The contribution of L-glutamine to L-citrulline and L-arginine synthesis, when L-alanyl-L-glutamine is supplied in an enteral or parenteral dose of 0,5 g/kg/day, in surgical patients

Numerous clinical studies have demonstrated that glutamine supplemention of
12-30 g/day results ina favorable outcome as reflected by a reduced length of
hospital stay, a reduction in mortility in intensive care patients, a reduction
in infectious morbidity in severe trauma patients, a reduction in post-ICU
interventions and a significant reduction in hospital costs.
However, the underlying mechanisms are not fully clear.
The positive effect of glutamine could partly be due to the substrate that
glutamine delivers for citrulline and subsequent arginine synthesis. Arginine
is important for wound healing, preservation of the immune system and it serves
as a nitrogen donor for nitric oxide. Nitric oxide can regulate flow towards
and through vital organs.
During trauma and sepsis, plasma concentrations of arginine are decreased due
to an increased requirement under these conditions of arginine for the
synthesis of NO, acute phase proteins and proteins in general.
In our previous studies, the importance of the contribution of glutamine for
citrulline and arginine synthesis was demonstrated. The route of administration
as well as the influence of the structure of glutamine (as a mono- or a
dipeptide) was studied.
As a result metabolism on organ and whole body level is now unraveled and it
appears that the gut metabolizes glutamine in a different way when glutamine is
supplied via different routes.

However, the effect of a relevant clinical dosage of glutamine (30 g; or 45 g
as a dipeptide) supplementation on organ and whole body level remain unclear.

The main objective of this clinical study is to investigate the effect of the
administration of glutamine, provided as alanyl-glutamine, supplemented
enterally or parenterally, on the synthesis of citrulline from glutamine and
the subsequent synthesis of arginine from citrulline.

The proposed study is an open, exploratory clinical study of balanced (sex and
age distribution), groups of surgical patients.

Group A (case: n=6): from the day before surgery and start tracer protocol
until closure of the tracer protocol: 0.042g/kg/h alanyl-glutamine IV.
Group B (case: n=6): from the day before surgery and start tracer protocol
until closure of the tracer protocol: 0.042g/kg/h alanyl-glutamine ENT. The
day before surgery alanyl-glutamine will be provided as a drink. During surgery
alanyl-glutamine will be supplied through a naso-duodenal tube, which will be
placed shortly after induction of anesthesia.
Group C (control: n=4): only tracers of glutamine, citrulline and arginine IV
Of all patients (n=16), we will study metabolism at whole body level and
metabolism of the portally drained viscera, the liver and kidneys.

Participation will be under anesthesia, and will therefore not be experienced
as a burden. Potential risk factors will be placement of the nasoduodenal tube
(by surgeon) and blooddrawing.