Meriva®

CurcuminPhytosome

Low-level chronic inflammation. Pioneering a contemporary approach to turmeric.

The concept of MERIVA®
based on the biomimetic principle
NATURE AS MEASURETM
sets off the energy ofa new historical cycle,
unavoidable today:a cycle in which the greatest levelof innovation is represented
by the intersection
between Nature and technology.
MERIVA®
#thelifeguardian

Contents

1. Executive summary
2. Background and reference market
3. The problem
4. The INDENA proposal
5. Benefits
6. Conclusion
7. Bibliography and online research material
8. Call To Action / Contacts

Executive summary

MERIVA® Curcumin Phytosome is a product that,
thanks to its characteristics, can represent
a reference model for a new type of relationshipbetween the active biological componentsof turmeric, namely curcuminoids, and themaintenance of our lives.
The MERIVA® concept is based on a biomimetic
scientific approach [bios = life; mimesis =imitation]. Observing Nature in all its forms andexploiting its beneficial effects on the lab bench has
been INDENA’s commitment for almost a century.
The Indena Phytosome, which is the basis
of MERIVA®, IS THE ONLY DELIVERY SYSTEM
OF BOTANICAL DERIVATIVES IN THE WORLDthat can claim a 100% foodgrade composition.
The application of the biomimetic principle
NATURE AS MEASURETM places this formulationout of the fierce and conceptually reductive
competition on the increase of bioavailability
levels. MERIVA® is much more: it optimizes
bioabsorption levels [NATURE AS MEASURETM]
according to the 3 basic parameters of
EFFECTIVENESS, TOLERABILITY OVER TIME, SAFETY.

1.

The clinical and scientific evidence gathered
since 2005 grants MERIVA® the roleof THE LIFE GUARDIANTM for the entire courseof our lives, since silent chronic inflammationis one of the great challenges of our time.
The clinically validated human dose resulting
from over 30 clinical studies is 1g, corresponding
to 200mg of curcuminoids. Such studies have not
only demonstrated the effectiveness of MERIVA®,
but also provided valuable insights into
the extremely high tolerability profileof the ingredient in the long term.
Sensitivity, scientific expertise, biomimetic scienceand critical thinking were the pillars that madethe development of MERIVA® Curcumin Phytosome
approach possible, exploring new potentials andsupporting its customers towards new futures.

The biomimetic approach of INDENA

The magic word is to mimic.
But to mimic what?
The answer is BIOSYSTEMS, Nature’s modelof diffused and creative intelligence, the functioningof natural molecules of biological interest, thus
replicating what molecules or their infinitely larger
and more complex assemblages do, for instanceenzymes and proteins.
For a whole generation of organic, inorganic,
biological and physical chemists, “mimicking”
biosystems is a continuous project framework
challenge.
Mimicking Nature, re-making it with the brain
power of researchers by building processes
and principles on the bench of a laboratory,
is irresistible for INDENA: not a mere embellishment
label, but a real scientific gem.
INDENA steps with rationality, attention and depthof views into a topic that today is a focal pointof the future and at which the company has beenworking for years.
The entry is that of natural derivatives, of theirinsightful and sensible use within the nutraceuticalfield, in an imitation of Nature aimed at achieving
advantages in terms of rationalization, simplification,
tolerability, health and people’s safety.

Background and reference market

In recent years the turmeric market has become
deeply crowded and “noisy”.
The attention paid to the original ingredientproducers compared to the brands that certify
curcumin-based products is scarce and limited
to a few very specific health-related sites.
There is general confusion about the terms
used, the absorption, the race forthe highest bioavailability and so on.
In essence, the sometimes too technical approach[and the related language] used by certain brands
confuses consumers who sometimes, without
expert guidance, cannot fully evaluate quality
and functionality.

The growing demand for quality
There is a growing need to scientifically support
consumers in making informed choices and avoiding
products of uncertain origins. They are now moredemanding of products backed up by a transparent
composition, obtained from production chains andprocesses carried out in full accordance to bestpractices and consistent with traditional dietary uses.

2.
Global Turmeric Market
By Region [2017]

EasternEurope

MEA

Japan

Latin
America

APEJ

WesternEuropeNorth
America

Source: Future Market Insights, Turmeric Market Report, 2017.

Attention to the maintenanceof our health
Consumers are adopting a healthier lifestyle.
The overweight population is increasingin European countries, as the United States.
And with increased age comes the increased riskof joint-related health conditions.
This generates a further escalation in the demand
for Curcuma longa as an important ingredientin their diet.

The increment of the markets
According to estimates by the Nutrition Business
Journal [NBJ], sales of turmeric in North America
reached $ 196 million in 2015 with an increaseof 20% over the previous year, and are expected
to reach $ 433 million by 2020.
Turmeric was the best-selling ingredient in herbal
medicine in 2016.
The Western European turmeric market is estimatedclose to US $ 800 million by 2017 and could increase
to a CAGR of 5.8% by 2027.
It is expected that the market will be valued at morethan US $ 1.300 million by the end of 2027.

The problem
Chronic inflammation is the silent killer of our health.
According to the World Health Organization,
more than a third of the 57 million deaths
each year in the world are provoked by chronic
diseases that are the main cause of death[cardiovascular diseases, type-2 diabetes,
hypertension, respiratory diseases and Alzheimer’s].
90% of these diseases have an inflammatory origin.
Chronic inflammation is mainly due to the Western
lifestyle, and understanding it has in fact becomea crucial goal of modern clinical research.
For centuries, scientists have debated whether
inflammation is good or bad for us.
Now they believe it is both: too little, and microbes
fester and spread in the body, or wounds fail to heal;
too much, and nearby healthy tissue can be degradedor destroyed.
The fire of inflammation must be tightly controlled:
turned on at the right moment and, just as critically,turned off.
Lately, however, several lines of research haverevealed that low-level inflammation can simmer
quietly in the body, in the absence of overt trauma
or infection, with profound implications for ourhealth.
Using advanced technologies, scientists havediscovered that heart attacks, diabetes andAlzheimer’s disease may be linked to smoldering
inflammation, and some researchers have evenspeculated about its role in psychiatric conditions.
As a result, understanding and controllinginflammation has become a central goal of modern
clinical investigation.
The internal research arm of the USA National
Institutes of Health recently designatedinflammation a priority, mobilizing several hundred
scientists and hundreds of millions of dollars
to better define its role in health and disease.

3.

The INDENA proposal

MERIVA®, THE LIFE GUARDIANTMMERIVA® is the patented Curcumin Phytosome
by INDENA, based on the scientific biomimetic
approach.
The application of the biomimetic principle
NATURE AS MEASURETM to its formulation
places MERIVA® out of the fierce and conceptually
reductive competition on the increaseof bioavailability levels, because with MERIVA®,INDENA has worked on the optimizationof bioabsorption levels [NATURE AS MEASURETM]
according to 3 basic parameters:
EFFECTIVENESS, TOLERABILITY OVER TIME, SAFETY.
Its level of bioavailability, absorption modality andtolerability over time make MERIVA® compatible
and appropriate to the permanent roleof THE LIFE GUARDIANTM over the levels of chronic
inflammation, during the entire course of our life.
Thanks to its Phytosome delivery system - whichtransports the 3 fundamental curcuminoids
in a phospholipidic formulation - systematic
supplementation with MERIVA® fosters
the maintenance of healthy level of inflammation.

4.
Effectiveness

MERIVA® shows a unique profileof plasma curcuminoids.
The dose of curcuminoids per 1gof MERIVA® is 200mg, which iscompletely in line with the average
Indian daily intake. This is the clinicallyvalidated dose and has proven effective
in over 30 human trials.

Tolerability over time
Numerous studies conducted on humans,even within a long-term scenario,
have validated the effectivenessof MERIVA®, proving that it can be taken
for extended periods of time, andmaking it appropriate for a long-termlife-maintenance strategy.

The average dose of curcumin in the Indian
diet is 2.5mg/kg [over 160mg/die foran adult]. Turmeric is mainly consumed
in an oily matrix that favors the absorptionof curcumin.
MERIVA® [with curcumin transported
together with phospholipids] isa sort of molecular translation of thisdietary habit. This is obtained without
resorting to pharmacological adjuvants
or synthetic ingredients, but instead
using simple interaction with a dietary
ingredient [phosphatidylcholine]
according to the unique Phytosome
delivery system.
MERIVA® is therefore the replicationof a dietary habit consolidated overthe centuries, because it mimics
its quantity and composition withthe added guarantee of rigorous
production standards in accordance
to absolute best practices.
Specific studies have also been conductedon safety in accordance with the mostmodern guidelines.

Visit http://www.MERIVA.info/en/MERIVA-bioavailable-curcumin/scientific-support/

MERIVA® contains all 3 curcuminoids[i.e. the active ingredients naturally
present in turmeric] in the same
proportions expected in Nature, and
it is the formulation with the highest
plasmatic levels of DMC [the mostpotent curcuminoid].

Introducing®
MERIVA

BIOMIMETICS is the science that studies the best
ideas in Nature and then imitates their design,plans and processes to solve human problems.
Summarizing the concept, one can speakof “innovation inspired by Nature”.
From the very notion of biomimetics in literatureand its philosophical origins, we distilled
the following concept:

Nature as
The strength of the primary concept of biomimetics is that Nature
is seen as the measure and the standard for judging appropriateness,sustainability and also the formal, strategic and ethical correctnessof our technological product and process innovations.
The central idea is that Nature, by necessity, has already solved manyof the problems we are dealing with. Plants and microbes are consummate
engineers. They have found what works, what is appropriate and what lasts
over time and why.
This is the true news of biomimetics: after 3.8 billion years of research anddevelopment, the failures have turned into fossils and what surrounds us is
the secret to survival.
So it is Nature, and only Nature, which can show us the way in a given
situation.
This is why NATURE AS MEASURETM is the biomimetic principle
chosen by INDENA for the design of its active ingredients basedon natural phytosomal extracts.

The basic steps of the biomimetic design
approach are:1
Identify / develop a brief for theneeds to be answered.

3
Explore / study: how does Nature
perform this function? How does
Nature NOT perform this function?

2
Translate / biologize the question,i.e. express the project brief froma biological point of view.

4
Discover: look for examples
in Nature that respond to thechallenge.

MeasureTM

5
Synthesize: find models andrepetitive processes within Naturethat do achieve success.

6
Emulate / develop ideas andsolutions based on natural models.

7
Evaluate how the identified solutionis aligned with the project brief andwith the principles of life, thus
the principles of success in Nature.

Researchers who pursue biomimetic approaches have barely
scratched the surface of biological inspiration. Biologists
from all disciplines have an extraordinary knowledge thatcan lead incursions into a much richer diversity of natural
systems. And this knowledge helps, encourages, orients andelectrifies the experimental approaches.

Advantages

The uniqueness of MERIVA® formulated curcumin
is its Phytosome delivery system, basedon the application of the biomimetic principle
NATURE AS MEASURETM.
The Phytosome delivery system within the fieldof food supplements was pioneered and developedby INDENA more than 20 years ago.
The INDENA Phytosome is the only delivery systemin the world entirely made of natural elements
and for this reason is thoroughly food grade,as it manages to mimic the absorption of a fatty
meal [fatty meals increase the absorption due to bile
acids], such as curcumin / curcuminoids mixed withmilk, a combination known as “golden milk”.
Therefore, the Phytosome delivery system
by INDENA is not only natural, but contains
phospholipids that are naturally present
in the cells of our body.
In the world of food supplements it is essential
to make sure that there are no “non-food grade”
excipients.
For all these reasons, MERIVA®
Curcumin Phytosome is not only BIOAVAILABLE
and BIO-ABSORBABLE at an endogenous level,
but EFFECTIVE, TOLERABLE OVER A LONGPERIOD OF TIME AND SAFE.

In almost 100 years of presence on the market,
the commitment of INDENA has constantly focusedon 2 main objectives: the development of extractive
practices that guarantee the absolute highest quality
standards of the extracts, and the finalizationof processes able to reproduce the action
mechanisms developed by Nature, to equip themwith an appropriate delivery.
In recent years, INDENA has used its capitalof profound scientific knowledge to further
increase the safety of its ingredients, developinga strategy that can map even the genetic identityof the raw materials used for its botanical extracts.
As no universal Genomic ID method is available,
this knowledge has allowed INDENA to develop
species-specific DNA identification analytical tools.
As part of its quality system, INDENA is able to apply
the appropriate technology to each case.

MERIVA® was independently endorsed by
the prestigious Cleveland Clinic in the US as the
curcumin formulation of choice in the turmeric market
Visit https://health.clevelandclinic.org/2015/08/
7-tips-for-taking-turmeric-infographic/

Find out more at http://www.indena.com/quality/dna-barcoding/

5.

MERIVA
at a glance®

Conclusion

6.

Is based on a natural and foodgradedelivery system [Phytosome] of astandardized turmeric extract containing
the full bouquet of curcuminoids,
not just curcumin.

Is documented with preclinical and clinicalpharmacokinetic studies as an orally
bioavailable and bioabsorbable product,with measurements related to the
3 curcuminoids of the natural mixture.

Is supported by GLP preclinical safety
studies.

Is proven to have a long term hightolerability profile demonstrated in an 18
month clinical study with no side effects.

Stands as the most pre-clinicallyand clinically documented curcuminbioavailable formulation.

Has been documented with over 30 clinicalstudies in 10 different conditions involving
2000 subjects.

Is now supported by different clinicalstudies validating its efficacy in the sports
nutrition and muscular preservation
categories.

Is the curcumin formulation of choice
for leading practitioners and their patients.

Was independently endorsed by theprestigious Cleveland Clinic in the US
as the curcumin formulation of choicein the turmeric market.

Bibliography and online research material

Bibliography_

Allegri P., et al. Clin Ophthalmol, 2010. 4: p. 1201-6.

_

Golombick T., et al. Journal of Cancer Therapy, 2015,
6 [7], 566-571.

_

Antiga A., et al. BioMed Research International, vol. 2015,
Article ID 283634.

_

Kayabasi U., et al. Int J Ophthalm Clin Res 2014 1:002.

_

Ledda A., et al. Panminerva Med, 2012. 54 [1 Suppl 4]: p. 17-22.

_

Maccio A., et al. Nutrition, 2015. 31[1]: p. 239-43.

_

Appendino G., et al. Panminerva Med, 2011. 53 [3 Suppl 1]:
p. 43-9.

_

Belcaro G., et al. Altern Med Rev, 2010. 15 [4]: p. 337-44.
_

Mazzolani F. Clin Ophthalmol, 2012. 6: p. 801-6.

_

Belcaro G., et al. Eur Rev Med Pharmacol Sci, 2014. 18 [24]:p. 3959-63.

_

Mazzolani F. and S. Togni Clin Ophthalmol, 2013. 7: p. 939-45.

_

Belcaro G., et al. Panminerva Med, 2010. 52 [2 Suppl 1]: p. 55-62.

_

Mazzolani F. and S. Togni, et al. Minerva Ophthalmol, 2016.
58: p 1-5.

_

Belcaro G., et al. Phytother Res, 2014. 28 [3]: p. 444-50.
__

Di Pierro F., et al. J Pain Res. 2013, 6, 201-205.

Pajardi G., et al. Evid Based Complement Alternat Med, 2014.
2014: p. 891310.

_

Di Pierro F. and R. Settembre J Pain Res, 2013. 6: p. 497-503.

_

Panahi Y., et al. J. Cardiovasc Pharmacol. 2016; 68: 223 -229.

_

Drobnic F., et al. J Int Soc Sports Nutr, 2014. 11: p. 31.

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Panahi Y., et al. Drug Res [Stuttg]. 2017 Apr; 67 [4]: 244-251.

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Ferguson, Jessica JA, et al. Metabolism [2017].

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Panhai Y., et al. J Functional Food 2014 [6] 615–622.

_

Franceschi F., et al. European Review for Medical andPharmacological Sciences. 2016; 20: 762-766.

_

Panahi Y., et al. Phytother Res, 2014. 28 [10]: p. 1461-7.

7.

Online research material_

Riva A., et al. European Review for Medical
and Pharmacological Sciences 2017; 21: 1684:1689.

_

https://academic.oup.com/eurheartj/article/
27/22/2640/2887469_

Sciberras J.N., et al. J Int Soc Sports Nutr, 2015. 12 [1]: p. 5.

_

https://www.futuremarketinsights.com/reports/
turmeric-market_

Serpe R., et al. 6th Cachexia Conference, Milan, Italy,
December 8–10, 2011.

_https://www.nature.com/articles/nature01322_

Soldà C., et al. International Journal of Pharmacology,
Phytochemistry and Ethnomedicine, Vol 2, 2017.

_https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1087185/_

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964958/_

Steigerwalt R., et al. Panminerva Med, 2012. 54 [1 Suppl 4]:
p. 11-6.

_

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488800/_

Szymanski M.C., et al. J Appl Physiol 2017. doi:
10.1152/japplphysiol.00515. 2017.

_

http://onlinelibrary.wiley.com/doi/10.1111/
j.1473-2165.2005.00194.x/full_

Tenero L., et al. Allergy Asthma Proc. 2016; 37:e8-e13.

_

http://www.who.int/bulletin/volumes/81/9/PHC.pdf_

Watson R.R., Preedy V.R., Bioactive Foods as Dietary
Interventions for Arthritis and Related Inflammatory
Diseases, Ch. n.5, Appendino, Togni, p. 66-81.

_

http://www.who.int/mediacentre/factsheets/fs311/en/_

http://www.who.int/mediacentre/factsheets/fs394/en/

Watson R.R., Foods and Dietary Supplements in the Prevention
and Treatment of Disease in Older Adults, Elsevier Science,
2015, p. 16.

_

http://www.who.int/medicines/areas/priority_medicines/
BP6_11Alzheimer.pdf_

http://www.who.int/medicines/areas/priority_medicines/
Ch6_12Osteo.pdf_

INDENA uses for MERIVA®,
and will always use for its
active ingredients,
a natural nutraceutical talentand biomimetic science,
to respond to the changing
needs of human beings,
to push the envelopeand support partners
and customers towards
new futures.
INDENA#scienceisournature

Call To Action / Contacts

Now imagine how theeffectiveness of MERIVA®
as THE LIFE GUARDIAN™
in a healthy life maintenancepersonal project should:

Enlarge your prospect target
to non-pathologic situations.

Widen the consumption window
either in terms of consumerage[aging – longevity – prevention]or in occasions of consumption.

Increase the average consumption
per capita.

Strengthen your customers’ brandadvocacy and loyalty:
INDENA will deploy a strong
communication and divulgative
program about MERIVA®
THE LIFE GUARDIANTM properties.

8.

Contact Us
INDENA S.p.A.
Viale Ortles, 12 - 20139 - Milano [Italy]
communication@indena.com
indena.com

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are the property of their respective owners.
This document is published in several Countries and so may contain statements that are not applicable to yourCountry, that may not comply with Reg. EC n. 1924/2006 and that have not been evaluated by the Food and Drug
Administration. Meriva® is not intended to diagnose, treat, cure or prevent any disease, and marketers of finishedproducts containing it are responsible for ensuring compliance with all applicable laws and regulations.

,

® TM

trademarks of Indena S.p.A., Italy. ©2020, Indena S.p.A., Italy.

DPR0303 - 02/2020

Low-level
Chronic
Inflammation

Low-level Chronic Inflammation

Chronic inflammationand turmeric
Chronic inflammation is associated witha constant increase of pro-inflammatory
biochemicals in our body. Drugs can only
contain but not cure this condition, because
they do not remove the cause of the disease:silent inflammation.

Silent inflammation is defined assilent because it is not perceived by
the individual, as opposed to acuteinflammation that causes pain, but
it can persist for years and provoke
damages that can result in chronic
diseases.

Inflammation is one of the primarymechanisms developed by nature to maintainour body’s health and immune homeostasis[which is the stable balance and condition of
the organism and its bodily functions] against
the thousands of attacks we receive every day
from the surrounding environment.

When this response is not properly
regulated, the concentrationof inflammatory markers rises
and remains high, leading toa physiological status known
as chronic inflammation.

Low-level Chronic Inflammation

Here are the main possible consequences of chronic
inflammation, at the level of the various systems:

Brain and central nervous
system: Alzheimer’s disease,
Depression. 1

Bone system:
Osteoarthritis, Osteopenia,
Osteoporosis. 2

Cardio-circulatory system:
Myocardial infarction,
Atherosclerosis, Arteriosclerosis. 3

Immune system:
Cancer, Fibromyalgia, Chronic
Fatigue Syndrome. 4

Organism in general:
Diabetes, Metabolic Syndrome,
Dismetabolism. 5

Skin:
Wrinkles, Cellulitis. 6

Sexual health:
Impotence, Organic Dysfunctions. 7

Thanks to recent progress inmolecular biology, today we know
more about the relationship between
what we eat and the genetic
expression of our inflammatory genes.
This is also useful when choosing
which supplements to add
to our diet, in order to address
specific conditions.

1. http://www.who.int/medicines/areas/priority_medicines/BP6_11Alzheimer.pdf
2. http://www.who.int/bulletin/volumes/81/9/PHC.pdf
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488800/
4. https://www.nature.com/articles/nature01322
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1087185/
6. http://onlinelibrary.wiley.com/doi/10.1111/j.1473-2165.2005.00194.x/full
7. https://academic.oup.com/eurheartj/article/27/22/2640/2887469

Therefore, silent inflammation is oneof our biggest challanges.

Turmeric has a long history of dietary andalso medicinal use in India to treat many
conditions.
Modern studies on turmeric have validated
most of its traditional uses and its potential
to address the natural living conditions
typical of Western peoples.
Dietary intake of curcumin in Asian countries
can reach 200mg/day.
Today, curcuminoids are in fact one of themost studied herbal therapies in the world. 8

8. Ronald Ross Watson, Foods and Dietary Supplementsin the Prevention and Treatment of Disease in Older Adults,
Elsevier Science, 2015, p. 16.

Low-level Chronic Inflammation

The reputation of curcumin as a powerfulanti-inflammatory substance is therefore
increasing. It is actually believed toaffect various stages of the inflammatory
progression at the molecular level. In short,
its action blocks the molecule known as
NF-kB, which penetrates into the cell
nuclei and triggers the genes related toinflammation. It is noted that NF-kb appears
prominently in many chronic diseases.
That said, and without delving
deeper into the complicated nature of
inflammation, the most important thing toremember is that the bioactive substanceof curcumin fights inflammation
at the molecular level. 9

9. Ronald Ross Watson, Victor R. Preedy - Bioactive Foods
as Dietary Interventions for Arthritis and Related Inflammatory
Diseases, Ch. n.5, Appendino, Togni, p. 66-81.

As a result, curcumin has emerged asa main switch to address the response
function to CHRONIC INFLAMMATION,
with a both direct and genomic activity
on relevant enzymes, transcription
factors and cytokines.

Low-level
Chronic
Inflammation