DIETARY NITRATE INTAKE IN PATIENTS WITH PERIPHERAL ARTERIAL DISEASE

Recent research has shown that intake of nitrate (NO3) can lead to an increase
in plasma nitrite and nitrate levels, and
a reduction in blood pressure at rest and pulmonary oxygen uptake during
exercise. These effects are related to the
endogenous production of nitric oxide (NO), which is associated with a rise in
plasma nitrite levels. Research in clinical populations is scare.

The consumption of vegetables declared for 60-80% of the daily intake of
nitrate. So far, studies using
sodium nitrate (NaNO3) and red beet juice to induce these metabolic effects. A
recent study from our group shows that
acute supplementation of nitrate-rich vegetables can provide the same effects
as sodium nitrate and red beet juice on
the rise in plasma nitrite and nitrate values and a reduction in blood
pressure, in healthy participants.

Based on the gaps in current literature, our main goal will therefore be to
gain further insight into the effect the supplementation with concentrated
nitrate-rich beet juice, high nitrate vegetables compared with placebo in
patients with peripheral arterial disease.

The aim of the current study is to compare the acute effect of nitrate
supplementation. Therefore, we will assess the impact of concentrated beetroot
juice, high nitrate vegetables versus nitrate depleted beetroot juice (placebo)
on exercise tolerance (peak walking time (PWT), walking distance (PWD),
claudication onset time (COT) and distance (COD), VO2), vascular function (Flow
Mediated dilation (FMD), blood pressure (BP), heart rate (HR), tissue
oxygenation (NIRS) and plasma nitrate and nitrite.

randomized cross-over intervention study

In a randomized cross-over manner, participants will follow an acute
supplementation protocol in which they will a high nitrate meal in de form of
vegetables and/or ingest 400 mg (6.5 mmol) nitrate in the form of concentrated
red beetroot juice and/or placebo.

Participants will be required to report to the laboratory for a total of 4
visits and one screening session for a total of maximally 15 h. Prior to the
first experimental visit, participants will be asked to record their diet for 3
days and refrain from physical exercise for the 24 h preceding the visit.
Participants will be asked to avoid caffeine and alcohol for 12 h and 24 h
preceding each visit, respectively. Participants will also be asked to arrive
fasted, so they are not allowed to eat or drink (except for water) from 22:00 h
the evening before.

The burden and risks associated with participation are small. In total,
participants will donate twelve blood samples, representing ~7.5 mL over the
course of three weeks. Insertion of the needle for blood sampling could result
in a small hematoma. In addition, the main time commitment will consist of
filling in three food diaries.
The administered dose of nitrate in beetroot juice has been used in multiple
clinical and exercise studies and is a commercially available supplement. The
most commonly reported side effect is beeturia (red-coloured urine/faeces,
15-20% of the population) and mild gastrointestinal distress (bloating,
belching), and occasional reports of mild headache (which may or may not be
associated with the nitrate). The vegetables used in the present study are
freely available natural products. The only comparison available is from the
ingestion of nitrate-rich beverages, which has sometimes been described to lead
to mild gastrointestinal distress (bloating, belching) in some cases. The long
term effects of nitrate ingestion still need to be fully investigated.
Participants consuming dietary nitrate could potentially benefit from
improvement of their cardiovascular (heart and blood vessels) health. There are
no notable risks of participating in this study.
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