Condition category
Nutritional, Metabolic, Endocrine
Date applied
07/04/2014
Date assigned
08/07/2014
Last edited
08/07/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Studies show that those who eat more wholegrain foods have a lower risk for developing long-term diseases including heart disease, stroke, diabetes and some cancers. However, the amount needed to give this beneficial effect is not known. To establish whether such a relationship does exist and to test it, we need to make an accurate assessment of peoples’ wholegrain food intake. However, using food records for this has been difficult because of poor definitions of wholegrain foods, limited information on portion/serving sizes and lack of detail on the wholegrain content of individual foods. Therefore, there is a need to assess wholegrain intake in individuals using other methods. One method is to look for chemical components that are only obtained from wholegrain foods in biological fluids such as blood or urine; the amount of these chemical components is affected by the amount of wholegrain eaten. Sometimes the component can be identified in the same form as occurs in the food, but sometimes as breakdown products (metabolites) formed from the original component can be identified instead. We believe that these components may be used as ‘biomarkers’ of wholegrain intake. Therefore, we designed this dietary intervention study in healthy volunteers, consuming known amounts of wholegrain foods based on either wheat or rye, to measure corresponding amounts of three candidate biomarkers of wholegrain intake, called alkylresorcinols, enterolactone and enterodiol, in blood and urine.

Who can participate?
Healthy adult men and women can take part in this study.

What does the study involve?
For the first 4 weeks volunteers should avoid eating any wholegrain foods. The volunteers are then randomly allocated to either the wheat group or the rye group. For the next 4 weeks they will then eat three servings per day (about 48 g per day) of either wheat or rye foods according to their group. After this they will eat six servings per day of the same wholegrain foods for another 4 weeks. The volunteers will provide samples of blood and urine at the end of each 4-week period. Once the amount of these components are determined, we will compare which of the three potential biomarkers is a better indicator of rye or wheat intake. We will use a new method of analysis, the metabolomic approach, to identify and quantify the amount of all small molecules present in the blood and urine samples, in order to get a pattern of these small molecules (metabolites) which might be indicative of a diet rich either in wheat or rye. This method also has the potential to identify new biomarkers related to wholegrain intake, especially metabolites derived from the two primary biomarkers being tested.

What are the possible benefits and risks of participating?
There will be no immediate benefit to those taking part, other than having a ‘health check’ as part of the screening. The results will be used to develop better methods to measure how much wholegrain people eat, which will help us quantify the health benefit of eating these foods. There are no risks to people taking part. There is a small risk of bruising when giving a blood sample, but we use experienced nursing staff so this is reduced.

Where is the study run from?
Human Nutrition Research Centre at Newcastle University (UK).

When is the study starting and how long is it expected to run for?
The study started in January 2008 and ended in July 2009.

Who is funding the study?
Food Standards Agency (UK).

Who is the main contact?
Prof Chris Seal
chris.seal@ncl.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Chris Seal

ORCID ID

Contact details

Human Nutrition Research Centre
School of Agriculture
Food & Rural Development
Newcastle University
Newcastle upon Tyne
NE1 7RU
United Kingdom
+44 (0)191 208 7650
chris.seal@ncl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N05075

Study information

Scientific title

Biomarkers of wholegrain intake: contribution of alkylresorcinols and mammalian lignans to the metabolome

Acronym

GrainMark

Study hypothesis

This is a dietary intervention study designed to compare three different biomarkers of wholegrain intake in response to changes in wholegrain wheat and wholegrain rye consumption.
The specific objectives of the study were:
1. To quantify the impact of increased intake of wholegrain wheat or rye on plasma concentrations of alkylresorcinols.
2. To quantify the impact of increased intake of wholegrain wheat or rye on plasma and urinary concentrations of mammalian lignans.
3. To describe the impact of increased intake of wholegrain wheat or rye on the pattern of metabolites (the metabolome) in plasma and urine.

Ethics approval

Northumberland Research Ethics Committee (NHS REC), 15/11/2007, ref.:07/H0902/53. Since the dietary intervention part of the study was undertaken at the Newcastle NIHR CRF, it required NHS Trust Approval which was obtained on 11/12/2007 (Ref. No. 4349).

Study design

Randomised diet intervention two-group parallel design with increasing intake of wholegrain wheat or rye

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Changes in concentrations of biomarkers in response to changing wholegrain intake

Intervention

The study is a randomised dietary intervention based on a two-group parallel design with increasing intake of wholegrain wheat or rye to validate two proposed groups of biomarkers of wholegrain intake, and to determine new potential biomarkers of wholegrain intake and overall changes in metabolite profile resulting from their consumption. The design of the intervention is as follows:

1. Wash-out period, 4 weeks: volunteers avoid all wholegrain foods from their diet.
2. Randomisation to study groups using minimisation procedure based on age, gender and BMI.
3. Period 1: three servings per day (equivalent to about 48 g of WG/d) of either WG wheat or WG rye foods for 4 weeks (Dose 1).
4. Period 2: six servings per day of the same WG foods they had during the Dose 1 period, for another 4 weeks (Dose 2).

During the dietary intervention, all wholegrain foods are provided, volunteers avoid all other wholegrain foods.
Wheat intervention group: 100% wholemeal wheat bread, Shredded Wheat Fruitful, Weetabix and 100% wholegrain wheat pasta.
Rye intervention group: 100% wholemeal rye bread, rye porridge, rye muesli and 20% wholegrain rye pasta.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Dose-response changes in plasma and urine concentrations of alkyresorcinols determined by gas chromatography mass spectroscopy, and mammalian lignans determined by high-performance liquid chromatography with Coularray detection. Samples collected after 4 weeks washout (wholegrain free), then 4 weeks consuming three servings of wholegrain per day and, finally, after a further 4 weeks consuming six servings of wholegrain per day.

Secondary outcome measures

Plasma and urine 'metabolome' profile identified by targeted and untargeted metabolite analysis by comprehensive mass spectroscopy analysis. Samples collected after 4 weeks washout (wholegrain free), then 4 weeks consuming three servings of wholegrain per day and, finally, after a further 4 weeks consuming six servings of wholegrain per day.

Overall trial start date

01/01/2008

Overall trial end date

01/07/2009

Reason abandoned

Eligibility

Participant inclusion criteria

Males and females aged over 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

64 volunteers; 32 male, 32 female

Participant exclusion criteria

1. Allergies or intolerances to intervention foods
2. Individuals receiving any form of clinical treatment, and/or taking prescribed medications (clinical treatment will affect metabolic profile and/or bioavailability of nutrients from the intervention diet, potentially masking true dietary effects)
3. Individuals taking any form of dietary supplements (dietary supplements may affect metabolic profile and/or bioavailability of nutrients from the intervention diet, potentially masking true dietary effects)
4. Having dietary restrictions, apart from being a vegetarian (for example being on a detox or slimming diet) (some dietary restrictions could interfere with metabolic profile in response to wholegrain diet)
5. Planning to change dietary habits, increase physical activity, change body weight, move away from the study centre locality or to take a lengthy vacation during the time of the study (approximately 12 weeks)
6. Smokers (may affect metabolic profile through increased oxidative stress)
7. History of alcoholism or substance abuse (may affect compliance to dietary intervention and/or metabolic profile)
8. Body Mass Index < 20 kg/m2 or > 30 kg/m2 (very underweight or overweight individuals are likely to have disturbed metabolic profiles and metabolic response to diet)
9. Currently pregnant, planning pregnancy or having had a baby in the past 12 months

Recruitment start date

01/01/2008

Recruitment end date

01/07/2009

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Human Nutrition Research Centre
Newcastle upon Tyne
NE1 7RU
United Kingdom

Sponsor information

Organisation

Food Standards Agency (UK)

Sponsor details

Aviation House
125 Kingsway
London
WC2B 6NH
United Kingdom
helpline@foodstandards.gsi.gov.uk

Sponsor type

Government

Website

Funders

Funder type

Government

Funder name

Food Standards Agency (UK), Ref. N05075

Alternative name(s)

FSA

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

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