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Yu W, Wang W, Sheng X. Effect of A1 protein-free formula versus conventional formula on acute respiratory infections and diarrhea in toddlers: A Randomized Controlled Trial. J Pediatr Gastroenterol Nutr 2025; 80:705-713. [PMID: 39895612 PMCID: PMC11959105 DOI: 10.1002/jpn3.12473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 12/12/2024] [Accepted: 12/18/2024] [Indexed: 02/04/2025]
Abstract
OBJECTIVES Acute respiratory infections (ARIs) and diarrhea are common in toddlers. Milk free of A1 β-casein (A1PF milk) may support the immune system, but few studies have investigated A1PF milk in toddler formula and any potential effects on ARI/diarrhea. This study's objective was to investigate the incidence of ARI and diarrhea with two toddler formulas, A1PF formula (A1PF) or conventional formula (CON), which differed in milk base and nutrient composition. METHODS This randomized, open-label, multicenter study (19 December 2022 to 17 May 2023) evaluated the occurrence of ARI and/or diarrhea in toddlers (aged 2-3 years) who consumed A1PF or CON over 90 days. RESULTS A total of 200 toddlers were enrolled, and 180 completed the study. The relative risk of ARI or diarrhea in the A1PF group versus the CON group did not differ significantly, but the median (interquartile range) ARI duration was significantly shorter in the A1PF group (3 [2-4] days vs. 5 [3-6] days, p = 0.012). At Day 90, toddlers consuming A1PF had significantly less severe bloating, gassiness, and fewer regurgitation events (all p < 0.05). Both formulas were well tolerated, and no serious adverse events were reported. CONCLUSION Toddlers who consumed A1PF had a reduced duration of ARI and improved diarrhea outcomes, reducing the burden on their families compared with toddlers who consumed CON. Although this is consistent with other studies, further research is required to determine whether these effects are solely attributable to the A1PF milk base or other differences between the formulas.
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Affiliation(s)
- Wen Yu
- Department of Child Health CareInternational Peace Maternal and Child Health Care HospitalShanghaiChina
| | - Weijie Wang
- Department of Child Health CareShanghai First Maternity and Infant HospitalShanghaiChina
| | - Xiaoyang Sheng
- Department of Developmental Behavioral Pediatric & Children Healthcare, Xinhua Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
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Faggion S, Degano L, Carnier P, Bonfatti V. β-Casein A2 affects milk renneting properties, cheese yield before and after ripening, and alters the texture of Caciotta cheese produced in field conditions. J Dairy Sci 2025; 108:3199-3213. [PMID: 39890074 DOI: 10.3168/jds.2024-25750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 12/19/2024] [Indexed: 02/03/2025]
Abstract
The aim of this study was to investigate the effect of β-CN genetic variants on milk coagulation properties, curd and cheese yield, efficiency of cheesemaking, and quality of Caciotta cheese after 15 d of ripening. Thirty-three cheesemaking experiments were carried out at an on-farm pilot-scale dairy plant. For each cheesemaking day, small groups of cows were selected and milked separately to obtain 2 milk pools, 1 with high proportion of β-CN A1 and B in β-CN (A1B milk) and 1 with high proportion of β-CN A2 (A2 milk) in β-CN, respectively. Each milk pool originated from at least 2 cows and was processed into Caciotta cheese, producing 2 cheese wheels of commercial size. Differences across milk pools in milk composition, coagulation properties, curd yield measured by laboratory-scale microcheesemaking, cheese yield after stewing, brining, and 15 d of ripening, whey composition, recovery rates, as well as cheese composition, color, and texture were estimated using a set of mixed linear models including the random effect of the processing day, and the linear effects of the major sources of variation of the investigated traits. Compared with A1B milk, A2 milk had a remarkably 2.8-min longer rennet coagulation time, lower curd yield measured by microcheesemaking (-0.5%), cheese yield after stewing (-1.15%), brining (-0.92%), and 15-d ripening (-0.36%). No significant variations associated with the milk pools were observed in cheese composition, but cheese from A2 milk exhibited significantly lower green-to-red axis value (a*) and higher hue angle values compared with cheese processed from A1B milk, although these differences are not expected to be perceived by the human eye. Cheese from A2 milk was also characterized by a significantly lower hardness, springiness, chewiness, and gumminess than cheese from A1B milk. Our results indicate that use of A2 milk for cheese production leads to inferior technological properties and a less efficient cheesemaking process. More studies are necessary to investigate the effect of β-CN variants on product quality and consumer perception.
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Affiliation(s)
- S Faggion
- Department of Comparative Biomedicine and Food Science (BCA), University of Padova, 35020, Legnaro, Padova, Italy
| | - L Degano
- Italian Simmental Cattle Breeder Association (ANAPRI), 33100, Udine, Italy
| | - P Carnier
- Department of Comparative Biomedicine and Food Science (BCA), University of Padova, 35020, Legnaro, Padova, Italy
| | - V Bonfatti
- Department of Comparative Biomedicine and Food Science (BCA), University of Padova, 35020, Legnaro, Padova, Italy.
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Chen X, Gulbahar K, Ding H, Nie C, Gao X. Comparative analysis of proteomics and transcriptomics reveals novel mechanism underlying the antibacterial activity and immune-enhancing properties of horse milk. Front Nutr 2025; 12:1512669. [PMID: 40135224 PMCID: PMC11932903 DOI: 10.3389/fnut.2025.1512669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 02/18/2025] [Indexed: 03/27/2025] Open
Abstract
Background Horse milk is a highly valuable organic food that is a promising alternative to cow milk, exhibiting plenty of healthy and immune benefits to human. However, identification of proteins associated human wellness and underlying molecular mechanism in horse milk remain unclear. Methodology Label-free mass spectrometry-based protein quantification technology was employed to investigate protein composition of animal milk, including cow, goat, camel and horse milk. Prokaryotic expression and disk diffusion assay were applied to acquire and evaluate in vitro antimicrobial activity of candidate proteins. RAW264.7 macrophage model cell line was used to validate effect of proteins on cytotoxicity, apoptosis and immune induction. ROS probe detected cell ROS change and RT-qPCR verified expression of immune response genes induced by proteins. Microscopy was used to observe the effects of protein on the morphological characteristics of bacteria, further transcriptome analysis was performed to investigate transcriptional changes of bacteria induced by candidate proteins. Results A total of 1,335 proteins was identified in cow, goat, camel and horse milk. GO enrichment analysis showed that the proteins related to protein degradation were highly expressed in horse milk compared to other three types of milk, contributing to easier assimilation and palatability. KEGG analysis showed that horse milk contained abundant antimicrobial associated proteins relevant to pathogenic bacterial resistance, leading to the decreased risk of pathogenic diseases. A higher accumulation of proteins associated with caffeine metabolism, amino acid biosynthesis, and glycolysis/gluconeogenesis in horse milk contributes to its distinctive flavor. Notably, highly expressed proteins in horse milk were closely linked to immune signaling pathways, functioning as immune modulators. Importantly, we identified four highly expressed antimicrobial associated proteins in horse milk including LPO, B2M, CD14 and PGL, among them, PGL functioned dually by in vitro antibacterial activity and immune activation. Further transcriptome analysis demonstrated that PGL exerted significant transcriptional changes to bacteria. Enrichment analysis showed PGL could inhibit growth of P. aeruginosa and E. coli by repressing the biosynthesis of secondary metabolites. Conclusion Comparative proteomics revealed immune enhancement and nutrient composition of horse milk compared to cow, goat and camel milk. Identification of PGL showed antibacterial activity and potential medicinal value.
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Affiliation(s)
- Xueshan Chen
- School of Pharmacy, Xinjiang Medical University, Xinjiang, China
| | - Kawuli Gulbahar
- School of Pharmacy, Xinjiang Medical University, Xinjiang, China
- Engineering Research Center of Xinjiang and Central Asian Medicine Resources, Ministry of Education, Xinjiang Medical University, Xinjiang, China
| | - Haiyan Ding
- School of Pharmacy, Xinjiang Medical University, Xinjiang, China
| | - Changhong Nie
- School of Pharmacy, Xinjiang Medical University, Xinjiang, China
- Engineering Research Center of Xinjiang and Central Asian Medicine Resources, Ministry of Education, Xinjiang Medical University, Xinjiang, China
| | - Xiaoli Gao
- School of Pharmacy, Xinjiang Medical University, Xinjiang, China
- Engineering Research Center of Xinjiang and Central Asian Medicine Resources, Ministry of Education, Xinjiang Medical University, Xinjiang, China
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4
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Robinson SR, Greenway FL, Deth RC, Fayet-Moore F. Effects of Different Cow-Milk Beta-Caseins on the Gut-Brain Axis: A Narrative Review of Preclinical, Animal, and Human Studies. Nutr Rev 2025; 83:e1259-e1269. [PMID: 39024213 PMCID: PMC11819488 DOI: 10.1093/nutrit/nuae099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/20/2024] Open
Abstract
The gut and brain communicate through bidirectional neural, endocrine, and immune signals to coordinate central nervous system activity with gastrointestinal function. Dysregulated inflammation can promote immune cell activation and increase entero-endocrine signaling and intestinal permeability; hence, a functional gut-brain axis is necessary for a healthy digestive system. The consumption of milk products can lead to gut discomfort via effects on gastrointestinal tract function and the inflammatory state, which, in turn, affect the brain. A1 β-casein and A2 β-casein are major components of bovine-milk protein, and their digestion may result in different physiological effects following the consumption of milk products. Peptides derived from A1 β-casein, such as β-casomorphins, may increase gut dysfunction and inflammation, thereby modulating the availability of bioactive metabolites in the bloodstream and contribute to changes in cognitive function. This narrative review examines the functional interrelationships between the consumption of cow-milk-derived β-caseins and their effect on the brain, immune system, and the gut, which together comprise the gut-brain axis.
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Affiliation(s)
- Stephen R Robinson
- School of Health and Biomedical Sciences, RMIT University, Bundoora, 3083 Victoria, Australia
| | - Frank L Greenway
- Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, United States
| | - Richard C Deth
- Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL 33328, United States
| | - Flavia Fayet-Moore
- Department of Science, FOODiQ, New South Wales, Sydney, Australia
- School of Environmental and Life Sciences, The University of Newcastle, Ourimbah, 2258 New South Wales, Australia
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Aitchison A, Edwards TS, Day AS. Simulated gastrointestinal digestion of milk caseins containing A1 β-casein does not lead to increased production of inflammatory proteins in intestinal epithelial cells in vitro when compared to milk caseins containing A2 β-casein. J Funct Foods 2025; 125:106669. [DOI: 10.1016/j.jff.2025.106669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2025] Open
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Ghadimi D, Fölster-Holst R, Blömer S, Ebsen M, Röcken C, Uchiyama J, Matsuzaki S, Bockelmann W. Intricate Crosstalk Between Food Allergens, Phages, Bacteria, and Eukaryotic Host Cells of the Gut-skin Axis. THE YALE JOURNAL OF BIOLOGY AND MEDICINE 2024; 97:309-324. [PMID: 39351325 PMCID: PMC11426303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 10/04/2024]
Abstract
Bacterial and food allergens are associated with immune-mediated food allergies via the gut-skin axis. However, there has been no data on the potential use of phages to rescue this pathological process. A human triple cell co-culture model incorporating colonocytes (T84 cells), macrophages (THP-1 cells), and hepatocytes (Huh7 cells) was established and infected with Pseudomonas aeruginosa PAO1 (P.a PAO1) in the absence or presence of its KPP22 phage in Dulbecco's Modified Eagle's Medium (DMEM), DMEM+ ovalbumin (OVA), or DMEM+β-casein media. The physiological health of cells was verified by assessing cell viability and Transepithelial electrical resistance (TEER) across the T84 monolayer. The immune response of cells was investigated by determining the secretions of IL-1β, IL-8, IL-22, and IL-25. The ability of P.a PAO1 to adhere to and invade T84 cells was evaluated. The addition of either OVA or β-casein potentiated the P.a PAO1-elicited secretion of cytokines. The viability and TEER of the T84 monolayer were lower in the P.a PAO1+OVA group compared to the P.a PAO1 alone and PAO1+β-casein groups. OVA and β-casein significantly increased the adherence and invasion of P.a PAO1 to T84 cells. In the presence of the KPP22 phage, these disruptive effects were abolished. These results imply that: (1) food allergens and bacterial toxic effector molecules exacerbate each other's disruptive effects; (2) food allergen and bacterial signaling at the gut-skin mucosal surface axis depend on a network of bacteria-phage-eukaryotic host interactions; and (3) phages are complementary for the evaluation of pathobiological processes that occur at the interface between bacteria, host cellular milieu, and food antigens because phages intervene in P.a PAO1-, OVA-, and β-casein-derived inflammation.
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Affiliation(s)
- Darab Ghadimi
- Department of Microbiology and Biotechnology, Max
Rubner-Institut, Kiel, Germany
| | - Regina Fölster-Holst
- Clinic of Dermatology, Venerology und Allergology,
University Hospital Schleswig-Holstein, Kiel, Germany
| | - Sophia Blömer
- Clinic of Dermatology, Venerology und Allergology,
University Hospital Schleswig-Holstein, Kiel, Germany
| | - Michael Ebsen
- Städtisches MVZ Kiel GmbH (Kiel City Hospital),
Department of Pathology, Kiel, Germany
| | - Christoph Röcken
- Institute of Pathology, Kiel University, University
Hospital, Schleswig-Holstein, Kiel, Germany
| | - Jumpei Uchiyama
- Department of Bacteriology, Graduate School of Medicine
Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Shigenobu Matsuzaki
- Department of Medical Laboratory Science, Faculty of
Health Sciences, Kochi Gakuen University, Kochi, Japan
| | - Wilhelm Bockelmann
- Department of Microbiology and Biotechnology, Max
Rubner-Institut, Kiel, Germany
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Sheng XY, Mi W, Yuan QB, Liu BY, Carnielli V, Ning YB, Einerhand AWC. An A2 β-casein infant formula with high sn-2 palmitate and casein phosphopeptides supports adequate growth, improved stool consistency, and bone strength in healthy, term Chinese infants: a randomized, double-blind, controlled clinical trial. Front Nutr 2024; 11:1442584. [PMID: 39206307 PMCID: PMC11351578 DOI: 10.3389/fnut.2024.1442584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 08/02/2024] [Indexed: 09/04/2024] Open
Abstract
The aim of this randomized, double-blind, controlled trial was to examine the effects of infant formula on the growth, stool consistency, and bone strength of infants (n = 120) over a period of 4 months. The investigational group was fed an A2 β-casein cow's milk infant formula containing casein phosphopeptides (CPP) and high sn-2 palmitate (54% of total palmitate at sn-2). The control group was fed a standard cow's milk formula without CPP and with low sn-2 palmitate (29% of total palmitate at sn-2). The third group was fed human milk (HM) (n = 60). All three groups had similar baseline characteristics, and maintained similar BMI, sleep habits, and growth rates in body weight and length throughout the study. However, compared to the control group, infants in the investigational and human milk groups had significantly: (i) greater body length at 90, 120, and 150 days of age; (ii) greater growth rate in head circumference from 30 to 60 days of age, with larger head circumference at 60 days of age; (iii) larger daily stool frequency at 60, 90, and 120 days of age; (iv) softer stool at 60, 90, and 120 days of age; (v) higher bone quality index and bone speed of sound at 150 days of age; (vi) fewer hours of crying at 60 and 90 days of age; (vii) less abdominal distention, burp, and flatus at 60, 90, and 120 days of age; and (viii) less constipation at 90 days of age. At other time points, no significant differences were observed between the three groups. No serious adverse events (AEs) related to the study products were reported, and significantly fewer infants in the investigational and HM groups experienced at least one AE compared to the control group. The study suggests that the A2 β-casein formula with high sn-2 palmitate and CPP supports adequate growth, is well tolerated, and may have beneficial effects on stool consistency, gastrointestinal comfort, crying duration, and bone density, comparable to HM. Clinical trial registration: https://clinicaltrials.gov/, NCT04749290.
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Affiliation(s)
- Xiao-Yang Sheng
- Department of Developmental Behavioral Pediatric and Children Healthcare, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Wiola Mi
- Bunge Nutrition, Shanghai, China
| | - Qing Bin Yuan
- Junlebao Nutrition Research Institute, Shijiazhuang, China
| | - Bryan Yanwen Liu
- College of Biotechnology, East China University of Science and Technology, Shanghai, China
| | - Virgilio Carnielli
- Division of Neonatology, Polytechnic University of Marche and ‘G. Salesi’ Children’s Hospital, Ancona, Italy
| | - Yi Bing Ning
- Junlebao Nutrition Research Institute, Shijiazhuang, China
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Choi Y, Kim N, Song CH, Kim S, Lee DH. The Effect of A2 Milk on Gastrointestinal Symptoms in Comparison to A1/A2 Milk: A Single-center, Randomized, Double-blind, Cross-over Study. J Cancer Prev 2024; 29:45-53. [PMID: 38957588 PMCID: PMC11215337 DOI: 10.15430/jcp.24.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 06/04/2024] [Accepted: 06/11/2024] [Indexed: 07/04/2024] Open
Abstract
β-Casein, a major protein in cow's milk, is divided into the A1 and A2 type variants. Digestion of A1 β-casein yields the peptide β-casomorphin-7 which could cause gastrointestinal (GI) discomfort but A2 milk containing only A2 β-casein might be more beneficial than A1/A2 (regular) milk. The aim of this study was to evaluate the differences in GI discomfort after ingestion of A2 milk and A1/A2 milk. A randomized, double-blind, cross-over human trial was performed with 40 subjects who experienced GI discomfort following milk consumption. For each intervention period, either A2 milk first (A2→A1/A2) or A1/A2 milk was first consumed for 2 weeks (A1/A2→A2) following a 2-week washout period. GI symptom rating scale (GSRS) scores, questionnaire for digestive symptoms, and laboratory tests including fecal calprotectin were evaluated. For symptom analysis, generalized estimating equations gamma model was used. A2 milk increased bloating (P = 0.041) and loose stools (P = 0.026) compared to A1/A2 milk in GSRS. However, A2 milk caused less abdominal pain (P = 0.050), fecal urgency (P < 0.001) and borborygmus (P = 0.007) compared to A1/A2 milk in questionnaire for digestive symptoms. In addition, fecal calprotectin also decreased or less increased after consumption of A2 milk compared to A1/A2 milk (P = 0.030), and this change was more pronounced in males (P = 0.005) than in females. There were no significant adverse reactions during the trial. A2 milk alleviated digestive discomfort in Koreans following A2 milk consumption (ClinicalTrials.gov NCT06252636 and CRIS KCT0009301).
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Affiliation(s)
- Yonghoon Choi
- Department of Internal Medicine and Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine and Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Chin-Hee Song
- Department of Internal Medicine and Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Seulgi Kim
- Department of Internal Medicine and Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine and Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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9
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Ramakrishnan M, Mysore Saiprasad S, Savaiano DA. Prolonged Consumption of A2 β-Casein Milk Reduces Symptoms Compared to A1 and A2 β-Casein Milk in Lactose Maldigesters: A Two-Week Adaptation Study. Nutrients 2024; 16:1963. [PMID: 38931316 PMCID: PMC11206509 DOI: 10.3390/nu16121963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 06/08/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024] Open
Abstract
Approximately 30% of milk protein is β-casein. We aimed to determine whether lactose maldigesters who chronically consumed two cups of A1/A2 milk (containing 75% A1 β-casein and 25% A2 β-casein) would adapt to have fewer intolerance symptoms, lower serum inflammatory markers, and/or altered glutathione levels similar to those consuming A2 milk (containing 100% A2 β-casein). A double-blinded, randomized, crossover trial was conducted. Sixteen confirmed lactose maldigesters consumed 250 mL of A1/A2 milk and A2 milk twice daily with meals for two weeks. At the end of the adaptation period on day 15, lactose maldigestion was measured after a challenge with the same milk used for adaptation (0.5 g of lactose per kg of body weight) with a hydrogen breath test. Fecal urgency was higher during the two-week consumption of A1/A2 milk compared to A2 milk (p = 0.04, n = 16). Bloating (p = 0.03, n = 16) and flatulence (p = 0.02, n = 16) were also higher on the 15th day with A1/A2 milk compared to A2 milk challenge. However, day-to-day symptoms, hydrogen, serum inflammatory markers, and antioxidant concentrations were not different after A1/A2 and A2 milk consumption adaptation periods. Adaptation over two weeks did not improve lactose digestion or tolerance of A1/A2 milk to match that of A2 milk.
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Affiliation(s)
- Monica Ramakrishnan
- Department of Nutrition Science, College of Health and Human Sciences, Purdue University, West Lafayette, IN 47907, USA; (S.M.S.); (D.A.S.)
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Sun Y, Ding Y, Liu B, Guo J, Su Y, Yang X, Man C, Zhang Y, Jiang Y. Recent advances in the bovine β-casein gene mutants on functional characteristics and nutritional health of dairy products: Status, challenges, and prospects. Food Chem 2024; 443:138510. [PMID: 38281416 DOI: 10.1016/j.foodchem.2024.138510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 01/04/2024] [Accepted: 01/17/2024] [Indexed: 01/30/2024]
Abstract
β-casein is the second most abundant form of casein in milk. Changes in amino acid sequence at specific positions in the primary structure of β-casein in milk will produce gene mutations that affect the physicochemical properties of dairy products and the hydrolysis site of digestive enzymes. The screening method of β-casein allele frequency detection in dairy products also has attracted the extensive attention of scientists and farmers. The A1 and A2 β-casein is the two usual mutation types, distinguished by histidine and proline at position 67 in the peptide chain. This paper summarizes the effects of A1 and A2 β-casein on the physicochemical properties of dairy products and evaluates the effects on human health, and the genotyping methods were also concluded. Impressively, this review presents possible future opportunities and challenges for the promising field of A2 β-casein, providing a valuable reference for the development of the functional dairy market.
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Affiliation(s)
- Yilin Sun
- Key Laboratory of Dairy Science, Ministry of Education, Department of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Yixin Ding
- Key Laboratory of Dairy Science, Ministry of Education, Department of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Biqi Liu
- Key Laboratory of Dairy Science, Ministry of Education, Department of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Jinfeng Guo
- Key Laboratory of Dairy Science, Ministry of Education, Department of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Yue Su
- Key Laboratory of Dairy Science, Ministry of Education, Department of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Xinyan Yang
- Key Laboratory of Dairy Science, Ministry of Education, Department of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Chaoxin Man
- Key Laboratory of Dairy Science, Ministry of Education, Department of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Yu Zhang
- Key Laboratory of Dairy Science, Ministry of Education, Department of Food Science, Northeast Agricultural University, Harbin 150030, China.
| | - Yujun Jiang
- Key Laboratory of Dairy Science, Ministry of Education, Department of Food Science, Northeast Agricultural University, Harbin 150030, China; Food Laboratory of Zhongyuan, Luohe, Henan 462300, China.
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11
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Kappes R, Schneider V, Schweizer H, Nüske S, Knob DA, Thaler Neto A, Scholz AM. Effect of β-casein A1 or A2 milk on body composition, milk intake, and growth in Holstein, Simmental, and crossbred dairy calves of both sexes. J Dairy Sci 2024; 107:4033-4044. [PMID: 38246546 DOI: 10.3168/jds.2023-24046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 12/15/2023] [Indexed: 01/23/2024]
Abstract
The aim of this study was to compare the effects of feeding homozygous β-CN A1 or A2 milk on the body composition, milk intake, and growth of German Holstein (GH), German Simmental (GS), and crossbred (CR) dairy calves of both sexes during the first 2 wk of life. A total of 104 calves (n = 54 female, f; and n = 50 male, m) from the breed groups GH (n = 23), GS (n = 61), and crossbred GH × GS (n = 20) were evaluated. Calves were weighed after birth and received colostrum ad libitum. On the second day, calves were alternately housed in pairs in double-igloo systems according to their random birth order and received either A1 milk (n = 52; 27 female and 25 male) or A2 milk (n = 52; 27 female and 25 male). They were offered 7.5 L/d, and the individual actual total milk intake was recorded. Daily energy-corrected milk intake was also calculated based on the milk composition (fat and protein). Fecal scores were recorded daily. On d 15, visceral adipose tissue (VAT) volume was assessed by open magnetic resonance imaging and dual-energy X-ray absorptiometry (DXA). In addition, fat and lean mass (g), as well as bone mineral content (g) and bone mineral density (g/cm2), were determined by DXA. The body composition, milk intake, and growth were similar between the 2 types of milk in the first 2 wk of life. Female calves had more VAT and fat mass, but less lean mass than male calves. GH and CR calves had more VAT and less lean mass than GS calves. Male calves were heavier than female calves after birth and on d 15. The average days with diarrhea and diarrhea occurrence were similar between calves fed A1 and A2 milk and between both sex groups. GS calves presented slightly more days with diarrhea and increased odds of having diarrhea compared with GH calves, not differing from CR.
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Affiliation(s)
- R Kappes
- Lehr- und Versuchsgut Oberschleißheim, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München (LMU), 85764 Oberschleißheim, Germany; Centro de Ciências Agroveterinárias, Universidade do Estado de Santa Catarina (CAV-UDESC), 88.520-000 Lages, Brazil.
| | - V Schneider
- Lehr- und Versuchsgut Oberschleißheim, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München (LMU), 85764 Oberschleißheim, Germany
| | - H Schweizer
- Lehr- und Versuchsgut Oberschleißheim, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München (LMU), 85764 Oberschleißheim, Germany
| | - S Nüske
- Lehr- und Versuchsgut Oberschleißheim, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München (LMU), 85764 Oberschleißheim, Germany
| | - D A Knob
- Organic Farming with Focus on Sustainable Soil Use, Justus Liebig University Giessen (JLU), 35394 Giessen, Germany
| | - A Thaler Neto
- Centro de Ciências Agroveterinárias, Universidade do Estado de Santa Catarina (CAV-UDESC), 88.520-000 Lages, Brazil
| | - A M Scholz
- Lehr- und Versuchsgut Oberschleißheim, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München (LMU), 85764 Oberschleißheim, Germany
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12
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Dantas A, Pierezan MD, Camelo-Silva C, Zanetti V, Pimentel TC, da Cruz AG, Verruck S. A discussion on A1-free milk: Nuances and comments beyond implications to the health. ADVANCES IN FOOD AND NUTRITION RESEARCH 2024; 110:197-241. [PMID: 38906587 DOI: 10.1016/bs.afnr.2024.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/23/2024]
Abstract
This chapter provides an overarching view of the multifaceted aspects of milk β-casein, focusing on its genetic variants A1 and A2. The work examines the current landscape of A1-free milk versus regular milk, delving into health considerations, protein detection methods, technological impacts on dairy production, non-bovine protein, and potential avenues for future research. Firstly, it discussed ongoing debates surrounding categorizing milk based on A1 and A2 β-casein variants, highlighting challenges in establishing clear regulatory standards and quality control methods. The chapter also addressed the molecular distinction between A1 and A2 variants at position 67 of the amino acid chain. This trait affects protein conformation, casein micelle properties, and enzymatic susceptibility. Variations in β-casein across animal species are acknowledged, casting doubt on non-bovine claims of "A2-like" milk due to terminology and genetic differences. Lastly, this work explores the burgeoning field of biotechnology in milk production.
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Affiliation(s)
- Adriana Dantas
- Food Quality and Technology, Institute of Agrifood Research and Technology (IRTA), Finca Camps i Armet, Monells, Girona, Spain
| | - Milena Dutra Pierezan
- Department of Food Science and Technology, Agricultural Sciences Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - Callebe Camelo-Silva
- Department of Food Chemistry and Engineering, Technological Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - Vanessa Zanetti
- Food Quality and Technology, Institute of Agrifood Research and Technology (IRTA), Finca Camps i Armet, Monells, Girona, Spain
| | | | - Adriano Gomes da Cruz
- Department of Food, Federal Institute of Education, Science and Technology of Rio de Janeiro (IFRJ), Rio de Janeiro, Rio de Janeiro, Brazil
| | - Silvani Verruck
- Department of Food Science and Technology, Agricultural Sciences Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
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13
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Morin CR, Baeva ME, Hollenberg MD, Brain MC. Milk and multiple sclerosis: A possible link? Mult Scler Relat Disord 2024; 83:105477. [PMID: 38308914 DOI: 10.1016/j.msard.2024.105477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 01/07/2024] [Accepted: 01/26/2024] [Indexed: 02/05/2024]
Abstract
Despite having been formally defined over 150 years ago, the etiology of multiple sclerosis (MS) is still relatively unknown. However, it is now recognized as a multifactorial disease in which genetics, infection, immune function, and environment play a role. We propose an additional piece to the puzzle: milk. In this review, milk is highlighted as a potential risk factor for MS. We examine the overall correlation between bovine milk consumption and the incidence of MS. We then discuss possible mechanisms that may explain the positive association between milk consumption and the development of MS. For instance, butyrophilin (BTN), a milk glycoprotein, can provide molecular mimicry of myelin oligodendrocyte glycoprotein and induce an autoinflammatory response against myelin. Other milk components such as casein, gangliosides, xanthine oxidase, and saturated fats are also analyzed for their potential involvement in the pathophysiology of MS. Finally, we fit milk alongside other well known risk factors of MS: vitamin D levels, Epstein Barr virus infection, and gut dysbiosis. In conclusion, this review summarizes potential mechanisms linking milk as an underappreciated potential risk factor for the development of MS.
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Affiliation(s)
- Caleb R Morin
- University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
| | | | - Morley D Hollenberg
- Department of Physiology & Pharmacology, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
| | - Michael C Brain
- Department of Biochemistry and Molecular Biology, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
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14
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Gai N, Uniacke-Lowe T, O'Regan J, Goulding DA, Kelly AL. Influence of β-casein genotype on physicochemical properties and functionality of bovine milk. J Dairy Sci 2023; 106:8357-8367. [PMID: 37641250 DOI: 10.3168/jds.2023-23687] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 07/02/2023] [Indexed: 08/31/2023]
Abstract
Several studies have been focused on the effect of milk protein genetic variants on milk physicochemical properties and functionality in recent years. β-casein, an important protein related to milk processibility, has been reported to have 2 main genetic variants A1 and A2, for which cows may be homozygous or heterozygous. In this study, several physicochemical properties of milk with β-casein variants A1A1, A1A2, and A2A2 from 3 collection occasions were analyzed. Higher manganese content and lower pH were found to be associated with the A1A1 variant compared with the other 2 genotypes. Better rennet and acid coagulation were found in A1A1 milk compared with A1A2 and A2A2 milk (although P > 0.05), whereas A2A2 milk was more stable to creaming compared with the other 2 genotypes, which may be linked to its smaller fat globule size. Thus, milk from cows with A1A1 genotype could be preferable for cheese making, while that with A2A2 variant can be used in formulations requiring good stability against creaming, and for example, yogurt making, where the softer yogurt texture may be easier to digest.
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Affiliation(s)
- N Gai
- School of Food and Nutritional Sciences, University College Cork, Cork, T12 YN60, Ireland
| | - T Uniacke-Lowe
- School of Food and Nutritional Sciences, University College Cork, Cork, T12 YN60, Ireland
| | - J O'Regan
- Nestlé Development Centre Nutrition, Wyeth Nutritionals Ireland, Askeaton, Co. Limerick, V94 E7P9, Ireland
| | - D A Goulding
- Nestlé Development Centre Nutrition, Wyeth Nutritionals Ireland, Askeaton, Co. Limerick, V94 E7P9, Ireland
| | - A L Kelly
- School of Food and Nutritional Sciences, University College Cork, Cork, T12 YN60, Ireland.
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15
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Gonzales-Malca JA, Tirado-Kulieva VA, Abanto-López MS, Aldana-Juárez WL, Palacios-Zapata CM. Worldwide research on the health effects of bovine milk containing A1 and A2 β-casein: Unraveling the current scenario and future trends through bibliometrics and text mining. Curr Res Food Sci 2023; 7:100602. [PMID: 37790856 PMCID: PMC10542606 DOI: 10.1016/j.crfs.2023.100602] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 09/19/2023] [Accepted: 09/22/2023] [Indexed: 10/05/2023] Open
Abstract
The possible adverse effect of consuming bovine milk with A1 β-casein (but not with A2 β-casein) on health aspects due to the release of β-casomorphin-7 (BCM-7) is currently under debate. The aim of this study was to perform a bibliometric analysis of studies extracted from Scopus to explore the relationship between BCM-7, A1 or A2 bovine milk with different aspects of health. Over time, several research groups were formed that are no longer active and although some authors have returned to the field of study, they have focused their efforts mainly on conducting reviews that show the same imprecise conclusions due to the few original articles. Research is concentrated in Europe and Asia, where New Zealand, China and Germany are the countries with the most publications, records and citations on the subject, respectively. On the other hand, no country in Africa or South America has scientific production, which opens the possibility of building collaborations between countries and exploring areas that lack scientific studies. Based on conflicting information from primarily in vitro and animal studies, and limited clinical trials with poor designs, A1 milk presents pro-inflammatory and oxidative activity, but the evidence is insufficient to associate its consumption with negative health effects. However, A2 milk may be better tolerated by the digestive system of some individuals, suggesting its possible modulating role in the intestinal microbiota. Stronger scientific evidence is needed to reach a consensus on whether the presence of β-casein A1 can significantly negatively affect health. The information shown will allow a better understanding of the subject and consumers will be able to make their own decisions regarding A1 or A2 milk.
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Affiliation(s)
- Jhony Alberto Gonzales-Malca
- Laboratorio de Tecnología de Alimentos y Procesos, Universidad Nacional de Frontera, Peru
- Laboratorio de Biología Molecular, Universidad Nacional de Frontera, Peru
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16
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Guingand DE Rivery M, Zeinab H, Cohen V, Baumstarck K, Luciano L, Vitton V. Does fecal calprotectin increase may be linked to lactose intolerance in patients with irritable bowel syndrome? Minerva Gastroenterol (Torino) 2023; 69:329-334. [PMID: 33829725 DOI: 10.23736/s2724-5985.21.02802-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a multifactorial condition without any specific investigation. Fecal calprotectin (FC) may be elevated in IBS without any explanation. In addition, some patients with IBS have symptoms related to lactose intolerance. Our main aim was to investigate whether an increase in FC could be related to lactose intolerance in patients with IBS. METHODS In this retrospective single-center study, all patients with IBS who have underwent a FC test and a lactose respiratory test within a period of less than 6 months were eligible. A FC greater than or equal to 50 μg/g was considered abnormal. RESULTS Severnty-six patients (48 females), mean age 38±15 years were included. Symptoms were respectively: bloating in 57%, diarrhea in 76% and abdominal pain in 46% of cases. Among the 76 patients: 22 (29%) had FC≥50 μg/g and 9/22 (41%) had a positive lactose test. No significant relationship could be identified between the increase in FC and the lactose test positivity. The value of the FC was also not related to the subtype of IBS or the positivity of the glucose test. CONCLUSIONS In our study, the increase in FC was not significantly related to the presence of lactose intolerance. Nevertheless, our work, despite its originality, is limited by its retrospective nature and small number of patients. Future studies including larger numbers of patients may identify the causes of elevated FC in patients with IBS to individualize different subgroups of patients to best adapt therapeutic management.
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Affiliation(s)
- Marine Guingand DE Rivery
- Unit of Gastroenterology, North Hospital, Assistance Publique-Hôpitaux de Marseille (AP-HM), Aix-Marseille University, Marseille, France -
| | - Hamidou Zeinab
- Unit of Chronic Diseases and Quality of Life-Research, EA3279-Public Health, Aix-Marseille University, Marseille, France
| | | | - Karine Baumstarck
- Unit of Chronic Diseases and Quality of Life-Research, EA3279-Public Health, Aix-Marseille University, Marseille, France
| | - Laure Luciano
- Department of Gastroenterology, Instruction Hospital of French Army Laveran, Marseille, France
| | - Véronique Vitton
- Unit of Gastroenterology, North Hospital, Assistance Publique-Hôpitaux de Marseille (AP-HM), Aix-Marseille University, Marseille, France
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17
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de Vasconcelos ML, Oliveira LMFS, Hill JP, Vidal AMC. Difficulties in Establishing the Adverse Effects of β-Casomorphin-7 Released from β-Casein Variants-A Review. Foods 2023; 12:3151. [PMID: 37685085 PMCID: PMC10486734 DOI: 10.3390/foods12173151] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 08/04/2023] [Accepted: 08/16/2023] [Indexed: 09/10/2023] Open
Abstract
β-Casomorphin-7 (BCM-7) is a peptide released through the proteolysis of β-casein (β-CN), which is considered a bioactive peptide displaying evidence of promoting the binding and activation of the μ-opioid receptor located in various body parts, such as the gastrointestinal tract, the immune system and potentially the central nervous system. The possible effects of BCM-7 on health are a theme rising in popularity due to evidence found in several studies on the modulation of gastrointestinal proinflammatory responses that can trigger digestive symptoms, such as abdominal discomfort. With the advancement of studies, the hypothesis that there is a correlation of the possible effects of BCM-7 with the microbiota-gut-brain axis has been established. However, some studies have suggested the possibility that these adverse effects are restricted to a portion of the population, and the topic is controversial due to the small number of in vivo studies, which makes it difficult to obtain more conclusive results. In addition, a threshold of exposure to BCM-7 has not yet been established to clarify the potential of this peptide to trigger physiological responses at gastrointestinal and systemic levels. The proportion of the population that can be considered more susceptible to the effects of BCM-7 are evidenced in the literature review. The challenges of establishing the adverse effects of BCM-7 are discussed, including the importance of quantifying the BCM-7 release in the different β-CN genotypes. In summary, the reviewed literature provides plausible indications of the hypothesis of a relationship between β-CN A1/BCM-7 and adverse health effects; however, there is need for further, especially in vivo studies, to better understand and confirm the physiological effects of this peptide.
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Affiliation(s)
- Marta Liliane de Vasconcelos
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga 13635-900, SP, Brazil; (M.L.d.V.); (L.M.F.S.O.)
| | - Luisa Maria F. S. Oliveira
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga 13635-900, SP, Brazil; (M.L.d.V.); (L.M.F.S.O.)
| | - Jeremy Paul Hill
- Department Sustainable Nutrition Initiative, Riddet Institute, Palmerston North, New Zealand, and Fonterra Research & Development Centre, Palmerston North 4472, New Zealand;
| | - Ana Maria Centola Vidal
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga 13635-900, SP, Brazil; (M.L.d.V.); (L.M.F.S.O.)
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18
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Bouzid YY, Chin EL, Spearman SS, Alkan Z, Stephensen CB, Lemay DG. No Associations between Dairy Intake and Markers of Gastrointestinal Inflammation in Healthy Adult Cohort. Nutrients 2023; 15:3504. [PMID: 37630694 PMCID: PMC10459578 DOI: 10.3390/nu15163504] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 08/04/2023] [Accepted: 08/07/2023] [Indexed: 08/27/2023] Open
Abstract
Dairy products are a good source of essential nutrients and past reviews have shown associations of dairy consumption with decreased systemic inflammation. Links between dairy intake and gastrointestinal (GI) inflammation are under-investigated. Therefore, we examined associations between reported dairy intake and markers of GI inflammation in healthy adults in a cross-sectional observational study, hypothesizing a negative association with yogurt intake, suggesting a protective effect, and no associations with total dairy, fluid milk, and cheese intake. Participants completed 24-h dietary recalls and a food frequency questionnaire (FFQ) to assess recent and habitual intake, respectively. Those who also provided a stool sample (n = 295), and plasma sample (n = 348) were included in analysis. Inflammation markers from stool, including calprotectin, neopterin, and myeloperoxidase, were measured along with LPS-binding protein (LBP) from plasma. Regression models tested associations between dairy intake variables and inflammation markers with covariates: age, sex, and body mass index (BMI). As yogurt is episodically consumed, we examined differences in inflammation levels between consumers (>0 cup equivalents/day reported in recalls) and non-consumers. We found no significant associations between dairy intake and markers of GI inflammation. In this cohort of healthy adults, dairy intake was not associated with GI inflammation.
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Affiliation(s)
- Yasmine Y. Bouzid
- USDA ARS Western Human Nutrition Research Center, Davis, CA 95616, USA
- Department of Nutrition, University of California, Davis, CA 95616, USA
| | - Elizabeth L. Chin
- USDA ARS Western Human Nutrition Research Center, Davis, CA 95616, USA
- Department of Nutrition, University of California, Davis, CA 95616, USA
| | - Sarah S. Spearman
- Department of Nutrition, University of California, Davis, CA 95616, USA
| | - Zeynep Alkan
- USDA ARS Western Human Nutrition Research Center, Davis, CA 95616, USA
| | - Charles B. Stephensen
- USDA ARS Western Human Nutrition Research Center, Davis, CA 95616, USA
- Department of Nutrition, University of California, Davis, CA 95616, USA
| | - Danielle G. Lemay
- USDA ARS Western Human Nutrition Research Center, Davis, CA 95616, USA
- Department of Nutrition, University of California, Davis, CA 95616, USA
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19
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Tagliamonte S, Barone Lumaga R, De Filippis F, Valentino V, Ferracane R, Guerville M, Gandolfi I, Barbara G, Ercolini D, Vitaglione P. Milk protein digestion and the gut microbiome influence gastrointestinal discomfort after cow milk consumption in healthy subjects. Food Res Int 2023; 170:112953. [PMID: 37316045 DOI: 10.1016/j.foodres.2023.112953] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 04/07/2023] [Accepted: 05/10/2023] [Indexed: 06/16/2023]
Abstract
Many healthy people suffer from milk-related gastrointestinal discomfort (GID) despite not being lactose intolerant; the mechanisms underpinning such condition are unknown. This study aimed to explore milk protein digestion and related physiological responses (primary outcome), gut microbiome and gut permeability in 19 lactose-tolerant healthy nonhabitual milk consumers [NHMCs] reporting GID after consuming cow milk compared to 20 habitual milk consumers [HMCs] without GID. NHMCs and HMCs participated in a milk-load (250 mL) test, underwent blood sample collection at 6 time points over 6 h after milk consumption and collected urine samples and GID self-reports over 24 h. We measured the concentrations of 31 milk-derived bioactive peptides (BAPs), 20 amino acids, 4 hormones, 5 endocannabinoid system mediators, glucose and the dipeptidyl peptidase-IV (DPPIV) activity in blood and indoxyl sulfate in urine samples. Subjects also participated in a gut permeability test and delivered feces sample for gut microbiome analysis. Results showed that, compared to HMCs, milk consumption in NHMCs, along with GID, elicited a slower and lower increase in circulating BAPs, lower responses of ghrelin, insulin, and anandamide, a higher glucose response and serum DPPIV activity. The gut permeability of the two groups was similar, while the habitual diet, which was lower in dairy products and higher in the dietary-fibre-to-protein ratio in NHMCs, possibly shaped the gut microbiome; NHMCs exhibited lower abundance of Bifidobacteria, higher abundance of Prevotella and lower abundance of protease-coding genes, which may have reduced protein digestion, as evidenced by lower urinary excretion of indoxyl sulfate. In conclusion, the findings showed that a less efficient digestion of milk proteins, supported by a lower proteolytic capability of the gut microbiome, may explain GID in healthy people after milk consumption.
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Affiliation(s)
- Silvia Tagliamonte
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
| | - Roberta Barone Lumaga
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
| | - Francesca De Filippis
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy; Task Force on Microbiome Studies, University of Naples Federico II, 80134 Naples, Italy
| | - Vincenzo Valentino
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy; Task Force on Microbiome Studies, University of Naples Federico II, 80134 Naples, Italy
| | - Rosalia Ferracane
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
| | - Mathilde Guerville
- Nutrition Department, Lactalis Research & Development, 35240 Retiers, France
| | - Ivana Gandolfi
- Nutrition Department, Lactalis Research & Development, 43038 Sala Baganza, Italy
| | - Giovanni Barbara
- Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna, 40138 Bologna, Italy
| | - Danilo Ercolini
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy; Task Force on Microbiome Studies, University of Naples Federico II, 80134 Naples, Italy
| | - Paola Vitaglione
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy; Task Force on Microbiome Studies, University of Naples Federico II, 80134 Naples, Italy.
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20
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Meng Y, Zhou Y, Li H, Chen Y, Dominik G, Dong J, Tang Y, Saavedra JM, Liu J. Effectiveness of Growing-Up Milk Containing Only A2 β-Casein on Digestive Comfort in Toddlers: A Randomized Controlled Trial in China. Nutrients 2023; 15:nu15061313. [PMID: 36986042 PMCID: PMC10058316 DOI: 10.3390/nu15061313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 02/28/2023] [Accepted: 03/03/2023] [Indexed: 03/30/2023] Open
Abstract
BACKGROUND Emerging clinical evidence indicates the potential gastrointestinal (GI) benefits of milk containing only A2 β-casein, but data from randomized controlled trials is sparse among pediatric populations. We aimed to evaluate the effectiveness of growing-up milk (GUM) containing only A2 β-casein on GI tolerance in toddlers. METHODS A total of 387 toddlers aged 12-36 months were recruited in Beijing, China, and randomized in a 1:1:1 ratio to consume one of two commercially available A2 GUMs (combined in the analysis as A2 GUM) or continue their current feeding regimen of conventional milk for 14 days. The primary outcome was the total Gut Comfort Score (GCS) (range: 10-60; higher values indicate greater GI distress) derived from a 10-item (score range: 1-6 per item) parent-reported questionnaire, reflecting GI tolerance. RESULTS The GCS (mean ± SD) was comparable between the A2 GUM and conventional milk groups on day 7 (14.7 ± 5.0 vs. 15.0 ± 6.1, p = 0.54) and day 14 (14.0 ± 4.5 vs. 14.3 ± 5.5, p = 0.51). Parents reported less constipation in those consuming A2 GUM vs. conventional milk on day 14 (1.3 ± 0.6 vs. 1.4 ± 0.9, p = 0.020). Among 124 participants with minor GI distress at baseline (GCS ≥ 17, top tertile range 17-35), GCS was significantly lower in those consuming A2 GUM on day 7 (18.2 ± 5.1 vs. 21.2 ± 6.8, p = 0.004) and day 14 (17.1 ± 5.3 vs. 19.6 ± 6.3, p = 0.026), as were individual GI symptoms (all p < 0.05). In the toddlers without GI issues at baseline (GCS < 17), a low GCS was maintained throughout the study period after switching to A2 GUM (mean values range 10-13). CONCLUSIONS Growing-up milk containing only A2 β-casein were well-tolerated and associated with lower parent-reported constipation scores after two weeks when compared to conventional milks. In healthy toddlers with minor GI distress, A2 GUM improved overall digestive comfort and GI-related symptoms within one week.
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Affiliation(s)
- Ying Meng
- National Health Commission Key Laboratory of Reproductive Health/Institute of Reproductive and Child Health, Peking University Health Science Center, 38 Xueyuan Rd., Beijing 100191, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Rd., Beijing 100191, China
| | - Yubo Zhou
- National Health Commission Key Laboratory of Reproductive Health/Institute of Reproductive and Child Health, Peking University Health Science Center, 38 Xueyuan Rd., Beijing 100191, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Rd., Beijing 100191, China
| | - Hongtian Li
- National Health Commission Key Laboratory of Reproductive Health/Institute of Reproductive and Child Health, Peking University Health Science Center, 38 Xueyuan Rd., Beijing 100191, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Rd., Beijing 100191, China
| | - Yipu Chen
- Nestlé Product Technology Center-Nutrition, 1800 Vevey, Switzerland
| | | | - Jie Dong
- Wyeth Nutrition, Shanghai 200040, China
| | - Youchi Tang
- Information Management Section, Chaoyang District Maternal and Child Health Hospital, Beijing 100021, China
| | - Jose M Saavedra
- Division of Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Jianmeng Liu
- National Health Commission Key Laboratory of Reproductive Health/Institute of Reproductive and Child Health, Peking University Health Science Center, 38 Xueyuan Rd., Beijing 100191, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Rd., Beijing 100191, China
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21
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Ramakrishnan M, Zhou X, Dydak U, Savaiano DA. Gastric Emptying of New-World Milk Containing A1 and A2 Β-Casein Is More Rapid as Compared to Milk Containing Only A2 Β-Casein in Lactose Maldigesters: A Randomized, Cross-Over Trial Using Magnetic Resonance Imaging. Nutrients 2023; 15:nu15040801. [PMID: 36839159 PMCID: PMC9963893 DOI: 10.3390/nu15040801] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 01/20/2023] [Accepted: 02/01/2023] [Indexed: 02/09/2023] Open
Abstract
Lactose maldigesters report an increase in abdominal pain due to the consumption of milk containing a mixture of A1 and A2 β-casein as compared to milk containing only A2 β-casein. Gastric transit affects gastrointestinal symptoms and rapid transit has been associated with an increase in abdominal pain. We conducted a double-blinded, randomized, crossover trial in 10 lactose maldigesters. Subjects consumed each of the two types of milk: conventional milk containing 75% A1 β-casein and 25% A2 β-casein and A2 milk containing 100% A2 β-casein. Magnetic resonance images were acquired, and abdominal pain was rated and recorded at 0, 10, 30, 60 and 120 min after milk consumption. The volume of milk in the stomach was calculated using FSL software. The volume of milk in the stomach after consuming milk with 75% A1 β-casein and 25% A2 β-casein was significantly lower at 30 (p = 0.01), 60 (p = 0.002) and 120 (p < 0.001) minutes as compared to milk with 100% A2 β-casein in the 10 lactose maldigesters. The transit of New-World milk containing A1 and A2 β-casein was more rapid as compared to Old-World milk containing only A2 β-casein. This difference in transit may mediate symptoms of lactose intolerance.
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Affiliation(s)
- Monica Ramakrishnan
- Department of Nutrition Science, College of Health and Human Sciences, Purdue University, West Lafayette, IN 47907, USA
- Correspondence:
| | - Xiaopeng Zhou
- School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA
| | - Ulrike Dydak
- School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA
| | - Dennis A. Savaiano
- Department of Nutrition Science, College of Health and Human Sciences, Purdue University, West Lafayette, IN 47907, USA
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Li A, Zheng J, Han X, Jiang Z, Yang B, Yang S, Zhou W, Li C, Sun M. Health implication of lactose intolerance and updates on its dietary management. Int Dairy J 2023. [DOI: 10.1016/j.idairyj.2023.105608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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Cieślińska A, Fiedorowicz E, Rozmus D, Sienkiewicz-Szłapka E, Jarmołowska B, Kamiński S. Does a Little Difference Make a Big Difference? Bovine β-Casein A1 and A2 Variants and Human Health-An Update. Int J Mol Sci 2022; 23:15637. [PMID: 36555278 PMCID: PMC9779325 DOI: 10.3390/ijms232415637] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
For over 20 years, bovine beta-casein has been a subject of increasing scientific interest because its genetic A1 variant during gastrointestinal digestion releases opioid-like peptide β-casomorphin-7 (β-CM-7). Since β-CM-7 is involved in the dysregulation of many physiological processes, there is a growing discussion of whether the consumption of the β-casein A1 variant has an influence on human health. In the last decade, the number of papers dealing with this problem has substantially increased. The newest clinical studies on humans showed a negative effect of variant A1 on serum glutathione level, digestive well-being, cognitive performance score in children, and mood score in women. Scientific reports in this field can affect the policies of dairy cattle breeders and the milk industry, leading to the elimination of allele A1 in dairy cattle populations and promoting milk products based on milk from cows with the A2A2 genotype. More scientific proof, especially in well-designed clinical studies, is necessary to determine whether a little difference in the β-casein amino acid sequence negatively affects the health of milk consumers.
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Affiliation(s)
- Anna Cieślińska
- Department of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Ewa Fiedorowicz
- Department of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Dominika Rozmus
- Department of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Edyta Sienkiewicz-Szłapka
- Department of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Beata Jarmołowska
- Department of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Stanisław Kamiński
- Department of Animal Genetics, University of Warmia and Mazury, 10-719 Olsztyn, Poland
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Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R. Cow's milk-induced gastrointestinal disorders: From infancy to adulthood. World J Clin Pediatr 2022; 11:437-454. [PMID: 36439902 PMCID: PMC9685681 DOI: 10.5409/wjcp.v11.i6.437] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 09/01/2022] [Accepted: 10/14/2022] [Indexed: 11/07/2022] Open
Abstract
Milk is related to many gastrointestinal disorders from the cradle to the grave due to the many milk ingredients that can trigger gastrointestinal discomfort and disorders. Cow's milk protein allergy (CMPA) is the most common food allergy, especially in infancy and childhood, which may persist into adulthood. There are three main types of CMPA; immunoglobulin E (IgE)-mediated CMPA, non-IgE-mediated CMPA, and mixed type. CMPA appears before the first birthday in almost all cases. Symptoms may start even during the neonatal period and can be severe enough to simulate neonatal sepsis. CMPA (often non-IgE mediated) can present with symptoms of gastroesophageal reflux, eosinophilic esophagitis, hemorrhagic gastritis, food protein-induced protein-losing enteropathy, and food protein-induced enterocolitis syndrome. Most CMPAs are benign and outgrown during childhood. CMPA is not as common in adults as in children, but when present, it is usually severe with a protracted course. Lactose intolerance is a prevalent condition characterized by the development of many symptoms related to the consumption of foods containing lactose. Lactose intolerance has four typical types: Developmental, congenital, primary, and secondary. Lactose intolerance and CMPA may be the underlying pathophysiologic mechanisms for many functional gastrointestinal disorders in children and adults. They are also common in inflammatory bowel diseases. Milk consumption may have preventive or promoter effects on cancer development. Milk may also become a source of microbial infection in humans, causing a wide array of diseases, and may help increase the prevalence of antimicrobial resistance. This editorial summarizes the common milk-related disorders and their symptoms from childhood to adulthood.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Algharbia, Egypt
- Department of Pediatrics, University Medical Center, Arabian Gulf University, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Department of Pathology, Microbiology Section, Salmaniya Medical Complex, Manama 26671, Bahrain
- Department of Pathology, Microbiology Section, Royal College of Surgeons in Ireland - Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Chest Diseases, Faculty of Medicine, Tanta University, Tanta 31527, Algharbia, Egypt
- Department of Chest Diseases, University Medical Center, Arabian Gulf University, Manama 26671, Bahrain
| | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland - Bahrain, Busiateen 15503, Muharraq, Bahrain
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Daniloski D, McCarthy NA, Huppertz T, Vasiljevic T. What is the impact of amino acid mutations in the primary structure of caseins on the composition and functionality of milk and dairy products? Curr Res Food Sci 2022; 5:1701-1712. [PMID: 36212081 PMCID: PMC9535159 DOI: 10.1016/j.crfs.2022.09.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/25/2022] [Accepted: 09/28/2022] [Indexed: 11/19/2022] Open
Abstract
The impact of amino acid mutations within the peptide structure of bovine milk protein is important to understand as it can effect processability and subsequently effect its physiological properties. Genetic polymorphisms of bovine caseins can influence the chemical, structural, and technological properties, including casein micelle morphology, calcium distribution, network creation upon gelation, and surface activity. The A1 and A2 genetic variants of β-casein have recently acquired growing attention from both academia and industry, prompting new developments in the area. The difference between these two genetic variants is the inclusion of either proline in β-casein A2 or histidine in β-casein A1 at position 67 in the peptide chain. The aim of this review was to examine the extent to which milk and ingredient functionality is influenced by β-casein phenotype. One of the main findings of this review was although β-casein A1 was found to be the dominant variant in milks with superior acid gelation and rennet coagulation properties, milks comprised of β-casein A2 possessed greater emulsion and foam formation capabilities. The difference in the casein micelle assembly, hydrophobicity, and chaperone activity of caseins may explain the contrast in the functionality of milks containing β-casein from either A1 or A2 families. This review provides new insights into the subtle variations in the physicochemical properties of bovine milks, which could potentially support dairy producers in the development of new dairy products with different functional properties.
Impact of β- and other caseins on the casein micelle structure and functionality. Proline and histidine in β-caseins play a key role in casein micelle conformation. Chaperone activity of β-casein A2 towards heat-induced aggregation of whey protein. Gels prepared of milks with β-casein A1 possess a denser and firmer structure. Ordered structure of β-casein A2 led to improved emulsion and foam formation.
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Affiliation(s)
- Davor Daniloski
- Advanced Food Systems Research Unit, Institute for Sustainable Industries and Liveable Cities and College of Health and Biomedicine, Victoria University, Melbourne, VIC, 8001, Australia
- Food Chemistry and Technology Department, Teagasc Food Research Centre, Moorepark, Fermoy, P61 C996, Cork, Ireland
| | - Noel A. McCarthy
- Food Chemistry and Technology Department, Teagasc Food Research Centre, Moorepark, Fermoy, P61 C996, Cork, Ireland
| | - Thom Huppertz
- Advanced Food Systems Research Unit, Institute for Sustainable Industries and Liveable Cities and College of Health and Biomedicine, Victoria University, Melbourne, VIC, 8001, Australia
- FrieslandCampina, Amersfoort, the Netherlands
- Wageningen University & Research, Wageningen, the Netherlands
| | - Todor Vasiljevic
- Advanced Food Systems Research Unit, Institute for Sustainable Industries and Liveable Cities and College of Health and Biomedicine, Victoria University, Melbourne, VIC, 8001, Australia
- Corresponding author.
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A2 Milk: New Perspectives for Food Technology and Human Health. Foods 2022; 11:foods11162387. [PMID: 36010390 PMCID: PMC9407547 DOI: 10.3390/foods11162387] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/02/2022] [Accepted: 08/06/2022] [Indexed: 11/18/2022] Open
Abstract
Although milk consumption is increasing worldwide, in some geographical regions, its consumption has persistently declined in recent decades. This fact, together with the increase in milk production prices, has caused both milk producers and the dairy industry to be immersed in a major crisis. Some possible solutions to this problem are to get people who do not currently consume milk to start drinking it again, or to market milk and dairy products with a higher added value. In this context, a type of milk called A2 has recently received attention from the industry. This type of milk, characterized by a difference in an amino acid at position 67 of the β-casein polypeptide chain, releases much smaller amounts of bioactive opioid peptide β-casomorphin 7 upon digestion, which has been linked to harmful effects on human health. Additionally, A2 milk has been attributed worse technological properties in the production of some dairy products. Thus, doubts exist about the convenience for the dairy industry to bet on this product. The aim of this review is to provide an update on the effects on human health of A2 milk, as well as its different technological properties to produce dairy products.
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Weimer DS, Demory Beckler M. Underlying Immune Mechanisms Involved in Cow’s Milk-Induced Hypersensitivity Reactions Manifesting as Atopic Dermatitis. Cureus 2022; 14:e27604. [PMID: 36059314 PMCID: PMC9433788 DOI: 10.7759/cureus.27604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 08/02/2022] [Indexed: 11/26/2022] Open
Abstract
Of the many symptoms associated with cow’s milk allergy (CMA), many populations face the burden of the appearance or worsening of atopic dermatitis (AD) when consuming milk products. Due to the prevalence and possible severity of symptoms, it is important to understand the underlying immune mechanisms involved in such reactions. Hypersensitivity reactions are exaggerated immune responses to often benign antigens, many times resulting in a cascade of pro-inflammatory processes. Of the four major types, type I and IV are of most relevance when considering atopic dermatitis worsened by cow’s milk. Considered a “true allergy,” type I (immediate) hypersensitivity reactions occur within hours after secondary exposure to an allergen and are primarily driven by antibodies and humoral immune responses. On the contrary, type IV (delayed) hypersensitivity reactions are driven by cell-mediated responses involving T-cell activation. Due to the array of symptoms induced by these complex reactions, it is imperative to diagnose early and treat appropriately. In this literature review, we aim to highlight the primary underlying immune contributors to hypersensitivity reactions, discuss AD as a manifestation of hypersensitivity reactions to cow’s milk, and consider current and future treatment options for combatting hypersensitivities manifesting as AD.
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Demographic pattern of A1/A2 beta casein variants indicates conservation of A2 type haplotype across native cattle breeds (Bos indicus) of India. 3 Biotech 2022; 12:167. [PMID: 35845115 PMCID: PMC9276908 DOI: 10.1007/s13205-022-03232-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 06/17/2022] [Indexed: 11/30/2022] Open
Abstract
Genetic variations of the beta casein gene hold importance because of their probable association with human health. Comparative sequence analysis of β-casein gene across Indian native, crossbred and exotic breeds in India revealed 15 SNPs and 4 INDELs corresponding to 14 haplotypes. The frequency of A2 type haplotype was maximum (0.941) across all Indian native breeds. Among the 15 variants reported for taurine breeds, only three (A1, A2 and B) were observed in analysed populations. Allelic profiling of A1/A2 β-casein variants in ~ 4000 animals belonging to three cattle types and breeding bulls also revealed the predominance of A2 allele (0.95) in Indian cattle. The high proportion of A2 allele/haplotype indicates that Indian native cattle are the best suited to meet the demands for A2 milk globally. However, a higher percentage of heterozygous genotype (A1A2) in breeding bulls warrants the need to screen sire lines so as to drift the herd towards A2. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03232-0.
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Jiménez-Montenegro L, Alfonso L, Mendizabal JA, Urrutia O. Worldwide Research Trends on Milk Containing Only A2 β-Casein: A Bibliometric Study. Animals (Basel) 2022; 12:ani12151909. [PMID: 35953898 PMCID: PMC9367265 DOI: 10.3390/ani12151909] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 07/16/2022] [Accepted: 07/22/2022] [Indexed: 11/26/2022] Open
Abstract
Simple Summary A1 β-casein has been correlated with adverse health outcomes, and, as a consequence, milk containing only A2 β-casein has emerged on the market. There has been a relevant increase in publications in this area since 2010. Food Science Technology and Agriculture were the main research areas of this topic. The term β-casomorphin was the most frequently used. The USA, New Zealand, and Australia were the most productive countries, though the most productive research institutions were, in absolute terms, from India, France, and Germany. The majority of the most cited studies that refer to A2 β-casein and health were reviews, and a few clinical trials have also been published. Abstract The protein fraction of β-casein may play a key role in the manifestation of a new intolerance: milk protein intolerance. The most common forms of β-casein among dairy cattle breeds are A1 and A2 β-casein. During gastrointestinal digestion of A1 β-casein, an opioid called peptide β-casomorphin-7 (BCM-7) is more frequently released, which can lead to adverse health outcomes. For that reason, novel products labelled as “A2 milk” or “A1-free dairy products” have appeared on the market. In this context, a bibliometric analysis on A2 β-casein research was carried out through the Web of Science (WoS) database. The main objective of this work was to provide an overview of the state of the art in the field of β-casein A2 by analyzing the number of publications per year, trends in thematic content, the most frequently used terms, and the most important institutions and countries in the field. This bibliometric study showed that a greater effort is needed to determine the possible implications of this novel product for human health and the market.
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Kaplan M, Baydemir B, Günar BB, Arslan A, Duman H, Karav S. Benefits of A2 Milk for Sports Nutrition, Health and Performance. Front Nutr 2022; 9:935344. [PMID: 35911103 PMCID: PMC9326461 DOI: 10.3389/fnut.2022.935344] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 06/17/2022] [Indexed: 11/13/2022] Open
Abstract
Bovine milk is one of the best pre-and pro-workout sources for athletes owing to its rich nutritional content. Even though bovine milk consumption significantly benefits athletes' health and performance, many athletes cannot consume bovine milk since they struggle with gastrointestinal problems caused after milk consumption. Especially, the consumption of regular milk, which contains A1 β-casein, is associated with a variety of diseases ranging from gastrointestinal discomfort to ischemic heart diseases. The main reason behind this is related to β-casomorphine 7 (BCM-7), which is derived from A1 β-casein during the digestion of A1 milk. A1 β-casein is formed as a result of a point mutation in the position of 67th in the amino acid sequence A2 β-casein by changing proline to histidine. Therefore, this mutated form of β-casein in regular milk cannot easily be digested by the human-associated digestion enzymes. A2 milk, which includes A2 β-casein instead of A1 β-casein, is the best substitute for regular milk with the same nutritional content. This natural form of milk positively affects the athlete's health as well as performance without causing any gastrointestinal discomfort or more serious problems which are seen in the consumption of regular milk. In this review, A2 milk and its potential health effects in comparison to diseases related to A1 milk consumption are discussed.
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Affiliation(s)
- Merve Kaplan
- Department of Molecular Biology and Genetics, Canakkale Onsekiz Mart University, Canakkale, Turkey
| | - Barış Baydemir
- Department of Coaching Education, Canakkale Onsekiz Mart University, Canakkale, Turkey
| | - Bilgetekin Burak Günar
- Department of Physical Education and Sports Teaching, Canakkale Onsekiz Mart University, Canakkale, Turkey
| | - Ayşenur Arslan
- Department of Molecular Biology and Genetics, Canakkale Onsekiz Mart University, Canakkale, Turkey
| | - Hatice Duman
- Department of Molecular Biology and Genetics, Canakkale Onsekiz Mart University, Canakkale, Turkey
| | - Sercan Karav
- Department of Molecular Biology and Genetics, Canakkale Onsekiz Mart University, Canakkale, Turkey
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31
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Review: The effect of casein genetic variants, glycosylation and phosphorylation on bovine milk protein structure, technological properties, nutrition and product manufacture. Int Dairy J 2022. [DOI: 10.1016/j.idairyj.2022.105440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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32
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Semwal R, Joshi SK, Semwal RB, Sodhi M, Upadhyaya K, Semwal DK. Effects of A1 and A2 variants of β-casein on human health—is β-casomorphin-7 really a harmful peptide in cow milk? NUTRIRE 2022; 47:8. [DOI: 10.1186/s41110-022-00159-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 04/19/2022] [Indexed: 01/03/2025]
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Prodhan UK, Milan AM, Shrestha A, Vickers MH, Cameron-Smith D, Barnett MPG. Circulatory amino acid responses to milk consumption in dairy and lactose intolerant individuals. Eur J Clin Nutr 2022; 76:1415-1422. [PMID: 35459911 PMCID: PMC9550627 DOI: 10.1038/s41430-022-01119-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 02/27/2022] [Accepted: 03/10/2022] [Indexed: 11/09/2022]
Abstract
Background/objectives Self-reported digestive intolerance to dairy foods is common. As dairy can be an important source of dietary protein, this study aimed to identify whether milk protein digestion is compromised in individuals with digestive intolerance. Subjects/methods Adult women (n = 40) were enroled in this double-blinded, randomised cross-over trial, with digestive symptoms characterised using a lactose challenge and self-reported digestive symptom questionnaire. Participants were classified as either lactose intolerant (LI, n = 10), non-lactose dairy intolerant (NLDI, n = 20) or dairy tolerant (DT, n = 10). In a randomised sequence, participants consumed three different kinds of milk (750 ml); conventional milk (CON), a2 Milk™ (A2M), and lactose-free conventional milk (LF-CON). Circulatory plasma amino acid (AA) concentrations were measured at baseline and every 30 min until 3 h post-ingestion. Results In all participants across all milk types, plasma AA concentrations (AUC0-180) increased after milk ingestion with no significant differences in responses observed between milk types or participants (P > 0.05), with the exception of the suppressed lysine response in the DT group following A2M ingestion, relative to the other two groups and milk types (P < 0.05). Conclusion Milk protein digestion, as determined by circulatory AAs, is largely unaffected by dairy- and lactose- intolerances. ![]()
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Affiliation(s)
- Utpal Kumar Prodhan
- Liggins Institute, The University of Auckland, 85 Park Road, Grafton, Private Bag 92019, Auckland, 1023, New Zealand.,The Riddet Institute, Palmerston North, 4442, New Zealand.,Department of Food Technology and Nutritional Science, Mawlana Bhashani Science and Technology University, Tangail, 1902, Bangladesh
| | - Amber Marie Milan
- Liggins Institute, The University of Auckland, 85 Park Road, Grafton, Private Bag 92019, Auckland, 1023, New Zealand.,Smart Foods Innovation Centre of Excellence, AgResearch Limited, Private Bag 11008, Palmerston North, 4442, New Zealand.,The High-Value Nutrition National Science Challenge, Auckland, 1023, New Zealand
| | - Aahana Shrestha
- Liggins Institute, The University of Auckland, 85 Park Road, Grafton, Private Bag 92019, Auckland, 1023, New Zealand.,The Riddet Institute, Palmerston North, 4442, New Zealand
| | - Mark Hedley Vickers
- Liggins Institute, The University of Auckland, 85 Park Road, Grafton, Private Bag 92019, Auckland, 1023, New Zealand
| | - David Cameron-Smith
- Liggins Institute, The University of Auckland, 85 Park Road, Grafton, Private Bag 92019, Auckland, 1023, New Zealand.,The Riddet Institute, Palmerston North, 4442, New Zealand.,Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research, Singapore, 117609, Singapore
| | - Matthew Philip Greig Barnett
- The Riddet Institute, Palmerston North, 4442, New Zealand. .,Smart Foods Innovation Centre of Excellence, AgResearch Limited, Private Bag 11008, Palmerston North, 4442, New Zealand. .,The High-Value Nutrition National Science Challenge, Auckland, 1023, New Zealand.
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Xiao S, Wang Q, Li C, Liu W, Zhang J, Fan Y, Su J, Wang H, Luo X, Zhang S. Rapid identification of A1 and A2 milk based on the combination of mid-infrared spectroscopy and chemometrics. Food Control 2022. [DOI: 10.1016/j.foodcont.2021.108659] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Bahbah WA, ElHodhod M, Salah M, AlRefaee F, AlTuraiki M, Mousa S, Al Mehaidib A, Ayesh WH, El-Bazzar AN, El Haddad J, El Khashab HY, El Zawahry A, Hasosah M, Shaaban SY, Vandenplas Y. A Survey to Identify the Current Management of Cow’s Milk Disorders and the Role of Goat Milk-Based Formulas in the Middle East and North Africa Region. Nutrients 2022; 14:nu14051067. [PMID: 35268042 PMCID: PMC8912394 DOI: 10.3390/nu14051067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 01/18/2022] [Accepted: 01/20/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Cow’s milk allergy (CMA) and cow’s milk intolerance (CMI) are the major cow’s milk disorders observed in infants and young children. This study investigates, for the first time, physician knowledge regarding CMA and CMI prevalence, diagnosis, and management in the Middle East and North Africa (MENA) region. In addition, we explore the role of goat milk-based formula as an alternative in infants suffering from CMI. Method: This cross-sectional survey was conducted from December 2020 to February 2021. A convenience sample of 2500 MENA-based physicians received the questionnaire, developed by a working group of pediatric experts. Results: 1868 physicians completed the questionnaire, including pediatric specialists (80.8%), training physicians (0.2%), dermatologists (0.1%), family/general physicians (12.9%), neonatologists (3.6%), neurosurgeons (0.2%), allergy nurse specialists (0.3%), pharmacists (2.1%), and public health workers (0.1%). Differentiation between CMA and CMI was recognized by the majority of respondents (80.7%), for which the majority of respondents (35.4%) identified that the elimination and challenge test was the best test to differentiate CMA from CMI, whereas 30.7% and 5.4% preferred the immunoglobulin E (IgE) test and skin prick test, respectively. In addition, 28.5% of respondents reported that there is no confirmatory test to differentiate CMA from CMI. The majority of respondents (47.3%) reported that amino acid-based formula (AAF)/ extensively hydrolyzed formula (EHF) is the cornerstone for the management of CMA. However, most respondents (33.7%) reported that lactose avoidance was best for the management of CMI. Overall, 65% of the respondents were aware of nutritionally adapted goat’s milk formula as an alternative to cow’s milk products and 37% would recommend its routine use in infants (≤2 years of age). Conclusion: The results of this survey demonstrate that the majority of physicians are aware of the underlying pathophysiology and management of CMA and CMI. However, a significant proportion of physicians do not follow the clinical guidelines concerning CMA/CMI diagnosis and management. Notably, this survey identified that goat’s milk formulas may offer a suitable alternative to AAF/EHF in infants with CMI as they contain β-casein protein which is easily digestible. In addition, goat’s milk formulas contain higher levels of oligosaccharides and medium-chained fatty acids compared with standard cow’s milk formulas, yet further clinical trials are warranted to support the inclusion of goat’s milk formulas in clinical guidelines.
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Affiliation(s)
- Wael A. Bahbah
- Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebin El-Kom 32511, Egypt;
| | - Mostafa ElHodhod
- Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt;
- Faculty of Medicine, October 6 University, Giza 12511, Egypt
| | | | - Fawaz AlRefaee
- Department of Pediatrics, Al Adan Hospital, Ministry of Health, Kuwait City P.O. Box 46969, Kuwait;
| | - Muath AlTuraiki
- Department of Pediatrics, King Salman Hospital, Riyadh 12769, Saudi Arabia;
| | - Samira Mousa
- Medical Department, Faculty of Veterinary Medicine, Benha University, Benha 13518, Egypt;
| | - Ali Al Mehaidib
- Department of Pediatrics, King Faisal Specialist Hospital & Research Center, Riyadh 11211, Saudi Arabia;
| | - Wafaa Helmi Ayesh
- Department of Clinical Nutrition, Dubai Health Authority, Dubai P.O. Box 4545, United Arab Emirates;
| | - Ahmed N. El-Bazzar
- Department of Pediatrics, Ministry of Health Hospitals, Cairo 12613, Egypt;
| | - Joseph El Haddad
- Department of Pediatrics and Neonatology, Saint George University Hospital, Beirut 1100, Lebanon;
| | - Heba Y. El Khashab
- Department of Pediatrics, Sulaiman Al Habib Medical Group, Riyadh 12214, Saudi Arabia;
- Department of Pediatrics, Ain Shams University, Cairo 11566, Egypt
| | - Amr El Zawahry
- Pediatrics Department, King’s College Hospital London, Dubai P.O. Box 340901, United Arab Emirates;
- Department of Pediatrics, Sharjah University, Sharjah P.O. Box 27272, United Arab Emirates
| | - Mohammed Hasosah
- King Abdullah International Medical Research Center, Pediatric Gastroenterology Department, National Guard Hospital, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 21482, Saudi Arabia;
| | - Sanaa Youssef Shaaban
- Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt;
| | - Yvan Vandenplas
- KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, 1090 Brussels, Belgium
- Correspondence:
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Prasad A, Kothari N. Cow products: boon to human health and food security. Trop Anim Health Prod 2021; 54:12. [PMID: 34894304 PMCID: PMC8665701 DOI: 10.1007/s11250-021-03014-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 12/03/2021] [Indexed: 02/05/2023]
Abstract
The world population exceeded 7.8 billion people in 2020 and is predicted to reach 9.9 billion by 2050 as per the current increasing rate of 25%. In view of this, ensuring human health and food security has become an issue of key importance to countries with different degrees of economic development. At the same time, the livestock sector plays a strategic role in improving the economic, environmental, and sociocultural stewardship of any nation. The cow (Bos indicus) has held a distinctive role in human history ever since its domestication because of its valued harvests like dairy products (milk, clarified butter, yogurt, curd, and buttermilk) excreta like dung and urine. These products, except dung, provide all the necessary energy and nutrients to ensure the proper growth and development of the human. They are the source of many bioactive substances, which possess immense pharmacotherapeutic action against various physiological, metabolic and infectious disorders, including COVID-19. The use of urine and dung can be considered a low-cost agricultural practice for farmers and has been extensively used in modern agriculture practices to ensure food security via soil fertility, plant pathogens, and pests. Cow urine mediated synthesized nanomaterial also display distinctive characteristics and novel applications in various fields of science and technology. Thus, this paper aims to provide a comprehensive overview of cow products, describing their biochemical constituents, bioactivities, and their utilization in the area ranging from human welfare to agriculture sustainability. An attempt is also made to present possible applications in bioenergy production and pollution reduction.
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Affiliation(s)
- Arti Prasad
- Laboratory of Public Health Entomology, Department of Zoology, M. L. Sukhadia University, Udaipur, Rajasthan, India
| | - Naresh Kothari
- Laboratory of Public Health Entomology, Department of Zoology, M. L. Sukhadia University, Udaipur, Rajasthan, India.
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Hockey M, Aslam H, Berk M, Pasco JA, Ruusunen A, Mohebbi M, Macpherson H, Chatterton ML, Marx W, O'Neil A, Rocks T, McGuinness AJ, Young LM, Jacka FN. The Moo'D Study: protocol for a randomised controlled trial of A2 beta-casein only versus conventional dairy products in women with low mood. Trials 2021; 22:899. [PMID: 34895297 PMCID: PMC8665310 DOI: 10.1186/s13063-021-05812-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 11/09/2021] [Indexed: 12/28/2022] Open
Abstract
Background Beta-casein is a major protein in cow’s milk, of which A1 and A2 are the most frequent variants. Recent evidence implicates A1 beta-casein consumption in mechanisms that are of potential importance to mental health, yet its possible effects on psychological endpoints remains unknown. The primary aim of the study is to evaluate the comparative effects of consumption of dairy products containing A2 beta-casein versus conventional dairy (i.e. containing both A1 and A2 beta-casein) on symptoms of psychological distress in women with low mood. Methods ‘The Moo’D Study’ is a 16-week, superiority, 1:1 parallel group, triple-blinded, randomised controlled trial. Ninety women with low mood (Patient Health Questionnaire score ≥ 5) will be randomised to consume either A2 beta-casein only or conventional dairy products. The primary outcome, symptoms of psychological distress, will be measured by the 21-item Depression, Anxiety and Stress Scale. Secondary outcomes will include symptoms of depression, anxiety and stress, severity of low mood, cognition, gut microbiota composition, gut symptomatology, markers of immune function, gut inflammation, systemic metabolites, endothelial integrity and oxidative stress, body composition, perceived wellbeing, sleep, quality of life, resource use and cost-effectiveness. Discussion This study will advance our understanding of the possible impact of milk proteins on psychological distress in women as well as elucidate mechanisms underpinning any association. Given dairy products form a substantial component of traditional and Western diets, the implications of these findings are likely to be of clinical and public health importance. Trial registration The trial protocol has been prospectively registered with the Australia and New Zealand Clinical Trials Registry, ACTRN12618002023235. Registered on 17 December 2018. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05812-6.
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Affiliation(s)
- Meghan Hockey
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia
| | - Hajara Aslam
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia
| | - Michael Berk
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia.,Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, The University of Melbourne, Melbourne, Australia
| | - Julie A Pasco
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia.,IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia.,Department of Epidemiology and Preventive Medicine, Monash University, Prahran, VIC, Australia.,Department of Medicine-Western Health, The University of Melbourne, St Albans, VIC, Australia
| | - Anu Ruusunen
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia.,Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.,Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland
| | - Mohammadreza Mohebbi
- Biostatistics Unit, Faculty of Health, Deakin University, Burwood, VIC, 3125, Australia
| | - Helen Macpherson
- Institute for Physical Activity and Nutrition, Faculty of Health, Deakin University, Burwood, VIC, 3125, Australia
| | - Mary Lou Chatterton
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia.,Institute for Health Transformation, Faculty of Health, Deakin University, Geelong, Australia
| | - Wolfgang Marx
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia
| | - Adrienne O'Neil
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia
| | - Tetyana Rocks
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia
| | - Amelia J McGuinness
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia
| | - Lauren M Young
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia
| | - Felice N Jacka
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia.
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A simple method to generate β-casomorphin-7 by in vitro digestion of casein from bovine milk. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104631] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Mayer HK, Lenz K, Halbauer EM. "A2 milk" authentication using isoelectric focusing and different PCR techniques. Food Res Int 2021; 147:110523. [PMID: 34399501 DOI: 10.1016/j.foodres.2021.110523] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 06/01/2021] [Accepted: 06/09/2021] [Indexed: 12/17/2022]
Abstract
Genetic variants of milk proteins have attracted great interest for decades as they are related to important issues such as the composition and technological properties of milk. More recently, an "A1/A2 hypothesis" was developed saying that β-casein variant A1 may be a dietary risk factor for cardiovascular diseases, type 1 diabetes, sudden infant death syndrome and neurological disorders due to the release of β-casomorphin-7, whereas no evidence for such adverse effects was assumed for β-casein A2. Thus, the aim of this study was to adapt and establish analytical methods for the identification of genetic variants of β-casein using isoelectric focusing of milk proteins as well as appropriate PCR techniques. Allele-specific polymerase chain reaction (AS-PCR) proved to be a reliable method for differentiating most common β-casein variants (A1, A2, B, C), amplification-created restriction site (ACRS)-PCR using three different restriction enzymes allowed also the detection of variant A3, and the restriction fragment length polymorphism (RFLP)-PCR method enabled the reliable discrimination between A2 (homozygote/heterozygote) and non-A2 animals. Since traces of β-casein A1 were also found in commercial "A2 milk" in Austria, the authentication of such expensive dairy products is urgently recommended, both by genotyping of all dairy cows at farm level (to confirm that all cows are homozygous β-casein A2A2) and by screening commercial products on the market (to confirm the absence of β-casein variants A1, B, and C in dairy products labelled "A2 milk") to protect consumers from this unexpected fraud.
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Affiliation(s)
- Helmut K Mayer
- Department of Food Science and Technology, Food Chemistry Laboratory, BOKU - University of Natural Resources and Life Sciences Vienna, Muthgasse 11, A-1190 Vienna, Austria.
| | - Kathrin Lenz
- Department of Food Science and Technology, Food Chemistry Laboratory, BOKU - University of Natural Resources and Life Sciences Vienna, Muthgasse 11, A-1190 Vienna, Austria
| | - Eva-Maria Halbauer
- Department of Food Science and Technology, Food Chemistry Laboratory, BOKU - University of Natural Resources and Life Sciences Vienna, Muthgasse 11, A-1190 Vienna, Austria
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An Overview on Nutritional Aspects of Plant-Based Beverages Used as Substitutes for Cow's Milk. Nutrients 2021; 13:nu13082650. [PMID: 34444815 PMCID: PMC8399839 DOI: 10.3390/nu13082650] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/25/2021] [Accepted: 07/27/2021] [Indexed: 01/09/2023] Open
Abstract
The presence of milk in meals and products consumed daily is common and at the same time the adoption of a milk-free diet increases due to milk allergy, lactose intolerance, vegan diets, and others. Therefore, there is an increasing demand for plant-based beverages, which present variable and, sometimes, unknown nutritional characteristics. This study sought to compare the nutritional aspects of plant-based beverages used as substitutes for cow’s milk described in scientific studies. Therefore, we used a review of the scientific literature on PubMed, Google Scholar, Scopus, Web of Science, Google Patents, Embase, and ScienceDirect databases. The inclusion criteria were scientific studies referring to plant-based beverage used as an alternative to cow’s milk; published in the English language; present data on the serving size, ingredients, and nutritional composition, containing at least data on energy and macronutrients of plant-based beverages. Ingredients and data on energy, macronutrients, and, if available, dietary fiber and some micronutrients of plant-based beverages were collected. Data were obtained from 122 beverages of 22 different matrices, with soy being the most used (27.87%, n = 34). The variation in the amount of nutrients found was 6–183 Kcal/100 mL for energy value; 0.00–22.29 g/100 mL for carbohydrate; 0.06–12.43 g/100 mL for protein; 0.00–19.00 g/100 mL for lipid; 0.00–4.40 g/100 mL for dietary fiber; 0.00–1252.94 mg/100 mL for calcium; 0.04–1.40 mg/100 mL for iron; 0.84–10,178.60 mg/100 mL for magnesium; 0.00–343.43 mg/100 mL for sodium. Salt was the most commonly found added ingredient in plant-based beverages. Some beverages have reached certain amounts of cow’s milk nutrients. However, studies have pointed out differences in their qualities/types. Thus, attention is needed when replacing milk with these alternatives.
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Woodford KB. Casomorphins and Gliadorphins Have Diverse Systemic Effects Spanning Gut, Brain and Internal Organs. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18157911. [PMID: 34360205 PMCID: PMC8345738 DOI: 10.3390/ijerph18157911] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 07/14/2021] [Accepted: 07/17/2021] [Indexed: 12/11/2022]
Abstract
Food-derived opioid peptides include digestive products derived from cereal and dairy diets. If these opioid peptides breach the intestinal barrier, typically linked to permeability and constrained biosynthesis of dipeptidyl peptidase-4 (DPP4), they can attach to opioid receptors. The widespread presence of opioid receptors spanning gut, brain, and internal organs is fundamental to the diverse and systemic effects of food-derived opioids, with effects being evidential across many health conditions. However, manifestation delays following low-intensity long-term exposure create major challenges for clinical trials. Accordingly, it has been easiest to demonstrate causal relationships in digestion-based research where some impacts occur rapidly. Within this environment, the role of the microbiome is evidential but challenging to further elucidate, with microbiome effects ranging across gut-condition indicators and modulators, and potentially as systemic causal factors. Elucidation requires a systemic framework that acknowledges that public-health effects of food-derived opioids are complex with varying genetic susceptibility and confounding factors, together with system-wide interactions and feedbacks. The specific role of the microbiome within this puzzle remains a medical frontier. The easiest albeit challenging nutritional strategy to modify risk is reduced intake of foods containing embedded opioids. In future, constituent modification within specific foods to reduce embedded opioids may become feasible.
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Armour M, Middleton A, Lim S, Sinclair J, Varjabedian D, Smith CA. Dietary Practices of Women with Endometriosis: A Cross-Sectional Survey. J Altern Complement Med 2021; 27:771-777. [PMID: 34161144 DOI: 10.1089/acm.2021.0068] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background: Endometriosis causes deleterious effects on the lives of sufferers across multiple domains impacting quality of life. Commonly utilized pharmaceutical interventions offer suboptimal efficacy in addition to potentially intolerable side effects for many women. There is some evidence for dietary therapies reducing endometriosis symptoms, but little data on dietary preferences/strategies used, and their impact, in a community setting. Methods: A cross-sectional online survey was conducted between October and December 2017 to investigate the self-management strategies employed by women with endometriosis. Participants were aged 18-45 years, living in Australia, and had a surgically confirmed diagnosis of endometriosis. Results: Four hundred eighty-four responses were included for analysis, with 76% of women reporting the use of general self-management strategies within the last 6 months. Of these, 44% of respondents reported using dietary strategies for symptom management. Reducing or eliminating gluten, reducing or eliminating dairy, and the low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet were the most commonly reported dietary strategies utilized. Respondents reported a 6.4/10 effectiveness score for reduction in pelvic pain with dietary changes, with no difference in pain reduction between the various diets used. Furthermore, women self-reported significant improvements in comorbidities such as gastrointestinal (GI) disturbance (39%), nausea and vomiting (15%), and fatigue (15%). Conclusions: Dietary modifications are a very common self-management strategy employed by people with endometriosis, with the greatest benefit reported on GI symptoms. Reducing or eliminating gluten, dairy, or FODMAPs or a combination of these was the most common strategy. No single diet appeared to provide greater self-reported benefits than others.
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Affiliation(s)
- Mike Armour
- NICM Health Research Institute, Western Sydney University, Penrith, Australia.,Translational Health Research Institute, Western Sydney University, Penrith, Australia
| | | | - Siew Lim
- Monash Centre for Health Research and Implementation, Monash University, Victoria, Australia
| | - Justin Sinclair
- NICM Health Research Institute, Western Sydney University, Penrith, Australia
| | - David Varjabedian
- NICM Health Research Institute, Western Sydney University, Penrith, Australia
| | - Caroline A Smith
- NICM Health Research Institute, Western Sydney University, Penrith, Australia.,Translational Health Research Institute, Western Sydney University, Penrith, Australia
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Liu X, Liu S, Tang Y, Pu Z, Xiao H, Gao J, Yin Q, Jia Y, Bai Q. Intragastric Administration of Casein Leads to Nigrostriatal Disease Progressed Accompanied with Persistent Nigrostriatal-Intestinal Inflammation Activited and Intestinal Microbiota-Metabolic Disorders Induced in MPTP Mouse Model of Parkinson's Disease. Neurochem Res 2021; 46:1514-1539. [PMID: 33719004 DOI: 10.1007/s11064-021-03293-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 02/21/2021] [Accepted: 02/26/2021] [Indexed: 12/11/2022]
Abstract
Gut microbial dysbiosis and alteration of gut microbiota composition in Parkinson's disease (PD) have been increasingly reported, no recognized therapies are available to halt or slow progression of PD and more evidence is still needed to illustrate its causative impact on gut microbiota and PD and mechanisms for targeted mitigation. Epidemiological evidence supported an association between milk intake and a higher incidence of Parkinson's disease (PD), questions have been raised about prospective associations between dietary factors and the incidence of PD. Here, we investigated the significance of casein in the development of PD. The mice were given casein (6.75 g/kg i.g.) for 21 days after MPTP (25 mg/kg i.p. × 5 days) treatment, the motor function, dopaminergic neurons, inflammation, gut microbiota and fecal metabolites were observed. The experimental results revealed that the mice with casein gavage after MPTP treatment showed a persisted dyskinesia, the content of dopamine in striatum and the expression of TH in midbrain and ileum were decreased, the expression of Iba-1, CD4, IL-22 in midbrain and ileum increased continuously with persisted intestinal histopathology and intestinal barrier injury. Decreased intestinal bile secretion in addition with abnormal digestion and metabolism of carbohydrate, lipids and proteins were found, whereas these pathological status for the MPTP mice without casein intake had recovered after 24 days, no significant differences were observed with regard to only treated with casein. Our study demonstrates that intestinal pathologic injury, intestinal dysbacteriosis and metabolism changes promoted by casein in MPTP mice ultimately exacerbated the lesions to dopaminergic neurons.
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Affiliation(s)
- Xinrong Liu
- School of Public Health and Management, Chongqing Medical University, 1Yi Xue Yuan Road, Chongqing, 400016, P.R. China
| | - Shuya Liu
- School of Public Health and Management, Chongqing Medical University, 1Yi Xue Yuan Road, Chongqing, 400016, P.R. China
| | - Yong Tang
- Chongqing Orthopedics Hospital of Traditional Chinese Medicine, Chongqing, 400039, P.R. China
| | - Zhengjia Pu
- School of Public Health and Management, Chongqing Medical University, 1Yi Xue Yuan Road, Chongqing, 400016, P.R. China
| | - Hong Xiao
- School of Public Health and Management, Chongqing Medical University, 1Yi Xue Yuan Road, Chongqing, 400016, P.R. China
| | - Jieying Gao
- School of Public Health and Management, Chongqing Medical University, 1Yi Xue Yuan Road, Chongqing, 400016, P.R. China
| | - Qi Yin
- School of Public Health and Management, Chongqing Medical University, 1Yi Xue Yuan Road, Chongqing, 400016, P.R. China
| | - Yan Jia
- School of Public Health and Management, Chongqing Medical University, 1Yi Xue Yuan Road, Chongqing, 400016, P.R. China
| | - Qunhua Bai
- School of Public Health and Management, Chongqing Medical University, 1Yi Xue Yuan Road, Chongqing, 400016, P.R. China.
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Abstract
Cow's milk is a highly nutritious biological fluid that provides nourishment and immunity to infants when breastfeeding declines. However, some infants, children, and adults are allergic to cow's milk because milk contains potential allergens in the form of proteins. Casein and whey proteins and their coagulated sub-fractions in the milk such as αS1-casein, αS2-casein, β-casein, κ-casein and α-lactalbumin, β-lactoglobulin, bovine serum albumin, immunoglobulins, lactoferrin, respectively are the major etiological determinant of cow's milk allergy (CMA). Moreover, milk processing techniques such as homogenization and pasteurization alter the milk fat and whey protein's molecular structure and serve them as allergens to the immune system of allergic individuals. Strict exclusion of nutrient-rich milk and other dairy products from diet puts children with CMA at higher nutritional risk. Thus, regular nutritional monitoring, the inclusion of protein and mineral-rich supplements as a substitute for cow's milk, management of animal genetics (sheep, goats, buffaloes, camel, mare, donkey, yak), and milk processing to produce non-allergenic milk by inactivating allergic proteins for designer nutrition is essentially required. This review paper details the prevalence, molecular profiling of milk allergens (proteins), body immune response against CMA, consequences of milk processing, treatment, and novel role of galectins as potentially allergy suppressors.
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Affiliation(s)
- Lily Jaiswal
- Department of Animal Sciences, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, USA
| | - Mulumebet Worku
- Department of Animal Sciences, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, USA
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Kay SIS, Delgado S, Mittal J, Eshraghi RS, Mittal R, Eshraghi AA. Beneficial Effects of Milk Having A2 β-Casein Protein: Myth or Reality? J Nutr 2021; 151:1061-1072. [PMID: 33693747 DOI: 10.1093/jn/nxaa454] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 10/14/2020] [Accepted: 12/28/2020] [Indexed: 01/03/2023] Open
Abstract
Diet has been shown to play an important role in maintaining normal homeostasis in the human body. Milk and milk products are a major component of the Western diet, but their consumption may predispose sensitive individuals to adverse health outcomes. Current literature about milk products recognizes various bioactive components including lactate, whey protein, and β-casein protein. Specifically, cow milk has 2 major subvariants of its β-casein protein, A1 and A2, due to a single nucleotide difference that changes the codon at position 67. Whereas the A2 polymorphism is unlikely to undergo enzymatic cleavage during digestion, the A1 polymorphism is more likely to undergo enzymatic cleavage resulting in the product peptide β-casomorphin-7, a known μ-opioid receptor agonist. The objective of this article is to review the current understanding of the 2 major β-casein subvariants and their effects on various organ systems that may have an impact on the health of an individual. Synthesis of the current existing literature on this topic is relevant given the increased association of milk consumption with adverse effects in susceptible individuals resulting in a rising interest in consuming milk alternatives. We discuss the influence of the β-casein protein on the gastrointestinal system, endocrine system, nervous system, and cardiovascular system as well as its role in antioxidants and methylation. A1 milk consumption has been associated with enhanced inflammatory markers. It has also been reported to have an opioid-like response that can lead to manifestations of clinical symptoms of neurological disorders such as autism spectrum disorder. On the other hand, A2 milk consumption has been associated with beneficial effects and is easier to digest in sensitive individuals. Further research is warranted to investigate the short- and long-term effects of consumption of A1 β-casein in comparison with milk with A2 β-casein proteins.
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Affiliation(s)
- Sae-In S Kay
- Dr. Kiran C Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Stefanie Delgado
- Hearing Research and Communication Disorders Laboratory, Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Jeenu Mittal
- Hearing Research and Communication Disorders Laboratory, Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Rebecca S Eshraghi
- Division of Gastroenterology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Rahul Mittal
- Hearing Research and Communication Disorders Laboratory, Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Adrien A Eshraghi
- Hearing Research and Communication Disorders Laboratory, Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami, FL, USA.,Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA.,Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, FL, USA
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Catanzaro R, Sciuto M, Marotta F. Lactose intolerance: An update on its pathogenesis, diagnosis, and treatment. Nutr Res 2021; 89:23-34. [PMID: 33887513 DOI: 10.1016/j.nutres.2021.02.003] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 02/15/2021] [Accepted: 02/27/2021] [Indexed: 02/07/2023]
Abstract
Lactose intolerance has a high prevalence worldwide, ranging between 57% and 65%. It is caused by a reduction or loss of the activity of the intestinal enzyme lactase-phlorizin hydrolase, responsible for the digestion of lactose. This alteration determines an increased osmotic load in the small intestine and the fermentation of lactose by the bacterial flora, which leads to a high production of short-chain fatty acids and gas. This is followed by the onset of abdominal pain, diarrhea, and flatulence. In addition to these problems, it was found that subjects with lactose intolerance have an increased risk of developing various extra-intestinal diseases, including cancers. The diagnosis is essential to undertake an adequate treatment and, for this purpose, different methods have been tested. These include genetic test, hydrogen breath test (HBT), quick lactase test, and lactose tolerance test. HBT is the most used method because it is non-invasive, inexpensive, and highly sensitive and specific, as well as easy to perform. In clinical practice, the other methods are mainly used as HBT integration tests. There are also many therapeutic options. An appropriate intervention concerns the dietetic style, such as the consumption of lactose-free foods, but with nutritional characteristics comparable to dairy products. Other valid choices are represented by the use of exogenous enzymes, probiotics, prebiotics, the selection of milk containing specific types of beta-caseins. This review is intended to illustrate the diagnostic methods currently available and the possible therapeutic options for lactose intolerance.
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Affiliation(s)
- Roberto Catanzaro
- Department of Clinical and Experimental Medicine, Gastroenterology Section, "Gaspare Rodolico" Policlinico Hospital, University of Catania, Catania, Italy.
| | - Morena Sciuto
- Department of Clinical and Experimental Medicine, Gastroenterology Section, "Gaspare Rodolico" Policlinico Hospital, University of Catania, Catania, Italy.
| | - Francesco Marotta
- ReGenera R&D International for Aging Intervention & San Babila Clinic, Milano, Italy.
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Daniloski D, Cunha NM, McCarthy NA, O'Callaghan TF, McParland S, Vasiljevic T. Health-related outcomes of genetic polymorphism of bovine β-casein variants: A systematic review of randomised controlled trials. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.02.073] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Abstract
A new type of cow’s milk, called A2 milk, has appeared in the dairy aisles of supermarkets in recent years. Cows’ milk generally contains two major types of beta-casein as A1 and A2 types, although there are 13 genetic variants of β-casein: A1, A2, A3, A4, B, C, D, E, F, H1, H2, I and G. Studies have shown that A1 β-casein may be harmful, and A2 β-casein is a safer choice for human health especially in infant nutrition and health. The A2 cow milk is reportedly easier to digest and better absorb than A1 or other types of milk. The structure of A2 cow’s milk protein is more comparable to human breast milk, as well as milk from goats, sheep and buffalo. Digestion of A1 type milk produces a peptide called β-casomorphin-7 (BCM-7), which is implicated with adverse gastrointestinal effects on milk consumption. In addition, bovine milk contains predominantly αs1-casein and low levels or even absent in αs2-casein, whereby caprine milk has been recommended as an ideal substitute for patients suffering from allergies against cow milk protein or other food sources. Since goat milk contains relatively low levels of αs1-casein or negligible its content, and αs2-casein levels are high in the milk of most dairy goat breeds, it is logical to assume that children with a high milk sensitivity to αs1-casein should tolerate goat milk well. Cow milk protein allergy (CMPA) is considered a common milk digestive and metabolic disorder or allergic disease with various levels of prevalence from 2.5% in children during the first 3 years of life to 12–30% in infants less than 3 months old, and it can go up to even as high as 20% in some countries. CMPA is an IgE-mediated allergy where the body starts to produce IgE antibodies against certain protein (allergens) such as A1 milk and αs1-casein in bovine milk. Studies have shown that ingestion of β-casein A1 milk can cause ischemic heart disease, type-1 diabetes, arteriosclerosis, sudden infant death syndrome, autism, schizophrenia, etc. The knowledge of bovine A2 milk and caprine αs2-casein has been utilized to rescue CMPA patients and other potential disease problems. This knowledge has been genetically applied to milk production in cows or goats or even whole herds of the two species. This practice has happened in California and Ohio, as well as in New Zealand, where this A2 cow milk has been now advanced commercially. In the USA, there have been even promotions of bulls, whose daughters have been tested homozygous for the A2 β-casein protein.
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Chen Y, Ren Y, Wang L, Huang Z. Analysis of A1-type and A2-type β-casein in Maiwa Yak and Pien-niu milk by HPLC-high-resolution MS and tandem MS. J Sep Sci 2021; 44:1913-1922. [PMID: 33665927 DOI: 10.1002/jssc.202001203] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 01/24/2021] [Accepted: 02/26/2021] [Indexed: 11/12/2022]
Abstract
In this study, a peptide-based method employing ultra high performance liquid chromatography electrostatic field orbitrap high-resolution mass spectrometry and triple quadrupole mass spectrometry was developed for quantification of A1-type and A2-type β-casein in milk from Yak, cows, and their offspring of crosses, Pien-niu. The specific peptides of A1-type and A2-type β-casein were screened and confirmed by protein software after analysis of high-resolution mass spectrometry. The multiple reaction monitoring method was established based on the qualitative results, and isotope-label peptides were used as internal standards. The linear correlation coefficients of this method were >0.99. The relative standard deviations of repeatability test were 0.2-3.6%. The recovery rate ranged from 93.3 to 114.4% with relative standard deviations <6% at three different spiking levels. The method was applied to analyze 45 milk samples from different species. The results showed that β-casein in Yak and Pien-niu milk was about 30% higher than that in cow milk. Furthermore, the β-casein in the Yak milk only contains A2-type β-casein. A1-type and A2-type β-casein coexist in most samples of Pien-niu and cow milk, a few samples contain only one type of β-casein. These results provide further understanding in nutritional value of milk from Yak and Pien-niu.
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Affiliation(s)
- Yutian Chen
- College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang, P. R. China
| | - Yiping Ren
- Analysis and Testing Center Analysis and Testing Center, Yangtze Delta Region Institute of Tsinghua University, Jiaxing, Zhejiang, P. R. China
| | - Lili Wang
- College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang, P. R. China
| | - Zhongping Huang
- College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang, P. R. China
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