THE EFFECT OF DIETARY NITRATE AND SUCROSE ON GI FUNCTION DURING EXERCISE

The gastrointestinal (GI) tract plays an important role in the human body. The
GI wall regulates the uptake of nutrients, and also has a very important
function as a barrier between the internal and external environment. The
penetration of harmful substances and microbiota from the GI lumen (external
environment) into the systemic circulation (internal environment) depends on
this barrier.
During high-intensity exercise, GI complaints and intestinal injury frequently
occur, thereby hampering exercise performance. Splanchnic hypoperfusion,
resulting in intestinal damage, has been postulated as one of the key
underlying mechanisms for exercise associated GI symptoms. Attenuating such
hypoperfusion therefore appears a promising strategy to reduce GI injury and
its negative effects on performance. During episodes of splanchnic
hypoperfusion, the synthesis of nitric oxide (NO) is suppressed. A previous
study of our group found that supplementation with L-citrulline as a donor of
the endogenous NOS dependent pathway lead to improved splanchnic blood flow and
reduced intestinal damage during high intensity exercise. By acting as a local
NO donor, through the nitrate-nitrite-NO pathway, dietary nitrate may also
increase microcirculatory blood flow in the splanchnic area. Next to NO,
macronutrients can also act as potential GI stimulators. The ingestion of
carbohydrates will directly stimulate an increase in splanchnic
microcirculatory blood flow, simply through the normal digestive processes
taking place. Thus, both ingestion of nitrate and carbohydrates may effectively
reduce intestinal damage, and as such prove valuable in reducing the negative
effects of exercise on the gut.

The aim of this study is to investigate the effects of both dietary nitrate and
sucrose ingestion on splanchnic perfusion and intestinal (enterocyte) damage
during high intensity exercise.

In a randomized, placebo-controlled, cross-over design, male cyclists will
perform 1 h of high-intensity exercise after the ingestion of: 1) a water
placebo (PLA), 2) a sodium nitrate drink (NIT), 3) a sucrose solution (SUC).
Splanchnic perfusion and enterocyte damage will be monitored during and up to 1
h after the exercise sessions.

On each test day the participants will perform 60 min of cycling at 70% Wmax,
were the effect of each intervention on GI parameters will be investigated.
NIT: 1.1 g of NaNO3 (sodium nitrate) dissolved in 200 mL water 2.5 h prior to
exercise. 200 mL water provided both 15 min prior and 30 min into exercise.
SUC: 1.1 g of NaCl (placebo) dissolved in 200 mL water 2.5 h prior to exercise.
20 g sucrose dissolved in 200 mL water provided both 15 min prior and 30 min
into exercise.
PLA: 1.1 g of NaCl (placebo) dissolved in 200 mL water 2.5 h prior to exercise.
200 mL water provided both 15 min prior and 30 min into exercise.

The risks involved in participating in this experiment are low. The insertion
of the nasogastric tonometry catheter is performed by a certified physician and
is a standard medical procedure (e.g. for enteral feeding). The insertion can
feel somewhat unpleasant, but is of very low risk. Some subjects experience the
urge to vomit. There is minor risk for complications (e.g. nose bleed,
sinusitis and transient sore throat); given the short time frame for which the
catheter is maintained in situ (i.e., 180 minutes), these risks are minimal.
The procedures have previously been safely applied and their risks are also
described in MEC09-3-005 and MEC10-3-064. Insertion of a catheter on the hand
is comparable to a normal blood draw and the only risk is a small hematoma.
The subjects will cycle for 60 min at 70% Wmax. This exercise protocol can lead
to tiredness in the hours after cycling and muscle soreness up to 1-2 days
after cycling. The same protocol has been applied in MEC09-3-005 and
MEC10-3-064.
The administered dose of nitrate has been used in multiple clinical and
exercise studies and is previously approved by the METC (e.g. MEC13-3-059). The
most commonly reported side effect is mild gastrointestinal distress (bloating,
belching), and occasional reports of mild headache (which may or may not be
associated with the nitrate). The long-term effects of nitrate ingestion still
need to be fully investigated. All supplements are produced according to GMP
standards and are safe for human use.