Tryptophan enriched diet to improve affective and cognitive functions in patients with multiple sclerosis

Multiple sclerosis is a chronic neurologic disease characterized by
physiological and/or immunological abnormalities that can diminish synthesis of
serotonin leading to metabolic deregulation or less efficient
neurotransmission. Based on the regulatory function of serotonin on mood, it is
very likely that a deficiency in serotonergic metabolism induced by MS-related
factors might at least partly underlie mood disturbances which could secondary
induce cognitive deficits and affect quality of life in MS patients.
Serotonin synthesis in brain is regulated by its precursor tryptophan (TRP).
Because tryptophan is an essential amino acid, modifying the availability of
tryptophan through dietary intake, can directly influence central serotonin
metabolism and consequently affective and cognitive processes. The hypothesis
is that an acute intake of a TRP enriched meal attenuates neuropsychological
dysfunctions in MS patients, especially when having mood disturbances.

The purpose of this study is to test the acute effects of a TRP enriched meal
in a dose-dependent manner in MS patients. The results of MS patients without
mood disturbances (control group) will be compared to MS patients with mood
disturbances (study group) in order to investigate whether the latter are more
sensitive to or have more benefit of this nutritional approach. As a result, we
can select the most optimal nutritional formulation for MS patients with
respect to neuropsychological functions. Based on the outcomes of these
studies, we can investigate the relationship between serotonergic system,
mental processes and MS in more detail. When finding proof-of-principle, a
larger group of patients will be used to identify specific markers that can
predict the therapeutic effects of a TRP-enriched diet on neuropsychological
functions and that can improve early recognition of the symptoms

The project comprises a phase II, double-blind placebo-controlled crossed-over
acute nutritional intervention study in which a whey protein meal with
additional TRP is given to MS patient with and without mood disturbances. To
examine the acute effects of this meal in a dose-dependent manner, each subject
will undergo four identical experimental test days, at least one week between
two test days. Each subject will receive a control condition (without TRP) and
three doses of TRP. This project is designed to give specific indications in
order to select the most optimal nutritional formulation for MS patients with
respect to neuropsychological functions. The combination of measuring plasma
TRP levels, assessment of mood and cognitive functions (i.e. attention and
memory) after nutritional intervention will enable quantification of the main
endpoints of this study.

We will test the acute effects of a whey protein meal where TRP levels can
easily be modified in a dose-dependent manner. On each experimental test
session, the subject is given a liquid whey protein meal with or without an
additional amount of TRP by bolus feeding (400 ml). Each subject will receive a
session with a whey protein mixture without TRP (placebo) and three sessions
with whey protein mixture added with different amount of TRP.

The potential benefits of this nutritional intervention will be substantial to
the patients in terms of an acute increase in mood state and cognitive
functionality. The burden associated with participation is limited to five
visits to the hospital. During each visit, neuropsychological assessments
(tests and questionnaires) are used to evaluate effects on affective and
cognitive processes. A catheter will be place before the start of every session
to reduce inconvenience of frequently collecting blood samples (5 times/
session). In addition, this nutritional intervention is essential risk-free,
although might result in temporary side effects such as nausea, drowsiness or
fatigue. These effects might be induced by the amount of liquid (400 ml) that
has to be consumed as quickly as possible. However, the risks are outweighed by
the benefit of the information that will be gained from the study. Increasing
TRP availability by nutritional intervention has to date not been used in MS
patients. By investigating the acute effects of this TRP-enriched meal in a
dose-dependent manner, we are able to select the most optimal nutritional
formulation for MS patients with respect to neuropsychological functions.
Additionally, such an approach holds promise for guiding the identification of
subgroups of patients most likely to benefit from TRP enriched meals.