10 Mar 2025
5 min read
by YINI Editorial team
Nutri-dense food

The secret life of dairy: Exploring the health potential of milk peptides

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Research on dairy food nutrition has conventionally focused on the composition and effects of individual nutrients. More recently, researchers have started to investigate the impact of the dairy matrix – including interactions between its components and the effects of food processing – on nutrition. This article focuses on the effects of specific milk peptides, a diverse group of bioactive compounds that can now be studied, classified and described.

A ripple of excitement is passing through the world of nutrition research as studies reveal that the health benefits of milk and dairy products go far beyond its role as a source of nutrients such as calcium and protein. It seems that milk also holds hitherto hidden treasures, in the form of tiny protein fragments. These bioactive peptides are released during processing, fermentation or digestion and are gaining attention for their health benefits.

A comprehensive database of bioactive dairy peptides

When dairy proteins, such as casein and whey, are partially digested, they break down into bioactive peptides. These peptides act as biological messengers, influencing several body functions and potentially boosting health in ways we’re only just beginning to understand.

Now, food scientists at Aarhus University in Denmark and Oregon State University in the USA have compiled a detailed catalogue of over 600 unique peptides across different milk types, bringing together decades of research. Recently, they updated this database to include newly-discovered milk peptides, gathering the latest findings on their diverse functions from lab, animal, and human studies (1).

Bioactive milk peptides have multiple functions

Results from the database show that dairy bioactive peptides have an array of poten­tial sites of action throughout the body – including the oral cavity, stomach, intestine, pancreas, liver, immune system, skeletal system, adipose tissue, muscle, nervous system and skin – although their ability to reach these sites in the human body has not yet been studied.

The search for newly published bioactive milk peptides identified an additional 202 peptides matched to specific functions, increasing the number of unique peptide sequence-function combinations within the database by 20%. These new peptides have a range of functions including:

  • Anti-oxi­dant; 70 peptides
  • Angiotensin-converting enzyme (ACE)-inhibitory – relating to blood pressure control; 44 peptides
  • Dipeptidyl peptidase-4 (DPP-IV)-inhibitory – relating to blood sugar control; 20 peptides
  • Anti-inflammatory; 15 peptides
  • Anti-microbial; 14 peptides

Among the 202 bioactives peptides, the researchers identified a total of 143 unique peptide sequences increasing the number of unique dairy bioactive peptides in the database by 14%. and 59 peptide sequences were attributed with more than one function. Most of these were derived from dairy casein proteins.

Bioactive milk peptides may resuls in multiple health benefits

The database results suggest that bioactive dairy peptides may influence a number of specific health areas including cardiovascu­lar (458 known bioactive peptides), gut (212 peptides), metabolic (83 peptides), immune (51 peptides), or bone health (12 peptides):

  • Cardiovascular health: The main functions of bioactive dairy peptides that might affect cardiovas­cular health are anti-oxidant, anti-hypertensive and ACE-inhibitory effects. A smaller number of peptides have demonstrated anti-inflammatory, anti-thrombin and anti-cholesterol effects in pre-clinical trials (2,3).
  • Gut health: Several biological functions of bioactive dairy peptides – including anti-microbial, digestive and mucin secretion effects – relate to gut health (4,5,6). The gastrointestinal system is one of the most likely sites of action for those bioactive peptides, and several studies have investigated the complex mixture of peptides produced in the gut after consuming dairy foods.
  • Metabolic health: Many pre-clinical studies show DPP-IV inhibitory activity of bioactive dairy peptides, which helps suppress glucagon synthesis, increasing insulin release and thus lowering blood glucose levels.Other bioactive peptides can enhance insulin signalling or promote pancreatic β-cell regeneration (7).
  • Immune health: Bioactive dairy peptides can stimulate or inhibit various functions of the immune system by interacting with a host of immune-related cells. Some dairy-derived immunomodulatory peptides are studied for their potential effect in immunotherapy as they are likely to lack unwanted side effects. Other peptides may have the potential to allevi­ate inflammation (8).
  • Cancer: Some bioactive peptides have been found to have potential anti-cancer activity, causing cancer cell death and suppressing tumour cell invasiveness in pre-clinical studies (9).
  • Bone health: Consuming dairy has been shown to promote bone formation in humans and animals. One type of bioactive peptides – casein phosphopeptides – potentially enhances the absorption of calcium, essential for bone health (10).

What is the relevance of milk bioactive peptide research?

The dairy bioactive peptide database is the most comprehen­sive database, covering all relevant functions. The researchers believe the database will help drive future research on the bioactivities of dairy peptides.

In the future, bioactive dairy peptides could be used as value-added food ingredients, supplements or medicines. For example, some milk peptides may have uses in food preservation such as antimicrobial peptides to prolong shelf-life or antioxidants to prevent oxidative changes to foods. Milk peptides may have fewer side-effects than traditional small-molecule drugs since they have evolved for safe nourishment and development of babies and infants.

“Overall, milk and milk products contain an immense array of known functional peptides that could affect cardiovascu­lar, immunological, digestive and skeletal health, as well as potentially glycaemic control, cancer development, skin health and the nervous system.”

Nielsen SD, et al., 2024

References
  1. (1)  Nielsen SD, Liang N, Rathish H, Kim BJ, Lueangsakulthai J, Koh J, Qu Y, Schulz HJ, Dallas DC. Bioactive milk peptides: an updated comprehensive overview and database. Crit Rev Food Sci Nutr. 2024 Nov;64(31):11510-11529.
  2. (2) Rojas-Ronquillo, R., A. Cruz-Guerrero, A. Flores-Nájera, G. Rodríguez-Serrano, L. Gómez-Ruiz, J. P. Reyes-Grajeda, J. Jiménez-Guzmán, and M. García-Garibay. 2012. Antithrombotic and angiotensin-converting enzyme inhibitory properties of peptides re­leased from bovine casein by Lactobacillus casei Shirota. International Dairy Journal 26 (2):147–54
  3. (3) Jiang, X. X., D. D. Pan, T. Zhang, C. Liu, J. X. Zhang, M. Su, Z. Wu, X. Q. Zeng, Y. Y. Sun, and Y. X. Guo. 2020. Novel milk casein-derived peptides decrease cholesterol micellar solubility and cholesterol in­testinal absorption in Caco-2 cells. Journal of Dairy Science 103 (5):3924–36. doi: 10.3168/jds.2019-1758
  4. (4) Magana, M., M. Pushpanathan, A. L. Santos, L. Leanse, M. Fernandez, A. Ioannidis, M. A. Giulianotti, Y. Apidianakis, S. Bradfute, A. L. Ferguson, et al. 2020. The value of antimicrobial peptides in the age of resistance. The Lancet. Infectious Diseases 20 (9):e216–e230.
  5. (5) Kaur, J., V. Kumar, K. Sharma, S. Kaur, Y. Gat, A. Goyal, and B. Tanwar. 2020. Opioid peptides: An overview of functional signifi­cance. International Journal of Peptide Research and Therapeutics 26 (1):33–41.
  6. (6) Fernández-Tomé, S., and B. Hernández-Ledesma. 2020. Gastrointestinal digestion of food proteins under the effects of released bioactive peptides on digestive health. Molecular Nutrition & Food Research 64 (21):e2000401
  7. (7) Acquah, C., C. K. O. Dzuvor, S. Tosh, and D. Agyei. 2022. Anti-diabetic effects of bioactive peptides: Recent advances and clinical implica­tions. Critical Reviews in Food Science and Nutrition 62 (8):2158–71
  8. (8) Sowmya, K., M. I. Bhat, R. K. Bajaj, S. Kapila, and R. Kapila. 2019. Buffalo milk casein derived decapeptide (YQEPVLGPVR) having bi­functional anti-inflammatory and antioxidative features under cellu­lar milieu. International Journal of Peptide Research and Therapeutics 25 (2):623–33
  9. (9) Bielecka, M., G. Cichosz, and H. Czeczot. 2022. Antioxidant, antimicro­bial and anticarcinogenic activities of bovine milk proteins and their hydrolysates - a review. International Dairy Journal 127:105208.
  10. (10) Ahn, C.-B., and J.-Y. Je. 2019. Bone health-promoting bioactive pep­tides. Journal of Food Biochemistry 43 (1):e12529.