Brief Summary
Formula composition is developed to resemble breast milk as close as possible, but there are
<br /> still considerable differences between formula and breast milk composition, probably
<br /> resulting in higher risk of overweight in childhood and higher incidence of infections in
<br /> formula-fed infants. Protein levels are still higher and constituents such as
<br /> alpha-lactalbumin lower in formula than in breast milk. By adding more alpha-lactalbumin to
<br /> formula, rich in tryptophan, the resulting amino acid composition will allow further
<br /> reduction of protein in formula. The investigators intend to include 320 infants, where 80
<br /> will be exclusively breastfed and the remainder assigned in a double blind, controlled,
<br /> randomized manner to one of three formula groups; two experimental, protein reduced formula
<br /> with two different levels of alpha-lactalbumin and one group given standard infant formula.
<br /> The intervention period is from 4-8 weeks until 6 months of age. The infants will be followed
<br /> by growth parameters, blood-, urine- and fecal biomarkers and health parameters until 5 years
<br /> of age. The experimental formula will possibly result in growth, metabolism and gut
<br /> microbiota as well as health parameters more similar to those of breastfed infants
Detailed Description
Background: Breast milk is the best source of nutrition for the rapidly growing infant since
it contains all the necessary nutrients in the right proportions. If the mother cannot
breast-feed, chooses not to breast-feed or has to stop early, an adapted formula is from a
nutritional perspective the only alternative during the first four to six months of age and
also the best alternative throughout the rest of the first year of life together with
suitable complementary foods. Formula composition has through the years developed to resemble
as close as possible the composition of breast milk resulting in physiological effects in the
infant to more resemble that of the breast-fed infant. However, there are still considerable
differences between the dietary intake of the breast-fed infant and its metabolism compared
to infants who are fed formula. Furthermore, research suggests that breast-fed infants have a
lower risk of overweight and obesity in childhood and adolescence, lower risk of acute otitis
media (AOM), upper airway- and gastrointestinal infections, and possibly a lower risk of high
blood pressure and diabetes type 2 as adults which probably depend on different protein
composition and concentration in formula and breastmilk. The optimal protein level of formula
is still under debate. The investigators know that the protein concentration of formula is
unnecessarily high, but until now it has been difficult to reduce it further due to the
potential risk of shortage of some of the essential amino acids, i.e. those amino acids that
have to be delivered from the diet.
The concentration of alpha-lactalbumin, the predominating whey protein in breast milk, is
still low in formula. The composition of the protein in breast milk and formula thus differs
considerably and consequently also the amino acid pattern in serum between infants who are
breast-, or formula-fed. Alpha-lactalbumin has many potential positive effects which may
explain some of the differences between breast-fed and formula-fed infants and when added to
formula makes it more similar to the composition of breast milk. Alpha-lactalbumin contains a
higher concentration of cysteine, a precursor of taurine, which is important for
neurodevelopment. However, it is foremost the concentration of tryptophan that is higher in
alpha-lactalbumin, an amino acid which otherwise is a limiting factor when lowering the
protein level in formula. Tryptophan is a precursor of serotonin, a neurotransmitter
important for stress management, cognition under stress and sleep latency.
Recently, new whey protein sources which contain higher concentrations of alpha-lactalbumin
have become available. Studies show that protein is still too high in formula resulting in
higher concentrations of urea nitrogen and most amino acids in infants who are fed formula
compared to those who are breast-fed, which indicates that formula-fed infants still have
excessive protein intake. Thus, there should be no problem in further reducing the protein
level of formula during the first 6 months of life by increasing the proportion of
alpha-lactalbumin. In this way the investigators might achieve a growth pattern and a
metabolism more similar to that of the breast-fed infant. Acid whey protein is already in use
today by some producers to obtain whey to casein ratio more similar to that of breast milk
and to increase the concentration of tryptophan, which is an alternative, in increasing the
proportion of alpha-lactalbumin. In this study the investigators intend to study both
possibilities.
Alpha-lactalbumin has been suggested to influence the gut bacterial flora with a positive
antimicrobial effect and improved immune function of the infant. Hypothetically, an increased
intake of alpha-lactalbumin may result in fewer infections in formula-fed infants and thus
decrease the differences in infection prevalence between formula- and breast-fed infants.
Alpha-lactalbumin also seems to influence the uptake of minerals, such as iron, which could
be important for iron status of the infant. Thus, iron status may improve in formula-fed
infants when alpha-lactalbumin is added to formula, which has previously been shown by us and
others.
With metabolomics, chemical processes involving metabolites, small molecule substrates,
intermediates and products of metabolism are studied. Specifically, metabolomics is
identifies a unique chemical fingerprints that specific cellular processes leave behind".
Differences in metabolomics between the different groups will be studied Objectives: The
purpose of the present study is to evaluate the effect of feeding infants a protein-reduced
infant formula with high or low levels of alpha-lactalbumin on growth, metabolic markers and
gut microbiota composition.
Methods: Healthy infants with normal growth parameters will be included. If the infant is
fully formula-fed at 4-8 weeks of age, he or she will be randomized in a double blinded
controlled manner to one of the three formula groups and receive the assigned infant formula
until 6 month of age. The investigators will also include exclusively breast fed infants,
whose mothers intend to breast-feed for at least 6 months, in a breastfed group.
From inclusion through the 12th month of age dietary intake, the incidence and duration of
illness, stool consistency, fever, gastrointestinal problems, respiratory problems, and
during the first 6 months also sleep- and crying time, will be recorded by the parents.
Hospitalization and unscheduled doctor's visits will also be recorded by parents as well as
medication (type, duration) and any adverse effects. Growth and well-being will be followed.
Blood samples will be taken for analyses of protein metabolism and metabolomics and fecal
microbiota will be analyzed as well as metabolites in urine.
Outcomes: Through this study the investigators should be able to clarify if feeding infants a
protein-reduced formula with addition of alpha-lactalbumin or acid whey protein will affect
growth, metabolic markers, gut microbiota composition and health parameters to approach those
of breast-fed infants with possibly lower risk of overweight in childhood and lower
incidences of infections in formula-fed infants.
