(P16-12-26) Does the A1-β-Casein Metabolite β-Casomorphin-7 Mediate Differential Gastric Emptying and Gastrointestinal Symptoms in Individuals With Lactose Intolerance?

Objectives: Bovine A1 and A2 milk differ in β-casein variant, with A1 yielding the opioid peptide β-casomorphin-7 (BCM-7) upon digestion. A previous MRI-based study reported faster gastric emptying with A1 compared to A2 milk in individuals with lactose maldigestion (Ramakrishnan et al; 2023). To investigate whether BCM-7-mediated µ-opioid receptor activation underlies this difference, oral naloxone (2 mg) was administered as an antagonist. We hypothesized that naloxone would attenuate differences in gastric emptying rate and gastrointestinal (GI) symptom scores between milk types.

Methods: Ten adults with lactose maldigestion were enrolled in this double-blind, randomized and cross-over trial. Participants were randomized to consume either A1 or A2 milk with 2mg oral naloxone across two visits spread at least a week apart. Gastric emptying assessed via MRI (0, 10, 30, 60 and 120 mins) and GI symptoms (abdominal pain, bloating, flatulence, diarrhea and fecal urgency) rated on a 6-point Likert scale over 2-hours were the primary and secondary outcomes respectively. GI symptom scores and gastric volumes were compared using Wilcoxon signed-rank test and paired t-test respectively with Bonferroni-corrections.

Results: Preliminary analysis was conducted on 8 of 10 enrolled participants. Participants had a mean age of 23.7 years (4 male, 4 female) with a mean BMI of 24.06 kg/m². Paired t-test analysis of gastric volumes at each time point revealed significant differences between A1 and A2 milk at 10 minutes (p=0.026*) and 30 minutes (p=0.029*), but not at 60 minutes (p=0.059) or 120 minutes (p=0.122). Comparative image analysis with Ramakrishnan et al.'s data showed greater non-homogeneity of the gastric contents at 60 and 120 minute timepoints. No significant differences in GI symptom scores were observed between A1 and A2 milk after Bonferroni correction (all adjusted p=1), consistent with previous study.

Conclusions: Preliminary findings suggest that µ-opioid receptor blockade via naloxone may attenuate the differential gastric emptying previously observed between A1 and A2 milk, supporting a BCM-7-mediated mechanism. Refined volumetric analysis and direct comparison with prior data are ongoing.

Funding Sources: Gift funds from a2 Milk Company