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Carlo
Maurizio
Cangiano,
Muscaritoli,
Fabrizio
Antonia
Antonucci, have shown
Cascino,
and that
Del
Ben,
Alessandro
Laviano,
Rossi-Fanelli in obese subjects (14). a 5-HTP The present study attempted to confirm verify by
ABSTRACT
ministration prescriptions
Previous
observations
of 5-hydroxytryptophan (5-HTP) causes anorexia, decreased food subjects. be To confirm these data adherence 20 obese and to verify whether improved by 5-HTP,
dietary these data over adherence and weight whether period administering
and to be improved
loss in obese
ofobservation tion could
a longer
subjects.
domly assigned to receive either 5-HTP The study was double-blinded and was periods. No diet was prescribed during kJ/d diet was observed recommended in 5-HTP-treated for the
(900 mg/d) or a placebo. for two consecutive 6-wk Subjects the first period, a 5040Twenty-eight second. Significant weight during both periods. age 43.2 40 were of
Subjects
and methods
obese,
hyperphagic
adult
female
subjects
loss was
patients
in carbohydrate intake and a consistent presence energy introduced with respect were also found. These findings together with the to sex, age, and physical observed suggest that 5-HTP may be safely used according intolerance, hyperlipidemia, or obesity. Am J Clin Nutr 1992;56:863-7. from the study. Eating obesity, loss behavior, adherence anorexia, to diet, 5-hydroxytrypappetite for
the energy need calculated activity. Subjects with glucose were excluded
hyperuricemia
tophan, bohydrates,
design research ofthe consent, protocol University subjects was approved by the Faculty After to Ethics giving receive starch, Inform of times was 6restricsubjects were sub-
Introduction
Pharmacological, accumulated rotonin has animals possible genesis this idea in animals reported in serotonin changes stitutes and role (5-7). in an biochemical, the last inhibitory
(
Sapienza. assigned
and
either 5-HTP (900 mg/d) mannitol, and magnesium has dustries, secapsules in of a per day, patho- subdivided Pomezia, Italy).
that do not dissolve until pH 8.6, was taken three 30 mm before each meal. The 12-wk-study period for each group of subjects into two consecutive period diet there was were The no 5040 dietary to U recommended
present
serotonin
hypothalamus
the second period ofobservation. have beenduring divided as follows: 53% from carbohydrates, increase 1 8% from proteins. No carbohydrate-rich may reflect and meals. in turn con-between feeding behavior responses of different measurements synapses to cause in obese both drugs Subjects were examined and body were performed
29% from lipids, foods were allowed every 2 wk blood at the to evaluate chemistry beginning
are coordinated with nutritional inputs (10). directand indirect-acting agonists at central such as dexfenfluramine and fluoxetine have weight loss as well as a marked reduction subjects caused (1 1- 1 3). However, the administration a high incidence of side effects 1 2, 13). (
From the Laboratory of Clinical Nutrition, 3rd Department of Internal Medicine; the Department ofHuman Biopathology; and Servizio di Dietetica, Istituto di Terapia Medica Sistematica, University of Rome, La Sapienza, Rome, Italy. In a previous short-term (5 wk), double-blind, crossover study 2 Address reprint requests to F Rossi-Fanelli. Laboratory of Clinical we observed that oral administration of the physiological sero- Nutrition, 3rd Department of Internal Medicine, Viale delIUniversit#{224} tonin precursor 5-hydroxytryptophan (5-HTP), without any 37, 00185 Rome, Italy. specific dietary prescription, was followed by the onset of typical Received January 22, 1991. anorexia-related signs, eg, decreased food intake and weight loss Accepted for publication May25, 1992.
intake
in,
C/in
Nior
1992:56:863-7.
Printed
in USA.
1992
American
Society
for Clinical
Nutrition
863
864
TABLE Baseline I characteristics of subjects5 Body weight kg Placebo 5-HTP
S
CANGIANO
ET
AL
Total
energy k/Id
Proteins g/d
Carbohydrates g/d
1 1.3 331 29.1 349 47.8
Lipids g/d
120 12.3
94.3 99.7
5.3
I I 398
5.9
13 528
1 020 I 033
104 1 17
8.8
144 12.6
groups.
and
at
the
end to
of
each
period
treatment, 24-h urinary acid (5-HIAA) was also al (1 5). energy intake may define by using
subjects and unpaired data; modifications observed within each treatment 5-hydroxy- group were compared or placebo and the 5-HTP groups were every 2 wk compared ( 1 7). The Chi-square test was used to compare the described by prevalence of both the anorexia-related symptoms and the side of effects observed during seThe minimum probability asicance was P < 0.05. inplacebo level and considered 5-HTP for treatments. statistical (17). signif-
To
test
2 wk
leftovers. All reports Twenty ofthe 28 subjects included completed the study. The To avoid reported eight dropouts (three in the study group and five in the control interference due to premenstrual depression, food-intake mea- group) did not complete the study for the following reasons: surements were not assigned to this time of the month 6). ( I three had family problems, two self-prescribed a low-energy diet To investigate anorexia, patients were invited to report the during the first study period, two self-administered other anopresence of a series of symptoms, namely meat aversion, tasterectic drugs, and one did not complete the follow-up. Two groups and smell alteration, nausea and/or vomiting, and early satiety. of 10 subjects each therefore were studied. As shown in Table All of these symptoms interfere with eating and are possibly 1, baseline characteristics were comparable for the two groups were related system invited ofside diarrhea, to a pathological (CNS) regulation to report effects, and at the including stipsis. modification of offeeding behavior end ofeach period myalgia, weakness, the (5, ofstudy drowsiness, central-nervous6). Subjects the were of subjects who did not differ intake, and specific-macronutrient Changes in body weight, in body weight, selection. expressed as percentage daily-total-energy ofbasal val-
food
presence vertigo,
Statistical
All data ing mean,
analysis
were subjected standard error, to standard statistical and Students t tests for
ues, are shown in Figure 1 . subjects receiving the placebo did not show any significant change in their body weight during either study period (94.3 5.6 vs 93.2 5.3 kg, I SE, basal vs end-of-study value). In contrast, subjects receiving 5analysis includ- value HTP showed a significant weight loss at the end ofthe first period both paired
of
basal
weight
100
--f-v
i(-___
_f1-____
-
NS
-
98 NO DIET
--
DIET
96
GA
10
12
weeks
FIG
periods P
<
I. Mean body-weight modifications, expressed as percentage of the basal value, ofobservation. D, placebo: #{149}, 5-hydroxytryptophan (S-HTP). 5Significantly different 0.03. 55Significantly different from value at 6 wk for S-HTP group. 0.02. P <
during from
5-HYDROXYTRYPTOPHAN (99.7 reduction ofobservation final weight loss of the Analysis 5.9 vs 98.0 (98.0 was mean body 5.0 kg, P
<
TREATMENT by a greater second group the quantities patients diet evaluation groups of
OBESITY during always 2). of anorexia showed the different symptoms by 100% behavior the higher second than period those in the included
of their
5.0
5. <1, 0.02). P
In the weight.
in the in 90% of a
energy
as calculated
subjects.
Among
included and
subjects reports, showed group during either period ofdaily observed significant, energy intake from at the end of the nor was the
changes in the placebo questionnaire, early satiety was reported spontaneous reduction subjects receiving 5-HTP during the first 1021 to 9778 907 kJ/d nods, respectively. Reports of early satiety was not decrease statistically cantly to 8644 group. higher Reports for of subjects nausea, receiving which during the last may The two groups 5-HTP was
and second study pewere always signifithan for period, the reported were to 20%, a transitory were (Fig 3). not control by
episodically
1 3 19 ki/d observed during the diet nificant reduction of total energy intake
HTP
total 647 The group intake that
from 13528
energy kJ/d total intake in the
period. There was a sig80% of subjects on 5-HTP in subjects receiving 5significantly reduced during to 7892 773 kJ/d. In these subjects, suggesting that this symptom a further significant reduction to 5326 effect of 5-HTP administration. study observed remained period. in macronutrient unmodified selections. in the reported differently by the
A specific
behavior protein
The occurrence of side effects such as weakness, myalgia, control drowsiness, vertigo, diarrhea, and stipsis were investigated. All In the 5-HTP group, protein of these symptoms were equally distributed in both groups of during the first period to values patients with no differences between the two periods of obserduring the second half of the vation (Fig 4). The total urinary 5-HIAA excretion showed a reduced, the control showed at was not50-fold difference group for subject-compliance a signifithe end between with the two groups and provided evidence treatment (Fig 5).
intake, though basal value for receiving intake of followed period 5-HTP
Conversely,
Discussion
role of amino acids in the regulation data of suggesting may modify of food intake has in by by experimental acid concentrations brain availability that changes food intake amino acid
carbohydrate
in the changes
dietary similar
was even lower than the quantities included been supported prescription. Finally, the lipid intake showed plasma amino to those observed for carbohydrates although affecting the
neurotransmitter
ENERGY
INTAKE
PROTEIN
INTAKE
12
12
we.ks
12
l2ws.ks
PLACEBO
S - HIP
PLACEBO
HIP
CARBOHYDRATE
INTAKE
LIPID
INTAKE
350
*0
C PLACEBO
12
B S
-
12w..ks
12
12
w..ks
HIP
PLACEBO
HIP
()
single B ()
diet
866
NO
20 40
CANGIANO
DIET
60 80 100 20 40
ET
AL
NO DIET
50 t 50 100 I I 20 40
DIET
00 50 100 20
DIET
60 50 100
Early
satisty
____________ _____________
I I I I I
40 I
I p<.0I
IIIII1
____
p<.005
I.
I
W#{149}skn#{149}ss
Nsus./Vomttng
pc04
Dtowsissss
Tssts
slt#{149}rstlon
Sm.tt
sttstlon
Dtsrthoss
I I
of no 0,
Msst
avirsion
of the side effects investigated in the two groups FIG 3. Prevalence of the symptoms used to evaluate anorexia in the FIG 4. Prevalence subjects during no-diet or diet periods of observation. There were two groups of subjects during no-diet and diet periods of observation. significant differences between groups or study periods. 5Significantly different from no diet for 5-hydroxytryptophan (5-HTP) statistically placebo; 0, 5-hydroxytryptophan (5-HTP). group, P < 0.01 . 0, placebo: 0, S-HTP.
precursors volved in
( 1 8). the
Of
the
two of
major feeding,
neurotransmitter the
systems
in-
low-energy
diet
period,
when
the
subverted
regulation
serotoninergic
seems
to Leibowitz sites and role eating believed patterns medial interact renergic and
play a specific role (19). A pharmacological et al (20), in fact, precisely characterized receptors involved as well as the possible serotonin selection. both the by activating in controlling In particular, energy satiety balance neurons natural serotonins and nutrient to influence of eating hypothalamus antagonistically receptors
and other carbohydrate-rich system as past small amounts. In addition, the study by the brain intake, argues physiological exerted patterns of action which in by favor 5-HTP. is usually of a specific Thus, in the subjects combination eaten effect
only in
in bread proteins,
ofendogenous
to dietary
ofa the circadian carbohydrate intake. localized in the relatively high serotonin seems to The ministration may raise and its 2-noradhave been responsible variations in activity (22, and also
incidence of nausea during 5-HTP adthe concern that it could, at least in part, for the 5-HTP effects observed. However, episodically. second 6-wk and weight
brain serotonin concentrations penmental animals result 1981, (24) people same important Wurtman have shown role in et al that large also (4) the
or serotoninergic in fluctuation ofappetite and more recently selection Hill system serotoninergic
note that for most subjects, nausea was reported in exNausea was significantly less frequent during the 23). In period when the greater reduction in food intake Blundell plays in loss was observed. an intensity and never obese We believe that the The lack be the control and with compliance
especially
Finally, when present, nausea was of low caused a subject to drop out of the study. effect of nausea on weight loss was negligible. reduction of body weight observed in both study periods (ie, both without diet) was likely due to subjects nonprescriptions as demonstrated by diet of this study seem to in the confirm regulation the
counteracted synthesis. concentrations fluramine and the drugs (12, reduce incidence was
pharmacologically
Pharmacological manipulation with serotoninergic-active and fluoxetine has been body weight in obese patients of side effects reported by higher study obese loss present during than we that reported that
brain like
to control food intake reports. In conclusion, (12, 1 3). Nevertheless, specific role played subjects receiving both in oral the control groups of food (14).
500 mg/24
h
by the
serotoninergic
system
observed
5-HTP intake
subjects without
those previously of observation, prescribed in of both body when subjects reduction charbread to the during during evalre- FIG the during and referred altered of
400L
300 lot-
subjects receiving 5-HTP at doses similar to those the previous study showed a significant reduction weight and daily carbohydrate intake. Moreover, were both actenstic second the uation duction at of in diet-free total given indices of a low-energy was the first lunch observed. Italian or dinner), of the intake period carbohydrate diet diet a further Because (ie, the early study intake. was pasta first, may also significant of the satiety have However,
meal-structure
protein
i1HHH
B 2 4 6 8 10 12 B 2 4 5 6
HTP
81012
weeks
PLACEBO
a significant observed
carbohydrate
groups
excretion
5-HYDROXYTRYPTOPHAN of feeding behavior was in fact followed in humans. The by a reduction to administration of both daily of total
IN
OBESITY
867
and carbohydrate intakes followed weight. The optimal adherence as the this obesity. good tolerance may to 5-HTP be safely used substance
treatment
treatment
B
14.
References
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