Formula composition is developed to resemble breast milk as close as possible, but there
are still considerable differences between formula and breast milk composition, probably
resulting in higher risk of overweight in childhood and higher incidence of infections in
formula-fed infants. Protein levels are still higher and constituents such as
alpha-lactalbumin lower in formula than in breast milk. By adding more alpha-lactalbumin
to formula, rich in tryptophan, the resulting amino acid composition will allow further
reduction of protein in formula. The investigators intend to include 320 infants, where
80 will be exclusively breastfed and the remainder assigned in a double blind,
controlled, randomized manner to one of three formula groups; two experimental, protein
reduced formula with two different levels of alpha-lactalbumin and one group given
standard infant formula. The intervention period is from 4-8 weeks until 6 months of age.
The infants will be followed by growth parameters, blood-, urine- and fecal biomarkers
and health parameters until 5 years of age. The experimental formula will possibly result
in growth, metabolism and gut microbiota as well as health parameters more similar to
those of breastfed infants

Growth and Metabolism in Infants Fed Protein-reduced, Alpha-lactalbumin Enriched Formula

Growth

Infection

Sleep

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.

Protein-reduced α-lactalbumin formula

Protein-reduced whey formula

Standard infant formula

ALFoNS - Growth and Metabolism in Infants Fed Protein-reduced, Alpha-lactalbumin Enriched Formula Compared to Breastfed Infants

MD, PhD, Senior Consultant

Protein-reduced whey formula with higher level of α-lactalbumin than in standard infant
formula

Protein-reduced formula with level of α-lactalbumin more similar to breast milk and
higher than in experimental whey formula and in standard infant formula

Growth and Metabolism in Infants Fed Protein-reduced, Alpha-lactalbumin Enriched Formula

About this trial

Study ID

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Type

Phase

Placebo

Accepting

Trial Timing

What is this trial about?

What are the Participation Requirements?

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