Cow milk allergy: Its clinical aspects, mechanisms, and innovative mitigation strategies beyond enzymatic hydrolysis

Cow milk allergy (CMA) is one of the most common food allergies. Traditional methods for reducing milk allergenicity, such as enzymatic hydrolysis, have limitations, including incomplete allergen degradation and the potential for residual allergenicity. This review aims to provide the current understanding of CMA, including its risk factors, allergen profile, immune mechanisms, and management strategies. It then examines the role of enzymatic hydrolysis in mitigating allergenicity, its applications, and its inherent limitations. Finally, the discussion turns to emerging innovative strategies such as high-pressure processing, pulsed electric fields, advanced glycation end-product modification, and recent advancements in biotechnology, such as CRISPR-Cas9 and microbial engineering which are designed to more effectively degrade cow milk allergens. These approaches aim to reduce allergenicity while preserving the nutritional and functional properties of milk, offering potential advancements in the field, and setting the stage for future directions in both research and clinical practice. • The current understanding of cow milk allergy is presented. • The role of enzymatic hydrolysis against allergenicity and its limitations are described. • More effective innovative strategies that can degrade cow milk allergens are discussed.