Clinical Study July 2009
MKG/BSL-0908 p1
CONFIDENTIAL
Clinical Study Evaluation of Cacti-Nea™’s diuretic effect in women showing water retention. Design of the clinical study : Monocentric, randomized, placebo-controlled, in parallel double-blind format 49 women divided into 2 groups Normal BMI, between 20 and 25 Aged between 20 and 60 28-days treatment Tested dosage of Cacti-Nea™ = 2g/day MKG/BSL-0908 p2
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Clinical Study
Parameters analysed during the study: Body water mass
Urinary parameters (sodium, potassium, uric acid)*
Body weight
Blood pressure
Body fat mass
Circumference: waist, hip, thigh, calf, ankle
Body lean mass *Urinary volumes/24H could not be measured within the framework of this study
MKG/BSL-0908 p3
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Clinical Study Process of the study Pre-inclusion
Inclusion
D-14
D0
Clinical exam
Clinical exam
2 weeks
D7
D14
D21
Clinical exam
Cacti-Nea™ 2g/d
1 week
1 week
Blood sampling
1 week
Placebo 2g/d
On the day of the visits : Collection of the 24h urines
Weighing, Bio-impedance analysis(Bodystat 1500MDD), anthropometric measures
MKG/BSL-0908 p4
D28
CONFIDENTIAL
1 week
Blood sampling
Clinical Study
Results presentation • per protocole population (47 women)* Placebo group: 24 women Cacti-Nea™ group: 23 women
• sub-group/FM, women who tend to gain body fat between D-14 & D0 (27 women) Placebo group: 12 women Cacti-Nea™ group: 15 women
* 2 volunteers did not respect the protocole and were withdrawn from the total population. MKG/BSL-0908 p5
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Results – per protocole population
Characteristics of the per protocole population at Day0 Average age
Average BMI at D0
Waist circumference at D0
Average weight at D0
Placebo
39.6
22.9
76.8 cm
60.4 kg
Cacti-Nea™
40.1
23.2
76.5 cm
61.3 kg
Body fat mass at D0
Body lean mass at D0
Body water mass at D0
Placebo
18.3 kg
42.1 kg
31.1 kg
Cacti-Nea™
18.9 kg
42.3 kg
31.2 kg
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Results – Sub-group/FM
Characteristics of the sub-group/FM at Day0 Average age
Average BMI at D0
Waist circumference at D0
Average weight at D0
Placebo
40.5
23.2
76.5 cm
59.8 kg
Cacti-Nea™
38.8
22.8
75.8 cm
61.2 kg
Placebo Cacti-Nea™
MKG/BSL-0908 p7
Body fat mass at D0
Body lean mass at D0
Body water mass at D0
18.8 kg
41 kg
30.6 kg
19 kg
42,2 kg
30.8 kg
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Results – Body Composition Per protocole Population No gain of body Fat Mass in the Cacti-Nea™ group Body fat mass variation between D0 & D28 1000
Up to +3kg of body fat mass in the Placebo group
Variation (g)
800 600 400 200 0 -200 -400
MKG/BSL-0908 p8
Placebo
Cacti-Nea
p= 0.0239
NS
CONFIDENTIAL
Results – Body Composition Sub-group/FM Sub-group Fat mass variation between D0 & D28 Placebo
Sub-group Fat mass variation between D7 & D28 Placebo
Cacti-Nea
1200
1200
900 Variation (g)
900 Variation (g)
Cacti-Nea
600 300 0
600 300 0
-300
-300
-600
-600
-900
-900
p= 0.0653
NS
p= 0.0273
Body fat mass D0 & D28 Significant trend in the Placebo group
MKG/BSL-0908 p9
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NS
Body Fat mass D7 & D28 Significant increase in the Placebo group
Results – Body Composition Per protocole population vs. Sub-group/FM Cacti-Nea™ seems to have a positive effect on the body composition balance. In the per protocole population , we observe a significant increase of the body fat mass in the Placebo group (+3.4%) whereas it does not vary in the CactiNea™ group. (Graph: Fat mass variation between D0 & D28).
This significant increase of the body fat mass in the Placebo group is confirmed in the sub-group/FM: +3.2% (Graphs : Sub-group fat mass variation between D0 & D28 and between D7 & D28)
The lean mass consistently follows the water mass evolution in both groups
MKG/BSL-0908 p 10
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Results – Body Composition
The gain of fat mass observed in women of the placebo group could be linked with two phenomenon: A reverse placebo effect : People selected for weight-management clinical studies could feel less guilty and allow themselves food misbehaviors. An effect “restriction/storage”: A strict restriction in sugar and fat could, as a paradox, favor the body fat storage in case of food misbehaviors. These misbehaviors and their consequences seem to be corrected and avoided thanks to Cacti-Nea™ whereas it is not the case in the Placebo group. MKG/BSL-0908 p 11
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Results – Water mass Per protocole population vs. Sub-group/FM Per protocole population
Sub-group/FM
Water mass variation between D7 & D28 Cacti-Nea
Placebo
0
0
-150
-150
-300
Variation ( g)
Variation ( g)
Placebo
Sub-group water mass variation between D7 & D28
-450 -600
-300 -450 -600
-750
-750
-900
-900
p= 0.0151
p= 0.0107
Cacti-Nea
NS
p= 0.0094
In this sub-group, Cacti-Nea™ induces a significant water mass reduction MKG/BSL-0908 p 12
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Results – Water mass Per protocole population vs. Sub-group/FM After 4 weeks treatment, a water mass decrease was observed in both groups on the per protocole population. After the first week: - Per protocole population: the water mass reduction observed in the CactiNea™ group becomes more important than the one observed in the Placebo group. (Graph : Water mass variation between D7 & D28).
- Sub-group/FM : the water mass loss is significant in the Cacti-Nea™ group whereas it is not significant in the Placebo group. (Graph: Sub-group water mass variation between D7 & D28).
The activity of Cacti-Nea™ in the organism may imply a physiological adaptation so that its effect can only be seen after a few days of treatment (D7). MKG/BSL-0908 p 13
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Results – Body weight Per protocole population After 4 weeks treatment, we observe a significant body weight loss in the Cacti-Nea™ group (between D7 & D28; D14 & D28; D21 & D28 ) whereas no effect is observed in the Placebo group. Body weight variation between D7 & D28 200
Up to 3.3kg of weight loss in the Cacti-Nea™ group
Variation (g)
0 -200 -400 -600 -800 Placebo
NS
MKG/BSL-0908 p 14
Cacti-Nea
p= 0.0487
CONFIDENTIAL
Results – Body weight Sub-group/ FM After 4 weeks treatment, we observe a body weight loss in the Cacti-Nea™ group (about -600g), according to a significant trend between D0 & D28. This weight loss becomes significant between D7 & D28, whereas no significant effect is observed in the Placebo group. Sub-group body weight variation between D0 & D28 Placebo
Sub-group body weight variation between D7 & D28 Placebo
Cacti-Nea
600
Variation (g)
Variation (g)
600 200 -200 -600
200 -200 -600
-1000
-1000
NS MKG/BSL-0908 p 15
Cacti-Nea
p= 0.0726 CONFIDENTIAL
NS
p= 0.0334
Results – Water Mass / Body Weight
Placebo vs. Cacti-Nea™ As no weight loss was observed in the Placebo group, we can consider that the water mass loss is entirely compensated by a fat mass gain. On the contrary, the water mass loss observed in the Cacti-Nea™ group goes along with a significant body weight loss in both studied populations : - Per protocole population : -0.430 kg (p=0.0487 between D7 & D28). - Sub-group/FM : -0.667 kg (p=0.0334 between D7 & D28).
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Results – Blood pressure Per protocole population Cacti-Nea™ does not show any side effect on blood pressure (systolic & diastolic) between D0 & D28, unlike other diuretic substances. Diastolic blood pressure variation between D0 & D28
Placebo
Cacti-Nea
1,5
mmHg
0 -1,5 -3 -4,5 -6
p= 0.0373
MKG/BSL-0908 p 17
NS
CONFIDENTIAL
No negative effect observed on blood pressure
Results – Blood pressure Sub-group/ FM In this sub-group, Cacti-Nea™ still does not show any side effect on blood pressure (systolic & diastolic) between D0 & D28, unlike other diuretic substances. Diastolic blood pressure variation between D0 & D28
150
100
120
80
90
60
mmHg
mmHg
Systolic blood pressure variation between D0 & D28
60 30
20
0
0
Placebo
NS
MKG/BSL-0908 p 18
40
Cacti-Nea
NS
Placebo
NS
CONFIDENTIAL
Cacti-Nea
NS
Results – Urinary parameters Per protocole population Urinary parameters and Mineral Balance: No significant difference observed between the Placebo group and the Cacti-Nea™ group concerning: • urinary rate of uric acid • urinary rate of sodium • urinary rate of potassium Cacti-Nea™ does not imply any side effect on the mineral balance : No excessive loss of mineral contrary to other diuretic substances.
MKG/BSL-0908 p 19
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Synthesis of the Results Per protocole population vs. Sub-group/FM Effects observed in the per protocole population are confirmed and even more notable in the sub-group/FM : the volunteers of the sub-group/FM seem to be more receptive to Cacti-Nea™. Water mass reduction between D7 and D28 : -0.647 kg in the Cacti-Nea™ sub-group/FM (Placebo: NS) ”Anti-Fat mass“ effect of Cacti-Nea™ against: +0.717 kg in the Placebo sub-group/FM Body weight loss between D7 and D28 : -0.667 kg in the Cacti-Nea™ sub-group/FM (Placebo: NS) In the Sub-group/FM, Cacti-Nea™’s effects are completed by an improvement of some anthropometrical parameters.
MKG/BSL-0908 p 20
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Results – Anthropometrical parameters Sub-group calf circumference variation between D7 & D28
Sub-group/FM
Placebo
Cacti-Nea
Sub-group ankle circumference variation between Placebo D0 & D28 Cacti-Nea 0,2
Variation (cm)
0,2 0,1 0 -0,1 -0,2
Variation (cm)
0,1 -0,3
0
NS
-0,1
p= 0.087
-0,2 -0,3
Sub-group waist circumference variation between PlaceboD14 & D28 Cacti-Nea
-0,4
p= 0.002
0,2
Up to 1.4 cm reduction of waist circumference in the Cacti-Nea™ group
Variation (cm)
NS
0,1 0
-0,1 -0,2 -0,3 -0,4
NS MKG/BSL-0908 p 21
CONFIDENTIAL
p= 0.0498
Results – Anthropometrical parameters Sub-group/FM In the sub-group/FM, anthropometrical parameters are significantly improved after 4 weeks of Cacti-Nea™ consumption. Between D0 and D28, the ankle circumference is significantly reduced in the Cacti-Nea™ group. (Graph : Sub-group ankle circumference variation between D0 & D28)
Between D7 and D28, the calf circumference is reduced according to a significant trend in the Cacti-Nea™ group. (Graph : Sub-group calf circumference variation between D7 & D28)
A significant reduction of waist circumference is observed in volunteers of the Cacti-Nea™ group between D14 & D28. (Graph : Sub-group waist circumference variation between D14 & D28)
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Discussion and Conclusions
Some element to discuss, & First Conclusions
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Discussion
The sub-group of women who tend to gain fat mass is particularly receptive to Cacti-Nea™. > A justified sub-group > Diuretic & Weight management : a potential solution against cellulite…
MKG/BSL-0908 p 24
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Discussion A justified sub-group This sub-group corresponds to women whose body fat mass increased before the beginning of the study (between D-14 pre-inclusion visit and D0 inclusion visit). = Fat mass increase, while they were not « treated » A lot of factors may influence the gain of fat mass (heredity, hormonal factors, food intake, lack of physical exercise…). This sub-group is absolutely legitimated : scientifically-speaking (evolution of fat mass observed before D0) and also strategically-speaking (27 volunteers out of 47 were concerned).
MKG/BSL-0908 p 25
CONFIDENTIAL
Discussion Diuretic and weight-management Cacti-Nea™ : A natural ingredient with DIURETIC and WEIGH-MANAGEMENT properties intimately linked. With Cacti-Nea™, the diuretic effect is followed by an improvement of the body composition and a moderate but steady weight loss. D0
4 weeks Cacti-Nea™
D7
Body adaptation
D14
D21
Growing diuretic effect Anti-fat mass effect Significant weight loss between D7 & D28, D14 & D28 and between D21 & D28
MKG/BSL-0908 p 26
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D28
Discussion Excess water reduction & Weight management : a potential solution against cellulite… The water mass reduction, the fat mass gain limitation, and the moderate weight loss observed can be considered as good indicators of Cacti-Nea™’s diuretic and weight management properties. On a targeted sub-group, Cacti-Nea™ also shows a positive effect on the silhouette. Excess water reduction / weight management / silhouette These results suggest that Cacti-Nea™ could have a beneficial effect on some kind of cellulite (adipose, aqueous or mixed cellulite)… For example, the significant effect of Cacti-Nea™ observed on ankle circumference reduction is to be linked with aqueous cellulite.
MKG/BSL-0908 p 27
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Conclusions Very positive results on a normal population (BMI between 20 & 25): Progressive induction of body water mass loss (linked to the diuretic effect already highlighted in the in vivo rat study)
Limitation of fat mass gain Help for weight control / moderate weight loss No side effect on blood pressure Preserved mineral balance
A particularly receptive population confirms the WEIGHT MANAGEMENT & WELL-BEING potential of the ingredient Cacti-Nea™ MKG/BSL-0908 p 28
CONFIDENTIAL
Conclusions Sub-group/FM (N=27) Placebo Body composition/ Weight
Anthropometrical sizes
Fat mass
(a)
Water mass
(a)
Body weight
(a)
Waist
(a)
Calf
(b)
Ankle
(a)
Acide urique
K+
Na+
Blood pressure Urinary parameters
(a): p<0.05 ; (b): p<0.1 MKG/BSL-0908 p 29
Cacti-NeaTM
CONFIDENTIAL
Many thanks for your attention !
MKG/BSL-0908 p 30
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