4. Discussion
thirst, gastrointestinal tolerance, infections, weight gain, satiety, breast milk
IRON DEFICIENCY, INFECTIONS
By increasing the proportion of α-lactalbumin-enriched whey or CGMP-reduced whey to infant formula, our study shows that the total protein concentration can be safely lowered to 1.75 g/100 kcal, which is slightly below the minimum regulation of 1.8 g/100 kcal according to the EU directive [Feeding infants formula with higher protein concentration has been shown to result in higher weight gain than if low-protein formula or breast milk were given [Our findings of lower ingested volumes of formula up to five months of age in EF compared to SF groups, resulting in lower energy intakes, despite practically isocaloric formulas, may indicate higher satiety among infants fed formulas with added α-lactalbumin-enriched or CGMP-reduced whey compared to those fed SF, also resulting in further reduced protein intakes. However, we did not find any differences in the appetite regulating hormone leptin. Another possibility is that the higher potential renal solute load (PRSL) of SF resulted in increased thirst in this group, and thus a higher volume intake.The lower serum BUN in infants fed EF compared to those fed SF, and the similar serum BUN in EF groups compared to BF infants in the present study, are not only the result of a lower protein intake in EF infants but could also indicate improved quality of formula protein, in accordance with other studies [BCAAs, considered to increase insulin secretion and thus growth, are traditionally found to be higher in FF compared to BF infants due to the higher protein concentration in formula. Feeding lower protein formula consequently results in lower serum BCAA concentrations closer to those of BF infants, as shown by us and others [Tryptophan is one of the limiting amino acids when lowering protein concentration in infant formula, and is necessary in the formation of serotonin and accordingly melatonin, thereby affecting sleep patterns [In contrast to other studies, serum histidine was marginally lower in all FF groups compared to the BF group during the intervention period, despite histidine concentration in all study formulas being higher than the minimum requirements (40 mg/100 kcal). The reason for this is unclear and is not considered a concern.Serum C-peptide has been reported to increase with increasing protein concentration in infant formula [Effects of protein intake on growth velocity could be mediated by IGF-1 [Since serum IGF-1 is the main growth factor during infancy, the positive correlation found between the difference in IGF1 between two and six month and weight gain from two to six months in all FF groups except for the BF group, is an interesting finding. Previous studies have conflicting results regarding IGF-1 levels in BF infants and infant growth [Leptin is essential in the complex regulation of food intake and energy metabolism. Previous studies [Excessive iron intake in healthy infants without iron deficiency may impair infant growth and increase susceptibility to infections [Some studies report improved gastrointestinal tolerance in infants fed α-lactalbumin enriched formula [A strength of this study is the randomized controlled trial (RCT) design, with large numbers of subjects and a low dropout rate. In addition, most infants were only introduced to small taste portions of complementary food between four and six months of age, thus limiting its influence on the results at five and six months. Furthermore, to our knowledge this is the first published RCT comparing infant formula with protein concentration slightly below new current regulatory limits (1.8 g/100 kcal) with either a higher concentration of α-lactalbumin-enriched whey or CGMP-reduced whey. A limitation of the study was that infants were not enrolled until five to eight weeks age, in order not to disturb the establishment of breastfeeding, and also that two thirds of the infants in the FF groups had received breast milk to some extent prior to enrollment, which may have affected our results. However, the period of breastfeeding was brief (about two weeks) and did not differ among the FF groups.In conclusion, feeding infants low protein infant formula enriched with either high concentration of α-lactalbumin-enriched whey or CGMP-reduced whey is safe and well tolerated, providing adequate growth and a metabolic profile closer to that of BF infants. Increasing the concentration of α-lactalbumin further enables a formula protein composition closer to breast milk. Even though growth velocity was similar at some time-points in infants fed low-protein α-lactalbumin-enriched formula and BF infants, overall growth was still slightly higher among infants fed the low-protein infant formulas compared to BF infants as were serum concentrations of BCAAs, IGF-1, insulin, and C-peptide. Thus, protein concentration can probably be further reduced in infant formulas, if protein quality is kept high. Long-term follow-up data on growth and metabolic profiles are desirable to evaluate whether improved infant formula composition will have long-term beneficial effects throughout childhood.