Danone magazine with research highlights and product news

1. the Danone Research newsletter 04
APRIL 09
MEDICAL
NUTRITION
The stakes 4
Danone’s Leading-edge Research: Our Dedication
to Improving Nutrition, Improving Lives 6
“The brain is different from other organs” 9
Fortisip Compact: Major technological breakthrough 11

2. EDITORIAL
UNDERsTANDINg
MEDICAL NUTRITION
In this edition of VIEW we offer an overview
What is medical nutrition? of how our Medical Nutrition Research &
Medical Nutrition manages disease-related
malnutrition and specific disease conditions Development teams are developing innovative
in all age groups. It can make medical treatment nutritional products that serve patients’
more effective by controlling malnutrition,
meeting special dietary needs, needs and open new growth opportunities
and can help to delay disease progression. for Danone.
We define it as nutritional intervention
that improves clinical outcomes.
Scientific credibility is vital to success
in this evolving sector and we have deep
scientific expertise in understanding
physiological disease processes and the role
How do people take them? of nutrients. At the same time, a strong
The products are administered via the gastro-
intestinal tract – taken orally as a beverage,
technological expertise is required to deal
soup, meal, or dessert, or through a feeding with complex formulations and to create
tube.
products with a long shelf life, that are good
tasting and appealing to our patients. “Medical Nutrition
Are these products food
or pharmaceuticals? R&D is a very
They are not pharmaceuticals. Medical Nutrition
products are unique compositions of specific
Our goal is that medical nutrition will be ambitious
an integral part of disease treatment plans
nutrients that cannot be obtained from
a normal diet. Our products are ‘advanced
for people of all ages – from premature
environment
nutrition’, and from a legislative perspective,
they are classified as food. birth to the terminal phases of life. with a strong
The beauty of our work is that we create pioneering spirit.”
How are they distributed?
Medical Nutrition products are usually
new horizons in science and technology,
prescribed or recommended by health and at the same time, our products Hanno Cappon
VP Medical Nutrition R&D
care professionals, and in many markets they
are reimbursed by health insurance. They are
are having a positive impact on people’s lives.
distributed in hospitals, care homes, pharmacies,
and special home-delivery channels.
03

3. THE sTAKEs
Nutrison
Nutrison reflects our R&D expertise to find innovative
The following topics explain the key issues that are impacting the medical solutions. The customized ready-to-use tube feeds
facilitate the dietary management of malnutrition
nutrition sector today, and in the future. in patients requiring tube nutrition, meeting each
patient’s specific needs. Certain varieties contain
our patented Multi Fibre mixture (MF6™) proven
to reduce constipation and diarrhoea, while others
(Diason) have a low glycaemic index to control
“The division’s science and R&D capability is Responding diabetes complications.
seen by health care professionals as a reference to opportunity
in the field of Advanced Medical Nutrition. and challenge
This is key to the acceptance of the value of our
Medical nutrition is an exciting new sector
products in hospitals and community channels.” for Danone with a high growth potential.
Flemming Morgan, President of Medical Nutrition at Danone Health care professionals are recognising that
our innovative nutritional products can be
a healthy complement to a patient’s medical
Scientific credibility treatment. These products are for people Regulatory environment Market Position
Scientific credibility is a top differentiator for success of any age and intend to manage a range From a European legislative perspective, medical nutrition Danone’s Medical Nutrition division is a high-growth busi-
in the medical nutrition sector. Danone has the advantage of conditions, such as childhood epilepsy is food and must comply with a specific legislation called ness. Our financial results for 2008 were very positive, with
because science is at heart of our business. This expertise or Alzheimer’s disease. ‘Foods for Special Medical Purposes’. This EU directive 854 million € sales (reflecting 12.7% growth). In Europe,
is very important for our relationships with medical authorities ensures product safety and suitability for the intended we are the market leader with about 40% market share.
and regulatory bodies. To secure registration and reimbur-
Older people are one of the major consumers purpose. It regulates vitamin and mineral composition, and Danone Medical Nutrition products are marketed under
of our products and this is a prime market
sement by health care policies, scientific substantiation labelling of these foods, including those for infants. Our the Advanced Medical Nutrition brand names Nutricia,
segment. As the ageing population in-
is crucial. We are making a strong emphasis on informing products are facing a comparable regulatory environment SHS and Milupa Metabolics. We have built a strong scien-
creases, managing healthcare expenses while
Health Care Professionals (HCPs) and Key Opinion Leaders in other markets, such as the USA. tific reputation and are recognized for our innovation.
providing optimal care will be a critical issue.
(KOLs) on the benefits and proven scientific evidence Medical nutrition offers key benefits: it is
behind our products. Our research results are published in designed to increase quality of life by slowing Consumer concerns
high quality peer-reviewed scientific journals and we present the progression of certain diseases and helps People rely on medical nutrition products for their health and
them at international scientific conferences. To build strong keep patients independent for longer. From a recovery – from sick infants to the diseased elderly, so the
relationships, we regularly invite HCPs, KOLs, and health financial perspective, the nutritional benefits safety and quality of our products has to be uncompromised.
policy makers to our research facilities to share and discuss can shorten hospital stays, thus reducing The additional challenge is that people need a pleasant-tas-
the science behind our products. healthcare costs. ting, easy-to-consume product – despite complex formula-
tions.
Along with opportunity there are also chal- We’re going to the next level to ensure positive consumer
lenges facing Danone. As we work to grow acceptance. Our technological expertise is enabling us to
our market share, we also face competition.
develop products that encourage patient compliance while
Flemming Morgan, President of Medical
delivering maximum clinical outcome. Our dedication to
Nutrition at Danone, explains: «Our strategy
seeing patients as people first is delivering positive results,
in innovation is to drive additional growth Neocate
through the development and commercia- both in building market share and recognition in the medical
Respifor lisation of breakthrough disease-targeted and scientific research community. Many infants and children have an allergy to cow’s
milk. Neocate has become the world leader in this
Respifor is an excellent example of our innovation- products and solutions.» market by providing a non-allergenic amino-acid
in-action. This specialised nutrition is for patients based substitute for milk-based formulas and foods.
with chronic lung-related diseases, for example,
He also notes that innovations and upgrades It is manufactured in the world’s only 100% dairy-free
lung emphysema. Its low volume formula (125 ml) facility in Liverpool. More than half a million infants
is high in protein to rebalance protein metabolism. already make up 30% of new sales growth
and children have benefited from Neocate,
Respifor is clinically proven to promote superior (2008), and with a very promising pipeline, and parents and prescribing health care professionals
weight gain as compared to standard medical this proportion is expected to increase in the alike rely on the product’s safety and purity.
nutrition, and also to improve physical performance The popular brand continues to grow in excess
- enhancing patient quality of life.
coming three years.
of 25% annually, due to scientific expertise, clinical
evidence and constant innovation.
04 05

4. REsEARCH Controlling Epilepsy
with Nutrition
Danone’s Leading-edge
consumption and alternated As early as 400 B.C., Hippocrates Highly skilled R&D
between recommending high noted that epilepsy can be treated
organisation
Research Our Dedication
or low carbohydrate foods. It by abstaining from food. By the
The new Danone Medical Nutrition R&D organisation
was also believed that adding 1920’s, the concept of epileptic
comprises almost 160 people, with expertises ranging
additional protein could slow the seizure control by fasting had
from cell biologists and physiologists to nutritionists
absorption of carbohydrates and gained substantial support. That’s
to Improving Nutrition, Improving Lives
and food technology scientists. We operate in 4
stabilise glucose levels. when scientists began to study the
countries: The Netherlands (Wageningen, Zoetermeer,
mechanism of fasting, discovering
Cuijk, Schiphol), UK (Liverpool), Germany (Friedrichs-
Today, modern studies are chal- that its benefits could also be
dorf) and China (Wuxi). We actively collaborate
At Danone, we know that disease isn’t just a clinical term. lenging these traditional beliefs simulated by fat-rich, low-carbo-
with the transversal expertise platforms such as
and scientists are re-examining hydrate diets. This state, known
It’s something that impacts people’s quality of life – quality that the role of protein and fat on as ketonaemia, gave rise to the
Gut & Microbiology, Immunology, Consumer Science
and Clinical Studies.
can be improved with state-of-the-art medical nutrition. Here is glucose response. International ketogenic diet.
an update about who we are and how we’re developing products that
bodies, such as the European
Association for the Study The ketogenic diet’s basic
Extensive international
of Diabetes (EASD), have released principle is that drastic reduction scientific network
work in sync with patients’ treatment plans – leading to better lives. new guidelines for the composition of carbohydrates stimulates the While internal expertise is a critical aspect of our
body – and particularly the brain – research focus, our multi-disciplinary teams also
of a diabetes patient’s diet, based
work in close collaboration with leading international
1 - The Evolving History of Medical Nutrition on the latest scientific insights. to switch from glucose to fat-derived
ketones as its primary source scientific centres. We are currently engaged in research
projects and clinical trials with more than 200
The scientific understanding of the role of nutrition on human Research Our first nutritionally complete oral of energy. Since the 1990’s,
universities, hospitals and industries across the globe.
health has significantly evolved over the last centuries. nutritional supplement, Diasip, the ketogenic diet has enjoyed
Traditionally, it was believed that food only provided energy
Breakthroughs a remarkable revival as a treatment This strategy will enable us to expand Danone’s
was low in carbohydrates
to the body. Around 1900, when confronted with deficiency in Diabetes: from and high in fat. It was specifically strategy for intractable epilepsy, leadership position in the specialised nutrition industry.
diseases, scientists started to discover the essential role starvation to 21st developed to give a lower glucose with several clinical studies
of specific nutrients, vitamins and minerals. Later, the effect century science response after a meal than stan- indicating its effectiveness.
of diet on chronic diseases, such as cancer and cardiovascular dard supplements. Then it was
diseases, became apparent. Diabetes Mellitus is a metabolic reformulated to meet the new In 2002, SHS International,
Today, we know that nutritional ingredients exist that can actively disorder that leads to high blood EASD standards. Launched a subsidiary of Danone and part
interfere with disease processes (somewhat like pharmaceutical glucose levels. Scientific understan- in the summer of 2008, second- of the Medical Nutrition division,
components). This means that through specific nutritional ding of this disease has continually generation Diasip features launched Ketocal, a ketogenic
intervention, we can improve peoples’ health and wellbeing. advanced over the years and a «triple action» for superior medical food that can be used
we were at the forefront of early glucose control. Carefully selected as part of the ketogenic diet
diabetes studies. The first Nutricia and tested carbohydrates, or as complete ketogenic nutrition.
Medical Nutrition product for diabetes combined with proteins In 2008, results of the first-ever
The first Nutricia Medical Nutrition patients was developed back and dietary fibre, ensure a healthy randomized controlled clinical
in 1905, pioneering the concept trial of the ketogenic diet were
product for diabetes patients of specialised nutrition. It was a milk
glucose metabolism in the
diabetic patient. To date, several published in The Lancet Neurology
was developed back in 1905, pioneering product low in lactose. intensive clinical studies in Type journal. This study, supported by
2 diabetes patients have already SHS, confirmed the clinical efficacy
the concept of specialised nutrition. By 1915, very controlled food intake provided convincing scientific of the diet and cements its place
was the standard treatment evidence to support our claims. as a bona fide therapeutic option
for diabetes. When insulin for intractable epilepsy.
was discovered in 1921, medical
professionals restricted sugar Thanks to Ketocal, people living
with epilepsy have a proven tool
to manage manage their symptoms
through diet.
06 07

5. 3 questions for...
REsEARCH
Richard Wurtman
2 - Strategic Competencies of Medical Nutrition R&D “The brain is different
from other organs”
To identify new nutritional intervention opportunities, Boosting metabolic Advanced Neurosciences Neuroscience, a field VIEW: What is the most intriguing
we need to research the complex interaction between
nutrition, biological processes and disease mechanisms
processes technology Nutrition plays an important role
devoted to the scientific finding of the last few years?
Diseases, surgery, ageing and Developing a product prototype is in the field of neuroscience.
in the human body. That’s why our strategic research axes R.W.: Perhaps the most interesting
wound healing impact metabolic a challenge -- we get a “shopping The brain uses nutrients as an study of the central finding is that not only the produc-
comprise almost all life science disciplines, as well as energy supply and they influence
product technology and sensory sciences.
processes. We are examining list” of necessary ingredients as and peripheral tion of neurotransmitters but also
how nutritional products well as the desired format, and the synthesis of neurotransmitters.
Preclinical studies indicate that
nervous system, the synthesis of unique synaptic
can boost these processes then we put innovative/ cutting- membranes can be affected
Protein metabolism: to enhance and maintain edge technology to work to make as dietary precursors, nutrients is opening the window
by nutrition. These processes
the base of life functionality, performance, and it happen. Ingredients need to be can synergistically increase Dr. Richard of discovery about can be increased by consuming
Protein, one of the body’s basic membrane and synapse J. Wurtman MD,
quality of life. stabilized for maximum efficacy
Cecil H. Green
how nutrition impacts three nutrients: uridine-
building blocks, is mostly found in Currently focusing on diabetes, and long shelf life, yet also have a formation, which are essential
muscle. Preserving muscle mass for proper brain function.
Distinguished
Professor of
brain cells. mono-phosphate, the omega-3
our researchers are looking at good flavour and pleasant texture. PUFA DHA, and choline.
is a challenge in the elderly and The results of the first clinical Neuropharmacology,
metabolic responses to diet We have the know-how to create Massachusetts VIEW: What role does nutrition As demonstrated in in-vivo
patients recovering from surgery and how it affects long-term complex formulations with optimal trial are encouraging and we are Institute of play in the field of neuroscience? models, these nutrients
or disease. Loss of muscle mass continuing to build the pyramid Technology (MIT).
complications in diabetes and ingredient interaction - whilst R.W.: The brain has all of increase both the lipid portions
naturally occurs with ageing and metabolic syndrome patients. remaining stable after sterilisation. of evidence (see diagram on page
the nutritional needs as the rest of these membranes and
is accelerated by inflammatory By understanding the Our R&D expertise drives the full 10). Additional longer-term trials
of the body. Deficiencies in some the specific proteins that are
conditions, inadequate dietary relationships between disease, product lifecycle, from checking with Souvenaid® (in Europe and
nutrients – like B vitamins, glucose, essential for neurotransmission.
protein intake and cancer. treatment, GI homeostasis, the feasibility of new processes, USA) have been designed and will
essential fatty acids, or protein Consequently, the neurons make
By identifying the gap between metabolic stress, and immunity, ingredients and food forms, to start in 2009. A large, dedicated
– can impair brain function and surface structures, dendritic
dietary protein intake and we can create specialised working with supply points for EU consortium called LipiDiDiet
cause well-established syndromes. spines, which can produce
need, we can support protein products designed to impact implementation and optimisation will conduct one of the trials.
But the brain is different from additional synapses. Theoretically,
metabolism with products such the progression of disease and of new technologies in the factory. Building on the knowledge gained
other organs – it has a special these nutrients could be used
as Fortimel, our high-protein treatment complications. in our Alzheimer project, we have
dependence on nutrient intake. to restore synapses when
formula. Developing new specific a great opportunity to bridge the
protein compositions enables us
The power gap between Alzheimer’s patients
It’s because many of the enzymes they’ve been damaged by disease.
that the brain uses to convert
to stimulate synthesis of muscle of immunity and the general population
nutrients to essential products VIEW: What could be the most
protein – increasing muscle mass IImmunity is the body’s defence of elderly people. We are now
have a low affinity for these promising application for nutrition
and function. This can improve mechanism against infection focussing on other diseases that
nutrients. If more of a nutrient in neurological disease in the
quality of life while reducing and disease. Using nutritional impact the growing number
is provided – usually by eating it – future?
complications and hospital stays. concepts, we search for of older people in today’s society.
the brain rapidly proceeds to make R.W.: One encouraging application
intervention opportunities to
more of the product. is Nutricia’s Souvenaid®, a formula
support the immune system
Brain cells, called brain neurons, containing uridine-mono-phosphate,
of elderly and immuno-
compromised individuals such as
“Our medical communicate with each other DHA, and choline, as well as the
cancer patients. The Immunology nutrition relies through synapses located necessary supporting nutrients.
at the ends of the neurons. It’s currently being tested for
Platform has a strategic alliance heavily on technology These synapses release messenger the management of Alzheimer’s
with the Utrecht Institute for
Pharmaceutical Sciences - this expertise molecules (neurotransmitters) disease. Virtually all neurologic
to transmit the message scientists agree that Alzheimer’s
and a network of academic enables us to the next cell. Specific nutritional patients suffer cognitive impair-
and industrial partners who
continuously investigate and
to produce best- ingredients can influence the ability ments because of synapse loss.
evaluate our products. in-class products.” of brain neurons to synthesize Perhaps the reduction in the
neurotransmitters, thus rapidly number of synapses can be com-
affecting the information carried pensated by a synapse-producing
across the brain’s synapses. preparation like Souvenaid®
08 09

6. CAsE sTUDy
Systematic review
& meta analysis
Fortisip Compact:
db-RCT
KEy INNOvATION in target group
AxE - BUILDINg Cohort
Gastrointestinal Sensory pyRAMID and case studies
functionality & and consumer Of EvIDENCE Expert opinion
Major technological breakthrough
tolerance science KOLs
One of our key competences Patients know that medical Proof of concept
is a thorough understanding nutrition products are not Healthy volunteer data
of nutrient metabolism a dietary treat, but they still want Mechanistic
Danone Research responded to the technological challenge of producing a complete yet
in the gastrointestinal tract. them to taste good and have experimental evidence condensed oral nutritional supplement (ONS). The result? Fortisip Compact, the first
This enables us to understand a pleasing texture to ensure
how the body breaks down compliance. Our challenge
State of the art nutritionally complete ONS in the world that offers 300 kcal, and 12 g protein in only 125 ml.
ingredient knowledge
nutrients so that they can be used is that many ingredients in these
to promote healing or support products naturally do not taste
optimal health. Our products must good (such as high levels of fish What is a medical
In February 2009, Fortisip Compact began its
rollout in the market, marking the successful
Beneficial to patient
be well tolerated by vulnerable oils, amino acids, minerals nutrition clinical study? conclusion of a major R&D effort at Danone. and provider
people with impaired health. and vitamins) and must be To produce this nutritionally complete,
When we identify innovative specially formulated for a long Fortisip Compact is beneficial for both patients
Clinical studies are a pivotal part of Danone’s protein-rich and energy dense compact ONS,
ingredients and develop new shelf life. Unusual combinations and health establishments. The average hos-
Medical Nutrition scientific credibility. These the edges of the laws of physics, state-of-
product formats, we perform of these ingredients make pital cost for nutritionally at-risk patients can
studies are conducted in patients and healthy the-art innovative processing techniques and
clinical studies to be sure that it even more challenging triple when compared to standard patient
volunteers to test the safety and efficacy new ingredient sources had to be explored.
these products are well tolerated. to develop a pleasant taste. costs, illustrating the high cost of malnutrition.
of our products. Trials are set up in close
Tolerance is a critical success Our current studies, In studies of hospital and community patients,
collaboration with (academic) hospitals,
factor for long-term compliance, which are mainly coordinated nursing homes and institutes.
Concentrated calories ONS use has been shown to improve energy
ensuring that the consumer/ in Wageningen, involve various The investigators are often Key Opinion for optimal nutrition and nutrient intake, increase body weight
and functional outcomes, reduce mortality
patient can receive all the intended types of patients and healthy Leaders or medical specialists.
health benefits of the product. elderly people and children, Clinical trials with medical nutrition are very Fortisip Compact targets the nutritional and complications, and reduce length of stay
from different parts in the world. different than product testing for healthy needs of hospitalized patients, nursing home in hospitalized patients when compared with
consumers. The people in medical nutrition residents, and older adults. Often these groups routine clinical care.
trials are often physically fragile and in health cannot consume enough solid food to main-
“Our defining difference care facilities or hospitals. The participants tain a balanced diet, leading to malnutrition.
is that with the acquisition in these studies must have the disease that Danone’s liquid compact ONS acts as a com-
the product is intended for – this enables us plement to regular meals, ensuring optimal
of Numico we are establishing nourishment.
to test the safety, efficacy and benefits of the
an unprecedented level product in the appropriate target population.
of excellence. Danone is truly Trials are conducted in full compliance Danone’s revolutionary supplement is designed
with ICH guidelines for Good Clinical Practice to work in tandem with the brain’s signals that
a pioneer – setting standards for and applicable local legislation. perceive fullness. These signals correspond
clinical trials and speaking These regulations safeguard the rights, more with the volume of food eaten, than
safety, and wellbeing of subjects as well with the actual calorie consumption. So peo-
Our dynamic simulator of the gut to European Union regulators.” ple tend to eat a certain volume and feel full,
is a computer-controlled model as ensure reliable results.
that allows us to study how Sven Thormahlen is Executive Vice President We’ve gone a step further with our ISO without taking in sufficient calories for proper
(and to what extent) our product of Research and Development 9001:2000 certification as an independent nutrition. Fortisip Compact’s easy-to-drink
ingredients are being digested and General Manager of Danone Research. formula gives a limited “full feeling” effect and
qualification of our methodology. It’s yet
or fermented in the various parts
another way we provide credible, convincing provides concentrated calories in a small volume.
of the gastrointestinal tract.
data for Health Care Professionals and It doesn’t disrupt calorie consumption during
authorities. normal meals – guaranteeing increased energy
intake in the short-term.
10 11

7. DID yOU
KNOW ?
MEDICAL NUTRITION
R&D LOCATIONs AND REsEARCH
COLLABORATIONs
UNITED-KINgDOM THE NETHERLANDs CUIJK: Powdered sWEDEN CHINA
LIVERPOOL: product WAGENINGEN: product formulations STOCKHOLM: WUXI: adaptation
formulations and clinical preclinical research; SCHIPHOL: medical Ersta Hospital of formulations,
research for metabolic consumer sciences; devices and clinical
Karolinska
diseases & cow’s milk new technologies; Institute studies for
allergy. clinical research VU University Chinese market
ZOETERMEER : liquid Medical Centre
University of Hull product formulations Amsterdam
University of Oxford University Hospital
Maastricht
University of Utrecht
UNITED-sTATEs
NEW YORK:
St. Luke’s-Roosevelt
Medical Center
ARKANSAS : University
for Medical Sciences
BOSTON
MIT
spAIN fRANCE gERMANy ITALy IsRAEL
BARCELONA: LYON: Hôpital FRIEDRICHSDORF: ROME: TEL AVIV:
University Edouard Herriot Metabolic University Sourasky
of Barcelona diseases of La Sapienza Medical
Center
Locations of R&D facilities for Medical R&D
International collaborations
Mirjam Govers - mirjam.govers@danone.com - office: +31 317 467 889 Danone Research-Centre for Specialised Nutrition - Bosrandweg 20 6704
PH Wageningen - The Netherlands / Writing: Patricia Philbin / Credits: Jaap van de Beukel / design: pixelis corporate