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How processing may affect milk protein digestion and overall physiological outcomes: A systematic review
Open accessAbstract
Dairy is one of the main sources for high quality protein in the human diet. Processing may, however, cause denaturation, aggregation, and chemical modifications of its amino acids, which may impact protein quality. This systematic review covers the effect of milk protein modifications as a result of heating, on protein digestion and its physiological impact. A total of 5363 records were retrieved through the Scopus database of which a total of 102 were included. Although the degree of modification highly depends on the exact processing conditions, heating of milk proteins can modify several amino acids. In vitro and animal studies demonstrate that glycation decreases protein digestibility, and hinders amino acid availability, especially for lysine. Other chemical modifications, including oxidation, racemization, dephosphorylation and cross-linking, are less well studied, but may also impact protein digestion, which may result in decreased amino acid bioavailability and functionality. On the other hand, protein denaturation does not affect overall digestibility, but can facilitate gastric hydrolysis, especially of β-lactoglobulin. Protein denaturation can also alter gastric emptying of the protein, consequently affecting digestive kinetics that can eventually result in different post-prandial plasma amino acid appearance. Apart from processing, the kinetics of protein digestion depend on the matrix in which the protein is heated. Altogether, protein modifications may be considered indicative for processing severity. Controlling dairy processing conditions can thus be a powerful way to preserve protein quality or to steer gastrointestinal digestion kinetics and subsequent release of amino acids. Related physiological consequences mainly point towards amino acid bioavailability and immunological consequences.
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“The decline from d 0 to d 20 likely resulted from the conversion of residual lactose into lactic acid, whereas the subsequent rise from d 20 to d 30 may be due to the formation of alkaline compounds from protein degradation (van Lieshout et al., 2020).”
From Impact of lactic acid bacteria coculture on the quality characteristics of goat cheese during ripening (2025) · cites this paper as van Lieshout et al., 2020
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Cites
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & for the PRISMA Group (2009) · BMJ · doi:10.1136/bmj.b2535 · Cited by 83,823
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & The PRISMA Group (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000097 · Cited by 64,042 · cited 1×
“Database search results according the PRISMA statement (Moher et al. 2009).”
INFOGEST static in vitro simulation of gastrointestinal food digestion
Brodkorb, A., Egger, L., Alminger, M., Alvito, P., Assunção, R., Ballance, S., Bohn, T., Bourlieu-Lacanal, C., Boutrou, R., Carrière, F., et al. (2019) · Nature Protocols · doi:10.1038/s41596-018-0119-1 · Cited by 5,199 · cited 1×
“In this respect, it is recommended to adopt a straightforward harmonized approach, as e.g. recently discussed by the INFOGEST network (Brodkorb et al. 2019).”
MethodWalstra, P., Walstra, P., Wouters, J. T. M., & Geurts, T. J. (2005) · doi:10.1201/9781420028010 · Cited by 1,788
Advanced glycation endproducts in food and their effects on health
Poulsen, M. W., Hedegaard, R. V., Andersen, J. M., de Courten, B., Bügel, S., Nielsen, J., Skibsted, L. H., & Dragsted, L. O. (2013) · Food and Chemical Toxicology · doi:10.1016/j.fct.2013.06.052 · Cited by 751
Scientific Opinion on Dietary Reference Values for protein
EFSA Panel on Dietetic Products, N. A. A. (. (2012) · EFSA Journal · doi:10.2903/j.efsa.2012.2557 · Cited by 739
Effect of heating on Maillard reactions in milk
van Boekel, M. A. J. S. (1998) · Food Chemistry · doi:10.1016/s0308-8146(98)00075-2 · Cited by 578
Towards microbial fermentation metabolites as markers for health benefits of prebiotics
Verbeke, K. A., Boobis, A. R., Chiodini, A., Edwards, C. A., Franck, A., Kleerebezem, M., Nauta, A., Raes, J., van Tol, E. A. F., & Tuohy, K. M. (2015) · Nutrition Research Reviews · doi:10.1017/s0954422415000037 · Cited by 343 · cited 1×
“…fermentation, microbiome protein fermentation is less extensively researched and the toxic potential of these compounds is predominantly derived from in vitro cell-toxicity and animal studies determining effects of purified individual protein fermentation by-products (Verbeke et al. 2015).”
BackgroundThe role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases
Maessen, D. E., Stehouwer, C. D. A., & Schalkwijk, C. G. (2015) · Clinical Science · doi:10.1042/cs20140683 · Cited by 342 · cited 1×
“The group where RAGE and AGER1 was increased also had the highest urinary excretion of the AGE methylglyoxal-derived hydroimidazolone, which is associated with age-related diseases (Maessen, Stehouwer, and Schalkwijk 2015).”
BackgroundFriedman, M. (1999) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf981000+ · Cited by 339 · cited 1×
“Several reviews already describe the effect of heating on food proteins in general (Friedman 1999; Gerrard et al. 2012; Mauron 1990).”
Background
Research works printed but not linked: 4
- Delorenzi N. J., 2011, Whey: Types, composition and health implications, 169
- Erbersdobler H., 1989, Bibliotheka Nutrio et Dieta, 43, 140
- 10.1021/jf981000 + · DOI
- Liusuwan R. A., 1996, FASEB Journal, 10
Cited by
Sorted by citations
Items 201–254 of 254
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Rendón-Rosales, M. Á., Torres‐Llanez, M. J., García‐Romo, J. S., Beltrán‐Barrientos, L. M., Mazorra-Manzano, M. A., Hernández‐Mendoza, A., González-Córdova, A. F., & Vallejo‐Córdoba, B. (2026) · Food Research International · doi:10.1016/j.foodres.2026.118405 · Cited by 1
Daniloski, D., McCarthy, N. A., Vasiljevic, T., Sharma, N., Fitzpatrick, C. J., Brodkorb, A., Le, T. T., Knudsen, L. J., Larsen, L. B., & Poulsen, N. A. (2026) · Food Chemistry · doi:10.1016/j.foodchem.2026.148157 · Cited by 1
Xu, Y., Wu, K., Wei, B., Song, G., Sun, C., Li, X., Liu, X., Ma, Z., Lv, M., Landman, J., et al. (2026) · Advanced Science · doi:10.1002/advs.202522455 · Cited by 3
Li, X., He, X., Huang, Z., Liu, X., Zhang, J., Gao, Y., Li, Q., & Yu, X. (2026) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.70483 · Cited by 1
Cheng, H., Chen, W., Yin, W., Tao, X., Liu, D., Huppertz, T., Liu, X., & Zhou, P. (2026) · Food Bioscience · doi:10.1016/j.fbio.2026.109123 · Cited by 1
Munhóz, B. A., Angelo, C. G., Silva, N. C., de Sousa, V. C., Lopes, A. D. S., & Baptista, D. P. (2026) · Food Research International · doi:10.1016/j.foodres.2026.119612 · Cited by 1
Processing Effects on Quinoa Protein Digestibility and Functional Properties: A Comprehensive Review
Bravo-Reyes, C., Opazo‐Navarrete, M., Chacón-Fuentes, M., Burgos‐Díaz, C., Armijo-Godoy, G., Domínguez-Valencia, R., & Lorenzo, J. M. (2026) · Current Food Science and Technology Reports · doi:10.1007/s43555-026-00088-w · Cited by 1
From Intermolecular Poses to Thermodynamics Using Subdivided Spheres
Vinterbladh, I., Bye, J., Curtis, R., Hatch, H., Grudinin, S., & Lund, M. (2026) · Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.6c01665 · Cited by 3
Human Milk as a Model for Next-Generation Infant Formula: Opportunities and Challenges
Ryan, M. B., Swackhamer, C., Donovan, S. M., Smilowitz, J. T., Kim, J. H., Stewart, C. J., Kuehn, D., Rauner, G., Hettinga, K. A., Demmer, E., et al. (2026) · Advances in Nutrition · doi:10.1016/j.advnut.2026.100710 · Cited by 1
“For example, glycation reactions reduce protein digestibility and amino acid absorption [144].”
Self-citationUnravelling elusive mysteries of bovine milk proteins by mass spectrometry
Gazi, I. (2023) · Utrecht University Repository (Utrecht University) · doi:10.33540/1904 · Cited by 1
Toxicological consequences of the Maillard reaction
Timme, V. D. L. (2020) · Research Publications (Maastricht University) · doi:10.26481/dis.20200918tl
Effect of Homogenization on Protein, Fat Structure and in vitro Protein Digestibility in Milk
Shetty, S. S., & Sharma, K. (2022) · Asian Journal of Dairy and Food Research · doi:10.18805/ajdfr.dr-1863
“Effect of homogenization is enhanced by intensive heat treatment by improving organization of whole milk and health properties (Van Lieshout et al. 2019).”
Protein digestion kinetics, a proxy for postprandial amino acid responses
Abrahamse, E. (2022) · doi:10.18174/568446
The Impact Of Dietary Advanced Glycation Endproducts
Linkens, A. M. A. (2022) · Research Publications (Maastricht University) · doi:10.26481/dis.20221005al
Russell, J. S., Khorozova, Y., Mehta, A., & Serventi, L. (2023) · Sustainable development goals series · doi:10.1007/978-3-031-12358-0_4
Effect of thermal processing on the digestion of dairy proteins
Ye, A., Li, S., & Roy, D. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-95052-7.00016-9
Modern adapted infant formulas: problem status and prospects for solving
Dmitriev, A. V., Gudkov, R. A., Petrova, V. I., Fedina, N. V., & Zaplatnikov, A. L. (2023) · Meditsinskiy sovet = Medical Council · doi:10.21518/ms2023-336
Pu, Z., Zhang, L., Zhang, K., Han, M., Hou, Y., Zhao, Y., & Zhou, P. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4668886
Munir, M., Nadeem, M., Qureshi, T. M., Gamlath, C. J., Ahmad, I., & Ashokkumar, M. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4788390
Casein: types, applications and gastric digestion
El-Bakry, M. M. A.-R., & Mehta, B. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15836-0.00020-2
Do Technological Operations Have an Impact on the Nutritional Properties of Dairy Products?
Gaucheron, F., & Boyer, C. (2024) · doi:10.1002/9781394312405.ch5
The challenges associated with a low protein diet (Review)
Qi, X., & Tester, R. F. (2025) · International Journal of Functional Nutrition · doi:10.3892/ijfn.2025.43
“…ileal digestibility is enhanced by heat‑pre‑treatment (63); b) milk protein denaturation (through cooking) does not affect overall digestibility (64); c) not specifically on the protein molecules per se, cooking improves plant protein quality (65); d) although discussing cereal proteins in the…”
Inhibition of Glyoxal‐Induced Protein Glycation by Quercetin in a Simulated Dairy System
Xu, J., Zhang, Y., Hu, Z., Du, Z., Xie, B., Hu, C., Liu, J., & Zhu, Q. Y. (2025) · Journal of Food Science · doi:10.1111/1750-3841.70252
The possibilities and contradictions of primary prevention of food allergies in early childhood
Dmitriev, A. V., Gudkov, R. A., Fedina, N. V., Petrova, V. I., & Zaplatnikov, A. L. (2025) · Экспериментальная и клиническая гастроэнтерология · doi:10.31146/1682-8658-ecg-233-1-99-106
Yu, Y., Zhang, L., Yan, D., Huppertz, T., & Zhou, P. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5365428
Fan, X., Qiu, L., Huang, L., Zhu, W., Tu, X., Gao, X., & Miao, Y. (2025) · Journal of Food Biochemistry · doi:10.1155/jfbc/5593333
Yu, Y., Zhang, L., Yan, D., Huppertz, T., & Zhou, P. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5688497
Csighy, A., Abdisa, K. B., Bánvölgyi, S., Lakner, Z., Szerdahelyi, E., Friedrich, L., Molnár, M. A., Nath, A., & Koris, A. K. (2025) · Progress in Agricultural Engineering Sciences · doi:10.1556/446.2025.00254
Cheng, H., Chen, W., Yin, W., Tao, X., Liu, D., Huppertz, T., Liu, X., & Zhou, P. (2026) · SSRN Electronic Journal · doi:10.2139/ssrn.6294692
Methodological approaches to assess protein digestibility with an emphasis on plant-derived foods
Accardo, F., Cutroneo, S., Calcinai, L., & Tedeschi, T. (2026) · Advances in food and nutrition research · doi:10.1016/bs.afnr.2026.03.003
Study of Alfalfa and Flaxseed Gums as Co-structurants in Probiotic Cryogel Scaffolds
Hellebois, T. (2023) · theses.fr (ABES) · doi:10.70675/7fc5548fz9c8fz4f0cza206z7f499edd9246
Milk reduces severity of dextran sulfate sodium induced colitis in rats
Sasaki, R., Noborio, S., Taoka, Y., Yamamoto, K., & Okada, K. (2026) · Academia Immunity and Disease · doi:10.20935/acadimmunodis8219
Mahapatra, S., Zeng, M., van Pijkeren, J., Paul, M., Thatoi, H., Oh, J., & Pan, X. (2026) · SSRN Electronic Journal · doi:10.2139/ssrn.6629799
Chapelain, T., Echeverry-Munera, J., Wilms, J. N., Costa, J. H. C., & Steele, M. A. (2026) · animal · doi:10.1016/j.animal.2026.101852
Chang, C., He, J., Wu, R., Gao, Z., Fang, F., Zhang, D., & Wang, Z. (2026) · Food Chemistry · doi:10.1016/j.foodchem.2026.149480
Feller, N., Föste, M., Hörmann, H., Verheyen, C., & Jekle, M. (2026) · European Food Research and Technology · doi:10.1007/s00217-026-05136-2
Yan, H., Wang, C. Y., Lu, X., Liu, L., & Shen, Y. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1882160
“The reduction in protein digestibility is primarily attributed to the obstruction of enzymatic cleavage sites by glycation, which may occur through the direct blocking of lysine residues, the indirect masking of cleavage sites, and steric hindrance resulting from protein cross-linking (9, 10).”
Exploring protein digestion in water buffalo milk vs. holstein milk: An in vitro comparative study
Wang, X., Gao, Y., Chai, H., Yang, K., Liao, J., Zhang, C., Wei, J., Ren, F., Wang, P., & Wang, Y. (2026) · Food Chemistry · doi:10.1016/j.foodchem.2026.150430
Digestion of whey and its products
Charris-Barreto, J. C., Quintanilla‐Carvajal, M. X., & Mehta, B. M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-27648-4.00008-6
Song, J., Huang, J., Lan, Y., Miao, R., Tang, Z., Wu, J., Yu, M., Bliki, K., Skirtach, A. G., Zhu, S., et al. (2026) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.70649
Hassan, S. M., Teka, T. A., Mahamed, S. A., Duale, M. M., Awale, A. T., & Urugo, M. M. (2026) · Food Chemistry X · doi:10.1016/j.fochx.2026.104459
“…prolonged heating, and severe drying conditions may produce different degrees and types of modification, and findings from one processing configuration should not automatically be generalized to all thermal treatments (Alhaj et al., 2026 ; Y. Wang et al., 2024 ; van Lieshout et al., 2020 ).”
Alonso‐Miravalles, L., Widmer, C., Gianfrancesco, A., Johnson, N. B., & Le, H. D. (2026) · Journal of Dairy Science · doi:10.3168/jds.2026-28906
Tan, Y., Xiang, H., Cao, Y., Lyu, S., Tao, W., Chen, C., Wu, J., Zhang, X., & Sun, X. (2026) · International Dairy Journal · doi:10.1016/j.idairyj.2026.106844
Leenders, L. M., Casagranda, S., Balvers, M. G. J., de Gier, G., Lambers, T. T., & Smeets, P. A. M. (2026) · medRxiv · doi:10.64898/2026.09.23.26363226
Self-citationTruzzi, F., Salvatore, S., Agosti, M., Marzocchi, S., Pasini, F., Caboni, M. F., & Dinelli, G. (2026) · Dairy · doi:10.3390/dairy7050086
Metadata
- Authors
- van Lieshout, G. A. A., Lambers, T. T., Bragt, M. C. E., & Hettinga, K. A.
- Affiliations
- FrieslandCampina, Amersfoort, the Netherlands
- FrieslandCampina (Netherlands) (NL)
- Wageningen University & Research (NL)
- Corresponding author
- Hettinga, Kasper A.
- Venue
- Critical Reviews in Food Science and Nutrition
- Publisher
- Informa UK Limited
- Published
- 2019-08-22
- Volume
- 60
- Issue
- 14
- Pages
- 2422-2445
- ISSN
- 1040-8398 (ISSN-L)
- 1549-7852
- OpenAlex
- W2969873245
- Cited by
- 254
- References
- 127
- Citations by year
- 2026: 30 · 2025: 40 · 2024: 34 · 2023: 48 · 2022: 41 · 2021: 36 · 2020: 24 · 2019: 1
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Critical Reviews in Food Science and Nutrition (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Proteins in Food Systems
- Life Sciences › Agricultural and Biological Sciences › Food Science › Protein Hydrolysis and Bioactive Peptides
- Life Sciences › Agricultural and Biological Sciences › Food Science › Food Nutrient Composition and Product Development
- Keywords
- milk protein digestion, dairy processing, heat treatment (food and biological processing), protein denaturation, glycation, amino acid bioavailability, lysine, protein oxidation, protein cross-linking, β-lactoglobulin, gastric emptying, protein quality
- MeSH terms
- Amino Acids, Animals, Digestion, Hot Temperature, Heating, Humans, Milk, Milk Proteins, Protein Denaturation, Pasteurization
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