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Melatonin and dopamine as biomarkers to optimize treatment in phenylketonuria: effects of tryptophan and tyrosine supplementation.
[phenylketonuria]
To
determine
whether
additional
supplementation
of
tryptophan
(
Trp
)
and
tyrosine
(
Tyr
)
improve
serotonin
and
dopamine
metabolism
in
individuals
with
phenylketonuria
treated
with
large
neutral
amino
acid
(
LNAA
)
tablets
.
Ten
adult
individuals
with
phenylketonuria
participated
in
a
randomized
,
double
-blind
,
placebo-controlled
cross-over
study
consisting
of
three
3
-
week
phases
:
washout
,
treatment
with
LNAA
tablets
plus
supplementation
with
either
Trp
and
Tyr
tablets
or
placebo
,
and
LNAA
tablets
plus
the
alternate
supplementation
.
An
overnight
protocol
to
measure
blood
melatonin
,
a
serotonin
metabolite
in
the
pinealocytes
,
and
urine
6
-
sulfatoxymelatonin
and
dopamine
in
first
-void
urine
specimens
was
conducted
after
each
phase
.
Serum
melatonin
and
urine
6
-
sulfatoxymelatonin
and
dopamine
levels
were
increased
in
the
LNAA
phase
(
LNAA
plus
placebo
)
compared
with
the
washout
phase
.
Serum
melatonin
and
urine
6
-
sulfatoxymelatonin
were
not
increased
in
the
active
phase
(
LNAA
plus
Trp
+
Tyr
)
compared
with
the
LNAA
phase
,
although
plasma
Trp
:
LNAA
was
increased
compared
with
the
LNAA
phase
.
Among
7
subjects
with
a
plasma
Trp
/
LNAA
>
0
.
03
,
a
negative
correlation
between
urine
6
-
sulfatoxymelatonin
and
plasma
phenylalanine
levels
was
observed
(
r
=
-
0
.
072
)
.
Urine
dopamine
levels
and
plasma
Tyr
:
LNAA
were
increased
in
the
active
phase
compared
with
the
LNAA
phase
.
Melatonin
levels
were
not
increased
with
the
higher
dose
of
Trp
supplementation
,
but
dopamine
levels
were
increased
with
the
higher
dose
of
Tyr
supplementation
.
Serotonin
synthesis
appears
to
be
suppressed
by
high
phenylalanine
levels
at
the
Trp
hydroxylase
level
.
Diseases
Validation
Diseases presenting
"blood melatonin"
symptom
phenylketonuria
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