Melissa officinalis - new technology

for brain & mind health

I. Vazquez, S. Buchwald-Werner

5. May 2015

Vitafoods Europe Conference – Cognitive Health

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Vital Solutions develops innovative condition specific natural health

ingredients for use in foods, dietary supplements, medicine devices and

cosmetics.

Based on a market-orientated dynamic strong R&D platform, we focus on

the development of natural ingredients which improve quality of human

life by feeling good and aging well. Our research is focusing on:

Digestive health & metabolism

Brain health

Anti-aging

Consumer are looking for natural support to improve cognitive

performance and to cope with daily requirements from high work load to

family issues, in a cool- headed, focused and structured way and without

compromising long-term health

Being smart is important to keep up with our performance based society

1. Vital Solutions- Company Introduction

3

Agenda

1. Consumer demand to improve mental performance

2. Biological targets for brain health

3. Melissa officinalis special extract for mental health

4. Melissa officinalis special extract – In vitro results

5. Melissa officinalis special extract – Human study to

investigate cognition and mood in a functional beverage

6. Application in food supplements and functional foods

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1. Consumer demand to improve mental performance

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Being smart is important to keep up with our

performance based society

Consumer are looking for natural support to cope with daily

requirements from high work load to family issues, in a cool-

headed, focused and structured way and without

compromising long-term health

The World Health Organization (WHO) says:

“Stress is one of the key health concerns”

Market products for mental health frequently combine several

ingredients supporting different mode of actions

Natural ingredients which combine different mode of actions

follow the market trend for natural, pure products and have

an advantage to gain consumers’ trust

1. Consumer demand to improve mental performance

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2. Biological targets for brain health

2. Monoamin

oxidase B

(MAO-B)

3. Gamma-

aminobutyric

acid (GABA) 4. Phospho

diesterase 4

(PDE4)

5. Adenosine

receptors

(A1,A2A)

Effects on

learning and

memory

Effects on mood

and memory

Effects on mood,

relaxation and

concentration

Effects on long

term memory

Effects on CNS

(excitation)

1. Muscarinic

receptor M1

http://www.cxvascular.com/nn-latest-news/neuro-news---latest-news/clinical-study-of-selective-muscarinic-m1-receptor-agonist-for-alzheimers-disease-patients-initiated

http://swissmodel.expasy.org/workspace/smtl/index.php?method=results&wt=1&pdbid=4a7aB

http://www.compoundchem.com/2014/02/27/chemical-structures-of-neurotransmitters/

http://www.nature.com/ijir/journal/v16/n1s/fig_tab/3901211f1.html#figure-title

http://www.diamond.ac.uk/Science/Research/Highlights/casestudy67.html

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Melissa officinalis leaf extract is obtained by water extraction

The proprietary Melissa officinalis leaf extract was especially

developed to support cognitive performance and mental health

In vitro studies investigating the potential CNS cholinergic

activity of different Melissa officinalis extracts confirmed that not

all extracts exhibit the expected CNS cholinergic receptor

binding properties

Phytochemical investigations and muscarinic M1 receptor

binding studies were used to select the proper raw material

Bluenesse® is standardized on muscarinic M1 receptor affinity

and on rosmarinic acid >6%

Bluenesse® is high quality, sustainable natural ingredient, which

is approved for use in dietary supplements & food

3. Melissa officinalis for mental health

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Anxiolytic & calming effects

aminobutyric acid (GABA)↑

GABA transaminase inhibition

by rosmarinic acid

Amelioration of

age-related cognitive deficit

Acetylcholine (ACH)↑

ACH esterase inhibition

by rosmarinic acid

Improved alertness and memory

Muscarinic M1 receptor agonistic effects↑

active compound(s) in lemon balm

Eff

ects

of

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st

lem

on

balm

vari

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es

Eff

ect

of

sp

ecia

l

lem

on

balm

vari

eti

es/

bre

ed

ing

lin

es

Bluenesse® guarantees all effects

3. Melissa officinalis for mental health

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4. Melissa officinalis special extract – In vitro study

T. Shinoe, M. Matsui, M.M. Taketo, T. Manabe. Modulation of Synaptic Plasticity by Physiological Activation of M1 Muscarinic Acetylcholine Receptors in the Mouse Hippocampus. The Journal of Neuroscience, November 30, 2005,

25(48):11194–11200

http://www.physiologie1.uni-erlangen.de/en/Alzheimer/index.shtml

Muscarinic M1 receptor

M1 receptors are most abundant in the brain (prefrontal cortex and

hippocampus) and they play an important functional role in higher

cognitive processes such as learning and memory

Its endogenous ligand is acetylcholine

Muscarinic M1 receptors are responsible for the efficient flow of

information between neurological cells, so-called “oscillation”, leading

to a better cognitive performance

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Muscarinic receptor binding was investigated in human

recombinant muscarinic M1 receptor expressed in CHO

(Chinese Hamster Ovary cells) for 3 different batches

Binding was measured by displacement of radio ligand

[3H ]pirenzepine (positive control)

Results:

Sample IC50-value (mg/ml)

Batch 1 1.26

Batch 2 0.75

Batch 3 0.40

Pirenzepine 0.0094

All batches showed specific

binding activity to the M1 receptor

Reduction of binding by more than

50% is considered to be significant

effect of the test compound

4. Melissa officinalis special extract – In vitro study

Receptor binding assays were conducted by Cereb, France

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To investigate effects on cognitive performance, stress & mood

Study design:

Double blind, randomized, placebo-controlled, balanced-crossover, monocentric

25 healthy people, ages 18-39, 8 male and 17 female

Non smoker

Study product formulation: water-based drink

2 test dosages of Melissa officinalis special extract 0.3g and 0.6g

Assessment after 1 and 3 hours

Controlled food intake on study days: e.g. no coffeine

The study was conducted by Prof. Andrew Scholey, Brain Institute at Swinburne

University, Australia

5. Melissa officinalis special extract - Human study

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Study Parameter:

1. DISS Method: Multi-purpose framework to investigate impact on

• Alertness

• Primary Memory - Word recall

• Mathematic processing

• Tracking

DISS is a validated method to investigate response to

stress (Wetherell et al, 2004).

Participants were required to simultaneously perform 4

tasks via computer for 20 minutes. Their accumulated

score was displayed in the central counter:

Mental Arithmetic:

“Additions”

The Stroop task, classic

psychological test for attention

& response inhibition: “To link

color name to color blocks”

Memory Search :

4 Letter code

“indication of single letter

appeared in the 4 letter code”

Visual monitoring for

psychomotor ability:“allow the

dot to travel, without letting it hit

the edge of the target, before

clicking on the reset button”

5. Melissa officinalis special extract - Human study

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Study Parameter:

2. Validated mood questionnaires

State-Trait Anxiety Inventory (STAI) to investigate anxiety

Bond-Lader mood scale to investigate mood (VAS)

Depression Anxiety and Stress Scale (DASS) - shortened version to

assess 3 negative affective states of depression, anxiety and stress

Symptoms checklist - 28 physiological / psychological problems

3. Determination of free cortisol - salivary samples using salivette

5. Melissa officinalis special extract - Human study

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Study flow:

Screening

1 practice day – visit 1

4 testing days – visit 2-5, separated by a wash out phase of 7 days

Testing day schedule:

STAI-T, DASS

Blocks

Symptoms checklist

5. Melissa officinalis special extract - Human study

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Results:

*

Mathematical processing

1h 3h

*

Working Memory

* 1h 3h

*

State anxiety

*

1h 3h

* *

1h 3h

Cortisol

Placebo

0.3g Lemon balm

0.6g Lemon balm

5. Melissa officinalis special extract - Human study

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Muscarinic M1

receptor (Agonist)

MAO-B (Inhibition)

PDE4 (Inhibition)

GABA

(GABA T- Inhibition)

Quadruple action

5. Melissa officinalis special extract - Summary

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Bluenesse® is a unique lemon balm extract

Bluenesse® is an exclusive Melissa officinalis extract developed

to support cognitive performance and mental health

Vital Solutions’ research and extensive know-how in natural products

enabled them to identify a special lemon balm breeding line

supporting cognitive effects, particularly alertness and memory

In vitro and human studies as well as phytochemical

investigation confirmed that Bluenesse® supports:

Alertness / concentration / mental focus

Working memory

A calm, positive mood

Ability to cope with occasional stress

Improvement of age-related cognitive impairment

5. Melissa officinalis special extract - Summary

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6. Application in food supplements and functional foods

1. Bluenesse® in energy drinks

As an alternative for caffeine, to follow the global

governmental recommendation

to reduce the use of caffeine

2. Bluenesse® in decaffeinated coffee

Get the mental boost and be still able to sleep

3. Bluenesse® for kids

For focus and concentration that kids may

need at school or at home

4. Bluenesse® in a chocolate bar as a healthy snack

For those who love chocolate and want

an extra benefit for cognitive health

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6. Application in food supplements and functional foods

5. Bluenesse® in food supplements

For those who prefer a traditional

application

6. Bluenesse® in dairy products as a meal before going to sleep

For those who want to have a relaxing time

and want to be able to disconnect from

work/ daily life’s problems in the evenings

7. Bluenesse® in a water based beverage for aging people

For those who want to maintain their cognitive

performance during aging

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Vital Solutions GmbH

Itxaso Vazquez

Hausinger Straße 6

D-40764 Langenfeld

Phone: +49 (0) 2173 10 98 205

E-Mail: Itxaso.Vazquez@vitalsolutions.biz

Thank you for your attention!

All information given in this presentation reflects our current knowledge and interpretation of relevant legislations and legal

practice. Vital Solutions expressly disclaims any responsibility for the suitability of this information for products and for any specific

or particular purposes intended by the user. Our suggestions do not release Vital Solutions´ customers from evaluating the

individual products as to their legal compliance. Vital Solutions does not assume any liability or risk involved in the use or

marketing of its products as the conditions of use are beyond its control. The user of the products is solely responsible for

compliance with all laws and regulations applying to the use of the products.

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