A Haplogroup-Dependent Mitochondrial Framework for Variability in Inflammatory Responses to β-Casomorphin-7

Inter-individual variability in inflammatory responses to dairy consumption, particularly responses not explained by lactose intolerance or classical food allergy models, remains incompletely understood. β-Casomorphin-7 (BCM-7), an opioid peptide released during digestion of A1 β-casein, has been implicated in gastrointestinal and inflammatory effects; however, findings from human studies have remained inconsistent. This article proposes a mitochondria-centered, haplogroup-dependent framework in which individuals belonging to mitochondrial DNA (mtDNA) haplogroups J and K may exhibit differences in the capacity to resolve BCM-7-associated bioenergetic and inflammatory stress signaling. The framework considers potential contributions from mitochondrial redox regulation, recovery dynamics, and genotype-dependent differences in oxidative phosphorylation efficiency. Direct experimental evidence linking BCM-7 to mitochondrial dysfunction remains limited. Accordingly, the present framework is presented as a testable first-principles hypothesis rather than an established causal mechanism. The concept of an Inflammation Drop Point is introduced to describe delayed symptom resolution following dietary withdrawal, and specific predictions are outlined for haplogroup-stratified study designs.