Research library
Clinical Studies on Beta-Casein Variants
Peer-reviewed clinical studies examining the effects of A1 and A2 beta-casein on human health, including digestion, inflammation and disease outcomes.
26 studies
All studies →Effect of Infant Formula Made With Milk Free of A1-Type β-Casein on Growth and Comfort: A Randomized Controlled Trial
From satisfaction surveys, a significantly higher percentage of the A1PF group had relieved gastrointestinal symptoms, reduced vomiting after feeding, improved digestion, and better stool characteristics (p < 0.05). Both formulas were generally well tolerated. Among mixed-fed infants, those who consumed A1PF infant formula had the same growth as those fed CON infant formula, and improved comfort (including relieved gastrointestinal symptoms and fewer crying episodes).
Lactase-Treated A2 Milk as a Feasible Conventional Milk Alternative: Results of a Randomized Controlled Crossover Trial to Assess Tolerance, Gastrointestinal Distress, and Preference for Milks Varying in Casein Types and Lactose Content
These findings suggest that adults who avoid conventional fluid milk consumption may experience minimal GI discomfort from lactose-free and/or A1-free milks.
Effect of β-casein A2 cow milk supplementation on physical growth, inflammation, growth, and metabolism hormonal profiles in stunted children
This study suggests that β-casein A2 milk supplementation was associated with improvements in physical growth and related biomarkers in stunted children. Additionally, β-casein A2 milk may produce fewer BCM-7 metabolites compared to β-casein A1 milk, which has been hypothesized to be associated with certain adverse health outcomes. However, further controlled studies are needed to confirm its efficacy as a dietary intervention.
Beneficial effect of consuming milk containing only A2 beta-casein on gut microbiota: A single-center, randomized, double-blind, cross-over study
Two weeks of A2 milk consumption led to significant alterations in gut microbiota, promoting beneficial microbes and related functions. A2 milk could be a suitable alternative for subjects who experience milk-intake-related GI discomfort.
Effects of A1-type β-casein protein free bovine milk on mothers and infants: a randomized double-blind controlled trial
Compared with mothers who drank conventional cow's milk, full-term mothers who drank A1PF milk showed lower levels of gastrointestinal and systemic inflammatory markers and improved gastrointestinal symptoms, and this effect may also be transmitted to full-term breastfed infants. This conclusion requires further research to confirm.
Effect of A1 protein-free formula versus conventional formula on acute respiratory infections and diarrhea in toddlers: A Randomized Controlled Trial
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.
Milk free of A1 β-casein supports superior gains in cognition and quality of life, relative to conventional milk, in older adults with mild cognitive impairment
Daily intake of A1PF milk for 90 days significantly improved cognition, QoL and muscle strength in a sample of older people with MCI. While these outcomes appear to be linked to increased serum titres of 25-hydroxyvitamin D3, further investigations are needed to confirm this association.
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
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.
The Effect of A2 Milk on Gastrointestinal Symptoms in Comparison to A1/A2 Milk: A Single-center, Randomized, Double-blind, Cross-over Study
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
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
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.
Effectiveness of Growing-Up Milk Containing Only A2 β-Casein on Digestive Comfort in Toddlers: A Randomized Controlled Trial in China
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.
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
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.
Circulatory amino acid responses to milk consumption in dairy and lactose intolerant individuals
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).
Milk Containing A2 β-Casein ONLY, as a Single Meal, Causes Fewer Symptoms of Lactose Intolerance than Milk Containing A1 and A2 β-Caseins in Subjects with Lactose Maldigestion and Intolerance: A Randomized, Double-Blind, Crossover Trial
Post hoc analysis with lactose maldigesters revealed statistically significantly improved symptom scores (p = 0.04) and lower hydrogen production (p = 0.04) following consumption of milk containing A2 β-casein only compared with conventional milk. Consumption of milk containing A2 β-casein only is associated with fewer GI symptoms than consumption of conventional milk in lactose maldigesters.
Evaluation of breath, plasma, and urinary markers of lactose malabsorption to diagnose lactase non-persistence following lactose or milk ingestion
The breath H2 optimal cut-off value was lower with a2 Milk™ (13 ppm) than conventional milk (21 ppm). Using existing literature cut-off values the sensitivity and specificity of breath H2 was greater than plasma glucose to detect LNP following lactose challenge whereas values obtained for urinary galactose/creatinine were lower than the existing literature cut-offs.
Comparison of the impact of bovine milk β-casein variants on digestive comfort in females self-reporting dairy intolerance: a randomized controlled trial
In LI individuals, LM and digestive comfort with lactose-containing milks was improved with milk containing exclusively A2 β-casein. Furthermore, self-reported dairy intolerance without LM (NLDI) is characterized by early-onset digestive discomfort following milk ingestion, irrespective of lactose content or β-casein type.
Effects of Conventional Milk Versus Milk Containing Only A2 β-Casein on Digestion in Chinese Children: A Randomized Study
Replacing conventional milk with milk containing only A2 β-casein reduced gastrointestinal symptoms associated with milk intolerance in Chinese preschool children, with corresponding improvements in aspects of cognitive performance.
Effects of cow's milk beta-casein variants on symptoms of milk intolerance in Chinese adults: a multicentre, randomised controlled study
Milk containing A2 β-casein attenuated acute gastrointestinal symptoms of milk intolerance, while conventional milk containing A1 β-casein reduced lactase activity and increased gastrointestinal symptoms compared with milk containing A2 β-casein. Thus, milk-related gastrointestinal symptoms may result from the ingestion of A1 β-casein rather than lactose in some individuals.
A2 Milk Enhances Dynamic Muscle Function Following Repeated Sprint Exercise, a Possible Ergogenic Aid for A1-Protein Intolerant Athletes?
Following muscle-damaging exercise, ingestion of 500 mL of A2 or regular milk can limit decrements in dynamic muscle function in male athletes, thus hastening recovery and improving subsequent performance. The findings propose A2 milk as an ergogenic aid following EIMD, and may offer an alternative to athletes intolerant to the A1 protein.
Clinical evaluation of glutathione concentrations after consumption of milk containing different subtypes of β-casein: results from a randomized, cross-over clinical trial
The current human study demonstrates that consumption of milk containing only A2 β-casein was associated with a greater increase in plasma glutathione concentrations compared with the consumption of milk containing both β-casein types, and did not increase plasma BCM-7 concentrations compared with the washout diet in the study participants. Thus, milk containing only A2 β-casein and not A1 β-casein has the potential to promote the production of the antioxidant glutathione in humans.
Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk
Consumption of milk containing A1 β-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 β-casein attenuated these effects, some symptoms of lactose intolerance may stem from inflammation it triggers, and can be avoided by consuming milk containing only the A2 type of beta casein.
Comparative effects of A1 versus A2 beta-casein on gastrointestinal measures: a blinded randomised cross-over pilot study
These preliminary results suggest differences in gastrointestinal responses in some adult humans consuming milk containing beta-casein of either the A1 or the A2 beta-casein type, but require confirmation in a larger study of participants with perceived intolerance to ordinary A1 beta-casein-containing milk.
The exogenous opioid peptides and DPPIV serum activity in infants with apnoea expressed as apparent life threatening events (ALTE)
Casein-derived peptides have been suggested to play a role in sudden infant death syndrome (SIDS). In this study, we have determined the content of bovine β-casomorphin-7 (bBCM-7) and the activity of dipeptidyl peptidase-IV (DPPIV) in sera of infants with apparent life threatening events (ALTE syndromes, 'near miss SIDS'). We have found that the sera of some infants after an apnoea event contained more β-casomorphin-7 than that of the healthy infants in the same age.
Beta-Casomorphins-7 in infants on different type of feeding and different levels of psychomotor development
The data indicate that breast feeding has an advantage over artificial feeding for infants' development during the first year of life and support the hypothesis for deterioration of bovine casomorphin elimination as a risk factor for delay in psychomotor development and other diseases such as autism.
Effect of dietary supplementation with beta-casein A1 or A2 on markers of disease development in individuals at high risk of cardiovascular disease
Endothelium function, measured as a vascular response using venous occlusion plethysmography to intra-arterial infusions of the endothelium-dependent agonist acetylcholine, were not different between the two casein interventions. Similarly, neither blood pressure nor measures of large artery stiffness were affected by differing the casein variant. We therefore conclude that there is no evidence from the present study that supplementation with casein A1 has any cardiovascular health disadvantage over consumption of casein A2.
A comparison of the effects of A1 and A2 beta-casein protein variants on blood cholesterol concentrations in New Zealand adults
Mean (S.D.) plasma total, low-density and high-density lipoprotein cholesterol concentrations were 5.60 (0.77), 3.73 (0.70) and 1.26 (0.34) mmol/L after the A1 diet and 5.63 (0.81), 3.75 (0.75) and 1.27 (0.37) mmol/L after the A2 diets. We found no evidence that dairy products containing beta-casein A1 or A2 exerted differential effects (P > 0.05) on plasma cholesterol concentrations in humans.