A1 and A2 Variants of Beta Caseins in Cow Milk and Human Health
Milk is a complex mixture of proteins, fats, carbohydrates, vitamins, and minerals, playing a crucial role in human nutrition. One group of proteins present in milk is caseins, and among them, beta-casein is a major component. Variations in the amino acid sequence of beta-casein give rise to different genetic variants, with A1 and A2 being the most well-known. This article provides an overview of A1 and A2 beta-casein variants in cow milk and explores their potential implications for human health.
Milk is a common source of animal protein and associated micro elements for vegetarians. It has body-building proteins, bone-forming minerals and health-giving vitamins and energy-giving lactose and fat. Milk is about 85% water. The remaining 15% is the milk sugar lactose, protein, fat, and minerals. The protein portion is 80% casein and 20% whey. The proteins present in milk are considered as complete proteins of high quality, i.e. they contain all essential amino acids in fairly large quantities. Recently, a relationship between disease risk and consumption of a specific bovine β-casein fraction with either A1 or A2 genetic variants has been identified.
Milk proteins
Six different types of proteins are present in milk out of which four are casein proteins (α, β, γ and K-casein) and two are whey proteins (β-lactoglobulin and αlactalbumin). Casein protein is peculiar because it is present only in milk and exists in the form of calcium caseinate-phosphate complex. β-casein is 30% of the total protein content in cow’s milk. It is the second most abundant protein in cow’s milk that contains 209 amino acids. There are 12 genetic variants of β-CN: A1, A2, A3, B, C, D, F, H1, H2, I and G out of which A1 and A2 are the most common. Milk high in β-casein Al is referred to as ‘Al milk’ while milk high in 3-casein A2 is called ‘A2 milk’. A1 variant has histidine at position 67 of the amino acid sequence while A2 possess proline at this position. A2 beta-casein is the beta-casein form cows have produced since before they were first domesticated, over 10,000 years ago. It is considered safe and nutritious and has no known negative effects on human health. Sometime in the past few thousand years, a natural mutation occurred in some European dairy herds that changed the beta-casein they produced. The gene encoding beta-casein was changed such that the 67th amino acid in the 209 amino acid chain that is the beta-casein protein was switched from proline to histidine. This new kind of β-casein that was created is known as A1 β-casein, and is generally more common in many of the big black-and-white cow breeds of European descent such as the Holstein and Friesian.
Human health hazards
Gastrointestinal proteolytic digestion of A1 variant of β-casein (raw/processed milk) leads to generation of bioactive peptide, beta casomorphin 7 (BCM7). Infants may absorb BCM-7 due to an immature gastrointestinal tract whereas adults gather the biological activity locally on the intestinal brush boarder. In hydrolysed milk with variant A1 of beta-casein, BCM-7 level is 4-fold higher than in A2 milk. Recently, a relationship between disease risk and consumption of a specific bovine βcasein fraction with either A1 or A2 genetic variants has been identified. BCM7 is suggested to be associated as a risk factor for human health hazards as it can potentially affect numerous opioid receptors in the nervous, endocrine and immune system. It is also known to be an oxidant of low dietary lipoproteins (LDL) and oxidation of LDL is believed to be important in formation of arterial plaque. Epidemiological evidences claim that consumption of beta-casein A1 milk is associated as a risk factor for type-1 diabetes, coronary heart disease, arteriosclerosis, sudden infant death syndrome, autism, schizophrenia etc. A broad range of studies from American and European investigations has shown reduction in autistic and schizophrenic symptoms with decrease in A1 milk intake. Further, animal trials have also supported the linking of type-1 diabetes to milk exposure in general and A1 beta-casein in particular. A2 milk has not been associated with these diseases. Symptoms of Al milk protein intolerance can be similar to those of lactose intolerance, including digestive issues such as bloating, abdominal pain, nausea, diarrhea and constipation. Human trials are needed before it can be said with confidence that the All A2 composition of milk is important in human health.
Status of Indian cows
Recent research has shown that Bos indicus cows (Indian cows) are potential sources of BCM 7 (Beta Casomorphine 7)-free A2 milk which is considered good milk, compared to Bos taurus cows (exotic cows), which produce Al milk. Initial studies on indigenous cow (Zebu type), buffalo and exotic cows (taurine type) have revealed that A1 allele is more frequent in exotic cattle while Indian native dairy cow and buffalo have only A2 allele, and hence are a source for safe milk.
Detection of A1 milk
A genetic test developed by the A2 Milk Company based in Australia determines whether a cow produces the A2 or Al type protein in its milk. This is done through a DNA test of a cow’s tail hair. The test allows the A2 Milk Company to give licenses to milk producers once these producers prove their cows produce A2 β-casein protein in their milk. Now, more and more Al companies are beginning to test their bulls to establish whether they carry the desirable A2 gene. Al milk has been implicated as a potential etiological factor in Type 1 Changing the dairy herds to more A2 producing cows on commercial basis may significantly improve public health. The Government of India has already taken steps to identify the breeds having A2 gene. Changing the dairy herds to more A2 producing cows on commercial basis may significantly improve public health. Selection for increasing milk yield may contribute for the higher proportion of undesirable A1 alleles in the population. Considering the public health implication, adequate weightage should be given to select bulls with A2A2 genotype while making selection for increasing milk yield of crossbreds. The Government of India has already taken steps to identify the breeds having A2 gene. Preliminary studies have confirmed the hypothesis that Indian breeds of cows produce the safe A2 type milk. The National Dairy Research Institute, Karnal recently fixed A2 casein allele in Deoni cattle and also reported that Malnad Gidda predominantly (151 out of 154) have casein allele. Research is already going on for fast DNA detection tools to identify Al/A2 milk producing cows in India.
A1 and A2 Beta-Casein Variants
- A1 Beta-Casein
The A1 beta-casein variant is characterized by a specific amino acid sequence, primarily involving histidine at position 67. The release of a bioactive peptide called beta-casomorphin-7 (BCM-7) during digestion is associated with A1 beta-casein.
- A2 Beta-Casein
In contrast, the A2 beta-casein variant has a different amino acid sequence at position 67, typically involving proline. The digestion of A2 beta-casein does not result in the production of BCM-7.
- Genetic Basis
The presence of A1 or A2 beta-casein in cow milk is determined by the genetics of the dairy cow. Different breeds and individual cows may carry the genes for either A1, A2, or a combination of both beta-casein variants.
Digestion and Production of BCM-7
- A1 Beta-Casein and BCM-7
During digestion of A1 beta-casein, particularly by the enzyme pepsin in the stomach, BCM-7 is released. BCM-7 is a bioactive peptide that has been studied for its potential effects on health.
- A2 Beta-Casein and Lack of BCM-7 Release
The digestion of A2 beta-casein does not lead to the release of BCM-7. Proponents of A2 milk suggest that this may be associated with a reduced likelihood of certain health concerns.
Implications for Human Health
- Digestive Comfort
Some individuals claim that consuming A2 milk, which lacks the release of BCM-7, may be associated with improved digestive comfort. However, scientific evidence supporting this claim is limited and subject to ongoing research.
- Inflammatory Response
There is a hypothesis that BCM-7, released during the digestion of A1 beta-casein, may contribute to an inflammatory response in the body. This has been suggested to be a potential factor in certain health conditions.
- Chronic Diseases
Associations have been proposed between the consumption of A1 milk and the risk of developing certain chronic diseases, including cardiovascular disease, diabetes, and autism. However, the scientific evidence supporting these associations remains inconclusive and warrants further investigation.
Challenges and Considerations
- Human Variability
Responses to A1 and A2 beta-casein variants can vary among individuals. Factors such as genetics, gut microbiota composition, and overall health may influence how individuals respond to the consumption of these variants.
- Research Gaps
While there is ongoing research on A1 and A2 beta-casein, much remains to be understood. The existing body of evidence is not yet robust enough to draw definitive conclusions about the health implications of consuming one variant over the other.
- Dietary Patterns
The overall dietary context, including other components of the diet and lifestyle factors, plays a crucial role in determining health outcomes. Focusing solely on the beta-casein variants without considering broader dietary patterns may limit the understanding of their impact.
Conclusion
The A1 and A2 beta-casein variants in cow milk have sparked interest and debate regarding their potential implications for human health. While some studies suggest associations between A1 milk consumption and certain health concerns, the evidence is inconclusive, and more research is needed. It is essential to approach this topic with a nuanced understanding of human variability, dietary patterns, and the complexities of individual health. As the scientific community continues to investigate the potential effects of A1 and A2 beta-casein, consumers are encouraged to make informed choices based on a balanced understanding of the available evidence.
Compiled & Shared by- This paper is a compilation of groupwork provided by the
Team, LITD (Livestock Institute of Training & Development)
Image-Courtesy-Google
Reference-On Request.
