Effects of Daily Nitrate Consumption on Oral Bacteria Composition, Blood Pressure and Vascular Function

NCT ID: NCT03784742

Last Updated: 2024-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-01
• Study Completion Date: 2021-12-01

Brief Summary

Diseases of the heart and blood vessels, including raised blood pressure, are one of the leading causes of death worldwide. Higher intakes of dietary nitrate, found abundantly in root vegetables such as beetroot, have been shown to have health benefits including lowering blood pressure and improving the elasticity of blood vessels. Bacteria which reside in the mouth and those in the gastrointestinal tract play an important role in converting dietary nitrate to nitrite and nitric oxide (a chemical which promotes the relaxation of blood vessels). In particular, removal of oral bacteria by using antiseptic mouthwash is accompanied by an increase in blood pressure in subjects with normal blood pressure, even after consuming nitrate-rich foods. To date, very little is known about the role of these oral bacteria in the control of blood pressure, and if there are any differences in bacterial composition between individuals.

Detailed Description

Interested volunteers will be provided with an outline of the study and asked to complete a medical and lifestyle questionnaire (in person, by email or over the phone). Potentially suitable participants will be identified and asked to attend a screening session after a 12 h overnight fast (not eating during this time and only drinking water) during which the study will be explained in more detail before a consent form is signed. Anthropometric measurements will then be taken including weight, height and blood pressure. A 9 ml blood sample will also be collected on site at the Department of Food and Nutritional Sciences (Hugh Sinclair Unit of Human Nutrition). Subjects who meet the initial inclusion criteria will be invited to a further screening session during which time a dentist will check for dental diseases (e.g. current dental cavities or periodontal infection) and saliva flow rate. Volunteers without periodontal disease and with normal saliva flow will then be invited to participate in the study.

Eligible subjects will then be randomised to one of two treatments: i) up to 70 ml (the amount given will be equivalent to 3.7 mg/kg body weight) beetroot juice (James White Drinks Limited, UK) or ii) a matched volume of placebo beetroot juice (control, James White Drinks Limited, UK) to be consumed daily for 8 weeks. As drinking water is a major source of dietary nitrate, subjects will be provided with a water filter to reduce the nitrate level in their tap water for drinking and cooking during the study period. There will be a wash out period of 4 weeks between the intervention juices. In total, volunteers will be involved in the study for 20 weeks (five months).

On the day before each baseline study visit (weeks 0 and 12), volunteers will be required to fast overnight after having a low nitrate evening meal and only drinking low nitrate mineral water (Buxton mineral water), which will be provided to them, during this time. They will refrain from strenuous exercise and alcohol. On the morning of the study visit, the volunteers will be asked not to brush their teeth before they come to the clinical unit for their study visit.

When they arrive in the fasted state, the participants will be asked to provide a spot urine sample and a stool sample. Body weight and composition will be measured using the Tanita weighing scale, saliva sample and an oral bacteria sample will be collected by swabbing the tongue with a cotton swab. Volunteers will be asked to lie down for 20 minutes prior to the measurement of blood pressure and pulse wave analysis (PWA) using the Mobil-O-Graph device followed by the assessment of microvascular reactivity using Laser Doppler Imaging with iontophoresis. A blood sample of 20 ml (equivalent to just over 1 tablespoon) will then be taken before a light breakfast is provided. Volunteers will then be given a toothbrush and toothpaste to brush their teeth and asked to complete an online food frequency questionnaire (EatwellUK).

During the four-week wash-out period between interventions, participants will be instructed to avoid any beetroot juice drinks and maintain their usual dietary and lifestyle habits.

Conditions

No Dental Disease; Non-smoking

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Nitrate-rich Beetroot juice

Nitrate-rich beetroot juice equivalent to 3.7 mg nitrate per kg body weight daily for 8 weeks.

Group Type: ACTIVE_COMPARATOR

Nitrate rich beetroot juice

Intervention Type: OTHER

James White Drinks Limited beetroot juice (0.4-0.45 g nitrate/70 ml drink).

Placebo beetroot juice

Placebo beetroot juice (equivalent volume to the amount of nitrate-rich beetroot juice consumed) daily for 8 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo beetroot juice

Intervention Type: OTHER

James White Drinks Limited Placebo beetroot juice (0 nitrate/70 ml drink).

Interventions

Nitrate rich beetroot juice

James White Drinks Limited beetroot juice (0.4-0.45 g nitrate/70 ml drink).

Intervention Type: OTHER

Placebo beetroot juice

James White Drinks Limited Placebo beetroot juice (0 nitrate/70 ml drink).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Male and female;

• A signed consent form;
• Blood pressure <140/90 mm Hg;
• BMI range 18.5 - 39.9 kg/m2;
• Age 18-64 years;
• Non-smoking;
• Not taking blood pressure lowering medication or using medications known to influence vascular function such as a glyceryl trinitrate (GTN) spray;
• No recent (within 3 months) or current use of antibiotics.

Exclusion Criteria

Diagnosed with a chronic illness;

• Anaemia defined as a haemoglobin < 115 g/l for women and <130 g/l for men;
• Individuals with food allergies or allergies to medicated mouthwash or ingredients in the oral products;
• Requirements to take long-term medication active on the oral cavity including prebiotics and probiotics or have taken antibiotics within the last 3 months;
• Gingivitis diagnosis, or periodontal disease or chronic oral complaints or existing oral pathology.
• Less than four natural (enamel) buccal surfaces of upper molars available;
• Presence of fixed or removable oral appliances (e.g., dentures, orthodontic wires); xerostomia (a persistent dry mouth) diagnosis;
• Current smoker;
• Already participating in a dietary intervention study or clinical trial;
• Excessive alcohol consumption (> 14 units/wk);
• Females who are pregnant or lactating;
• Individuals not willing to give up using mouthwash or change their dental hygiene routine. Regular consumption or use of xylitol-based products such as toothpaste and chewing gum.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Saudi Cultural Bureau

UNKNOWN

Sponsor Role: collaborator

University of Reading

OTHER

Sponsor Role: lead

Responsible Party

Julie Lovegrove

Professor of Human Nutrition, Head of the Hugh Sinclair Unit of Human Nutrition

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Julie A Lovegrove, BSc, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Reading

Locations

Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading

Reading, Berkshire, United Kingdom

Countries

United Kingdom

Other Identifiers

347890

Identifier Type: -

Identifier Source: org_study_id