NZ719161B2 - Fermented formula with non digestible oligosaccharides - Google Patents
Fermented formula with non digestible oligosaccharides Download PDFInfo
- Publication number
- NZ719161B2 NZ719161B2 NZ719161A NZ71916114A NZ719161B2 NZ 719161 B2 NZ719161 B2 NZ 719161B2 NZ 719161 A NZ719161 A NZ 719161A NZ 71916114 A NZ71916114 A NZ 71916114A NZ 719161 B2 NZ719161 B2 NZ 719161B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- formula
- infant
- follow
- lactic acid
- oligosaccharides
- Prior art date
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- 229920001542 oligosaccharide Polymers 0.000 title claims abstract description 92
- 150000002482 oligosaccharides Polymers 0.000 title claims abstract description 92
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Abstract
The present invention relates to a fermented infant or follow on formula comprising a fermented ingredient, non-digestible oligosaccharides including galacto-oligosaccharides, lactate and lactic acid for decreasing duration of crying, reducing crying episodes, and incidence of colics in infants.
Description
FERMENTED FORMULA WITH NON DIGESTIBLE OLIGOSACCHARIDES
FIELD OF THE INVENTION
The present invention is in the field of infant nutrition.
OUND OF THE INVENTION
After birth the digestive tract of an infant has to adapt to full enteral feeding. At the same time
the still immature digestive tract has to develop and mature. Human milk is the preferred method
of feeding for infants. However, there are circumstances that make breast-feeding impossible or
1O less desirable. In those cases infant formulae can be considered an alternative. The composition
of modern infant formulae is adapted in such a way that it meets many of the special nutritional
requirements of the fast growing and developing infant.
ile colic is a widespread clinical problem in infants. It is the cause of 10 to 20 % of all
early paediatrician visits and often leads to al exhaustion and stress. An increased risk of
maternal postpartum depression has been observed. Infantile colic is observed in 10 to 30 % of
the infants, who are otherwise healthy. Typically colic in an infant occurs between the age of 2
weeks to 4 months.
2O The causes of ile colics are not fully tood, and this makes it difficult to find a good
prevention or treatment. olinergic drugs such as dicyclomine and dicycloverine are
sometimes used, but they are not recommended because of their serious side effects. The role of
nutrition has been the subject of research, and in those cases where cow’s milk allergy is the
underlying cause of the colics, a hypoallergenic formula may solve the problem. However, cow’s
milk allergy is only present in a small population of the s suffering from colics.
EP 2 520 181 discloses the use of a fermented or partly fermented infant formula for promoting
gut health, including t others the ent and/or prevention of colics or cramps. Savino
et al, 2006, Eur J Clin Nutr 60, 1304-1310, disclose that the use of a partially hydrolysed formula
supplemented with fructo- and galacto-oligosaccharides and comprising low lactose and
sed palmitic acid at the beta position induces a reduction in colic episodes, measured as
wed by page 2A)
crying episodes, in infants with colics after 7 and 14 days. EP1685763 disclosed the use of a
combination of GOS and polyfructose for amongst others colic and/or abdominal cramps.
discloses the use of antibiotics or probiotics for the treatment of gut motility
disorders.
Y OF THE INVENTION
The present invention particular provides a method for
- reducing the incidence of colics in an infant,
- reducing the number of crying e s per day in an infant and/or
- decreasing the duration of crying in an infant,
comprising administering to said infant an infant formula or follow on a comprising:
- 25 to 99.5 wt.% of a fermented ingredient based on dry weight of the infant or follow
on formula, wherein the ted ingredient is fermented byStreptococcus philus
and/or bacterium breve,
- 2.0 to 7.5 wt.% non digestible oligosaccharides based on dry weight of the infant
formula or follow on formula wherein the non digestible oligosaccharides comprise galactooligosaccharides
, and
- 0.25 to 1.5 wt.% of the sum of l actate and lactic acid based on dry weight of the infant
formula or follow on formula, wherein the sum of L-lactic acid and L-lactate is more than 50
wt.% based on the sum of total lactic acid and lactate.
In certain embodiments the infant formula or follow on formula is for providing nutrition to
infants with an age of 6 months or below.
In still further embodiments, the infant a or follow on formula comprises at least two
different non digestible oligosaccharides, ably galacto-oligosaccharides and fructooligosaccharides.
In still further embodiments the infant formula or follow on formula comprises Streptococcus
thermophilus and/or Bifidobacterium breve. In certain embodiments the infant formula or
follow on formula comprises at most 1x105 cfu of lactic acid ia per g dry weight of the
infant or follow on formula. In other embodiments the infant formula or follow on formula
comprises 1x102 - 1x 105 cfuStreptococcus thermophilus per g dry weight of the infant or
follow on formula.
wed by page 3)
In still r embodiments the infant formula or follow on formula is in the form of a powder.
Other embodiments are also described herein for completeness.
DETAILED DESCRIPTION OF THE INVENTION
The present inventors found that when a partly fermented infant formula comprising at least 2
non digestible oligosaccharides was administered to infants, the incidence of colics and the
number of crying episodes per day was statistically significantly reduced compared to controls
that ned either only a partly fermented infant a without non-digestible
oligosaccharides, or a non-fermented infant formula that contained non-digestible
oligosaccharides. The reduction was unexpectedly much higher than observed when partly
fermented infant formula without non digestible oligosaccharides were given, or when nonfermented
infant formula with non digestible oligosaccharides were given.
Thus, the t ion concerns a method for reducing the incidence of colics in an infant,
comprising administering to said infant an infant formula or follow on formula comprising:
- a fermented ingredient, in particular a composition fermented by lactic acid bacteria,
- 0.5 to 20 wt.% non digestible oligosaccharides based on dry weight of the infant formula
or follow on formula, and
- 0.25 to 1.5 wt.% of the sum of lactate and lactic acid based on dry weight of the infant
formula or follow on formula, wherein the sum of ic acid and L-lactate is more than
50 wt.% based on the sum of total lactic acid and lactate.
In other words, the t invention concerns the use of a fermented ingredient, in particular
a composition fermented by lactic acid bacteria, and non-digestible oligosaccharides in the
manufacture of an infant or follow on formula for use in reducing the incidence of colics in an
infant, wherein the infant formula or follow on formula comprises:
- 0.5 to 20 wt.% non digestible oligosaccharides based on dry weight of the infant a
or follow on formula, and
- 0.25 to 1.5 wt.% of the sum of lactate and lactic acid based on dry weight of the infant
formula or follow on formula, wherein the sum of ic acid and L-lactate is more than
50 wt.% based on the sum of total lactic acid and lactate.
The invention can also be worded as an infant formula or follow on formula comprising:
- a ted ingredient, in particular a ition fermented by lactic acid bacteria,
- 0.5 to 20 wt.% non digestible oligosaccharides based on dry weight of the infant formula or
follow on a, and
- 0.25 to 1.5 wt.% of the sum of lactate and lactic acid based on dry weight of the infant
formula or follow on formula, wherein the sum of L—lactic acid and ate is more than
50 wt.% based on the sum of total lactic acid and lactate,
for use in reducing the nce of colics in an infant.
Preferably, the infant formula or follow on formula is for ing nutrition to an infant with an
age of 6 months or below. In one embodiment, the infant is suffering from colics or is at risk of
developing colics. In one embodiment, the infant is suffering from colics.
The present invention also concerns a method for reducing the number of crying episodes per
day in an infant, comprising administering to said infant an infant formula or follow on formula
comprising:
- a ted ingredient, in particular a composition fermented by lactic acid bacteria,
- 0.5 to 20 wt.% non digestible oligosaccharides based on dry weight of the infant formula or
follow on formula, and
- 0.25 to 1.5 wt.% of the sum of lactate and lactic acid based on dry weight of the infant
formula or follow on formula, wherein the sum of L—lactic acid and L-lactate is more than
50 wt.% based on the sum of total lactic acid and lactate.
In other words, the invention also concerns the use of a fermented ingredient, in particular a
composition fermented by lactic acid bacteria, and non-digestible oligosaccharides in the
manufacture of an infant or follow on formula for use in reducing the number of crying episodes
per day in the infant, wherein the infant formula or follow on formula comprises:
0.5 to 20 wt.% non digestible oligosaccharides based on dry weight of the infant formula or
follow on formula, and
- 0.25 to 1.5 wt.% of the sum of lactate and lactic acid based on dry weight of the infant
formula or follow on a, wherein the sum of L—lactic acid and L-lactate is more than
50 wt.% based on the sum of total lactic acid and lactate.
The invention can also be worded as an infant formula or follow on formula comprising:
- a fermented ingredient, in ular a composition fermented by lactic acid bacteria,
- 0.5 to 20 wt.% non digestible oligosaccharides based on dry weight of the infant formula or
follow on a, and
- 0.25 to 1.5 wt.% of the sum of e and lactic acid based on dry weight of the infant
formula or follow on formula, wherein the sum of L—lactic acid and L-lactate is more than
50 wt.% based on the sum of total lactic acid and lactate,
for use in reducing the number of crying episodes per day in an infant.
In one embodiment, the use for reducing the number of crying episodes per day is for reducing
the incidence of colics in the infant.
The term reducing the number of crying episodes per day can also be referred to as reducing
crying.
The present invention also concerns a method for decreasing the duration of crying in an infant,
comprising stering to said infant an infant formula or follow on formula comprising:
- a fermented ingredient, in ular a composition ted by lactic acid bacteria,
- 0.5 to 20 wt.% non ible oligosaccharides based on dry weight of the infant formula or
follow on formula, and
- 0.25 to 1.5 wt.% of the sum of lactate and lactic acid based on dry weight of the infant
formula or follow on formula, wherein the sum of L—lactic acid and L-lactate is more than
50 wt.% based on the sum of total lactic acid and lactate.
In other words, the invention also concerns the use of a fermented ingredient, in particular a
composition fermented by lactic acid bacteria, and non-digestible oligosaccharides in the
manufacture of an infant or follow on formula for use in decreasing the on of crying in the
infant, wherein the infant formula or follow on formula comprises:
- 0.5 to 20 wt.% non digestible oligosaccharides based on dry weight of the infant formula or
follow on formula, and
- 0.25 to 1.5 wt.% of the sum of lactate and lactic acid based on dry weight of the infant
formula or follow on formula, wherein the sum of L—lactic acid and L-lactate is more than
50 wt.% based on the sum of total lactic acid and lactate.
The invention can also be worded as an infant formula or follow on formula comprising:
- a fermented ient, in particular a composition fermented by lactic acid bacteria,
- 0.5 to 20 wt.% non ible oligosaccharides based on dry weight of the infant formula or
follow on formula, and
- 0.25 to 1.5 wt.% of the sum of lactate and lactic acid based on dry weight of the infant
formula or follow on formula, wherein the sum of L—lactic acid and L-lactate is more than
50 wt.% based on the sum of total lactic acid and lactate,
for use in decreasing the duration of crying in an infant.
In one embodiment, the use for decreasing the duration of crying is for reducing the incidence of
colics in the infant.
Preferably, the infant formula or follow on formula is for providing nutrition to an infant with an
age of 6 months or below. In one embodiment, the infant is suffering from crying episodes or is
at risk of ping crying episodes. In one embodiment, the infant is suffering from crying
episodes.
Fermented ingredient
tation is the process of deriving energy from the oxidation of carbohydrates, such as the
e present in milk, using an endogenous electron or, which is usually an c
compound. This is in contrast to cellular respiration, where electrons are donated to an
exogenous electron acceptor, such as oxygen, via an electron transport chain. In the present
invention, fermentation of a composition by lactic acid producing bacteria has the common
meaning of the conversion of carbohydrates present in the ition to organic acids. These
organic acids formed may comprise, besides lactic acid, also other organic acids such as acetic
acid. In the context of the present invention, organic acids are understood to include the
corresponding conjugate bases (e.g. lactic acid may include lactate and acetic acid may include
acetate).
Thus, according to the present ion, a fermented ingredient is used. The fermented
ingredient is a composition that is fermented by lactic acid bacteria. Preferably the composition
that is ted by lactic acid bacteria comprises lactose and/or protein, preferably the
composition that is fermented by lactic acid bacteria comprises at least lactose. In a further
1O preferred embodiment, the composition that is fermented by lactic acid bacteria ses
lactose and protein. More preferably, the composition that is ted by lactic acid bacteria is
a milk-derived composition. The carbohydrate that is fermented is preferably lactose. In the
context of this invention, Wherever ‘fermented’ is mentioned. ‘fermented by lactic acid bacteria’
is meant.
Lactic acid bacteria are also ed to as lactic acid producing bacteria and include ia of
the genus Streptococcus, Lactococcus, Lactobacillus, Leuconostoc, Enterococcus, Oenococcus,
Pediococcus, and Bifidobacterium.
2O According to the present invention, the infant or follow on formula comprises a fermented
ient. The infant or follow on formula in the method or use according to the present
invention, preferably comprises a fermented milk-derived ition. This fermented milk-
derived composition is obtained by incubation of a combination of milk, e.g. skim milk, or a
milk-derived product, e.g. Whey, With at least one strain of lactic acid bacterium, such as
lactococci, lactobacilli, streptococci and bifidobacteria, preferably the fermented milk-derived
composition is obtained by incubation With at least one strain selected from occi,
lactobacilli and ococci, preferably With at least one strain selected from streptococci.
Preferably lactic acid bacteria Which perform homolactic fermentation are used for fermentation,
since in this case two lactic acid les are ed per sugar moiety and no gas is formed.
Homolactic lactic acid bacteria e Streptococcus thermophilus, Lactococcus s,
preferably Lactococcus lactis, and Group I lactobacilli such as Lactobacillus acidophilus,
Lactobacillus helveticus and Lactobacillus rius and facultative heterofermentative
Lactobacilli which produce two lactic acid from hexose sugars, and which include Lactobacillus
casei, Lactobacillus paracasei, Lactobacillus rhamnosus, acillus plantarum,
Lactobacillus sakei. Thus in one embodiment, preferably the fermented milk-derived
composition is obtained by incubation of a combination of milk, e.g. skim milk, or a milk
derived product, e.g. whey, with at least one strain selected from Streptococcus thermophilus,
occus lactis, Lactobacillus acidophilus, Lactobacillus helveticus, Lactobacillus salivarius,
Lactobacillus casei, Lactobacillus paracasei, Lactobacillus rhamnosus, acillus plantarum
and acillus sakei, preferably the fermented milk-derived composition is obtained by
1O incubation with Streptococcus thermophilus. Preferably the combination is incubated for 10
minutes to about 6 hours. The temperature during incubation is preferably between 20 and 50 °C.
In one embodiment, after incubation the incubated composition is preferably subjected to a heat
ent. By this heat treatment preferably at least 90 % of living lactic acid bacteria are
inactivated, more preferably at least 95 %. Preferably the fermented ingredient, more preferably
the infant formula or follow on formula, comprises less than 1x105 colony forming units (cfu)
lactic acid bacteria per g dry weight. The heat treatment preferably is performed at a temperature
between 80 and 180 °C. Inactivation of the lactic acid ium ageously results in less
post acidification and a safer product. This is especially advantageous since the infant or follow
on formula that is manufactured is to be administered to infants. Thus in one embodiment, the
2O fermented ingredient, more preferably the infant formula or follow on formula, comprises
inactivated lactic acid bacteria. Procedures to e ted ingredients suitable for the
purpose of the present invention are known per se. EP , which is incorporated herein by
reference, discloses in particular in example 7 a suitable process for preparing a fermented
ingredient. FR 2723960, which is incorporated herein by reference, ses in particular in
example 6 a suitable s for preparing a fermented ingredient.
Briefly, a milk d composition, preferably pasteurised, containing lactose and optionally
further macronutrients such as fats, preferably vegetable fats, casein, whey protein, vitamins
and/or ls etc. is concentrated, e.g. to between 15 to 50% dry matter and then inoculated
with S. thermophilus, for example with 5% of a culture containing 106 to 1010 ia per ml.
Preferably this milk derived composition comprises milk protein es. Temperature and
duration of fermentation are as mentioned above. Suitably after fermentation the fermented
ingredient may be pasteurised or sterilized and for example spray dried or lyophilised to provide
a form suitable to be formulated in the end product.
The bacterial strains of S. thermophilus that are preferably used to prepare the fermented
ingredient for the purpose of the present invention develop beta-galactosidase activity in the
course of fermentation of the substrate. Preferably alactosidase activity ps in parallel
with acidity. Selection of a suitable strain of S. thermophilus is described in example 2 of EP
778885 and in example 1 of FR 2723960. It is preferred that in the infant or follow on formula
ing to the method or use of the invention, at least part of the beta-galactosidase ty
that has developed during fermentation is retained. Preferably the at least part of the beta-
galactosidase activity that is ed is lactase activity. Upon digestion in the infant, lactase
activity in the infant or follow on formula has a beneficial effect on promoting intestinal tract
health. Preferably according to the present ion, per gram dry weight the infant or follow on
formula comprises 0.2 — 4 U (units) beta-galactosidase activity, ably the infant or follow on
formula comprises per gram dry weight 0.2 — 4 U lactase activity. A beta-galactosidase activity
of 1.0 U (one unit) ponds to the capacity to hydrolyze 1.0 umole of o-nitrophenyl B-D-
opyranoside to o-nitrophenol and D-galactose per min at pH 7.3 at 37 0C.
In a r red embodiment according to the present invention, the infant or follow on
formula comprises at most 1x105 cfu living bacteria of S. thermophilus, preferably the infant or
follow on formula comprises at most 1x104 cfu living bacteria of S. thermophilus based on g dry
weight. In one embodiment, preferably not all lactic acid ia, preferably not all S.
thermophilus, is inactivated. Thus preferably the infant or follow on formula comprises at least
1x102 cfu living bacteria of S. thermophilus, preferably the infant or follow on formula
comprises at least 1x103 cfu living bacteria of S. thermophilus per g dry weight.
Preferred strains of S. thermophilus to prepare a fermented ingredient, ably a fermented
milk-derived composition, for the purpose of the present invention have been deposited by
Compagnie Gervais Danone at the Collection Nationale de Cultures de Microorganismes
(CNCM) run by the Institut Pasteur, 25 rue du Docteur Roux, Paris, France on 23 August 1995
under the accession number 1-1620 and on 25 August 1994 under the accession number I-l470.
The strains I-1620 and I-1470 have been disclosed in EP 0778885.
Preferably, in the preparation of the ted ingredient additionally one or more further strains
of lactic acid bacteria are present or, either simultaneously or consecutively, the composition
additionally is supplemented With or fermented by one or more further strains of lactic acid
bacteria. The one or more further s are each a different strain than the first strain used for
fermenting the composition as described above, preferably a different strain than S.
tbermopbilus. Such ent s of lactic acid bacteria are preferably selected from the group
consisting of Lactobacillus and Bifidobacteria, more preferably Bifidobacterium breve, most
1O preferably Bifidobacterium breve strain deposited by Compagnie Gervais Danone at the CNCM
under number I-2219 on 31 May, 1999. Strain I-2219 has been disclosed in EP 1615657.
In one embodiment, the fermented ient comprises Streptococcus tbermopbilus, and/or
Bifidobacterium breve. In one embodiment, the fermented ingredient is fermented by
ococcus tbermopbilus, and/or Bifidobacterium breve.
In one embodiment, the infant or follow on formula comprises a ted ingredient, wherein
the lactic acid bacteria are inactivated after fermentation.
Preferably the composition that is ted by lactic acid bacteria is not fermented by
2O Lactobacillus icus. L. bulgaricus ted products are considered not suitable for
infants, since in young infants the ic dehydrogenase that converts ate to pyruvate is
far less active than the dehydrogenase Which converts L-lactate.
The fermented ingredient preferably comprises protein. The protein is preferably selected from
the group consisting of non-human animal ns, preferably non-human milk proteins. The
fermented composition preferably contains casein, and/or Whey protein, more preferably bovine
Whey proteins and/or bovine casein.
The infant or follow on formula for use according to the present invention preferably comprises
25 to 100 wt.%, more preferably 30 to 99.5 wt.%, of the fermented ingredient, preferably the
fermented milk-derived composition, based on dry weight of the infant or follow on formula. In
one embodiment the present infant or follow on formula preferably contains 30 to 99 wt.%, more
preferably 30 to 70 wt.%, more preferably 40 to 60 wt.%, of the fermented ingredient, based on
dry weight of the final infant or follow on formula. Higher concentrations of fermented
composition, e.g. 25, preferably 30 wt.% or above) advantageously improve the effect on colics
incidence and crying episodes.
The pH of the present infant or follow on a is preferably between 5.0 and 7.5, more
preferably between 5.0 and 7.0, even more preferably between 5.5 and 7.0, most preferably
between 5.5 and 6.0.
The infant or follow on formula for use according to the t invention comprises lactic acid
and/or lactate. Lactic acid and/or lactate is formed upon fermentation by lactic acid bacteria. The
present infant or follow on a comprises 0.25 to 1.5 wt.% of the sum of lactic acid and
lactate, preferably 0.30 to 1.0 wt.%, more preferably 0.4 to 0.7 wt.% of the sum of lactic acid and
lactate based on dry weight of the infant or follow on a. The more lactate and lactic acid is
present the more the infant or follow on formula comprises of the fermented ingredient.
Preferably at least 50 wt. %, even more preferably at least 90 wt.%, of the sum of lactic acid and
lactate is in the form of L-isomer. Thus in one embodiment the sum of L-lactic acid and L-lactate
is more than 50 wt. %, more preferably more than 90 wt.%, based on the sum of total lactic acid
and lactate. L-lactate and L—lactic acid is the same as L-(+)-lactate and L-(+) lactic acid. In one
embodiment the infant or follow on formula comprises from 0.25 to 1.5 wt.% of the sum of
lactate and lactic acid, preferably 0.30 to 1.0 wt.%, of the sum of lactate and lactic acid based on
dry weight of the infant or follow on formula and wherein the sum of ic acid and L-lactate
is more than 50 wt. % based on the sum of total lactic acid and lactate.
Non-digestible accharides
According to the present invention, the infant or follow on formula ses gestible
oligosaccharides. Non-digestible oligosaccharides were found to synergistically act with the
fermented ingredient to reduce the incidence of colics and number of crying episodes per day.
Advantageously and most preferred, the non-digestible oligosaccharides are water-soluble
ding to the method sed in L. Prosky et al, J. Assoc. Anal. Chem 71: 1017-1023,
1988) and are ably oligosaccharides with a degree of polymerisation (DP) of 2 to 200. The
average DP of the gestible oligosaccharides are preferably below 200, more preferably
below 100, even more preferably below 60, most preferably below 40. The non-digestible
oligosaccharides are not digested in the intestine by the action of digestive enzymes t in
the human upper digestive tract (small intestine and stomach). The non-digestible
oligosaccharides are fermented by the human intestinal microbiota. For example, glucose,
fructose, galactose, e, lactose, maltose and the maltodextrins are considered digestible. The
non-digestible oligosaccharide raw als may comprise monosaccharides such as glucose,
fructose, fucose, galactose, se, xylose, glucuronic acid, GalNac etc., but these are not part
1O of the non digestible oligosaccharide fraction of the infant or follow on formula according to the
present invention.
The non-digestible oligosaccharides included in the infant or follow on a according to the
methods or use ing to the present invention preferably include a mixture of at least two
different non-digestible oligosaccharides.
The gestible oligosaccharides are preferably selected from the group consisting of fructo-
oligosaccharides (such as inulin), non-digestible ns, galacto-oligosaccharides (such as
transgalacto-oligosaccharides), xylo-oligosaccharides, arabino-oligosaccharides, ogalacto-
oligosaccharides, oligosaccharides, gentio-oligosaccharides, glucomanno-
2O oligosaccharides, galactomanno-oligosaccharides, mannan-oligosaccharides, isomalto-
accharides, nigero-oligosaccharides, chito-oligosaccharides, soy oligosaccharides, uronic
acid oligosaccharides, sialyloligosaccharides (such as 3-sialyllactose (3-SL), 3-sialyllactose (6-
SL), lactosialylterasaccharide (LST) a,b,c, disialyllactoNtetraose (DSLNT), sialyl-lactoNhexaose
(S-LNH), sialyl-lactoNhexaose (DS-LNH)), fuco-oligosaccharides (such as (un)sulphated
fucoidan oligosaccharides, 2’-fucosyllactose (2’-FL), 3’-fucosyllactose (3-FL), difucosyllactose,
lacto-N—fucopenatose (LNFP) I, II, 111, V, Lacto-N—neofucopenaose (LNnFP), Lacto-N—
difucosyl-hexaose (LNDH)) and mixtures thereof, more preferably selected from the group
consisting of fructo-oligosaccharides, galacto-oligosaccharides, uronic acid oligosaccharides,
fuco-oligosaccharides and mixtures thereof, even more ably selected from the group
consisting of fructo-oligosaccharides, galacto-oligosaccharides and mixtures thereof. In one
embodiment, the non digestible oligosaccharides consist of transgalacto-oligosaccharide, inulin
2014/050762
and/or uronic acid oligosaccharides, most preferably at least transgalacto-oligosaccharides are
included. In one embodiment, the non digestible oligosaccharides are selected from the group
consisting of transgalacto-oligosaccharides, -oligosaccharides and galacturonic acid
oligosaccharides and mixtures of thereof.
The gestible oligosaccharides are preferably selected from the group consisting of B-
galacto-oligosaccharide, (x-galacto-oligosaccharide, and galactan. According to a more preferred
embodiment non-digestible oligosaccharides are B-galacto-oligosaccharide. Preferably the non-
digestible oligosaccharides comprises galacto-oligosaccharides with B(1,4), B(1,3) and/or B(1,6)
1O glycosidic bonds and a terminal glucose. Transgalacto-oligosaccharide is for example available
under the trade name ViVinal®GOS (Borculo Domo Ingredients, Zwolle, Netherlands), Bi2muno
(Clasado), Cup-oligo (Nissin Sugar) and Oligomate55 (Yakult).
The non-digestible oligosaccharides preferably comprise fructo-oligosaccharides. A -
oligosaccharide may in other context have names like fructopolysaccharides, oligofructose,
polyfructose, polyfructan, inulin, levan and fructan and may refer to accharides comprising
B-linked fructose units, which are preferably linked by B(2,1) and/or B(2,6) glycosidic linkages,
and a preferable DP between 2 and 200. Preferably, the fructo-oligosaccharide contains a
terminal B(2,1) glycosidic linked glucose. Preferably, the fructo-oligosaccharide ns at least
2O 7 B-linked fructose units. In a further preferred embodiment inulin is used. Inulin is a type of
fructo-oligosaccharide wherein at least 75% of the glycosidic linkages are B(2,1) linkages.
Typically, inulin has an average chain length between 8 and 60 ccharide units. A suitable
fructo-oligosaccharide for use in the compositions of the present ion is commercially
ble under the trade name Raftiline®HP (Orafti). Other suitable sources are raftilose
(Orafti), fibrulose and fibruline (Cosucra) and Frutafit and frutalose (Sensus).
ably the infant or follow on formula comprises a e of galactooligosaccharides and
fructooligosaccharides in a weight ratio of from 1/99 to 99/1, more preferably from 1/19 to 19/1,
even more preferably from 1 to 19/ 1.
Preferably the infant or follow on formula comprises a mixture of short chain
fructooligosaccharides, and long chain fructooligosaccharides in a weight ratio of from 1/99 to
99/1, more preferably from 1/19 to 19/1, even more preferably from 1 to 19/1.
Preferably the infant or follow on formula ses a mixture of F) 1,3 galactooligosaccharides
and F) 1,4 and/or [31,6 ooligosaccharides, in a weight ratio of from 1/99 to 99/1, more
preferably from 1/ 19 to 19/ 1, even more preferably from 1/ 19 to 1.
Preferably the infant or follow on formula comprises a mixture of transgalacto-oligosaccharide
with an average DP below 10, preferably below 6 and a -oligosaccharide with an e
DP below 10, preferably below 6.
Most ably the infant or follow on formula comprises a mixture of fructo-oligosaccharide
with an average DP below 10, preferably below 6 and a fructo-oligosaccharide with an average
DP above 7, ably above 11, even more preferably above 20.
Most preferred is a mixture of transgalacto-oligosaccharide with an average DP below 10,
preferably below 6 and a fructo-oligosaccharide with an average DP above 7, preferably above
11, even more preferably above 20.
The present infant or follow on formula comprises 0.5 to 20 wt.% total non-digestible
oligosaccharide, more preferably 1 to 10 wt.%, even more preferably 2 to 10 wt.%, most
preferably 2.0 to 7.5 wt.%, based on dry weight of the t infant or follow on formula.
Based on 100 ml, the present infant or follow on formula, when in liquid form, e.g. as a ready-to-
feed liquid, preferably comprises 0.1 to 2.5 wt.% non-digestible oligosaccharide, more preferably
0.2 to 1.5 wt.%, even more preferably 0.4 to 1.5 wt.%, based on 100 ml of the present infant or
follow on formula.
Infant ow on formula
Infant formula relates to a nutritional composition for particular nutritional uses by infants during
the first months of life and ying by themselves the nutritional requirements of such infants
until the introduction of appropriate complementary feeding. Infant formula is sometimes also
referred to as a starter formula or a stage 1 formula. Typically an infant formula is used until the
infant has reached an age of 4 to 6 months.
Follow on formula relates to a nutritional ition for particular ional use by infants
when appropriate complementary nutrition is introduced and tuting the principal liquid
element in a ssively diversified diet of such infants. Follow on formula is sometimes also
referred to as a stage 2 (infant) formula. Typically a follow on formula is used from 4-6 month of
age to 12 months of age.
An infant is a human child with an age of 0 to 12 months.
Infant and follow on formula is subjected to international regulatory ation. Codex-Stan 72-
1981 gives the international standard for infant formula and formula for special medical purposes
intended for infants. In Europe for example infant and follow on formula further have to comply
with the Commission Directive 2006/141fliC of 22 December 2006 on infant formulae and
follow-on formulae. GB10765-2010 and GB10767-2010 are the national food safety standards
for infant formula and older infants and young children formula in China. In the United ,
US Food and Drug Administration 21 CFR Ch 1 part 107 applies to infant formulae. In a
preferred embodiment, the t infant formula or follow on formula as used according to the
present invention complies with the appropriate legislation.
The present infant or follow on formula is preferably particularly suitable for providing the
complete daily nutritional requirements to a human subject with an age below 12 months, more
preferably below 6 months. The present nutritional composition is not a yogurt, since yoghurt
ns by convention L. bulgaricus (Codex rd for ted Milks Codex Stan 243-
2003).
The present infant or follow on formula ses a digestible ydrate component.
Preferred digestible carbohydrate components are lactose, glucose, sucrose, fructose, galactose,
e, starch and extrin. Lactose is the main digestible carbohydrate present in human
milk. The present infant or follow on formula preferably comprises lactose. As the present infant
or follow on formula comprises a composition fermented by lactic acid bacteria, the amount of
lactose is reduced compared to its source due to the tation whereby lactose is converted
into lactate and/or lactic acid. Therefore in the preparation of the present infant or follow on
formula lactose is preferably added. Preferably the present infant or follow on formula does not
comprise high amounts of carbohydrates other than lactose. Compared to digestible
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carbohydrates such as maltodextrin, sucrose, glucose, maltose and other digestible carbohydrates
with a high glycemic index, lactose has a lower glycemic index and is therefore preferred. The
present infant or follow on formula ably comprises digestible carbohydrate, wherein at
least 35 wt.%, more ably at least 50 wt.%, more preferably at least 60 wt.%, more
preferably at least 75 wt.%, even more preferably at least 90 wt% most preferably at least 95
wt% of the digestible carbohydrate is e. Based on dry weight the present infant or follow
on formula preferably comprises at least 25 wt.% lactose, preferably at least 40 wt.%, more
preferably at least 50 wt% lactose.
When in liquid form, e.g. as a ready-to-feed liquid, the infant or follow on formula preferably
comprises 3.0 to 30 g digestible carbohydrate per 100 ml, more preferably 6.0 to 20, even more
preferably 7.0 to 10.0 g per 100 ml. Based on dry weight the present infant or follow on formula
preferably comprises 20 to 80 wt.%, more preferably 40 to 65 wt.% digestible carbohydrates.
Based on total calories the infant or follow on formula preferably comprises 9 to 14 g digestible
carbohydrates per 100 kcal.
The present infant or follow on formula comprises a lipid component. The lipid component of
the present infant or follow on formula provides 2.9 to 6.0 g, more preferably 4 to 6 g per 100
kcal of the infant or follow on formula. When in liquid form, e.g. as a ready-to-feed liquid, the
infant or follow on formula preferably comprises 2.1 to 6.5 g lipid per 100 ml, more preferably
3.0 to 4.0 g per 100 ml. Based on dry weight the present infant or follow on formula ably
comprises 12.5 to 40 wt.% lipid, more ably 19 to 30 wt.%.
The lipid ent comprises the essential fatty acids alpha-linolenic acid (ALA), linoleic acid
(LA) and preferably long chain saturated fatty acids (LC-PUFA). The A, LA
and/or ALA may be provided as free fatty acids, in triglyceride form, in eride form, in
monoglyceride form, in phospholipid form, or as a mixture of one of more of the above.
Preferably the present infant or follow on formula contains at least one, preferably at least two
lipid sources selected from the group consisting of rape seed oil (such as colza oil, low erucic
acid rape seed oil and canola oil), high oleic sunflower oil, high oleic safflower oil, olive oil,
marine oils, microbial oils, coconut oil, palm kernel oil and milk fat.
The present infant or follow on formula comprises a n component. The protein used in the
infant or follow on formula is preferably ed from the group consisting of non-human
animal proteins, preferably non-human milk proteins, vegetable proteins, such as preferably soy
protein and/or rice protein, and mixtures thereof. The present nutritional composition preferably
contains casein, and/or whey protein, more preferably bovine whey proteins and/or bovine
casein. Thus in one embodiment the protein component comprises protein selected from the
group consisting of whey protein and casein, preferably both whey protein and , and
ably the whey protein and/or casein is from cow’s milk. Preferably the protein comprises
less than 5 wt.% based on total protein of free amino acids, dipeptides, tripeptides or hydrolyzed
protein. The present nutritional composition ably comprises casein and whey proteins in a
weight ratio casein:whey protein of 10:90 to 90:10, more ably 20:80 to 80:20, even more
preferably 35:65 to 55:45.
The present infant or follow on formula comprises protein providing 1.8 to 5.5, preferably 1.8 to
3.5 g protein per 100 kcal of the infant or follow on formula, preferably providing 1.8 to 2.5 g
per 100 kcal of the infant or follow on formula. In one embodiment, the infant or follow on
formula ing to the invention comprises protein preferably in an amount of 2.0 g per 100
kcal or less. When in liquid form, e.g. as a ready-to-feed liquid, the infant or follow on formula
preferably comprises 0.5 to 6.0 g, more preferably 1.0 to 3.0 g, even more ably 1.0 to 1.5 g
protein per 100 ml, most preferably 1.0 to 1.3 g protein per 100 ml. Based on dry weight the
t infant or follow on formula comprises 5 to 20 wt.% protein, preferably at least 8 wt.%
protein based on dry weight of the infant or follow on formula, more preferably 8 to 14 wt.%,
even more preferably 8 to 9.5 wt.% protein based on dry weight of the infant or follow on
formula.
The wt.% n based on dry weight of the t infant or follow on formula is calculated
according to the Kjeldahl-method by measuring total nitrogen and using a conversion factor of
6.38 in case of casein, or a conversion factor of 6.25 for other proteins than casein. The term
‘protein’ or ‘protein component’ as used in the present invention refers to the sum of ns,
peptides and free amino acids.
ably the lipid component provides 2.9 to 6 g lipid per 100 kcal, ably the protein
component provides 1.8 to 5.5 g per 100 kcal, ably 1.8 to 2.5 g per 100 kcal and preferably
the digestible carbohydrate component provides 9 to 14 g per 100 kcal, of the final infant or
follow on a, wherein preferably the digestible carbohydrate component ses at least
60 wt.% lactose based on total ible carbohydrate, more preferably at least 75 wt.%, even
more preferably at least 90 wt.% lactose based on total digestible carbohydrate. The amount of
total calories is determined by the sum of calories derived from protein, lipids, digestible
carbohydrates and non digestible oligosaccharides.
In one ment the infant or follow on formula is in a liquid form. In another embodiment
the infant or follow on formula is in the form of a powder, preferably a powder suitable for
making a liquid ready to drink infant or follow on formula after reconstitution with an aqueous
solution, preferably with water. Preferably the infant or follow on formula is a powder to be
reconstituted with water. Preferably the liquid ition has a viscosity below 100 mPa.s,
more preferably below 60 mPa.s, more preferably below 35 mPa.s, even more preferably below
6 mPa.s as measured in a Brookfield viscometer at 20°C at a shear rate of 100 s'l. A low
viscosity is important for infant or follow on formula, since it mimics the viscosity of breast milk
and can then be administered via a teat. Preferably according to the present invention the
2O nutritional composition has a viscosity when administered close to that of human milk. Thus in
one embodiment ing to the present invention the nutritional composition does not
se a thickener, preferably it does not comprise a thickener selected form the group
consisting of locust bean gum, tara gum, gum tragacanth, guar gum, and eek gum,
preferably it does not comprise any of locust bean gum, tara gum, gum tragacanth, guar gum or
fenugreek gum.
In order to meet the caloric requirements of an infant, the infant or follow on formula preferably
ses 60 to 85, more preferably 60 to 70 kcal/100 ml liquid. This caloric density ensures an
optimal ratio between water and calorie consumption. The osmolarity of the present composition
is preferably between 150 and 420 mOsmol/l, more preferably 260 to 320 mOsmol/l. The low
osmolarity aims to further reduce the gastrointestinal stress.
When the infant or follow on formula is in a liquid form, the preferred volume administered on a
daily basis is in the range of about 80 to 2500 ml, more preferably about 200 to 1200 ml per day.
Preferably, the number of feedings per day is between 1 and 10, preferably between 3 and 8. In
one embodiment the infant or follow on formula is administered daily for a period of at least 2
days, preferably for a period of at least 7 days, preferably for a period of at least 2 weeks,
ably for a period of at least 4 weeks, ably for a period of at least 8 weeks, more
preferably for a period of at least 12 weeks, in a liquid form wherein the total volume
administered daily is between 200 ml and 1200 ml and wherein the number of feedings per day
is between 1 and 10.
Application
The present inventors found that when a partly fermented infant formula comprising non
digestible oligosaccharides was stered to infants, the nce of colics and the number
of crying episodes per day was statistically significantly reduced compared to the study groups of
infants to whom partly fermented infant formula without non digestible oligosaccharides were
given, or when non-fermented infant a with non digestible oligosaccharides were given.
Also it was found that the duration of crying was statistically significantly decreased compared
to the study group of infants receiving non-fermented infant formula without non ible
oligosaccharides .
The present infant or follow on formula is used for providing nutrition to an infant, a human
subject with an age of 0 to 12 . The present infant or follow on formula is preferably
orally administered. As colics and crying episodes are particularly prominent in young infants,
the present a is preferably an infant formula and/or the formula is used for providing
nutrition to a human subject with an age of 0 to 6 months, more preferably 0 to 4 .
Colics are defined as a duration of crying for more than three hours a day, for at least three days
a week.
Reduction in colics is to be tood as a reduction in colics in an infant administered with the
infant or follow on formula according to the invention, compared to an infant administered with
an infant or follow on formula containing only a partly fermented infant formula without non-
digestible oligosaccharides as defined herein or compared to an infant administered With a non-
fermented infant a that contained non-digestible oligosaccharides as defined herein.
Reduced number of crying episodes per day is to be understood as a lower absolute number of
crying episodes per day in an infant administered With the infant or follow on formula according
to the invention, compared to an infant administered With an infant or follow on formula
containing only a partly fermented infant formula t non-digestible oligosaccharides as
defined herein or compared to an infant administered With a non-fermented infant formula that
contained non-digestible oligosaccharides as defined herein.
Episodes of crying per day is the same as number of crying times per day.
1O Duration of crying refers to the length in time of a crying episode.
In one embodiment, the present invention concerns reducing the incidence of colics in an infant
and reducing the number of crying episodes per day in an infant by administering an infant
a or follow on formula comprising a fermented ingredient and non-digestible
oligosaccharides as defined herein above. In one embodiment, the present invention concerns
reducing the incidence of colics in an infant and decreasing the on of crying in an infant by
administering an infant formula or follow on formula comprising a fermented ingredient and
gestible oligosaccharides as defined herein above. In one embodiment, the present
invention ns reducing the number of crying episodes per day in an infant and sing
2O the on of crying in an infant by administering an infant formula or follow on formula
comprising a fermented ingredient and non-digestible accharides as d herein above.
In one embodiment, the present invention concerns reducing the incidence of colics in an infant
and reducing the number of crying episodes per day in an infant and decreasing the duration of
crying in an infant by administering an infant formula or follow on formula sing a
fermented ient and non-digestible oligosaccharides as defined herein above.
In this document and in its claims, the verb ”to comprise" and its conjugations is used in its non-
limiting sense to mean that items following the word are included, but items not specifically
mentioned are not excluded. In addition, reference to an element by the indefinite article ”a" or
"an" does not e the possibility that more than one of the element is present, unless the
context clearly requires that there be one and only one of the elements. The indefinite article ”a"
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or "an" thus usually means ”at least one. Wt. means weight.
EXAMPLES
1) Efi‘ect of a formula comprising a fermented composition and non digestible oligosaccharides
on incidence of colics and number of crying episodes in infants
Healthy full-term (237 weeks and 5 42 weeks) infants whose mothers had decided not to start
feeding or had already d breastfeeding at the time of information about the study
were recruited. At the time of enrolment, the infants had to be 5 28 days old and a birth weight
between 2.5-4.5 kg, or within normal range for gestational age and sex (10’h to 90th percentile
according to the locally applicable growth charts. s were excluded if they 1) were
diagnosed with a congenital ion and/or current illnesses that could interfere with the study
2) had an increased risk for cow’s milk protein y or known cow’s milk protein allergy, soy
allergy and/or lactose allergy 3) have a mother who suffered from diabetes during pregnancy 4)
were already participating in another clinical trial. Written informed consent was obtained from
either both parents or legal representatives of all participants. A number of 431 infants were
ered for the intention to treat (ITT) analysis.
Participants were randomised to receive one of the four igational products, which were all
complete standard cow’s milk-based infant formula: test diet 1 containing 50% LactofidusTM and
a specific mixture of 90% chain galacto-oligosaccharides (scGOS) and 10% long-chain
-oligosaccharides ) or test diet 2 containing 15% LactofidusTM and the specific
mixture of 90% scGOS and 10% lcFOS or control diet 3 containing only 50% LactofidusTM or
control diet 4 containing only the specific mixture of 90% scGOS and 10% lcFOS. All products
were produced by Danone, Steenvoorde, France. This was a prospective, randomized, double-
blinded, controlled, parallel-group, multicenter, clinical study, conducted in 24 sites in three
countries (Ireland (7 sites), Belgium (10 sites), France (7 sites). At enrolment, baseline
measurements were taken and infants were randomly assigned to receive one of the two test or
one of the two control diets. Parents were given the assigned infant formula and instructions for
its preparation and were advised to feed infants ad libitum. They were also provided with a diary
and asked to keep record of their infants crying and sleeping duration, providing the total
duration in hours/day and the number of crying episodes/day. Growth ements were taken.
The primary outcome was weight gain and secondary outcomes were recumbent length and head
circumference. Also crying and sleeping were evaluated based on records kept by the parents.
Diaries were included in the statistical analysis if there were at least 3 days recorded.
At 4 weeks the number of crying es (times per day) was analysed by using wilcoxon rank
sum test.
The incidence of colics was defined based on the parent reported duration of crying in the
diaries. Colics were defined as “YES” (present), according to adopted Wessel criteria if the
children had for at least 3 days a duration of crying for 3 hours per day. The analysis was
performed by using Chi-square test/fisher’s exact test.
The following diets were tested:
Diet 1 Infant formula 1 comprising per 100 ml 66 kcal, 1.35 g protein (bovine whey
protein/casein in 1/1 weight ratio), 8.2 g digestible carbohydrate (of which 5.6 g lactose, and 2.1
g maltodextrin), 3.0 g fat (mainly vegetable fat), 0.8 g non-digestible oligosaccharides of scGOS
e Vivinal® GOS) and lcFOS (source RaftilinHP®) in a 921 wt ratio.
Of this infant formula 50 % based on dry weight is derived from LactofidusTM, a commercially
available infant formula ed under brand name Gallia. LactofidusTM is a 100 % ted
milk derived composition and is produced by fermenting with S. thermophilus and comprises B.
breve. A heat ent is employed to inactivate the lactic acid bacteria.
The infant formula comprises about 0.55 wt.% lactic acid + lactate based on dry weight, of
which at least 95% is L- lactic acid/lactate. The composition r comprises vitamins,
minerals, trace elements and other micronutrients ing to international directive
2006/l4lflEC for infant formula.
Diet 2 Infant formula 2, r to infant a 1, but comprising 15 % wt% idusTM
instead of 50 %, and hence about 0.16 wt% lactic acid + lactate.
Diet 3 Infant formula 3, similar to infant formula 1, but without the 0.8 g non-digestible
oligosaccharides of scGOS (source Vivinal® GOS) and lcFOS (source RaftilinHP®) in a 921 wt
ratio.
Diet 4 Infant formula 4, a non fermented infant formula with 0.8 g non-digestible
oligosaccharides of scGOS (source Vivinal® GOS) and lcFOS (source inHP®) in a 921 wt
ratio, and for the remainder with similar composition as infant formula 1.
Results:
Population
In total 431 infants were included and randomised. There was no statistically significant
difference in the dropout rates between the test and control groups (Fisher’s exact test, P > 0.05).
Crying and colics
At 4 weeks mean crying episodes were lowest in the group receiving diet 1 (3.03 i sd 1.92), in
the group receiving diet 2 the mean was 3.64 i 2.19, in the group receiving diet 3 3.72 i 1.98
and in the group receiving diet 4 3.46 i 1.92. r since the data are not normally
distributed, the value of the median is more relevant. At 4 weeks the median number of crying
episodes per day was lowest in the group of infants having consumed diet 1 (50% LactofidusTM
with scGOS/lcFOS). At 4 weeks, the number of crying episodes per day was significantly lower
in the group receiving diet 1 (50% LactofidusTM with scGOS/lcFOS) compared to the control
group receiving diet 3 (50% LactofidusTM) (median: 2.6 vs. versus 3.4 times/day, Wilcoxon rank
sum test, p = 0.030), see table 1 showing the results for the ITT (intention to treat) group. The
number of crying episodes was also lower compared to the group fed with diet 4 (0%
LactofidusTM with scGOS/lcFOS). Diet 2 (15% idusTM with lcFOS) was less
ive in reducing number of crying episodes per day than diet 1.
At 4 weeks the incidence of colics was lowest in the group of infants having consumed diet 1
(50% LactofidusTM with scGOS/lcFOS). The incidence of colics was lowest in the test group
having ed diet 1 (50% LactofidusTM with lcFOS) and significant ent
compared to control group having consumed diet 3 (50% LactofidusTM) (8% vs. versus 20%,
Chi-square test, P = 0.036), and control group having consumed diet 4 (scGOS/lcFOS) (8% vs.
versus 20%, Chi-square test, P = 0.034), see table 2 showing the results of the ITT group. Diet 2
(15% LactofidusTM with scGOS/lcFOS) was less effective than diet 1, in reducing incidence of
colics.
Table 1: Number of crying es at 4 weeks (times/day)
Baseline 4 weeks Baseline 4 weeks
mean mean median (range) median P—Value
(range)
diet 1 (50% LF + 4.15 i 2.32 3.03 i 1.92 4.0 (0.0 — 9.0) 2.6 (0.0 — 7.6) 0.100 a
prebiotics; N (n=86) (11:74) 0.030le
109) 0.072”
diet 2 (15% LF + 3.88 i 2.36 3.64 i 2.19 4.0 (0.0 — 8.0) 3.6 (0.0 — 9.4) 0.591 a
prebiotics; N (11:93) (11:72)
111)
diet 3 (50% LF; N 4.31 i 2.45 3.72 i 1.98 5.0 (0.0 — 10.0) 3.4 (0.0 — 8.7)
= 107) (11:87) (n=70)
diet 4 (prebiotics; 3.56 i 2.26 3.46 i 1.92 3.0 (0.0 — 8.0) 3.4 (0.0 — 9.3)
N = 104) (n=86) (n=75)
N is the total number of infants in the intention to treat group, n is number of infants contributing
to analysis Diary was included in is if there were at least 3 days recorded. Statistical
nce was calculated using Wilcoxon rank sum test; [a] vs. diet 4; [b] vs. diet 3; [c] vs. diet
Table 22 incidence of colics at 4 weeks (adapted from the Wessel criteria)
incidence of colics at 4 weeks No Yes
n (%) n (%) P—Value
diet 1 (50% LF + prebiotics; 69 (92.0) 6 (8.0) 0.034fi]
N = 109) 0.036le
0109“]
diet 2 (15% LF + prebiotics; 60 (83.3) 12 (16.7) 0.602 a
N = 111)
diet 3 (50% LF; N = 107) 56 (80.0) 14 (20.0)
diet 4 (prebiotics; N = 104) 60 (80.0) 15 (20.0)
N is the total number of the infants in the ITT group, n is number of infants contributing to
analysis. Colics are defined as ‘Yes‘ if infant has a crying duration of at least 3 hours per day for
at least 3 days a week. Baseline is not ed, because there was no 7 day diary at baseline.
Diary was included in analysis if there were at least 3 days recorded. P-Value was calculated
WO 65194
using Chi-square test: [a] VS. diet 4; [b] VS. diet 3; [C] VS. diet 2.
2) Efi‘ect of a formula comprising a fermented composition and non digestible oligosaccharides
on incidence of colics in infants.
A clinical trial was performed with Similar assessments and Visit as abOVe. In this clinical trial
200 subjects were randomized to either diet 5 or Diet 6.
A number of 199 infants were considered for the intention to treat (ITT) analysis and n=l98 for
the all-subjects treated (AST). Subjects were randomized to receiVe one of the two diets, which
were all complete standard cow’s ased infant formula. This was a prospectiVe,
1O ized, double-blinded, controlled, parallel-group, multicenter, clinical study, conducted in
two countries, Italy and Spain.
Parents completed standardized diaries to assess crying duration. For eVery subject the crying
duration per day (h/day) was calculated.
ExcessiVe crying was defined as a crying on > 3 h/day. The incidence of colics was defined
based on the parent reported duration of crying in the diaries. Colics were defined as “YES”
(present), according to adapted Wessel criteria if the children had for at least 3 days within a
period of 7 days a duration of crying for 3 hours per day. The analysis was performed by using
repeated measures logistic regression.
2O Diet 5: Infant formula comprising per 100 ml 66 kcal, 1.2 g protein e whey protein/casein
in 1/1 weight ratio), 7.7 g ible ydrate (of which 7.6 g lactose), 3.4 g fat (mainly
ble fat), 0.8 g non-digestible oligosaccharides of scGOS (source ViVinal® GOS) and
lcFOS (source RaftilinHP®) in a 921 wt ratio.
Of this infant a 30% based on dry weight was deriVed from LactofidusTM. The infant
formula comprised about 0.33 wt.% lactic acid + e based on dry , of which at least
95% is L-lactic acid + L-lactate. The composition further comprised Vitamins, minerals, trace
elements and other micronutrients according to international directiVe 2006/l4lflEC for infant
formula.
Diet 6: Infant formula, Similar to infant formula of diet 5, but did not comprise LactofidusTM and
no added non-digestible oligosaccharides of scGOS and lcFOS.
WO 65194
Results:
Population
In total 200 infants were randomised. There was no statistically significant difference in the
number of early terminations between the test and control groups (Chi-square test, P > 0.05).
Crying and colics
It was found that of the infants with an age > 7 days after start of using the study diet, the
duration of crying, the incidence of excessive crying, and incidence of colics was lower in the
s receiving diet 5 when compared to the infants receiving diet 6. For the statistic effects,
see table 3 below.
Table 3: Statistical analysis
p—value test vs. control treatment p—value test vs. control treatment
for subgroup > 7 days after start for subgroup > 21 days after start of
of study diet use study diet use
ITT Crying duration
ITT Excessive Crying
ITT Colics
n is number of infants contributing to analysis
Furthermore in the AST population infantile colics ered by the investigator as adverse
effect was significantly lower in the infants consuming diet 5 (1 out of 94 infants, 1.1%)
compared to infants ing diet 6 (9 out of 104 infants, 8.7%) ue 0.020).
Claims (14)
1. A method for - reducing the incidence of colics in an , - ng the number of crying e pisodes per day in an infant and/or - decreasing the duration of crying in an , comprising administering to said infant an infant formula or follow on formula comprising: - 25 to 99.5 wt.% of a fermented ingredient based on dry weight of the infant or follow on formula, wherein the fermented ingredient is fermented by ococcus thermophilus and/or Bifidobacterium breve, - 2.0 to 7.5 wt.% non digestible oligosaccharides based on dry weight of the infant formula or follow on formula wherein the non digestible oligosaccharides comprise galacto-oligosaccharides, and - 0.25 to 1.5 wt.% of the sum of e and lactic acid based on dry weight of the infant formula or follow on formula, wherein the sum of L-lactic acid and L-lactate is more than 50 wt.% based on the sum of total lactic acid and lactate.
2. The method according to claim 1, wherein the infant formula or follow on formula is for providing nutrition to infants with an age of 6 months or below.
3. The method according to any one of the preceding claims, wherein the infant formula or follow on formula comprises at least two ent non ible oligosaccharides.
4. The method according to claim 3, wherein the infant formula or follow on a comprises galacto-oligosaccharides and fructo-oligosaccharides.
5. The method according to any one of the preceding claims, wherein the infant formula or follow on formula comprises per g dry weight 0.2 – 4 U beta-galactosidase activity.
6. The method according to any one of the preceding claims, wherein the infant formula or follow on formula comprisesStreptococcus thermophilus and/or Bifidobacterium breve.
7. The method according to any one of the preceding claims, wherein the infant formula or follow on a comprises at most 1x105 cfu of lactic acid bacteria per g dry weight of the infant or follow on formula.
8. The method according to any one of the preceding claims, wherein the infant formula or follow on formula comprises 1x102 - 1x105 cfu Streptococcus thermophilus per g dry weight of the infant or follow on formula.
9. The method according to any one of the ing claims, wherein the infant formula or follow on formula comprises inactivated lactic acid bacteria.
10. The method according to any one of the preceding claims, wherein the infant formula or follow on formula is in the form of a powder.
11. The method according to any one of the preceding , which is for reducing the incidence of colics in an .
12. The method according to any one of claims 1-10, which is for reducing the number of crying episodes per day in an infant.
13. The method according to any one of claims 1-10, which is for decreasing the duration of crying in an .
14. A method according to claim 1, substantially as herein described or exemplified.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13191392.3 | 2013-11-04 | ||
| EP13191392 | 2013-11-04 | ||
| PCT/NL2014/050762 WO2015065194A1 (en) | 2013-11-04 | 2014-11-04 | Fermented formula with non digestible oligosaccharides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ719161A NZ719161A (en) | 2021-02-26 |
| NZ719161B2 true NZ719161B2 (en) | 2021-05-27 |
Family
ID=
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