**5. Infant formula: looking for the best alternative**

Although human milk contains all nutrients and provides diverse bioactive ingredients and considered the first functional food in infant life, it is not generally attractive, adequate, or acceptable or it is not available; in some cases, the infants cannot be breastfed. Thus, looking for a suitable alternative is of importance.

In these cases, infant formulas play an indispensable role in infant nutrition. All efforts of industry are aimed to resemble human milk composition [67]. The accumulated knowledge about human milk composition highly assists in infant formula development. However, the human milk composition is not stable, since it changes along breastfeeding period [68], as well as depending on different factors such as environment, mother's diet, and so on. Nowadays, companies and research centers are devoted to prepare these formulas focused on enhancing the quality of infant formulas, not only adapting the concentration of macronutrients and micronutrients but also the composition of bioactive compounds to make it as similar as possible to human milk [69] where the final aim of infant formula development is not necessarily to mimic the composition of human milk in every respect but to achieve physiological effects as in breastfed infants [70].

Nowadays, there are numerous infant formulas adapted to special physiological state and infant formula based on soy or without lactose, among others. But, in this chapter, we are focused on those formula based on supplemented cow milk with functional ingredients. The current trend of infant formula manufacturing is to enrich it with the functional ingredients that naturally found in human milk. Thus, these ingredients such as probiotics, prebiotics (oligosaccharides), proteins such as lactoferrin and α-lactalbumin, nucleotides,and polyunsaturated fatty acids (mainly docosahexaenoic and arachidonic acids) among others are incorporated in infant formulas to make them more functional [71]. In fact, many studies revealed the higher efficacy of infant formulas supplemented with certain bioactive ingredients than the unsupplemented ones [72].

#### **5.1. Nutritional components of infant formula**

to formula-fed infants. The positive microbial intestinal balance partially attributed to HMOs

Nucleotides, another bioactive ingredient of human milk, are nitrogenous compounds which play a main role in various metabolism processes, such as energy transfer, nucleic acid synthesis (DNA and RNA), and carbohydrates, lipids, and proteins synthesis. Nucleotides are found in human milk in free form as ribonucleotides and ribonucleosides accounting 2–5% of nonprotein nitrogen and participate in protein utilization by breastfed infants [35]. Free nucleotide content is higher in human milk than cow milk. Additionally, some related components such as nucleosides, purine and pyrimidine bases, nucleic acids, and products derived from them (such as uridine diphosphate galactose) have been found in human milk [64]. Human milk contains a higher content of free nucleotides than cow milk. Thus, it is recommended to enrich cow milk-based formulas with the nucleotide level similar to that found in human milk [65]. Recently, legislation allows the addition to infant formulas and follow-on formula, nucleotides in quantities of: 1.5 mg adenosine-5-phosphate/100 kcal, 2.5 cytosine-5-phosphate/100 kcal, 0.5 kcal guanosine-5-phosphate/100 mg, 1.75 mg uridine-5-phosphate/100 kcal, 1 mg inosine-5-phosphate/100 kcal, until a total concentration of 5 mg/100 kcal, which is similar to the amounts of free ribonucleotides in milk (4–6 mg/100 kcal) [25]. Also in this context, Koletzko et al. [15] reported that ESPGHAN supports the optional addition of nucleotides in amounts not to exceed 5 mg/100 kcal as adverse effects have been seen with higher concentrations.

Addition of nucleotides to infant formulas have been found to increase the probiotic bacteria counts and reduce the pathogen counts in stool samples in infants fed on nucleotide-supplemented formula as compared to whose fed standard infant formula, but probiotic counts in the stool of breastfed infants were still higher. The intestinal microflora modulation attributed to nucleotides due to that nucleotides serve as an energy source of intestinal microflora. Because probiotic bacteria are characterized by a higher growth rate than pathogenic bacteria, they limit the growth of pathogens. Thus, supplementation with nucleotides able to positively modulate the intestinal microbial balance, leading to increase probiotic growth and limit the

Although human milk contains all nutrients and provides diverse bioactive ingredients and considered the first functional food in infant life, it is not generally attractive, adequate, or acceptable or it is not available; in some cases, the infants cannot be breastfed. Thus, looking

In these cases, infant formulas play an indispensable role in infant nutrition. All efforts of industry are aimed to resemble human milk composition [67]. The accumulated knowledge about human milk composition highly assists in infant formula development. However, the human milk composition is not stable, since it changes along breastfeeding period [68], as well

plays a pivotal role in improving the gut health.

**4.3. Nucleotides**

18 Selected Topics in Breastfeeding

growth of the pathogens [66].

for a suitable alternative is of importance.

**5. Infant formula: looking for the best alternative**

Human milk must be always selected as the first option for the best infant nutrition. However, when it is impossible, an adequate substitute should be found. Historically, milk from different animals was studied, obtaining the best results for the cow. However, some problems have been found after using cow milk as a substitute, since the high-protein content, the different protein composition, and the sodium content, among others, could induce some metabolic problems to the not fully developed gastrointestinal system of newborns. From last decades until now, the infant formula has been developed trying to mimic to human milk in macronutrients and energy density, but it is in the most recent past when the functional ingredients are included in the infant formulation to simulate the beneficial health effects of breast milk. **Table 3** shows the composition of infant formula supplemented or not including legal limits according to the European Commission [73].

As can be seen, different compounds are included in supplemented infant formulas in different concentrations. The caloric values have also been considered to establish a minimum or maximum legal limit for each one. Prebiotics (FOS and GOS) are considered as key compounds in human milk in order to promote an adequate intestinal microbiota; for this reason, infant formulas should be adequately supplemented. Beneficial bacteria of human milk should be also included in infant formulas; however, it is very difficult that added bacteria achieve colon as live microorganisms with beneficial effects on health.

#### **5.2. Functional components of infant formula: resembling the standard model**

One of the functional ingredients added to infant formula is oligosaccharides (fructo- and/ or galactooligosaccharides) since they are in human breast milk providing a beneficial effect


iron and vitamin B12, respectively [76]. Vitamin B12 in human milk is mostly bound to haptocorrin, and these proteins have also been suggested to inhibit pathogenic bacterial growth by tightly

Bioactive Components of Human Milk: Similarities and Differences between Human Milk and…

http://dx.doi.org/10.5772/intechopen.73074

21

Another important human milk protein is alpha-lactalbumin (15% of the total protein content). This protein is responsible, in the mammary gland, for lactose synthesis, but it is also secreted in the milk. This functional protein is easily digested, forming peptides that may provide different bioactivities in the upper gastrointestinal tract (duodenum and jejunum) [78]. Alphalactalbumin, after gastrointestinal digestion, serves as a good source of essential amino acids.

Breastfeeding during the first 6 months of infant life represents the cornerstone of building his body and maintaining his health status. Feeding of an infant during this critical period of life has several short-term and long-term effects. So, breastfeeding is recommended exclusively after birth till 6 months; then, the complementary food must be included to meet the increasing nutrients needed. As we know, human milk is the optimal food during this early stage of life. In some cases, infant formulas represent the best alternative for infant feeding which must resemble human milk composition not only in its macronutrients but also in its functionality.

, Ruben Lopez-Nicolas<sup>3</sup>

1 Special Foods and Nutrition Department, Food Technology Research Institute,

2 Dairy Technology Research Department, Food Technology Research Institute, Agricultural

[1] Howie PW, Forsyth JS, Ogston SA, Florey CD. Protective effect of breastfeeding against

[2] Giribaldi M, Cavallarin L, Baro C, Di Nicola P, Coscia A, Bertino E. Biological and nutritional aspects of human milk in feeding of preterm infants. Food and Nutrition Sciences.

3 Food Science and Nutrition Department, Faculty of Veterinary Sciences, University of

, Carmen Frontela-Saseta3

and

binding and withholding vitamins and minerals from the bacteria [77].

**6. Conclusion**

**Author details**

Gaspar Ros-Berruezo<sup>3</sup>

Research Center, Giza, Egypt

Murcia, Espinardo, Spain

**References**

, Aliaa Ali Darwish2

Agricultural Research Center, Giza, Egypt

infection. British Medical Journal. 1990;**300**:11-16

2012;**3**:1682-1687. DOI: 10.4236/fns.2012.312220

\* \*Address all correspondence to: gros@um.es

Esmat Aly1

**Table 3.** The composition of different infant formulas. Values are expressed as grams per 100 mL of reconstituted formula.

on newborns due to its prebiotic activity. Furthermore, these compounds show anti-adhesive properties, protecting the intestinal epithelium against pathogens as well as enhancing the immune system that, in infants younger than 6 months, is not still fully developed.

Polyunsaturated fatty acids can be produced by newborns using its precursors (linolenic and linoleic acid), but this transformation pathway is not fully developed at this age. For that, most infant formulas are enriched with arachidonic and docosahexaenoic acids (ARA and DHA, respectively), since they play an important role in neuronal function and cognitive and visual development [74].

Other important bioactive compounds present in human milk are polyamines that are nitrogen compounds and are present in a very low concentration in cow's milk. Nowadays, based on different studies, polyamines should be added to infant formula; however, due to the scarce information found in the literature about its specific function and the effect on human health on medium-long term, more studies should be developed. Studies performed show an interesting role of polyamines in the maturation of intestinal and immune systems of infants [75].

Studies in infant formula composition must be studied in detail. Related to this, there is no doubt that the proteins in human milk provide an important source of amino acids to rapidly growing breastfed infants. However, this is not the only one role of milk proteins since many of them also play a role in facilitating the digestion and uptake of other nutrients in breast milk. Included in this group of functional proteins are lactoferrin and haptocorrin, which may assist in the absorption of iron and vitamin B12, respectively [76]. Vitamin B12 in human milk is mostly bound to haptocorrin, and these proteins have also been suggested to inhibit pathogenic bacterial growth by tightly binding and withholding vitamins and minerals from the bacteria [77].

Another important human milk protein is alpha-lactalbumin (15% of the total protein content). This protein is responsible, in the mammary gland, for lactose synthesis, but it is also secreted in the milk. This functional protein is easily digested, forming peptides that may provide different bioactivities in the upper gastrointestinal tract (duodenum and jejunum) [78]. Alphalactalbumin, after gastrointestinal digestion, serves as a good source of essential amino acids.
