk profiles enables detection of improvements in health after WGW consumption. The investigators therefore aim to include 50 middle aged and overweight males or postmenopausal females (45-70yrs and BMI between 25-35 kg/m2) that have mildly elevated levels of cholesterol (cholesterol levels > 5 mmol/L). In case the inclusion of subjects with mildly elevated levels of total cholesterol is too difficult, normal levels of total cholesterol (< 5 mmol/L) can be accepted, but with a minimum total cholesterol level of 4.5 mmol/L. Inclusion Criteria: Males or postmenopausal females (target 50: 50 for both genders) For females: menstrual cycle absent for more than 1 year Age 45-70yrs BMI between 25 and 35 kg/m2 Signed informed consent Normal food habit of bread and cereal consumption Exclusion Criteria: Not having a general practitioner Having a history of medical or surgical events that may significantly affect the study outcome Smoker Use of cholesterol lowering medication Mental status that is incompatible with the proper conduct of the study Aversion, intolerance to gluten, whole wheat or other items in the intervention products Alcohol consumption of > 21 glasses a week Abuse of drugs Recent use of antibiotics (<1 month prior to day 01 of the study) Reported weight loss or weight gain of > 5 kg in the month prior to pre-study screening Reported slimming or medically prescribed diet Reported vegan or macrobiotic life-style Not willing to give up blood donation during the study Personnel of Wageningen University, department of Human Nutrition, their partner and their first and second degree relatives Current participation in other research (with the exception of NQplus) Contraindication for MRI Having blood vessels that are too difficult for inserting a cannula

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: whole grain wheat<br>98g whole grain wheat per day for 12 weeks | Other: whole grain wheat<br>* A twelve week intervention of 98g whole grain wheat in the form of 4 slices of bread (is in total 100g bread) and 2 servings of ready to eat cereals (RTEC, is in total 33.4g RTEC).<br>|
| Experimental: refined wheat<br>coloured refined wheat control intervention | Other: refined wheat<br>* A twelve week control intervention of refined wheat in the form of 4 slices of bread (is in total 100g bread) and 2 servings of ready to eat cereals (RTEC, is in total 33.4g RTEC).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardio-metabolic health parameters (composite) | parameters include change in cholesterol, TAG, glucose, insulin, FMD (Fasting only), pulse wave analysis (Fasting and 120, 240min postprandial), blood pressure(Fasting and 120, 240min postprandial), blood cell activation (Fasting only) and plasma markers of cardio-vascular health | Baseline and after 12 week intervention (at 0 and 12 weeks) , during fasting and in response to a mixed meal challenge test (at 30,60,120,240 min postprandial) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in liver-and adipose tissue health parameters (composite) | parameters include change in intrahepatic lipid accumulation (by MRS, at -1 and 11 weeks), abdominal body fat distribution (by MRI, at -1 and 11 weeks), adipose tissue gene expression (adipose tissue biopsy, fasting only), blood markers of liver health | Baseline and after 12 week intervention (at 0 and 12 weeks), during fasting and in response to a mixed meal challenge test (at 30,60,120,240 min postprandial) | 
| Change in do-it-yourself measure outcomes (composite) | DIY tests are optional and include glucose, cholesterol, blood pressure and a OGTT (only week 8). These tests are performed by the subjects. | At baseline and every two weeks during the intervention (at 0,2,4,6,8,10,12 weeks) | 
| Change in health and mood questionaire outcomes | health and mood questionaires (some questionaires are every 4weeks) | At baseline and every two weeks during the intervention (at 0,2,4,6,8,10,12 weeks) | 
| Change in blood markers of whole grain intake | such as alkylresorinol | before and after 12 week intervention (at 0 and 12 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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resilience, challenge test, whole grain wheat, metabolic flexibility, cardio-metabolic, liver and adipose tissue