8]. At least some of these changes in the composition of breast milk during lactation reflect changes in the requirements of infants, which are linked to changes in growth velocity and maturation of immunological and physiological functions. The complexity is also given by the diverse composition of breast milk. Nutrients (such as proteins, lipids, carbohydrates, minerals, vitamins and trace elements) are of high importance to meet the nutritional needs of young infants and ensure healthy normal growth and development, but human milk also contains numerous bioactive proteins and peptides including antimicrobial and immune-modulating factors, enzymes, hormones and growth factors [9, 10]. Several of these compounds affect the infant’s immune status, conferring a passive protection against infection, and facilitate immune development and maturation.
Although it is variable within mothers and across lactation, the macronutrient composition of human milk is conserved across populations. The mean macronutrient composition of mature, term milk is estimated to be approximately 0.9-1.2 g/dl for proteins, 3.2-3.6 g/dl for fat and 6.7-7.8 g/dl for lactose [11].
The proteins of human milk are divided into the whey and casein fractions comprising a large number of different proteins and peptides [12, 13]. The most abundant proteins are caseins, α-lactalbumin, lactoferrin, secretory IgA, lysozyme and serum albumin [9]. Nonprotein nitrogen-containing compounds, including urea, ureic acid, creatinine, creatine, amino acids and nucleotides, cover approximately 25% of human milk nitrogen.
Both total protein content and concentrations of individual proteins in human milk change throughout the first year of lactation to match the needs of the infant. Protein levels decrease in human milk over the first 4-6 weeks regardless of the timing of delivery (from 12-18 g/l in early milk to 8-9 g/l in mature milk) [14].
Infant Formula
Infant formulas have been designed for infants who cannot be breastfed. Until the 20th century, there was no safe and reliable alternative to breastfeeding. With the increasing knowledge on the composition of milk (linked to the development of techniques for chemical analyses of milk), better assessment of the energy requirements of infants and advances in dairy technology, substitutes for breast milk were developed from the milk of other mammals. Successive improvements enabled the launch of the first whey-dominant formula in 1961 and the first Codex Alimentarius standard for infant formulas was issued in 1972. Today, besides breast milk, infant formula is the only other milk product which the medical community considers nutritionally acceptable for infants under the age of 1 year (as opposed to unmodified cow’s or goat’s milk).
Protein sources and processes have been modified along the years to optimize both the quality and the quantity of proteins in infant formulas in order to be closer to the composition but also the functional outcomes of breast milk.
Modern infant formulas provide similar amino acid profiles and protein contents as those found in breast milk. The most commonly used infant formulas contain purified cow’s milk whey and casein as a protein source. The composition of milk varies according to the mammal from which it comes, providing the correct rate of growth and development for the young of that species; thus for the human infant, human milk is obviously more suitable than cow’s milk. While cow’s milk and human milk contain a similar percentage of water, the relative amount of carbohydrates, proteins, fats, vitamins and minerals varies, because they are fine tuned to meet the nutritional requirements of that particular animal (table 2). As an example, the protein content in cow’s milk (5 g/100 kcal) is more than 3 times higher that of human milk (1.5 g/100 kcal). The ratio between caseins and whey proteins is also very different between cow’s milk and human milk: human milk contains 30% caseins/70% whey proteins, while in cow’s milk the ratio is 80:20, respectively (table 2). Given that the amount of total protein in cow’s milk is more than double that of human milk, cow’s milk clearly contains considerably more caseins than human milk. Although cow’s milk is the basis of almost all infant formulas, plain cow’s milk is not suited for infants because of its high casein content and low whey content, which may stress infant’s immature kidneys. Therefore, unmodified cow’s milk is not recommended before the age of 12 months.
Table 2. Composition of mature breast milk and cow’s milk (in g/kg of milk)
| Breast milk | Cow’s milk | |
| Lipids | 38 | 35 |
| Proteins (% whey/% caseins) | 15 (70/30) | 35 (20/80) |
| Carbohydrates | 70 | 48 |
| Minerals | ||
| K | 0.51 | 1.4 |
| Na | 0.15 | 0.5 |
| Ca | 0.30 | 1.2 |
| Mg | 0.04 | 0.12 |
| P | 0.14 | 0.95 |
| Cl | 0.41 | 1.1 |
Looking at these figures (the quantity and the quality of proteins in human milk and cow’s milk), it is virtually impossible to obtain an amino acid profile similar to human milk using unmodified cow’s milk protein fractions, and, in order to do so, it would be necessary to provide more protein to ensure enough of the limiting amino acids.
To circumvent this issue, cow’s milk used for infant formula undergoes processing. This includes steps to make proteins more easily digestible and to alter the whey/casein protein balance in order to be closer to that of human milk. Improvements in the quality of the proteins (an amino acid composition similar to that of breast milk) allowed manufacturers to reduce the quantity of proteins in infant formula to better mimic the growth pattern of formula-fed infants to that of the breastfed infants. Different manufacturing processes have been developed by infant formula companies such as using sweet whey to demineralize and fractionate the proteins of sweet whey by the removal of CaseinGlycoMacroPeptides (Nestlé-patented process). Using this optimized process and protein fractions made thereof, the amino acid profile and the protein content of the infant formula (1.8 g/100 kcal) moved a further step closer to that of breast milk. The use of this type of infant formula has indeed been shown to support similar weight gain, body mass index and head circumference as observed in breastfed infants [15, 16].
Clinical data showing that lower