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Molecular Nutrition Research as a Basis for Disease Prevention and Health +++ The German Institute of Human
Nutrition Potsdam-Rehbrücke – Our Research Focus +++ Health and Nutrition at the TU Berlin – the Center for
Preventive Foods +++ The “Brandenburger Ernährungs- und Krebsstudie”: A Potsdam Contribution to the Euro-
pean Prospective Investigation into Cancer and Nutrition (EPIC) +++ Nutrigenomics in Berlin-Brandenburg +++
BEN – the Food Network for the Capital Region +++ Nutrigenomics and Gene Regulation +++ Food Technology for
New Markets from TU Berlin +++ ORGANOBALANCE – From Spin-Off to Successful Probiotics Producer
Journal of Biotechnology in Berlin-Brandenburg
Issue 36 · January 2009
Molecular Nutrition Research
and Food Technology
2
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
Content
Impressum
Publisher: BioTOP Berlin-Brandenburg
Fasanenstraße 85 · D-10623 Berlin
Phone +49 30 318622-11
Fax +49 30 318622-22
· www.biotop.de
Editor: Thilo Spahl
Design & Production: supiran.de
Translation: Textbüro Reul GmbH · Frankfurt
Photos: page 3: dreamstime.com/Christophe Testi · page 11:
dreamstime.com/Milosluz · page 14/15: dreamstime.com/
Shaik Dawood/Titania1980/Jack Kunnen/Liga Lauzuma/
Janpietruszka/Dorlies Fabri/Missjelena/Evestock/Olga
Langerova/Sergei Didyk/Elnur · page 19: BASF SE ·
others: authors or BioTOP
BioTOP is a joint initiative of the state of Berlin and the state of Brandenburg under the umbrella of the TSB Innovationsagentur Berlin GmbH.
BioTOP is funded by the federal state of Berlin, the federal state of Brandenburg and the Investitionsbank Berlin, cofunded by the European
Union (European Fund for Regional Development). BioTOP coordinates the implementation of the master plan of the health region Berlin-


Brandenburg in the eld “Biomedicine/Biotechnology”
Molecular Nutrition Research as a Basis for Disease Prevention and Health 3
The German Institute of Human Nutrition Potsdam-Rehbrücke –
Our Research Focus 4
Health and Nutrition at the TU Berlin – the Center for Preventive Foods 6
The “Brandenburger Ernährungs- und Krebsstudie”:
A Potsdam Contribution to the European Prospective Investigation
into Cancer and Nutrition (EPIC) 8
Nutrigenomics in Berlin-Brandenburg 10
BEN – the Food Network for the Capital Region 13
Nutrigenomics and Gene Regulation 14
Food Technology for New Markets from TU Berlin 16
ORGANOBALANCE – From Spin-Off to Successful Probiotics Producer 18
3
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
Molecular Nutrition Research as a Basis for
Disease Prevention and Health
A third of all health spending is accounted for by illnesses whose origin and progression
are inuenced directly or indirectly by dietary factors. The molecular basis of diet-related
illnesses is therefore a challenging area of research for which the bioregion Berlin-
Brandenburg has strong credentials. The close links that exist here between genome
research, molecular and clinical nutrition research and plant biotechnology have supported
the development of new strategies in recent years to diagnose, prevent and treat diet-
related illnesses.
Dr. Kai Bindseil
Director
BioTOP Berlin-Brandenburg
Particularly in the eld of nutrigenomics, which
focuses on the interaction between diet or
food components and the human genome, the

region has produced many new ideas. BioProl
Nutrigenomik, funded by the German Ministry
of Education and Research (BMBF), is a network
in which basic research and its application take
place side by side and where research institutes
and biotech companies have joined forces to
develop new products, particularly for diagnostics.
The area’s outstanding research facilities, like
the German Institute of Human Nutrition, the
Innovation Center Health and Nutrition (IGE)
of the Technische Universität Berlin, the Max
Planck Institute for Molecular Plant Physiology
and Charité – Universitätsmedizin Berlin, form
the basis for this fruitful cooperation.
Alongside advancements in biotechnology,
many preventive measures are available today
that can help considerably to reduce the inci-
dence of many chronic illnesses. For the eld of
preventive health to benet as quickly as pos-
sible from new scientic ndings, the master plan
of the health cluster Berlin-Brandenburg has
made “Prevention, Health Promotion, Rehabili-
tation and Diet” an independent eld of activi ty
that cooperates closely with the eld “Biotech-
nology and Biomedicine”. Here the goal is to
make Berlin-Brandenburg into a science-led
model region for nutrition, health and food.
In this issue of BioTOPics some of the most
im portant nutrition researchers in Berlin-Bran-
denburg report on research projects and product

developments.
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B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
The German Institute of Human Nutrition
Potsdam-Rehbrücke – Our Research Focus
The German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) investigates the ori-
gins of nutrition-associated diseases with the aim of developing new preventive strate-
gies, treatments and dietary recommendations. The scientists engaged in interdisciplinary
research at the institute use a broad spectrum of scientic, medical and epidemiological
research methods. The institute’s research is currently focussed on the most important
diseases that are associated with dietary factors: obesity, diabetes and cancer.
Research Focus Metabolic Syndrome and Type-2 Diabetes
Metabolic syndrome is the term used to describe a complex of
symptoms that include overweight, high blood pressure, insulin
resistance and disorders of the lipid metabolism. The syndrome
has a genetic basis but is usually only triggered by the positive
energy balance (high calorie intake and little exercise) that occurs
frequently in countries with a “western lifestyle”. Incidence as
well as severity of this syndrome and its main secondary compli-
cation, type-2 diabetes, have increased dramatically in all west-
ern countries. This trend can also be observed in the Potsdam
EPIC (European Prospective Investigation into Cancer and Nutri-
tion) study conducted at the DIfE (Figure 1).
Type-2 diabetes is one of the most common and cost intensive
chronic diseases today. According to the assessment of the CoDiM
(Costs of Diabetes Mellitus) study, the direct costs of diabetes in
Germany were 30.6 billion euros or 14.2 percent of total spend-
ing in the health care system in 2001. Given that the prevalence
of diabetes is expected to rise by almost 50 percent between 2000
and 2030, a huge increase in costs must be expected. In addi-

tion, despite treatment, the secondary complications of metabol-
ic syndrome shorten life expectancy by approximately eight years.
We can therefore expect a fall in average life expectancy and an
explosion in expenses unless we manage to reverse or at least to
slow down this trend. To do so, we need fundamental insights
into the causes of metabolic syndrome and effective strategies for
the prevention and treatment of obesity and diabetes.
Using data from the Potsdam EPIC study, the DIfE has therefore
developed a diabetes risk test which is already being used by
health insurance funds. At the same time, DIfE scientists have
made important advances in determining the genetic origins
of the metabolic syndrome. In a mouse model (Figure 2), they
identied a natural mutation in the Tbc1d1 gene which affects
the regulation of the energy metabolism in the muscles. Due
to this mutation, the mice lack a particular metabolic enzyme
that enables them to remain slim even when fed a high-fat diet,
and also protects them against diabetes. In the course of their
research, the scientists gained profound insight into the function
of the gene. This provides the basis for developing new therapy
and prevention strategies.
In addition, DIfE scientists are using epidemiological and clinical
studies to investigate the interactions between diet, genes and
diabetes. In the context of the Potsdam EPIC Study, they recently
succeeded in showing that a variation of the TCF7L2 gene can
determine whether a person can reduce the risk of developing
diabetes by eating wholegrain products.
Prof. Dr. Hans-Georg Joost
Scientic Director · German Institute of Human Nutrition
Potsdam-Rehbrücke (DIfE)
Figure 1

Tromso
Umea
Aarhus
Oxford
Cambridge
Utrecht
Malmo
Copenhagen
Potsdam
Heidelberg
Turin
Milan
Florence
Naples
Ragusa
Athens
Paris
Lyon
Oviedo
San Sebastian
Granada
Murcia
Barcelona
Pamplona
Centres of the European Prospective Investigation into Cancer and Nutrition
(EPIC)
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B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
They also found a link between a high-fat diet, genetic variations
of a liver protein that binds fatty acids (FABP) and the human

sugar metabolism.
Research at the institute also focuses on the biological mecha-
nisms that may be responsible for dietary preferences. In large
sectors of society, people know what constitutes a healthy diet.
Yet, paradoxically, this knowledge has had little effect on their
eating habits. Many people still prefer to eat high-calorie food
that is less satiable and promotes the development of obesity
and type-2 diabetes. To determine the role that gustation plays
in this phenomenon, scientists at the DIfE are investigating the
molecular mechanisms responsible for taste perception. They
have already succeeded in nding different receptor variants
associated with different taste perceptions.
Links between Diet and Cancer
Many epidemiological data conrm the assumption that diet
plays a major role in the development of cancer. The DIfE has con-
tributed to this insight with its participation in the multi-centre
Europe-wide EPIC study. The ndings of this study show that a
low consumption of bers and a high consumption of red meat
is associated with a higher incidence of colorectal cancer. DIfE
also investigated the effect of fruit and vegetable consumption on
different types of cancer and found indications of a reduced risk
for cancer of the lung and of the oropharyngeal epithelium. The
study also indicated that overweight is an important risk factor
for colon cancer (men and women) and for cancer of the kidney
and breast (women).
However, epidemiological studies do not unequivocally prove
causal connections between diet and cancer. This is why the DIfE
is also using biochemical, molecular and microbiological meth-
ods as well as cellular testing systems and animal models to
establish causality of the associations between cancer and diet.

Preliminary ndings support the assumption that the metabolic
conversion of foreign substances absorbed with food may play
a role in the development of cancer. Metabolism of xenobiot-
ics can inactivate carcinogenic substances, but can also activate
them. Here, the genetically determined variants of the enzymes
involved in the so-called “detoxication metabolism” play a
decisive role. Researchers at the institute were able to show that
the bacteria in normal intestinal ora (Figure 3) can convert for-
eign substances into toxic, mutagenic or possibly carcinogenic
substances. One example is the transformation of arbutin into
the mutagenic substance hydrochinone, which triggered cancer
in animal experiments. High concentrations of arbutin are found
in pear skins and in wheat. Researchers at the DIfE are also study-
ing the inuence of micronutrients like selenium on the develop-
ment of colon cancer and have already succeeded in identifying a
selenium protein (an enzyme) produced by the body itself which
is synthesized more intensively in human colon tumors and can
be induced by components of cruciferous plants.
However, more research is required to show the signicance of
these processes for the development or prevention of cancer. The
scientists at the institute have therefore developed “humanized”
animal models which they will use to study the relationship
between nutrition, inammatory processes and the development
of colon cancer in vivo.
Figure 2
The New Zealand obese mouse gains weight rapidly under a high-fat diet and
develops obesity, whereby the proportion of body fat can increase to over 40
percent (left). Despite a very high fat diet, the mice of the Swiss Jim Lambert
strain did not gain weight but stayed lean, due to their genetic makeup
(right).

Figure 3
Fluorescence marked intestinal bacteria. Intestinal bacteria can transform
nutritional components into toxic substances, which may play a role in
carcinogenesis.
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B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
The concentration of scientists in agricultural,
food and nutritional research in Berlin-Bran-
denburg is among the highest in Europe. The
leading institutions in this eld are the three
universities of Berlin, the University of Potsdam,
the institutes of the Max Planck, Fraunhofer and
Leibniz societies and the universities of applied
sciences in Berlin and Brandenburg. The food
industry, which plays an important role in the
economy of the Berlin-Brandenburg region, is
also an important actor in this eld.
The Aims of the Center
One aim of the Center for Preventive Foods is
to bring together existing resources along the
entire added value chain and develop networks
between them. This is both desirable and nec-
essary, because demand for interdisciplinary
cooperation in both national and international
projects is growing steadily. Linking up the com-
petences of relevant regional research institu-
tions and industrial companies will produce
synergy effects, which in turn allow us to press
ahead with the development
of functional foods with a pre-

ventive effect.
A further goal of the CPF is to
provide new dynamism for
industry by innovations in
the food and nutrition sci-
ences and enhance knowledge
transfer in the functional food
sector by purposefully net-
working science and industry.
The CPF mission is to conduct
research into food components,
starting with agricultural pro-
duction and looking at the
whole value-added chain all
the way to the consumer. In
doing so, we hope to provide
scientic evidence of their
health-promoting effects and
to produce targeted preventive
foodstuffs.
Our research aims to identify
food components with preven-
tive effects and analyze com-
pounds along the value added
Health and Nutrition at the TU Berlin –
the Center for Preventive Foods
The Center for Preventive Foods (CPF), founded in 2007 by the Technical University of Berlin,
brings together important actors from nutrition-relevant sectors of the research environ-
ment in Berlin-Brandenburg. It combines R&D activities in the eld of preventive foods
and will intensify interdisciplinary cooperation between biotechnology, food chemistry

and technology, nutrition science, biology and medicine.
Dr. Edeltraud Mast-Gerlach
Center for Preventive Foods

Figure 1
VLB
TFH
HU
OB
TU
FU
BioTOP
WVEB
BAM
BfR
FH Lausitz
IGZ
IGV
DIfE
UP
MPI Golm
Fraunhofer IAP
ATB
BEN
The research network of the Center for Preventive Foods
– Research institutes, companies and associations
participating in the CPF.
Research
u BfR – Federal Institute for Risk Assessment
u ATB – Leibniz Institute of Agricultural Engineering in

Bornim
u DIfE - German Institute of Human Nutrition in Nuthetal
u IGZ – Institute of Vegetable and Ornamental Crops in
Großbeeren
u Fraunhofer IAP – Fraunhofer Institute for Applied
Polymer Research in Golm
u BAM – Federal Institute for Materials Research and
Testing in Berlin
Industry
u IGV- Institut für Getreideverarbeitung GmbH in
Nuthetal
u OB – Organobalance GmbH in Berlin
NGOs
u BioTOP
u WVEB – Association of the Food Industry in Berlin and
Brandenburg
u BEN – Brandenburg Food Network
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B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
chain, from biosynthesis to processing, and ultimately to con-
sumption. “Our great strength is that we can study the entire food
chain from production to the consumer”, says the spokesman of
the Center, Prof. Dr. Dietrich Knorr. “Our focus is on functional
food components of plant or microbial origin with a health-pro-
moting effect. We are interested, for example, in sweet proteins
as non-caloric sweeteners as well as avonoids and other sec-
ondary plant metabolites, trace elements and polyunsaturated
fatty acids. What is always important for foods with functional
components are sound scientic data and that the nutrition
character of the products is preserved”.

The use of foods that show additional health benets must always
be accompanied by a public information campaign about a bal-
anced diet to ensure that foods with additional health benets
supplement the regular diet in a sensible way.
New Requirements for Food
Dietary awareness and the eating habits of the population have
changed considerably in recent years. In the past it was impor-
tant to eat enough protein, essential fatty acids and vitamins,
whereas now the emphasis is on healthy nutrition. Secondary
food components like avonoids or polyphenols are increasingly
becoming valuable elements of our diet. These bioactive com-
pounds can have a preventive effect and lower the risk of devel-
oping certain diseases like cancer or cardio-vascular disease. The
molecular mechanisms underlying this effect are still unknown,
however. Often it is not the original substance but metabolites
produced either by the organism itself or by intestinal bacteria
that have positive properties. In our research, we aim to identify
these metabolites as well as the original substances and test them
to discover their properties. The CPF has various model systems,
ranging from animal models, cell cultures and reporter gene con-
structs to the spectroscopic methods used to demonstrate cancer-
preventing effects on the skin. The studies are intended to show,
for example, whether endogenous protective mechanisms can be
induced or strengthened. The idea would then be to nd comple-
mentary combinations of food components and possibly preserve
and rene them by cultivation and processing. We intend to focus
on redox systems as well as probiotics and prebiotics and develop
an integrated matrix of coordinated projects for gentle and con-
sumer-friendly processing. The CPF will implement all steps, from
optimizing the formation of the substances in plants, micro-

organisms and/or plant cell cultures to raising the level of the
food components in foodstuffs during processing, identifying the
presence of food components in the organism and demonstrating
their bioavailability and biological effects. We intend to focus on
plant products and look at the entire chain from cultivation to
harvest, and from processing to food intake and biological effect.
Ultimately the medical, nutritional and biotechnological knowl-
edge so obtained will provide the know-how for the industrial
production of preventive foodstuffs and for the manufacture of
health-promoting products.
Together with the Center for Innovative Health Technologies ZiG,
the Center for Preventive Foods will work in the pioneering eld of
TU Berlin: “Health and Nutrition”. The committees of the TU Berlin
recently approved the launch of the Innovation Centre Health and
Nutrition. In these pioneering elds of technology and innova-
tion, we will search for long-term solutions to important social
needs and global problems.
Figure 2: The interdisciplinary research concept of the CPF – Research along the value added chain
Detection methods
Production
Food processing and analytics
Food component extraction · Post-harvest technology · Processing
Bioactivity studies and molecular mechanisms
Bioavailability · Health benefits/prevention · Toxicology
Functional foods
Communication
Target substances
Production systems
Root cell cultures · Cell and tissue cultures · Plants and algae · Microorganisms
Figure 3

Innovation Center Health and Nutrition
Health Technologies
ZiG
Communication
Monitoring
Health sector
ZiG and CPF
CPF
Nutrition and
Preventive Foods
Teaching and Training
Knowledge and Technology Transfer
8
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
These initial foundations later evolved to
become an Institute of the Academy of Sciences,
and the research into nutrition conducted in
Rehbrücke during this period not only had an
impact on research in this eld in the countries
of the Warsaw Pact but also on nutrition research
in West Germany. As a student at the University
of Giessen in West Germany, I often heard lec-
turers referring to the research being conducted
at this Institute and express the wish for the dif-
ferent nutrition research centres in Germany to
cooperate more closely.
When the German Institute of Human Nutrition
was founded as a Leibniz Institute in Potsdam-
Rehbrücke following German reunication,
nutrition research was put on a new scientic

and nancial basis. The founding members con-
sidered it particularly important to orient the
Institute more strongly towards research into
human nutrition and to translate basic research
ndings into dietary habits of the population
on sound scientic grounds. Epidemiology was
assigned such a function alongside with clini-
cal research. Epidemiology therefore initially
became a working group and in 1996 a depart-
ment at the DIfE.
Epidemiology is a relatively new research disci-
pline in Germany. One of its tasks is to discover
ways of lowering the risk of disease by obser-
vation and targeted intervention. The obser-
vational approach requires large groups of the
population as participants and active coopera-
tion from many people to draw long-term con-
clusions about how to prevent chronic diseases.
For the DIfE, dietary and diet-related factors
like obesity are of prime concern. The launch
of a major observational study was discussed
intensively in various European working groups
during the 1990s. Under the coordination of
the International Cancer Research Agency in
Lyon, they formed a consortium, which initially
included the German Cancer Research Centre in
Heidelberg as the German partner. The founding
of the German Institute of Human Nutrition and
the establishment of the working group “Medi-
cal Epidemiology” there offered an opportunity

to apply the approaches being discussed at the
European level in Brandenburg too. At that time,
the consortium took a certain amount of con-
vincing to persuade it that Potsdam was a suit-
able study centre, because all the other 22 cen-
tres of the EPIC consortium came from regions
that had been part of the West during the Cold
War (Figure 1, Page 4).
The Brandenburg component of the European
long-term EPIC study was launched in 1994
with funding from the German Federal Minis-
try of Research and Technology. Some 120,000
inhabitants of Brandenburg received letters ask-
ing them to take part in the study and more
than 27,500 of them agreed. All participants
were asked to ll out questionnaires at home
and then invited to come to a study centre at
the Health Authority of the City of Potsdam,
where further interviews were conducted, the
participants’ blood pressure was measured,
and anthropometric measurements were taken
together with a blood sample. This collection
of data and biological materials forms the basis
for assessing the risks of developing a range of
chronic diseases.
The “Brandenburger Ernährungs- und
Krebsstudie”: A Potsdam Contribution to the
European Prospective Investigation into Cancer
and Nutrition (EPIC)
The long tradition of nutrition research in Brandenburg began when the Russian military

administration decided on 10 June 1946 to move the Institute for Nutrition and Food
Science from Dahlem to Potsdam-Rehbrücke. It was joined in 1948 by the Institute for
Vitamin Testing and Vitamin Research from Leipzig.
Prof. Dr. Heiner Boeing
German Institute of Human Nutrition
Potsdam-Rehbrücke
Department of Epidemiology

9
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
To evaluate the relationships between the risk of disease and
diet and other life-style factors, it is necessary to record medi-
cal events in the cohorts for the disease end points comprehen-
sively and accurately over a number of years that are of interest to
researchers. To do so, all participants in the study are contacted
by questionnaire every two to three years and asked to report on
their new diseases. In this mailed questionnaires, participants
with a new disease are asked to provide information about the
treating physician, whom we then contact to obtain a medical
diagnosis according to the international classication of diseas-
es according to the World Health Organization. A key factor in
the scientic quality of a long-term study is the percentage of
returned questionnaires. Due to the strong commitment of all
study participants, our response rate is high compared to other
studies world-wide, with a return rate for each of the question-
naires (with one exception) of more than 95 %.
The extensive collection of data on dietary and lifestyle factors
gathered at the beginning of the study will be supplemented
by further information enquired during the course of the study.
Together with the information on participants’ diseases, it forms

the basis for the assessment of risk for the various chronic diseas-
es. These risk analyses are conducted both for the EPIC Potsdam
population and jointly with other European study centres. Overall,
the EPIC consortium has been very successful in recruiting study
participants and now has data on more than 520,000 study par-
ticipants. The study is therefore one of the largest worldwide
and a leader in the assessment of risk relationships in Europe.
The focus on diet in this study is of considerable scientic impor-
tance for the Department of Epidemiology, since diet is one of
the institute’s main research themes. Potsdam’s contribution to
the EPIC consortium therefore includes methodology for recording
dietary data, evaluating dietary patterns and investigating the
role of dietary factors for predicting various diseases. A further
focus is on anthropometric parameters and indices, including the
distribution of body fat. The endpoints of interests are type-2
diabetes, cardio-vascular diseases and cancer.
Obesity has an important role to play in this research, for it is
both conditioned by diet and also has major consequences for
the body’s metabolism. Following this sequence of relationships
from diet to adipositas and further to risk of disease is a further
research focus of the Department of Epidemiology.
With its large cohort size, the EPIC consortium is one of the most
active research groups with more than 500 publications up to
now. We estimate that around 200 scientists currently work
with the EPIC data, including the roughly ten researchers at the
Department of Epidemiology at the DIfE. The EPIC research themes
are not always of direct interest to the study participants; rather,
EPIC research sometimes addresses very specic research ques-
tions. However, also their ndings will be used in the long-term
to prevent disease.

From the ndings of this and other available studies we are
beginning to identify a set of dietary and lifestyle factors that
can lead to a considerable reduction of disease risk. This includes
a diet with a strong component of wholemeal cereal products
and high consumption of fruit and vegetables, in combination
with stable body weight – around 25 BMI – over the course of
a lifetime and a minimum level of physical exercise. Another
important factor, of course, is not to smoke. In our study we were
able to show that subjects with a lifestyle of this kind had only a
quarter the risk of developing diseases as those with all risk fac-
tors (Figure 2).
In this way, the study participants from Brandenburg have helped
establish further milestones in determining how we should shape
our lifestyles to avoid the occurrence of chronic diseases in youth
and middle-age and reduce the risk of mortality.
Figure 2
Relative Risk
Preventive Factors
1,2
1,0
0,8
0,6
0,4
0,2
0
0 1 2 3 4
Reducing the combined risk of type-2 diabetes, heart attack, stroke and cancer in the EPIC-Potsdam Study in connection with the presence of preventive factors
(no smoking, no adipositas, a healthy diet and sufcient exercise)
10
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y

The many steps involved, from food ingestion
and chewing, to its breakdown into small-
er units during digestion in the intestines, its
absorption by the body and transportation to
the cells, require many special functions of indi-
vidual organs, which then provide the energy to
different functions of the organism – as in the
heart, brain, muscles or sensory organs.
All these processes are carried out by proteins,
whose structure and function are dened in the
genome and which every human being possess-
es in a large number of variations, which differ
only minimally from those of others. These tiny
differences are what makes every individual dif-
ferent and determine his or her individual food-
processing prole.
Nutrigenomics is devoted to trying to under-
stand these differences and includes two main
elds of research:
One eld concerns differences in the genetic
blueprints, which ultimately produce different
metabolic functions and hence variations in the
risk of developing certain diseases. The other
eld describes the direct reaction of the metab-
olism to the intake of food, through changes in
gene expression in various organs. To give an
example: eating potatoes – i.e., carbohydrates
– causes the organism to react immediately,
programming the organ systems involved to be
ready for future intake of food and thus ensuring

that they remain in a t state for that activity.
The study of these nutrigenomic processes has
produced the rst advances in recent years.
Which strategy can be used to nd out to deter-
mine the genetic differences which are impor-
tant to the metabolism? First of all, we need
a sufcient number of people willing to be
examined more closely and who will consent to
researchers studying their genetic prole. A col-
lective of this kind, which now comprises 2,600
participants, was established in our Department
of Clinical Nutrition at the German Institute for
Human Nutrition under the auspices of a BMBF
project entitled MESY-BEPO – Metabolisches Syn-
drom Berlin Potsdam. In a rst step, we char-
acterised the metabolism of the study subjects,
looking at their blood fat values and at the vari-
ous blood enzymes in the liver, intestines, fat
tissue, muscles and other organs. We then asked
the participants to undergo a glucose tolerance
test. Here the test subjects drink 75 grams of
sugar, and researchers then study the reaction
of the metabolism over a period of three hours,
measuring both the rise in the blood sugar level
and the hormonal responses to the sugar. This
test provides a lot of information about the
metabolism. We also characterised the test sub-
jects with regard to the presence of many genes
in their metabolism.
A rst example concerns how eating a healthy

diet affects the metabolism. It is necessary rst
of all to nd out how quickly the metabolism
reacts to food intake. For these tests we used
pairs of twins and asked one of them to eat a
healthy diet and the other an unhealthy diet for
a period of four weeks. During this time we char-
acterised their metabolism. It was found that,
even after just four weeks, the sugar metabolism
of the twin eating a healthy diet had improved
signicantly – the rise in the blood sugar level
after drinking 75 grams of sugar was lower and
required considerably less insulin to absorb the
sugar into the metabolism. In other words, the
twins eating a healthy diet had high insulin
Nutrigenomics in Berlin-Brandenburg
The metabolism is the basis for all life because it provides the energy for the biologi-
cal processes in the body. This involves a complex network of biological reactions which
facilitate the conversion of the energy gained from food into metabolic energy and at the
same provide the components for constructing and maintaining the organism. Metabolic
pathways are like a transport network within a cell, which must manage many diverse
functions ranging from the intake and utilisation of food to getting rid of waste.
Prof. Dr. Andreas F.H. Pfeiffer
German Institute of Human
Nutrition Potsdam-Rehbrücke and
Charité – Universitätsmedizin Berlin
11
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
efcacy. The other twins, who had eaten a diet richer in fat and
lower in bre – a diet rather typical for Germany – showed a
deterioration of the metabolism, with a greater rise in the sugar

level in the glucose tolerance test and a considerable rise in the
level of insulin, indicating lower insulin efcacy or insulin resis-
tance. It is known from population studies that insulin resistance
is associated with disorders of the fat metabolism, high blood
pressure and an increased tendency towards diabetes and, in the
long term, a higher risk of heart attack and stroke.
Determining the function of variants of individual genes is con-
siderably more complicated. One way of doing so is to use the
hypothesis-driven approach in which a hypothesis about the
function of a particular protein is used as a starting point. We
employed this approach to study a fatty acid binding protein from
the liver. We knew from earlier studies that the sugar production
of the liver is increased by free fatty acids. These, in turn, increase
after food intake, causing the liver to produce more sugar. We
therefore asked two groups of 10 test subjects from our study
collective, which had either a particular genetic variant of this
fatty acid binding protein or the opposite variant, to participate
in the study. Here fat was infused into the subjects to produce a
level of fatty acids resembling that following a heavy meal. At the
same time the various hormones like insulin, growth hormones
or glucagon, which regulate the liver metabolism, were turned
off by administering the inhibitor hormone somatostatin, and
physiological levels of these hormones were produced through
infusions. The purpose of this procedure was to control the regu-
lation of the metabolism by food-dependent hormones. Under
these conditions, we were able to investigate how gene poly-
morphism controls the sugar production of the liver. In fact, the
experiment showed that one gene variant led to marked sugar
production in response to the fats, whereas the other showed
much less marked sugar production. Among the subjects making

up the MESY-BEPO collective, this gene variant was consistently
associated with a signicantly higher body weight of about one
body mass index unit, in other words, an additional kilogram of
body weight per square metre of body surface.
To identify a larger number of gene variants that are signicant
for nutrigenomics without using hypotheses, we need more
precise information about individual differences in the food
response and the scale of the differences. We are currently con-
ducting experiments to determine these differences. With the
information obtained, we plan to conduct a genome-wide study
to map the relationship between certain reactions to food intake
and gene polymorphism in the entire genome. Studies of this
kind, which examine around one million gene variants per per-
son, have recently succeeded in identifying new gene loci, which
may determine a tendency towards overweight, diabetes or sim-
ply body size.
Another strategy for investigating individual responses to food
intake uses so-called gene expression analysis. Here we exam-
ine how certain tissues behave
in response to food-related
stimuli. Important stimuli of
this kind are the hormonal
responses triggered by food
intake. We know, for example,
that the release of insulin is
triggered in this way and that
insulin regulates several hun-
dred genes in the liver. Every
time food is eaten, intestinal
hormones – so-called incre-

tins – are released, which both
intensify the release of insu-
lin triggered by food intake
and also perform other func-
tions that we as yet know little
about. To study their function
in more detail we gave 15 vol-
untary test subjects an infu-
sion of the incretin “Glucose-induced Insulino-mimetic Pep-
tide” (GIP) and looked at the impact it had on gene expression
in fat tissue. GIP is normally released by the cells in the intestinal
mucosa, so that the level of GIP rises after every meal. The more
carbohydrates and fat a meal contains, the greater the increase
in the level of this hormone. We infused this hormone by a drip
over a period of four hours and took a small sample of tissue from
the stomach fat before and after the infusion. From this fat tis-
sue we extracted the information for the protein blueprints, the
mRNA, and then tested the change of its expression levels with a
so-called gene array. Using such a high density of gene samples
on a slide is now standard research practice. In our case, they
contained 44,000 different gene probes, which cover practically
all known human genes at least once. With these gene arrays,
mRNA production can be measured quantitatively.
We were surprised to nd that the GIP stimulated the expression
of genes that play a role in inammatory reactions. This ts with
our observation that when a person becomes overweight and the
amount of abdominal fat increases, an inammatory reaction
occurs in the fat tissue. Among overweight people, the number of
inammatory cells in fat tissue is raised, probably to protect the
fat tissue from infection in the event of injury. The astonishing

thing is that it only takes a food stimulus to trigger the release
of hormones that attract inammatory cells to the fat tissue. An
example of a messenger substance of this kind is MCP1 (mono-
cyte chemoattractant protein 1), a so-called chemokine. Other
interesting genes that we found were those that regulate fat
absorption and storage and those that regulate the biorhythms
and energy balance. All in all, GIP has proven to be a hormone
that manages energy intake and storage very effectively. For this
reason, it is conducive to weight gain. Foods that cause less GIP to
be released are therefore probably helpful in maintaining normal
body weight.
12
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
This study enabled us to better understand the function of indi-
vidual metabolic pathways and ultimately to characterise them in
individuals. Because people’s genetic make-up differs, we would
expect some people to remain healthier if they eat a lot of car-
bohydrates, whereas for others carbohydrates are less important
or even harmful and they do better with a high-protein or even
a high-fat diet. This almost certainly applies to the propensity to
put on weight as well. We expect that it will in the future become
far more plausible to offer people customised dietary advice and
information and that we will be able to predict which foods they
should eat if they wish to live a long and healthy life.
We also expect to be able to inuence the risk of developing
quite a number of diseases by the diet. Examples include long-
chain fatty acids, which are connected with inammatory reac-
tions. They include alpha-linoleic acid, an omega 6 fatty acid, or
alpha-linolenic acid, an omega 3 fatty acid. We already know
that people with gene variants in the enzymes that process these

fatty acids, e.g. delta-6-desaturation and delta-5-desaturation,
are prone to hay fever and allergic eczema to different degrees.
If we can determine more accurately how this connection works,
we will be able to inuence the incidence of these diseases via
diet.
Inuence of Diet on the Risk of Metabolic Illnesses through Hormonal Regulation: After four weeks on a healthy DGE [German Nutrition Society] diet
0 30 60 90 120
Insulin mlU/ml
Time of measurement (minutes)
0 30 60 90 120
Glucose mg/dl
Time of measurement (minutes)
22.06.2007
20.07.2007
22.06.2007
20.07.2007
21-year-old woman 162 cm, 64.5 kg (BMI 24.6 kg/m
2
) = > 63.7 kg (BMI 24.3 kg/m
2
) · Waist: 76.5 =>74.9 cm. Hips: 98.5 =>96.5
(WHR: 0.777 = > 0.776) · 24.3 kg (37.7%) proportion of fat =>24.1 kg (37.7%) · 40.1 kg (62.3%) fat-free mass =>39.7 kg (62.3%)
13
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
In the Capital Region , industry and science are integrated closely.
Following this trend, the food industry has formed a successful
network– the Brandenburg Food Industry Network (BEN), which
is managed jointly by the Potsdam Chamber of Commerce and
Industry and pro agro e. V.
The Food Industry – An Important Sector

With more than 10,000 employees and sales worth more than 2.5
billion Euros a year, the mainly small and medium-sized compa-
nies in the food industry form one of the most important industries
in Brandenburg. The food sector includes many agricultural enter-
prises and food processing companies, which produce mainly
meat and sausage, but also bakery products, confectionery, fruits
and vegetables, and dairy products. Alongside well-known com-
panies like Campina Milchprodukte GmbH, Katjes Bonbonfabrik
GmbH or Coca Cola GmbH, which have production facilities in the
region around Berlin, a number of regional companies like the
fruit and vegetable processing company Spreewaldkonserve Golßen
GmbH, Werder Feinkost GmbH or JÜTRO Konservenfabrik GmbH &
Co. KG have succeeded in establishing themselves on the market.
The Network
To support these companies, the Potsdam Chamber of Industry
and Commerce (IHK) founded the Brandenburger Ernährungs-
Netzwerk (Brandenburg Food Industry Network) in 2004. Funded
by the Brandenburg Ministry of Labor, Social Affairs, Health and
Family, the network provided assistance for 30 companies within
two years. As part of the funding program of the Brandenburg
Ministry of Economics, the network was reorganized in 2008. IHK
Potsdam and pro agro – the Association for Promoting Rural Areas
in the State of Brandenburg – now work hand in hand to network
and support companies in the food sector. The aim is to improve
cooperation between companies and institutions that have close
links with industry both in- and outside the region and thereby
increase their competitiveness. A particularly important concern is
technology transfer. The network now includes 54 member com-
panies and institutions. Nine working groups, established and
led by members of BEN e. V., have met to discuss issues like prod-

uct development, logistics, regional products, agriculture, healthy
nutrition, marketing and food safety.
Product Innovation
Although our food has come from the same sources for thousands
of years, innovations are just as important in the food industry
as in other sectors. Small and medium-sized companies, which
often do not have R&D departments of their own, need networks
and cooperation to benet from application-oriented research
conducted in the scientic institutions and universities of the
region. Based on their good knowledge of markets and prod-
ucts, they are well placed to assess requirements very well and
request the specic technical solutions they need. The relevant
issues range from questions of product presentation and pack-
aging to many different incremental innovations in production
processes or quality features, or the development of new prod-
ucts, particularly for market niches. Themes that currently receive
a lot of attention are hypoallergenic foods and the development
and marketing of products for the elderly. The network organizes
workshops on these issues and provides support, such as check-
lists, to help companies tailor products to particular target groups.
Food Safety and Hygiene
Food safety continues to be a highly sensitive issue. Here both the
market and the authorities continually demand improvements.
At the same time, there is a steady supply of new ndings from
microbiological research, which can be translated into quality
assurance technologies in cooperation with the companies using
them. The network allows its members to stay up to date with
developments in the eld of food hygiene and helps them apply
new advances in practice. Here it has two experienced and com-
mitted partners in IFTA Akademie GmbH and matec GmbH from

Wildau. A tradition of cooperation between these companies
and rms in the food industry going back many years ensures an
atmosphere of openness and trust in meetings and discussions.
Cooperation Beyond the Region and Internationalization
BEN has also cooperated with organizations outside the region
for many years. The association holds regular meetings with food
networks from other parts of Germany to exchange experiences.
Particularly the older networks in this “Cluster Council” are enor-
mously important to BEN as providers of know how. A number of
joint projects are planned for the future. International networks
are also important for Brandenburg’s food industry. BEN is there-
fore cultivating contacts with partners in a number of countries,
including Belgium and England, to meet other regional food net-
works and develop joint projects, mainly devoted to know-how
transfer. The international cooperation event PROMOFOOD, which
takes place in Potsdam every year, offers an excellent forum for
exchange between national and international cooperation partners.
The region’s companies have recognized the opportunities that
networking with each other and with research facilities and tech-
nology providers offers. The projects in hand are challenging -
requiring successful implementation – as a network we can make
that happen.
BEN – the Food Network for the Capital Region
Anja-Christin Faber
Service- und BeratungsCenter (SBC) Industrie- und Handelskammer Potsdam

14
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
One emphasis of our research
group lies in analysing the

modulation of gene expression
in cellular differentiation. This
process can be signicantly
inuenced through the inter-
action between genes and
naturally occurring compounds found in edi-
ble biomaterials. Consequently, as the second
emphasis of our research group we study the
capability and mechanisms of natural products
to interact with genes and gene products. The
multidisciplinary approach of our research group
consists of fundamental as well as applied
research. The data obtained by our systematic
studies, described in more detail for the natu-
ral product resveratrol below, will be useful for
modeling effects of natural products on, for
instance, fat cell differentiation. Clearly, natural
products with a benecially active prole can be
further exploited, for the development of nutra-
ceuticals and/or for the development of novel
chemical structures for treating insulin resis-
tance and obesity.
To Your Health!
When toasting with a glass of wine, we say
“Zum Wohl” in German, “Santé” in French,
“Alla salute” in Italian, and “Salud” in Span-
ish. Coincidently, all literal translations refer to
“to your health” in English. Perhaps since long
ago, people have already realized the associa-
tion between wine and health. But not until

1992 a natural compound called resveratrol was
identied in red wine. Since then scientists have
become interested in exploring the potential
health benets of resveratrol. The discovery of
resveratrol also leads to the speculation that it
might help explain the “French Paradox”, the
observation that the French have relatively low
incidence rates of heart disease, dispite having a
diet relatively rich in fats. Nevertheless, how can
resveratrol benet our health?
Resveratrol in Wine
Resveratrol is a phytoalexin produced by several
plants when undergoing attack by pathogens
such as bacteria or fungi. After fermentation of
red grapes, resveratrol is easily released from
the skin. Therefore, red wine is the best natural
source of resveratrol. To date, there is mounting
evidence on the potential benets of resvera-
trol in slowing the aging process, extending the
lifespan, and preventing the manifestation of
type II diabetes.
Resveratrol and Sirtuin 1
Resveratrol is thought to interact with a
human deacetylating enzyme called “sirtuin
1”. The potential resveratrol-sirtuin interaction
deserves much attention because sirtuin 1 has
been demonstrated to inuence the activity of
metabolic sensors and their subsequent effect
on gene expression. In rodents, resveratrol has
been shown to mimic dietary energy/calorie

restriction (that is, food deprivation without
malnutrition) by activating sirtuin 1 and extend
the healthy lifespan of animals fed a high-fat
diet. This is accompanied by lower blood glu-
cose and increased insulin sensitivity in diabet-
ic-prone rodents. Other protective functions of
sirtuin have been proposed in the regulation of
molecular key players that are involved in gene
expression and post-translational modications
of proteins. For example in fat cells, sirtuin 1 can
inhibit adipogenesis by decreasing white adipo-
cyte formation through nuclear receptor PPARg
inhibition by deacetylating the repressor-pro-
Nutrigenomics and Gene Regulation
As a newly founded research group in 2008 at the Max Planck Institute for Molecular
Genetics, the Nutrigenomics and Gene Regulation Laboratory has been exploring health
implications of the interaction between nutrition and genomics or the so-called “nutri-
genomics”. The interaction and the regulation of genes play an important role in various
molecular processes of human metabolic diseases.
Chung-Ting Han
Susanne Holzhauser
Sascha Sauer
Max Planck Institute for
Molecular Genetics

Myristicin
Saponins
Quercetin
15
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y

tein NCoR. In the pancreas, sirtuin 1 is shown to improve insulin
secretion by repressing the UCP-2 protein in the -cells. In the
liver, sirtuin 1 promotes gluconeogenesis via FOXO1 and PGC-1a
by inhibiting glucose formation and stimulating glucose uptake
by cells. Moreover, sirtuin 1 is a positive regulator of LXR, which
is a cholesterol sensor in the liver and regulates whole-body
cholesterol and lipid homeostasis. In the mitochondria of brown
adipose tissue and skeletal muscle cells, sirtuin 1 can stimulate
the turnover of cellular energy metabolism also with the help
from PGC-1a. Additionally, sirtuin 1 promotes the survival of
muscle cells in the heart and protects neurons from cell death
via NFkB signaling cascade in the brain tissue. Sirtuin 1 can also
deacetylate histones of the chromatin to repress gene transcrip-
tion on a more global level. In a nutshell, sirtuin 1 seems like a
promising target in the discovery of dietary therapeutics that can
either activate or inhibit the enzymatic activity of this protein.
Our Approach
Although resveratrol is a strong activator of sirtuin 1, the bio-
availability of resveratrol is fairly low in humans. In order to
identify alternative sirtuin modulators, we utilize a systematic
approach to screen and characterise more potent compounds that
are derived from edible biomaterials (Figure 2). In the rst screen
we identied a number of molecules that showed signicantly
higher activation for sirtuin 1 than resveratrol.
The interactions of these molecules with sirtuin 1 are currently
being characterised using biophysical, cell-based biochemical,
physiological and modern genomic methods, such as second-
generation sequencing. Second-generation sequencing with
Solexa technology (www.illumina.com) can be applied ef-
ciently for studying RNA expression. Secondly, the interaction of

DNA-binding proteins such as nuclear receptors can be analysed
accurately in different cell states. Therefore, a specic antibody
against the protein under investigation is used for immuno-
precipitation including the DNA sequences of the genome that
interact with the precipitated protein. The DNA sequences of the
genome that bind with the protein of interest are then identi-
ed and quantitatively analysed using the Solexa sequencer. In
order to ascertain the effects of natural products on the proteome
quantitatively, high-resolution electrospray ionisation (ESI) mass
spectrometry will be employed.
Our Projects
In different projects funded by the BMBF, our research group
studies the mechanisms of a number of nuclear receptors and
chromatin-modifying proteins involved in metabolic processes as
well as the interaction of these proteins with small molecules, i.e.
natural products. To pursue our research goals, in the frame of
the European FP-7 large-integrated project READNA, we are addi-
tionally and actively developing modications of cutting-edge
technologies such as second-generation sequencing for covering
the spectrum of our research projects.
ZeaxanthinNaringenin
SulphoraphaneResveratrol -Carotene
Lutein
Lycopene
Anthocyanins
Figure 2
High-
throughput
Screening
in vitro in vivo

Biophysical
Property
Genomic and
Proteomic
Profiling
Mathematical
Modelling of
Cellular Pathways
Animal
Model
Molecular
Pathways
High-
throughput
Screening
in vitro in vivo
Biophysical
Property
Genomic and
Proteomic
Profiling
Mathematical
Modelling of
Cellular Pathways
Animal
Model
Molecular
Pathways
With a broad spectrum of research objectives, dynamic approaches are used to discover potential sirtuin 1 modulators for the prevention and treatment of
metabolic diseases.

A wide variety of phytochemicals can be found in food supply. (modied from photo by Keith Weller, USDA/ARS)
16
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
Food Processing
The main priorities in food processing are that
the products are safe, the methods of process-
ing them are sustainable and that the products
themselves are functional ().
Current research in food process engineering
at Berlin University of Technology focuses on
developing sustainable and gentle processing
technologies. The methods investigated include
hydrostatic high pressure, pulsed electric elds,
ultra-sound, super-critical carbon dioxide,
high-pressure homogenization, light pulses
(with Cornell University, Ithaca, NY), infra-red
radiation (with SiK, Gothenburg), cold plasma
(with the Leibnitz Institute of Agricultural Tech-
nology Bornim), sub-critical water (with the
German Institute for Food Technology, Quaken-
brück) and combinations of these methods.
Food Safety
Based partly on research conducted at TU Ber-
lin, hydrostatic high pressure technology, in
which water or oils are used as the pressure-
transmitting media, is now being used industri-
ally worldwide to pasteurize and modify foods
and food constituents. High-pressure steriliza-
tion, which uses a combination of high pressure
and temperature, is very close to being ready for

industrial use. Basic research at Berlin University
of Technology, which showed that not only bac-
terial spores, but prions and viruses, too, can be
successfully inactivated, has won international
research prizes (www.tu-berlin.de/~foodtech).
In high-pressure/high-temperature processes,
the adiabatic heat generated and the fairly even
distribution of temperature within the products
are used to guarantee the gentle processing of
foods and thereby prevent the destruction of
nutrients.
High-pressure low-temperature processes per-
mit foods to be frozen and thawed without
destroying nutrients and open up a wide range
of new applications, such as storing organs at
low temperatures and inactivating pathogenic
micro-organisms in frozen foods by alterna-
tion of pressure-induced ice-crystal forms and
the associated changes in volume. The principle
of action of high-pressure processes (activation
volume) differs from that of thermal (activa-
tion energy) processes and acts specically on
pathogenic micro-organisms like salmonella
or listeria. Since only non-covalent bonds are
affected, valuable food components (like vita-
mins or aromas) are preserved. The Senate Com-
mission on Food Safety (SKLM) of the German
Research Foundation (www.dfg.de) has issued
a safety evaluation of the process, the rst one
world-wide.

Sustainable Processes
Pulsed electric eld treatment can be used to
stress biological membranes and permeabi-
lize them reversibly or irreversibly. This makes
it possible to accelerate mass transfer opera-
tions (e.g., drying, extraction, compression,
expression) and to implement selected struc-
tural changes, for instance to also improve water
absorption. About 250 kJ/kg are required for
thermal permeabilization of plant membranes
(e.g. of sugar beet). Permeabiliziation using
pulsed electric elds requires only 5-10 kJ/kg
and processing times in the order of seconds.
In cooperation with the German Institute for
Food Technology (DIL) and as part of an inte-
grated EU project (www.novelq.org), applied
basic research is being conducted into this pro-
cess to make it industrially viable. This process,
too, has been subjected to a safety evaluation
Food Technology for New Markets from
TU Berlin
Every 18 to 21 days, we need to consume a volume of food and uids equivalent to our
body weight. Within an average life-span, we therefore need around 100 tons of food.
Because of the growing world population and the associated reduction in agricultural
areas, it is essential to nd ever more efcient ways of producing and processing food,
which use resources sparingly.
Prof. Dr Ing. Dietrich Knorr
Berlin University of Technology
Institute of Food Biotechnology and
Food Chemistry

Department of Food Biotechnology
and Food Process Engineering

17
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
by the SKLM of the DFG (www.dfg.de). High-pressure treatment
in the lower pressure area of approx 100 MPa can be used to
induce stress and thereby raise the thermal resistance of pro-
biotic starter cultures. The cultures can then be preserved using
the spray-drying method rather the freeze-drying method more
common in the food sector. This reduces the energy required from
around100,000 kJ/kg water removed to 4,000–6,000 kJ/kg.
Production Functionality
Modern targeted and customized processing methods for func-
tional foods should not only aim to ensure product safety and
quality. They should also provide additional benets, such as
superior nutritional quality. Pulsed electric elds in the low-
energy range facilitate stress induction (for example, in apples,
grapes and oil seeds) to increase the production of secondary
metabolites like polyphenols and phytosterol with anti-microbial
and anti-oxidative properties. Pulsed electric eld treatment may
also facilitate the inactivation of pathogenic micro-organisms in
raw milk and human milk under preservation of natural anti-
microbial enzymes like lactoperoxidase or the anti-microbial lac-
toferine, which are inactivated in conventional thermal pasteuri-
zation processes.
The Importance of Food Technology
One of the most important goals of the European Technology Plat-
form: Food for Life () is to create functional foods
tailored to the preferences acceptance and needs of consumers,

with the long-term objective of personalizing food. To generate
tailor made foods, it is essential to understand the relationships
between food and food component processing and the structures
and functions affected. This research challenge is reected in the
development plan of the Food Technology Department at Berlin
University of Technology, in which the three disciplines
_
Food biotechnology and process engineering
_
Food quality and functionality and
_
Food process engineering
will jointly investigate this central theme of the process-struc-
ture-functionality interactions.
A further important goal of the ETP is the integration of the food
chain from food production all the way to consumption. The
excellent concentration of research institutes in this eld in the
Berlin-Brandenburg area ensures that this integration is achieved
here at a level that is unique in Germany. It is and will be imple-
mented successfully in the Center for Preventive Foods (CPF) and
the Innovation Center Health and Nutrition (IGE).
Figure 1
Facility for pulsed electric eld (A) – and high-pressure treatment (B) on a pilot
scale at Berlin University of Technology. Parameters for a) continuous 600 kg/h,
maximum voltage 50 kV, maximum frequency 400 Hz; b) batch max. pressure
800 MPa, max. T 60°C, volume 0.7 L.
BA
18
B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y
What was originally conceived as a means of

promoting intestinal health is now increasingly
subjected to scientic scrutiny to understand the
underlying mechanisms. In some cases probiot-
ics have been developed as a form of preventive
medicine. Studies have been published showing
that certain probiotic strains can be used suc-
cessfully to alleviate the symptoms of the bowel
disease Morbus Crohn or to alleviate cold symp-
toms and make colds clear up more quickly.
The New Probiotics
When ORGANOBALANCE was founded in 2001,
many of today’s applications of probiotic cul-
tures as specic promoters of health still had to
be explored. The word “probiotic” means simply
“for life”, and dates back to the early twentieth
century when scientists noticed that the regular
consumption of food fermented with lactic acid
bacteria brought health benets. This is what
convinced ORGANOBALANCE that there was still
much to be discovered about the real benets of
probiotics and that naturally occurring probiotic
strains probably offer enormous potential for
development and benets for consumers.
Therefore we began to evaluate the large variety
of naturally occurring “good micro-organisms”
systematically and built our own collection of
strains of micro-organisms, specializing in food-
grade lactic acid bacteria and yeasts, which has
been expanded continuously for fty years. In
recent years we have used innovative screening

methods and raster scans to identify new strains,
characterize them and then develop them to
product maturity. In some cases these efforts
have led to completely unexpected and innova-
tive applications.
As an illustration of our work in this eld, we
would like to present a project here whose
development is already advanced. In close
cooperation with BASF Future Business GmbH,
ORGANOBALANCE has succeeded in identifying
and describing a naturally occurring bacterium
of the
Lactobacillus paracasei species, which
selectively recognizes the caries pathogen
Strep-
tococcus mutans and binds it. In highly sensitive
screening assays developed specically for this
purpose by ORGANOBALANCE, we ltered a strain
from our own collection of bacteria, which can
recognize and bind the caries pathogen under
the conditions that prevail in the mouth. The
Lactobacillus cells function as molecular hooks,
which attach themselves to the surface of the
mutans cells. Mutans cells masked in this way
can no longer adhere to the teeth as micro-
aggregates, where they usually embed them-
selves using self-generated mutan, if sugar
is present, and produce cariogenic acids. The
mutans bacteria can thereby be gently and
effectively removed from the mouth (for exam-

ple, during teeth-brushing) without harming
other oral ora.
Probiotics and the Health Claims Regulation
Consumer-protection regulation requirements
mean that it is of utmost importance for this new
generation of probiotics to be selected accord-
ing to their function and effects if they are to
be brought to market. In Europe, health-related
claims made for functional components in foods
must be tested and evaluated under the Euro-
pean Health Claims Regulation. This means that
all products for which health-related claims are
asserted must have proven their relevance for
the health benet in question in efcacy stud-
ies. Terminology like “supports”, “regulates” or
ORGANOBALANCE – From Spin-Off to Successful
Probiotics Producer
Probiotic bacteria have been widely discussed for a number of years, especially in Europe.
They rst became known as relatively unremarkable “useful bacteria” in special yoghurts
with rather vague promised effects (like boosting our immune system). Now, however,
they increasingly present themselves as probiotic strains with special properties, which
are used for various purposes and in different forms. These include traditional dairy prod-
ucts – still the main application eld –, dietary supplements in tablet form and cosmetic
products.
Prof. Dr. Christine Lang
CEO
OrganoBalance GmbH

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B i o T O P i c s 3 6 _ M o l e c u l a r N u t r i t i o n R e s e a r c h a n d F o o d Te c h n o l o g y

“improves the immune system” will no longer be permitted unless
the relevant company can present intervention studies that prove
the claim and hence the efcacy of the component concerned.
The success of these complex and expensive intervention studies
depends on being able to perform step-by-step selection pro-
cesses during product or active ingredient development until the
best candidate is found (a standard procedure in drug develop-
ment). From the large number of existing strains, ONE is thereby
eventually selected that exhibits the desired properties. At this
stage, the candidate in question will already have proven its
efcacy in in vitro studies and possibly in animal models too.
ORGANOBALANCE uses this search strategy to lter out the “dia-
mond” from a large collection of wild-type strains systematically
by ever more stringent test procedures. We demonstrated in ini-
tial assays that it is possible using this method to prove conclu-
sively the effect-related properties identied at laboratory level
as an effective principle in animal studies and in studies using
test subjects, thus paving the way to market maturity. As a new
form of application, the active strains are also eligible for patent
protection.
ORGANOBALANCE Markets and Fields of Business
Using its own collection of strains and its specially developed
OASSYS® screening technology, ORGANOBALANCE has succeeded in
tapping the potential of new effective micro-organisms for many
areas of application.
Alongside new strains of probiotic bacteria for use in cosmetics
(active agents derived from lactic acid bacteria that specically
stabilize and regenerate the protective micro-ora of the skin),
our developments include strains for food applications, such as
an antagonist to combat caries-generating bacteria or the stom-

ach germ Helicobacter pylori, as well as probiotics for animal
health.
ORGANOBALANCE started out as a spin-off of Technische Univer-
sität Berlin. Today, the company has 28 employees and is con-
sciously customer-oriented. We predominantly conduct projects
in the form of license models.
This makes us a reliable and innovative cooperation partner for
the manufacturing industry in the eld of R&D. One example is
our strategic partnership with BASF, with whom we have coop-
erated successfully in a range of projects since 2002. We are
engaged in many other development projects, some of which are
at laboratory and others already at pilot stage, in close coop-
eration with medium-sized and large companies in Germany,
Europe and North America.
In these projects, we use synergies in order to bring together the
expertise and the proprietary bacterial strains of ORGANOBALANCE
with the market and product know-how of our partners as effec-
tively as possible. ORGANOBALANCE thereby also makes available
its know-how in process development and formulations. Since
2007, we have also been able to offer pilot production facili-
ties. With 150 liters of fermentation and drying capacity, we can
provide product batches for testing purposes. ORGANOBALANCE is
consequently well placed to begin producing its own cultures.
For the coming period, we also see great development potential
for specic functional natural components or strains, especially in
the elds of nutrition and preventive medicine. Micro-organisms
traditionally used in foods, such as lactobacillae and yeast, which
have GRAS (generally recognized as safe) or QPS (qualied pre-
sumption of safety) status, therefore have a very good chance of
reaching consumers soon.

During the next twelve to eighteen months, we expect to see the
rst of our products (“Invented in Berlin”) to come on the market
– perhaps with the eld of dental care taking the lead.
Figure 1
Scanning EM: Photo of a co-aggregate of Lactobacillus and
Streptococcus mutans (Copyright: BASF SE)
Paving the way from idea to proof of concept to commercial success
TOP 50
is aimed at scientists who are planning to commercialize their
scien tic projects in the form of a spin-off, cooperation with a
company or by licensing.
TOP 50
is a joint project of Freie Universität Berlin, Charité - Universitäts medizin
Berlin, the University of Potsdam and BioTOP Berlin- Brandenburg. It is
devoted to intensifying technology transfer in the life sciences.
TOP 50
is focusing on the decisive step of proof of concept. The conversion
of new scientic insights into innovations often fails because indi-
vidual projects are not developed far enough or proof of concept is
not achieved, so that the concept is not adopted by industry. We
help to close this gap between fundamental and applied, commer-
cially oriented research and development.
www.biotop.de/top50/

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