Influence of Dietary Nitrate on Vascular Dysfunction and Inflammation

A Double-blind, Randomised, Placebo-controlled Parallel Study to Investigate the Effect of Dietary Nitrate on a Model of Vascular Dysfunction in Healthy Volunteers

The principal research objective is to determine whether inorganic nitrate in the form of beetroot juice compared to placebo control prevents the systemic inflammation that underlies typhoid vaccine-induced endothelial dysfunction

We wish to determine in a prospective manner whether inorganic nitrate affects the endothelial dysfunction induced by systemic inflammation. At baseline we will measure flow-mediated dilatation (FMD) and peripheral augmentation index, as well as aortic stiffness, as measured by pulse wave velocity (PWV). Volunteers will then receive ~8 mmols of dietary nitrate or nitrate free placebo juice once daily for 6 days. After this, depending on availability, volunteers will receive a typhoid vaccine Typherix®, GlaxoSmithKline UK or Typhim Vi ™, AAH Pharmaceuticals Ltd). This vaccine generates a mild systemic inflammation that is associated with vascular dysfunction. All vascular function measures will be repeated at 8 hours and 32 hours after vaccine administration.

Inclusion Criteria:

1. Healthy volunteers
2. Aged 18-45
3. Volunteers who are willing to sign the consent form.
4. Normal resting blood pressure (<140/90 mmHg)

Exclusion Criteria:

1. Healthy subjects unwilling to consent
2. Pregnant, or any possibility that a subject may be pregnant unless in the latter case a pregnancy test is performed with a negative result
3. History of any serious illnesses, including recent infections or trauma
4. Subjects taking systemic medication (other than the oral contraceptive pill)
5. Subjects with self-reported use of mouthwash or tongue scrapes
6. Subjects with recent (3 months) or current antibiotic use
7. Subjects with a history, or recent treatment of (within last 3 months) any oral condition (excluding caries), including gingivitis, periodontitis and halitosis
8. Subjects with a history of typhoid vaccination in the last 6 months
9. Subjects with any history of a blood-borne infectious disease such Hepatitis B or C virus, or HIV