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LESAFFRE HUMAN CARE supported by


more than 150 years of experience in
biotechnology proposes
1- stable Probiotic yeasts (Boulardii and
pro GI + clinically tested on IBS) and
Bacteriae (B Subtilis)
2- Mineral Yeasts: SeleniumChromium- Zinc
3- inactive yeasts, Glutathione yeast,
B Vitamins yeast, Beta-Glucans.
Vit B yeasts and Mineral yeasts support a
wide range of generic EFSA claims (ask
for our brochures)
www.lesaffrehumancare.com

www.stolz-concept.de

Were taking a (super)critical look at extract quality

FLAVEX Naturextrakte GmbH info@flavex.com www.flavex.com

0_Sommario:Sommario 01/10/12 12:27 Pagina 1

CONTENTS

y
r
o
t
c
e
r
i
D

VITAMINS

Direttore Responsabile (Editor)


Franca Leone Mori
franca@b5srl.com

Direttore Generale / General Manager


Michaela (Micky) Carmagnola
micky@b5srl.com

Herbal ingredients: The solution to


innovate in health and nutrition
Thomas Pauquai
Jrme Cantin

Benegut - Beneficial effects for


digestively- stressed consumers
Sybille Buchwald-Werner

The effect of NutriMore on satiety


and energy intake
Sonia Pombo
Roberta Re

Promozioni / Sales
Maurizio Bozzoli
maurizio@b5srl.com
Marco
marco@b5srl.com
David Bozzoli
david@b5srl.com

Abbonamenti / Subscriptions & Accounts


Stefania
stefania@b5srl.com

B5 srl
via Mario Donati, 6 - 20146 Milano - Italy
Tel. 0039.02.83241119
Fax 0039.02.8376457

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Web site

Special regulation for the authors: upon acceptance of an


article by the journal, the author/s will be asked to transfer
copyright of the article to the publisher. This transfer will ensure
the widest possible dissemination of information. The ideas
expressed in the journal are those of the authors and not those
of the publisher.
DTP: Graphia Studio, Pavia - Printing: PI-ME, Pavia.

16 The use of Medium Chain


Triglycerides (MCTs) as medical
foods
Hiskias G. Keizer

20 M.E.D. Integral Propolis: The


evolution of the working process in
natural complex matrix
Alfredo Fachini
Nicola Volpi

VITAMINS

All right reserved to B5 srl. No part of this publication may be


reproduced, stored in a retrieval system or transmitted in any
form or by any means: electronic, mechanical, photocopy,
recording, or otherwise without the prior permission of the
publisher B5 srl.

of BCM-95 Curcumin
Terry Lemerond

Directory

www.b5srl.com

11 The incredible natural power

1_PAUQUAI:Ingredients 02/10/12 08:44 Pagina 2

ingredients

Herbal ingredients: The


solution to innovate in
health and nutrition
THOMAS PAUQUAI
JRME CANTIN
Nutraveris
Parc Technologique du Zoople
18 C rue du Sabot
22440 Ploufragan, France
www.nutraveris.com

ABSTRACT
Whereas the Regulation (EC) 432/2012 of 16 May 2012 has been published, 222 approved claims have appeared on the community
list, concerning principally vitamins and minerals. But what are the remaining possibilities in terms of communication? Thats the
question we want to bring some answers
It was only a few months ago when some people believed that the
previously heralded big Health Claims revolution was never going to
happen. Today, it is clear to everyone that the implementation of
Regulation (EC) 1924/2006 on nutrition and health claims has
already made good progress through the publication of the
Regulation (EC) 432/2012 of 16 May 2012 establishing a list of
permitted health claims made on foods, other than those referring
to the reduction of disease risk and to childrens development and
health.
From then, five scenarios have to be considered for claims:
Approved claims appear on the community list, and are usable in
the whole European Union, if conditions for use are
respected.
Unapproved claims are included in a
community register, and must be
removed from labels and from
any communication before the
end of a transition period of 6
months, the 14th December
2012.
Claims that were not
submitted for evaluation,
and therefore that do not
appear on any list, must
be pulled off from the
market if not done
before.

Unevaluated claims will be taken care of later and therefore


remain usable.
On-hold claims, including some plants and other ingredients,
are also usable.
It is therefore clear that adding all those claims related to plants to
list of on-hold claims, whereas they had been previously
negatively evaluated by EFSA, constitutes a real breath of oxygen for
products developers, who can now plan to communicate in the
short term, on slimming as well as on water elimination or joint
health, which was not possible in 2011.
However, several questions remain For how long is this going
to be possible? When will these claims be then evaluated? Although
no date or time length has been provided by the Commission,
everything suggests that many discussions are going to be held
between Commission and EFSA, in order to determine how these
claims are, from now on, going to be re-evaluated. Assuming that
there is at least one year left does therefore not sound unrealistic
Until now, the vast majority of claims accepted by EFSA refer to
vitamins and minerals. And even if the process for evaluation of
plants has quickly been put on hold, plants already evaluated by
EFSA received negative opinions. Hence, whereas communicating
on health benefits of vitamins and minerals will remain possible,
there is much more uncertainty about communication on plants.
This general concern about health claims eclipses another
essential question, about the use of plants in health and nutrition
products. Indeed, innovation and differentiation between products

1_PAUQUAI:Ingredients 02/10/12 08:45 Pagina 3

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come from plants, and will continue to do so. The realm of


possibility on vitamins and minerals is very small. Thus, to innovate,
you have to use new plants or new extracts. Such raw materials
must, prior to their use, be authorized and meet requirements of
Regulation (EC) 258/97.
Although an extract of green tea, fennel or harpagophytum for
example, can be easy to find for a contract manufacturer, question
about their regulatory status is inevitably asked when formulating
the product. In contrast with vitamins and minerals, whose
authorized forms in dietary supplements or other foodstuffs appear
in positive lists that are valid across all European Union, there is no
European harmonization for plants. National legislations are
therefore the ones that apply, each country being free to establish
its own lists of authorized and/or banned plants. Thus, most of
Member States have positive and even negative lists of plants for
dietary supplements.
As long as national legislation applies with implementation of
these positive and negative lists, it must establish its own safety
criteria. Lets take the example of green tea again: whereas only
aqueous extracts are authorized in France, Belgium allows
marketing of hydro-alcoholic extracts made with low alcohol
concentration solvents on its territory, hence creating a disparity
within the EU. What does Europe think of this then? EFSA has
deeply considered the question of safety of green tea in a
compendium firstly published in 2009 and replaced in 2012 by the
Compendium of botanicals reported to contain naturally occuring
substances of possible concern for human health when used in
food and food supplements (EFSA Journal 2012, 10 (5), 2663).
Considering the scientific literature available at this time, the
European agency has decided that only aqueous extracts produced
with the same manufacturing method as for traditional green tea
infusions are considered as safe, if their concentration in
polyphenols does not exceed the amounts normally contained in a
traditional consumption of green tea. Thus, French regulation
corroborates EFSAs opinion, but the latter discredits Belgian
regulation, therefore reinforcing the feeling of disharmony in the EU.
If the plant does not appear in any list, and if no significant
consumption has been recorded prior to 1997 in the EU, then it
falls under the scope of European Regulation (EC) 258/97, which is
currently under revision. This plant will therefore be considered as a
new food product or novel food. Before being approved for
marketing, a novel food must be the subject of a scientific
evaluation. It is on this basis that an authorization will be or will not
be delivered for marketing of the considered product in the
Community. Novel foods may neither represent a danger to
consumer, nor be misleading, nor have an unfavorable nutritive
effect. Procedure described in Regulation (EC) 258/97 provides

that the applicant shall submit a dossier to the competent authority


in the first Member State where product will be marketed. The
concerned Member State must complete a first evaluation of the
product, then decides whether an additional risk evaluation is
necessary or not, and transmits its evaluation report to European
Commission and to other Member States. Among the large diversity
of ingredients or food products concerned by this regulation can be
mentioned Magnolia tree bark, guar gum, noni juice, dehydrated
baobab fruit pulp, etc.
A simplified procedure called substantial equivalence procedure
may apply if a novel food or food ingredient is found to be
substantially equivalent to an existing food or food ingredient. It is
therefore necessary to prove, on the basis of available and generally
accepted scientific data or following opinion from competent
authority, that the novel food is equivalent to the existing one in
terms of composition, nutritive value, metabolism, expected use
and amounts of undesirable substances. In that case, the complete
novel food procedure is not necessary, a simple notification is
considered.
In nutrition and health, innovation and differentiation has come and
will keep coming from plants, the realm of possibility with other
active compounds (vitamins, minerals, omega-3) being quite
small. Even if the use of plants is more and more regulated and
controlled (novel food, claims, positive and negative lists, limit
doses), which creates new time and financial constraints for
industrialists (analysis, studies, dossiers, evaluations), they allow a
real distinction and add value to products.
Finally, it is true that this market gets tougher and tougher for
offer saturation reasons as well as for regulatory reasons.
Concerning offer, the number of proposed products is very large,
and they have been very similar to one another for several years
without any real innovation or distinction. Regulatory reasons are
constraints when launching (regulatory status of ingredients) and
especially when communicating on a product. These are stronger
than five years ago.
Though, one has to admit that despite these constraints, the
Western European market for dietary supplements represents 8
billion (roughly 500 million units), with a two-digit growth rate
(+10% per year average), catching up with the US market, the
historic leader, which is worth 10 billion (source Euromonitor,
2011). And in this growing market, plants play a very
important role since in France for example, they are the
one category that pulls the market up (source
Syndicat de la Dittique et des Complments
Alimentaires, SDCA, France,
Chiffres cls 2010,
April 2011).

2_BUCHWALD:Ingredients 01/10/12 12:31 Pagina 4

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Benegut - Beneficial effects


for digestively- stressed
consumers
SYBILLE BUCHWALDWERNER
Vital Solutions GmbH
Hausinger Strasse 4-8
D-40764 Langenfeld, Germany
Tel
+49 (0) 2173 10 98 202
Fax
+49 (0) 2173 10 98 210
Sybille.Buchwald-Werner@
vitalsolutions.biz
www.vitalsolutions.biz

Vital Solutions is launching a new intelligent, science-backed ingredient for gut health.

IMPORTANCE OF GUT HEALTH


Maintaining optimal digestive health is particularly important to
vitality and well being throughout all stages of life. Normal bowel
habits vary considerably from person to person with regard to
frequency of bowel movements, bulk and consistency of stools. The
efficiency of each persons digestive tract can make all the
difference to daily energy and overall health. Nearly everybody
experiences gastrointestinal discomfort, which affects quality of life.
Symptoms can be bloating, altered intestinal mobility and transit as
well as abdominal pain or cramps and rumbling. Often these
symptoms are combined with poor mood, lack of concentration and
energy and may consequently prevent people from
sleeping, working, exercising and socializing with
friends. A survey of over one thousand
US consumers reported that poor
digestive health impacts
lifestyle, with 34% feeling
uncomfortable in social
situations and nearly 20%
being limited in physical
activity and exercise (1).
Gastrointestinal
discomfort is mainly
triggered by ileum
contractions, which can
be caused by several
factors. For example:

daily stress; food sensitivity and allergies; infections; genetic


predisposition; altered gut flora or deregulation of brain-gut crosstalk; any of which may lead to the development of gastrointestinal
disorders, dyspepsia or irritations like irritable bowel syndrome
(IBS).
Promoting digestive comfort includes regulation of transit
through the gastrointestinal tract and easing of pain associated with
digestion as well as support for the reduction of the causes that
lead to gastrointestinal discomfort. The reduction of gastro-intestinal
discomfort is considered to be an indicator of improved gastrointestinal function, and to have a beneficial physiological effect (2).
Gastrointestinal disorders are divided into structural and
functional disorders. Structural diseases, e.g. hemorrhoids, or types
of colitis like Crohn's Disease, can be identified by pathologists and
at times cured by medical technology. The nonstructural, functional
gastrointestinal disorders, like functional dyspepsia (FD) or IBS are
less amenable to explanation or effective treatment. On the one
hand physicians traditionally look for structural evidence in order to
make diagnoses and on the other hand patients are reluctant to
speak clearly about their bowel and its malfunctions. This leads to
the situation that functional gastrointestinal disorders are often not
diagnosed and
treated correctly
(3,4). Consumers are
actively searching for
alternatives to
medical advice from
within the food

2_BUCHWALD:Ingredients 01/10/12 12:31 Pagina 5

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supplement
and OTC
segment as
well as the
functional
food
market.
Recent
scientific
studies link
the mind
and body
into a
system where their dysregulation can produce discomfort and
disease. Early in life, genetics, in addition to environmental factors
such as family influences on illness expression, abuse, major losses,
or exposure to infections, may affect ones psychosocial
development in terms of susceptibility to life stress or psychological
state and coping skills, as well as susceptibility to gut dysfunction
abnormal motility, altered mucosal immunity, or visceral
hypersensitivity. Furthermore, these brain-gut variables reciprocally
influence their expression. Therefore, functional gastrointestinal
disorders are products of this interaction of psychosocial factors and
altered gut physiology via the brain-gut axis (4).

GUT HEALTH MARKET AND CONSUMER DEMAND


It is estimated that 10 to 20% of the worlds total population is
affected by IBS and that amongst this total, 60% are females and
40% are males. It is also believed that about 70% of those affected
with IBS do not seek a doctors help. IBS is a common problem but
most of the people affected by it are either unaware of the problem
or tend to avoid the issue and do not discuss it with their physician.
This demonstrates an interesting business opportunity for
digestive health ingredients manufacturers and suppliers who are
able to educate and create awareness among these consumers. The typical gut health consumer can be placed in one of two
categories. The first category includes a growing number of people
experiencing digestive discomfort, including the middle aged as well
as older generations that have started using functional and natural
foods and beverages for improved digestion. The overall wellbeing
trend including Asian cultural influences has changed the perception
of the intestinal system in the Western population. In Asia the gut is
a central element, being recognized as the center of the soul and
the centre of spiritual and physical strength. Today many Western
consumers also believe that digestive health is an essential part of
their bodys ability to detoxify and promote immunity, and they are
looking for solutions to optimize digestive function. These younger
potential consumers represent the second target group for gut
health products.
Consumers need help with digestion and therefore it is not
surprising that gut health is a mega trend the biggest segment of
the functional foods market and healthy digestion is becoming a
top priority for consumers. This has been recognized by marketing
professionals aiming to transfer the European dairy success story to

other food segments, particularly beverage applications, as well as


to food supplement products.
The New Nutrition Business annual analysis of the key trends in
the business of food, nutrition and health lists digestive health as a
key trend for 2012 (6).
Datamonitor predicts that the immune and digestive health
food market is growing annually by about 7.7%, reaching $14.13 bn
in 2014 (5). In the U.S. the gut health ingredient market is currently
valued at $265.9 million. It is expected to grow to $495.3 million in
2015 at a compound annual growth rate (CAGR) of 13.2% (7).

GUT HEALTH INGREDIENTS AND TRENDS


Probiotics have been the leading group of digestive ingredients,
followed by fibers, particularly in solid food formulations and
enzymes. Probiotic strains are in most cases patent protected and
used by dedicated companies in selected brands. They support a
healthy gut flora contribution to digestion and the immune system.
More flexibility and overlapping are seen in the use of fibers.
Traditional fibers like inulin or galacto-oligosaccharide (GOS) are
used as well as trendy fibers such as baobab, kiwi, chia or berries
to support additional selling points like taste, exotic origin and
sustainability. Fibers trigger bowel movement through their bulking
properties. In addition, several blends are marketed with
antioxidative natural ingredients or anti-inflammatory natural oils like
fish oils.
A selection of different gut health ingredients is needed, because
digestive discomfort varies considerably from person to person and
also from day to day. The onset is often unpredictable and on one
occasion it may be initiated by food; another time by stress. The key
success factor in this product category is that consumers are able to
recognize for themselves within days the beneficial effects of gut
health ingredients on the bowel function. They can feel the
difference, no medical diagnoses or determinations of biomarkers are
necessary to guarantee that the product works.
Consumer trust in gut health products has been established
even though only a few applications for EFSA health claims have
been approved up to now. Dropping health claims had no
detrimental impact on sales of Danones probiotic yogurt, begging
the question of how much credence consumers give to on-pack
claims, so long as they feel the benefit.
Food market analysts tend to say that in the US
consumers are looking more for dietary supplements
that support digestion whereas in Europe
functional foods are more in demand.
However this is not totally correct
for this product category. There is
a well established self medication
use of OTC probiotics and
food supplement products in
Europe, purchased
preferably in pharmacies.
European consumers have
used probiotic products
for decades to recover

2_BUCHWALD:Ingredients 01/10/12 12:31 Pagina 6

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the intestinal flora after treatment with antibiotics or to strengthen


the immune system to cope with allergies like hay fever. This
traditional use and knowhow worked together to establish the trust
in functional food gut health ingredients.
Consumers generally believe in the effectiveness of gut health
ingredients and a high degree of brand loyalty can be observed.
Nevertheless, if a competing brand promotes a new or advanced
concept, consumers are going to test the product and if it works
better they will switch to this product even if it is another brand.
Innovation gets paid back within the gut health market and the
introduction of new ingredient blends or innovative ingredients has
a high probability of market success, particularly because the gut
health ingredients available today do not address all consumer
needs. Consumer research initiated by Novartis Consumer Health
indicated that a third of shoppers leave the digestive health aisle
without buying something, including people who are actively
suffering from a health condition (8).
The challenge is not only the development of new effective gut
health ingredients but also the setting up of educational awareness
programs and marketing campaigns to communicate the specific
functions of these digestive health ingredients to potential
consumers.

is able to inhibit bowel movement, contraction that can turn into


cramps.
Benegut is unique, because it combines prokinetic as well as
antispasmodic efficacy leading to an immediately feel-able
balancing effect on bowel function. Benegut is able to normalize gut
functions, having a beneficial physiological effect, maintaining
normal digestion and preventing or improving gut regularity.
Efficacy of the product has been confirmed in several in vitro
studies. First, the relaxant effect on isolated adult male Wistar rats
ileum contraction was investigated and an antispasmodic effect,
inhibiting neurotropic and musculotropic activity was observed.
Second, the acute neuroactive effect on the neuronal activity of
murine frontal cortex networks was tested by means of
electrophysiological multi-channel recording. Benegut demonstrated
prokinetic activity. In addition Benegut showed anti-inflammatory
effects in a human ex vivo study, being able to reduce tumor
necrosis factor alpha (TNF).
Benegut is a natural, IP protected ingredient which fulfills the
legal requirements for the application in food supplements in
Europe and the US.

CONCLUSION
BENEGUT THE INTELLIGENT NEW GUT HEALTH
INGREDIENT
Benegut is a new intelligent food ingredient, which targets the
consumer benefit platform of digestive health and which
contributes to overall quality of life.
Daily stress, food sensitivity and allergies, infections, genetic
preposition, altered gut flora or deregulation of brain-gut cross-talk
may lead to the development of gastrointestinal discomfort.
Physiologically the discomfort is mainly caused by ileum
contractions, which lead to altered intestinal mobility and symptoms
such as cramps, bloating and rumbling. The aim of a suitable gut
health ingredient is to balance the ileum contractions and to adjust
the mobility back to a physiological level. Currently available
ingredients targeting the bowel movement may counteract each
other often resulting in a change from constipation to diarrhea and
vice versa.
Benegut is an intelligent gut health ingredient,
which helps to balance bowel activity to
normal physiological levels. Benegut
demonstrates prokinetic effects,
which support bowel
movement and help to
regulate transit through the
gastrointestinal tract. At the
same time Benegut has
antispasmodic effects and

Benegut is a new intelligent gut health ingredient that is able to


normalize bowel functions. Benegut has a beneficial physiological
effect in maintaining normal digestion as well as to prevent and
improve gut regularity. Furthermore, it is an innovative ingredient
that improves functional gastrointestinal discomfort and prevents
disease linked to gut irregularity and inflammation, such as IBS.

REFERENCES
1) Market Tools, Inc.; www.tummywise.com/release-survey.html.
2) EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) Guidance
on the scientific requirements for health claims related to gut and immune
function EFSA Journal 2011, 9 (4), 1984.
3) www.theibsnetwork.org
4) Drossmann D.A. The functional gastrointestinal disorder and the Rome III
process Gastroenterology 2006, 130, 1377-90.
5) Watson E. Brain food ripe for growth, but who will lead the charge?
Nutraingredients-USA.com, 12 May 2011.
6) 10 Key Trends in Food, Nutrition and Health 2012; New Nutrition Business:
London, 2012.
7) U.S. Digestive Health Enzymes, Prebiotics & Probiotics Market (20102015) marketsandmarkets.com, November 2010;
http://www.marketsandmarkets.com/Market-Reports/digestive-health225.html.
8) http://www.progressivegrocer.com/products/
supplier-news/id994/category-captain-digestive-health-novartis-consumerhealth/

3_POMBO:Ingredients 01/10/12 12:34 Pagina 7

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The effect of NutriMore on


satiety and energy intake
SONIA POMBO
ROBERTA RE 2

Leatherhead Food Research


Randalls Road
Leatherhead KT22 7RY, UK
www.leatherheadfood.com
1. Tel +44 (0)1372 822293
spombo@leatherheadfood.com
2. Tel+44 (0)1372 822354
rre@leatherheadfood.com

ABSTRACT
There is an urgent need for effective measures to prevent weight gain in the population at large. Time and research have shown that
the solution is not simple, and that just telling people that they should eat less and exercise more does not work for the majority of
individuals. The food industry worldwide is now implementing innovative ingredients thought to control our appetite and keep us feeling
fuller for longer in an attempt to combat this health issue. Food products high in protein are generally thought to increase satiety to a
greater extent than carbohydrate or fat, and may facilitate a reduction in energy intake. Consumption of soy protein, for example, has
increased in the western world dramatically in the last decade. This increase in popularity can be linked to consumer understanding of
the health benefits of soy and other protein foods, with weight management being one of many. However, with soy flour having a strong
taste and smell, its applications as an added food ingredient are limited.
This article looks at the benefits of using a soy-based product, NutriMore, and describes a study carried out by Leatherhead Food
Research to assess its effects on appetite control when consumed as a mid-morning snack. NutriMore is a soy-derived value-added food
ingredient that has none of the palatability issues of other soy products. As such it allows application in a variety of food products
reducing the need to mask taste or smell. Nutrimore, a by-product of soy processing, is the high-protein, high-fibre insoluble pulp that
remains when the soy milk is extracted from the beans.

INTRODUCTION
With over one billion adults globally being overweight, of which
approximately a third are classified as obese, it is evident that
obesity is a growing problem in our society. Defined as a body mass
index (BMI) greater than 30 kg/m2, obesity is associated with many
chronic lifestyle-related diseases including type 2 diabetes,
cardiovascular disease and cancer (1). Obesity rates have increased
dramatically over the last three decades, having more than doubled
in all ages of the population since the 1960s (2). No one single
factor is to blame from the onset and progression of obesity. Some
factors stem from biological and psychological reasons, but social
and environmental aspects also play a huge role. Our diets have
completely changed in the last 50 years, with increased availability
and consumption of more energy-dense foods, along with larger
portion sizes and the ever-increasing prevalence of fast-food
restaurants. This, coupled with reduced physical activity across all

ages, has led to the increase in overweight and obesity. As such,


this has driven the need for the development of new dietary
strategies described from the results of increased research
and the development of specific weight management
foods in an attempt to help combat the health
problem obesity represents.
Satiety is a term used to describe
the effects that foods have on our
desire to eat. Satiation is the
feeling of fullness immediately
following food consumption.
The satiating effects of
different foods are a topic
of great interest to the
food industry, since the
more satiating a food is,
the lesser the desire

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to eat. This means that highly satiating foods are a useful tool in
weight management. It is well established that different foods exert
different effects on satiety, with a supposed hierarchy of satiation
occurring between protein, carbohydrate and fat, protein being the
most satiating (3).
Satiation and satiety both affect eating behaviour, and can be
measured either directly via food intake measurements or indirectly
via subjective measurements. Measuring satiety is a complex task as
a number of psychological and environmental factors can affect the
relationship between appetite and food intake. For example, people
often eat in the absence of hunger, for reasons such as boredom,
stress, or increased palatability of a certain food.
Visual analogue scales (VAS) are commonly used as a simple
means of self-reporting feelings of hunger and fullness in studies
looking at eating behaviour (4). Consisting of a 100-150 mm line,
participants are required to respond to a question by placing a mark
on the line that is anchored with an extreme answer at either end
of the line (Figure 1),
for example, the
question How full
do you feel? would
be anchored with
Not at all full and
Extremely full, with
the minimum value
on the left end of
Figure 1 Visual Analogue Scale (VAS).
the scale.
Energy intake can be measured by providing participants with
an ad libitum meal. Individuals are offered a pre-weighed amount
of food at a defined period after consuming the test product and
the amount remaining after they have eaten is measured (5). The
meal that follows a preload must be sensitive to the manipulations
of the preload, and the food given must be acceptable to all
subjects: this should be assessed in pre-screening tests. Care must
be taken to instruct the subjects about the point at which they
should stop eating: they must be instructed to eat until they feel
comfortably full.

SOYA PROTEIN AND SATIETY


Many studies have investigated the effect of protein
on satiety and proteins have
consistently been shown to have a
stronger effect on satiety than
equivalent quantities of energy
from other macronutrients.
Protein is thought to aid in
weight loss by increasing
satiety and augmenting
thermogenesis (increased
heat production), resulting
in a decreased uptake of
energy. This increased
rate of thermogenesis
is thought to be a

result of a greater energy requirement for


digestion, absorption and the use of
nutrients consumed (6).
Soya beans provide one of the most
abundant plant sources of dietary protein.
Soy protein is considered a complete
protein in that it contains sufficient amounts of all the essential
amino acids and has a nutritional value roughly equivalent to animal
proteins. Soy as a food product has obtained a lot of attention over
the last few years, mainly due to the health benefits associated with
its use. Soy protein is thought to assist in weight control and
increase energy expenditure (7,8) with animal and cross-sectional
studies showing an association between soy intake and lower body
weight. An observational study carried out in nearly 1,500 women
in Hawaii, found that those who commonly ate more soy-based
products had a lower BMI than those who didnt (9). The satiating
effects of soy protein also appear to be dose-related, with increased
satiety observed between a high (25%) soy
protein breakfast compared to a normal
(10%) soy protein breakfast in 25 healthy
people (10).
Consumption of soy has an abundance of
beneficial health effects. Not only is it thought
to increase satiety and reduce risk of coronary
heart disease, but there is also research which
suggests soy can reduce the glycaemic index
(GI) value of foods. GI is the quantitative
assessment of food based on the rate at which they release glucose
into the bloodstream (11,12). Different foods provoke different
glycaemic responses depending on their nature and the extent to
which they have been processed. The principle is that the slower
the rate of glucose absorption the lower the subsequent increase in
blood glucose, thus resulting in a more sustained release of energy.
This in turn would potentially make people feel less hungry for a
longer period of time. Studies have found the presence of soy
protein within a food product to reduce the GI value (13,14).
Due to the number of published data indicating its benefits, soy
consumption has increased dramatically in the western world within
the last decade. This increase in popularity can be linked to
consumer understanding of its health benefits, with weight
management being one of many. Soy protein is now often used in
breakfast products with the aim of releasing energy slowly, a
growing area of innovation, as consumers are increasingly seeking
breakfast cereals which keep hunger at bay until lunch. However,
soy flour has a noticeably strong taste and smell; therefore its
applications as a food ingredient have been limited.

NUTRIMORE
In 2008, NutriGal, a division of Israeli ingredients company Galam
Group, launched a versatile, neutral tasting ingredient called
NutriMore, a naturally rich soy protein and fibre fraction from okara,
obtained through a natural extraction process using non-GMO
special grade soy beans. This product is thought to have all the
satiating benefits of soy protein with an added benefit of being

3_POMBO:Ingredients 01/10/12 12:35 Pagina 9

ingredients

Figure 2 Mean energy intake from the ad libitum meal at 120


minutes for each of the test products.
Values are expressed as mean + SEM

Figure 3 Change in mean VAS scores for the question How


strong is your desire to eat? in response to consumption of the
test product (t=0) and subsequent consumption of the ad libitum
meal (t=120) for all three test sessions.

bland in taste. This is promising news for the industry, as it means it


can easily be incorporated to many products without affecting
palatability of the product (15). As a result, NutriMore has been
used in various lines of products such as:
Baked Goods;
Beverages;
Breakfast Cereals and Flakes;
Energy and Nutritional Bars;
Pasta.
Based on the published literature surrounding the satiating benefits
of soy protein, Leatherhead Food Research, on behalf of NutriGal,
carried out a double-blind clinical intervention study assessing the
effects of varying concentrations of NutriMore on satiety and
subsequent food consumption.

METHODS
Thirty-five healthy male and female subjects were recruited based
on a set of inclusion and exclusion criteria. Subjects between the
ages of 20 and 60, with a healthy BMI (18.5-25 kg/m2) and no
reported metabolic diseases or gastrointestinal disorders were
asked to visit Leatherheads Nutrition Unit on three occasions, with
a weeks wash out period between each visit.
The aim of the intervention trial was to assess the satiating

effects of NutriMore when consumed as a mid-morning snack.


NutriMore was incorporated into a bread roll. We hypothesised that
consumption of a bread roll containing NutriMore as a mid-morning
snack would result in decreased feelings of hunger throughout the
morning. As a result of this, it was thought that a subsequent
reduction in energy intake at the next meal would also occur.
Each volunteer was randomly assigned to receive one of three
bread rolls matched for weight, calorie content (115 kcal) and size,
to be consumed as a mid-morning snack. One of the bread rolls
contained 25% NutriMore, with 5 g protein and 3.3 g fibre, another
bread roll consisted of 33% NutriMore with 5.6 g protein and 4.6 g
fibre, and the final bread roll acted as the control product, with no
NutriMore added. This was tested to ensure any differences
between the products were due to the presence of the high protein
and fibre soy by-product.
Following an overnight fast, subjects were provided with a
standard breakfast, consisting of cornflakes and semi-skimmed milk,
followed by the test product as a mid morning snack. Energy intake
at the next meal was also assessed, by providing volunteers with a
large portion of pasta for lunch and instructing them to eat until
they felt comfortably full. Satiety scores were recorded at regular
intervals during the test day using electronic Visual Analogue Scales
(eVAS) on hand-held computers (iPAQs), which prompted subjects
for a response in a pre-programmed manner.

RESULTS
Following consumption of the bread roll mid-morning, no significant
differences in the total amount of calories consumed at lunch were
found between the control bread and the breads containing
NutriMore (Figure 2).
Results from subjective ratings of satiety demonstrated a
stronger desire to eat after consumption of the control bread
compared to 33% NutriMore. This difference was also observed
after consumption of 25% NutriMore, however these figures were
statistically insignificant. Subjects felt fuller for a longer period of
time after consumption of 25% NutriMore compared to the control.
Fullness was also increased after 33% NutriMore, however feelings
returned back to normal at a faster rate, thus resulting in an
insignificant score (Figure 3).
The results of this preliminary study would suggest that
although no significant differences in the change in
perception of satiety were shown after consumption
of NutriMore, a clear trend could be detected in
subjective ratings of satiety, suggesting
a more satiating effect from the
bread product containing the
NutriMore ingredient. Although
this effect was more
pronounced in the higher
dose group, it was already
clear in the lower dose
bread roll, suggesting a
dose response effect.
Questions on

3_POMBO:Ingredients 01/10/12 12:35 Pagina 10

ingredients

product liking of were asked to assess if a strong dislike of the test


products could have had an impact on satiety responses. The
results suggested that there were no obvious differences in liking
between the three test products. This confirms that the differences
in perceptions of hunger were not affected by the individuals
opinion of the product itself. This also confirms that the inclusion of
NutriMore into food products does not alter the products taste or
texture, something that is commonly observed with other soy-based
products.
Questions on physical discomfort were also asked to assess
whether any discomfort experienced during the study was due to
the product, and whether this would have had any impact on
satiety. The results suggested no obvious differences between the
three test products two hours after consumption. This is promising
news, as high protein and fibre products have been known to
increase symptoms of physical discomfort, such as bloating.
This study is a first step towards claiming NutriMore as a
satiating ingredient; further research will be able to assess ideal
condition of use and dose required to obtain a more pronounced
effect. Nava Almog, general manager of NutriGal, was pleased with
these preliminary results, which signals a more promising future:
The study does not give grounds for claiming a satiety effect, but it
is in keeping with general observations that proteins and fibres help
people feel fuller for longer. Data from this study can be used to
power further intervention trials to optimise the condition of use of
NutriMore to control satiety. These promising results are in keeping
with general observations that proteins and fibres help people
control appetite, and the versatility of this ingredient would mean
increased incorporation in a wide range of food products.

10

REFERENCES
1) Guh D.P., Zhang W., Bansback N., Amarsi Z., Birmingham C.L, Anis A.H.
BMC Public Health 2009, 9, 88.
2) Ludwig D.S. Journal of Nutrition 2000, 130, 280S-3S.
3) Poppitt S.D., McCormack D., Buffenstein R. Physiology and Behaviour
1998, 64 (3), 279-85.
4) Mattes R.D., Hollis J., Hayes D., Stunkard A.J. Journal of the American
Dietetic Association 2005, 105, 87-97.
5) Hill A., Rogers P., Blundell J. International Journal of Obesity 1995, 19, 361-75.
6) Halton T., Hu F. Journal of the American College of Nutrition 2004, 23 (5), 373-85.
7) Anderson J.W., Fuller J., Patterson K., Blair R., Tabor A. Metabolism 2007,
56, 280-8.
8) Bathena S.J., Velasquez M.T. 2002. American Journal of Clinical Nutrition 2002,
76, 1191-201.
9) Maskarinec G., Aylward A.G., Erber E., Takata Y., Kolonel L.N. European
Journal of Nutrition 2008, 47, 138-44.
10) Veldhorst M.A., Nieuwenhuizen A.G., Hochstenbach-Waelen A. British
Journal of Nutrition 2009, 101, 295-303.
11) Jenkins D.J.A., Wolever T.M.S., Taylor R.H. American Journal of Clinical
Nutrition 1981, 34, 362-6.
12) Jenkins D.J.A., Wolever T.M.S., Jenkins A., Josser R.G., Wong G.S. Lancet
1984, 2, 388-91.
13) Torres N., Palacios-Gonzlez B., Noriega-Lpez L., Tovar-Palacio A.R.
Revista de Investigacion Clinica; Organo del Hospital de Enfermedades de la
Nutricion 2006, 58 (5), 487-97.
14) Oku T., Nakamura M.,Takasugi A., Hashiguchi-Ishiguro M., Tanabe K.,
Nakamura S. International Journal of Food Sciences & Nutrition 2009, 60,
224-31.
15) Schved F., Hassidov B. Supplement to AgroFOOD industry high-tech 2010,
21 (2), 38-40.

4_LEMEROND-CRODA:Ingredients 01/10/12 12:38 Pagina 11

ingredients

The incredible natural

power of BCM-95
Curcumin

TERRY LEMEROND
www.TerryTalksNutrition.com

Recent breakthroughs using absorbable curcumin have made health headlines lately, and for good reason. Few natural ingredients
deserve the attention more than this one.

TURMERIC VS. CURCUMIN


Before we go any further, lets make sure we clear up any confusion
about the root turmeric and its key beneficial compound, curcumin.
The plant turmeric is very well known in India. The root is harvested,
cleaned, dried, and powdered to be used as a spice (turmeric gives
curry its beautiful golden yellow color) and as a medicine.
Traditionally, turmeric was used for nearly every health condition
known from smallpox to a sprained ankle. The reason for its health
effects is the compound known as curcumin. Just as oranges are a
source of vitamin C, turmeric is a source of curcumin. Today, we
extract curcumin from turmeric to use as a natural medicine (1).
But getting the right kind of curcumin is crucial.
Despite the incredible benefits of curcumin, one of the biggest
challenges for using it medicinally and as a supplement has been
absorption.
Thats why clinical trials have had to use increasingly larger
dosages some up to 12 grams daily. Thats just to get a small
amount into the bloodstream. Again, were not talking about any
toxicity here, but at those high dosage levels cost, comfort and
compliance can be a real problem.

The majority of
turmeric products on
the market are
regular formulas,
standardized to 95%
curcumin.
Unfortunately, this
formulation of
curcumin is poorly
bioavailable, so it
doesnt pass easily from the
gastrointestinal tract into the
bloodstream. And, much of the
curcumin that does reach the
bloodstream quickly converts
into other compounds.
None of this has gone
unnoticed, and there have
been many attempts to
make curcumin more
absorbable and have it

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4_LEMEROND-CRODA:Ingredients 01/10/12 12:39 Pagina 12

ingredients

Figure 1 Absorption comparison of different formulations of


curcumin (2).

remain in the bloodstream longer so it can be more beneficial. Many


products and research have focused on adding piperine, for instance.
But piperine can have some big disadvantages. It interferes with
almost every prescription drug and can have terrible effects on the
liver.
But theres a better way. Its BCM-95 high-absorption curcumin.
BCM-95 curcumin, the most successful curcumin extract to date,
combines micronized (small particle size) curcumin with turmeric
essential oils. It has up to 10 times the absorption and greater
blood retention time than standard 95% curcumin extracts (Figure
1). That is why this specific bioavailable curcumin is being used in
important disease research around the world (2,3).

BCM-95 CURCUMIN ITS ORIGIN


The fields where the turmeric is grown and harvested for BCM-95
are located on the border of India and Nepal. It is believed that the
soil, climate, and elevation in this part of India are ideal
for growing turmeric plants with high concentrations
of curcumin. The farmers here use
traditional, sustainable methods to
improve the quality of their
turmeric crops.
They use natural fertilizers
(animal manure), dig the
turmeric roots and rhizomes,
burn the leaves and till the
ash back into the soil as
additional fertilizer. The
work is done almost
entirely by hand,
involving little or no
machinery. Turmeric is

12

an important crop in this region. Careful attention is paid to the


plants, regular and optimum irrigation, and sustainable and ecofriendly cultivation.
The people who plant, tend and harvest the turmeric crop for
BCM-95 are independent local farmers, and not employed by the
company. They are paid fair-trade wages that they are able to put
back into their own communities. The Spice Board of India (a
governmental agency) and the Agriculture Department assist farmers
in improving their farming and cultivation techniques. This
cooperative also provides farmers with information related to new
farming techniques and promotes government programs to
encourage good agricultural practices.
Incoming raw material is regularly analyzed for contaminants
(including heavy metals), in addition to other parameters such as
curcumin content and moisture.
At the facilities where the curcumin is processed, it is naturally
enhanced to be absorbed in the body at a rate 10 times that of
standard curcumin using micronization (reducing to a small particle
size) and blending the powder with turmeric essential oils. Potency is
also verified at this time.
And this natural processing is something important to note
theres no potentially dangerous piperine being added, and no
untested (and never before in our diets) nanotechnology being
employed, either. Just good, solid science.

INFLAMMATION AND CHRONIC DISEASES THE


CRITICAL CONNECTION
Curcumin in general, and BCM-95 in particular, has incredible antiinflammatory power. That means more than just pain relief
although that is a major benefit. And there is one thing that heart
disease, cancer, diabetes, arthritis, asthma, Alzheimers, bowel
disorders, and even obesity have in common oxidative stress
caused by free radicals and inflammation.
Free radicals and inflammation go hand in hand. Inflammation
damages cells and tissues by creating free radicals. Free radicals
damage cellular DNA and weaken our immune system. Chronic
inflammation combined with a weakened immune system is
extremely dangerous. Experts have estimated that free-radical
damage contributes to more than one-third of all deaths and about
40% of total medical expenses in industrialized countries. Free
radicals can negatively affect all key bodily systems, including our
inflammatory response.
The key to preventing and treating illness is to use a multifaceted
approach. Rather than influencing just one pathway, as most drugs do,
curcumin has 112 different molecules which simultaneously influence
multiple pathways on multiple levels.

CURCUMIN AND CANCER


Curcumin has clearly been shown to prevent and inhibit cancer
development in a number of studies. By stimulating immunity so we
can kill cancer cells and stop them from multiplying, reducing
inflammation, and improving detoxification so we can eliminate

4_LEMEROND-CRODA:Ingredients 01/10/12 12:39 Pagina 13

ingredients

cancer cells, curcumin has the potential to treat many different types
of cancer (4-6).
While common chemotherapeutic drugs cause serious side
effects, curcumin produces none. Common anticancer drugs are
immunosuppressive. Curcumin is an immunorestorer.
Furthermore, common anticancer drugs cannot cross the blood brain
barrier. Curcumin can.
Positive research results involving curcumin have been seen with
breast, ovarian, pancreatic, prostate, colon, and lung cancers. In fact,
MD Anderson Hospital researchers have reported that curcumin has
potent anticancer properties by influencing something known as
epigenetic activity.
Epigenetics is a fascinating realm of study. It
delves into the ways that our genes are influenced
by our diet and environment, and looks at which
factors turn certain genes on and which factors turn
them off. In other words, while we may have
genetic tendencies toward certain health concerns,
we can actually do something about it.
When cancer cells flourish, it is due to a process
called methylation. Essentially, it silences certain
genes that are designed to suppress tumors, and
circumvents our bodys own defense mechanisms.
But curcumin changed that. It was able to
reawaken the sleeping genes that power the
bodys own tumor suppression activity that keeps
cancerous tumors from growing and spreading.
The best part is, researchers say it may prove
effective for both prevention and treatment (6).

destruction of beta amyloid plaque. Other studies have shown that


curcumin plays a role in neuronal regeneration. All these properties
contribute to its potential utility in addressing this brain disease.
In fact, curcumin is more effective in inhibiting formation of beta
amyloid protein fragments than many other drugs being tested as
Alzheimers treatments! One of the most prestigious Alzheimers
research institutes in the world, the McCusker Alzheimers Research
Foundation (supporting research at Edith Cowan University, Perth,
Australia) is focused on learning more on the benefits of curcumin
for treating AD. In a ground-breaking new study, a specialized, highly
absorbable form of curcumin is being administered to patients with
mild to moderate dementia in order to learn more about how

CURCUMIN AND ALZHEIMERS DISEASE


NATURAL HOPE
The cause of Alzheimers disease (AD) is not
entirely known. However, certain characteristic
changes are found in the brains of people with this
condition accumulated clusters of a protein called
beta amyloid, and clumps of dead and dying nerve
and brain cells. These clusters and clumps, called
plaques and tangles, are believed to interfere with
the proper transmission of messages between
brain cells, and the death of the cells themselves.
Inflammation is also believed to be involved,
causing the accumulation of plaques and tangles to
have even more damaging effects.
This has lead researchers to consider a more
natural approach. Because of the known anti-inflammatory effects
of curcumin, researchers are now looking at its effects in treating
AD. What they have discovered is astonishing (7,8).
Not only does curcumin protect brain cells from damaging
inflammation, in experimental models of Alzheimers disease,
curcumin was able to reduce beta amyloid levels and shrink the
size of accumulated plaques by over 30%! (8)
So curcumin studies in animal models of Alzheimers disease
have demonstrated that it can play a significant role in the

curcumin can be used as an


effective treatment of AD.

CURCUMIN AND
DEPRESSION
Stress and anxiety create
oxidative damage in

13

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ingredients

the brain. Aside from curcumins ability as a strong anti-inflammatory


and antioxidant, which reduces DNA damage to cells throughout the
body, curcumin reverses other physical effects of stress and
depression. It reduces inflammatory markers in the bloodstream,
which travel through the brain, and it prevents low levels of
serotonin, noradrenaline, and dopamine. Plus, research shows that
curcumin also promotes neurogenesis brain cell formation
notably in the frontal cortex and hippocampal regions of the brain
(9-11).

OVERALL PURE CURCUMIN SUPPLEMENT


For overall anti-inflammatory, cellular, and neurological support, look
for a pure
BCM-95 product that provides 500 mg of pure curcuminoids per
softgel. Just check the supplement facts box. Now, consider this:
since BCM-95 has up to 10 times better absorption, that 500 mg
curcumin equals up to 5,000 mg of potential blood levels of
curcumin. If youve been searching for a natural insurance policy,
this is it!

CURCUMIN MATCHES DRUGS FOR INFLAMMATION


BUT WITHOUT SIDE EFFECTS!
If youre active, or would like to be more so without pain the
best formula uses BCM-95 high-absorption curcumin with three
other ingredients; boswellia, DLPA, and nattokinase.
Boswellia is especially potent at reducing joint pain associated
with arthritis by inhibiting the inflammatory enzyme,
5-LOX. A specialized high-AKBA (acetyl-11-keto--boswellic acid)
boswellia in this combination is low in -boswellic acid (which
interferes with beneficial activity) and has higher levels of AKBA to
really boost the effectiveness of the extract (12,13).
The amino acid combination DLPA (D,L-phenylalanine) improves
mood-elevating chemicals in the brain (dopamine, epinephrine, and
norepinephrine) and relieves muscle pain. The enzyme nattokinase
helps promote blood flow so that other compounds that are carried
in the bloodstream (such as curcumin, boswellia, and pain-killing
endorphins) can reach the areas where they are
needed the most (14-18).
BCM-95 curcumin has been
featured in published clinical studies
concerning pain and
inflammation. One study used a
combination of BCM-95 and
high-AKBA boswellia in a
study of osteoarthritis relief.
The other, focused on
rheumatoid arthritis (RA)
using BCM-95 alone.
The osteoarthritis
study compared the two
botanicals to a generic
celecoxib (known

14

under the brand name Celebrex) for individuals with osteoarthritis.


One group received celecoxib, 100 mg, twice daily while the second
group received a 500 mg blend of the BCM-95 curcumin and the
high-AKBA, low-beta boswellia extract twice daily.
When it came to relieving pain, 64% of those taking the herbal
ingredients versus 29% in the drug group improved to such a high
degree that they were able to move from having moderate to
severe arthritis to mild to moderate arthritis (19).
The RA study followed 45 individuals, randomized to three
groups. Group one received diclofenac sodium, 50 mg, twice daily;
group two received 500 mg
BCM-95 curcumin twice daily; and group three received both
diclofenac sodium and BCM-95 curcumin.
In the BCM-95 curcumin groups, there were no drop outs due to
adverse effects, but in the diclofenac sodium group, 14% withdrew
due to adverse effects.
In the Disease Activity Score (known as DAS) 28 assessment,
BCM-95 curcumin had the highest impact for reducing disease
symptoms, followed by the combination therapy of BCM-95
curcumin with diclofenac sodium. Interestingly, the diclofenac
sodium-alone group scored in last place (20).
One of the reasons curcumin is such an effective anti-inflammatory
agent is because it is a potent antioxidant as well, protecting the
body while fighting inflammation. This is the most likely reason as to
why curcumin is not only effective, but also does not cause side
effects. Antioxidants have been proven to prevent a wide range of
illnesses and help protect the body from disease.
And these are just two studies! But consider how important they
are. If you can get the same benefits of a prescription drug without
the side effects and health risks, why wouldnt you want an
effective, natural alternative?

A NATURALLY BETTER CURCUMIN


Your health deserves the best. This specialized extract is truly
amazing and is being investigated at prestigious research centers for
its ability to slow the development of Alzheimers disease, and
prevent and treat cancer, arthritis, and other painful and debilitating
diseases.
Remember that BCM-95 is a natural source of curcumin and
turmeric essential oils. It doesnt introduce anything strange,
untested, or potentially harmful to make it effective. If you could take
just one supplement, curcumin should be it. Just make sure youre
getting the curcumin that truly makes a difference BCM-95.

REFERENCES
1)
2)
3)
4)

Goel A., Kunnumakkara A.B., Aggarwal B.B. Biochem. Pharmacol. 2008, 75


(4), 787-809.
Antony B., Merina B., Iyer V.S., Judy N., Lennertz K., Joyal S. Ind. J. Pharm. Sci.
2008, 445-9.
Benny B., Antony B. Spice India 2006, September, 11-5.
Johnson S.M., Gulhati P., Arrieta I. et al. Anticancer Res. 2009, 29 (8), 3185-90.

4_LEMEROND-CRODA:Ingredients 01/10/12 12:39 Pagina 15

ingredients

5)
6)

Ravindran J., Prasad S., Aggarwal B.B. AAPS J. 2009, 11 (3), 495-510.
Link A., F. Balaguer F., Shen Y., Jos Lozano J., Leung H.E., Boland C.R.,
Goel A. Gastroenterology 2010, 138 (5), Suppl. 1, S-349; DOI:
10.1016/S0016-5085(10)61608-3.
7) Zhang C., Browne A., Child D., Tanzi R.E. J. Biol. Chem. 2010, 285 (37),
28472-80.
8) Garcia-Alloza M. J. Neurochem. 2007, 102, 1095-104.
9) Xu Y., Ku B.S., Yao H.Y., Lin Y.H., Ma X., Zhang Y.H., Li X.J. Pharmacol.
Biochem. Behav. 2005, 82 (1), 200-6.
10) Kulkarni S., Dhir A., Akula K.K. Scientific World Journal 2009, 9, 1233-41.
11) Li Y.C., Wang F.M., Pan Y., Qiang L.Q., Cheng G., Zhang W.Y., Kong L.D.
Prog. Neuropsychopharmacol. Biol. Psychiatry 2009, 33 (3), 435-49.
12) Ammon H.P. Planta Med. 2006, 72 (12), 1100-16.

13) Poeckel D., Tausch L., Altmann A. et al. Br. J. Pharmacol. 2005, 146 (4),
514-24.
14) Ehrenpreis S. Prog. Clin. Biol. Res. 1985, 192, 363-70.
15) Ehrenpreis S. Acupunct. Electrother. Res. 1982, 7 (2-3), 157-72.
16) DLPA in: PDR for Nutritional Supplements, 2nd Edn., Hendler S.S. Ed;
Physicians Desk Reference: Montvale, NJ, 2008, p.189.
17) Hsia C.H., Shen M.C., Lin J.S. et al. Nutr. Res. 2009, 29 (3), 190-6.
18) Fujita M., Hong K., Ito Y., Fujii R., Kariya K., Nishimuro S. Biol. Pharm.
Bull. 1995, 18 (10), 1387-91.
19) Antony B., Kizhakedath R., Benny M., Kuruvilla B.T. Abstract 316,
Osteoarthritis Cartilage 2011, 19, S145-6.
20) Chandran B., Goel A. Phytother. Res. 2012, doi: 10.1002/ptr.4639.

Olive Lifesciences Pvt. Ltd. 60 word profile


Olive Lifesciences Pvt. Ltd., manufactures and exports herbal/botanical extracts,
phytochemicals, cosmetic ingredients, food and beverage ingredients. Company
engages in the entire spectrum of activity right from the cultivation of medicinal plants,
their processing and extraction. Products are manufactured in compliance with stringent
global standards of plant operations, quality and safety. R&D focuses on development of
clinically proven ingredients.

15

5_KEIZER:Ingredients 01/10/12 12:47 Pagina 16

ingredients

The use of Medium Chain


Triglycerides (MCTs) as
medical foods
HISKIAS G. KEIZER
Stepan Specialty Products B.V.
Museumlaan 16
1541 LP Koog aan de Zaan,
The Netherlands
Tel +31 (0) 75-727-1000
info@lipidnutrition.com

A large proportion of the calories (+40%) from a healthy diet comes from triglycerides. Medium chain triglycerides form a special
category of triglycerides which are almost absent from most normal diets. They are metabolized more easily and more quickly than long
chain dietary triglycerides and use metabolic routes which are independent of those used by long chain triglycerides to yield cellular
energy.
As a consequence of these properties, MCTs are suitable to be used in many diseases in which lipid breakdown or lipid uptake is
compromised. The heart and the brain are both fully dependent on a constant and high capacity supply of cellular energy. Energy
supply for these organs may get restricted under certain pathological conditions. Under such conditions MCTs can help to relieve this
problem as it fuels cellular energy by pathways which are not fully used under normal dietary conditions.
Since MCTs are safe and use metabolic routes largely independently from those used by normal dietary ingredients, MCTs are
recommended as nutritional support in the pharmacological treatment of various types of gastrointestinal, cardiovascular and
neurological diseases.

INTRODUCTION
A large proportion of the calories (+ 40%) from a healthy diet
comes from triglycerides. Most dietary triglycerides are built from fatty
acids with a chain length of 14 or more (Figure 1). They are called
long chain fatty acids (LCTs). Medium chain triglycerides
(MCTs) are special types of triglycerides which only
contain fatty acids with chain lengths
between 6 and 12.
MCTs have a lower caloric
content, are easier to digest, are
taken up more quickly, are
metabolized more easily, are
metabolized differently and
are transported completely
differently in the body
than LCTs. Consequently
MCTs have physiological
effects which are different
from that of the normal
dietary triglycerides.
Various diseases and

16

disorders can profit


from exchanging a
part of the dietary
triglycerides for MCTs.
This brochure will give
an overview of a
selection of human
disorders which may Figure 1 MCTs are fatty acids which are
profit from treatment structurally comparable to prevalent dietary
fatty acids like palmitic acid. Chemically, MCTs
with MCTs.
just have shorter chain lengths. Physically
The normal fate of
they are more soluble in water and more
LCTs after ingestion is miscible with water than LCTs. Physiologically
that they induce the
and metabolically MCTs are also different
release of bile salts
from LCTs.
and pancreatic
lipases. The LCTs are emulsified by the bile salts in the intestinal
lumen and thereafter the lipases split off the sn1 and sn3 fatty acids
from the triglycerides. The fatty acids and monoglycerides which are
formed in this process are taken up by the epithelial cells of the gut
(Figure 2).
In the intestinal epithelium the triglycerides are reassembled
again from the monoglycerides and fatty acids and exported to the

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Figure 2 After uptake long chain triglycerides (LCTs) in the intestines,


LCTs are mixed with bile acids and micelles are formed. Thereafter
they are broken down by pancreatic lipases which split off the outer
two fatty acids (FFA at sn1 and at sn3 positions from the triglycerides.
The monoglycerides (still containing the sn2 fatty acids) and fatty
acids which are formed during this process are taken up by
transporters on the surface of epithelial cells.

lymphatic system in the form of chylomicrons. The lymphatic system


transports the chylomicrons to the blood. Lipases in blood and
tissues are used to make the fatty acids available which can be used
in beta-oxidation which yields energy for maintaining basic
physiological processes. Beta-oxidation of long chain fatty acids
(LCFAs) in mitochondria requires carnitine and the presence of the
enzyme Carnitine Palmitoyl Transferase, which forms the rate limiting
step for the beta-oxidation of LCFAs.

GASTRO-INTESTINAL DISEASE
In contrast to LCTs, MCTs due to their different physicochemical
properties do not need bile acids to be taken up by the intestines.
MCTs are more easily broken down by pancreatic lipases than LCTs,
are completely broken down into fatty acids (and not as
monoglycerides) and are rapidly taken up. MCTs are even taken up
in the absence of bile acids or pancreatic lipases. Since no
chylomicrons need to be formed, the fatty acids of MCTs (MCFA)
become quickly available in the circulation. The MCFAs are transported
directly to the blood, in which they are transported in complex with
serum albumin. Therefore MCTs do not induce lymph flow. In
summary, MCTs are taken up more quickly and more completely in the
circulation than LCTs, MCTs do not induce lymph flow in the intestines
and uptake of MCTs is less dependent upon the presence of bile salts
and pancreatic enzymes than that of LCTs (1).
For reasons mentioned above, MCTs can be used in all diseases in
which lipid breakdown or lipid uptake is compromised, in situations in
which gall bladder or pancreas is dysfunctional or in diseases in which
anomalies occur in the lymph flow. These conditions include but are
not limited to: Major resections of esophagus, stomach or duodenum,
biliary atresia, obstructive jaundice, primary biliary cirrhosis, blind-loop
syndrome, gastrointestinal cancer, pancreatitis, cystic fibrosis, Celiac
disease, Whipple disease, Crohns disease, enteritis, gluten enteropathy,
intestinal lymphangiectasia, chylous ascites, chylothorax, fistulas and
cholestasis.

CARDIOVASCULAR DISEASE
Various cardiovascular diseases like dilated cardiomyopathy,
hypertropic cardiomyopathy , childhood cardiomyopathy and

arrhythmia can have a mitochondrial defect as basis (2).


Furthermore, classic risk factors for cardiovascular disease incl.
diabetes, age and oxLDL can contribute to mitochondrial
dysfunction due to free radical formation (3). This suggests that
regulation of cardiac mitochondrial metabolism can play an important
role in the management of various types of cardiovascular disease.
Since MCTs are more easily taken up and metabolized by cardiac
cells than LCTs, they can support a failing mitochondrial energy
supply in the heart and can be used as metabolic therapy in cardiac
disease (4). In 2002, Roe et al showed a quite spectacular
improvement of the condition of a patient with a fat-oxidation
disorder by dosing odd-chain medium chain triglycerides instead of
the regularly used even-chain MCTs (5). The anaplerotic effects of
odd-chain MCTs are considered to play a role in this protection
(Figure 3).
In conclusion, since MCTs can support a failing mitochondrial
energy supply in the heart under various pathological conditions they
can be used in the nutritional support of various types of
cardiomyopathies.

NEUROLOGICAL DISEASE
Neurological diseases are difficult to treat pharmacologically.
Furthermore, in many of them, including Alzheimers disease (6),
Multiple sclerosis (7) and Parkinsons disease (8), neurons appear to
suffer from a defective mitochondrial energy supply (Figure 4). Also
free radical damage in various neurological diseases is indicative of
mitochondrial malfunctioning as complex I of mitochondria is
considered to be an important source of production of radical oxygen
species. MCTs can be used as an alternative energy supply for
mitochondria of neurons and at the same time inhibit formation of
free radicals in target tissues. Therefore MCTs can be used for the
nutritional support in the treatment of various neurological diseases.
In Epilepsy, a ketogenic diet has shown to be effective in
pharmacoresistant forms of epilepsy, including catastrophic cases of
infantile spasms, the multiple seizures types associated with the
Lennox-Gastaut syndrome and certain inherited metabolic disorders
with more than half of the patients experiencing at least 50%
decrease in seizures. Ketone bodies are likely to play an important
role in the beneficial effects of ketogenic diets in Epilepsy (9).
Since dietary MCTs efficiently form ketone bodies, and in
animals models MCTs potentiate the activity of antiepileptic drugs (10), dietary MCTs have promise to
be used as standard nutritional support
in the treatment of epilepsy.
In Alzheimers disease, defective
utilization of glucose is an
early sign of the disease.
Ketone bodies would be an
alternative for glucose as
energy supply for the
brain. Ketone bodies are
normally produced

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chain ketone bodies have the potential to limit neurological damage


in Parkinsons disease (9,13). Odd-chain ketone bodies may even
have higher potential to be protective against Parkinsons disease
since in comparison to even chain MCTs, odd chain MCTs provide
relatively more FADH2 (Figure 5).
Therefore dietary supply of odd-chain MCTs may potentially
bypass the Parkinsons disease related defect in complex I of
mitochondria. In the early phases of Parkinsons disease, drugs like
dopamine agonists can relieve most symptoms. However due to the
progressive character of the disease, these drugs stop working after
several years. If progression of the disease could be halted by using
odd chain MCTs, Parkinsons patients could have longer or even
lasting normal lives by using dopamine agonistic drugs in
combination with odd chain MCTs.

Figure 3 The citric acid cycle plays a crucial role in energy supply of
cardiac cells. LCTs are normally the major dietary energy source for
the heart. If the supply of long chain fatty acids is insufficient eg due
to damage to the LCT transporting system, MCTs can provide the
required Acetyl CoA for feeding the citric acid cycle. Odd-chain MCTs
like heptanoate produce less Acetyl CoA, but feed the citric acid cycle
by providing succinyl CoA. Direct supply of citric acid intermediates is
called anaplerosis and can have profound positive effects on the
regulation of the energy metabolism in mitochondria.

during fasting. Therefore a natural but alternative route to supply


brains with energy is by increasing ketone body levels in the blood.
Dietary MCTs are almost completely metabolized by the liver into
ketone bodies and can therefore be used as alternative natural fuel
for the brain. Ketone bodies also protect hippocampal cells against
toxicity of amyloid-beta and protect against hypoglycemia (9). Also
the free radical production in hippocampal cells treated with
acetoacetate (an inhibitor of glycolysis) was reduced by ketone
bodies (9). Probably as a consequence of all this, treatment with
MCTs leads to improved cognitive task performance in
Alzheimer patients (11). Therefore MCTs
can be used for the nutritional support
in the treatment of Alzheimers
disease.
In Parkinsons disease, a
defective complex I of the
oxidative phosphorylation of
mitochondria appears to
play an important role in
its etiology (12). This
defect probably reduces
the availability of cellular
energy and causes
oxidative stress. Even-

18

In Multiple sclerosis (MS), recent research has resulted in


convincing evidence that axonal degeneration is a crucial element in
the etiology of the disease. Mitochondrial function is crucial in
preserving axonal integrity in both acute inflammatory and
progressive stages of MS, and has been shown to be partially
defective in MS at complexes I, III and IV (7). The defective oxidative
phosphorylation as observed in MS is likely to contribute to the
oxidative stress as observed in this disease. Since ketone bodies and
medium chain triglycerides can potentially inhibit free radical
production (9), and supply energy from sources which are hardly
present in the normal diet, MCTs have promise as nutritional support
in the treatment of multiple sclerosis.
Many neurological diseases have in common that diseased cells
appear to suffer from energy depletion and from free radical damage.
Since MCTs are not part of the normal diet but supply metabolic
energy by processes which are different from those used for

Figure 5 The mitochondrial electron transport chain. The citric acid


cycle yields NADH and FADH2 which fuel the electron transport chain
with electrons. NADH donates its electrons to complex I (Compl. I).
From there, electrons are transported to Ubiquinone (Q), complex III,
cytochrome C (C) and complex IV which ultimately donates its
electrons to molecular oxygen. During this process ATP is formed.
FADH2 donates its electrons to complex II. These electrons also flow to
complex IV, but bypass complex I. In Parkinsons disease the electron
flow from complex I to complex II is disturbed. This defect is causally
involved in the disease. Fueling the electron transport chain with
electrons at complex II may counteract energy loss by a deficient
electron transport between complex I and II. This may slow down
progression of the disease.

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metabolism of normal food constituents and


since MCTs potentially reduce free radical
damage in various models, MCTs are valuable
tools in the nutritional support of medical
treatment of neurological diseases.

CONTRA-INDICATIONS
Patients with poorly controlled diabetes often
have plasma ketone levels which are too high.
Under these conditions the capacity of extrahepatic tissues to use ketone bodies is
saturated. Adding MCTs may worsen the lack
of metabolic control in these patients. People
with severe liver cirrhosis suffer from reduced
liver function and may not metabolize MCTs
completely into ketone bodies. In addition,
such patients cannot produce sufficient
albumin. Since medium chain free fatty acids
have powerful biological activity which is
reduced by protein binding, severe
albuminemia caused by liver cirrhosis or other
conditions is seen as contraindicative for use
of high doses of MCTs. However for most
illnesses, doses of up to 25 grams MCTs per
day are well tolerated as part of a balanced
diet. If the disease would require a higher
dose for optimal treatment, doses of 1-2 g
MCT/kg body weight can be tolerated if they
are used in combination with other foods and
by dividing the total daily MCT dose over
various meals.

Figure 4 Neurons normally use glucose as major energy source. However in certain diseases
normal mitochondrial energy supply from glucose is hampered. Dietary MCTs are directly
transported to the liver, where they are metabolized into ketone bodies (BHB), which can fuel
neuronal mitochondria.

REFERENCES
1)
2)
3)
4)

Bach A.C. et al. Am. J. Clin. Nutr. 1982, 36, 950-62.


Marin-Garcia M.D. et al. J. Card. Fail. 2002, 8 (5), 347-61.
Ballinger S.W. Free Rad. Biol. Med. 2005, 38, 1278-95.
Labarthe F. Cardiovasc. Drugs Ther. 2008, 22, 97-106.

5)
6)
7)
8)
9)
10)
11)
12)
13)

Roe C.R. et al. J. Clin. Inv. 2002, 110, 259-69.


Reddy P.H. et al. Trends Mol. Med. 2008, 14 (2), 45-53.
Mao P. et al. Biochim, Biophys. Acta 2010, 1802 (1), 66-79.
Cohen G. et al. PNAS 2007, 13 (10), 4890-4.
Maalouf M. et al. Brain Res. Rev. 2009, 59 (2), 293-315.
Wlaz P. et al. Neuropharmacol. 2012, 62 (4), 1882-9.
Henderson S.T. Neurotherapeutics 2008, 5 (3),470-80.
Schapira A.H. et al. J. Neurochem. 1990, 54 (3), 823-7.
Imamura K. et al. J. Neurosci. Res. 2006, 84 (6), 1376-84.

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M.E.D. Integral Propolis:


The evolution of the
working process in natural
complex matrix
ALFREDO FACHINI
NICOLA VOLPI 2
1.

B Natural srl
Via Gran Sasso, 33
20011 Corbetta (MI), Italy
Tel +39 02 49470332
bnatural@bnatural.it
www.bnatural.it

2.

Universit di Modena,
Dipartimento di Biologia
Via Giuseppe Campi 183
41124 Modena, Italy

INTRODUCTION
During the centuries plants have developed defence systems
against atmospheric agents and microorganisms. In order to protect
the young buds and the wounds on the trunks they secrete
resinous substances rich in polyphenols. In particular, these resins
have antibacterial and antiviral activities in order to protect the
plants from microorganisms as well as an antioxidant activity as
protection from UV rays. Worker bees pick up these
resins and they process them producing
Propolis which is a unique synergy
between flora and fauna. Thanks to
propolis no infections proliferate
inside the beehive where the
temperature is very high and
the ambient overcrowded.
Bees use propolis
everywhere inside the
beehive thanks to its
chemical-physical
characteristics: Propolis is
not only used for
sealing or reducing the

20

openings in the hive, for enforcing the structure or for fixing the
honeycomb but also for painting inside the free cells before the
spawn by the bee queen and for covering the small predators
butterflies, rats, lizards killed inside the beehive in order to
prevent from infections onset.
Propolis is composed of ~50% resin, it is rich in polyphenols
(free forms of flavonoids, phenolic acids and aglycon bioflavonoids
and glycosides), ~30% beeswax, ~10% essential oils, 5% pollen
and 5% different organic compounds.
Propolis is widely used in the traditional medicine and it is
proved that its extracts act as natural antiseptics, antibacterial,
antimycotics, antivirals having immunostimulant, anti-inflammatory,
and antioxidant properties (3,4), healing and local anesthetic thanks
to particular components inside propolis.
Nowadays, Propolis is mainly used in ethanolic extract products
based for the treatment of cold syndromes diseases of the upper
respiratory tracts, influenza or para-influenza, common cold as
well as in dermatological preparations to be used for wounds and
acne, herpes simplex or genitalis, and neurodermatitis (3).
A great deal of research has been carried out in recent years on
polyphenols, flavonoids and phenolic acids in order to deeply
investigate their beneficial effects on the human health, for example
for their antimutagenic, anti-cancer and antiatherogenic effects. In
particular, flavonoids generated great interest after having been

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PROPOLIS CHARACTERIZATION

Figure 1

studied and observed their ability to inhibit the low density


lipoprotein oxidase, inhibiting then the arachidonic acid metabolism
and the blood coagulation process, thus reducing possible liver
damages assuming also chemo-preventive properties linked to
pathologies connected with cancer (4-6).
Propolis cannot be used as raw material as it is, it must be
purified by solvent extraction in order to separate the inert fraction,
the waxes, and then to concentrate the phenolic fraction.
The classical working process takes into consideration the
extraction after dewaxing by ethanol and high volumes (70-80)
and obtaining a fluid extract which can be used only when the
alcohol degree is reduced or once reduced to powder. However,
this working process has a limit. By that way we can only extract
some active ingredients with good solubility in ethanol but we lose
others having different solubility degrees as, for example, some
glucosilate fractions.
It is now clear that the aim is to try to separate all the active
fractions from the others in order to obtain a product having all the
therapeutic effect and which is workable for the preparation of
pharmaceutical, nutritional and cosmetic preparations.
By enhancing of technical equipments, analytical testing and
modern extraction technologies we succeeded in obtaining much
more complete extracts.
The complex of the matrix itself has put to a hard test all
researchers of the world who were oriented to the use of a multistep extraction by ethanol which allows to obtain propolis extracts
without wax and rich in phenolic components (1,2) completed by
molecules having different but polar solubility: the main problem
was to better identify the active fractions, testing the solubility and
adapting the working process in order to obtain an integral extract.
Great importance was then given to precise and reliable analytical
methods.

The complexity of a natural matrix as propolis has caused many


difficulties in terms of extracts. The evolution of the products from
herbal to nutritional ones, the wide offer of propolis-based
preparations, the availability of a great number of scientific studies
have involved into this evolution the analytical tests, too. New
methods have been tested in order to quantify all the single active
ingredients inside the phenolic complex in a precise way.
The most used analytical methods are based on
spectrophotometry which is simple, quick, efficient and with a good
repeatability. However, they have a limit, they can determine only
total polyphenols and flavonoids without characterization of single
components. Because of the complexity of the matrix this can bring
to over- or under-estimation of the molecules present. The most
popular spectrophotometric method is the Folin-Ciocalteau one,
widely used for the determination of total polyphenols.
An important evolution is due to the performance of HPLC
methods which represent today the preferred analytical tests for the
determination and characterization of the phenolic compound in
propolis. HPLC together with Mass (and also NMR) have bettered
the analysis on the non volatile species in order to determine a
definitive structure. Moreover, the electrospray ionization (ESI) allows
the direct ionization and the transfer of the molecules to the mass
spectrometer, thus enlarging the MS application to a variety of new
class of molecules with thermal instability, high polarity and high

Figure 2

mass. Volpi et al. have performed this complex


analytical approach (HPLC-UV-ESI-MS) which has
characterized the different polyphenolic
matrices of propolis from different
origins allowing to study
extraction technologies which
could grant the best
purification of the actives
present (1).
Moreover, the method
which can examine the
complex chemical
composition of

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Propolis ESIT Water-soluble dry


extract.

propolis is NMR
spectroscopy. By this
method we can have quite
precise data on the content
of bioflavonoids. By using tit
you can prepare standards
suitable for the evaluation
of different propolis.
Nowadays the use of a
single or small number of
flavonoids identified as
standard for example
galangin or pinocembrin

can determine incorrect results.


HPLC-UV-ESI-MS together with NMR for the preparation of the
House-Standards are now necessary instruments for the chemical
classification of propolis and they should be used for the
performing of the correct extraction process for active ingredients.

M.E.D. TECHNOLOGY (DYNAMIC MULTI EXTRACTION)


The approach with a natural matrix presenting chemical-physical
differences, also important, was simplified thanks to results
obtained by these new analytical methods which have allowed to
fingerprint propolis dividing it into macro groups with similar

Figure 3 Antioxidant activity of different propolis items.

characteristics eg South Europe, East


Europe, Center of Asia, South
China, Brown South America,
Green South America, Red
South America, Pacific, and
so on (1) (Figure 1).
By the determination
of polyphenolic,
triterpenic species, wax
percentage and so on
new protocols for
working process have
been studied

22

enhancing the flexibility during the working phases in terms of


temperature, degree and solvents types, pH, and so on.
This new multi-step extraction technology is called M.E.D.
(Dynamic Multi Extraction). It allows to modify some parameters
such as solvent degree, temperature, pH... during the extraction
phase thanks to a series of modular equipment and according to
the raw material to be worked out. The results are then
standardized extracts richer in integral polyphenols (Phenolic acids,
Bioflavonoids aglycons and glucosides) (Figure 2).
The technology of Dynamic Multi Extraction starts from some
important concepts:
Polyphenols have different
solubilities, some of them are
completely soluble in water,
others totally insoluble.
Propolis of different origins are
different from each other not only from a chemical point of view
but also aromatically and physically. For this reason they must
be processed as per different procedures in order to keep the
integrality in the extract.
In order to start this working process you need a refined
analytical control system (HPLC-UV-ESI-MS).
It is possible to use only solvents authorized for food working
process and it is impossible to extract, for example, by using
non-polar solvents (besides the complicated, critical and
expensive CO2) which could allow to extract at very low
solubility.
Thanks to this technology it is now possible to obtain an integral
product where both fractions are present, active and non active
ones, and the content in polyphenols is much richer thanks to the
integration of propolis of different origins.
The product obtained is a soft high concentrated extract
(mother extract), and for its use it must be dried and supported on
excipients (maltodextrins, cyclodextrins, gum arabic) which can
better the working process and the relevant solubility, otherwise it
can be dissolved in hydroalcoholic or hydroglyceric solutions
resulting much richer than the standard extracts and made suitable
for nutritional or cosmetic formulations.

STANDARDIZATION IN ANTIOXIDANT ACTIVITY


The activity of M.E.D. Integral Propolis is based on facts proving that
each single polyphenol singly taken does not have the same activity of
the entire complex and, as consequence, a wrong extraction or a
further purification could reduce part of the activity itself even if the
content in bioflavonoids remain elevated.
The M.E.D. method allows to keep integral the fractions contained
in propolis: phenolic acids, aglycon bioflavonoids and glucosides.
As for all the matrices with same complexity the difficulty of a
chemical characterization induced to study a titration system not
based on the percentage content in polyphenols but on the activity of
the extract.
This innovative approach, carried on by the Modena and Reggio
Emilia University, has tested the antioxidant activity as scavenger of
propolis comparing M.E.D. Integral propolis (called ESIT) with other

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Figure 4 Dosage on TNF-alpha in cell culture CTR-, CTR+


and treated with tested product. The results are expressed as
mean value s.e. (expressed in pg/ml) and as % variation
(mean value s.e.) compared to CTR-; anti-inflammatory
activity is expressed as reduction of cytokine level compared
to CTR+.

propolis, extracts or raw, showing that the activity is correlated to the


keeping of the integrity of the characteristic flavonoidic complex rather
than with the absolute quantity.
The used method is the TEAC (Trolox Equivalence Antioxidant
Capacity) (7) test which is used for the measurement of the total
antioxidant activity on pure substances, biological fluids and vegetal
compounds. It is based on the reaction of the antioxidants with the
cationic radical ABTS (2,2-azinobis 3-ethylbenzthiazoline-6-sulfonic
acid). This cationic radical is metastable, it must be generated just
before the experiment by oxidation of ABTS with potassium persulfate.
The solution of cationic radical obtained is then diluted in ethanol or
buffered at pH 7,4.
This radical can be reduced with corresponding loss of absorbance
by an antioxidant which scavenger capacity can be measured at 734
nm by spectrophotometry. The test is carried on at 37C and the results
are obtained from the relation with Trolox (synthetic antioxidant,
hydrophilous E vitamin analog) defining then the millimolar
concentration of a Trolox solution which has antioxidant property
equivalent to a 1 mM solution of the testing substance (TEAC).
We also compared two different raw propolis, only dewaxed but
not extracted, five standard hydroalcoholic Propolis extracts present on
the market with a content in polyphenols from 6% up to 15% and two
M.E.D. Integral Propolis extracts (ESIT6 e ESIT12) with a content in
polyphenols of 6 and 12%.
The results (Figure 3) show that propolis richer in polyphenols
species are much more active apart from the absolute content. As
shown, the antioxidant activity of our ESIT extracts is better than in
other ones confirming that it is much more important the number and
the richness of bioflavonoids rather than their quantities.

THE ACTIVITY OF M.E.D. INTEGRAL PROPOLIS: ANTIINFLAMMATORY EFFICACY (8-10)


Different clinical studies, in vivo as well in vitro, are running in order to
show the activity of our M.E.D. Integral Propolis.
The first results obtained are about the anti-inflammatory efficacy.
Experimental Study
In vitro efficacy study in vitro evaluation of the anti-inflammatory
activity of a nutritional active for food supplements on cell culture.

Figure 5 Dosage on TNF-alpha in cell culture CTR-, CTR+


and treated with tested product. The results are expressed as
average value s.e. (expressed in pg/ml) and as % variation
(average value s.e.) compared to CTR-; anti-inflammatory
activity is expressed as reduction of cytokine level compared
to CTR+.

Study Aim
The study described in this report deals with the in vitro
evaluation of the capability of the tested products to
modulate the inflammatory events
induced in human fibroblasts (ATCCCRL-2703). The anti-inflammatory
activity study was performed by
dosing an inflammation
marker, the pro-inflammatory
cytokine TNF-alpha, by
means of ELISA assay.
The testing items are
M.E.D. INTEGRAL PROPOLIS
ESIT 12F (Esit12)

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Preparation of the Test Items and Cell Exposure


The efficacy test was carried out in the experimental conditions better
representing the real product use:
Propolis ESIT 12F can be systemically administered at 500 mg/die;
Propolis ESIT 12F can be locally administered at 100 mg/die;
According to the following use condition, the following experimental
conditions were used for the efficacy testing:
For the evaluation of systemic anti-inflammatory activity, Propolis
ESIT 12F was tested at 0.1 mg/ml and 0.05 mg/ml: these
concentrations represent the product concentrations in the
systemic circulation (5 L average volume in adult man) when it is
completely absorbed or partially absorbed in measure of 50%
(0.05 mg/ml);
For the evaluation of local anti-inflammatory activity, Propolis
ESIT 12F was tested at 2.5 mg/cm2 and 1.25 mg/cm2. These
dosages represent respectively the product quantity for surface unit
in contact with the oro-pharyngeal region (surface measure of
about 45 cm2) when it is nebulized (2.5 mg/cm2) and the same
half dosage (1.25 mg/cm2).
Different experimental conditions were used in this protocol for the
pro-inflammatory marker (TNF-alpha) dosage:
untreated cell culture (negative control, CTR-);
cell culture in which an acute inflammation was experimentally
induced (positive control, CTR+);
cell cultures in which an acute inflammation was experimentally
induced and that were simultaneously treated with tested products.
The acute inflammation was induced by means of a 24 hour-treatment
with a bacterial pro-inflammatory agent (Lipopolysaccharide, LPS). At
the end of the treatment period, culture media were collected and
stored at -80C until ELISA determinations were performed.
Four trials were carried out for each experimental conditions.
Anti-Inflammatory Activity Study
Culture media of CTR-, CTR+ and cells treated with tested product
were used for the dosage of pro-inflammatory cytokine TNF-alpha by
means of ELISA method.
A commercial kit was used for the determination. ELISA assay uses
the competitive binding between an antigen (in this case the molecule
TNF-alpha) and its primary antibody. The immune complex (antigenantibody) was bound by a secondary antibody
conjugated to a peroxidase. The addition of the
enzyme substrate gives a colorimetric
reaction with intensity proportional to the
immune complex presence, and
so to the TNF-alpha quantity.
The quantitative
determination uses a
calibration curve made-up of
standard known and

24

growing concentrations. The results are quantitatively expressed as TNFalpha pg/ml and as % variation of the cytokine release vs. the controls.
Statistical Analysis
Obtained results were subjected to statistical analysis by means of
Student test. Variations are considered statistically significant for
p<0.05.

RESULTS
Data obtained for each tested series are reported in Figures 4 and 5.
The results are expressed as TNF-alpha released in the media
during experimental period (average value expressed as pg/ml s.e.)
and as % variation (average value s.e.) compared to the controls.
The cell treatment with M.E.D. Integral Propolis ESIT 12F K have
highlighted a significant reduction of the TNF-alpha release in the
cells subjected to inflammatory stress in all the considered
experimental conditions; the product shows an effective antiinflammatory activity.

CONCLUSION
Different scientific studies show that propolis has various and
interesting activities as prevention and treatment of many pathologies.
This activity is due mainly to the richness of polyphenols contained.
Aim of the new M.E.D. technology (Dynamic Multi Extraction) is to
evolve the classical hydroalcoholic extraction using sophisticated
analytical methods which allow to modulate the process.
By this method we obtain an intermediate product, very rich in
polyphenols, from which it is possible to produce commercial extracts
having an elevated and sure activity apart from the excipients or
solvents used.

REFERENCES
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2)
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4)
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6)
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8)
9)
10)

Volpi N, Bergonzini G. J. Pharm. Biomed. Anal. 2006, 42 (3) 354-61.


Volpi N. Electrophoresis 2004, 25 (12) 1872-8.
Banskota A.H., Tezuka Y., Kadota S. Phytother. Res. 2001, 15, 561-71.
Barak V., Birkenfeld S., Halperin T., Kalickman I. Isr. Med. Assoc. J. 2002, 4, 919-2.
Cos P., Rajan P., Vedernikova I., Calomme M., Pieters L., Vlietinck A.J.,
Augustyns K., Haemers A., Vanden Berghe D. Free Radic. Res. 2001, 36, 711-6.
Sforcina J.M., Bankova B. Journal of Ethnopharmacology 2011, 133, 253-60.
Re R., Pellegrini N., Proteggente A., Pannala A., Yang M., Rice-Evans C.
Free Radical Biology & Medicine 1999, 26 (9/10) 1231-7.
Bonavida B. Biotherapy 1991, 3, 127-33.
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Blankenstein T. et al. Journal of Experimental Medicine 1991, 173, 1047-52.

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Liver
Health
and
Body Fat
Reduction

Xanthigen
burns up to
400 kcal per day
more than
placebo.
Xanthigen Body Fat and Liver Fat
Reduction Compared to Placebo*

Fat Amount Changed

Placebo Liver/
Body Fat

Liver Fat
Xanthigen
Body Fat
Xanthigen

Significant reduction in liver fat ( )


Followed by significant reduction in body fat ( )

7
8
9 10
Time (Weeks)

11

12

13 14

Excess liver fat is


linked to excess
body fat.

The liver sheds fat


then liver function and fat
metabolism improves.

Improved metabolic
function results in
reduced body fat.

Introducing Xanthigen a new class of weight management supplement


that supports body fat reduction, weight loss and promotes liver health.
Xanthigen is a novel, patent-pending, synergistic composition of brown
seaweed extract standardized for fucoxanthin and pomegranate seed oil
standardized for punicic acid. Xanthigen helps the liver to shed stored
fats, improving metabolic function and energy expenditure. And Xanthigen

15

16

*Diagrams provided for educational purposes, based upon peer-reviewed


published research.
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent
any disease.
Xanthigen is a registerd trademark exclusively licensed to PoliNat,
Spain. PL Thomas 2011. All rights reserved.

supports healthy body fat reduction.


The liver acts as a filter in the body and once it is clogged with fat, it
cannot function properly a condition clearly linked with fat accumulation
in other body organs and tissues. A recent clinical study with Xanthigen
strongly suggests that unclogging the liver may play an essential role in

Scan this QR Code with your


smart phone to get more detailed
information about Xanthigen.

the fight against excess body fat. Promoting liver fat and body fat reduction
results in a healthier body over all. The new road to body weight
management: healthy liver, healthy weight, healthy body.

973-984-0900 x214
plt@plthomas.com
www.plthomas.com/brands

Copertina_ok:Copertina 01/10/12 15:32 Pagina 4

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