The Role of Digestive Peptides from p-Casein and the A2 Milk

Some peptides produced by gastric and gut enzymes during human digestion by hydrolysis of p-casein A1, with the amino acid histidine at residue 67, for example, the casomorphin peptide p-CM-7 (Tyr-Pro-Phe-Pro-Gly-Pro-Ile) are believed to be potentially involved with some diseases, like cardiovascular diseases or type I diabetes (Bell et al., 2006). Other researches do not support these findings (Truswell, 2005, Clemens 2011). A scientific opinion by EFSA (2009) states, “Based on the present review of available scientific literature, a cause-effect relationship between the oral intake of BCM7 or related peptides and aetiology or course of any suggested non-communicable diseases cannot be established.”

Because of the potential relationship between opioid peptides and the pathogenesis of autism in children, there is increasing interest in the use of casein free diets for children with autism spectrum disorders. It was shown that autistic children have significantly higher levels of urine CM-7 than control children (Sokolov et al., 2014), overpassing the findings of Cass and co-authors (2008) that did not find opioid peptiduria by CM-7. However, in general it has to be remembered that the connection of cow's milk to autistic spectrum disorders is lacking, and even a cause-effect relationship with type I diabetes mellitus has not been established because many factors may concur (Agostoni et al., 2011).

However, as the A2 variant of p-casein, with proline in position 67 does not favor or hinder the production of the peptide CM7. A2 milk is considered “safer” and alternative to the A1 milk produced by most of European dairy cow breeds. In late 1990s, the “The a2 milk company” started to produce at least 99% pure A2 milk in New Zealand (www., and the worldwide movement toward the genetic selection of A2 cows continues, despite the lack of clear scientific demonstration of the benefits of A2 milk or concerns related to A1 milk.

A precautionary position is represented by Swinburn (2004), concluding a report to the New Zealand Food Safety Authority with the following: “As a matter of individual choice, people may wish to reduce or remove A1 f-casein from their diet (or their children’s diet) as a precautionary measure. This may be particularly relevant for those individuals who have or are at risk of the diseases mentioned (type I diabetes, coronary heart disease, autism and schizophrenia). However, they should do so knowing that there is substantial uncertainty about the benefits of such an approach.”

A2 milk is the key ingredient of some lines of infant formula (e.g., a2 Platinum Premium Infant Formula) (Synlait, 2015). The producer claims that A2 milk is easier for newborns to digest because of its greater similarity with human milk. Human p-casein, as sequenced by Greenberg and co-authors (1984), is however different from cow A2 variant.

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