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Le Svetol ®, un extrait de café vert décaféiné, induit une perte de poids et augmente le ratio masse maigre sur masse grasse chez des volontaires en surcharge pondérale

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  • Indigo therapeutics

Abstract and Figures

Pour tester les effets du Svetol®, un extrait de café vert décaféiné possédant un ratio spécifique entre l’acide 5-caféyl-quinique (acide chlorogénique) et les autres isomères d’acides caféylquiniques, sur la perte de poids, 50 volontaires ayant un indice de masse corporelle (IMC) supérieur à 25 ont été sélectionnés. Ils ont été randomisés en deux groupes : l’un (n = 20) recevant le placebo, l’autre (n = 30) recevant le Svetol® en parallèle d’une alimentation légèrement hypocalorique. Chaque volontaire consomme une capsule de Svetol® ou de placebo deux fois par jour pendant 60 jours, au moment des repas principaux. Le poids, l’IMC, le ratio masse maigre/masse grasse (MM/MG) et l’auto-évaluation de l’aspect physique ont été déterminés à Jo et J60. Après 60 jours de traitement, une réduction significative du poids de 4,97 +/- 0,32 kg (5,7 %) a été observée dans le groupe Svetol® comparé au groupe contrôle (p < 0,001). Le ratio MM/MG est augmenté de façon significative dans le groupe Svetol® comparé au groupe contrôle : 4,1 +/- 0,7 %vs 1,6 +/- 0,6 % respectivement (p < 0,01). Ces résultats démontrent que le Svetol® est capable d’augmenter l’effet d’une alimentation légèrement hypocalorique chez des volontaires ayant des problèmes de surpoids. Cet effet pourrait être expliqué par une meilleure utilisation des graisses et par la prévention de leur accumulation.
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Svetol®, green coffee extract, induces weight loss and increases the lean to fat mass ratio
in volunteers with overweight problem
Dellalibera O°, Lemaire B and Lafay S
° Ospedale SS. Antonio e Margherita, Dipartimento Medico-Ambulatorio Obesità, Tortona, Italy
Berkem®, Le Marais ouest, BP 4, 24 680 Gardonne, France
ABSTRACT
In order to test the effects of Svetol®, a green coffee extract rich in chlorogenic acids with specific ratio between
5-caffeoylquinic acid and others caffeoylquinic acid isomers, on weight loss, 50 volunteers with body mass
index superior to 25 were selected. They were randomized in two groups, control group (n = 20) receiving a
placebo, treated group (n = 30) receiving Svetol®. Each volunteer took one capsule of Svetol® or placebo twice a
day with the main meal, for 60 days. Changes in weight, body mass index (BMI), Muscle Mass/Fat Mass ratio
(MM/FM) and self-evaluation of physical aspect were recorded at T0 and T60. After 60 days of treatment, a
mean reduction in weight of 4.97 +/- 0.32 kg (5.7%) was observed in the Svetol® group compared to control
group in which the mean reduction was 2.45 +/- 0.37 kg (2.9%) (p < 0.001). Consequently, body mass index
decreased significantly in the Svetol® group compared to the control group. Moreover, MM/FM ratio was
increased significantly in the Svetol® group compared to the control group: 4.1 +/- 0.7% vs 1.6 +/- 0.6
respectively
(p = 0.01). The significant decrease of weight, boby mass index and fat mass showed that Svetol® is able to
exacerbate the effect of a bland low caloric diet in volunteers who are overweight. This effect could be explained
by increasing the consumption of fatty deposits, as shown by the change in the MM/FM ratio, and by preventing
them from being accumulated.
To conclude, Svetol® could be used to aid the recommended diet in a useful and positive manner.
Key words: chlorogenic acids, Svetol® , weight, muscle mass/fat mass ratio
INTRODUCTION
Hydroxycinnamic acids are one of the major classes
of phenolic compounds. They are present in a large
variety of fruits and vegetables [1, 2]. The major
representative of hydroxycinnamic acids in food is
caffeic acid. It largely occurs conjugated with
quinic acid as in chlorogenic acid (5-caffeoylquinic
acid) (Figure 1). Coffee, one of the most widely
consumed beverages in the world, is the major
dietary source of chlorogenic acids.
Chlorogenic acid has antioxidant properties showed
by its ability to scavenge various free radicals when
tested in vitro [3-5]. Moreover, chlorogenic acid
reduces glucose uptake by favouring the dissipation
of the Na+ electrochemical gradient [6] and inhibits
the activity of hepatic glucose-6-phosphatase which
is implicated in glucose homeostasis [7, 8].
In vivo, when ingested under coffee form,
chlorogenic acid increases the plasma antioxidant
capacity [9]. Chlorogenic acid is also able to
reverse the prooxidant effects of drugs such as
paraquat [10] and have been reported to prevent
different cancers and cardiovascular diseases in
several experimental studies on animal models [11-
15]. Therefore, we hypothesized that chlorogenic
acid modulating glucose metabolism and
decreasing oxidative stress could limit overweight,
obesity development and secondary diseases
associated with as type 2 diabetes mellitus or
cardiovascular problems.
The aim of the present work was to evaluate if
Svetol®, a green coffee extract, could decrease
overweight in volunteers who had body mass index
(BMI) superior to 25.
SUBJECTS AND METHODS
Chemicals
Svetol®, decaffeinated green coffee extract, were
purchased from Berkem® SA (Gardonne, France).
Figure 1: Chemical structure of caffeic (A) and chlorogenic
acids (B)
A
CH
C
H
HOOC
OH
OH
3
4
HO
OH
HO
COOH
C
H
OH
C
O
O
OH
C
H
5’
4’
3’
B
Figure 1: Chemical structure of caffeic (A) and chlorogenic
acids (B)
A
CH
C
H
HOOC
OH
OH
3
4
HO
OH
HO
COOH
C
H
OH
C
O
O
OH
C
H
5’
4’
3’
HO
OH
HO
COOH
C
H
OH
C
O
O
OH
C
H
5’
4’
3’
B
Subjects
Fifty volunteers of both sexes, aged from 19 to 75,
were assigned at random to the group of 30 in
active treatment, and 20 in placebo treatment. The
participants of both groups were homogeneous in
weight and muscle mass/fat mass (MM/FM) ratio,
characterized by an overweight problem, BMI
superior to 25, and the acceptance of a bland low
caloric diet. Exclusion criteria were as follows:
acute or chronic gastro-intestinal pathologies;
gastro-intestinal infections and/or parasitosis;
severe hyper-tension (P.A. above 120 mm.); gastro-
intestinal cancers; serious or chronic metabolic
pathologies; big drinkers; assumption of products
for the control of weight and glycaemia; a known
intolerance to any of the components of the product
under examination.
Svetol® supplementation
The product was prepared in jars of 30 capsules
absolutely identical. Composition of the product
(active capsules) under experimentation was given
in table 1. Placebo capsules contained the same
components as the active capsule, Svetol® was
substituted by an identical quantity of maltodextrin
(200 mg).
Study design
Volunteers took one capsule with each main meal,
twice a day, for 60 days. Every participant was
given treatment sufficient for 30 days (two jars)
when they began the study (T0) and the rest (two
jars) at the T30 day.
Data collection and parameters of evaluation
In the course of the first check-up, the following
data were gathered: age, height, sex, weight, BMI,
MM/FM ratio, self-evaluation of physical aspect.
Changes in weight, BMI, MM/FM ratio, self-
evaluation of physical aspect were recorded again at
T60. An evaluation of compliance and verification
of the presence of side effects was undertaken at
T30 and T60.
MM/FM ratio was determined by Bioelectric
Impedance Analysis. Self-evaluation of physical
aspect was done by scale from 0 = very negative to
10 = excellent.
Evaluation of effectiveness, compliance and
tolerability
At the end of treatment, effectiveness, compliance
and tolerability were verified with regard to the
end-points by comparing the changes in the data
recorded at T60 to those at T0.
Therefore, changes of weight, BMI, MM/FM ratio,
self-evaluation of physical aspect in the active
group were compared to those recorded in the
placebo group.
The effectiveness was based on those participants
who completed the study. Compliance and
tolerability were based on all participants.
Statistical analysis
Numerical values are mean +/- SEM (n = 20 for
control group or 30 for treated group). Data were
entered into Instat statistical analysis program
(Instat, San Diego, CA). Student t-test (parametric
test) or Mann-Whitney test (non-parametric test)
determined the difference between values.
Differences with p 0.05 were considered
significant.
RESULTS
Weight loss and Body Mass Index
After 60 days of treatment, a mean reduction in
weight of 4.97 +/- 0.32 kg (-5.7 +/- 0.3%) was
observed in the Svetol® group compared to the
control group in which the mean reduction was 2.45
+/- 0.37 kg (-2.9 +/- 0.4%). These means are
significantly different (p < 0.001) (Figure 2A).
Consequently, body mass index decreased
significantly in the Svetol® group compared to the
control group (-1.9 +/- 0.1 kg/m2 vs -0.9 +/- 0.1
kg/m2 ; p < 0.001 ) (Figure 2B).
Muscle Mass/ Fat Mass ratio
In Svetol® group, MM/FM ratio was increased
significantly compared to the control group: +4.1
+/- 0.7% vs +1.6 +/- 0.6 respectively (p =0.01)
(Figure 3).
Self-evaluation of physical aspect
No significant difference about the appearance was
observed between both groups at T60 (6.6 +/- 1.05
vs 6.5+/- 1.31 for placebo and Svetol® groups
respectively) but both groups observed an
amelioration of the physical appearance between T0
and T60 (p < 0.05 for each group).
DISCUSSION
Table 1: Composition of the Svetol
®
capsule
Svetol®
Starch
Magnesium stereate
Silica micronized
White gelatine
200
0.04
0.015
0.008
0.087
mg/capsule
Table 1: Composition of the Svetol
®
capsule
Svetol®
Starch
Magnesium stereate
Silica micronized
White gelatine
200
0.04
0.015
0.008
0.087
mg/capsule
Obesity is a serious public health problem [16].
Overweight and obesity are the cause of health
problems of varying degrees of seriousness:
asthenia, osteo-arthicular, psychological and cardio-
vascular problems.
The reality is that this condition has a negative
impact on the quality of life, and in the case of
obesity, it can even lead to a reduction in life
expectancy.
With the exception of serious neuro-endocrine
pathologies the problem is caused mainly by
lifestyle. A rational diet in quantity and quality,
combined with some physical exercise can help to
obtain some loss of weight. A change in lifestyle is
not simple so in order to reach the desired goal of
controlling weight pharmaceutical products are
used as well as nutritional supplements with various
compositions, fat burners, all with the aim of
contrasting the lack of balance between the number
of calories introduced and the number of those
consumed which leads to overweight. There is a
relationship between the amount of carbohydrates
in the diet and the amount of fats in the adipose
reserves since the carbohydrates are responsible for
most of the calories introduced [17] and the intake
of sugars reduces energy consumption. In normal
production and activity of insulin, the calories
introduced are burnt up without transforming the
lipids into stock. On the other hand, if the amount
of glucose present in the blood is in excess with
regards to its use and to the hepatic glycogenesis,
this excess glucose (owing to the insulin which has
been increased by the hyperglycemia) enters into
the adipocytes where it is stored as fat reserves
[18]. The consequences are: (i) the fat reserves are
not used to produce energy; (ii) an increase of
adipocytes.
In diets the lower quantity of carbohydrates
consumed is a way to “force” the organism to burn
up the fat which has been deposited in the
adipocytes and therefore to lose weight. It is
possible to improve the effect of the lower amounts
of carbohydrates consumed by exploiting the
hepatic activity to regulate the glycemia level.
When glucose level in the blood is lower than 1g/L,
the liver synthesized glucose-6-phosphate (G6P) by
an hexokinase, hydrolysed G6P by means of a
glucose-6-phosphatase and released glucose into the
bloodstream. It’s glycogenolysis. If this sequence is
interrupted the fatty deposits do not increase, but
are instead used for the production of energy.
The aim of the present work was to evaluate if
Svetol®, green coffee extract concentrated in
chlorogenic acids with specific ratio between 5-
caffeoylquinic acid and others caffeoylquinic acid
isomers, could decrease overweight in volunteers
by fat burning action as suggested by in vitro
studies showing inhibition of the activity of hepatic
glucose-6-phosphatase by 5-caffeoylquinic acid [7,
8].
The significant decrease of weight and fat mass
showed that Svetol® is able to exacerbate effect of a
bland low caloric diet in volunteers who were
overweight. This effect could be explained by
increasing the consumption of fatty deposits, as
shown by change in the MM/FM ratio, and by
preventing them from being accumulated.
From results presented here and bibliography,
Svetol®’s mechanism could be proposed: first of all,
associated with the diet, it inhibits glucose
absorption in the small intestine[6]. In addition, by
inhibiting the activity of glucose-6-phosphatase [7,
8], it limits the release of glucose into the general
circulation [19, 20] and therefore limits
insulinemia. This mechanism engenders two
results: (i) less fatty deposits in the adipose tissue
and a more difficult access into the adipose cells
owing to a reduction in insulin activity; (ii)
consumption of fat reserves, where there is a lack of
glucose, as a source of energy at the disposition of
Figure 3: Variation of muscle Mass/ fat Mass
ratio after 60 days of treatment (%). Values are
means +/- SEM, n = 20 for control group, n = 30
for Svetol
®
group. Means are significantly
different (**, p = 0.01 vs. control group).
0
1
2
3
4
5
6
Variation of
Muscle Mass/ Fat Mass (%)
Svetol
®
Control
B
Decrease of
Body Mass Index (kg/m
2
)
-2
-1
0
A
Weight loss (%)
Figure 2: (A) Weight loss (%) and (B) decrease of
BMI (kg/m
2
) after 60 days treatment. Values are
means +/- SEM, n = 20 for control group, n = 30
for Svetol
®
group. Means are significantly different
(*, p < 0.001 vs. control group).
-6
-4
-2
0
***
***
**
Svetol
®
Control
Svetol
®
Control
Figure 3: Variation of muscle Mass/ fat Mass
ratio after 60 days of treatment (%). Values are
means +/- SEM, n = 20 for control group, n = 30
for Svetol
®
group. Means are significantly
different (**, p = 0.01 vs. control group).
0
1
2
3
4
5
6
Variation of
Muscle Mass/ Fat Mass (%)
Svetol
®
Control
Svetol
®
ControlControlControl
B
Decrease of
Body Mass Index (kg/m
2
)
-2
-1
0
A
Weight loss (%)
Figure 2: (A) Weight loss (%) and (B) decrease of
BMI (kg/m
2
) after 60 days treatment. Values are
means +/- SEM, n = 20 for control group, n = 30
for Svetol
®
group. Means are significantly different
(*, p < 0.001 vs. control group).
-6
-4
-2
0
***
***
**
Svetol
®
Control
Svetol
®
ControlControlControl
Svetol
®
Control
Svetol
®
ControlControlControl
the organism and therefore, as in the previous case,
a case of loss of weight.
However, mechanism proposed depends on
bioavailability of chlorogenic acid. Recently, fate
and metabolism of chlorogenic acid (5-
caffeoylquinic acid) in the gastro-intestinal tract of
rats were explored to determine the form under
which this ester of caffeic acid is absorbed through
the different parts of the gut barrier.
After analysis of the different gastro-intestinal
contents, it appeared that chlorogenic acid is stable
in the stomach and the small intestine but cleaved
into caffeic acid in the caecum by the microflora
[21]. Consequently, stability of chlorogenic acid in
the small intestine is coherent with glucose
absorption inhibition in this part of the gut.
Moreover, whereas it was shown that chlorogenic
acid was hydrolysed into enterocytes before
secretion on the serosal side [22], it was absorbed
under intact form from the stomach [21] and found
in gastric vein and aorta without conjugation
(glucuronidation, sulfation or methylation). This
result suggests that chlorogenic acid is able to
rejoin the liver without modification, which is in
accordance with its activity of hepatic glucose-6-
phosphatase inhibition.
Thus, chlorogenic acid bioavailability studies
supported Svetol®’s mechanism proposed.
To conclude, Svetol® has demonstrated its validity
and could be used to aid the dietetics prescription in
a useful and positive manner.
BIBLIOGRAPHY
1. Clifford, M.N., Chlorogenic acids and
other cinnamates - Nature, occurence and
dietary burden. J. Sci. Food. Agric., 1999.
79: p. 362-372.
2. Manach, C., et al., Polyphenols - Food
sources and bioavailability. Am. J. Clin.
Nutr., 2004. 79(5): p. 727-747.
3. Ohnishi, M., et al., Inhibitory effects of
chlorogenic acids on linoleic acid
peroxidation and haemolysis.
Phytochemistry, 1994. 36(3): p. 579-583.
4. Rice-Evans, C.A., N.J. Miller, and G.
Paganga, Structure-antioxidant activity
relationships of flavonoids and phenolic
acids. Free Rad. Biol. Med., 1996. 20(7):
p. 933-956.
5. Foley, S., et al., Singlet oxygen quenching
and the redox properties of
hydroxycinnamic acids. Free Radic Biol
Med, 1999. 26(9-10): p. 1202-8.
6. Welsch, C.A., P.A. Lachance, and B.P.
Wasserman, Dietary phenolic compounds:
inhibition of sodium-dependant D-glucose
uptake in rat intestinal brush border
membrane vesicles. J. Nutr., 1989.
119(11): p. 1698-1704.
7. Arion, W.J., et al., Chlorogenic acid and
hydroxynitrobenzaldehyde: new inhibitors
of hepatic glucose 6-phosphatase. Arch
Biochem Biophys, 1997. 339(2): p. 315-
22.
8. Hemmerle, H., et al., Chlorogenic acid and
synthetic chlorogenic acid derivatives:
novel inhibitors of hepatic glucose-6-
phosphate translocase. J Med Chem, 1997.
40(2): p. 137-45.
9. Natella, F., et al., Coffee drinking
influences plasma antioxidant capacity in
humans. J Agric Food Chem, 2002.
50(21): p. 6211-6.
10. Tsuchiya, T., O. Suzuki, and K. Igarashi,
Protective effects of chlorogenic acid on
paraquat-induced oxidative stress in rats.
Biosci Biotechnol Biochem, 1996. 60(5):
p. 765-8.
11. Mori, H., et al., Inhibitory effect of
chlorogenic acid on methylazoxymethanol
acetate-induced carcinogenesis in large
intestine and liver of hamsters. Cancer
Lett, 1986. 30(1): p. 49-54.
12. Tanaka, T., et al., Inhibition of 4-
nitroquinoline-1-oxide-induced rat tongue
carcinogenesis by the naturally occurring
plant phenolics caffeic, ellagic,
chlorogenic and ferulic acids.
Carcinogenesis, 1993. 14(7): p. 1321-5.
13. Tanaka, T., et al., Inhibitory effects of
chlorogenic acid, reserpine, polyprenoic
acid (E-5166), or coffee on
hepatocarcinogenesis in rats and hamsters.
Basic Life Sci, 1990. 52: p. 429-40.
14. Zhou, J., et al., Protective Effect of
Chlorogenic Acid on Lipid-Peroxidation
Induced in the Liver of Rats by Carbon-
Tetrachloride or Co-60-Irradiation. Journal
of Clinical Biochemistry and Nutrition,
1993. 15(2): p. 119-125.
15. Suzuki, A., et al., Green coffee bean
extract and its metabolites have a
hypotensive effect in spontaneously
hypertensive rats. Hypertension Research,
2002. 25(1): p. 99-107.
16. Guy-Grand, B., Obésité: génétique,
physiopathologie et thérapeutique à l'aube
d'une révolution conceptuelle. 2005:
Institut Pasteur, Centre d'information
scientifique.
17. Liotta, S., Obesita e le adiposità
localizzate. 1974, Roma.
18. Anthoni, C. and N. Kolthoff, Fondamenti
di anatomia e fisiologia dell'uomo, C.E.
Ambrosina, Editor. 1977: Milano. p. 433.
19. Herling, A.W., et al., Pharmacodynamic
profile of a novel inhibitor of the hepatic
glucose-6- phosphatase system. Am J
Physiol, 1998. 274(6 Pt 1): p. G1087-93.
20. Simon, C., et al., Upregulation of hepatic
glucose 6-phosphatase gene expression in
rats treated with an inhibitor of glucose-6-
phosphate translocase. Arch Biochem
Biophys, 2000. 373(2): p. 418-28.
21. Lafay, S., et al., Chlorogenic acid is
absorbed in its intact form in the stomach
of rats. J. Nutr, 2006. 136(5); 1192-1197
22. Lafay, S., et al., Absorption and
metabolism of caffeic acid and chlorogenic
acid in the small intestine of rats. Br. J.
Nutr, 2006. under press.
Phytothe
´rapie expe
´rimentale
Le Svetol
®
,unextraitdecafe
´vert de
´cafe
´ine
´, induit
une perte de poids et augmente le ratio masse maigre
sur masse grasse chez des volontaires en surcharge ponde
´rale
O. Dellalibera
1
,B.Lemaire
2
,S.Lafay
2
1
Ospedale SS, Antonio e Margherita, Dipartimento Medico-Ambulatorio Obesita
`,Tortona,Italie
2
Berkem, Le Marais Ouest, 24680 Gardonne, France
Correspondance : e-mail : sophie.lafay@berkem.com
Re
´sume
´:Pour testerles effets du Svetol
®
,unextraitdecafe
´vert
de
´cafe
´ine
´posse
´dant un ratio spe
´cifique entre l’acide 5-cafe
´yl-
quinique (acide chloroge
´nique) et les autres isome
`res d’acides
cafe
´ylquiniques, sur la perte de poids, 50 volontaires ayant un
indice de masse corporelle (IMC) supe
´rieur a
`25 ont e
´te
´
se
´lectionne
´s. Ils ont e
´te
´randomise
´s en deux groupes : l’un
(n = 20)recevant le placebo, l’autre (n = 30) recevant le Svetol
®
en paralle
`le d’une alimentation le
´ge
`rement hypocalorique.
Chaque volontaire consomme une capsule de Svetol
®
ou de
placebo deux fois par jour pendant 60 jours, au moment des
repas principaux. Le poids, l’IMC, le ratio masse maigre/masse
grasse (MM/MG) et l’auto-e
´valuation de l’aspect physique ont
e
´te
´de
´termine
´sa
`J0 et J60. Apre
`s 60 jours de traitement, une
re
´duction significative du poids de 4,97 +/0,32 kg (5,7 %) a e
´te
´
observe
´e dans le groupe Svetol
®
compare
´au groupe contro
ˆle
(p < 0,001). Le ratio MM/MG est augmente
´de fac¸on
significative dans le groupe Svetol
®
compare
´au groupe
contro
ˆle : 4,1 +/0,7 % vs 1,6 +/0,6 % respectivement
(p < 0,01). Ces re
´sultats de
´montrent que le Svetol
®
est capable
d’augmenter l’effet d’une alimentation le
´ge
`rement hypocalo-
rique chez des volontaires ayant des proble
`mes de surpoids.
Cet effet pourrait e
ˆtre explique
´par une meilleure utilisation des
graisses et par la pre
´vention de leur accumulation.
Mots cle
´s: Acides chloroge
´niques – Svetol
®
– Poids –
Masse maigre/masse grasse (MM/MG)
Svetol
®
, green coffee extract, induces weight
loss and increases the lean to fat mass ratio
in volunteers with overweight problem
Abstract: In order to test the effects of Svetol
®
,agreen
coffee extract with specific ratio between 5-caffeoylquinic acid
and others caffeoylquinic acid isomers, on weight loss, 50
volunteers with body mass index superior to 25 were selected.
They were randomized in two groups, control group (n = 20)
receiving placebo, treated group (n = 30) receiving Svetol
®
with bland low calory diet. Each volunteer took one capsule of
Svetol
®
or placebo twice a day with main meal, for 60 days.
Changes in weight, body mass index (BMI), Muscle Mass/Fat
Mass ratio (MM/FM) and self-evaluation of physical aspect
were recorded at T0 and T60. After 60 days of treatment,
a significant reduction in weight of 4.97 +/0.32 kg (5.7 %)
was observed in the Svetol
®
group compared to control group
(p < 0.001). Moreover, MM/FM ratio was increased signifi-
cantly in Svetol
®
group compared to control group : 4.1 +/
0.7 % vs 1.6 +/0.6 respectively (p < 0.01). The significant
decrease of weight and increase of MM/FM ratio showed that
Svetol
®
is able to exacerbate effect of a bland low caloric diet in
volunteers who have overweight. This effect could be
explained by increasing the consumption of fatty deposits
and by preventing them from being accumulated.
Keywords: Chlorogenic acids – Svetol
®
– Weight – Muscle
mass/fat mass ratio
Introduction
Lesacideshydroxycinnamiques constituent une des
classes majeures de polyphe
´nols. Ils sont pre
´sents dans
de nombreux fruits et le
´gumes [3, 11]. L’acide hydro-
xycinnamique majoritairement repre
´sente
´dans l’alimen-
tation est l’acide cafe
´ique.Onletrouvetre
`slargement
conjugue
´avec un acide quinique, appele
´alors acide
chloroge
´nique(acide5-cafe
´ylquinique) (Fig. 1).
Le cafe
´, une des boissons les plus consomme
´es dans le
monde, est la source alimentaire principale d’acide chloro-
ge
´nique et de ses isome
`res. L’acide chloroge
´nique a des
proprie
´te
´s antioxydantes mises en e
´vidence par sa capacite
´a
`
pie
´ger diffe
´rents radicaux libres in vitro [4, 14, 15]. De plus,
il est capable de re
´duire l’absorption du glucose en favorisant
la dissipation du gradient sodique e
´lectrochimique [21] et
d’inhiber l’activite
´de la glucose-6-phosphatase qui est
implique
´e dans l’home
´ostasie glucidique [2, 6].
In vivo, lorsqu’il est inge
´re
´sous forme de cafe
´,lacide
chloroge
´nique augmente la capacite
´antioxydante plasmatique
[13]. Il est aussi capable de re
´verser les effets pro-oxydants de
Phytothe
´rapie (2006) Nume
´ro 4: 1–4
©Springer 2006
DOI 10.1007/s10298-006-0181-7
drogues telles que le paraquat [20] et de pre
´venir diffe
´rents
cancers et maladies cardio-vasculaires dans diffe
´rentes e
´tudes
expe
´rimentales sur des mode
`les animaux [12, 17-19, 22]. Ainsi,
l’acide chloroge
´nique, en modulant le me
´tabolisme du glucose
et en diminuant le stress oxydant, pourrait limiter le surpoids,
l’obe
´site
´et les maladies secondaires associe
´es telles que le
diabe
`te ou les proble
`mes cardio-vasculaires.
Le travail pre
´sente
´ici avait pour but d’e
´valuer si le Svetol
®
,
un extrait de cafe
´vert de
´cafe
´ine
´riche en acides chloroge
´ni-
ques, e
´tait capable de diminuer le surpoids de volontaires
ayant un indice de masse corporelle (IMC) supe
´rieur a
`25.
Sujets et me
´thodes
Compose
´schimiques
Le Svetol
®
, extrait de cafe
´vert de
´cafe
´ine
´,ae
´te
´fourni par la
socie
´te
´Berkem SA (Gardonne, France).
Sujets
50 volontaires des deux sexes, a
ˆge
´sde19a
`75 ans, ont e
´te
´
re
´partis de fac¸on randomise
´e en deux groupes, un groupe
recevant le Svetol
®
(n = 30), l’autre groupe recevant le
placebo (n = 20). Les participants des deux groupes
constituent une population homoge
`ne en termes de
poidsetderatiomassemaigresurmassegrasse(MM/
MG). Ils ont tous un proble
`me de surpoids, leur IMC e
´tant
supe
´rieur a
`25, et ont tous accepte
´de se soumettre a
`une
alimentation le
´ge
`rement hypocalorique pendant la dure
´e
de l’e
´tude. Les crite
`res d’exclusion sont les suivants :
pathologies gastro-intestinales aigue
¨s ou chroniques,
infections gastro-intestinales ou parasitoses, cancers gas-
tro-intestinaux, hypertension se
´ve
`re (pression arte
´rielle
supe
´rieure a
`120 mm Hg), maladies me
´taboliques chroni-
ques, forte consommation d’alcool, consommation de
produits re
´gulant le poids et/ou la glyce
´mie, intole
´rance
connue a
`un des composants du produit teste
´.
Supple
´mentationenSvetol
®
Le produit ou le placebo est conditionne
´dans des boı
ˆtes
sous forme de capsules (30 capsules par boı
ˆte) absolument
identiques. La composition du produit teste
´(capsules
actives) est donne
´e dans le Tableau 1.
Les capsules placebo contiennent les me
ˆmes composants
que les capsules actives, le Svetol
®
e
´tant substitue
´par une
quantite
´identiquedemaltodextrine(200mg).
Protocole
Les volontaires prennent une capsule deux fois par jour
pendant soixante jours, au moment des repas principaux.
Chaque participant posse
`de un traitement suffisant pour
un mois (2 boı
ˆtes) lorsqu’il de
´marre l’e
´tude (J0), le reste
du traitement e
´tant donne
´au jour J30.
Donne
´es collecte
´es et parame
`tres d’e
´valuation
Au de
´part de l’e
´tude (J0), les donne
´es suivantes ont e
´te
´
rassemble
´es : a
ˆge, taille, sexe, IMC, ratio MM/MG et
autoe
´valuation de l’aspect physique. A
`J60, les me
ˆmes
parame
`tres ont e
´te
´a
`nouveau enregistre
´s. Une e
´valuation
du suivi du protocole et une ve
´rification de la pre
´sence
d’effets secondaires sont entreprises aussi a
`J30 et a
`J60.
Le ratio MM/MG est de
´termine
´par analyse bioe
´lectrique
de l’impe
´dance. L’autoe
´valuation de l’aspect physique est
effectue
´egra
ˆce a
`une e
´chelle allant de 0 = tre
`sne
´gatif a
`
10 = excellent.
E
´valuation de l’efficacite
´,delatole
´rance
et du suivi du protocole
A
`la fin du traitement, l’efficacite
´,latole
´ranceetlesuivi
du protocole sont ve
´rifie
´s par comparaison des variations
obtenues sur les donne
´es enregistre
´es a
`J0 et a
`J60.
Ainsi, les changements de poids, d’IMC, de ratio MM/
MG et l’autoe
´valuation des aspects physiques du groupe
traite
´ont e
´te
´compare
´sa
`ceux qui ont e
´te
´mesure
´spourle
groupe placebo. L’efficacite
´ae
´te
´de
´termine
´esurlabase
des participants ayant acheve
´l’e
´tude, le suivi du protocole
et la tole
´rance se fondant sur l’ensemble des participants.
Analyses statistiques
Les valeurs nume
´riques donne
´es sont des moyennes +/
SEM (n = 20 pour le groupe placebo ou n = 30 pour le
groupe traite
´). Les donne
´es sont entre
´es dans le pro-
gramme d’analyse statistique Instat (Instat, San Diego,
CA). Un test de Student (test parame
´trique) ou un test de
Mann-Whitney (test non parame
´trique) a permis de
de
´terminer les diffe
´rences entre les valeurs. Les diffe
´rences
avec p < 0,05 sont conside
´re
´es significatives.
A
CH
C
H
HOOC
OH
OH
3
4
HO
OH
HO
COOH
C
H
OH
C
O
O
OH
C
H
5’
4’
3’
B
C
Fig. 1. Structure chimique des acides cafe
´ique (A) et chloroge
´nique (B)
Tableau 1. Composition d’une capsule de Svetol
®
mg/capsule
Svetol
®
200
Amidon 0,04
Ste
´arate de Magnesium 0,015
Silice micronise
´e0,008
Ge
´latine blanche 0,087
2
Re
´sultats
PertedepoidsetIMC
Apre
`s soixante jours de traitement, une re
´duction
moyennesignificativede4,97+/0,32 kg (–5,7+/0,3 %)
est observe
´edanslegroupetraite
´(Svetol
®
)compare
´au
groupe placebo pour lequel la re
´duction moyenne est de
2,45 +/0,37 kg (–2,9 +/0,4%;p<0,001)(Fig.2A).Par
conse
´quent, l’IMC diminue significativement dans le
groupe Svetol
®
compare
´au groupe placebo (–1,9 +/0,1
kg/m
2
vs –0,9 +/0,1 kg/m
2
;p<0,001)(Fig.2B).
Ratio masse maigre/masse grasse (MM/MG)
Dans le groupe Svetol
®
,leratioMM/MGestaugmente
´
significativement compare
´au groupe placebo : +4,1 +/
0,7 vs +1,6 +/0,6 % respectivement (p = 0,01) (Fig. 3).
Autoe
´valuation de l’aspect physique
Aucune diffe
´rence significative sur l’aspect physique n’a
e
´te
´observe
´e dans les deux groupes a
`J60 (6,6 +/1,05 vs 6,5
+/1,31 pour les groupes placebo et Svetol
®
respective-
ment). Cependant, les deux groupes observent une
ame
´lioration significative de leur apparence entre J0 et
J60 (p < 0,05 pour chaque groupe).
Discussion
L’obe
´site
´est un important proble
`me de sante
´publique [5].
Le surpoids et l’obe
´site
´sontlacausedeproble
`mes de sante
´
plus ou moins graves tels que des proble
`mes oste
´o-
articulaires, cardio-vasculaires mais aussi psychologiques.
Cet e
´tat physique a un impact ne
´gatif sur la qualite
´de vie
et, dans le cas de l’obe
´site
´, peut engendrer une re
´duction
de l’espe
´rancedevie.
A
`l’exception des pathologies neuroendocriniennes,
l’origine du proble
`me est ge
´ne
´ralement le style de vie. Une
alimentation de qualite
´et limite
´e en quantite
´,associe
´ea
`des
exercices physiques re
´guliers, peut aider a
`obtenir une perte de
poids, cependant un changement de style de vie n’est pas
simple. Ainsi, dans le dessein d’atteindre l’objectif de contro
ˆler
son poids, des produits pharmaceutiques sont utilise
´saussi
bien que des supple
´ments nutritionnels de diffe
´rentes
compositions, bru
ˆle-graisses ou composition qui permet de
diminuer la balance entre le nombre de calories consomme
´es
et le nombre de calories de
´pense
´es.
Par ailleurs, il existe une relation entre la quantite
´de
glucides dans l’alimentation et la quantite
´de graisses dans les
re
´serves adipeuses, les glucides e
´tant responsables de
la majorite
´descaloriesinge
´re
´es [10] et leur ingestion re
´duisant
la consommation d’e
´nergie endoge
`ne. Apre
`sunrepas,sila
production et l’activite
´de l’insuline sont normales, le glucose
inge
´re
´est « bru
ˆle
´», transforme
´en e
´nergie (par l’interme
´diaire
de la glycolyse) ou accumule
´sous forme de glycoge
`ne (c’est la
glycogene
`se he
´patique). Cependant, si l’apport alimentaire est
trop important, la glycolyse et la glycogene
`se he
´patique
saturent et l’exce
`sdeglucosepre
´sent dans le sang entre dans
les adipocytes (gra
ˆce a
`l’insuline dont la se
´cre
´tion est
augmente
´e par l’hyperglyce
´mie) ou
`il est stocke
´sous forme
de lipides [1]. Les conse
´quences sont alors les suivantes :
–les re
´serves lipidiques ne sont pas utilise
´es pour
produire de l’e
´nergie ;
une augmentation du nombre d’adipocytes est observe
´e.
Une faible consommation de glucides oblige donc
l’organisme a
`utiliser les lipides stocke
´sdanslesadipo-
cytes et permet ainsi de perdre du poids. Il est alors
possible d’augmenter cet effet en modulant les activite
´s
he
´patiques re
´gulant la glyce
´mie.
Lorsque la glyce
´mie est infe
´rieure a
`1g/L,lefoielibe
`re
du glucose stocke
´sous forme de glycoge
`ne et synthe
´tise
du glucose-6-phosphate au moyen d’une hexokinase. Ce
glucose-6-phosphate est ensuite hydrolyse
´gra
ˆce a
`la
glucose-6-phosphatase, le glucose re
´sultant est de
´verse
´
dans la circulation sanguine : c’est la glycoge
´nolyse. Si
B
Diminution de
l’IMC (kg/m 2)
-2
-1
0
A
Perte de poids (%)
-6
-4
-2
0
***
***
Svetol
®
Contrôle
Svetol
®
Contrôle
2)
®®
®®
Fig. 2. (A) Perte de poids (%) et (B) diminution de l’IMC (kg/m
2
)apre
`s 60 jours
de traitement. Les valeurs sont les moyennes +/SEM, n = 20 pour le groupe
contro
ˆle, n = 30 pour le groupe Svetol
®
. Les moyennes sont significativement
diffe
´rentes (***, p < 0,001 vs. contro
ˆle)
0
1
2
3
4
5
6
Variation du ratio
Masse maigre / Masse grasse (%)
Svetol
®
Contrôle
**
Fig. 3. Variation du ratio Masse maigre/Masse grasse apre
`s 60 jours de traitement (%). Les
valeurs sont les moyennes +/SEM, n = 20 pour le groupe contro
ˆle, n = 30 pour le
groupe Svetol
®
. Les moyennes sont significativement diffe
´rentes (**, p = 0,01 vs. contro
ˆle)
3
cette se
´quence est interrompue, les lipides stocke
´sdansles
adipocytes sont alors utilise
´s pour produire de l’e
´nergie.
L’objectif du travail pre
´sente
´ici e
´tait d’e
´valuer si le Svetol
®
,
un extrait de cafe
´vert de
´cafe
´ine
´riche en acides chloroge
´niques
et posse
´dant notamment un ratio spe
´cifique entre l’acide
5-cafe
´ylquinique et les autres isome
`res cafe
´ylquiniques,
pouvait diminuer le surpoids de volontaires gra
ˆce a
`une action
«bru
ˆle-graisse » comme cela a e
´te
´sugge
´re
´par des e
´tudes in
vitro montrant une inhibition de l’activite
´de la glucose-
6-phosphatase he
´patique par l’acide 5-cafe
´ylquinique [2, 6].
La baisse significative de poids, et particulie
`rement de
la masse grasse, met en e
´vidence que le Svetol
®
est capable
d’augmenter les effets d’un re
´gime faiblement hypocalo-
rique chez des volontaires ayant des proble
`mes de surpoids.
Ceteffetpourraite
ˆtre explique
´par une augmentation de
la consommation des lipides stocke
´s comme cela a e
´te
´mis
en e
´vidence par l’augmentation du ratio MM/MG, et par la
pre
´vention de l’accumulation de ces lipides.
A
`partir de ces re
´sultats et de la bibliographie, un me
´canisme
d’action du Svetol
®
peut e
ˆtre propose
´: tout d’abord, associe
´a
`
l’alimentation, il inhiberait l’absorption de glucose au niveau
de l’intestin gre
ˆle [21]. Par ailleurs, en inhibant l’activite
´de la
glucose-6-phosphatase [2, 6], il limiterait la libe
´ration de
glucose issu du glycoge
`ne dans la circulation ge
´ne
´rale [7, 16] et
l’insuline
´mie. Ce me
´canisme engendrerait alors deux re
´sultats
aboutissant a
`une perte de poids :
un moindre stockage des lipides dans les adipocytes,
la re
´duction de l’insuline
´mie diminuant l’accessibilite
´aux
cellules adipeuses ;
– l’utilisation des re
´serves lipidiques comme source
d’e
´nergie pour compenser le manque de glucose.
Cependant, le me
´canisme propose
´de
´pend de la biodis-
ponibilite
´de l’acide chloroge
´niqueetdesesisome
`res.
Re
´cemment, le devenir et le me
´tabolismedelacide
chloroge
´nique dans le tractus gastro-intestinal de rats
ont e
´te
´e
´tudie
´safindede
´terminer sous quelle(s) forme(s)
cet ester d’acide cafe
´ique e
´tait absorbe
´au niveau des
diffe
´rentes parties de l’appareil digestif.
Apre
`s analyse des diffe
´rents contenus gastro-intesti-
naux,ilestmisene
´vidence que l’acide chloroge
´nique est
stable dans les lumie
`res stomacale et intestinale mais
hydrolyse
´en acide cafe
´ique au niveau du caecum par la
microflore [8]. La stabilite
´de l’acide chloroge
´nique dans
l’intestin gre
ˆle est donc cohe
´renteavecuneinhibitionde
l’absorption du glucose dans cette partie du tube digestif.
De plus, alors qu’il a e
´te
´de
´montre
´que l’acide chloroge
´-
nique e
´tait hydrolyse
´dans les ente
´rocytes avant d’e
ˆtre
se
´cre
´te
´du co
ˆte
´se
´rique [9], il est absorbe
´intact au niveau
de l’estomac et retrouve
´dans la veine gastrique et l’aorte
non conjugue
´(glucuronidation, sulfatation, me
´thylation)
[8]. Ce dernier re
´sultat sugge
`re que l’acide chloroge
´nique
est donc capable d’atteindre le foie sans aucune modifica-
tion structurale, cela supportant son activite
´d’inhibition
de la glucose-6-phosphatase mise en e
´vidence in vitro. Les
e
´tudes de biodisponibilite
´de l’acide chloroge
´nique sou-
tiennent donc le me
´canisme d’action du Svetol
®
propose
´.
En conclusion, le Svetol
®
ade
´montre
´sa capacite
´a
`
favoriser une perte de poids et pourrait donc e
ˆtre utilise
´
aise
´ment pour renforcer les prescriptions die
´te
´tiques.
Bibliographie
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and hydroxynitrobenzaldehyde: new inhibitors of hepatic glucose
6-phosphatase. Arch Biochem Biophys 339(2): 315-22
3. Clifford MN (1999) Chlorogenic acids and other cinnamates. Nature,
occurrence and dietary burden. J Sci Food Agric 79: 362-372
4. FoleyS,NavaratnamS,McGarveyDJ,et al. (1999) Singlet oxygen
quenching and the redox properties of hydroxycinnamic acids. Free
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synthetic chlorogenic acid derivatives: novel inhibitors of hepatic
glucose-6-phosphate translocase. J Med Chem 40(2): 137-45
7. Herling AW, Burger HJ, Schwab D, et al. (1998) Pharmacodynamic
profile of a novel inhibitor of the hepatic glucose-6-phosphatase
system. Am J Physiol 274(6 Pt 1): G1087-93
8. Lafay S, Gil-Izquierdo A, Manach, et al. (2005) Chlorogenic acid
is absorbed in its intact form in the stomach of rats. J Nutr, under press
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metabolism of caffeic acid and chlorogenic acid in the small
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`localizzate, Roma
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of chlorogenic acids on linoleic acid peroxidation and haemolysis.
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glucose 6-phosphatase gene expression in rats treated with an inhibitor of
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4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis by
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Biotechnol Biochem 60(5): 765-8
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4
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... In another study, 50 overweight subjects aged 19-75 years were randomly allocated to receive a green coffee bean extract (Svetol) in capsule form for 60 days. 25 The investigators reported a significant change in body weight and BMI compared to placebo (p < 0.001). However, in this study, the blinding of the intervention is not clearly stated. ...
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