Unraveling the Biological Properties of Whey Peptides and Their Role as Emerging Therapeutics in Immune Tolerance.

Whey is a natural by-product of the cheese-making process and represents a valuable source of nutrients, including vitamins, all essential amino acids and proteins with high quality and digestibility characteristics. Thanks to its different techno-functional characteristics, such as solubility, emulsification, gelling and foaming, it has been widely exploited in food manufacturing. Also, advances in processing technologies have enabled the industrial production of a variety of whey-based products exerting biological activities. The beneficial properties of whey proteins (WPs) include their documented effects on cardiovascular, digestive, endocrine, immune and nervous systems, and their putative role in the prevention and treatment of non-communicable diseases (NCDs). In this regard, research on their application for health enhancement, based on the optimization of product formulation and the development of pharmaceuticals, is highly relevant. Beyond the health and nutritionally relevant effects as in in vivo animal studies, the allergenicity of WPs and WP hydrolysates is also herein tackled and discussed, as well as their potential role as therapeutics for immune tolerance and so-called tolerogenic effects. Grounded on the WPs' health-promoting functions, this paper presents the latest research showing the potential of whey-derived peptides as an alternative strategy in NCD treatment. This work also reports a careful analysis of their current use, also revealing which obstacles limit their full exploitation, thus highlighting the future challenges in the field. Concluding, safety considerations, encompassing WP allergenicity, are also discussed, providing some insights on the role of WPs and peptides in milk allergen immunotolerance.