Table 1.
Characteristics of included studies and reported outcomes (comparison A2- vs. A2 beta-casein)
| Study | Country | Study population | Aims of the study (short description) | Intervention (I) / Control intervention (C) | Dose | Summary on reported outcomes | Study funding | |
|---|---|---|---|---|---|---|---|---|
| 1 | Barnett 2014 [16] | New Zealand | 48 male Wistar rats, 4 weeks old | To measure gastrointestinal effects of A1 or A2 beta-casein on rats fed for 36 or 84 h |
I: Skim-milk diets containing A1 beta-casein C: Skim-milk diets containing A2 beta-casein |
Not reported | Gastrointestinal markers* (incl. gastrointestinal transit time (GITT), intestinal inflammation) | A2 Corporation Limited and the New Zealand Government Foundation for Research Science and Technology (FRST) |
| 2 | Beales 2002 [12] | New Zealand, Canada and UK | 315 non-obese diabetic (NOD) mice, aged 17–21 days; and 270 BioBreeding (BB) rats, aged 23 days | To ascertain whether A1 beta-casein was more diabetogenic than A2 and to test the diabetogenicity of a milk-free diet in animals representing different forms of spontaneous Type I (insulin-dependent) diabetes mellitus |
I: Oral diets containing A1 beta-casein: (a) Hydrolysed casein based formula (Progestimil) with A1 beta-casein, or (b) Soy isolate based infant formula (ProSobee) with A1 beta-casein C: Various oral diets: (a) Progestimil, (b) ProSobee, (c) Progestimil containing whole casein, (d) Progestimil with A2 beta-casein, (e) ProSobee with A2 beta-casein, or (f) plant-based diet without milk proteins and containing mainly wheat (NTP-2000) |
Not reported |
Intermediate markers related to diabetes*: glucose concentration in blood and urine Insulitis (inflammation of the islets of Langerhans of the pancreas) Survival Body weight |
New Zealand Dairy Board, Juvenile Diabetes Research Foundation, Canadian Institutes of Health Research, und Ontario Research and Development Challenge Fund and Health Canada |
| 3 | Chia 2018 [13] | Australia | Newly weaned NOD/ShiLtJArc mice, aged 3–4 weeks; and their breeded further 4 generations of mice (total number of included animals was not reported) | To test whether a diet supplemented with A1 or A2 beta-casein would increase the incidence of type 1 diabetes in genetically susceptible female NOD mice over generations |
I: Oral administration of A1 beta-casein supplement with normal diet C: Oral administration of A2 beta-casein with normal diet |
Not reported |
Outcomes were reported for the included mice and their further 4 generations of breeded mice: Incidence of diabetes* Blood parameters, incl. glucose, insulin, immune profile, etc Gut microbiota, and permeability |
Innovation Connections Grant (Nr. RC54051) of the Department of Industry, Innovation and Science, Australia; and a2 Infant Nutrition Australia Private Limited, Sydney, Australia |
| 4 | Kaminski 2012 [15] | Poland | 6 pigs (cross of Polish Large White and Polish Landrace), 83 days old and weighing 33 kg | To verify the hypothesis whether consumption of cow's milk containing A1 variant or A2 variant of beta-casein will affect basic parameters of blood |
I: Oral administration of A1 milk (as supplement) C: Oral administration of A2 milk (as supplement) |
Dose increased during the study and each pig received the following dose (either I or C): Week 1: 0 kg/day Week 2: 0.32 kg/day Week 3: 0.54 kg/day Week 4: 0.72 kg/day Week 5: 1 kg/day Week 6: 1.5 kg/day |
Intermediate markers related to CVD*: blood lipids Intermediate markers related to diabetes*: glucose concentration Other blood parameters (incl. white blood cells, red blood cells, platelets, creatinine, urea) |
University of Warmia and Mazury (No. 0105-0804) |
| 5 | Tailford 2003 [17] | Australia | 60 rabbits (New Zealand white/Lop cross rabbits), aged 16–24 weeks | To determine whether dietary administration of beta-casein A1 in a rabbit model of atherosclerosis promotes the disease state compared with rabbits fed beta-casein A2 |
I: Various intervention groups with different concentrations of A1 beta-casein given orally (pellets) C: Various control groups with different concentrations of A2 beta-casein and with or without whey protein given orally (pellets) |
Oral diets had the following concentrations of either A1- or A2 beta-casein: 10%, 3.5%, or 20% Rabbits were fed with one of the diets for 6 weeks and the number of pellets eaten by each rabbit was recorded daily |
Intermediate marker related to CVD (atherosclerosis)*: aortic fatty streak and advanced lesions in carotid arteries Body weight Various blood parameters (incl. blood lipids, homocysteine) |
Not reported |
| 6 | Haq 2014a [14] | India | 24 Swiss albino male mice, weighing between 20 and 25 kg | To study the effect of feeding three genetic variants (A1A1, A1A2, and A2A2) of cow beta-casein milk on gastrointestinal immune system of mice |
I: Oral administration (intubation) of: (a) A1 beta-casein, or (b) A1- and A2 beta-casein C: Oral administration (intubation) of A2 beta-casein |
Mice received the following dose of either A1- or A2 beta casein: 85 mg/mice/day for 30 days |
Gut immune response*, measured with immunoglobulins, intestinal leucocyte infiltration, etc | National Dairy Research Institute (ICAR) |