Hydrolysates, based on cow’s milk proteins, are becoming increasingly popular for use in formulas for infants with general, nonspecific gastrointestinal problems because these hydrolysate-based formulas are easier to digest. FrieslandCampina Domo develops and manufactures hydrolysates which are used in Easy-to-Digest (or Comfort) infant formulas. This overview gives background information about these formulas, why they are used and the range of hydrolysates that Domo has developed for these products.
Importance of cow’s milk for infant nutrition
Breast milk is the best choice for newborn infants. However, When breast milk is limited or impossible, infant formulas are the only food products that satisfy the nutritional requirements of infants during the first months of life (EU2006/141). Cow’s milk proteins are rich in all the essential amino acids and they have a high nutritional quality, in contrast to vegetable proteins*. The predominant milk proteins are casein and whey. While most infants grow up health with common cow’s milk-based formulas, some suffer from general, non-specific digestive problems, like abdominal cramps, colic, diarrhea, regurgitation or constipation22. For these infants, formulas have been developed based on slightly hydrolysed cow’s milk proteins, which retain the high nutritional quality of cow’s milk proteins but are provided in a predigested form.
Ingested proteins are enzymatically hydrolysed into short peptides and constituent amino acids in the gastrointestinal tract. The first step of protein digestion occurs in the stomach, where the secretion of hydrochloric acid results in a low pH. The acidity of the gastric juice causes globular proteins to denature or unfold, rendering their internal peptide bonds more accessible to enzymatic hydrolysis1.
This low pH is also important in the second step involving the enzyme pepsin, which hydrolyses long polypeptide chains into a mixture of smaller peptides. The resulting peptides are further hydrolysed into smaller peptides in the small intestine by the enzymes trypsin and chymotrypsin. This stage of protein digestion is accomplished very efficiently because pepsin, trypsin and chymotrypsin have different amino acid specificities in hydrolysing polypeptide chains. Degradation of the short peptides in the small intestine is completed by carboxyl peptidase and aminopeptidase, which remove successive carboxylterminal and amino terminal residues from short peptides respectively. Due to the sequential action of these proteolytic enzymes and peptidases, ingested proteins are ultimately hydrolysed to yield a mixture of free amino acids and di- and tripeptides, which are then transported across the epithelial cells lining the small intestine1.
Protein digestion in infants and the facilitating role of hydrolysates
As mentioned above, the acidity of gastric juice is important for the enzyme pepsin, which hydrolyses long polypeptide chains into a mixture of smaller peptides. Pepsin is effective in the pH range of 1.5 to 2.52. In adults, the stomach pH is regulated at about pH 23. However, the pH of the gastric contents among infants is about 4.54, and rises above 5 postprandially, remaining high for more than an hour5. Such pH values are far from the pH optimum of pepsin, and it has been demonstrated that this results in reduced hydrolysis of proteins6.
Moreover, the postprandial pepsin output is significantly lower in preterm infants than in adults7. Therefore, gastric proteolysis is assumed to be low in infants7,8, which suggests that a greater effort is required from the second stage of protein digestion in the small intestine. It is proposed that moderate predigestion (hydrolysis) of the proteins in infant formulas assists the digestion process. This is supported by the finding of Calbet et al.9, which substantiated that the speed of intestinal amino acid absorption is slower for intact casein protein than for hydrolysed casein protein, intact whey protein and hydrolysed whey protein. They also showed that hydrolysed proteins elicit about 50% more gastric secretion than the whole protein9, which could also improve the digestibility.
Hydrolysates and their role in common digestive problems in healthy, thriving infants
A common problem among infants during their first months of life is infantile colic, which is defined as excessive crying in a healthy baby. This syndrome typically has its onset in the first few weeks and spontaneously resolves by the age of 4 to 6 months10. The prevalence of colic ranges from 5% to 40%, depending on the definition and diagnosis method used10. The exact cause of infantile colic is not yet fully understood, but it is potentially related to a problem with the gut11. Features are painful gut contractions, abdominal distension, passing of gas and difficulties in passing stools.
In a recent prospective, randomised controlled study by Arikan et al12. involving 175 infants with infantile colic, hydrolysed formula was the
most effective in reducing the duration of crying when compared with the control and other interventions including massage, sucrose solution and herbal tea. In the review by Lucassen et al.13, it was concluded that substituting intact protein formulas with hydrolysed protein formulas has a clear beneficial effect on infantile colic. However, there is no evidence that low lactose formulas or fibre enriched formulas are effective. Moreover, the effectiveness of substituting cows’ milk with soy formulas has also not been established. Therefore, a protein hydrolysate derived from cow’s milk is recommended as the preferred treatment for colicky infants.
Although Lucassen’s review only concerns trials with casein hydrolysates14,15, whey hydrolysates have been demonstrated to exhibit the same beneficial role in infantile colic16,17. In a recent randomised, double-blind, parallel trial18, intake of a whey hydrolysate-based formula by infants with colic resulted in a significant decrease of crying duration. When standard formula was administered again, the duration of crying increased.
Other common digestive problems in infants are regurgitation, vomiting and gastro esophageal reflux (GER). GER affects about 20% of formula-fed infants. Reducing the gastrointestinal transit time can prevent these problems. Hydrolysate-based formulas accelerate the gastrointestinal transit of milk and stools19,20,21 and can therefore significantly reduce these symptoms.
Models to show digestibility of protein hydrolysates
The best way to demonstrate that a formula is well tolerated is to perform clinical studies with infants studying digestion kinetics and physiological outcomes. However, as in vitro digestion models can be used. A first indicative in vitro experiment is curd formation in acidic environment. A softer curd or curd absence can indicate easier digestibility of the formula.
An experiment performed by Domo with two infant formulas – one based on intact proteins (casein:whey 40:60) and one on slightly hydrolysed casein and intact whey (40:60) – has shown that substitution of intact casein by slightly hydrolysed casein prevented curd formation (see figure 1). This suggests that formulas based on hydrolysed casein could be more easily digested in the infant’s digestive tract.
Figure 1: Substitution of intact casein by slightly hydrolysed casein prevents curd formation in the acidic environment as present in the infant’s stomach.
The information on this page is intended for industrial customers only and not intended for consumers. Potential consumer benefits are not to be considered as health claims. They should be considered as potential leads that might be developed into health claims complying with the local legal requirements.