Randomised Controlled Trial to Investigate N-nitrosamine Formation After Meat Intake - Meat Study of the Nitrate INFORMER Studies; Nitrate INFORMER Studies: Is Nitrosamine FORMation dEpenent on souRce
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Edith Cowan University
- Enrollment
- 25
- Locations
- 2
- Primary Endpoint
- N-nitrosamines in urine post intervention (up to 24 hours)
Study Overview
Brief Summary
Nitrate is a controversial component of vegetables, meat, and drinking water. The now well-established benefits of nitrate, through the enterosalivary nitrate-nitrite-nitric oxide (NO) pathway, on cardiovascular risk factors and long-term cardiovascular disease risk are tarnished by a continuing concern about a link between nitrate ingestion and cancer. This can result in misguided advice to avoid consumption of high-nitrate leafy green vegetables by both the media and the scientific literature. A recent media headline stated, "Cancer alert over rocket: trendy salad leaves exceed safe levels of carcinogenic nitrates in one in every ten samples". One scientific review stated, "the presence of nitrate in vegetables, as in water and generally in other foods, is a serious threat to man's health". Controversy in the literature, and gaps in the knowledge are leading to confusing messages around vegetables that may play a critical role in cardiovascular health.
The major dietary sources of nitrate are vegetables, meat, and drinking water. Source of nitrate could be a crucial factor determining whether the consumption of nitrate is linked with beneficial (such as improving cardiovascular health) versus harmful (N-nitrosamine formation) effects. For example, unlike meat and water-derived nitrate, vegetables contain high levels of vitamin C and/or polyphenols that may inhibit the production of N-nitrosamines. So far, no study has investigated the formation of N-nitrosamines after consumption of these different sources in humans. This study will compare N-nitrosamine formation after intake of meat with and without added nitrate.
Detailed Description
Study design
A crossover study design will be used with a 1-week washout period between interventions. Participants diet for the day before and the day of the intervention will be standardised (food choices on visit 1 will be matched for visit 2) as follows:
For the day before the study visit:
- A choice of 3 breakfasts: cornflakes with milk; rice krispies with milk; white bread toast with eggs.
- Lunch will be provided comprising pumpkin soup and white bread/or rice
- Dinner: a low nitrate vegetarian meal
- All water will be provided
- Participants will be asked to refrain from drinking coffee and any alcoholic beverage and do any exercise 24 hours prior to their study visit.
For the day of the study visit:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Prevention
- Masking
- Single (Outcomes Assessor)
Masking Description
Given the nature of the interventions, participants, and the investigators responsible for delivering the interventions will be unblinded throughout the trial. However, all researchers performing the laboratory analyses and data analyses will be blinded to the interventions that the participants received until after the data analysis has been performed.
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •The recruitment will be as inclusive as possible so that the results are relevant to much of the general population. Twenty-five men and women will be recruited from the Perth general population according to the following criteria:
- •aged between 18 to 70 years old
- •healthy, ambulant, community-dwelling
- •with no history of major chronic disease
Exclusion Criteria
- •Individuals volunteering to participate in the study will be excluded according to the following criteria:
- •current or recent (<12 months) smoking
- •body mass index (BMI) <18 or > 35 kg/m2
- •systolic blood pressure > 160 mmHg
- •diastolic blood pressure > 100 mmHg
- •any major illness such as cancer, psychiatric illness, diagnosed diabetes
- •use of any of the following medications: statins, antihypertensives, nitric oxide donors, antithrombotic medication, anti-coagulant medication, anti-arrhythmic drugs, beta-blockers, regular aspirin use, regular proton pump inhibitor use
- •alcohol consumption > 30g/day
- •who are pregnant, lactating, or wishing to become pregnant during the study
- •use of antibiotics within the previous 12 weeks of the study
- •regular use of mouthwash and not willing to cease mouthwash use for the duration of the study
- •participation on other research studies
- •major gastrointestinal tract condition e.g. Crohns disease and inflammatory bowel disease
- •and inability or unwillingness to follow the study protocol.
Outcomes
Primary Outcomes
N-nitrosamines in urine post intervention (up to 24 hours)
Time Frame: At each clinic visit, all urine from the start of intervention up till 24 hours will be collected.
Participants will be provided with sterilized containers and instructions to collect all urine until 24 hours post intervention. Urine aliquots will be frozen at -80°C until analysis. N-nitrosamines will be measured by gas chromatography mass spectrometry (GCMS).
N-nitrosamines in stool samples post intervention (up to 24 hours)
Time Frame: At each clinic visit, all stool samples from the start of intervention up till 24 hours will be collected.
Participants will be provided with instructions and a stool sample collection pack (collection bags, cable ties, large zip lock bags, freezer ice blocks and a designated cooler bag for transport). Collected stool samples will be weighed and frozen at -80°C until analysis. N-nitrosamines will be measured by gas chromatography mass spectrometry (GCMS).
Secondary Outcomes
No secondary outcomes reported