Bioactive peptides from milk

bioactive peptides

Bioactive peptides: are milk products a source of healthy compounds?

Bioactive peptides in western diets derive mainly from milk consumption (Boutrou, Gwénaële and Sanchez-Rivera, 2015). These bioactive peptides have shown to have several health effects… at least in theory.

What are bioactive peptides? As many other animal products, milk is rich in proteins which can be divided in two big groups: whey (lactoferrin, albumin, a-lactalbumin, b-lactoglobulin, immunoglobulin, etc.) and casein proteins (a, b, g, k-caseins). The hydrolysis of milk proteins results in the production of many bioactive peptides. Whey proteins alone are able, once hydrolyzed, to produce approximately a hundred different peptides (Dalgalarrondo et al., 1995; García-Montoya et al., 2012).

Protein hydrolysis can occur at different stages: during milk secretion, storage, processing and digestion. This enzymatic hydrolysis occurs thanks to the diligent work of those enzymes that are naturally contained in milk, or of digestive and microbial enzymes derived from starter and non-starter cultures used in milk fermentation (Albenzio et al., 2017).

Yogurt and fermented cheese products usually contain bioactive peptides that are mainly derived from casein hydrolysis. The latter is performed by proteases and peptidases originating from milk, rennet, starter- and non-starter bacteria (Barać et al., 2017). Not all dairy products contain the same amount of peptides, since the degree at which they are formed is influenced by several factors, including the type of milk, the type of heat treatment applied (e.g. pasteurization, UHT), not to mention the stage and the conditions of ripening, as in the case of cheese (Barać et al., 2017). Cheese ripening process, in particular, includes several proteolytic, lipolytic and glycolytic processes (Roudot-Algaron et al., 1994; Singh, Fox and Healy, 1997). Since different dairy cultures have different proteolytic abilities, the type of probiotic used during cheese production also determines what type of peptides will originate.

Now that you know more about them, let me give you a few details about what makes bioactive peptides so interesting from a health perspective.

First of all, milk peptides seems to be responsible of several favorable health effects, including: immune-stimulatory, anti-inflammatory, antimicrobial effects (Korhonen et al., 1998; Korhonen and Pihlanto, 2006).

An interesting effect is the inhibition of Angiotensin-1 Converting Enzymes (ACE-1), which are involved in the regulation of blood pressure (Boutrou, Gwénaële and Sanchez-Rivera, 2015). Cheese, as a fermented product, represents a source of peptides with ACE-inhibitory activity (Paul and Van Hekken, 2011) and one could therefore hypothesize that its consumption could potentially contribute to a lower blood pressure. Some milk peptides seem also able to regulate glucose uptake in skeletal muscle (Horner, Drummond and Brennan, 2016).

However, the effects of milk peptides vary depending on several factors. Diet, gene-diet interactions, the individual gut microbiota or even the mastication process, can influence the extent at which dairy products can favorably influence health (Horner, Drummond and Brennan, 2016).

However, as I clearly explained in my latest speech at the International Conference of the Functional Food Center, we have one big problem:

bioactive peptides from milk have a very low (if not null) bioavailability (Mozaffarian and Wu, 2018)!


Too bad, right?


Let me get this straight: all the biological effects mentioned above, are largely dependent on the probability that milk peptides will remain intact until reaching the target organ (Segura-Campos et al., 2011). And, unfortunately, this probability is almost equal to zero…

Indeed, peptides are prone to extensive hydrolysis in the gastro-intestinal (GI) tract by stomach, small intestinal and brush border peptidases. As a result, most peptides never reach the absorption stage. Proteases are active all over in the GI tract: they can be found in the membrane’s villi, they are produced by the gut microflora, they are present in the brush border and even in plasma! As a matter of fact, the efflux of intact peptides into the general circulation system is negligible (Daniel, 2004).


Therapeutic use of peptides has remained limited due to their high instability in biological environments, rapid depuration from the blood, poor membrane transportability and effective digestion in the GI tract.


It is worth mentioning that the study of health effects related to exposure to milk peptides is further complicated by the fact that their biological effects may be masked by the presence of other healthy or unhealthy nutrients in the diet (Hansen et al., 1997). The presence of other food compounds can also influence both the susceptibility to peptidase degradation and their intestinal transport (Charman et al., 1997).To establish a cause-effect relationship between consumption of milk bioactive peptides and positive health effects, is therefore not so easy.

A lot of food companies have spent huge amounts of money trying to come up with new functional foods that could have beneficial health effects thanks to the presence of milk peptides in their composition. However, all attempts have failed so far, but not all hope is lost.

In my next post, I will explain how scientists are trying to increase the bioavailability of milk peptides. Stay tuned!


Did you know that?

Most of the data in the literature relate to peptides from cow milk cheeses, more investigations could reveal interesting properties of goat and sheep milk.



Albenzio, M. et al. (2017) ‘Bioactive Peptides in Animal Food Products’, Foods, 6(5), p. 35. doi: 10.3390/foods6050035.

Barać, M. B. et al. (2017) ‘White cheeses as a potential source of bioactive peptides’. Available at:ć-Pešić/94b9ae4b2be3c093b9f3af63d36cbf08cf163a80 (Accessed: 11 October 2018).

Boutrou, R., Gwénaële, H. and Sanchez-Rivera, L. (2015) ‘On the trail of milk bioactive peptides in human and animal intestinal tracts during digestion: A review’, Dairy Science and Technology, 95, pp. 815–829.

Calbet, J. A. L. and MacLean, D. A. (2002) ‘Plasma Glucagon and Insulin Responses Depend on the Rate of Appearance of Amino Acids after Ingestion of Different Protein Solutions in Humans’, The Journal of Nutrition, 132(8), pp. 2174–2182. doi: 10.1093/jn/132.8.2174.

Charman, W. N. et al. (1997) ‘Physicochemical and Physiological Mechanisms for the Effects of Food on Drug Absorption: The Role of Lipids and pH’, Journal of Pharmaceutical Sciences, 86(3), pp. 269–282. doi: 10.1021/js960085v.

Dalgalarrondo, M. et al. (1995) ‘Proteolysis of β-lactoglobulin and β-casein by pepsin in ethanolic media’, International Dairy Journal. Elsevier, 5(1), pp. 1–14. doi: 10.1016/0958-6946(94)P1595-5.

Daniel, H. (2004) ‘Molecular and Integrative Physiology of Intestinal Peptide Transport’, Annual Review of Physiology, 66(1), pp. 361–384. doi: 10.1146/annurev.physiol.66.032102.144149.

García-Montoya, I. A. et al. (2012) ‘Lactoferrin a multiple bioactive protein: An overview’, Biochimica et Biophysica Acta (BBA) – General Subjects, 1820(3), pp. 226–236. doi: 10.1016/j.bbagen.2011.06.018.

Hansen, M. et al. (1997) ‘Casein phosphopeptides improve zinc and calcium absorption from rice-based but not from whole-grain infant cereal.’, Journal of pediatric gastroenterology and nutrition, 24(1), pp. 56–62. Available at: (Accessed: 11 October 2018).

Horner, K., Drummond, E. and Brennan, L. (2016) ‘Bioavailability of milk protein-derived bioactive peptides: A glycaemic management perspective’, Nutrition Research Reviews, 29(1), pp. 91–101. doi: 10.1017/S0954422416000032.

Korhonen, H. et al. (1998) ‘Impact of processing on bioactive proteins and peptides’, Trends in Food Science & Technology. Elsevier, 9(8–9), pp. 307–319. doi: 10.1016/S0924-2244(98)00054-5.

Korhonen, H. and Pihlanto, A. (2006) ‘Bioactive peptides: Production and functionality’, International Dairy Journal, 16(9), pp. 945–960. doi: 10.1016/j.idairyj.2005.10.012.

Morifuji, M. et al. (2010) ‘Comparison of Different Sources and Degrees of Hydrolysis of Dietary Protein: Effect on Plasma Amino Acids, Dipeptides, and Insulin Responses in Human Subjects’, Journal of Agricultural and Food Chemistry, 58(15), pp. 8788–8797. doi: 10.1021/jf101912n.

Mozaffarian, D. and Wu, J. H. Y. (2018) ‘Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health’, Circulation Research, 122(2), pp. 369–384. doi: 10.1161/CIRCRESAHA.117.309008.

Nakamura, Y. et al. (1995) ‘Purification and Characterization of Angiotensin I-Converting Enzyme Inhibitors from Sour Milk’, Journal of Dairy Science, 78(4), pp. 777–783. doi: 10.3168/jds.S0022-0302(95)76689-9.

Nongonierma, A. B. and FitzGerald, R. J. (2015) ‘The scientific evidence for the role of milk protein-derived bioactive peptides in humans: A Review’, Journal of Functional Foods. Elsevier Ltd, 17, pp. 640–656. doi: 10.1016/j.jff.2015.06.021.

Paul, M. and Van Hekken, D. L. (2011) ‘Short communication: Assessing antihypertensive activity in native and model Queso Fresco cheeses1’, Journal of Dairy Science, 94(5), pp. 2280–2284. doi: 10.3168/jds.2010-3852.

Power, O., Hallihan, A. and Jakeman, P. (2009) ‘Human insulinotropic response to oral ingestion of native and hydrolysed whey protein’, Amino Acids, 37(2), pp. 333–339. doi: 10.1007/s00726-008-0156-0.

Roudot-Algaron, F. et al. (1994) ‘Phosptiopeptides from Comté Cheese: Nature and Origin’, Journal of Food Science. Wiley/Blackwell (10.1111), 59(3), pp. 544–547. doi: 10.1111/j.1365-2621.1994.tb05558.x.

Segura-Campos, M. et al. (2011) ‘Bioavailability of bioactive peptides’, Food Reviews International, 27(3), pp. 213–226. doi: 10.1080/87559129.2011.563395.

Singh, T. K., Fox, P. F. and Healy, A. (1997) ‘Isolation and identification of further peptides in the diafiltration retentate of the water-soluble fraction of Cheddar cheese.’, The Journal of dairy research, 64(3), pp. 433–43. Available at: (Accessed: 11 October 2018).

Uenishi, H. et al. (2012) Isolation and identification of casein-derived dipeptidyl-peptidase 4 (DPP-4)-inhibitory peptide LPQNIPPL from gouda-type cheese and its effect on plasma glucose in rats., International dairy journal. Elsevier Science. Available at: (Accessed: 11 October 2018).


Gianluca Tognon

Gianluca Tognon

Gianluca Tognon is an Italian nutrition coach, speaker, entrepreneur and associate professor at the University of Gothenburg. He started his career as a biologist and spent 15 years working both in Italy and then in Sweden. He has been involved in several EU research projects and has extensively worked and published on the association between diet, longevity and cardiovascular risk across the lifespan, also studying potential interactions between diet and genes. His work about the Mediterranean diet in Sweden has been cited by many newspapers worldwide including the Washington Post and The Telegraph among others. As a speaker, he has been invited by Harvard University and the Italian multi-national food company Barilla.

Leave a Replay

About Me

I’m an Italian nutrition coach, speaker, entrepreneur and associate professor at the University of Gothenburg. I started MY career as a biologist and spent 15 years working both in Italy and then in Sweden.

Recent Posts

Sign up for our Newsletter

We never send Spam