Milk Free From A1 Beta-Casein and Its Positive Impact on B Vitamins / Vitamers Levels, Absorption and Bioavailability: Mechanistic and Clinical Findings

Objectives: The A1 and A2 variants of beta-casein (A1bCN, A2bCN) in milk differ at amino acid position 67, resulting in high release of Beta-casomorphin-7 (BCM-7) from A1bCN and low or none from A2-bCN. Previous clinical studies have reported that A1bCN can result in elevated gut inflammatory markers. However, the effects of A1bCN/BCM-7 vs A2bCN on absorption and bioavailability of other micronutrients from milk is not investigated. Cow's milk is a significant source of a range of B-vitamins (one glass of milk can provide ∼46%DV for vitamin B12 and ∼32%DV for riboflavin), and regular dairy consumption elevates these vitamins in vulnerable populations, including young children and older adults. Hence, the objective of this study was to investigate the impact of BCM-7, a bioactive peptide derived from A1bCN, on absorption and bioavailability of vitamin B levels from milk. Methods: A multifaceted methodology was used, including in vitro assays on Caco2 & SH-SY5Y cells, a 16-week in vivo rat study. 21 days old rat pups (N=10/group) were fed either a diet free from A1bCN or casein-control diet; and growth, tissue inflammation and nutrient bioavailability were assessed. Similarly, cells were exposed to BCM-7 (1uM-1nM) for 4-24 hours, and B-vitamin levels and related gene expression for enzymes, cofactors, and transporters were measured. Clinical trial involved participants with or without lactose intolerance consuming a glass (240 mL) of milk naturally free from A1 beta-casein (A1PF) coupled with pre- and post-intervention serum samples collection and analyses of vitamin B levels. Results: In vitro results showed BCM-7 reduced vitamin B12 levels and altered gene expression, e.g., LRP2 and TCN2. The data from the independent clinical trial revealed increased serum vitamin B12 and B3 in the A1PF group post milk consumption in comparison to conventional milk. Preliminary rodent data suggested gut inflammation, which may affect vitamin levels. More tissue specific analyses of B Vitamins / vitamers will be completed and results presented at the meeting. Conclusions: The study suggests BCM-7 negatively affects vitamin B12 cellular levels, but milk free from A1bCN elevates serum vitamin B12 as well as B3 levels as demonstrated in the study participants. Funding Sources: This study was funded by The a2 Milk Company.