Milk Protein Hydrolysates Research Articles

Efeitos da modificação ambiental multimodal em felinos com cristais doenças do trato urinário inferior relacionadas a cristais

ABSTRACT This study aims to analyze the effects of multimodal environmental modification (MEMO) of cats with recurrence of lower urinary tract signs (LUTS). Treatment of FLUTD included pharmacological treatment, dietary management, and multimodal environmental modification approaches. Twenty client-owned indoor-housed cats with recurrence of lower urinary tract signs had been covered in this observation. Diagnosis of lower urinary tract was made primarily based on the cat's clinical signs, results of laboratory parameters, urinalysis and ultrasonographic examination. Cats were divided into two groups as cefovecin (8 mg/kg sc, single time use) + meloxicam (0.1mg/kg q24h, 3 days) + dry food including l-tryptophan and milk protein hydrolysate to dissolve struvite stones (Group 1) and cefovecin + meloxicam + dry food including l-tryptophan and milk protein hydrolysate to dissolve struvite stones + multimodal environmental modification (Group 2). Clinical and urinary parameters are scored as 0, 1, 2, 3 or 4 points on initial, third, seventh days. Scores of clinical parameters were significantly different between (p<0.05) group 2 and group 1 on the third and seventh days and scores of urinary parameters are significantly different between (p<0.05) group 2 than group 1 on the seventh day. Clients who were contacted after 1 year reported that they did not see any clinical signs of urinary tract diseases.

P03-059-23 A Milk Protein Hydrolysate Decreases Inflammation on a Model of mBSA-Induced Arthritis Mice

P03-059-23 A Milk Protein Hydrolysate Decreases Inflammation on a Model of mBSA-Induced Arthritis Mice

In vitro gastric digestion of an experimental infant formula containing both intact and hydrolyzed milk proteins

Milk protein hydrolysates may have several benefits for digestion and digestion-related complications in infants, whereas intact milk proteins have been demonstrated to provide functionality beyond their nutritional value. In this study, in vitro digestion of an experimental infant formula containing both intact milk proteins and a milk protein hydrolysate was determined. Relative to an intact milk protein control formula, the experimental formula displayed a higher initial protein digestion during simulated gastric digestion as illustrated by a larger proportion of smaller peptides and higher level of available amino groups during digestion. Gastric protein coagulation was not affected by the hydrolysate addition. Further in vivo studies should demonstrate whether partial replacement of the protein source by a hydrolysate and observed differences in in vitro protein digestion result in overall altered protein digestion and absorption kinetics or affect functional gastrointestinal disorders as has been demonstrated for full hydrolysate formula.

High angiotensin I‐converting enzyme inhibitory activity, bioaccessibility and bioavailability of milk protein hydrolysate by commercial proteases formulated with Pseudomonas aeruginosa protease

Milk protein hydrolysate was optimally prepared by Protamex and PaproA (MP‐PP) exhibiting excellent angiotensin I‐converting enzyme (ACE) inhibitory activity (89.6%) at 0.5 mg/mL and protein recovery rate (79.0%). Meanwhile, MP‐PP was stable for acid–base and heat treatments, and even presented 80.5% of ACE inhibitory activity after handling in gastrointestinal fluids. However, transepithelial transportation via Caco‐2 cell monolayer lowered ACE inhibition of MP‐PP. Following the fractionation of MP‐PP, IESPPEI was identified as an outstanding ACE inhibitory peptide (IC50 of 6.4 μM), comparable with commercial VPP and IPP. Overall, MP‐PP and IESPPEI are potential functional ingredients to develop antihypertensive products.

Extensive hydrolysis of milk protein and its peptidomic antigenicity analysis by LC-MS/MS.

Milk protein concentrate (MPC) is considered an ideal substitute of cow milk because of its similar protein and nutrition. In this study, MPC was hydrolyzed to peptides by alcalase and neutrase, and the properties of hydrolysate were evaluated. When MPC was hydrolyzed at the ratio of alcalase and neutrase of 1:1 and enzyme to substrate ratio of 6000U/g MPC at 50°C, pH 8.5 for 3h, the proportion of peptides with molecular weights <1kDa was 85.31%, and the antigenicity reduction rates of casein and β-lactoglobulin were 33.76% and 22.38%, respectively. Moreover, LC-MS/MS peptide identification revealed that the alcalase and neutrase disrupted a total of 65 epitopes of casein and 21 epitopes of whey protein, which further elucidated the mechanism of complex enzyme hydrolysis to reduce milk protein allergenicity.

Enzymatic proteolysis during the conversion of milk into cheese

The transformation of milk into cheese occurs under the influence of many physicochemical, biochemical and microbiological processes, among which proteolysis plays a very important role. Proteolysis belongs to the most complex type of irreversible post-translational modification of proteins. Enzymatic proteolysis catalysts at different stages of cheese production are native milk enzymes, exo- and endopeptidases of starter and non-starter microorganisms, and milk-clotting enzymes. The article presents a brief overview of modern ideas about the properties, mechanism of action and specificity of the main representatives of enzymes that hydrolyze milk proteins at the stages of preparing milk for coagulation, during rennet coagulation and subsequent maturation of cheeses. These include the plasmin system of milk, enzymes of psychrotrophic bacteria and lactic acid microorganisms that enter milk both accidentally (non-starter microflora) and planned in the form of starter cultures from specially selected strains. Milk-clotting enzymes, having fulfilled their main function — milk coagulation — partially pass into cheese and, along with enzymes of starter microorganisms and plasmin, participate in proteolytic processes during cheese ripening. It is generally accepted that proteolysis in ripening cheeses is the most significant biochemical process that affects the formation of taste, aroma and texture along with lipolysis and glycolysis. The combination of proteolysis products (peptides, amino acids, amines, etc.) is individual for different types of cheese and varies depending on the technological parameters of production, including the duration of maturation. Proteolysis in cheeses has been studied by many scientists in various aspects. This review supplements the known information with new information, without claiming to be comprehensive.

Physicochemical properties, antigenicity and allergenicity of yoghurt fermented by Lactiplantibacillus plantarum AHQ‐14 combined with starter

SummaryCow milk proteins is one of the major food allergens, and some probiotics can abate allergenicity to some extent. Lactiplantibacillus plantarum AHQ‐14 isolated from the traditional dairy products in Xinjiang Province, China, has good ability to reduce the allergenicity of β‐lactoglobulin (LG) and good probiotic properties. In the presented study, L. plantarum AHQ‐14 was used to replace half of the commercial yoghurt starter to ferment yoghurt, and the effects of L. plantarum AHQ‐14 fortification on microstructure, textural and rheological attributes of yoghurt were investigated. In addition, milk protein hydrolysis, antigenicity and allergenicity of yoghurts during 28 days of cold storage were detected. The results indicated that AHQ‐14 and YC‐X11 fermentation could enhance the texture and rheological properties of yoghurt by reducing the syneresis (37%) and firmness (14%) and improving the cohesiveness by 50%. In addition, AHQ‐14 and YC‐X11 fermentation can shorten the fermentation time by about 30 min, SDS‐PAGE displayed that AHQ‐14 and YC‐X11 fermentation had stronger hydrolysis of whey protein compared with YC‐X11 yoghurt. Additionally, the fermentation by L. plantarum AHQ‐14 and YC‐X11 could significantly reduce the antigenicity and IgE‐binding ability of skim milk by 82% and 94%, respectively, thus reducing milk‐allergic reactions in patients significantly.

In vitro antidiabetic and antihypercholesterolemic activities of camel milk protein hydrolysates derived upon simulated gastrointestinal digestion of milk from different camel breeds

Milk protein hydrolysates derived from 4 camel breeds (Pakistani, Saheli, Hozami, and Omani) were evaluated for in vitro inhibition of antidiabetic enzymatic markers (dipeptidyl peptidase IV and α-amylase) and antihypercholesterolemic enzymatic markers (pancreatic lipase and cholesterol esterase). Milk samples were subjected to in vitro simulated gastric (SGD) and gastrointestinal digestion (SGID) conditions. In comparison with intact milk proteins, the SGD-derived milk protein hydrolysates showed enhanced inhibition of α-amylase, dipeptidyl peptidase IV, pancreatic lipase, and cholesterol esterase as reflected by lower half-maximal inhibitory concentration values. Overall, milk protein hydrolysates derived from the milk of Hozami and Omani camel breeds displayed higher inhibition of different enzymatic markers compared with milk protein hydrolysates from Pakistani and Saheli breeds. In vitro SGD and SGID processes significantly increased the bioactive properties of milk from all camel breeds. Milk protein hydrolysates from different camel breeds showed significant variations for inhibition of antidiabetic and antihypercholesterolemic enzymatic markers, suggesting the importance of breed selection for production of bioactive peptides. However, further studies on identifying the peptides generated upon SGD and SGID of milk from different camel breeds are needed.

Antibacterial Activity From Goat’s Milk Whey Hydrolized by Protease Enzyme of Bacillus Lincheniformis

Food additives had been used to prevent and inhibit the growth of microorganisms and extend shelf life of food. Based on the safety of their used, it has an impact such as microorganism resistance to synthetic antimicrobials. This encourages the development of antimicrobials derived from natural ingredients, especially from milk. The bioactive components of milk protein have not always existed in their natural state, including precursors or peptides that will only be active if they have been hydrolyzed in vitro from their natural proteins. Hydrolysis of milk protein can be carried out using proteolytic enzymes from various sources, including protease extracted from Bacillus lincheniformis. This study used different concentrations of the protease extracted from Bacillus lincheniformis (0.5%, 1% and 1.5%) to produce hydrolyzate which has antibacterial activity in terms of protein content, SDS PAGE profile and the size of the inhibition zone (disc method). The results showed that the best activity of the whey hydrolyzed on Gram-negative Escherichia coli was 1% concentration of protease enzyme. In comparison, Gram positive Staphylococcus aureus can be inhibited with 0.5% concentration of protease enzyme.

The Impact of Low-Temperature Inactivation of Protease AprX from Pseudomonas on Its Proteolytic Capacity and Specificity: A Peptidomic Study

The destabilization of UHT milk during its shelf life can be promoted by the residual proteolytic activity attributed to the protease AprX from Pseudomonas. To better understand the hydrolysis patterns of AprX, and to evaluate the feasibility of using low-temperature inactivation (LTI) for AprX, the release of peptides through AprX activity on milk proteins was examined using an LC-MS/MS-based peptidomic analysis. Milk samples were either directly incubated to be hydrolyzed by AprX, or preheated under LTI conditions (60 °C for 15 min) and then incubated. Peptides and parent proteins (the proteins from which the peptides originated) were identified and quantified. The peptides were mapped and the cleavage frequency of amino acids in the P1/P1′ positions was analyzed, after which the influence of LTI and the potential bitterness of the formed peptides were determined. Our results showed that a total of 2488 peptides were identified from 48 parent proteins, with the most abundant peptides originating from κ-casein and β-casein. AprX may also non-specifically hydrolyze other proteins in milk. Except for decreasing the bitterness potential in skim UHT milk, LTI did not significantly reduce the AprX-induced hydrolysis of milk proteins. Therefore, the inactivation of AprX by LTI may not be feasible in UHT milk production.

Increased Amino Acid Absorption Mediated by Lacticaseibacillus rhamnosus IDCC 3201 in High-Protein Diet-Fed Mice.

The use of dietary protein products has increased with interests in health promotion, and demand for sports supplements. Among various protein sources, milk protein is one of the most widely employed, given its economic and nutritional advantages. However, recent studies have revealed that milk protein undergoes fecal excretion without complete hydrolysis in the intestines. To increase protein digestibility, heating and drying were implemented; however, these methods reduce protein quality by causing denaturation, aggregation, and chemical modification of amino acids. In the present study, we observed that Lacticaseibacillus rhamnosus IDCC 3201 actively secretes proteases that hydrolyze milk proteins. Furthermore, we showed that co-administration of milk proteins and L. rhamnosus IDCC 3201 increased the digestibility and plasma concentrations of amino acids in a high-protein diet mouse model. Thus, food supplementation of L. rhamnosus IDCC 3201 can be an alternative strategy to increase the digestibility of proteins.

Galactomyces candidus diversity in the complex mycobiota of cow-milk bryndza cheese comprising antagonistic and sensitive strains

Galactomyces candidus (orthographic variant: Galactomyces candidum) is a heterogeneous species of Saccharomycetales that comprises dimorphic yeasts described previously under various names (e.g. Geotrichum, Dipodascus). Its strains are common components of the cheese surface mycobiota. This study identified genetically and physiologically heterogeneous G. candidus strains in the complex mycobiota of artisanal cow-milk bryndza samples. The traditional Slovak bryndza is a cheese produced from ewe's milk in cooler mountainous regions and from cow's milk in warmer low-land regions. The taxonomic analysis of the culturable yeasts of the latter version carried out in this study revealed considerable differences from the yeast biota previously described for ovine bryndza. However, the conventional D1/D2- and ITS-based barcode analyses could not assign unanimously all isolates to species because of the intragenomic barcode diversity in certain groups and the discordance between the D1/D2 and ITS results in other groups. The identified species and groups of isolates had different abilities to utilise the carbon and energy sources (lactose, lactate, lipids and proteins) available in milk and ripening cheese. The G. candidus strains did not metabolise lactose and lactate, hydrolysed milk proteins with diverse, usually moderate efficiency and only could grow on certain amino acids as only energy sources. Their preferred substrate was lipid. Under aerobic conditions, its hyphae penetrated the lipid droplets and degraded their content from inside by developing a dense internal mycelium. Sporulation and different MLST (multilocus sequence typing) patterns indicated that the Galactomyces strains could sexually interact and their genomes could recombine. The Galactomyces and Kluyveromyces isolates had antagonistic effects against other members of the mycobiota.

Impact of Flaxseed Gums on the Colloidal Changes and In Vitro Digestibility of Milk Proteins.

Flaxseed (Linum usitatissimum L.) mucilage is one of the most studied plant seed gums in terms of its techno-functional and health-promoting properties. Nonetheless, the interplay of flaxseed gum (FG) with other food biopolymers, such as milk proteins, under in vitro digestion conditions remains underexplored. The aim of the present work was to investigate the colloidal interplay between flaxseed gum (golden or brown) and milk proteins (sodium caseinate or whey protein isolate) under simulated in vitro digestion conditions and its relationship with the attained in vitro protein digestibility. The presence of flaxseed gum in the milk protein food models and in the oral food boluses obtained was associated with the occurrence of segregative microphase separation. Flaxseed gum exhibited a prominent role in controlling the acid-mediated protein aggregation phenomena, particularly in the sodium caseinate gastric chymes. The addition of FG in the food models was associated with a higher amount of intact total caseins and β-lactoglobulin at the end of the gastric processing step. Monitoring of the intestinal processing step revealed a very advanced cleavage of the whey proteins (&gt;98%) and caseins (&gt;90%). The degree of the milk protein hydrolysis achieved at the end of the intestinal processing was significantly higher in the systems containing flaxseed gum (i.e., 59-62%) than their gum-free protein counterparts (i.e., 46-47%). It was postulated that the electrostatic milk protein complexation capacity and, to a lesser extent, the thickening effect of flaxseed gum influenced the in vitro digestibility of the milk proteins.

Modeling Tool for Studying the Influence of Operating Conditions on the Enzymatic Hydrolysis of Milk Proteins.

Systematic modeling of the enzymatic hydrolysis of milk proteins is needed to assist the study and production of partially hydrolyzed milk. The enzymatic hydrolysis of milk proteins was characterized and evaluated as a function of the temperature and protease concentration using Alcalase, Neutrase and Protamex. Modeling was based on the combination of two empirical models formed by a logarithmic and a polynomial equation to correlate the kinetic constants and the operating conditions. The logarithmic equation fitted with high accuracy to the experimental hydrolysis curves with the three proteases (R2 &gt; 0.99). The kinetic constants were correlated with the operating conditions (R2 &gt; 0.97) using polynomial equations. The temperature and protease concentration significantly affected the initial rate of hydrolysis, i.e., the kinetic constant a, while the kinetic constant b was not significantly affected. The values for the kinetic constant a were predicted according to the operating conditions and they were strongly correlated with the experimental data (R2 = 0.95). The model allowed for a high-quality prediction of the hydrolysis curves of milk proteins. This modeling tool can be used in future research to test the correlation between the degree of hydrolysis and the functional properties of milk hydrolysates.

E-nose, E-tongue Combined with GC-IMS to Analyze the Influence of Key Additives during Processing on the Flavor of Infant Formula.

In order to analyze the influence of key additives during processing on the flavor of infant formula, the headspace-gas chromatography-ion mobility spectrometry, electronic tongue, and electronic nose techniques were used to evaluate flavor during the processing of stage 1 infant formula milk powder (0-6 months), including the analysis of seven critical additives. A total of 41 volatile compounds were identified, involving 12 aldehydes, 11 ketones, 9 esters, 4 olefins, 2 alcohols, 2 furans, and 1 acid. The electronic nose metal oxide sensor W5S had the highest response, followed by W1S and W2S, illustrating that these three sensors had great effects on distinguishing samples. The response results of the electronic tongue showed that the three sensory attributes of bitter, salty, and umami, as well as the richness of aftertaste, were more prominent, which contributed significantly to evaluating the taste profile and distinguishing among samples. Raw milk is an essential control point in the flavor formation process of stage 1 infant formula milk powder. Demineralized whey powder is the primary source of potential off-flavor components in hydrolyzed milk protein infant formula. This study revealed the quality characteristics and flavor differences of key additives in the production process of stage 1 infant formula milk powder, which could provide theoretical guidance for the quality control and sensory improvement of the industrialized production of infant formula.

A Method for Screening Proteases That Can Specifically Hydrolyze the Epitope AA83-105 of αs1-Casein Allergen.

Milk protein hydrolysates are common in infant formula, but some of them retain allergenicity due to incomplete hydrolysis of the epitopes for milk allergens. This study explored a method for screening proteases that could specifically hydrolyze the epitope of αs1-casein allergen. Firstly, the αs1-casein epitope AA83-105 was synthesized by the solid-phase synthesis method. Then, after purification and identification, the complete antigen was prepared through coupling with bovine serum albumin (BSA) and was used to raise monoclonal antibodies (mAb) in BALB/c mice. Additionally, an indirect competitive-enzyme-linked immunosorbent assay (icELISA) was established. The mAb raised against αs1-casein protein was used as a control. The results showed that the purity of the synthetic epitope was &gt;90%, and the coupling rate with BSA was 6.31. The mAb subtype is IgG1, with a titer of 1:320,000. The mAb reacted specifically with αs1-casein but did not cross-react with soybean protein. The linear regression equation of the competitive inhibition curve was y = -9.22x + 100.78 (R2 = 0.9891). The detection limit of icELISA method was more sensitive, and the method showed good accuracy and repeatability. The amounts of antigen residues in papain protease hydrolysates were relatively small, and the epitope fragment was detected in papain hydrolysate via mass spectrometry. This study provides ideas and methods for screening proteases that specifically hydrolyze the epitopes of milk allergens and also provides a superior foundation for the development of an advanced hypoallergenic formula.

Enzymatic hydrolysis of milk protein by complex enzyme mixture of alcalase and neutrase: Kinetic model and hydrolysis control

In order to achieve accurate control of the hydrolysis of cow milk protein, a kinetic model for the hydrolysis of milk protein by a complex enzyme composed of alcalase and neutrase was established. The kinetic model was degree of hydrolysis and the kinetic constants of k2, kd and c0 were 23.752 min−1, 3.545 min−1 and 1.495 × 10−3 g/L, respectively. The relationship between hydrolysis conditions, DH and molecular weight was further investigated and quantified, which contributes to the quality control of protein hydrolysates and also provides a theoretical basis for the control of milk protein hydrolysis by complex enzyme.

Premature delivery impacts the concentration of plasminogen activators and a plasminogen activator inhibitor and the plasmin activity in human milk.

Background and aimsPlasmin in human milk partially hydrolyzes milk proteins within the mammary gland and may enhance the hydrolysis of milk proteins within the infant’s stomach. This study examined the effects of extremely preterm (EP)-, very preterm (VP)-, and term-delivery on plasmin activity and the concentrations of plasminogen activators [urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA)], plasminogen activator inhibitor type 1 (PAI-1) and the complexes of PAI-1/uPA and PAI-1/tPA in human milk.Materials and methodsHuman milk samples were collected from mothers who delivered extremely preterm infants [24–27 weeks gestational age (GA), n = 20], very preterm infants (28–32 weeks GA, n = 12), and term infants (38–39 weeks GA, n = 8) during 2–72 days postnatally. Plasmin activity was determined using fluorometric substrate assay, whereas concentrations of uPA, tPA, PAI-1, the PAI-1/uPA complex and the PAI-1/tPA complex were quantified by ELISA.ResultsPlasmin activity, uPA and tPA were detected in all human milk samples, PAI-1 and the PAI-1/uPA complex were present in 42.5 and 32.5% of milk samples, respectively, and the PAI-1/tPA complex was not detected. Plasmin activity was correlated negatively with postnatal age and postmenstrual age (PMA) in the VP group and positively with postnatal age in the term group. uPA and tPA concentrations decreased with increasing postnatal age in both EP and VP groups but did not correlate in the term group. uPA concentration was correlated positively with GA in the VP group and tended to be elevated with increasing GA in the combined three groups. In contrast, tPA concentrations were correlated negatively with GA and PMA in the combined three groups (P < 0.008) and with PMA in the EP and VP groups. PAI-1 concentration tended to be correlated positively with postnatal age in the combined three groups. No correlation was detected with the PAI-1/uPA complex.ConclusionPremature delivery impacted the plasmin activity and the concentrations of uPA, tPA, and PAI-1 in human milk. Whether these changes in milk plasminogen activators and inhibitors have a role in balancing the proteolytic digestion of premature infants remains to be investigated.

Мультикомпонентные композиты нанокомплексов циклодекстрина с биологически активными веществами для функциональных продуктов питания

Enzymatic protein hydrolysates of milk are used as a protein component of functional foods intended for children, athletes, and senior citizens. They are easy to absorb and possess hypoallergenic, antioxidant, antimicrobial, and antimutagenic properties. However, the peptides in their composition have a bitter taste, which limits the use of milk protein hydrolysates in food industry. Functional foods are often fortified with fat-soluble vitamins and other hydrophobic ingredients. They require multicomponent compositions that contain both hydrophilic and hydrophobic compounds. Complexes of β-cyclodextrins with peptides of whey protein hydrolyzates and fat-soluble vitamins can solve this problem. &#x0D; The present research featured nanocomplexes of β-cyclodextrins with whey peptides and their multicomponent mixes with vitamins D3 and A. The methodology involved HPLC-MS, electrophoresis, thermogravimetry, and fluorimetry. &#x0D; The obtained clathrates were used to develop new multicomponent compositions for functional nutrition. The article introduces a new production method for hypoallergenic peptide fractions with a molecular weight of 300–1500 Da from enzymatic whey protein hydrolyzates. The obtained peptides contained 6–14 amino acid residues and demonstrated hypoallergenic properties because they contained no antigenic determinants capable of causing IgE synthesis. The complexes of inclusion contained hydrolyzate peptides of dairy proteins and fat-soluble vitamins A and D3. The research revealed some antioxidant and antimutagenic properties, as well as the toxicological and hygienic profile of the clathrates. The resulting peptide clathrates had a less bitter taste. The inclusion complexes of fat-soluble vitamins D3:β-cyclodextrins, and A:β-cyclodextrins could be converted from an olive oil solution into a soluble powder. 100 g of the multicomponent composite contained 47.0 g of whey protein hydrolyzate of low molecular weight fraction peptides, 1.06 mg of vitamin D3 (42 500 IU), 3.44 mg of vitamin A (10 000 IU), and 1.54 g of olive oil. The article also describes the structural and functional properties of the inclusion complexes. Nanocomplexes of whey protein hydrolyzate of low molecular weight fraction peptides:β-cyclodextrins, D3:β-cyclodextrins, and A:β-cyclodextrins and their multicomponent composite were tested for toxicological and hygienic properties using Tetrahymena pyriformis. They appeared to belong to the 5th hazard class in terms of the average lethal dose (non-hazardous substances). &#x0D; The obtained powder forms of fat-soluble vitamins and peptides are easily dosed and can be used to design new functional foods.

Relevance of Early Introduction of Cow's Milk Proteins for Prevention of Cow's Milk Allergy.

Food allergy incidence has increased worldwide over the last 20 years. For prevention of food allergy, current guidelines do not recommend delaying the introduction of allergenic foods. Several groundbreaking studies, such as the Learning Early About Peanut Allergy study, showed that the relatively early introduction of this allergenic food between 4–6 months of age reduces the risk of peanut allergy. However, less is known about the introduction of cow’s milk, as many children already receive cow’s-milk-based formula much earlier in life. This can be regular cow’s milk formula with intact milk proteins or hydrolyzed formulas. Several recent studies have investigated the effects of early introduction of cow’s-milk-based formulas with intact milk proteins on the development of cow’s milk allergy while breastfeeding. These studies suggest that depending on the time of introduction and the duration of administration of cow’s milk, the risk of cow’s milk allergy can be reduced (early introduction) or increased (very early introduction followed by discontinuation). The aim of this narrative review is to summarize these studies and to discuss the impact of early introduction of intact cow’s milk protein—as well as hydrolyzed milk protein formulas—and the development of tolerance versus allergy towards cow’s milk proteins.