<p>  </p> <p><strong>Background information:</strong> </p> <p>Lactose is a disaccharide found in milk and milk products. Lactose is digested by the enzyme lactase. Lactase non-persistence is a genetic trait in which individuals have low lactase activity. Approximately 70 percent of the world population is lactase non-persistent. It is a major cause of lactose maldigestion. An increase of 20 ppm hydrogen in breath within six hours of a lactose challenge dose (0.5 g of lactose per kg bodyweight) indicates lactose maldigestion. On the other hand, lactose intolerant individuals experience abdominal pain, bloating, diarrhea, and flatulence on consuming dairy. Therefore, lactose intolerant individuals avoid milk, which is a rich source of calcium. Consequently, lactose intolerance has been associated with reduced calcium intake and low bone mineral density. There are two mechanisms for lactose intolerance. The first mechanism is dependent on lactose dose and the second one is independent of lactose. Recently, A1 and A2 β-caseins have been associated with lactose intolerance. Studies conducted in China, New Zealand and Australia demonstrated fewer symptoms on consumption of milk containing only A2 β-casein as compared to milk containing both A1 and A2 β-casein. However, no study was conducted in the population residing in United States, where crossbred cows producing milk containing both A1 and A2 β-casein is the norm. Moreover, no study compared tolerance and digestion on consuming milk with different proportions of A1 and A2 β-casein. Lactose intolerant individuals can include A2 milk in their diet to meet the calcium requirement, if milk containing only A2 β-casein causes fewer symptoms and less maldigestion. </p> <p><strong>Objectives:</strong></p> <p>1. To determine if a single meal of A2 milk containing only A2 β-casein would be better tolerated, producing fewer GI symptoms and less maldigestion, than conventional milk containing 75 percent A1 β-casein and 25 percent A2 β-casein</p> <p>2. To determine if a single meal of Jersey milk containing 25 percent A1 β-casein and 75 percent A2 β-casein would produce less maldigestion and intolerance, than conventional milk containing 75 percent A1 β-casein and 25 percent A2 β-casein</p> <p>3. To determine if the gastric emptying time of milk containing only A2 β-casein and milk containing 75 percent A1 β-casein and 25 percent A2 β-casein was different </p> <p>4. To determine if inflammation, maldigestion and intolerance is lower with a two-week daily consumption of milk containing only A2 β-casein as compared to milk containing 75 percent A1 β-casein and 25 percent A2 β-casein</p> <p><strong>Methods:</strong> </p> <p>Three randomized, double-blinded, crossover trials were conducted. The first study was conducted to determine tolerance and digestion of milk containing different proportions of A1 β-casein and A2 β-casein in subjects residing in the United States. There were four milk interventions in the study: A2 milk (milk containing 100% A2 β-casein), Jersey milk (milk containing 25%/75% A1/A2 β-casein), conventional milk (milk containing 75%/25% A1/A2 β-casein) and lactose-free milk (milk containing 60%/40% A1/A2 β-casein). Lactose intolerance in subjects was determined using a Qualifying Lactose Challenge Symptom Score after a challenge milk dose of 0.5 g of lactose/kg bodyweight. Subjects were screened for lactose maldigestion with a six-hour Hydrogen Breath Test. Symptoms and madigestion response to a single meal of milk (dose calculated as 0.5 g of lactose/kg bodyweight) containing different proportions of A1 and A2 β-casein were determined in lactose intolerant subjects and lactose maldigesters. </p> <p>The second study was conducted to examine the difference in gastric transit between A2 milk and conventional milk in lactose maldigesters. Magnetic Resonance Imaging (MRI) technique was used to observe gastric emptying. Subjects rated abdominal pain after consumption of the two milk interventions using a six-point Likert scale.</p> <p>The final study was conducted to determine symptoms, maldigestion and inflammation due to consumption of A2 milk and conventional milk for fourteen days on a daily basis in lactose maldigesters. Subjects rated lactose intolerance symptoms every day during the fourteen days using a six-point Likert scale. Breath hydrogen, serum inflammatory markers and serum antioxidant concentrations were measured on day 15 after the two-week milk consumption.  All the studies were registered at clinicaltrials.gov. </p> <p><strong>Results: </strong></p> <p>Results from the first study indicated that abdominal pain due to a single meal of A2 milk in lactose intolerant subjects was lower by twenty-three percent as compared to conventional milk (p=0.004, n=25). Similarly, there was a twenty-eight percent decrease in abdominal pain score on consumption of A2 milk as compared to conventional milk in lactose maldigesters (p=0.001, n=33). All the other symptoms were not different between A2 and conventional milk in lactose intolerant subjects and lactose maldigesters. A single meal of A2 milk reduced the total hydrogen production (p=0.04, n=33) by sixteen percent and total symptoms production (p=0.04, n=33) by eighteen percent in lactose maldigesters as compared to conventional milk. However, the total hydrogen and total symptoms produced were not different in lactose intolerant subjects between A2 and conventional milk. Similarly, individual GI symptoms, total symptoms and total hydrogen were not different between jersey and conventional milk in lactose intolerant subjects and lactose maldigesters.</p> <p>Results from gastric transit study indicated that volume of A2 milk in the stomach was higher by twenty-four percent at 30 (p=0.01, n=10), forty-six percent at 60 (p=0.002, n=10) and one hundred and sixty-one percent at 120 (p<0.001, n=10) minutes as compared to conventional milk in lactose maldigesters. </p> <p>Results from the last study suggested a fecal urgency score lower by thirty-three percent (p=0.033, n=10) in lactose maldigesters due to daily consumption of A2 milk for two weeks as compared to conventional milk. The other symptoms, inflammation markers, antioxidant and breath hydrogen production were not different between A2 and conventional milk due to two-week milk consumption.</p> <p><strong>Conclusion:</strong> </p> <p>Total intolerance symptoms and total hydrogen production were lower due to consumption of a single meal of A2 milk than conventional milk in lactose maldigesters. Gastric transit of A2 milk was slower as compared to conventional milk in lactose maldigesters. Daily consumption of A2 milk for two-weeks reduced fecal urgency as compared to conventional milk in lactose maldigesters. </p> <p>  </p>