Inter-individual Variation in the Blood Pressure Lowering Effects of Dietary Nitrate

Study Overview
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Brief Summary
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Dietary nitrate supplementation, often in the form of beetroot juice, has been shown to lower blood pressure and could play a role in preventing or treating hypertension. However, it is currently unclear: a) how reproducible this response is within the same individual on different occasions, and b) whether there are genuine individual differences in the blood pressure lowering effects of dietary nitrate. This study will use a novel replicated cross-over design (2 x nitrate conditions, 2 x placebo conditions) to examine the reproducibility and inter-individual variability in the blood pressure lowering effects of dietary nitrate supplementation.

Detailed Description
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The investigators will undertake a replicated cross-over randomised controlled trial (i.e., a study involving 2 x identical experimental conditions and 2 x identical control conditions), to explore the reproducibility of the blood pressure lowering effects of nitrate-rich beetroot juice, and to identify if there are genuine individual differences in the blood pressure-lowering effects of this supplement. Participants will be recruited via posters, email and social media, and interested individuals will be invited to attend the laboratory on 5 occasions. Visit 1: Potential participants will be invited to attend a screening session at Newcastle University to identify if they are eligible to participate. They will have an opportunity to discuss the study with a researcher and will provide written consent. They will then complete a screening questionnaire and provide a measure of their height, weight and blood pressure. Eligible participants will be invited to attend 4 experimental trials (2 x nitrate-rich beetroot juice conditions, 2 x placebo conditions) over 2-3 weeks with a minimum of 3 days wash-out between visits. If individuals are ineligible to participate this will be explained to them and they will be thanked for their time. Visits 2-5: On the day before the first trial, participants will be asked to record what they eat and then replicate this as closely as possible for all future visits. In the morning of each trial, participants will be asked to arrive at the laboratory between 7-9 am having fasted since 10 pm the night before. The participants will be required to rest for 10 minutes, after which a measure of their blood pressure will be obtained. Participants will then be provided with breakfast (a bowl of porridge) and 140 ml concentrated nitrate-rich ( 12.5 mmol nitrate) or nitrate-depleted beetroot juice ( 0 mmol nitrate). Participants will then be asked to sit in the laboratory for 2.5 hours, during which time they can read quietly or use a computer. The investigators will then obtain a further measure of their blood pressure and collect a blood sample from a vein in their arm via venepuncture, to measure markers of nitric oxide, a signalling molecule in the body which is thought to mediate the blood pressure lowering effects of nitrate-rich beetroot juice.

Official Title
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Effects of Dietary Nitrate on Blood Pressure: Exploring the Repeatability and Inter-individual Variation in Responses

Conditions
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Blood Pressure

Intervention / Treatment
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* Dietary Supplement: Beet It Sport Shot
* Dietary Supplement: Beet It Sport Shot Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers Aged 18 - 45 years Exclusion Criteria: Aged less than 18 or more than 45 years old Female Currently taking any medication or antibiotics Attending general practitioner for a health problem or on a hospital waiting list Currently taking part in another research study which could conflict with the requirements for this investigation Regularly use antibacterial mouthwash and unwilling to stop using this throughout the study period Current smoker History of kidney, liver or cardiovascular disease Have diabetes Have a gastrointestinal disorder Recent history (past 1 year) of cancer Use of other dietary supplements e.g., pre and probiotics Currently dieting Have a known allergy to any components within the dietary supplement

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Replicated cross-over trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental condition 1<br>Acute supplementation with 140 ml Beet It Sport Shots, James White Ltd ( 400mg dietary nitrate) | Dietary Supplement: Beet It Sport Shot<br>* Acute supplementation with 140 ml Beet It Sport Shots, James White Ltd, containing  400mg dietary nitrate<br>|
| Experimental: Experimental condition 2<br>Acute supplementation with 140 ml Beet It Sport Shots, James White Ltd ( 400mg dietary nitrate) | Dietary Supplement: Beet It Sport Shot<br>* Acute supplementation with 140 ml Beet It Sport Shots, James White Ltd, containing  400mg dietary nitrate<br>|
| Placebo Comparator: Control condition 1<br>Acute supplementation with 140 ml nitrate-depleted Beet It Sport Shots, James White Ltd ( 0mg dietary nitrate) | Dietary Supplement: Beet It Sport Shot Placebo<br>* Acute supplementation with 140 ml Beet It Sport Shots Placebo, James White Ltd, in which the nitrate has been removed via an ion exchange resin, containing   0 mg dietary nitrate<br>|
| Placebo Comparator: Control condition 2<br>Acute supplementation with 140 ml nitrate-depleted Beet It Sport Shots, James White Ltd ( 0mg dietary nitrate) | Dietary Supplement: Beet It Sport Shot Placebo<br>* Acute supplementation with 140 ml Beet It Sport Shots Placebo, James White Ltd, in which the nitrate has been removed via an ion exchange resin, containing   0 mg dietary nitrate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure of the brachial artery | Blood pressure of the brachial artery | Immediately prior to supplementation and for 2.5 hours after supplementation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma nitrite concentrations | Plasma nitrite concentrations | 2.5 hours after supplementation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Personalized nutrition, Nitric oxide, Beetroot juice