Extensively hydrolyzed formulas (eHFs) are recommended for the dietary management of cow's milk protein allergy (CMPA) in non-exclusively breastfed infants. Studies show that peptide profiles differ between eHFs. This short review aims to highlight the variability in peptides and their ability to influence allergenicity and possibly the induction of tolerance by different eHFs. The differences between eHFs are determined by the source of the protein fraction (casein or whey), peptide size-distribution profile and residual β-lactoglobulin which is the most immunogenic and allergenic protein in bovine milk for human infants as it is not present in human breastmilk. These differences occur from the hydrolyzation process which result in variable IgE reactivity against cow's milk allergen epitopes by subjects with CMPA and differences in the Th1, Th2 and pro-inflammatory cytokine responses elicited. They also have different effects on gut barrier integrity. Results suggest that one particular eHF-casein had the least allergenic potential due to its low residual allergenic epitope content and demonstrated the greatest effect on restoring gut barrier integrity by its effects on mucin 5AC, occludin and Zona Occludens-1 in human enterocytes. It also increased the production of the tolerogenic cytokines Il-10 and IFN-γ. In addition, recent studies documented promising effects of optional functional ingredients such as pre-, pro- and synbiotics on the management of cow's milk allergy and induction of tolerance, in part via the induction of the production of short chain fatty acids. This review highlights differences in the residual allergenicity, peptide size distribution, presence of optional functional ingredients and overall functionality of several well-characterized eHFs which can impact the management of CMPA and the ability to induce immune tolerance to cow's milk protein.
The prevalence of food allergy has increased over the last 20-30 years, including cow milk allergy (CMA) which is one of the most common causes of infant food allergy. International allergy experts met in 2019 to discuss broad topics in allergy prevention and management of CMA including current challenges and future opportunities. The highlights of the meeting combined with recently published developments are presented here. Primary prevention of CMA should start from pre-pregnancy with a focus on a healthy lifestyle and food diversity to ensure adequate transfer of inhibitory IgG- allergen immune complexes across the placenta especially in mothers with a history of allergic diseases and planned c-section delivery. For non-breastfed infants, there is controversy about the preventive role of partially hydrolyzed formulae (pHF) despite some evidence of health economic benefits among those with a family history of allergy. Clinical management of CMA consists of secondary prevention with a focus on the development of early oral tolerance. The use of extensive Hydrolysate Formulae (eHF) is the nutrition of choice for the majority of non-breastfed infants with CMA; potentially with pre-, probiotics and LCPUFA to support early oral tolerance induction. Future opportunities are, among others, pre- and probiotics supplementation for mothers and high-risk infants for the primary prevention of CMA. A controlled prospective study implementing a step-down milk formulae ladder with various degrees of hydrolysate is proposed for food challenges and early development of oral tolerance. This provides a more precise gradation of milk protein exposure than those currently recommended.