Condition category
Circulatory System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
There is a lot of epidemiological evidence to suggest that eating more wholegrain foods, for example millet, brown rice and oatmeal, reduces the risk of developing several diseases including cardiovascular disease (e.g. heart disease), type 2 diabetes and some cancers. This had led to a dietary recommendation of eating 48g of whole grains being suggested in the United States and 75g per day being recommended in Denmark. In other European countries, there is no specific dietary recommendation, but it is recognized that whole grains should be an important part of a healthy diet. Although the epidemiological evidence is strong, results from studies that compare different diets (intervention studies) have been more varied. Some studies have shown a whole grain diet as beneficial, others have not. This means that, at the moment, no definite conclusions regarding the protective role of whole grains against disease can be made. In particular, the amount of whole grains that should be eaten in order to get any health benefits is not proven, with estimates ranging from as little as one to more than three servings per day. We have already carried out two large intervention studies looking at including whole grains in the diet. One study, the WHOLEheart study, showed no beneficial effects of eating whole grains, but the amount of whole grain being eaten was not well controlled and the participants ate mixtures of grains (wheat, rice and rye). In our second study, the GrainMark study, the amount of whole grain being eaten was much better controlled and the participants ate only wholegrain wheat or wholegrain rye foods. This time, there was significant improvements in cholesterol levels and blood pressure, but, as the study did not include a control group (a group of participants that did not eat a whole grain diet) we cannot say for sure that these improvements were due to the whole grains. Here, we are doing a third whole grain intervention study, building on our previous experiences, using a “gold standard” experimental design developed to reduce the variability of the whole grains being eaten, to ensure a substantial increase in the amount of whole grains being eaten compared to the average in the UK and to improve statistical robustness.

Who can participate?
Generally healthy nonsmoking men and women aged between 40-70, with a BMI between 25 and 35 kg/m2, slightly increased blood pressure and slightly increased cholesterol levels.

What does the study involve?
Participants are asked not to eat any wholegrain foods for the four weeks leading up to the start of the study. After this “washout period” they are randomly allocated into one of two groups. Those in group 1 are given a wholegrain bread and breakfast cereal to eat in place of that they normally eat and asked to eat 4 servings per day if a woman and 6 servings a day if a man for 4 weeks. One serving is equal to one slice of bread or half a bowl of cereal. Those participants in group 2 are given similar instructions but are given bread and breakfast cereal made from refined wheat. After the 4 weeks, all participants are asked to not eat wholegrain foods for a further 4 weeks before swapping diets. This means that those in group 1 now eat the refined bread and cereal and group 2 the wholegrain foods for the last 4 weeks of the study. Urine and blood samples from each participant are taken at 4-weekly intervals throughout the trial. On the evening before samples are collected, each participant is asked to eat a supplied standard meal and then fast from 9pm. Height, weight, waist, hip, body fat and blood pressure measurements are also taken throughout the trial and the participant asked to fill in questionnaires.

What are the possible benefits and risks of participating?
If any abnormalities of significance are discovered while measuring their cholesterol, blood pressure or blood glucose levels, we will tell the participant and their GP so that appropriate steps can be made. Taking blood samples can cause minor discomfort and bruising. If a new diagnosis of high blood pressure is made, however, this could affect a person’s future life or private medical insurance.

Where is the study run from?
The Clinical Research Facility, Royal Victoria Infirmary (Newcastle)

When is the study starting and how long is it expected to run for?
June 2014 to June 2015

Who is funding the study?
Cereal Partners Worldwide (Switzerland)

Who is the main contact?
Professor Chris Seal

Trial website

Contact information



Primary contact

Prof Chris Seal


Contact details

Nu Food
Agriculture Building
Newcastle University
Newcastle Upon Tyne
United Kingdom
+44 (0) 191 2087650

Additional identifiers

EudraCT number number

Protocol/serial number

013.WG wheat and heart health.UK.2013

Study information

Scientific title

Wholegrain wheat and cardiovascular health


Study hypothesis

The proposed research is a dietary intervention study to investigate the health benefits of increased consumption of wholegrain wheat. There is strong evidence from observational (epidemiological) studies to suggest that consumption of wholegrain foods is beneficial in reducing the risk of heart disease, although evidence from intervention studies is more mixed. The aim of this study is to investigate the impact of consuming whole and refined wheat products on markers of cardiovascular disease. The objective is to carry out a controlled 16 week dietary intervention in crossover design to investigate the effects of consuming whole and refined grain wheat products in equal amounts on cardiovascular disease risk factors, in particular LDL cholesterol concentration. The purpose is to provide evidence to support public health messages to increase consumption of wholegrain foods.

Ethics approval

London city and east NHS research committee, 20/12/2013, ref. 13/LO/1883

Study design

Randomised crossover dietary intervention.

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Cardiovascular health


Participants will first be asked to avoid wholegrain foods for 4 weeks. They will then be randomly allocated into one of two groups.
1. Participants will be provided with wholegrain bread and cereals to consume for 4 weeks.
2. Participants will be provided refined grain bread and cereals to consume for 4 weeks.
They will then be a "wash out" period, where participants are asked to avoid whole grain foods for another 4 weeks. They then "swap over" to the other group - so that group 1 now eats the refined grain foods and group 2, the wholegrain foods, for a further 4 weeks.

Intervention type



Not Applicable

Drug names

Primary outcome measures

To assess the impact of increasing consumption of wholegrain wheat for 4 weeks on markers related to cardiovascular health, including lipid profile and 24-hour blood pressure:
1. Resting blood pressure (Screening visit and 0,4,6,8,12,14,16 weeks)
2. 24 hour blood pressure (Screening visit and 0,4,8,12,16 weeks)
3. Lipid profile (Screening visit and 0,4,8,12,16 weeks)

Secondary outcome measures

1. To quantify the impact of increased intake of wholegrain wheat on metabolites of alkylresorcinols in urine as biomarkers of whole grain intake:
1.1. Venous blood samples (Screening Visit and 0,4,8,12,16 weeks) for C17, C19, C21, C23, C24 alkylresorcinols
1.2. 24 hour urine and spot urine samples (Screening Visit and 0,4,8,12,16 weeks) for 3,5 dihydroxybenzoic acid (DHBA) and 3,5-dihydroxyphenylpropionoic acid (DHPPA)
2. To use plasma concentrations of alkylresorcinols as biomarkers for whole grain intake:
2.1. Venous blood samples (Screening visit and 0,4,8,12,16 weeks)
3. To evaluate the impact of increased consumption of wholegrain wheat on plasma biomarkers of CVD risk:
3.1. Intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin (screening visit and 0,4,8,12,16 weeks).
3.2. To describe the impact of increased consumption of wholegrain wheat on anthropometric measures including weight, waist circumference, body composition and BMI
3.3. Anthropometric measurements: Height (at Screening Visit only), weight, body mass index, body composition by bioelectrical impedance, waist and hip measurements (screening visit and 0,4,8,12,16 weeks)
4. To assess diet acceptance:
4.1. Digestive health questionnaire, (screening visit and 0,4,8,12,16 weeks)
4.2. Food frequency questionnaire (screening visit and 0,2,4,6,8,10,12,14,16 weeks)

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Aged 40-70 years.
2. Generally healthy subjects, as determined by clinical examination and medical history.
3. BMI between 25 and 35 kg/m2.
4. Slightly elevated blood pressure after 5 minutes supine position (systolic blood pressure >120mmHg).
5. Mildly elevated plasma cholesterol (> 5.5mM).
6. Nonsmoking.

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Known allergy to study (wheatbased) foods.
2. History of metabolic disease (i.e.diabetes, cardiovascular disease) relevant for drug treatment.
3. Chronic renal insufficiency.
4. Local or general treatment (i.e. prescription medications, overthecounter medications, dietary supplements or herbal supplements) known to interfere with the evaluation of the studied parameters.
5. Subject having had a general anaesthesia in the month preceding inclusion, or gastrointestinal surgery.
6. Pregnant or breastfeeding subject.
7. Use of laxatives.
8. Known allergies to cereals.
9. Dislike of provided study foods.

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Nu Food
Newcastle Upon Tyne
United Kingdom

Sponsor information


Cereal Partners Worldwide (Switzerland)

Sponsor details

Chemin du Viaduc 1

Sponsor type




Funder type


Funder name

Cereal Partners Worldwide (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes