YUZIM® monography

Therapeutic indications:
Helps relaxation and stress reduction by enhancing alpha brain wave.
Promotes better sleep.

Pharmacokinetic and pharmacodynamics:

The cause of stress can be varied, for example environment, work or family and can be
trigger easily especially with age. Even if stress is a banal issue, it can have a big impact
in the organism. At short term stress can cause headache, fatigue, sleeping troubles
and concentrating difficulty, upset stomach and irritability. At long term it can lead to
serious issue like skin disease, high blood pressure, weight gain or heart disease.
YUZIM® is an essence of fruits obtains from Citrus junos Sieb ex. Tanaka with a special
extraction process. Citrus junos Sieb ex. Tanaka an Asian citrus native to Japan that
looks somewhat between a grapefruit and a mandarin and is commonly named Yuzu.

YUZIM® contains a high amount of polyphenols: limonin, nomilin, limonene,

bioflavonoids. YUZIM® also contains ascorbic acid, citric acid and antioxidants pigments
like carotenoids.

YUZIM® volatile polyphenols triggers the olfactory nerves via receptors located in the
olfactory mucosa. Olfactory nerves transmit signals to the central nervous system,
including limbic system and amygdala, which are in charge of emotions, mood and
memory. These systems also connected to the autonomic nervous system and
parasympathetic nervous system, which regulate breath rythm, heart rate and blood
pressure, body relaxation.

YUZIM®, even at low dose, triggers a physical response in the body and this effect is
long lasting even after the scent is gone.

Additionally, YUZIM® strengthens the blood vessels and promotes improvement in

blood circulation.

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YUZIM® targets stress impact on the body:

 Enhance alpha brain wave

 Reduce stress hormone
 Decrease stress and anxiety
 Improve sleep and concentration

Route of excretion of the active ingredients:

Hepatic and Renal excretion.

Clinical study:
A) Clinical evaluation of efficacy of YUZIM® against stress
1. TYPE OF STUDY
Double blind, two-arm, parallel group, placebo-controlled, single centre randomized
clinical trial study comparing the efficacy of YUZIM® to a Placebo.

2. STUDY OBJECTIVES
To evaluate the effect of YUZIM® on stress reduction by measuring Chromogranin A
level in Saliva.

3. LABORATORY
MEDICA Clinical testing unit.

4. STUDY POPULATION
20 healthy non-pregnant non-smokers women aged between 35 and 50 years old with
an average of 44 years old without any known disease. The participants were randomly
assigned to either consume 0.1 mL of YUZIM® or a placebo. None of the subjects had
history of CVD, hypertension and diabetes.

5. MEASUREMENTS
The subjects were required to abstain from eating and drinking except water and
brushing teeth 1h before the test. Mental stress (mental arithmetic) was provoked in
the subjects for 5 min. CgA concentrations were measured at 4 points: before the test,
at T0, T20 and T50. Each time, 1ml of saliva was collected and centrifuged. Using a

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Human chromogranin A EIA kit (Yanaihara institute, Tokyo), the CgA concentrations was
measured by the total proteins expressed as pmol/ml.

6. DURATION OF TREATMENT
The CgA concentrations were measured during 50 minutes after ingestion of 0.1 mL of
YUZIM® or a placebo.

7. RESULTS
The level of salivary chromogranin A after consumption of placebo and YUZIM® are
shown on the following table and graph:

ChromograninA (pmol/mL) Before 0 min 20 min 50 min

Placebo 0.95 0.45 0.7 1.7
YUZIM® 1.05 0.4 0.46 0.3

2
ChromograninA (pmol/mL)

1.5

0.5

0
Before 0 20 50
Time after stress loading (min)
Control YUZIM

ChromograninA (CgA) is an index of mental stress as its secretion increases with stress
loading. We observed that consumption YUZIM® decreased the level of salivary
chromogranin A while the placebo increased the level of stress marker. Furthermore, at
50 minutes, we observe the chromogranin A pick of secretion in saliva reduces by 1.4
pmol/mL in the YUZIM® group compare to placebo group.

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8. CONCLUSION AND DISCUSSION
The results showed that YUZIM® reduce significantly by 82% the chromogranin A pick
of secretion in saliva compare to placebo. The most visible results have been observed
for subjects aged 46 and 48 years old. These results suggest that a supplementation in
YUZIM® might have a safe therapeutic use in prevention of stress and anxiety and to
improve relaxation and quality of sleep with a special attention for aged peoples.

B) Effect of Yuzim on brain waves profile

1. TYPE OF STUDY
Double blind, two-arm, parallel group, placebo-controlled, single centre randomized
clinical trial study comparing the efficacy of YUZIM® to a Placebo.

2. STUDY OBJECTIVES
To evaluate the effect of YUZIM® on brain waves.

3. LABORATORY
MEDICA Clinical testing unit.

4. STUDY POPULATION
20 healthy non-pregnant non-smokers women aged between 35 and 50 years old with
an average of 44 years old without any known disease. The participants were randomly
assigned to either consume 0.1 mL YUZIM® or a placebo. None of the subjects had
history of CVD, hypertension and diabetes.

5. MEASUREMENTS
The subjects were required to abstain from eating and drinking except water 1h before
the test. The topography of Alpha and Theta brainwaves was measured at 30 minutes
after ingestion of YUZIM® in the 2 groups.

6. DURATION OF TREATMENT
The topography of brainwaves was measured at 30min after ingestion of YUZIM® after
ingestion of 0.1 mL of YUZIM® or a placebo.

7. RESULTS
The intensity of Alpha and Theta brainwaves after consumption of placebo or YUZIM®

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are shown on the following FFT (Fast Fourier Transform) relative power difference
graphs. The relative intensity varies from weak in blue to strong in red.
FFT relative power difference graphs at T30:
Control group: YUZIM®:

Theta and Alpha brainwaves are marker for stress and anxiety when weak or relaxation
mental state when strong. We observed that consumption YUZIM® increase expression
of Theta, Alpha 1 and 2 brainwaves.

8. CONCLUSION AND DISCUSSION

The results showed that YUZIM® increase significantly expression of Theta, Alpha 1 and
2 brainwaves. These results suggest that a supplementation in YUZIM® decrease
anxiety and stress and increase relaxation and concentration. We can conclude that
YUZIM® might be a safe therapeutic supplement in prevention of stress and anxiety.

Contraindications:
Hypersensitivity to the herbal extracts.

Special precautions:
Do not exceed the recommended daily dosage.

Dosage and route of administration:

The recommended daily dosage is 0.1 mL by oral intake.

1 Place Marie Curie, 74000 ANNECY, France

Tel.: +33 4 50 32 21 31 – Fax: +33 9 70 62 21 14