Year 2021, Volume 7 , Issue 2, Pages 128 - 137 2021-03-09

A1 Milk and Beta-casomorphin-7

Seval ANDİÇ [1] , Rozelin Münevver AYAZ [2] , Şehriban OĞUZ [3]

Milk is composed of water, proteins, lipids, lactose, vitamins, and minerals. More than 80% of most mammals’ milk proteins are constituted by caseins. Casein is a group of proteins and they are sub-divided into αs1-, αs2-, β- and β-casein families. Among these casein families, -casein is the second most abundant protein. Different mutations in the cow milk β-casein gene led to 12 genetic variants and most common of these are genetic variants A1 and A2. The A1 and A2 variants differ only at amino acid position 67, which is histidine in A1 or proline in A2 milk. This difference in amino acid sequence suggests a conformational change in the secondary structure of the expressed β-casein. Milk that contains A1 β-casein and A2 β-casein are known as A1 milk and A2 milk, respectively. A1 β-casein milk releases an amino acid bioactive peptide called beta-casomorphin-7 (βCM-7) in small intestine. Beta-casomorphin-7 released from A1 β-casein is responsible for many human disorders like type-1 diabetes, autism, schizophrenia, alzheimer’s disease (AD), attention deficit hyperactivity disorder (ADHD), multiple sclerosis (MS) and heart diseases.
A1 Milk, A2 Milk, βCM-7, Casein, Health
  • Abrahams, B.S., Geschwind, D.H. (2008). Advances in autism genetics: on the thresholdof a new neurobiology. Nature Reviews Genetics, 9(5), 341-55.
  • Anthony, M.S., Clarkson, T.B., Williams, J.K. (1998). Effects of soy isoflavones on atherosclerosis: potential mechanisms. American Journal of Clinical Nutrition, 68, 1390-1393.
  • Banerjee, S. (2018). A2 Milk: The unknown story about a milk protein. Acta Scientific Nutritional Health, 2(3), 28-31.
  • Barnett, M. P., McNabb, W. C., Roy, N. C., Woodford, K. B., Clarke, A. J. (2014). Dietary A1 β-casein affects gastrointestinal transit time, dipeptidyl peptidase-4 activity, and inflammatory status relative to A2 β-casein in Wistar rats. International Journal of Food Sciences and Nutrition, 65, 720-727.
  • Boro, P., Naha, B.C., Saikia, D.P., Prakash, C. (2016). A1 and A2 milk & its impact on human health. International Journal of Science and Nature, 7(1), 01-05.
  • Brambilla, F., Guareschi-Cazzullo, A., Tacchini, C., Musetti, C., Panerai, A.E., Sacerdote, P. (1997). Beta endorphin and cholecystokinin-8 concentrations in peripheral bloodmononuclear cells of autistic children. Neuropsychobiology, 35(1), 1-4.
  • Buchberger, J. (1995). Genetic polymorphism of milk proteins: Differences between breeds. Bulletin IDF, 304, 5-6.
  • Cade, R., Wagemaker, H., Privette, R.M., Fregly, M.S., Rogers, J., Orlando, J. (1990). The effect of dialysis and diet on schizophrenia. Psychiatry: A World Perspective, 3, 494-500.
  • Chia, J. S. J., McRae, J. L., Kukuljan, S., Woodford, K., Elliott, R.B., Swinburn, B., Dwyer, K. M. (2017). A1 beta-casein milk protein and other environmental pre-disposing factors for type 1 diabetes. Nutrition & Diabetes, 1(7), 1-7.
  • Chia, J.S.J., McRae, J.L., Enjapoori, A.K., Lefèvre, C.M., Kukuljan, S., Dwyer, K.M. (2018). Dietary Cows’ Milk Protein A1 Beta-Casein Increases the Incidence of T1D in NOD Mice. Nutrients, 10(9), 1291.
  • Crane, L., Chester, J.W., Goddard, L., Henry, L.A., Hill, E. (2016). Experiences of autism diagnosis: A survey of over 1000 parents in the United Kingdom. Autism, 20(2), 153-162.
  • Damodaran, S. (1996). Amino Acids, peptides, and proteins. In Fennema, O. R. (Ed.), Food Chemistry (p. 321-425). Marcel Dekker, Inc. New York. ISBN: 0849384737, 9780849384738
  • Davoodi, S. H., Shahbazi, R., Esmaeili, S., Sohrabvandi, S., Mortazavian, A.M., Jazayeri, S., Taslimi, A. (2016). Health-Related Aspects of Milk Proteins. Iranian Journal of Pharmaceutical Research, 15(3), 573-591, 2016.
  • Elliott, R.B., M. Martin, J.M. (1984). Dietary protein: a trigger of insulin-dependent diabetes in the BB rat? Diabetologia, 26(4), 297-299.
  • Elliott, R.B., Wasmuth, W.H., Bibby, N.J., Hill, J.P. (1997). The role of β-casein variants in the induction of insulin-dependent diabetes in the non-obese diabetic mouse and humans. Food and Agriculture Organization, Brussels, Belgium, IDF Special Issue, No. 9702, 445-453.
  • Fox, P.F., Uniacke-Lowe, T., McSweeney, P.L.H., O’Mahony, J.A. (2015). Dairy Chemistry and Biochemistry (p. 584). Second Edition, Switzerland: Springer, Cham. ISBN: 978-3-319-14892-2.
  • Fox, P.F., Guinee, T.P., Cogan, T.M., McSweeney, P.L.H. (2017). Fundamentals of cheese science (p. 799). Boston: Springer, US. ISBN: 978-1-4899-7681-9
  • Gimeno, S.G., de Souza, J.M. (1997). IDDM and milk consumption. A case-control study in Sao Paulo, Brazil. Diabetes Care, 20(8), 1256–1260.
  • Jaiswal, K.P., De, S., Sarsavan, A. (2014). Review on bovine beta-casein (A1, A2) gene polymorphism and their potentially hazardous on human health. International Journal of Environment & Animal Conservation, 3(1), 1-12.
  • Jarmołowska, B., Sidor, K., Iwan, M., Bielikowicz, K., Kaczmarski, M., Kostyra, E., Kostyra, H. (2007). Changes of -casomorphin content in human milk during Lactation. Peptides, 28, 1982-1986.
  • Kadam, B.R., Ambadkar, R.K., Rathod, K.S., Pandiyan, C. (2017). A1/A2 milk and human health: A brief review. Journal of Environment and Bio-Sciences, 31(2), 357-362.
  • Kamiński, S., Kamiński, A., Kostyra, E. (2007). Polymorphism of bovine beta-casein and its potential effect on human health. Journal of Applied Genetics, 48(3), 189-198.
  • Knip, M., Virtanen, S.M., Seppa, K., Ilonen, J., Savilahti, E., Vaarala, O., Reunanen, A., Teramo, K., Hämäläinen, A.M., Paronen, J., Dosch, H.M., Hakulinen, T., Akerblom, H.K. (2010a). Dietary intervention in infancy and later signs of beta-cell autoimmunity. New England Journal of Medicine, 363(20), 1900-1908.
  • Knip, M., Virtanen, S.M., Akerblom,, H.K. (2010b). Infant feeding and the risk of type 1 diabetes. American Journal of Clinical Nutrition, 91(5), 1506S-1513S.
  • Knip, M., Akerblom, H.K., Becker, D., Dosch, H.M., Dupre, J., Fraser, W., Howard, N., Ilonen, J., Krischer, J.P., Kordonouri, O., Lawson, M.L., Palmer, J.P., Savilahti, E., Vaarala, O., Virtanen, S.M. (2014). Hydrolyzed infant formula and early beta-cell autoimmunity: a randomized clinical trial. Journal of the American Medical Association, 311, 2279-2287.
  • Kost, N.V., Sokolov, O.Y., Kurasova, O.B., Dmitriev, A.D., Tarakanova, J.N., Gabaeva, M.V., Zolotarev, Y.A., Dadayan, A.K., Grachev, S.A., Korneeva, E.V., Mikheeva, I.G., Zozulya, A.A. (2009). β-Casomorphins-7 in infants on different type of feeding and different levels of psychomotor development. Peptides, 30, 1854-1860.
  • Lamb, M.M., Miller, M., Seifert, J.A., Frederiksen, B., Kroehl, M., Rewers, M., Norris, J.M. (2015). The effect of childhood cow's milk intake and HLA-DR genotype on risk of islet autoimmunity and type 1 diabetes: The Diabetes Autoimmunity Study in the Young. Pediatr Diabetes, 16(1), 31-38.
  • Laugesen, M., Elliott, R.B. (2003). Ischaemic heart disease, type 1 diabetes, and cow milk A1 β-casein. New Zealand Medical Journal, 116(1168), 1-19.
  • Leboyer, M., Philippe, A., Bouvard, M., Guilloud-Bataille, M., Bondoux, D., Tabuteau, F., Feingold, J., Mouren-Simeoni, M.C., Launay, J.M. (1999). Whole blood serotonin and plasma beta-endorphin in autistic probandsand their first-degree relatives. Biological Psychiatry, 45(2), 158-163.
  • Lorenzo, J.M., Munekata, P.E.S., Gómez, B., Barba, F.J., Mora, L., Pérez-Santaescolástica, C., Toldrá, F. (2018). Bioactive peptides as natural antioxidants in food products – A review. Trends in Food Science & Technology, 79, 136-147.
  • Mallepalli, S., Kumar, R.K., Sriram, N. (2017). Difference between A1 and A2 milk: Risk of A1 milk. International Journal of Allied Medical Sciences and Clinical Research, 5(1), 163-167.
  • McLachlan, C.N. (2001). B-kazein A1, ischaemic heart disease mortality and other illness. Medical Hypotheses, 56(2), 262-267.
  • Mehta, B.M (2015). Chemical composition of milk and milk products. In Cheung, P. C. K., Mehta, B. M. (Eds): Handbook of Food Chemistry, (p. 511-553), Berlin: Springer-Verlag. ISBN: 978-3-642-36604-8
  • Mohanty, D.P., Mohapatra, S., Misra, S., Sahu, P.S. (2016). Milk derived bioactive peptides and their impact on human health – A review. Saudi Journal of Biological Sciences, 23(5), 577-583.
  • Nagamitsu, S., Matsuishi, T., Kisa, T., Komori, H., Miyazaki, M., Hashimoto, T., Yamashita, Y., Ohtaki, E., Kato, H (1997). CSF beta-endorphin levels in patients with infantile autism. Journal of Autism and Developmental Disorder, 27(2), 155-163.
  • Nguyen, D.D., Solah, V.A., Johnson, S.K., Charrois, J.W. A., Busetti, F. (2014). Analytical Methods Isotope dilution liquid chromatography–tandem mass spectrometryfor simultaneous identification and quantification of beta-casomorphin 5 and beta-casomorphin 7 in yoghurt. Food Chemistry, 146, 345-352.
  • Nguyen, D.D., Johnson, S.K., Busetti, F., Solah, V.A. (2015). Formation and degradation of beta-casomorphins in dairy processing. Critical Reviews in Food Science and Nutrition, 55(14), 1955-1967.
  • Ni, W., Tsuda, Y., Sakono, M., Imaizumi, K. (1998). Dietary soy protein isolate, compared with casein, reduces atherosclerotic lesion area in apolipoprotein E-deficient mice. Journal of Nutrition, 128(11), 1884-1889.
  • Nongonierma, A.B., FitzGerald, R.J. (2015). The scientific evidence for the role of milk protein-derived bioactive peptides in humans: A Review. Journal of Functional Foods, 17, 640-656.
  • Pal, S., Woodford, K., Kukuljan, S., Ho, S. (2015). Milk intolerance, beta-casein and lactose. Nutrients, 7(9), 7285-7297.
  • Parashar, A., Saini, R.K. (2015). A1 Milk and its controversy-A review. International Journal of Bioassays, 4(12), 4611-4619.
  • Park, Y.W., Nam, M.S. (2015). Bioactive peptides in milk and dairy products: A Review. Korean Journal for Food Science of Animal Resources, 35(6), 831-840.
  • Patton, S. (2017). Milk: Its remarkable contribution to human health and well-being (p. 276), New York: Routledge. ISBN: 1412805112
  • Priyadarshini, P., Mishra, C., Mishra, B., Swain, K., Rout, M., Mishra, S.P. (2018). Impact of milk protein on human health: A1 verses A2. International Journal of Chemical Studies, 6(1), 531-535.
  • Shattock, P., Whiteley, P. (2002). Biochemical aspects in autism spectrum disorders: updating the opioid-excess theory and presenting new opportunities for biomedical intervention. Expert Opinion on Therapeutic Targets, 6(2), 175-183.
  • Sokolov, O., Kost, N., Andreeva, O., Korneeva, E., Meshavkin, V., Tarakanova, Y., Dadayan, A., Zolotarev, Y., Grachev, S., Mikheeva, I., Varlamov, O., Zozulya, A. (2014). Autistic children display elevated urine levels of bovinecasomorphin-7 immunoreactivity. Peptides, 56, 68-71.
  • Sun, Z., Cade, J.R. (1999). A peptide found in schizophrenia and autism causes behavioral changes in rats. Autism, 3(1), 85-95.
  • Sun, Z., Cade, J.R., Fregly, M.J., Privette, R.M. (1999). β-casomorphin induces Fos-like immunoreactivity in discrete brain regions relevant to schizophrenia and autism. Autism, 3(1), 67-83.
  • Sun, Z., Zhang, Z., Wang, X., Cade, R., Elmer, Z., Fregly, M. (2003). Relation of beta-casomorphin to apnea in sudden infant death syndrome. Peptides, 24, 937-943.
  • Tailford, K.A., Berry, C.L., Thomas, A.C., Campbell, J.H. (2003). A casein variant in cow's milk is atherogenic. Atherosclerosis, 170(1), 13-9.
  • Tordjman, S., Anderson, G.M., Botbol, M., Brailly-Tabard, S., Perez-Diaz, F., Graignic, R., Carlier, M., Schmit, S., Rolland, A.C., Bonnot, O., Trabado, S., Roubertoux, P., Bronsard, G. (2009). Pain reactivity and plasma beta-endorphin in children and adolescents with autistic disorder. PLOS ONE, 4(8), e5289.
  • Ul Haq, M.R., Kapila, R., Saliganti, V. (2014a). Consumption of β-casomorphins-7/5 induce inflammatory immune response in mice gut through Th2 pathway. Journal of Functional Foods, 8(1), 150-160.
  • Ul Haq, M.R., Kapila, R., Sharma, R., Saliganti, V., Kapila, S. (2014b). Comparative evaluation of cow β-casein variants (A1/A2) consumption on Th2-mediated inflammatory response in mouse gut. European Journal of Nutrition, 53(4), 1039-1049.
  • Ul Haq, M.R., Kapila, R., Kapila, S. (2015). Release of β-casomorphin-7/5 during simulated gastrointestinal digestion of milk β-casein variants from Indian crossbred cattle (Karan Fries). Food Chemistry, 168, 70-79.
  • Virtanen, S.M., Rasanen, L., Ylonen, K., Aro, A., Clayton, D., Langholz, B., Pitkäniemi, J., Savilahti, E., Lounamaa, R., Tuomilehto, J., Åkerblom, H.K. (1993). Early introduction of dairy products associated with increased risk of IDDM in Finnish children. The childhood in diabetes in Finland study group. Diabetes, 42(12), 1786-1790.
  • Virtanen, S.M. (2014). Hydrolyzed infant formula and early beta-cell autoimmunity: A randomized clinical trial. Journal of the American Medical Association, 311, 2279-2287.
  • Wasilewska, J., Sienkiewicz-Szłapka, E., Kuźbida, E., Jarmołowska, B., Kaczmarski, M., Kostyra, E. (2011). The exogenous opioid peptides and DPPIV serum activity in infants with apnoea expressed as apparent life threatening events (ALTE). Neuropeptides, 45(3), 189-195.
  • Zeng, L., Mathew, A. V., Byun, J., Atkins, K.B., Brosius, F.C., Pennathur, S. (2018). Myeloperoxidase-derived oxidants damage artery wall proteins in an animal model of chronic kidney disease–accelerated atherosclerosis. Journal of Biological Chemistry, 293(19), 7238-7249.
  • Zikakis, J.P., Haenlein, G.F., Hines, H.C., Mather, R.E., Tung, S. (1974). Gene frequencies of electrophoretically determined polymorphisms in Guernsey blood and milk. Journal of Dairy Science, 57(4), 405-410.
Primary Language en
Subjects Food Science and Technology
Journal Section Review Articles

Orcid: 0000-0002-8306-0222
Author: Seval ANDİÇ (Primary Author)
Country: Turkey

Orcid: 0000-0002-8818-9850
Author: Rozelin Münevver AYAZ
Country: Turkey

Orcid: 0000-0001-6889-9487
Author: Şehriban OĞUZ
Country: Turkey


Application Date : May 25, 2020
Acceptance Date : October 4, 2020
Publication Date : March 9, 2021

Bibtex @review article { jfhs742564, journal = {Food and Health}, issn = {}, eissn = {2602-2834}, address = {Vidin Caddesi No:28 D:4 Kocamustafapaşa 34107 Fatih İstanbul}, publisher = {Özkan ÖZDEN}, year = {2021}, volume = {7}, pages = {128 - 137}, doi = {10.3153/FH21014}, title = {A1 Milk and Beta-casomorphin-7}, key = {cite}, author = {Andiç, Seval and Ayaz, Rozelin Münevver and Oğuz, Şehriban} }
APA Andiç, S , Ayaz, R , Oğuz, Ş . (2021). A1 Milk and Beta-casomorphin-7 . Food and Health , 7 (2) , 128-137 . DOI: 10.3153/FH21014
MLA Andiç, S , Ayaz, R , Oğuz, Ş . "A1 Milk and Beta-casomorphin-7" . Food and Health 7 (2021 ): 128-137 <>
Chicago Andiç, S , Ayaz, R , Oğuz, Ş . "A1 Milk and Beta-casomorphin-7". Food and Health 7 (2021 ): 128-137
RIS TY - JOUR T1 - A1 Milk and Beta-casomorphin-7 AU - Seval Andiç , Rozelin Münevver Ayaz , Şehriban Oğuz Y1 - 2021 PY - 2021 N1 - doi: 10.3153/FH21014 DO - 10.3153/FH21014 T2 - Food and Health JF - Journal JO - JOR SP - 128 EP - 137 VL - 7 IS - 2 SN - -2602-2834 M3 - doi: 10.3153/FH21014 UR - Y2 - 2020 ER -
EndNote %0 Food and Health A1 Milk and Beta-casomorphin-7 %A Seval Andiç , Rozelin Münevver Ayaz , Şehriban Oğuz %T A1 Milk and Beta-casomorphin-7 %D 2021 %J Food and Health %P -2602-2834 %V 7 %N 2 %R doi: 10.3153/FH21014 %U 10.3153/FH21014
ISNAD Andiç, Seval , Ayaz, Rozelin Münevver , Oğuz, Şehriban . "A1 Milk and Beta-casomorphin-7". Food and Health 7 / 2 (March 2021): 128-137 .
AMA Andiç S , Ayaz R , Oğuz Ş . A1 Milk and Beta-casomorphin-7. Food Health. 2021; 7(2): 128-137.
Vancouver Andiç S , Ayaz R , Oğuz Ş . A1 Milk and Beta-casomorphin-7. Food and Health. 2021; 7(2): 128-137.
IEEE S. Andiç , R. Ayaz and Ş. Oğuz , "A1 Milk and Beta-casomorphin-7", Food and Health, vol. 7, no. 2, pp. 128-137, Mar. 2021, doi:10.3153/FH21014