The Gliadin and Casein Metabolism: Synthesis of Gliadomorphin and Casomorphin and Their Biological Consequences

Authors

  • MD. Tanzimur Rahman Tamim Research Assistant https://orcid.org/0009-0009-1690-7946
  • Rashed Ahmed Department of Pharmaceutical Sciences, Associate Editor, NSU Journal of Student Research, North South University, Dhaka, Bangladesh

DOI:

https://doi.org/10.56778/rjhs.v3i2.474

Keywords:

Gliadomorphin, casomorphin, exorphins, gluten-free and casein-free (GFCF) diet, opioid receptors

Abstract

Gliadin (from gluten) and casein (from milk) are major dietary proteins that, upon incomplete digestion, yield biologically active opioid peptides known as gliadomorphin and casomorphin, collectively referred to as "exorphins." These peptides are increasingly recognized for their role in numerous physiological and pathological processes, particularly concerning the gut-brain axis. Methodology and Findings: This analysis describes the intricate enzymatic hydrolysis of gliadin and casein, resulting in the creation of these opioid peptides. Gliadomorphin and casomorphin are shown to cross the intestinal and blood-brain barriers, subsequently binding to opioid receptors. Their activity influences pain sensitivity, immunity, mood regulation, and mental processing. Emerging evidence suggests their involvement in disease states such as celiac disease, autism spectrum disorder (ASD), schizophrenia, and irritable bowel syndrome (IBS) through mechanisms involving altered neurotransmission, immune activation, inflammation, oxidative stress, and increased intestinal permeability. Interventions and future directions: Current and potential interventions focus on mitigating these harmful effects. Strategies include the consumption of gluten-free and casein-free diets, supplemental enzyme use (e.g., Dipeptidyl Peptidase IV/DPP-IV), modulation of the gut microbiota, and pharmacological interventions like opioid receptor antagonists and zonulin blockers. Future research necessitates the development of sophisticated diagnostic instruments and tailored nutritional regimens based on genetic and microbiome evaluations to formulate targeted therapeutic strategies. The metabolism of gliadin and casein into potent exorphins highlights a critical link between diet and the health of the gut, immune system, and brain. Further studies of gliadomorphin and casomorphin development promise novel therapeutic strategies for individuals affected by their biological activity.

Author Biography

MD. Tanzimur Rahman Tamim, Research Assistant

Department of Pharmaceutical Sciences

Associate Editor

NSU Journal of  Student Research

North South University, Dhaka, Bangladesh

References

Ahmed, R. (2024). Cyber Harassment in the Digital Age: Trends, Challenges, and Countermeasures. Computer Science and Mathematics. https://doi.org/10.20944/preprints202409.1882.v1

Ahmed, R. (2025). Human Metapneumovirus (HMPV): Epidemiology, Pathophysiology, Clinical Management, and Future Prospects in Treatment and Prevention. RADINKA JOURNAL OF HEALTH SCIENCE, 2(3), 312–327. https://doi.org/10.56778/rjhs.v2i3.417

Ahmed, R. & Tanzimur Rahman Tamim. (2025). Enhancing Medication Safety: The Role of Community and Hospital Pharmacists in Modern Healthcare Systems. RADINKA JOURNAL OF HEALTH SCIENCE, 2(3), 328–355. https://doi.org/10.56778/rjhs.v2i3.418

Autore, S., & De, S. (2021). Effects of COVID-19 on Global Healthcare Research and Management. https://doi.org/10.21467/preprints.314

Braconi, D., Bernardini, G., Millucci, L., & Santucci, A. (2018). Foodomics for human health: Current status and perspectives. Expert Review of Proteomics, 15(2), 153–164. https://doi.org/10.1080/14789450.2018.1421072

Chiarelli, R., Caradonna, F., & Naselli, F. (2024). Autophagy and nutrigenomics: A winning team against chronic disease and tumors. Frontiers in Nutrition, 11, 1409142. https://doi.org/10.3389/fnut.2024.1409142

Dhar, P. (2024). Advanced nutritional research from a physiological standpoint. INDIAN JOURNAL OF PHYSIOLOGY AND ALLIED SCIENCES, 76(01), 4–8. https://doi.org/10.55184/ijpas.v76i01.212

Di Cagno, R., De Angelis, M., Lavermicocca, P., De Vincenzi, M., Giovannini, C., Faccia, M., & Gobbetti, M. (2002). Proteolysis by Sourdough Lactic Acid Bacteria: Effects on Wheat Flour Protein Fractions and Gliadin Peptides Involved in Human Cereal Intolerance. Applied and Environmental Microbiology, 68(2), 623–633. https://doi.org/10.1128/AEM.68.2.623-633.2002

DiMagno, E. P. (1990). Fate of Pancreatic Enzymes During Gastrointestinal Transit. In H. G. Beger, M. Büchler, H. Ditschuneit, & P. Malfertheiner (Eds.), Chronic Pancreatitis (pp. 144–146). Springer Berlin Heidelberg. https://doi.org/10.1007/978-3-642-75319-0_17

Elder, J., Kreider, C., Schaefer, N., & deLaosa, M. (2015). A review of gluten- and casein-free diets for treatment of autism: 2005–2015. Nutrition and Dietary Supplements, 87. https://doi.org/10.2147/NDS.S74718

Foxx, R. M., & Mulick, J. A. (Eds.). (2015). The Gluten-Free, Casein-Free Diet. In Controversial Therapies for Autism and Intellectual Disabilities (0 ed., pp. 430–441). Routledge. https://doi.org/10.4324/9781315754345-35

Griffith, C., & La France, B. (2018). Neuro Effects of Opioids on the Human Brain. Biochemistry and Modern Applications, 6–8. https://doi.org/10.33805/2638-7735.113

Herrera, M. G., Zamarreño, F., Costabel, M., Ritacco, H., Hütten, A., Sewald, N., & Dodero, V. I. (2014). Circular dichroism and electron microscopy studies in vitro of 33‐mer gliadin peptide revealed secondary structure transition and supramolecular organization. Biopolymers, 101(1), 96–106. https://doi.org/10.1002/bip.22288

Khavkin, A. I., Vasia, M. N., & Novikova, V. P. (2022). The biological role of casomorphins (part 2): Role in human pathology. Experimental and Clinical Gastroenterology, 12, 110–118. https://doi.org/10.31146/1682-8658-ecg-196-12-110-118

Liu, Z., & Udenigwe, C. C. (2019). Role of food-derived opioid peptides in the central nervous and gastrointestinal systems. Journal of Food Biochemistry, 43(1), e12629. https://doi.org/10.1111/jfbc.12629

Nascimento, H. H. S., Oliveira, V. H. L. D., Reis, E. B. B. D., Souza, D. M., & Ferreira, M. B. (2022). Leaky gut – terapêutica e tratamento da síndrome do intestino permeável: Uma revisão bibliográfica. Research, Society and Development, 11(16), e513111638739. https://doi.org/10.33448/rsd-v11i16.38739

Nilsson, P. D., Newsome, J. M., Santos, H. M., & Schiller, M. R. (2019). Prioritization of Variants for Investigation of Genotype-Directed Nutrition in Human Superpopulations. International Journal of Molecular Sciences, 20(14), 3516. https://doi.org/10.3390/ijms20143516

Pomorska, D., Gach, K., & Janecka, A. (2015). Immunomodulatory Effects of Endogenous and Synthetic Peptides Activating Opioid Receptors. Mini-Reviews in Medicinal Chemistry, 14(14), 1148–1155. https://doi.org/10.2174/1389557515666150101095237

Reissmann, A. (2020). Gluten-free and casein-free diets in the management of autism spectrum disorder: A systematic literature review. Movement and Nutrition in Health and Disease, Vol. 4 (2020). https://doi.org/10.5283/MNHD.9

Saad, K., Shabaan, I., Hassan, A.-E.-M. M., Ezzat, M., Abouzed, M. A., Hamed, Y., Ibrahim, M. F. M., & Gad, E. F. (2024). Gluten-Free, Casein-Free Diet for Children with Autism Spectrum Disorder: A Case-Controlled Study. Journal of Pharmacy and Bioallied Sciences, 16(Suppl 1), S905–S908. https://doi.org/10.4103/jpbs.jpbs_1074_23

Shahnawaz, M., & Soto, C. (2021). Identification of biomarkers for diagnosing and monitoring therapy in the treatment of neurologic disorders. In Neurotherapeutics in the Era of Translational Medicine (pp. 291–310). Elsevier. https://doi.org/10.1016/B978-0-12-816475-4.00020-3

Singar, S., Nagpal, R., Arjmandi, B. H., & Akhavan, N. S. (2024). Personalized Nutrition: Tailoring Dietary Recommendations through Genetic Insights. Nutrients, 16(16), 2673. https://doi.org/10.3390/nu16162673

Sridhar Anakal & S. Soumya. (2024). Literature Review: The Use of AI in Healthcare. Journal of Scientific Research and Technology, 81–84. https://doi.org/10.61808/jsrt143

Stefanucci, A., Mollica, A., Macedonio, G., Zengin, G., Ahmed, A. A., & Novellino, E. (2018). Exogenous opioid peptides derived from food proteins and their possible uses as dietary supplements: A critical review. Food Reviews International, 34(1), 70–86. https://doi.org/10.1080/87559129.2016.1225220

Tarnowska, K., Gruczyńska–Sękowska, E., Kowalska, D., Majewska, E., Kozłowska, M., & Winkler, R. (2023). The opioid excess theory in autism spectrum disorders—Is it worth investigating further? Critical Reviews in Food Science and Nutrition, 63(19), 3980–3993. https://doi.org/10.1080/10408398.2021.1996329

Ul Haq, M. R. (2020). Significant Food-Derived Opioid Peptides. In M. R. Ul Haq, Opioid Food Peptides (pp. 1–20). Springer Singapore. https://doi.org/10.1007/978-981-15-6102-3_1

Wageningen University & Research, & Fj Savelkoul, H. (2017). Treating Autism Spectrum Disorder with Gluten-Free and Casein-Free Diet: The Underlying Microbiota-Gut-Brain Axis Mechanisms. Clinical Immunology & Immunotherapy, 3(1), 1–11. https://doi.org/10.24966/CIIT-8844/100009

Woodford, K. B. (2021). Casomorphins and Gliadorphins Have Diverse Systemic Effects Spanning Gut, Brain and Internal Organs. International Journal of Environmental Research and Public Health, 18(15), 7911. https://doi.org/10.3390/ijerph18157911

Zafirovski, K., Aleksoska, M. T., Thomas, J., & Hanna, F. (2024). Impact of Gluten-Free and Casein-Free diet on the quality of life of Autistic children and Adolescents: A Scoping review. Public Health and Healthcare. https://doi.org/10.20944/preprints202405.2068.v1

Zhu, C. H. (2024). Advances in Research on the Relationship between Diet, Gut Microbes, and Health. Journal of Clinical and Nursing Research, 8(8), 213–217. https://doi.org/10.26689/jcnr.v8i8.7712

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Published

2025-11-24

How to Cite

Mr. MD.TANZIMUR RAHMAN TAMIM, M. M. R. T., & Rashed Ahmed. (2025). The Gliadin and Casein Metabolism: Synthesis of Gliadomorphin and Casomorphin and Their Biological Consequences . RADINKA JOURNAL OF HEALTH SCIENCE, 3(2), 486–502. https://doi.org/10.56778/rjhs.v3i2.474