Title: Acceleration of the rate of digestion of a
United States Patent: 6,544,515
Issued: April 8, 2003
Inventors: Dangin; Martial (Clermont-Ferrand, FR); Garcia-Rodenas;
Clara Lucia (Mollie-Margot, CH); Beaufrere; Bernard (Chamalieres, FR);
Ballevre; Olivier (Lausanne, CH)
Assignee: Nestec S.A. (Vevey, CH)
Appl. No.: 588650
Filed: June 7, 2000
The invention thus relates to a method for accelerating the rate of
digestion of a protein matter, in which a protein matter is treated with
transglutaminase, and it is mixed with anionic polysaccharides. The
invention also relates to the use of the rapidly digested protein matter for
preparing a food or pharmaceutical composition intended for oral
administration to a mammal, to induce a postprandial peak of plasmatic
increase in amino acids. This composition is intended for modulating the
postprandial protein gain, limiting the problems linked to gastrointestinal
motility disorders, limiting the postprandial sensations of nausea in
pregnant women, and/or limiting the postprandial risks of regurgitation
and/or gastro-esophageal reflux. Finally, a subject of the invention is also
a food or pharmaceutical composition comprising anionic polysaccharides and
a protein matter treated with transglutaminase.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Contrary to all expectations, the rate of digestion of a protein can be
accelerated without previously carrying out its hydrolysis. Similarly,
despite past convictions, proteins which are treated with transglutaminase
and/or proteins to which anionic fibers are attached have an accelerated
rate of digestion. WO 97/05785 (Milupa GmbH) claimed, without
demonstrating it, that treating proteins, in particular milk casein, with
transglutaminase made it possible to slow their rate of digestion.
Similarly, as dietary fibers increase the viscosity of the
gastrointestinal content, it was estimated that the time for digestion of
all the nutrients present in a meal containing these fibers had,
therefore, to be increased (see U.S. Pat. No. 5,126,332).
Finally, the treatments according to the invention, which aim to
accelerate the rate of digestion of proteins, did not take place to the
detriment of the digestibility of the proteins. The proteins thus treated
do not therefore substantially induce an increase in the ratio calculated
between the amount of protein ingested orally and the amount of protein
absorbed by the body (as an example, see Vaughan et al., Am. J. Olin.
Nutrition, 30, 1709-1712, 1977).
In the context of the present invention, "substantially" means within 10%,
preferably within 5%, more preferably within 2%.
In the context of the present invention, the expression "plasmatic
postprandial peak of amino acids" corresponds to a rapid and noticeable
increase in the plasmatic level of amino acids after a meal, followed by a
decrease which is virtually as rapid (see FIG. 3).
To implement the present method, a protein matter is used, i.e. all kinds
of matter comprising proteins, whether they are of animal, plant or
microbial origin, in particular proteins from milk, oilseeds, legumes, egg
yolk, or brewer's yeast, for example.
Milk is intended firstly to refer to a milk of animal origin, such as the
milk of a cow, goat, sheep, buffalo, zebra, horse, ass, camel, and the
like. The term milk also applies to what is commonly called a vegetable
milk, i.e. an extract of treated or untreated vegetable matters, such as
legumes (soybean, chickpea, lentil, and the like) or oilseeds (rapeseed,
soybean, sesame, cotton, and the like), said extract containing proteins
in solution or in colloidal suspension, which can coagulate in acid
medium. Finally, the term "milk" also refers to mixtures of animal milks
and of vegetable milks.
Protein matters with a high nutritive value, according to the recommended
rations, such as casein and proteins from egg, from soybean, from pea,
from bean, from lentils, from chickpea, from lupin, from carob, from
rapeseed or originating from other sources recognized for their nutritive
values are particularly indicated in the context of the present invention
(FAO/WHO, Protein Quality Evaluation, No. 51, Rome 1991). These proteins
can contain a balanced and high content of each of the amino acids which
are essential for the body, such as lysine, tryptophan, leucine,
isoleucine, valine, phenylalanine, methionine and threonine, for example.
Preferably, the untreated protein matter comprises slowly digested
proteins, i.e., proteins which, when ingested by rats weighing 140 to 200
g, can lead to a disappearance of half the ingested nitrogen present in
the digestive tract in more than 80 minutes. Proteins which coagulate in
the stomach, such as casein, are most frequently slowly digested proteins.
Specifically, it is known that the rate of digestion of food proteins is
controlled by the stomach, and more specifically by gastric emptying (Gaudichon
et al., American Institute of Nutrition, Milk and Yoghurt Digestion
1970-1977, 1994). The coagulum formed in the stomach in this way has
trouble leaving, which delays the digestion of the protein.
To implement the present method, this protein matter is then treated with
transglutaminase to catalyze polymerization, deamidation, and
amine-incorporation reactions (Nielsen, Food biotechnol., 9, 119-156,
1995). The treatment conditions can vary according to the requirements of
the present invention. As a general rule, the proteins are suspended in an
aqueous medium in a proportion of 1 to 30% by weight, transglutaminase is
added in a proportion of 100 to 100,000 units/L, the suspension is
subjected to optimal conditions for hydrolysis (pH 7, 5000 units/L), and
the enzyme is inactivated by heat and/or by hydrostatic pressure of 300 to
1100 MPa (see EP 686352 and EP 748592 of S.P.N.).
Anionic polysaccharides, in particular chosen from alginates, xanthan, gum
arabic, pectins, kappa-carrageenans, iota-carrageenans, lambda-carrageenans,
carboxymethylcellulose, sulfated dextrans and/or gellan gum, are then
added to the protein matter, before or after treatment with the
transglutaminase. The treatment conditions can vary according to the
requirements of the present invention. As a general rule, between 0.05 and
30% by w/v of anionic polysaccharides are added.
The conditions for treating the protein matter should preferably be chosen
so as to reach a level of acceleration of the rate of digestion of the
protein matter such that, when the treated protein matter is administered
orally to rats weighing 140 to 200 g, it leads to a disappearance of half
the ingested nitrogen present in the digestive tract in less than 70
minutes, for example.
The protein matter thus treated can be used advantageously for preparing a
food or pharmaceutical composition intended for oral administration to a
mammal, to induce a plasmatic postprandial peak of amino acids, and, as a
result, to accomplish one or more of the following: to modulate the
postprandial protein gain; to limit the problems linked to
gastrointestinal motility disorders; to limit the postprandial sensations
of nausea in pregnant women; and/or to limit the postprandial risks of
regurgitation and/or gastro-esophageal reflux.
The present use is not however limited to a protein matter treated
according to the invention. Specifically, other treatments can also induce
an acceleration of the rate of digestion of a protein matter. The present
use thus also aims to use any protein matters which have been pretreated
so as to transform the slowly digested proteins that it contained into
rapidly digested proteins which have at least substantially conserved the
same initial molecular weight.
For this, one of the abovementioned protein matters, which has however
been treated with transglutaminase, such as those described in WO 97/05785
(Milupa GmbH) can be used, for example. In this case, the molecular weight
of the proteins thus treated increases as a result of the polymerization
of the proteins.
It is also possible to use only mixtures of proteins and of anionic
fibers, such as those described in U.S. Pat. No. 5,126,332, in particular
making use of the above-mentioned polysaccharides, for example. In this
case, the molecular weight of the proteins thus treated remains identical,
but their physicochemical properties are modified as a result of the
interaction with the polysaccharides.
Preferably, to implement the present methods, a protein matter which
initially contained slowly digested proteins is used, i.e., proteins
which, when ingested by rats weighing 140 to 200 g, lead to a
disappearance of half the ingested nitrogen present in the digestive
tract, in more than 80 minutes.
Protein matters which have a high nutritive value are also particularly
indicated. These matters can be exploited in people with a physiological
requirement for rapidly digested proteins, such as patients who are in a
postoperative or post-traumatic period, children or sportspersons who have
just undergone effort, or in people who have a physiological aversion to
consuming slowly digested proteins, such as elderly people, people
suffering from anorexia, or pregnant women subject to nausea.
The food or pharmaceutical compositions which comprise these
accelerated-digestion protein matters are preferably used in the context
of diets, or even of therapeutic treatments, for preventing or treating
problems linked to specific pathological or physiological states. The
conditions governing these diets depend in fact on the categories of
people concerned. As a general rule, it will be considered that the
composition comprises an amount of protein matter which is sufficient and
effective in inducing a postprandial plasmatic peak of amino acids.
More particularly, these compositions are aimed at athletes who are
looking to increase their body mass, and more specifically their muscle
mass. These compositions can thus comprise a source of proteins which
represents 15% to 100% of the total energy. This source can consist
essentially of at least one of the treated protein matters described
above. Preferably, these compositions comprise treated casein, this casein
comprising about 22% valine, leucine and isoleucine, the amino acids being
used in the muscle as energetic substrates (Kasperek et al., Am. J.
Physiol., 252, E33-37, 1987), and allowing carbohydrate stores to be saved
(Blomstrand et al., Nutrition., 12, 485-490, 1996).
Children who exercise physically also have the same physiological
requirements as an athlete, particularly after an intense effort. The food
compositions for children are preferably formulated to be particularly
revitalizing. For this, they comprise, in addition to the source of
proteins, a source of carbohydrates which can be rapidly assimilated,
lipids, as well as mineral salts and vitamins.
Finally, patients who are in a postoperative or posttraumatic period also
have considerable physiological requirements for amino acids. The food
compositions are preferably formulated to also be revitalizing. For this,
they also comprise, in addition to the source of proteins, a source of
carbohydrates which can be rapidly assimilated, lipids, as well as mineral
salts and vitamins.
Gastrointestinal motility disorders are often associated with ageing and
with pathological states such as anorexia, diabetes, the presence of a
gastric carcinoma, neurological disorders (e.g., Parkinson's disease),
drug dependency, alcoholism, and the like. The time required for gastric
emptying and digestion in these people is abnormally high, which leads to
symptoms of anorexia, nausea, and vomiting. These people can thus also
have a sensation of satiety which is too strong and protracted after a
meal, such that they have difficulties in eating regularly and
sufficiently. A composition comprising proteins of high nutritive value,
which are rapidly evacuated from the stomach and which are rapidly
digested, participates in the elimination of these problems. This
composition can thus comprise a source of proteins which represents 10% to
30% of the total energy. This source of proteins can essentially consist
of at least one of the treated protein matters described above.
During pregnancy, because of the increase in body mass due to the
conception (foetus, placenta) and the hypertrophy of various maternal
tissues (uterus, breasts, extracellular fluids), the energy and protein
requirements are greater. Many pregnant women suffer from temporary
nausea, however, and this hinders them from maintaining a balanced diet. A
composition comprising proteins of high nutritive value, which are rapidly
evacuated from the stomach and which are rapidly digested, participates in
the reduction or elimination of these problems. This composition can thus
comprise a source of proteins which represents 10% to 30% of the total
energy. This source of proteins can essentially consist of at least one of
the treated protein matters described above.
Problems of gastro-esophageal reflux are often observed in pregnant women,
newborn babies or premature babies, in particular after ingestion of milk.
Current treatments consist in thickening foods and/or in accelerating
gastric emptying and in increasing the tonus of the gastro-esophageal
sphincter by means of medicaments. The compositions according to the
invention are particularly suitable for preventing, or even treating,
these problems. These compositions can thus comprise a source of proteins
which represents 10% to 40% of the total energy. This source of proteins
can essentially consist of at least one of the treated protein matters
More particularly, the compositions comprising anionic polysaccharides
have a three-fold advantage for treating problems of reflux. Firstly, the
protein matters have a viscosity which limits problems of reflux.
Secondly, these protein matters are rapidly removed from the stomach,
which also limits problems of reflux. Thirdly, these protein matters are
very easily digested.
Finally, newborn babies or patients fed by the enteral route also have
problems of regurgitation, which can lead to obstruction of the
respiratory pathway. The enteral compositions use complex mixtures of
micro- and macro-nutriments in order to improve the nutritional state of
the patients. To date, three sources of amino acids have generally been
used for these patients, i.e. intact proteins, hydrolyzed proteins
(peptides) and amino acids. Amino acids and peptides have an unpleasant
taste, and cause an increase in gastrointestinal osmolarity, this
parameter leading to the appearance of diarrhea. In addition, the
nutritive value of free amino acids is not comparable to that of intact
proteins. For intact proteins, most of the enteral compositions use
casein. Unfortunately, it coagulates in the stomach and gastric emptying
is thus protracted. The present invention aims to use a composition with a
good taste, comprising nonhydrolyzed protein matters which are digested
very rapidly. This composition can thus comprise a source of proteins
which represents 15% to 25% of the total energy. This source of proteins
can essentially consist described above.
The food or pharmaceutical compositions comprise, preferably, a source of
carbohydrates which provides 50 to 70% of the total energy. Carbohydrates,
in particular after a physical effort, after a postoperative trauma,
during pregnancy and in newborn babies, are important nutrients for
restoring sugar stores, and avoiding hypoglycemia. All the carbohydrates
can be used, in particular maltodextrins, saccharose, lactose and glucose.
The food or pharmaceutical compositions can comprise a source of lipids
which provides 15 to 35% of the total energy. Vegetable oils are
recommended, in particular those originating from soybean, oil palm,
coconut palm, sunflower, etc. Minerals, vitamins, salts, emulsifiers or
flavor-enhancing compounds can also be added to the compositions,
according to the desired requirements.
The food or pharmaceutical compositions can be prepared in all kinds of
ways, the manufacturing steps generally including a dispersion of the
ingredients in water, and a pasteurization. The compositions can be
prepared in the form of drinks or of liquid concentrates, or in the form
of a powder which can be reconstituted in water, etc.
Claim 1 of 20 Claims
What is claimed is:
1. A method for accelerating the rate of digestion of milk protein matter,
which comprises treating milk protein matter with transglutaminase under
conditions sufficient to catalyze polymerization, deamidation, or
amine-incorporation reactions in the milk protein matter to obtain treated
milk proteins, optionally followed by the mixing of the treated milk
proteins with one or more anionic polysaccharides to form a mixture,
wherein the treated milk proteins have an accelerated rate of digestion
compared to the untreated milk protein matter.
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