U.S. patent application number 14/391494 was filed with the patent office on 2015-03-19 for nutritional composition.
The applicant listed for this patent is HERO AG. Invention is credited to Olle Hernell, Bo Lonnerdal, Lars-Borje Sjoberg, Catharina Tennefors.
Application Number | 20150079225 14/391494 |
Document ID | / |
Family ID | 48289048 |
Filed Date | 2015-03-19 |
United States Patent
Application |
20150079225 |
Kind Code |
A1 |
Lonnerdal; Bo ; et
al. |
March 19, 2015 |
NUTRITIONAL COMPOSITION
Abstract
A nutritional composition having a total energy content of 67
kcal/100 ml or lower and including: a protein content which is 1.25
g/100 ml or lower, an energy content from protein of 7.2-8.4% of
the total energy content of the nutritional composition, an energy
content from fat which is at least 49% or more of the total energy
content of the nutritional composition, a medium chain fatty acid
content comprising 8 to 10 carbons which is less than 3 wt % of
total amount of fatty acids, a sialic acid content of 10-25 mg/100
ml, a cholesterol content of 5-10 mg/100 ml, and a sphingomyelin
content of 9-15 mg/100 ml is disclosed.
Inventors: |
Lonnerdal; Bo; (Davis,
CA) ; Hernell; Olle; (Umea, SE) ; Sjoberg;
Lars-Borje; (Vallentuna, SE) ; Tennefors;
Catharina; (Enebyberg, SE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
HERO AG |
Lenzburg |
|
CH |
|
|
Family ID: |
48289048 |
Appl. No.: |
14/391494 |
Filed: |
April 9, 2013 |
PCT Filed: |
April 9, 2013 |
PCT NO: |
PCT/EP2013/057405 |
371 Date: |
October 9, 2014 |
Current U.S.
Class: |
426/2 ; 426/590;
426/69 |
Current CPC
Class: |
A23L 33/17 20160801;
A23L 33/30 20160801; A23L 33/40 20160801; A23V 2002/00 20130101;
A23L 33/18 20160801; A23L 33/12 20160801 |
Class at
Publication: |
426/2 ; 426/590;
426/69 |
International
Class: |
A23L 1/29 20060101
A23L001/29 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 10, 2012 |
SE |
1250357-9 |
Claims
1. A nutritional composition, as a ready-to-use product or a
ready-to-use product reconstituted with water from a manufactured
powder, wherein the total energy content is 67 kcal/100 ml or lower
and the composition comprises: a protein content which is 1.25
g/100 ml or lower, an energy content from protein of 7.2-8.4
percentage of the total energy content of the nutritional
composition, an energy content from fat which is at least 49
percentage or more of the total energy content of the nutritional
composition, a medium chain fatty acid content comprising 8 to 10
carbons which is less than 3 weight % of total amount of fatty
acids, a sialic acid content of 10-25 mg/100 ml, a cholesterol
content of 5-10 mg/100 ml, and a sphingomyelin content of 9-15
mg/100 ml.
2. A nutritional composition according to claim 1, wherein the
total energy content is 62 kcal/100 ml or lower and the composition
comprises: a protein content which is 1.25 g/100 ml or lower, an
energy content from protein of 7.8-8.4 percentage of the total
energy content of the nutritional composition, an energy content
from fat which is at least 50 percentage or more of the total
energy content of the nutritional composition, a medium chain fatty
acid content comprising 8 to 10 carbons which is less than 3 weight
% of total amount of fatty acids, a sialic acid content of 10-25
mg/100 ml, a cholesterol content of 5-10 mg/100 ml, and a
sphingomyelin content of 10-15 mg/100 ml.
3. The nutritional composition according to claim 1 wherein the
composition further comprises lipid bound sialic acid as
gangliosides and wherein the content of lipid bound sialic acid as
gangliosides is 1.5-5 weight % of total sialic acid content.
4. The nutritional composition according to claim 1, wherein the
cholesterol content is 0.2-0.3 weight % of the total fat content of
said nutritional composition.
5. The nutritional composition according to claim 1, wherein the
cholesterol content is 7-9 mg/100 ml.
6. The nutritional composition according to claim 1, wherein said
cholesterol is milk derived cholesterol.
7. The nutritional composition according to claim 1, wherein the
energy content from protein is 8.0-8.3% of the total energy content
of the nutritional composition.
8. The nutritional composition according to claim 1, wherein the
medium chain fatty acid (comprising 8 to 10 carbons) content is
less than 2% of total amount fatty acids.
9. The nutritional composition according to claim 1, wherein energy
content from fat is 50-54% of the total energy content of the
nutritional composition.
10. The nutritional composition according to claim 1, wherein the
energy content in the nutritional composition is lower than 60
kcal/100 ml.
11. The nutritional composition according to claim 1, wherein the
protein content of the nutritional composition is between 1.1 g and
lower than 1.25 g/100 ml.
12. The nutritional composition according to claim 1, wherein the
sialic acid is 18-20 mg/100 ml.
13. The nutritional composition according to claim 1, wherein the
content of sphingomyelin in the composition is between 9 and 13
mg/100 ml.
14. The nutritional composition according to claim 1, wherein the
composition has a non protein nitrogen (NPN) value of 0.015-0.020
g/100 ml.
15. The nutritional composition according to claim 1, wherein the
composition comprises whey protein concentrate solids rich in
phospholipids enriched composition in 5-6 weight % of the total dry
weight of said nutritional composition.
16. The nutritional composition according to claim 1, wherein the
composition comprises intact or partly hydrolysed milk protein.
17. The nutritional composition according to claim 1, wherein the
amino acid content in the composition is originated from milk
solids, sweet whey solids, casein solids, and cream solids, whey
protein concentrate rich in phospholipids.
18. The nutritional composition according to claim 1, wherein the
cholesterol content is 7-10 mg/100 ml.
19. The nutritional composition according to claim 1 comprising:
sweet whey solids in an amount of 32-40 kg/1000 kg dry powder
composition; sodium caseinate in an amount of 4.6-5.7 kg/1000 kg
dry powder composition; skim milk solids in an amount of 66-81
kg/1000 kg dry powder composition; whey protein concentrate solids
rich in phospholipids in an amount of 47-58 kg/1000 kg dry powder
composition; and cream solids in an amount of 117-143 kg/1000 kg
dry powder composition.
20. The nutritional composition according to claim 1, wherein the
composition comprises: sweet whey solids of 36.3 kg/1000 kg dry
powder composition, sodium caseinate of 5.18 kg/1000 kg dry powder
composition, skim milk solids of 73.7 kg/1000 kg dry powder
composition, whey protein concentrate solids rich in phospholipids
of 52.4 kg/1000 kg dry powder composition, and cream solids of 130
kg/1000 kg dry powder composition.
21. The nutritional composition according to claim 19, wherein
kg/1000 kg powder is the same as kg/8770 L of ready to drink
nutritional composition.
22. A method of using the nutritional composition according to
claim 1, comprising providing the nutritional composition to a user
as an infant formula or as a follow on formula.
23. A method of using the nutritional composition according to
claim 1, comprising providing the nutritional composition to a user
to achieve a development and/or growth pattern and/or morbidity
more similar to breast-fed infants and/or regarding parameters
which is any of growth, body composition wt % fat, cholesterol
level, blood urea nitrogen (BUN), sialic acid in saliva, fasting
insulin levels or decreased risk for obesity in childhood, insulin
resistance, total thickness of intimate and media of the vessel
wall of carotid communis, inflammation parameters, microbiological
parameters, plasma amino acids, IGF-1, and dietary intake.
24. The nutritional composition according to claim 1, wherein the
composition is a powder suitable for making a liquid composition
after reconstitution with water.
25. The nutritional composition according to claim 1, wherein the
ready-to-use product or the ready-to-use product reconstituted with
water from a manufactured powder is made by mixing 114 g of the
nutritional composition powder with 900 ml water to make 1000 ml of
liquid composition.
26. A method for producing a nutritional composition in order to
get a high sialic acid content and a high cholesterol content in
combination with low protein and energy content, comprising the
steps of: providing at least the following ingredients per 1000 kg
dry powder or per 8770 L ready to drink nutritional composition:
sweet whey solids in an amount of 32-40 kg/1000 kg dry powder
composition or per 8770 L ready to drink nutritional composition;
sodium caseinate in an amount of 4.6-5.7 kg/1000 kg dry powder
composition or per 8770 L ready to drink nutritional composition;
skim milk solids in an amount of 66-81 kg/1000 kg dry powder
composition or per 8770 L ready to drink nutritional composition;
whey protein concentrate solids rich in phospholipids in an amount
of 47-58 kg/1000 kg dry powder composition or per 8770 L ready to
drink nutritional composition; cream solids in an amount of 117-143
kg/1000 kg dry powder composition or per 8770 L ready to drink
nutritional composition; and optionally vitamins, minerals, fats,
lactose and other essential nutrients; and mixing the
ingredients.
27. The method for producing a nutritional composition according to
claim 26, wherein no free amino acids are added other than
naturally occurring free amino acids present in milk raw materials.
Description
FIELD OF INVENTION
[0001] The present invention concerns the field of nutritional
compositions and infant formulas.
BACKGROUND
[0002] Research has shown that birth weight and growth patterns
during the first years of life are relevant to the development of
the metabolic syndrome with obesity, insulin resistance, type 2
diabetes and increased risk of cardiovascular disease in adulthood
(D. J. P. Barker. Hormone Research 2005; 64 (suppl. 3):2-7).
According to "the growth acceleration hypothesis" a fast growth
during the first year of life, probably due to imprinting effects
on the metabolic system in the body, results in an increased risk
to develop metabolic syndrome, type-2 diabetes and coronary heart
diseases later in life. (A. Singhal et al. The Lancet, 2004, vol.
363: 1642-1645).
[0003] Formula-fed infants put on weight faster during the first
year of life compared to breastfed infants (J. Baird et al.
Paediatric and Perinatal Epidemiology, 2008, Vol. 22, 575-586. K.
G. Dewey. Biol Neonate, 1998; 74:94-105).
[0004] Infants who are formula-fed have in adulthood increased risk
of impaired glucose tolerance and unfavourable lipid profile with
low HDL-cholesterol and high LDL-cholesterol, all known risk
factors for cardiovascular disease (A. C. J. Ravelli et al. Arch
Dis Child 2000; 82:248-252). If the infant formula is made more
like human milk this may possibly give a reduction of these
differences and, it could provide a substantial reduction of
morbidity in the population.
[0005] Infant formula is commonly based on cow's milk proteins,
which differ from breast milk proteins in their amino acid
composition. To cover infant's needs of amino acids the protein
level in the infant formula therefore has to be higher. This gives
a much higher total intake of protein by formula-fed infants, which
can give a metabolic stress on the infants.
[0006] Koletzko B et al. suggest that limiting the protein content
of infant and follow-on formula and, more generally, the dietary
protein intake during infancy might constitute a potentially
important approach to reducing the risk of childhood overweight and
obesity. A large randomized controlled trial showed significant
effects of a lower protein intake from infant formula on weight,
weight-for-length, and BMI during the first 2 years of life. (B.
Koletzko et al. Am J Clin Nutr, 2009; 89:1836-1845).
[0007] Increased protein intake as is the result of using the high
protein formulas out on the market today leads to higher insulin
levels in the infants. Formula-fed infants get about 70% more
protein than breastfed infants between 3-6 months of age (M. J.
Heinig et al. Am J Clin Nutr, 1993; 58:152-156). More figures
regarding increased protein intake are also shown in a more recent
European study. (Koletzko B. et al, Adv Exp Med Biol. 2005;
569:69-79).
[0008] Infant formula fed children also have a higher energy intake
than breastfed children. The reason why formula-fed children have a
higher risk of getting too much energy relative to their need to
meet their growth is multifactorial. Mothers who give food in the
bottle have a greater tendency to "maternal control", i.e. the
child is less able to control its own intake, compared with
breastfed children (T. E. M. Taveras et al. Pediatrics, 2004, vol.
114 (5) e577-e584).
[0009] In a study of cholesterol intake by Demmers T. A. et al. the
formula-fed infants had at 4 months of age 40% higher energy intake
than the breastfed infants. (T. A. Demmers et al. Pediatrics, 2005,
vol. 115 (6) 1594-1601). Increased "maternal control" has been
shown to accelerate overweight among heavy children and also to
increase the problem with underweight among children with
difficulties to put on weight (C. Farrow et al. Pediatrics, 2006,
vol. 118 (2) e293-e298).
[0010] Infants fed with different formulas with different energy
density appeared able to compensate to some extent for greater or
lesser energy density by adjusting the quantity of food consumed,
but a higher energy density of the formula tends to increase the
calorie intake of the infant (S. J. Fomon et al. J. Nutrition,
1969, 98: 241-254 and S. J. Fomon et al. Acta Paediatr Scand 64:
172-181, 1975). There is a big interest in these issues but only a
few studies available.
[0011] There are differences seen in morbidity between breastfed
and formula-fed infants. Breastfed infants have less respiratory
infections, ear infections and gastroenteritis than formula-fed
infants. (A. L. Wright et al. BMJ, vol. 299, 946-949, B. Duncan et
al. Pediatrics, 2003, vol. 91 (5) 867-873, G. Aniansson et al.
Pediatr Infect Dis J, 1994, vol. 13 (3) 182-188 and K. G. Dewey et
al. J Pediatr, 1992, vol. 126 (No. 5) part 1 695-702). One possible
explanation is that breast milk contains more immune modulating
substances than cow's milk.
[0012] Sialic acid is found in milk both bound to proteins, e.g.
kappa-casein with its content of glyco macro peptide (cGMP), and
lipid bound in gangliosides. Sialic acid is found in high
concentrations in human brain and breast milk, and has been
proposed as a milk factor that could have an impact on the
development of the central nervous system (B. Wang et al. Eur J
Clin Nutr, (2003) 57, 1351-1369). Enrichment of sialic acid in the
diet of piglets has been shown to improve memory and learning (B.
Wang et al. Am J Clin Nutr, 2007; 85:561-569).
[0013] Furthermore, long-chain polyunsaturated fatty acids (LCPUFA)
have a clear impact on the developing nervous system. Breastfed
children have higher levels of arachidonic acid (ARA) and
docosahexaenoic acid (DHA) in both blood and brain than children
who received formula without the addition of ARA and DHA (M.
Makrides et al. Am J, Clin Nutr 1994; 60:189-94).
[0014] Dietary sphingomyelin is probably also important for the
development of an infant's nervous system. In studies with rat it
is shown that enrichment with sphingomyelin in the diet increases
the myelisation of the nervous system (K. S. T. Oshida et al.
Pediatr Res, 2003. 53: p. 589-593). Breast milk contains
sphingomyelin and the amount is between 4-9 mg/100 g.
[0015] Using new technology within the milk industry, purification
enables new fractions of milk to be separated. An example of such a
fraction is "milk fat globule membrane" (MFGM), which comprises 120
different proteins in a phospholipidic double layer which surrounds
fat droplets within the milk. Sphingomyelin, phosphatidyl choline,
phosphatidyl serine and phosphatidyl ethanolamine are the
dominating phospholipids. Butyrophilin, MUC1 and PAS6/7
(lactadherin), CD14, TLR1 and TLR4 are examples of the dominant
proteins which all have antimicrobiological effect (V. L.
Spitsberg. J Dairy Sci, 2005. 88: p. 2289-2294, T. A. Reinhardt
& J. D. Lippolis. J Dairy Res, 2006. 73(4): p. 406-416).
[0016] The cholesterol level in breast milk is much higher than in
a regular vegetable oil based infant formula. The level in breast
milk is around 10 mg/100 ml and the level in infant formulas on the
market is around 0.2-1.0 mg/100 ml. Therefore breastfed infants
today get a much higher intake of cholesterol than formula-fed
infants. This gives a higher blood cholesterol level in breastfed
infants during infancy. However at older age, >17 years,
breastfed infants show a lower blood cholesterol level, which is
associated with lower risk for development of cardiovascular
disease compared to children who were formula-fed (C. G. Owen et
al. Am J Clin Nutr, 2008; 88:305-314, T. A. Demmers et al.
Pediatrics, 2005, vol. 115 (6) 1594-1601). The blood cholesterol
level in infants is not only dependent on the oral intake of
cholesterol, but also of the endogenous synthetic rate of
cholesterol. Studies on infants have shown that formula-fed
infants, who have a low blood cholesterol level, have an up
regulated endogenous synthetic rate of cholesterol, in comparison
with breastfed infants. Maybe this is an effort to try to
compensate for the low oral intake. In spite of this endogenous up
regulation of cholesterol synthesis, formula-fed infants have a
lower level of blood cholesterol than breastfed infants. Efforts
have therefore been made to add cholesterol to infant formula to
mimic the level in breast milk and increase the blood level of
cholesterol in formula-fed infants (T. M. Bayley et al. Metabolism
2002; 51:25-33). To shed further light on this Demmers et al.
performed a clinical study on infants, where cholesterol was added
to infant formula as solved in ethanol to increase the
availability. Blood cholesterol and FSR (fractional synthesis rate)
were analysed up to 18 months of age. They demonstrated decreased
cholesterogenesis and increasing circulating plasma cholesterol
concentration at 4 months of age as the dietary cholesterol
increased. But these differences were not seen at 18 months of age.
The ratio of total cholesterol/HDL-cholesterol differed between
breastfed and cholesterol supplemented cow's milk formula group at
4 months which indicates a different cholesterol metabolism between
breastfed and cholesterol supplemented group. Since the study group
was only followed up to 18 months the long term consequences of
this is not known. Although the results confirmed the results from
other studies that an increased cholesterol intake during the first
months gives a higher total blood cholesterol level, both the
importance of how the cholesterol is added and the long term
consequences on cholesterol level at adulthood have to be further
studied. (T. A. Demmers et al. Pediatrics, 2005, vol. 115 (6)
1594-1601).
Specific Background
[0017] There is a need for a nutritional composition or an infant
formula which gives the formula-fed infant for example a growth
pattern, metabolic burden and level of blood cholesterol similar to
breastfed children and also at the same time for example reduces
risk of morbidity during infancy as well as later in life.
[0018] There is also a need for a production method for such a
nutritional composition which has all the desired ingredients in
order to achieve a nutritional composition which gives the
nutritional composition formula-fed infants a similar growth and
development pattern as breastfed children. There is also at the
same time need of a production method to produce a nutritional
composition which allows for a good taste for such a nutritional
composition, for example similar to the taste of breast milk.
[0019] There is a need to develop an infant formula with reduced
protein content and low energy content, which still covers the
infant's need of amino acids and other nutrients.
PRIOR ART
[0020] None of the prior art discloses a nutritional composition
according to the invention;
[0021] Several attempts of making an infant formula more like human
milk have been performed:
[0022] Methods for producing low protein and high calorie content
formulas are shown in EP1841330B1. However the method described in
EP1841330B1 does not include a method for producing a formula with
increased level of sialic acid and cholesterol and it is not a
formula with reduced energy. In US 2008003330 a method to make a
formula with increased level of sialic acid and phospholipids is
disclosed, but with a standard high level of proteins as well as a
standard level of energy and cholesterol. The infant formula
described in US2008003330 uses MFGM additions.
[0023] WO2007073192 shows an infant formula depleted from
casein-glyco-macropeptide (cGMP).
[0024] Infant formulas with increased concentrations of
a-lactalbumin have also been presented in order to mimic breast
milk composition but with a standard high level of proteins and
energy (for example; E. L. Lien. Am J Clin Nutr, 2003; 77
(suppl):1555S-1558S). The objective of the described study was to
study the effects of glyco macro peptide- or
.alpha.-lactalbumin-supplemented infant formulas on growth, mineral
status, iron-, zinc- and calcium absorption, as well as plasma
amino acids, blood urea nitrogen and plasma insulin concentrations.
Breastfed infants and infants fed with .alpha.-lactalbumin enriched
formula had similar plasma essential amino acid and insulin
profiles, which were different from those of infants fed with glyco
macro peptide or control formula.
[0025] WO 2010/027258 A1 shows an infant formula comprising a lipid
component which has a larger lipid globule size and wherein the
protein source for example is based on acid whey or sweet whey from
which casein-glyco-macropeptide (cGMP) has been removed. The infant
formula in WO 2010/027258 A1 preferably has a protein content of
1.25-1.35 g/100 ml.
[0026] In previous developed infant formulas, the cGMP content in
the infant formulas was lowered to reduce the amount of threonine
(see for example WO2006069918, page 4).
OBJECT OF THE INVENTION
[0027] The general object of the invention is to find a new
nutritional composition, for example an infant formula or a follow
on formula which results in the same or similar growth and
development and morbidity as for breastfed children within the
first months in an infant's life but also the same growth and
development later in life when the infants or children become
grown-ups. There is a need for a nutritional composition which
results in growth and development of formula-fed infants in a
similar manner as breastfed children and which still doesn't
unnecessary burden the infants' metabolic and renal systems and
which also is similar in taste as breast milk. There is also a need
for a production method for producing such a nutritional
composition.
SUMMARY OF THE INVENTION
[0028] Infant formulas are for example intended to be used as the
only dietary source for infants that are not breastfed or as a
supplement to partially breastfed infants or as a part of the diet
after weaning. To be able to fulfil this, the product has to cover
many different dietary requirements of the infant. It was therefore
a great challenge to formulate an adequate nutritional composition
according to the invention.
[0029] The challenges known to the skilled person, but not at
present satisfactory taken care of are: protein content and protein
quality, energy density, content of essential fatty acids, content
of medium chain fatty acids (MCT), content of sialic acid,
gangliosides, sphingomyelin, and the content and quality of
cholesterol in the formulas out on the market today. According to
the present invention it has surprisingly been possible to improve
all these parameters without at the same time negatively affect the
overall composition of the product.
[0030] Protein quantity and protein quality: There shall be an
adequate amount of protein, but not too high level (as referred to
above) and the protein quality must be such that it is well
digested by the infant and will cover the amino acid requirement of
the infant in as low quantity of protein as possible. Since the
amino acid requirement absolutely must be covered one has earlier
been forced to add an excess of protein due to the composition of
the protein sources used. There was therefore a need to invent a
product that within a lower protein level can cover the amino acid
requirement. At the same time it is important to keep the
non-protein nitrogen (NPN) at a low level. All this is achieved
with the nutritional composition and the production method
according to the present invention.
[0031] Energy density: It is well known that infants fed a standard
formula show a more rapid weight gain than breastfed infants. This
is due to several factors: A higher protein intake, a higher
caloric intake due to a higher energy density of the formula and a
less developed self-regulation of caloric and volume intake. Since
a part of the total carbohydrates in breast milk (the
oligosaccharides) are not used as an energy source and the lactose
content in infant formula earlier was regarded as the same as the
total carbohydrate content in breast milk. The content of lactose
in the nutritional composition according to the invention is
reduced in order to reach a nutritional composition with decreased
energy density (kcal/100 ml). No one has before developed a product
where both protein content and caloric content are reduced which
still has all other nutrients present in desired levels. According
to the present invention such a formula has been developed. The
nutritional composition according to the invention has been tested
in a clinical study. The growth of the infants using the
nutritional composition according to the invention was similar to
the growth of breastfed infants. The study thereby shows that the
content of energy and amino acids was satisfactory.
[0032] Phospholipids, sphingomyelin, sialic acid, gangliosides are
all nutrients which are recognized as important nutrients for the
infant. The challenge has been to be able to incorporate suitable
sources of these nutrients into the composition of the formula
without negative effect on other important nutrients and the
general composition of the product. In the present invention this
incorporation has been performed in levels close to the level in
breast milk without any negative effect on the total
composition.
[0033] Cholesterol is also recognized as an important component in
infant formula. However, so far, a method to include available
cholesterol in the product in such a manner that it is well
absorbed and metabolized has not been developed. Addition of free
cholesterol has been tested in previous studies, but there are
questions about its availability, metabolism and protection against
oxidation during processing. In the present invention this has been
solved by addition of cholesterol rich raw materials, without
negative effect on other important parameters.
[0034] Other important ingredients as essential fatty acids, long
chain poly unsaturated fatty acids, medium chain triglycerides,
minerals, vitamins have all been added as carefully selected raw
materials.
[0035] The result of the invention is a formula where the above
mentioned challenges have all been possible to fulfill
simultaneously, without compromising with ingredients in the
general composition of the product. A clinical study with a formula
according to the invention has been performed. The result verifies
the goal of the invention. The overall aim with the nutritional
composition for example an infant formula according to the
invention is to reach an outcome similar to breastfed infants with
regard to development of infants fed with the composition according
to the invention rather than to reach an infant formula which has
ingredients present in similar levels as in breast milk.
[0036] The production method according to the invention; i.e. the
careful selection of ingredients present in the described amounts
according to the invention is not an obvious selection to a person
skilled in the art. Surprisingly the selection of ingredients at
the present levels according to the invention makes the formula
both fulfil the nutritional requirements of the authorities and at
the same time, due to the special composition selection, makes
infants fed with the nutritional composition according to the
invention behave and develop more like breastfed infants. Finding a
nutritional composition which makes the infant, fed with the
formula behave and develop similar to infants fed with breast milk
is a known problem which until now has remained unsolved. A
nutritional composition is invented which has a low protein content
as well as low energy content and this is combined with a high
content of milk derived phospholipids and sialic acid and
cholesterol and further in combination with no addition of free
amino acids. The formula according to the invention has a low
protein content, expressed in g/100 ml, which still gives a low
energy percentage (E %) derived from proteins compared to standard
formula in spite of the reduced energy content of the formula.
[0037] This nutritionally complete formula will contribute to that
the development of the child regarding growth, body composition,
metabolic parameters, morbidity and neurological development
becomes more similar to that of breastfed children.
[0038] Parameters which are influenced when using the formula
according to the invention are for example growth, body composition
(% fat), blood cholesterol, blood urea nitrogen (BUN), sialic acid
in saliva, fasting insulin, blood pressure, morbidity short term,
immunological parameters, neurological parameters and micro flora.
Long term parameters are for example decreased obesity and
morbidity in childhood as well as adulthood. The infants fed with
the nutritional composition according to the invention surprisingly
develop in a manner closer to breast-fed infants' development.
[0039] A nutritional composition according to the invention fulfils
the objectives of making the infant fed with the composition to
grow and develop in the same manner as breastfed infants.
[0040] Use of the nutritional composition during the first 6 months
of life of an infant as the only nutrition, or from birth to up to
12 months of age as a complementary diet may for example minimize
the difference in growth and/or body composition (weight (wt) %
fat) and/or cholesterol levels and/or blood urea nitrogen values
and/or plasma amino acids and/or sialic acid in saliva and/or
fasting insulin levels and/or morbidity and/or inflammation
parameters and/or occurrence of obesity in childhood between
breastfed and formula-fed children in combination with that the
nutritional composition according to the invention gives no
unnecessary burden to the metabolic system of the formula-fed
infants.
[0041] Previously infant formulas were made using whey protein
concentrate from which the cGMP was removed. This is for example
described in EP 2046149. Surprisingly, due to the special selection
of ingredients present in the composition according to the
invention, cGMP does not have to be removed and this facilitates
for presence of high sialic acid levels in the nutritional
composition according to the invention. In the formula according to
the invention the threonine content is not too high. The amino acid
levels in the invention formula are in line with the limits set up
by the government Commission Directive 2006/141/EC and still the
formula also is within limits for protein and energy content as set
up according to the directive. No one has previously produced a
formula with both low protein and low energy content, which in
combination with this has high sialic acid content and high content
of milk derived cholesterol. There is nothing in the literature
that would instruct the person skilled in the art how to produce
such a formula. Since there are that many different parameters
which have to be considered it is not obvious how to compose an
infant formula which fulfils the need of the infants as well as the
commission directive, national legislations and recommendations
within the paediatric nutritional field.
[0042] The purpose of the invention is not to be as close as
possible in composition as breast milk, but to be as close as
possible in outcome for the infants fed with the formula according
to the invention. Uptake and availability of nutrients are
different from the formula compared to breast milk.
[0043] The infants have a growth and development more similar to
breastfed infants when they are fed with the formula according to
the invention.
[0044] Below different embodiments according to the invention are
shown, the embodiments are exemplifying embodiments and not
limiting the scope of the invention:
[0045] In one embodiment of the invention the nutritional
composition according to the invention comprises; [0046] a total
energy content of 67 kcal/100 ml or lower, for example 62 kcal/100
ml or lower, especially lower than 60 kcal/100 ml or between 58-62
kcal/100 ml or for example 58-60 kcal/100 ml [0047] a protein
content of 1.25 g/100 ml or lower, or for example lower than 1.25
g/100 ml or for example between 1.1-1.25 g/100 ml or between 1.1
g/100 ml to lower than 1.25 g/100 ml.
[0048] In one embodiment of the invention the nutritional
composition according to the invention has a total energy content
of 62 kcal/100 ml or lower and the composition comprises; [0049] a
protein content which is 1.25 g/100 ml or lower, [0050] a
cholesterol content of 5-10 mg/100 ml.
[0051] In one embodiment of the invention the nutritional
composition according to the invention has a total energy content
of 62 kcal/100 ml or lower and the composition comprises; [0052] a
protein content which is 1.25 g/100 ml or lower, [0053] an energy
content from protein of 7.8-8.4 percent of the total energy content
of the nutritional composition, [0054] an energy content from fat
which is at least 49 percent or more of the total energy content of
the nutritional composition, [0055] a medium chain fatty acid
comprising 8 to 10 carbons content which is less than 3 weight % of
total amount of fatty acids, [0056] a sialic acid content of 10-25
mg/100 ml or higher, [0057] a cholesterol content of 5-10 mg/100 ml
[0058] a sphingomyelin content of 9-15 mg/100 ml or higher
[0059] In another embodiment of the invention the nutritional
composition according to the invention comprises; [0060] a total
energy content of 62 kcal/100 ml or lower, or for example lower
than 60 kcal/100 ml or between 58-62 kcal/100 ml or for example
58-60 kcal/100 ml [0061] a protein content of 1.25 g/100 ml or
lower, or for example lower than 1.25 g/100 ml or for example
between 1.1-1.25 g/100 ml or between 1.1 g/100 ml to lower than
1.25 g/100 ml. [0062] an energy content from protein of 7.8-8.4
percent of the total energy content of the nutritional composition
or for example 8.0-8.3 percent of the total energy content of the
nutritional composition [0063] a fat content which is at least 49
percent or more of the total energy content of the nutritional
composition or especially 50 percent or more for example 52-53 E %
fat, for example 52.5% of the energy of the formula is derived from
fat [0064] a medium chain fatty acid comprising 8 to 10 carbons
content which is 0.5-3 wt % of total amount of fatty acids or for
example 1-3% or for example 1-2% of total amount fatty acids in the
composition. [0065] sialic acid content of 18 mg/100 ml or higher,
or between 18-25 mg/100 ml [0066] a sphingomyelin content of 9-15
mg/100 ml or more than 10 mg/100 ml or especially 13 mg/100 ml
[0067] a cholesterol content of between 5-10 mg/100 ml or between
7-10 mg/100 ml or for example 0.2-0.3 weight % of cholesterol
expressed as percentage of total fat content of the formula or for
example 8 mg/100 ml which is 0.23 wt % cholesterol expressed as
percentage of total fat content of the formula.
[0068] In another embodiment of the invention the nutritional
composition according to the invention further comprises [0069]
lipid bound sialic acid as gangliosides of between 1.5-5 wt % of
total sialic acid content, or for example 4 wt % lipid bound sialic
acid of total sialic acid content.
[0070] In one embodiment of the invention the energy content in the
nutritional composition according to the invention is for example
58-60 kcal/100 ml, wherein 51.8-53.4 E % fat. The protein content
is for example 1.1-1.25 g/100 ml and 7.8-8.2 E % protein, and a low
NPN content, is for example a NPN content between 0.015-0.020 g/100
ml and a high sialic acid content is for example 18-20 mg/100 ml.
The level of milk derived cholesterol is for example 7-9 mg/100
ml.
[0071] In another embodiment of the invention the energy content in
the nutritional composition according to the invention is 60
kcal/100 ml and the composition comprises 52.5 E % fat. The protein
content is 1.2 g/100 ml and the composition comprises 8 E %
protein. In another embodiment of the invention the energy content
in the nutritional composition according to the invention is 60
kcal/100 ml and 52.5 E % fat, the protein content is for example
1.2 g/100 ml and the composition comprises 8 E % protein, with
non-protein-nitrogen (NPN) content of 0.015-0.020 g/100 ml or for
example 0.016 g/100 ml and 13 mg/100 ml of sphingomyelin and a high
sialic acid content is for example 19 g/100 ml. The level of milk
derived cholesterol is for example 8 mg/100 ml and the composition
comprises a medium chain fatty acid (comprising 8 to 10 carbons)
content which is less than 3 wt % of total amount of fatty
acids
[0072] A nutritional composition according to the invention, or the
use according to the invention, may also refer to the composition
of the invention as a powder suitable for making a liquid
composition after reconstitution with water.
[0073] The nutritional composition according to the invention may
be prepared from powder by mixing 114 g of a nutritional
composition powder with 900 ml water to make 1000 ml of liquid
composition according to the invention.
[0074] The nutritional composition according to the invention
further comprises the following features in any combination;
[0075] In other embodiments according to the invention the formula
comprises 5-6 wt % whey protein concentrate solids rich in
phospholipids and 12-15 wt % cream solids expressed as percentage
of the total weight of the solids in the composition.
[0076] In one embodiment according to the invention the formula
further comprises a sphingomyelin content in the formula is for
example between 9-15 mg/100 ml, or 10 mg/100 ml or higher for
example 13 mg/100 ml.
[0077] Further embodiments are also alternative embodiments
according to the invention;
[0078] A nutritional composition according to the present invention
wherein the composition comprises intact or partly hydrolysed milk
protein.
[0079] A nutritional composition according to the present invention
wherein the amino acid content in the composition is originated
from sources selected from for example; sweet whey solids, casein
solids, milk solids and cream solids.
[0080] A nutritional composition according to the present invention
wherein the sphingomyelin content in the composition according to
the invention is between 9-15 mg/100 ml, or 10 mg/100 ml or higher,
especially 13 mg/100 ml.
[0081] A nutritional composition according to the present invention
wherein the composition is comprised from the following raw
materials; [0082] sweet whey solids 32-40 kg/1000 kg dry powder
composition or between 32.6-39.9 kg/1000 kg dry powder composition
[0083] sodium caseinate between 4.6-5.7 kg/1000 kg dry powder
composition or between 4.66-5.69 kg/1000 kg dry powder composition
[0084] skim milk solids between 66-81 kg/1000 kg dry powder
composition or between 66.3-81 kg/1000 kg dry powder composition
[0085] whey protein concentrate solids rich in phospholipids
between 47-58 kg/1000 kg dry powder composition or between
47.1-57.6 kg/1000 kg dry powder composition [0086] cream solids
between 117-143 kg/1000 kg dry powder composition.
[0087] A nutritional composition according to the present invention
wherein the composition comprises; sweet whey solids of 36.3
kg/1000 kg dry powder composition, sodium caseinate of 5.18 kg/1000
kg dry powder composition, skim milk solids of 73.7 kg/1000 kg dry
powder composition, whey protein concentrate solids of 52.4 kg/1000
kg dry powder composition, cream solids of 130 kg/1000 kg dry
powder composition.
[0088] A nutritional composition according to the present invention
wherein the values described above defining the ingredients in the
composition in kg/1000 kg powder is the same when defining the
ingredients in the composition by kg/8770 L of ready to drink
nutritional composition.
[0089] Further the composition may comprise vitamins (see for
example vitamins mentioned in Formula A below), minerals (see for
example minerals mentioned in Formula A below), fats (see for
example fats mentioned in Formula A below or in the detailed
description), lactose and/or other essential nutrients (for example
choline, taurine, inositol, carnitine, fructo oligo saccharides
(FOS), galacto oligo saccharides (GOS), probiotics or
nucleotides).
[0090] Further, the nutritional composition according to the
invention may comprise smaller amounts of other ingredients, for
example less than 7 wt % of the total formula weight. Examples of
such other ingredients are other milk solids (not in specified
formula) e.g. acid whey protein concentrate, butter milk solids,
whole milk solids etc. Said other ingredients may be present as
long as the specification of the nutritional composition, described
above of the invention is fulfilled.
[0091] A nutritional composition according to the present invention
wherein the composition comprises; sweet whey solids of 36.3
kg/1000 kg dry powder composition, sodium caseinate of 5.18 kg/1000
kg dry powder composition, skim milk solids of 73.7 kg/1000 kg dry
powder composition, whey protein concentrate solids rich in
phospholipids of 52.4 kg/1000 kg dry powder composition, cream
solids of 130 kg/1000 kg dry powder composition. Further the
composition may comprise vitamins (see for example vitamins
mentioned in Formula A below), minerals (see for example minerals
mentioned in Formula A below), fats (see for example fats mentioned
in Formula A below), lactose and/or other essential nutrients (for
example choline, taurine, inositol, carnitine).
[0092] Further, the nutritional composition according to the
invention may comprise other ingredients as long as the
specification of the nutritional composition, described above of
the invention is fulfilled.
[0093] Use of a composition according to the present invention as a
nutritional composition or as an infant formula or as a follow-on
formula.
[0094] Use of a nutritional composition according to the present
invention as an nutritional composition for achieving a development
and/or growth pattern and/or morbidity more similar to breast-fed
infants and/or regarding parameters which is any of growth, body
composition wt % fat, cholesterol level, blood urea nitrogen (BUN),
sialic acid in saliva, fasting insulin levels or decreased obesity
and or morbidity in childhood.
[0095] Further the production method of the invention is described
according to the following embodiments;
[0096] A method for producing a nutritional composition according
to the present invention in order to get a high sialic acid content
and a high cholesterol content in combination with low protein and
energy content, comprising the steps; [0097] providing ingredients
per 1000 kg dry powder or per 8770 L ready to drink nutritional
composition; [0098] sweet whey solids between 32-40 kg/1000 kg dry
powder composition or per 8770 L ready to drink nutritional
composition [0099] sodium caseinate between 4.6-5.7 kg/1000 kg dry
powder composition or per 8770 L ready to drink nutritional
composition [0100] skim milk solids between 66-81 kg/1000 kg dry
powder composition or per 8770 L ready to drink nutritional
composition [0101] whey protein concentrate solids rich in
phospholipids between 47-58 kg/1000 kg dry powder composition or
per 8770 L ready to drink nutritional composition [0102] cream
solids between 117-143 kg/1000 kg dry powder composition or per
8770 L ready to drink nutritional composition [0103] Further
additionally comprising for example vitamins, minerals, fats,
lactose and other essential nutrients (for example choline,
taurine, inositol, carnitine); and, [0104] mixing the
ingredients.
[0105] A method for producing a nutritional composition according
to the invention wherein no free amino acids are added other than
naturally occurring free amino acids present in milk raw
materials.
[0106] It is further possible to add small amounts of other
ingredients into the composition according to the invention as long
as the specification of the nutritional composition, described
above of the invention is fulfilled. For example, acid whey solids
can be used.
[0107] A method according to the present invention for producing a
nutritional composition according to the invention wherein no free
amino acids are added other than the additions made by adding raw
materials from sources selected from; sweet whey solids, casein
solids, milk solids and cream solids.
DETAILED DESCRIPTION
Introduction
[0108] The general object of the invention is to find a nutritional
composition, for example an infant formula which generates growth
and development, in short and long term, in formula-fed children
similar to breastfed children.
[0109] The growth and development for the infants fed with the
nutritional composition according to the invention is similar to
the growth and development in short and long time as for breastfed
children and this without unnecessary burden on the metabolic
system of the infants due to overload of nitrogen sources, for
example protein in too high amounts.
[0110] A nutritional composition according to the invention is for
example an infant formula which is defined as foodstuff intended
for particular nutritional use by infants from birth and during the
first 6 months of life and satisfying by itself the nutritional
requirements of this category of persons. Further, for example the
nutritional composition according to the invention may be intended
to be used as a follow-on formula which is defined as a complement
or as a part of a progressively diversified diet wherein the
formula feeding starts for example when the infant is at the age of
4 months and then the feeding of formula is a part of the infant
diet up to the infant is 12 months of age. The infant may start to
include the formula according to the invention between the age of
4-6 months which is the time when most infants start with solids,
or at least when the breastfed infants nutrient intake is
complemented with solids from 6 months of life up to 12 month of
life. A nutritional composition according to the invention may for
example be an infant formula or a follow-on formula. The
nutritional composition according to the invention may also be
abbreviated to as "a formula" or "a composition". An infant formula
is a formula intended to be used as the only source of nutrients
from birth and up to 6 months of age and a follow-on formula may be
defined as a formula intended to be used from 6 months onwards
during the weaning period, as a-complement to the solids which are
introduced in the infant's diet at the same age.
[0111] A nutritional composition also referred to as a formula
according to the invention is for example a powder intended to be
mixed with water before use or a liquid ready-to-use product.
[0112] The term "ready-to-use product" as used herein, unless
otherwise specified, refers to liquid formulas suitable for direct
oral administration to an infant, wherein the formulas are ready
to-feed liquids, reconstituted powders, or diluted
concentrates.
[0113] Definition of an infant is a child under the age of 12
months.
[0114] The solution to the problem stated above is a nutritional
composition according to the invention which minimizes the
difference in growth and insulin levels between breastfed children
and formula-fed children.
[0115] A nutritional composition according to the invention has low
energy content in combination with low protein content. A
nutritional composition according to the invention is more
nutritional complete and comprises several milk derived raw
materials including sweet whey, whey protein concentrate rich in
phospholipids, cream rich in cholesterol and also comprises gluco
macro peptide (cGMP) which allows for a higher sialic acid content.
Another important factor of the present invention is that it
further may have low non-protein nitrogen content (NPN).
[0116] There are several reasons for why formula-fed children have
a higher risk of getting too much energy relative to the need for
their growth. Increased protein intake leads to higher insulin
levels and formula-fed infants get about 70% more protein than
breast-fed infants between 3-6 months of age (M. J. Heinig et al.
Am J Clin Nutr, 1993; 58:152-156). (B. Koletzko et al. Am J Clin
Nutr, 2009; 89: 1836-1845). Mothers who give food in the bottle
have a greater tendency to "maternal control", i.e. the child has
less control of their own intake, compared to breastfed children
(E. M. Taveras et al. Pediatrics, 2004, vol. 114 (5) e577-e584. and
R. S. Gross et al. Academic Pediatrics, 2010; 10:29-35 and L.
Ruowei et al. Pediatrics, 2008; 122:S77-S85).
[0117] The effect of increased "maternal control" has been twofold:
to provide an accelerated rate of obesity for heavy children, but
also increasing problems with underweight children (C. Farrow &
J. Blissett. Pediatrics, 2006, vol. 118 (2) e293-e29). There are
also some studies which have shown that young infants are able to
down, and up regulate food intake, respectively depending on the
energy density of the infant formula (S. J. Fomon et al. J.
Nutrition, 1969, 98: 241-254 and S. J. Fomon et al. Acta Paediatr
Scand 64: 172-181, 1975).
[0118] The formula according to the invention comprises a low level
of protein and also a low level of total energy content.
Energy Density
[0119] The invented formula has an energy level of for example
67-58 kcal/100 ml, or lower or for example lower than 60 kcal/100
ml or between 58-62 kcal/100 ml or for example 58-60 kcal/100 ml.
These selected energy levels are at the lowest level of the
Commission Directive 2006/141/EC. In the report of the Scientific
Committee on Food on the revision of Essential Requirements of
Infant formula and Follow-on Formula it is said that "It should be
emphasized that an energy intake below the recommended intake does
not mean that individually this intake is deficient and can be
harmful for the subject." The invented formula has a lower energy
density than conventional formulas and is nutritional complete and
fulfills the nutritional needs of a fast growing infant during the
first year of life.
[0120] Since a part of the total carbohydrates in breast milk (the
oligosaccharides) is not used as an energy source and the lactose
content in infant formula earlier was regarded as the same as the
total carbohydrate content in breast milk, the content of lactose
in the invention formula is reduced in order to reach a nutritional
composition with decreased energy density (kcal/100 ml).
Protein Content
[0121] Further, the formula according to the invention comprises a
low level of protein, in g/100 ml, and still a low percentage of
energy (E %) derived from proteins compared to a standard formula.
The nutritional composition according to the invention comprises
7.2-8.4 E % protein, especially 7.8-8.4 E % protein or for example
8.0-8.3 E % protein.
[0122] The protein content of the ready to drink nutritional
composition is for example lower than 1.25 g/100 ml or for example
lower than 1.25 g/100 ml or for example between 1.1-1.25 g/100 ml
or between 1.1 g/100 ml to lower than 1.25 g/100 ml.
Fat Content
[0123] The invented formula further has a high E % (derived) from
fat. The fat content of the nutritional composition according to
the invention is at least 49% or more of the total energy content
of the nutritional composition, for example, a fat content which is
49-54% or for example, 50-54%, especially 52-53%, or for example
51.8-53.4% of the total energy content of the nutritional
composition.
[0124] Fat is necessary in the diet of infants and young children
because of their extraordinary energy needs and limited dietary
intake capacity. In addition, different fat sources provide poly
unsaturated essential fatty acids as linoleic- and linolenic acids
as well as long chain poly unsaturated essential fatty acids as
arachidonic acid and docosahexaenoic acid.
[0125] Deficiencies in the amounts of these long-chain poly
unsaturated fatty acids in the diet during infancy may affect the
maturation of the central nervous system, including visual
development and intelligence (see for example E. E. Birch et al.
Early Hum Dev, 2007, Vol. 83, 279-284 and M. S. Kramer et al. Arch
Gen Psychiatry, 2008; 65(5)578-584).
[0126] The nutritional composition according to the invention
further comprises for example 0.43-0.47% or for example 0.45%
arachidonic acid (ARA) (n-6 20:4) and for example 0.26-0.30% or for
example 0.28% docosahexaenoic acid (DHA)(n-3 22:6) of total fatty
acids, respectively. To get these fatty acids in these percents and
ratios raw material from algal oil and fungal oil are used. Further
the invention formula may comprise rape seed oil, palm olein oil,
sun flower oil and sun flower high oleic oil to get a fatty acid
pattern similar to breast milk. The sun flower oils contribute
mainly with the essential fatty acid linoleic acid (n-6 18:2). And
the rape seed oil contributes mainly with the essential fatty acid
linolenic acid (n-3 18:3). Other oils which also may be used are:
rape seed oil (high oleic), soybean-, maize-, safflower-, evening
primrose-, borage-, palm-, palm olein-, palm kernel-, coconut-,
babassu-, fish oil, egg lipids, structured fat with high percent
palmitic acid esterified to .beta.-position in the triglycerides
and lard. In order to even better mimic the fat composition in
breast milk cream is used.
[0127] The use of dairy cream as an ingredient in the present
nutritional composition (or the use of dairy cream solids when
making a nutritional composition powder to be mixed with water)
contributes to the high levels of milk derived cholesterol in the
nutritional composition according to the invention. This dairy
cream usage contributes to the high levels of cholesterol (5-10
mg/100 ml) in the composition according to the invention. Due to
the special composition according to the invention the addition of
cholesterol as an ingredient (due to addition of dairy cream and
whey protein concentrate rich in phospholipids) gives a similar
blood cholesterol level as in breastfed infants during the feeding
period but also later in life for those infants fed with the
nutritional composition according to the invention.
[0128] The cream also improves the taste of the invention formula.
The formula also contains whey protein concentrate rich in
phospholipids which also contribute to the content of milk derived
cholesterol in the invention formula as well as of the milk derived
phospholipid sphingomyelin. Sphingomyelin is included in an amount
of 10 mg/100 ml or higher. The invention formula comprises for
example on dry basis between 26-32 weight percent fat or for
example on dry basis 30.7 weight percent fat whereof between 15-19
weight percent of the total amount fat is vegetable fat, or for
example 18.5 weight percent of total fat content is vegetable
fat.
[0129] The content of medium chain fatty acids (MCT) comprising 8
to 10 carbons in the nutritional composition according to the
invention is for example 0.5-3 weight percent of total amount of
fatty acids or for example 1-2 weight percent of total amount fatty
acids in the composition. The invention formula mimics the content
of MCT in breast milk. Mature breast milk has 1-2 weight percent
MCT of total fatty acids (R. A. Gibson et al. Am. J. Clin. Nutr.
34: 252-257, 1981).
[0130] The use of sweet whey, cream and whey protein concentrate
rich in phospholipids, during manufacturing of the nutritional
composition or infant formula according to the present invention,
makes the nutritional composition comprise a high amount of sialic
acid and milk derived phospholipids. The nutritional composition
may for example comprise a sialic acid content of 10 mg/100 ml or
higher or 18 mg or higher or for example a sialic acid content of
between 10-25 mg/100 ml or between 18-25 mg/100 ml. For example
sweet whey solids, cream solids and whey protein concentrate solids
rich in phospholipids may also be used to produce a powder formula
according to the invention which is intended to be mixed with water
before usage.
[0131] The use of these solids or ingredients also makes the
nutritional composition according to the invention to comprise
lipid bound sialic acid as gangliosides of between 1.5-5% of total
sialic acid content or for example 4% of total sialic acid content.
Said lipid bound sialic acid, as gangliosides, content in the
formula according to the invention is between 0.03-0.08 weight
percent of total fat content of the formula or for example 0.05
weight percent of total fat content of the formula.
[0132] Gangliosides stimulate intestinal maturation and support a
healthy micro flora and also the neuronal development and brain
development. Sialic acid plays a role in cognitive development and
can protect against enteric infection.
[0133] Further the formula according to the invention comprises
cholesterol which is a sterol that is mainly synthesized in the
liver but also in other tissues. It is used to produce hormones in
cell membranes and is transported in the blood plasma of all
mammals. Breast milk comprises cholesterol. By using dairy cream
and whey protein concentrate rich in phospholipids as raw material
the invented formula's content is high in cholesterol, similar to
the level in breast milk.
[0134] The nutritional composition according to the invention has a
cholesterol content of between 5-10 mg/100 ml, or between 7-10
mg/100 ml or for example 8 mg/100 ml which for example is between
0.2-0.3 weight percent of the total fat content of the nutritional
composition or for example 0.23 weight percent of the total fat
content of the nutritional composition according to the
invention.
[0135] Further sweet whey, cream and whey protein concentrate rich
in phospholipids, all comprise cGMP. By, for example not removing
cGMP from the nutritional composition according to the invention
the sialic acid content is kept high. High sialic acid content is
for example about 10-25 mg/100 ml or between 18-20 mg/100 ml of the
nutritional composition according to the invention. By not removing
cGMP from the raw materials used to produce the formula, the
nutritional composition according to the invention is likely to for
example increase the level of sialic acid in saliva (more similar
to breastfed). The higher intake of sialic acid can have an effect
on for example morbidity and cognitive behaviour in the invention
formula-fed infants.
[0136] Sphingomyelin is the major component of the phospholipid
fraction in breast milk, and is found in lower concentrations in
conventional nutritional compositions compared to the formula
according to the invention. Sphingomyelin is metabolized to
ceramide which concentration correlates with degree of myelination
of the nervous system. Experiments on rats with experimentally
inhibited myelination have shown that supplements of sphingomyelin
increases myelination (K. Oshida et al. Pediatr Res, 2003, vol. 53
(4) 589-593). The milk derived sphingomyelin content in the formula
according to the invention is 9 mg/100 ml or higher, or between
9-15 mg/100 ml, or 13 mg/100 ml.
[0137] The nutritional composition according to the invention
comprises a special composition of raw materials. The nutritional
composition according to the present invention still has a low
burden-effect on the metabolic system of the formula-fed infant
although it comprises cGMP.
[0138] The levels of arachidonic acid (ARA) and docosahexaenoic
acid (DHA) in the nutritional composition according to the
invention are of similar levels as present in breast milk.
[0139] The present invention provides a nutritional composition and
a method for producing such a composition.
Non-Protein-Nitrogen
[0140] Non-protein nitrogen (NPN) is a term used to refer
collectively to components which are not proteins which are present
in food and which comprise nitrogen. (NPN in milk is mainly
urea-nitrogen (about 50%), creatine, creatinine, NH3 etc.)
[0141] Since it is important not to have a surplus of nitrogen in
formulas for infants we have endeavoured to have a low level of NPN
<20 mg/100 ml in the nutritional composition according to the
invention, for example a low non-protein nitrogen (NPN) value
between 0.015-0.020 g/100 ml. Surprisingly the invention formula
has a low NPN value although it has a total new composition of raw
materials.
Amino Acid Profile
[0142] It is known that an infant formula needs a predetermined
amino acid profile to fulfill the children's need. This is also
regulated by the government Commission Directive 2006/141/EC. The
amino acid supply in an infant's first months of life must be
sufficient in quantity as well as quality to fulfill the needs of
this period of life. Guidelines, recommendations with minimum
values have been established with regard to amino acid composition
of infant formulas. An amino acid profile of the nutritional
composition according to the invention is presented in the table
below. The clinical study confirms that the amino acid composition
in the invention formula is adequate for the requirement for
growth.
TABLE-US-00001 Minimum value Commission Directive Interval
according to the Amino acid (mg/100 kcal) invention (mg/100 kcal)
Leucine 166 197-229 or 217 Lysine 113 165-192 or 180 Methionine 23
36-42 or 40 Cystine 38 40-46 or 44 Phenylalanine 83 83-96 or 87
Tyrosine 76 64-74 or 72 Threonine 77 114-132 or 124 Tryptophan 32
35-41 or 39 Valine 88 116-135 or 127 Isoleucine 90 116-135 or 127
Histidine 40 46-53 or 50 Cystine + Methionine* 61 76-88 or 84
Phenylalanine + Tyrosine* 159 147-170 or 159
[0143] The concentration of methionine and cysteine can be
calculated together since the amino acid cysteine can be formed
from methionine. And the concentration of tyrosine and
phenylalanine can be calculated together since the amino acid
tyrosine can be formed from phenylalanine. Therefore also combined
levels of these amino acids are specified in the table above*.
[0144] Amino acid sources of the present nutritional
composition:
[0145] The formula according to the invention has a composition
which is such that the wanted amino acid profile is achieved
without addition of any free amino acid. The formula according to
the invention is manufactured without addition of any free amino
acid (or isolated amino acids) to get a desired amino acid
profile.
[0146] The wording free amino acids or isolated amino acids in this
application mean descriptions for an amino acid substance which is
isolated as a free acid or as a salt.
[0147] The formula according to the present invention is therefore
not enriched with isolated amino acids, for example free amino
acids. This is an advantage since free amino acids are usually
bitter in taste. It is also expensive to add amino acids in their
pure form. By using the ingredients according to the present
invention the nutritional composition according to the invention
does not need further addition of free or isolated amino acids and
is therefore more similar to breast milk in taste.
Production Method
[0148] The formula according to the invention is according to one
embodiment produced by mixing the below ingredients in kg per 1000
kg nutritional composition dry powder or kg per 8770 L finished
nutritional composition.
TABLE-US-00002 Amount in the formula according to the Interval in
the formula invention according to the (kg/1000 kg dry invention
(kg/1000 kg powder or Raw material dry powder or kg/8770 L) kg/8770
L) Sweet whey solids 32-40 36 .+-. 2 Sodium caseinate 4.6-5.7 5.2
.+-. 0.3 Skimmed milk solids 66-81 74 .+-. 4 Whey protein
concentrate 47-58 52 .+-. 3 solids (rich in phospholipids) Cream
solids 117-143 130 .+-. 6
[0149] The nutritional composition may further comprise vitamins,
minerals, fats, lactose and/or other essential nutrients (for
example choline, taurine, inositol, carnitine, nucleotides).
[0150] Further, the nutritional composition according to the
invention may comprise other ingredients as long as the
specification of the nutritional composition, described above of
the invention is fulfilled.
Whey Protein Concentrates Solids (Rich in Phospholipids)
[0151] Whey protein concentrate solids rich in phospholipids used
as a component in the nutritional composition according to the
invention is a whey protein concentrate with a high concentration
of bioactive proteins and lipids. The whey protein concentrate has
a high nutritional value, and is applicable in infant and clinical
nutrition. Whey protein concentrate solids rich in phospholipids
contain most of the insoluble membrane protein fragments from MFGM
originally present in the whey, in addition to residual whey
components, proteins, lactose and salts. The invention utilizes,
whey protein concentrate solids rich in phospholipids obtained
after removal of the major whey proteins by known industrial
processing, such as filtration, ion-exchange chromatography, and
the like. This fraction contains most of the insoluble membrane
fragments, which contain protein and associated fat. The whey
protein concentrate solids rich in phospholipids contains bioactive
compounds, such as lactoferrin, .alpha.-lactalbumin, butyrophilin,
MUC1, PAS6/7 (lactadherin), gangliosides, CD14, TLR1 and TLR4, IgG,
cGMP, sialic acid and phospholipids (for example sphingomyelin,
phosphatidyl choline, phosphatidyl serine and phosphatidyl
ethanolamine). Phospholipids are important constituents of cellular
membranes contributing significantly to the membrane structure and
function.
[0152] Lacprodan MFGM-10 (from Arla foods) or similar raw materials
from other suppliers may be used as enriched phospholipid whey
protein concentrate solids in a formula according to the invention.
For example the source of enriched phospholipid whey protein
concentrate solids comprises at least 20 wt % phospholipids based
on total lipid content, for example 20 to 70 wt % or for example 25
to 55 wt % phospholipids based on total lipid of the enriched
phospholipid whey protein concentrate solid source.
[0153] The whey protein concentrate solids rich in phospholipids
used in the nutritional composition according to the present
invention is not depleted of cGMP.
[0154] The components of the whey protein concentrate solids rich
in phospholipids may affect the development of the nervous system,
morbidity and psychomotor development in a positive manner for
infants fed with the nutritional composition according to the
invention compared to infants fed standard infant formula or the
control formula according to the invention.
[0155] Whey protein concentrate solids rich in phospholipids from
bovine milk contain unique polar lipids and membrane specific
proteins, for example lactoferrin, butyrophilin, MUC1 and PAS6/7
(lactadherin), CD14, TLR1, and TLR4 and phospholipids (including
for example sphingomyelin and gangliosides). These components are
recognized as nutritional and bioactive milk constituents and are
present only scarcely in bovine milk compared to human milk.
[0156] Whey protein concentrate solids comprise gangliosides,
sialic acid, sphingomyelin, phosphatidyl serine, phosphatidyl
choline, phosphatidyl ethanolamine, lactoferrin, a-lactalbumin,
etc.
Sweet Whey
[0157] Sweet whey is rich in .alpha.-lactalbumin. The high
a-lactalbumin content makes it ideally suited as a protein source
in infant formulas in order to fulfil desired amino acid pattern.
Sweet whey also contains cGMP which is a source of sialic acid.
Cream
[0158] Cream is a natural and valuable source of short and medium
chain fatty acids as well as milk derived cholesterol. The milk
derived phospholipids in cream are besides important nutritional
substances also valuable emulsifiers. The formula according to the
invention may be manufactured using cream or cream solids. The fat
content of the cream used according to the invention is for example
of 36-40 wt % fat or 37 wt % fat.
Caseinate
[0159] Sodium caseinate or partly other salts of caseinates may be
used in the invention formula.
Hydrolysed Protein
[0160] The protein source in the invention formula may be a
hydrolysed protein.
[0161] Below is an exemplified description of the production
process of the formula according to the invention, the following
example of the invention is not limiting the scope of the
invention:
[0162] The present invention provides a ready to drink nutritional
composition or a powder formula intended to be reconstituted with
water to a ready to drink nutritional composition and a method for
producing such compositions.
[0163] In one embodiment the composition is a powder suitable for
making a liquid composition after reconstitution with water. Or for
example the composition is a ready to use liquid product.
[0164] Below is an example of ingredients for making the
nutritional composition according to the invention.
[0165] Example of amounts of ingredients (kg/1000 kg) of a dry
powder formula according to the invention which is intended to be
reconstituted with water before usage (amounts of ingredients for
the a ready to drink formula is below described in kg/8770 L);
TABLE-US-00003 Amount (interval) (kg/1000 kg or Description kg/
8770 L)) Lactose 476-527 Cream solids 123-136 Skim milk solids
70.0-77.3 Rape seed oil 51.6-57.0 Palm olein oil 51.6-57.0 Whey
protein concentrate solids rich in 49.7-55.0 phospholipids Sun
flower oil 38.3-42.3 Sweet whey solids 34.5-38.1 Sun flower oil HO
24.9-27.6 Minerals 16.1-17.8 Sodium caseinate 4.92-5.44 Dry
lecithin 4.26-4.70 Arachidonic acid oil 1.60-3.50 Docosahexaenoic
acid oil 1.60-2.17 Vitamin mix 1.29-1.43 Choline, taurine,
myo-inositol, L-carnitine 1.21-1.34
[0166] Examples of production methods according to the invention,
not limiting the scope of the invention;
[0167] Production method of a powder nutritional composition
according to the invention:
[0168] Milk based raw materials are mixed to a slurry. Standardized
milk or milk powder and liquid whey or whey powder are mixed, if
necessary, with additional water. Suitable equipment mixes the
slurry in a tank with negative pressure to reduce foaming and
incorporation of air.
[0169] Emulsifier and fat soluble vitamins are added to a blend of
vegetable oils. The fat phase is then incorporated in the milk
phase either in the mixing tank or dosed in line before
homogenization. In line dosing of oil means that a part of the milk
phase is heated, oil is dosed into the stream, homogenized and
cooled down again.
[0170] Water soluble vitamins, additives such as taurine and
minerals with a pro oxidative effect such as ferrous- and copper
salts are added just before concentrating the slurry by means of a
finisher to a final dry matter content of 50-55%. The concentrate
is then heat treated to ensure the microbiological quality, spray
dried, the powder cooled and stored. After quality control, product
is packed or, if it is a semi product, first blended, combining the
spray dried semi product with additional minerals, vitamins,
bioactive ingredients and citric acid.
[0171] Production method of a Ready-to-drink nutritional
composition according to the invention:
[0172] Water, made alkaline with calcium hydroxide, is mixed with
whey or whey powder. The solution is neutralized before adding the
carbohydrate source and standardized milk. Additional ingredients
such as choline, taurine, inositol and carnitine are added before
pasteurisation and fat phase injection and homogenization. The fat
phase is made up of vegetable oils, emulsifiers and fat soluble
vitamins. Before sterilization, vitamins are added and quality
check is performed. The product is UHT-treated, a quick heat
treatment at about 140.degree. C. for 5 seconds, cooled and
aseptically packed. [0173] (UHT means Ultra High Temperature.
Products from an UHT-process have good keeping qualities with
retained nutritional values).
[0174] Below is an example of the nutritional composition according
to the invention and also a description of a control formula, both
used in a comparative study. The below example of the invention is
not limiting to the scope of the invention;
[0175] The infant formula (Formula A) used in the study is an
example of a nutritional composition according to the invention.
The Control Formula is used for comparison. The comparative Control
Formula is a representative infant formula of good quality
available on the market.
[0176] The formulas included in the study have the following
compositions (see table below)--
[0177] Formula A is an example of the nutritional composition
according to the invention;
TABLE-US-00004 Formula A Control Formula Description (kg/1000 kg)
(kg/1000 kg) Lactose 502 536 Cream solids 130 89.6 Skim milk solids
73.7 105 Rape seed oil 54.3 43.4 Palm olein oil 54.3 75.9 Whey
protein concentrate solids (rich in 52.4 phospholipids) Sun flower
oil 40.3 30.7 Sweet whey solids 36.3 61.1 Sun flower oil HO 26.3
30.7 Minerals 17.0 10.1 Sodium caseinate 5.18 6.56 Dry lecithin
4.48 4.03 Arachidonic acid oil 3.33 2.91 Docosahexaenoic acid oil
2.07 1.80 Vitamin mix 1.38 1.48 Choline, taurine, myo-inositol, L-
1.27 1.04 carnitine L-arginine 0.689 Potassium citrate 4.68 2.58
Calcium carbonate 3.33 3.33 Potassium chloride 3.08 2.19 Calcium
hydrogenphosphate 1.94 Magnesium sulphate 1.78 0.583 Sodium
chloride 1.40 0.972 Ascorbic acid 1.08 1.22 Choline chloride 0.648
0.486 Sodium citrate 0.500 Taurine 0.415 0.370 Ferrous sulphate
0.178 0.150 myo-Inositol 0.135 0.120 Zinc sulphate 0.0863 0.0769
Ascorbyl palmitate 0.0782 0.0751 L-carnitine 0.0756 0.0656 Vitamin
D3 0.0539 0.0480 Vitamin A 0.0476 0.0424 DL-a-tocopherol 0.0350
0.0362 Calcium D-pantothenate 0.0296 0.0263 Niacin 0.0180 0.0160
Copper sulphate 0.00846 0.00754 Thiamine hydrochloride 0.00676
0.00602 Vitamin K1 0.00561 0.00500 Pyridoxine hydrochloride 0.00546
0.00486 Potassium iodide 0.00073 0.00073 Folic acid 0.00062 0.00055
Sodium selenite 0.00039 0.00039 Biotin 0.00011 0.00010
[0178] Formula A, which is a nutritional composition according to
the invention, with the ingredients described above, comprises the
nutritional values presented below as ready for consumption (114 g
of powder formula A is mixed with 900 ml water which gives 1000 ml
ready to drink product); [0179] a total energy content of 60
kcal/100 ml, [0180] a protein content of 1.2 g/100 ml, [0181] an
energy content from protein of 8.0 (E %) of the total energy
content of the nutritional composition [0182] a protein:energy
ratio of 2.0/100 kcal [0183] a fat content which is 52.5 (E %) of
the total energy content of the nutritional composition according
to Formula A [0184] a medium chain fatty acid (comprising 8 to 10
carbons) content of 1.6 wt % of total amount of fatty acids in
Formula A [0185] sialic acid content of 19 mg/100 ml [0186] a
cholesterol content of 8 mg/100 ml [0187] lipid bound sialic acid
as gangliosides of 4 wt % of total sialic acid content [0188]
sphingomyelin content of 13 mg/100 ml
[0189] Formula A has a high content of sialic acid from natural
sources compared to standard formulas. The sialic acid content
comes from two different sources, one, from whey protein
concentrate solids (rich in phospholipids), which is lipid bound
and the other from GMP, which is bound to carbohydrates. Formula A
has a high milk derived content of sphingomyelin from natural
sources compared to the Control Formula, namely whey protein
concentrate solids (rich in phospholipids). It is an advantage to
use said natural sources of sialic acid and sphingomyelin.
[0190] Energy % (E %) is a normal way to express the amount of
kcal, which comes from fat, protein and carbohydrates in a
nutritional formulation. The National food agency in Sweden
(Livsmedelsverket) has identified this on
http.//www.slv.se/sv/grupp1/Mat-och
naring/Svenska-narings-rekommendationer/Kalorier-kilojoule-och
energiprocent---hur raknar-man/
[0191] The control formula, with the ingredients described in the
table above, comprises the nutritional values presented below as
ready for consumption (130 g of powder control formula is mixed
with 900 water gives 1000 ml ready to drink product); [0192] a
total energy content of 66 kcal/100 ml [0193] a protein content of
1.27 g/100 ml, [0194] an energy content from protein of 7.7 (E %)
of the total energy content of the nutritional composition
according to the control formula [0195] a fat content of 44.7 (E %)
of the total energy content of the nutritional composition
according to the control formula [0196] a medium chain fatty acid
(comprising 8 to 10 carbons) content of 1.5 wt % of total amount of
fatty acids in the control formula [0197] sialic acid content of 16
mg/100 ml [0198] a cholesterol content of 4 mg/100 ml [0199] lipid
bound sialic acid as gangliosides of 2 wt % of total sialic acid
content according to the control formula [0200] sphingomyelin 1.8
mg
Study
Study Design
[0201] The study is a randomized double-blind intervention trial
with exclusively breastfed infants as a reference group which means
that three groups of children participate in the study:
1) Children who are breastfed. 2) Children who receive modified
infant formula, "Formula A", according to the invention (see
description above). 3) Children who receive a representative infant
formula of good quality, herein called "Control Formula" (see
description above)
Group Size
[0202] The study was set up to detect a possible difference of 0.5
standard deviation (SD) for each outcome variable, which
corresponds to a weight difference of about 0.4 kg at 6 months or a
difference of 3.25 percent of body fat measured by plethysmography
at 2 months of age. The visual acuity equivalent to 0.5 SD is 0.25
octaves at 4 months of age, which is the difference seen when
compared to children with feeding with or without DHA supplement.
With a statistical "power" of 80% a group size of just over 60
children is required. 80 children were recruited per group, which
gave a sufficient number of children per group completing the
study.
Infants Included in the Study
[0203] From March 2008 to February 2012, 160 formula-fed infants
(80 girls and 80 boys) and a breast-fed reference (BFR) group with
80 infants (40 girls and 40 boys), all born at Umea University
Hospital, Umea, Sweden, were recruited after inviting parents by
telephone. Inclusion criteria were <2 months of age, gestational
age at birth 37-42 weeks, birth weight 2500-4500 g, absence of
chronic illness, and exclusive formula-feeding or, for the BFR
group, exclusive breastfeeding at inclusion and mother's intention
to exclusively breastfeed until 6 months. Formula-fed infants were
stratified for sex and randomized to receive a low energy, low
protein experimental formula (Formula A) or a standard formula
(Control Formula) from inclusion until 6 months of age. Twins were
co-randomized to the same intervention group. The intervention was
blinded both to parents and staff until all infants had finished
the intervention. Powdered formula was distributed to families
together with preparation instructions in identical boxes marked
with a code number.
Exclusion Criterion
[0204] Children with chronic diseases that may affect the outcome
variables, such as neurological, endocrine or mal absorption
illness are excluded from the study.
[0205] Even children who for various reasons are not able to
complete the study will be monitored and included in the
statistical analysis according to the "intention to treat".
Outcome Parameters
[0206] The children will be followed from the time of enrollment up
to 1 year of age with blood, saliva and stool samples and other
tests, see below. The study is divided in two parts. The first
study part is from inclusion up to 12 months of age, and the second
part of the study is at 5 years of age.
Assessment of Growth
[0207] Visits were made at baseline (<2 months), 4 months and 6
months. At each visit, weight (Seca 757, Seca, Hamburg, Germany),
length (Seca 416, Seca, Hamburg, Germany) and head circumference
(Seca 212, Seca, Hamburg, Germany) were measured. Weight was
recorded with an accuracy of 5 grams, length and head circumference
with an accuracy of 0.1 cm. At inclusion and 4 months, body
composition was measured using air-displacement plethysmography
(PeaPod.COPYRGT.), Life Measurement Inc, Concord, Calif., USA).
Age-adjusted z-scores for weight, length, head circumference and
body mass index (BMI) were calculated using the WHO growth
standards.
Blood Samples and Analyses
[0208] At each visit, venous blood samples were drawn >2 h after
the latest meal. From each group (FA, CF and BF), samples from 20
randomly selected infants (10 girls and 10 boys) were analyzed for
plasma amino acid pattern. After acidifying plasma samples with
sulfosalicylic acid, centrifuging and diluting the supernatant with
Li-diluent spiked with AE-Cys, amino acids were separated by
ion-exchange chromatography followed by analysis with a ninhydrin
reaction detection system (Hitachi L-8900 Amino Acid Analyzer).
[0209] Apo A1, apo B, cholesterol, HDL and triglycerides were
analysed with Vitros Chemistry ApoA1 reagent, ApoB reagent, CHOL
slides, dHDL slides and TRIG slides on Vitros 5.1 FS (Ortho
Clinical Diagnostics Inc). LDL was estimated by Friedewald's
formula (Friedewald, W. T. et al Estimation of the concentration of
low-density lipoprotein cholesterol in plasma, without use of the
preparative ultracentrifuge. Clin Chem, 1972, 18, (6): p
499-502).
Metabolomics
[0210] Metabolomics was studied in the metabolites resulting from
cellular metabolism. Metabolomics was used in order to detect
specific metabolic differences between breastfed and formula-fed
infants as well as between formula fed infants.
Development
[0211] The neurologic development can be measured with greater
accuracy, the older the child is. At 12 months a psychologist
performed a test with Bayley Scales of Infant and Toddler
Development-III.
[0212] By the age of 5 years again a cognitive testing will be
done, this time with the Wechsler Preschool and Primary Scale of
Intelligence (WPPSI-R).
Dietary Record
[0213] Each month, starting from baseline, parents or caregivers
record the type and amount of each food item consumed by the infant
during 3 consecutive days up to 6 months of age.
Statistics
[0214] All analyses are presented on an intention-to-treat basis.
Statistical calculations were made using IBM SPSS Statistics
Version 19 (.COPYRGT.IBM 1989, 2010). Comparisons of proportions
were made by chi-square test or, when the expected count in any
cell was less than 5, by Fisher's exact test. Comparisons of means
were made by independent samples t-test. Variables that were not
normally distributed were log-transformed before calculations and
transformed back for presentation as geometric means and 95%
confidence intervals. Adjusted p-values for differences between the
Formula A and Control Formula groups were calculated in a
multivariate model, including those background variables that
significantly differed between the groups. Differences in levels of
amino acids were calculated with ANOVA, and compensated for
multiple comparisons by Bonferroni post-hoc test.
Results
[0215] The growth between the breast fed infants and the Formula A
fed infants did not differ. The new nutritional composition
according to the invention reduces the differences between
breastfed and formula-fed infants in terms of metabolic factors, as
well as neurological development.
GROWTH
[0216] There were no differences in age-adjusted z-scores for
weight (FIG. 1), length (FIG. 2), head circumference (FIG. 3) or
body mass index (FIG. 4), between the Formula A group and the
breast fed group or between the Formula A and the control formula
group up to 6 months of age.
[0217] In earlier studies it is consistently shown that the weight
at a certain age is higher for formula fed infants compared to
breast fed infants.
[0218] Nor were there differences in body fat % between the Formula
A and the breast fed group or the Formula A and the Control Formula
groups, cf Table 1.
TABLE-US-00005 TABLE 1 Body composition Formula A Control Breast
fed p (adjusted p.sup.1) p BF vs (% fat) (FA) formula (CF) (BF) FA
vs CF FA + CF Baseline 20.6 .+-. 4.5 21.2 .+-. 4.3 21.6 .+-. 4.1
0.43 (0.22) 0.26 4 months 26.4 .+-. 4.4 26.3 .+-. 4.7 26.5 .+-. 3.9
0.91 (0.68) 0.78 .sup.1= adjusted for weight gain during pregnancy,
gestational diabetes, parental BMI and age at inclusion
Plasma Amino Acid Levels
[0219] The levels of the plasma amino acids were within a satisfied
range table 2 and show that the lower level of protein per 100 ml
fulfil the need of a growing infant. Normally tryptophane is the
limiting amino acid in infant formula. However, it was shown that
the plasma level of tryptophane in this study was not different
between the Formula A group and the breast fed group.
[0220] Although the Formula A contains cGMP, which has a higher
level of threonine, the results show that the plasma level of
threonine in Formula A fed infants was in an accepted range.
TABLE-US-00006 TABLE 2 Mean levels of plasma amino acids in Formula
A (FA), control formula (CF) and breast-fed (BF) groups
(.mu.mol/ml), n = 20 in each group. Baseline 4 months 6 months FA
CF BF FA CF BF FA CF BF Essential Isoleucine 0.76.sup.ab 0.84.sup.a
0.66.sup.b 0.74.sup.a 0.90.sup.b 0.66.sup.a 0.76.sup.a 0.74.sup.ab
0.61.sup.b Leucine 0.121 0.130 0.122 0.111 0.130 0.113 0.119.sup.a
0.110.sup.ab 0.097.sup.b Lysine 0.21.sup.ab 0.22.sup.a 0.18.sup.b
0.19.sup.a 0.20.sup.a 0.16.sup.b 0.17.sup.a 0.17.sup.a 0.14.sup.b
Methionine 0.031.sup.a 0.032.sup.a 0.025.sup.b 0.025.sup.a
0.025.sup.a 0.018.sup.b 0.019 0.018 0.016 Phenylalanine
0.057.sup.ab 0.060.sup.a 0.051.sup.b 0.053.sup.ab 0.057.sup.a
0.050.sup.b 0.056 0.057 0.052 Threonine 0.23 0.25 0.14 0.20.sup.a
0.22.sup.a 0.14.sup.b 0.17.sup.a 0.18.sup.a 0.13.sup.b Tryptophan
0.123 0.094 0.114 0.089 0.110 0.098 0.096 0.095 0.081 Valine
0.21.sup.a 0.22.sup.a 0.17.sup.b 0.19.sup.a 0.22.sup.b 0.17.sup.a
0.21.sup.a 0.20.sup.ab 0.17.sup.b Non-essential Alanine 0.40 0.45
0.36 0.40.sup.a 0.44.sup.b 0.39.sup.a 0.38 0.38 0.35 Arginine 0.68
0.83 0.81 0.79 0.90 0.82 0.78 0.95 0.76 Asparagine 0.26 0.54 0.22
0.29.sup.ab 0.32.sup.a 0.24.sup.b 0.26 0.24 0.21 Aspartic
0.29.sup.ab 0.33.sup.a 0.24.sup.b 0.23.sup.a 0.28.sup.b 0.22.sup.a
0.23.sup.ab 0.28.sup.a 0.22.sup.b Glutamic 0.44.sup.a 0.45.sup.a
0.55.sup.b 0.34.sup.a 0.36.sup.ab 0.40.sup.b 0.31.sup.a 0.32.sup.ab
0.37.sup.b Glutamine 0.24 0.20 0.21 0.46 0.42 0.49 0.43 0.38 0.37
Glycine 0.25 0.25 0.23 0.23 0.22 0.21 0.22 0.21 0.19 Histidine
0.101 0.099 0.094 0.089 0.092 0.088 0.086 0.081 0.085 Proline 0.20
0.23 0.20 0.17.sup.a 0.22.sup.b 0.22.sup.b 0.18 0.21 0.20 Serine
0.15 0.17 0.16 0.16 0.17 0.18 0.14 0.15 0.14 Tyrosine 0.088 0.091
0.090 0.083 0.082 0.076 0.080.sup.a 0.076.sup.ab 0.062.sup.b
Statistical test with ANOVA (IBM SPSS Statistics 19), differences
are considered significant at a level of p < 0.05 after
Bonferroni post hoc test for multiple comparisons (.sup.a differs
from .sup.b).
Cognitive Performance
[0221] In the preliminary analysis, 70, 64 and 71 infants have been
tested with Bayley Scales of Infant and Toddler Development-III at
12 months in the Formula A, Control Formula and breast fed groups,
respectively. It was found that infants fed the Formula A had a
higher cognitive score at 12 months compared to infants fed the
Control Formula, table 3. The Formula A fed infants had a cognitive
score similar to the breast fed infants. The magnitude of the
difference between the groups is well in line with a meta-analysis
of studies on cognitive function in formula fed compared to breast
fed infants This implies that one or several factors in Formula A
are needed for optimal cognitive development and that those factors
can reduce the differences in cognitive function observed between
breast-fed and formula-fed infants.
TABLE-US-00007 TABLE 3 Bayley-III composite score (mean .+-. SD) at
12 months for the Formula A (FA), Control formula (CF) and breast
fed (BF) groups. p-value p-value (FA vs (FA vs FA CF BF CF) BF)
Cog- 105.9 .+-. 9.2 101.8 .+-. 8.0 106.4 .+-. 9.5 0.007 0.73 nitive
Motor 98.7 .+-. 9.3 98.2 .+-. 9.0 100.2 .+-. 7.2 0.76 0.25 Verbal
102.6 .+-. 10.5 102.5 .+-. 8.9 106.7 .+-. 10.7 0.92 0.022
Blood Lipids
[0222] There were differences in blood lipids between the Formula A
and Control Formula groups. The Formula A contained a higher level
of cholesterol than the Control formula which also resulted in
higher level of plasma cholesterol in Formula A fed infants which
also was similar to the breast fed group. Longer follow-up is
needed, to have more clear interpretations on programming effects
of this early intervention on future risk for cardiovascular
disease. There are no differences in plasma triglycerides levels
between Formula A, Control Formula and breast fed groups.
Cholesterol
[0223] Both the Formula A and the Control Formula used in the study
contained a higher than normal level of cholesterol. The control
formula 40 mg/l and the Formula A 80 mg/l. The cholesterol level in
breast milk is often said to contain about 120 mg/l, but is
dependant of many factors. Most standard infant formula contains
less than 10 mg/ of cholesterol. The cholesterol level in the
Formula A was increased by using a recipe containing milk cream,
milk protein fractions containing MFGM (milk fat globule membrane)
and other milk protein fractions containing cholesterol. The
acquired level of cholesterol, 80 mg/l, has previously only been
reached by adding pure cholesterol, lard or egg preparations.
[0224] The control formula used in this study contained 40 mg/l of
cholesterol. The recipe used contained milk cream and some milk
protein preparations that contained cholesterol.
[0225] In previous performed studies breast fed infants have a
higher plasma cholesterol level than formula fed infants. This is
especially seen during the first 6 months of life. After that there
is a diminished difference in plasma cholesterol levels between
breast fed and formula fed infants.
[0226] The results from this study show that, by increasing the
cholesterol level in the Formula A by incorporating various
cholesterol containing milk products into the product, we have
managed to reach a plasma cholesterol level at 6 months similar to
the group that was breast fed. Breast fed 2,20 plus/minus 0.55 and
Formula A group 1.99 plus/minus 0,55. This was achieved in spite of
a much lower base line plasma cholesterol level in the Formula A
group in comparison with the breast fed group. These differences in
the base line levels might be due to that the infants in this
group, before entering the study had consumed an infant formula
with a low level of cholesterol.
[0227] The infants, who consumed the control formula did not reach
a plasma cholesterol at 6 months, similar to the breast fed group.
However it is important to observe that the control formula used in
this study contained higher level of cholesterol than most formula
on the market.
[0228] Breast fed infants had a higher ratio of LDL/HDL than both
infant formula groups at 6 months. But this difference was already
seen at the baseline. There was no difference between the groups
regarding plasma tri glyceride levels.
Other Metabolic Parameters
[0229] Plasma analyses show that important metabolic compounds such
as myo-inositol in formula A fed infants were similar to breast fed
infants, but significantly different from control formula fed
infants.
Dietary Intake
[0230] The finding in the present study that energy intake
regulation of formula-fed infants occur even at a modest (9%)
difference in energy density, has not been shown previously. It can
be concluded that infants fed with Formula A had a growth similar
to breast fed infants.
CONCLUSION
[0231] Although the Formula A had a lower energy content and lower
protein content per 100 ml, than the control formula (CF), which
represents a standard formula of high quality, the results show
that the composition of the Formula A fulfil the requirements for
growth and body composition of an Formula A fed infant in the same
way as breastfed infants. There were no differences in age-adjusted
z-scores for weight, height, head-circumference or BMI between the
Formula A and the breast fed groups or between the Formula A and
the Control formula fed groups. Nor were there differences in body
fat % between the Formula A and the breast fed groups or the
Formula A and the Control formula fed groups. The Formula A with
its low protein level also met the requirements for adequate growth
and metabolism of infants.
[0232] Further the results from this study show that, by increasing
the cholesterol level in the Formula A, by incorporating various
cholesterol containing milk products into the product, we have
managed to reach a plasma cholesterol level at 6 months
substantially the same as for the group that was breast fed.
[0233] It was also found that infants fed the Formula A had a
higher cognitive score at 12 months compared to infants fed the
Control Formula. The Formula A fed infants had a cognitive score
similar to the breast fed infants. The magnitude of the difference
between the Formula A and the Control Formula groups is well in
line with a meta-analysis of studies on cognitive function in
formula fed compared to breast fed infants. This implies that one
or several factors in Formula A are needed for optimal cognitive
development and that those factors can reduce the differences in
cognitive function observed between breast-fed and formula-fed
infants.
[0234] Further this study showed that the maternal control effect,
which has been seen earlier in studies, did not affect the intake
of energy in the study infants, on the contrary the infants were
able to regulate the intake of the volume of the formula and thus
also the energy intake from both Formula A as well as from the
Control Formula in order to grow similar as breast fed infants.
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