Eating behavior in obese adult

Carlo
Maurizio

and adherence subjects treated

Ceci,
Fabiola

to dietary prescriptions with 5-hydroxytryptophan12

Maria
Filippo oral ad-

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,

without intake, over

dietary these data over adherence and weight whether period administering

longer period of observation to dietary restriction could to obese hyperphagic

and to be improved

loss in obese
ofobservation tion could

a longer

subjects.

to dietary restricpatients were ran-

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

Downloaded from www.ajcn.org by guest on November 28, 2011

obese,

hyperphagic

adult

female

subjects

(mean 30 and of daily

loss was

patients

A reduction early satiety good tolerance to treat KEY

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

y I .7: SE) with studied. Hyperphagia

body mass indexes between was defined as the excess to

the energy need calculated activity. Subjects with glucose were excluded

hyperuricemia

WORDS serotonin, weight

tophan, bohydrates,

Study carThe Committee informed

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
(

of Rome, La were randomly or a placebo stearate The drug,

Sapienza. assigned

and

behavioral suggesting on eating

evidence that behavior brain both

either 5-HTP (900 mg/d) mannitol, and magnesium has dustries, secapsules in of a per day, patho- subdivided Pomezia, Italy).

composed (both from which was

ofcorn Sigma-Tau in the

two decades, influence I -4). Reported the serotoninergic in different in the

in humans played by Changes

studies in favor system in the diseases of further brain states a marked

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

ofanorexia experiencing (8, 9). Food metabolism

present

metabolism nutritional producing lateral

serotonin

During the first support wk periods. tions, whereas a 5040-kJ/d

different deprivation in the

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

in the availability ofbrain a potential mechanism

tryptophan; this by which behavioral

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). (

A variety serotonin been shown in food of

weight. Routine for each subject

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

SE: n = 10 for both

groups.

and

at

the

end to

of

each

period

of observation. excretion determined

compliance 3-indoleacetic by the Udenfriend Daily lection, sessed cluding working

treatment, 24-h urinary acid (5-HIAA) was also al (1 5). energy intake may define by using

chromatographic-colorimetnc et total which every as well a subjects a 3-d

method as diet single eating diary. by subjects instructed

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

macronutrient behavior, Food to were diaries,

2 wk

all beverages, days. Each before meals validated by

were compiled subject was and then a next of

for 3 consecutive Results carefully weigh

Downloaded from www.ajcn.org by guest on November 28, 2011

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

reweigh any kins signature.

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

both no-diet and diet beginning of study,

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

IN consumed were (Fig

OBESITY during always 2). of anorexia showed the different symptoms by 100% behavior the higher second than period those in the included

865 5-HTPin the

0.03) at the basal

followed end body intake, of the

of their

weight vs 94.7 of the 5% total no

period treated prescribed The from two

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

significant (Fig 2). The 1 1399

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

first study period further negligible

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

1033 showed second was intake

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

first study the

6 wk ofobservation be considered other symptoms of subjects

A specific

behavior protein

during the study was progressively were not further

period. reduced modified

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).

Downloaded from www.ajcn.org by guest on November 28, 2011

study (Fig statistically (Fig cant 2). 50%

2). The carbohydrate different from the subjects of their reduction

intake, though basal value for receiving intake of followed period 5-HTP

Conversely,

carbohydrates by a further during which

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

ofthe first reduction

study period. This was in the second study intake

significant the total The

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

()

FIG 2. Mean SE modifications of total periods of observation in the two groups

energy and of subjects.

single B ()

macronutrient basal records;

intakes during PD., prescribed

both (0) and no-diet diet.

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

meal food in significant

structure were allowed

was reduction with on may satiety

subverted

Downloaded from www.ajcn.org by guest on November 28, 2011

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,

combination of carbohydrates adherence 5-HTP early

appetite, prebeen lowhave and

ofendogenous

optimal receiving ofboth

to dietary

(19). In this process, with norepinephrine (2 ). 1Pharmacologically induced

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

scription observed is the consequence

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

macronutrient amounts demonstrated

especially

consuming authors have by

ofcarbohydrate-rich that such enhancing of agents reported brain

food. The behavior can serotonin serotonin dexfen-

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

of a significant group during the low-energy with dietary the results

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

13). In a previous to and adult weight

observed

administration by decreased subjects mood

5-HTP intake

subjects without

was followed affecting the

The results ofthe reported. In fact,

study seem the diet-free,

to confirm 6-wk period

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

5. Mean total 5-hydroxy-3-indoleacetic the l2-wk study period in both

groups

acid (5-1-IIAA) of subjects.

excretion

5-HYDROXYTRYPTOPHAN of feeding behavior was in fact followed in humans. The by a reduction to administration of both daily of total

TREATMENT 5-HTP energy

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

by a significant loss dietary prescription observed long-term in the

treatment

of body 12. as well 13. suggest that of

treatment

B
14.

References
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