(P06-33-26) Differential Effects of Lactose-Free A1/A2 Versus A2/A2 Milk on Digestive Discomfort and Gut Inflammation in Adults With Perceived Dairy Intolerance

Objectives: Digestive discomfort from dairy is often attributed to lactose intolerance; however, many individuals reporting dairy intolerance are not lactose maldigesters. β-casomorphin-7, an inflammatory metabolite of A1 β-casein may contribute to these symptoms. We hypothesize that lactose free A2/A2 milk would cause less digestive discomfort and gut inflammation compared with A1/A2 milk, isolating the effect of β-casein.

Methods: This study was approved by the Purdue University Institutional Review Board (IRB-2024-1469). In a double-blind, randomized, controlled crossover trial, 18 individuals with perceived dairy intolerance completed a 14 day dairy-free washout before receiving either A1/A2 or A2/A2 milk interventions for 14 days, followed by a second washout (14 days) and crossover to the alternate milk. Lactose challenges were conducted at baseline (D0 of the washout 1) and after each intervention. Symptom scores and blood were collected at each challenge. Serum IL-4, IL-6, IL-10, TNF-α, glutathione/oxidized glutathione (GSH/GSSG), and S-adenosylmethionine/S-adenosyl homocysteine (SAM/SAH) were analyzed. Symptom scores were assessed using cumulative link mixed models, and biomarkers using linear mixed-effects models in R.

Results: Out of 18, 8 participants were lactose maldigesters. The oxidative stress marker GSH/GSSG showed a significant intervention × status interaction (p=0.0099) and period effect (p=0.033). Post-hoc comparisons indicated a difference between interventions among non-maldigesters, while no difference was observed among maldigesters. No significant effects of intervention, lactose maldigestion status, or their interaction were observed for IL-4, IL-6, IL-10 or SAM/SAH. Gastrointestinal symptoms were unaffected by intervention or status of lactose maldigestion.

Conclusions: The increased symptoms of intolerance to A1/A2 milk appear to be mediated by lactose.  Under lactose-free conditions, both A1/A2 and A2/A2 milk were similarly tolerated with respect to digestive symptoms and inflammatory biomarkers in this cohort, with differences observed only for the oxidative stress marker GSH/GSSG.

Funding Sources: Gift funds from a2 milk company