Nutraceuticals from milk bioactive peptides: solutions to the bioavailability problem

Nutraceuticals from milk peptides? Not an easy task!

In my previous post, I described the potential health effects of bioactive peptides derived from milk. In the same article though, I’ve also told you about the biggest problem that these peptides have: their extremely low bioavailability due to the fact that they get extensively hydrolyzed in the gastrointestinal tract.

This is bad news for the nutraceuticals industry, which was hoping to use these compounds for new, healthy food products. Indeed, the European Food Safety Authority (EFSA) has recently expressed a negative opinion about the effects of the bioactive peptide b-casomorphyn-7 on various health conditions, based on the fact that this peptide had a low characterization, low dose-response, low bioavailability, and potency.

But not all hope is lost.

There are some possibilities to increase the bioavailability of these compounds and, in this post, I would like to tell you a little about them. Are you ready? Let’s dig into this topic!

Milk bioactive peptides originate from the hydrolysis of dairy proteins such as caseins and whey proteins, and this phenomenon also happens during cheese ripening. You already know this. However, an appealing idea is to use milk bioactive peptides as ingredients in nutraceuticals and supplements. Also, tailor-made small peptides targeted at specific receptors and enzymes could also be developed, in order to obtain selected health effects.



…the effects observed by supplementing bioactive peptides might be smaller than those obtained with pharmaceutical drugs.


Despite this potential drawback, many researchers are still trying to come up with a strategy that could potentially increase the efficacy of milk peptides by enhancing their bioavailability. One important thing to know in this respect is the fact that these compounds possess (in theory) the ability to resist enzymatic degradation and this ability largely depends on their composition in terms of amino acids. For instance, the presence of proline and hydroxyproline in the sequence of a specific peptide makes the latter less likely to be degraded. Particularly relevant is the presence of these amino acids at the C- or N-terminal positions because the latter strongly influence the biological activity of peptides.

Unfortunately, not all milk peptides have a favorable amino acid composition that makes them resistant to enzymatic degradation. In this case, other strategies to increase the bioavailability are under study, including microencapsulation, lipidation, PEG-ylation, interfacial polymerization, spray-drying, solvent-evaporation, and other techniques. Obviously, increasing the administered dose can be a possible solution as well. However, some peptides might have a particularly low acceptance level by consumers, due to their tendency to have a bitter taste.

Enzyme-inhibitors and absorption enhancers have also been tested as strategies to “protect” milk peptides from degradation. Finally, carriers (such as lipid vesicles, colloidal carriers, liposomes, emulsions, etc.), can also be used with the same purpose.

Overall, I hope some interesting new nutraceuticals will be available soon on the market, although there is one last issue: the fact that we need better guidelines to evaluate the effects of these peptides on human health. Indeed, most studies were performed in vitro and the few that were performed in humans were often underpowered, meaning they recruited too few participants and they were not able to find significant results. Although they are expensive and tedious to conduct, double-blinded RCTs are the best practice and I hope to see more such studies in this field soon. Knowing the plasma concentrations and kinetics of orally-administered peptides will obviously be essential for planning future intervention studies.


Did you know that?

If their structure is known, bioactive peptides can also be synthesized.



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: 12 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.

Foltz, M., van der Pijl, P. C. and Duchateau, G. S. M. J. E. (2010) ‘Current In Vitro Testing of Bioactive Peptides Is Not Valuable’, The Journal of Nutrition, 140(1), pp. 117–118. doi: 10.3945/jn.109.116228.

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.

Nongonierma, A. B. and FitzGerald, R. J. (2015a) ‘Bioactive properties of milk proteins in humans: A review’, Peptides. Elsevier Inc., 73(0), pp. 20–34. doi: 10.1016/j.peptides.2015.08.009.

Nongonierma, A. B. and FitzGerald, R. J. (2015b) ‘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.

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


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.

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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.

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