Beta-casein is a 209 amino acid protein that makes up about 30% of the total protein contained in milk (1), or roughly 2.5 grams per glass. Due to natural genetic variation, beta-casein can be present as one of two major types, A1 or A2. The single difference between these two types of beta-casein is an amino acid substitution at the 67th residue of the beta-casein protein chain. The subtle structural difference between these two beta-casein types means they are digested differently. The digestion of A1 beta-casein in the gut by the action of digestive enzymes can produce the exogenous opioid peptide called beta-casomorphin-7 (BCM-7) (2-5) (Figure 1). In contrast, A2 beta-casein releases much less and probably minimal amounts of BCM-7 under normal gut conditions (3-6), because for A2 beta-casein “the enzymatic hydrolysis of the Ile66-Pro67 bond does not occur or occurs at a very low rate” (2).
Epidemiological studies have found a correlation between A1 beta-casein intake and the incidence of certain non-communicable conditions (see Figure 2) (8-10). While epidemiological data cannot demonstrate a cause-effect relationship, it does provide population level information regarding exposure to environmental factors and disease outcomes and prompt scientists to investigate important scientific questions arising from observed relationships.
Research studies in animals suggest that A1 beta-casein feeding has the potential to stimulate symptoms of digestive discomfort. Two recent animal studies have investigated A1 versus A2 beta-casein on gastrointestinal effects directly (11, 12). Barnett et al. (2014) showed that feeding rodents milk containing A1 beta-casein resulted in significantly delayed gastrointestinal transit time compared to milk containing A2 beta-casein (12), which may affect symptoms of digestive discomfort. In addition, Haq et al. (2013) showed in mice fed a milk free basal diet supplemented with A1 relative to A2 beta-casein that gut inflammation markers were increased significantly with A1 beta-casein whereas A2 beta-casein had no effect relative to control animals (11), effects which a follow up study by the same research group suggest may be mediated by BCM-7 (13). There have been various other animal studies which have examined the effects of BCM-7 on markers of digestive wellbeing. The results from such studies suggest that the opioid activity of BCM-7 is linked to the stimulation of mucous production and thickening from goblet cells in digestive tissue in rodents (14-16).
In human adults, Boutrou et al. (2013) have shown recently that bovine BCM-7 is produced in the intestines following milk casein protein intake in amounts sufficient to elicit a biological action (17). In human infants, studies have shown further that BCM-7 is absorbed into the circulation of formula-fed human babies (18, 19), where there appears to be variation in the ability to eliminate BCM-7 between babies and that this could be due to variable activity of the enzyme needed to break down BCM-7 (19). More recently, Sokolov et al. (2014) have detected BCM-7 in the urine of children (20).
While further research is needed to establish a cause-effect relationship between exposure to BCM-7 and non-communicable disease conditions, there is research to suggest that BCM-7 is linked to various unwanted physiological effects. Notably, Professor Boyd Swinburn (Professor of Global Health and Nutrition , The University of Auckland) in his Report to the New Zealand Food Safety Authority entitled ‘Beta casein A1 and A2 in milk and human health’ (2004) (21) stated:
“……The appropriate government agencies have several important responsibilities in this matter: to support further research in the area (especially clinical research); to clearly communicate the state of knowledge and judged risks to the public, and; to take specific actions to promote and protect the health of the public, where appropriate”.
“As a matter of individual choice, people may wish to reduce or remove A1 beta-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…”.
The material contained within this website’s Health Professionals’ pages is intended solely for presentation to Health Care Professionals (HCPs). The purpose of the materials contained within these pages is threefold:
1) to highlight the extensive body of literature in the A1 beta-casein and beta-casomorphin related areas;
2) to review some of the relevant literature; and
3) to stimulate interest amongst HCPs to obtain and review some of the relevant literature directly.
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