Milk A1 β-casein and health-related outcomes in humans: a systematic review

Context Various epidemiological studies suggest a positive association between exposure to cow's milk A1 β-casein protein and risk for noncommunicable chronic diseases. The consumption of A2 cow's milk is increasing, likely because A2 milk is postulated to have positive effects on digestive health. Objective A systematic review was conducted to investigate associations between A1 β-casein and health-related outcomes in humans. Data sources Five electronic databases, 3 clinical trial registries, and the internet were searched systematically. Study selection Using predefined inclusion criteria, 2 authors independently selected studies investigating the effect of A1 β-casein or β-casomorphin-7 intake/exposure on any health-related outcome in humans. Discrepancies were resolved by consensus. Data extraction Two authors independently extracted data and assessed risk of bias. The certainty of evidence per outcome was evaluated using the GRADE approach. Discrepancies were resolved by consensus. Results Fifteen randomized controlled trials, 2 case-control studies, and 8 ecological studies were included. Most randomized controlled studies and case-control studies investigating a potential effect on various outcomes were based on intermediate markers and found no significant difference between the 2 milk types. In contrast, most ecological studies reported that population-level A1 β-casein exposure is associated with adverse health outcomes. The certainty of the evidence for the included outcomes, as assessed by the GRADE approach, was rated as moderate for digestive symptoms and as low to very low for all other outcomes. Conclusions Human-based evidence from clinical trials and epidemiological studies published prior to October 2017 provides moderate certainty for adverse digestive health effects of A1 β-casein compared with A2 β-casein but low or very low certainty for other health effects. These conclusions may change in the future, given the emergent nature of this topic and the ongoing research in this area. Systematic review registration PROSPERO registration number CRD42016043795.