A1 and A2 Bovine Milk and the Risk of Beta – Casmorphin- 7 in Human Health
- Chitra
Assistant Professor
Department of Veterinary and Animal Sciences
Agricultural College and Research Institute,
Tamil Nadu Agricultural University,
Coimbatore – 641 003, Tamil Nadu, India
Corresponding E mail : drpchithupsc@gmail.com
Abstract
Milk is the ideal food for all age groups of human being. Milk proteins are generally composed of proteins such as casein, lactalbumin, lactoglobulin, blood serum albumin, and immunoglobulin. Casein is the chief component of the milk proteins and consists of fractions such as alpha, beta, kappa and gamma proteins of which about 30 percent is beta- casein. The major beta- casein variants are A1 and A2. Beta- casein consist a chain of 229 amino acids. Cows that produce milk contain proline amino acid are called as A2 cows. A2 milk is found basically in indigenous cows and buffaloes of India. Around 5,000 years ago, a mutation occurred in this proline amino acid, converting it to histidine amino acid at 67 th position. Cows that have this mutated beta casein protein are called A1 cows. Different mutations bovine beta casein produce 13 genetic variants and out of these A1 and A2 are the most common. A1 β casein is enzymatically broken down in the intestine to produce beta – casmorphin- 7 (β-CM-7) which is an opioid peptide similar to morphine. BCM -7 interacts with the human gastrointestinal tract, internal organs and brainstem. BCM -7 adversely affects the immune response and is also considered as a risk factor for chronic heart diseases (CHD) and juvenile insulin dependent type I diabetes mellitus (DM-I).
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Keywords : Bovine milk, Beta – casein , Beta – casmorphin- 7, Human health
Introduction
Milk has been considered as a perfect food in all age groups including infants. Cow milk is closest to breast milk. It’s one of the inseparable parts of daily diet. Cow milk is a resource of fat, lactose, proteins, vitamins and minerals and also it contains several nutrients needed for growth and development. In health aspects, it contains immunoglobulin, hormones, growth factors, cytokines, nucleotides, peptides, polyamines, enzymes and several others bioactive peptides. Milk contains lactoferrin which is microbicidal. Cow milk is constituted of carbohydrate (Lactose) – 4.8% , Fat – 4%, Protein (Casein, Whey, Glycoprotein) – 3.5%, Minerals (Ca, K, I) – 0.8%, and Vitamins (A, B2, B12) and supplies 66 kcal of energy per 100 grams whereas Human milk contains an average 1.1% protein, 4.2% fat, 7.0% lactose and supplies 72 kcal of energy per 100 grams. Many cow products are used for their health promoting, disease-preventing and therapeutic purposes. Besides its nutritive use, milk and milk products are used in conjunction with medicines to enhance their pharmacokinetic and dynamic benefits. However an extensive body of evidence now exists that one particular type of milk containing specific beta casein protein might be harmful to the body.
Bovine Milk Protein: Beta casein
Bovine milk consist of about 87 percent of water and the remaining 13 per cent milk solids constituting fat, lactose, proteins and minerals. Cow milk is generally contains about 3.5% proteins, of which approximately 80% are caseins (αS1-, αS2-, β-, k-CN) and 20% are whey proteins (α-La and β-LG). Casein protein becomes a major source for supply of all essential amino acids (except sulphur-containing amino acids – methionine and cysteine). Casein protein constitutes of 36% α-Casein, 30 % β-Casein, 9% κ-casein and 25% peptides and amino acids. Among the caseins, beta casein is the second most abundant protein and has excellent nutritional balance of amino acids.
A1 and A2 milk
Milk that contains A1 β-Casein and A2 β-Casein are known as A1 milk and A2 milk respectively. Cows that produce milk contain proline (a specific amino acid) at 67 th position are called as A2 cows i.e. the original breeds of cows. A2 milk is found basically in indigenous cows and buffaloes of India. Around 5,000 years ago, a mutation occurred in this proline amino acid, converting it to histidine (a different type of amino acid). Cows that have this mutated beta casein protein are called A1 cows. A1 protein variant is commonly found in milk from crossbred and European breeds of cattle. The A1 or A2 status of a cow is determined by a pair of genes on the sixth chromosome of bovine genome (Parashar, A and Saini, R.K., 2015, Boro, P et al., 2016). There are two major alleles of the genes, these are called A1 and A2 beta casein alleles. A cow carries two copies of the beta casein gene, she can carry either of A2A2 (homozygous), A1A2 (heterozygous or A1A1 (homozygous) alleles. The A1 and A2 variants of bovine beta casein differ at amino acid position 67 with histidine in A1 and proline in A2 milk. The mutation that gives rise to this difference is the result of a single nucleotide difference at codon 67 of beta casein gene CCT (A2, proline) and CCT (A1, Histidine). Depending upon the presence of proline and histidine at position 67, the other variants have also been categorized as A2 or A1 type
The A2 allele gene in Indian milk breeds of cows and buffaloes are 100% (Red Sindhi, Sahiwal, Tharparkar, Gir and Rathi), other Indian breeds used for farming, is around 94 per cent (Joshi, 2011) and while in foreign breeds (HF and Jersey), it is around 60 per cent (NBAGR, 2011). A1 β-casein is absent in the milk of pure Asian and African Cattle.
Beta-Casomorphin-7 (BCM 7 ) and the risk of human health
A1 β casein is enzymatically broken down in the intestine to produce β-CM-7 which is an opioid peptide similar to morphine and named as β- casomorphins (β-CMs). It is a small protein that does not digest in human body. This can lead to indigestion and many types of research have shown that it may lead to various other problems or diseases like type-1 diabetes, coronary heart disease, arteriosclerosis, sudden infant death syndrome, autism and schizophrenia. In A2 milk, the proline amino acid found in 67 th position of the β-casein prevents BCM 7 formation in our body. But, A1 milk containing β-casein variants that has histidine at the 67th position of the β-casein allows the cleavage at this position by different gastrointestinal enzymes to release BCM-7.
Proline has a strong bond to a small protein called BCM7 and therefore stops the BCM7 from getting into milk. So essentially, no BCM7 is found in the urine, blood or gastro-intestinal tracts of the original A2 cows. Histidine, the mutated protein, does not have a strong bond to hold on to BCM7. Hence, on consumption of the A1 milk, this protein BCM7 gets into the gastro-intestinal tract of animals and humans. A2 beta-casein milk, the milk proteins are broken down into peptides, which in turn are broken down into amino acids. This type of milk is easily digestible. However, in the case of the A1 beta-casein milk, the peptides cannot be broken down into amino acids, and so, are indigestible. These A1 beta-casein protein fragments that enter the bloodstream through leakages in the guts cause serious ailments, including coronary heart disease, Type I diabetes and autism.
The A1 and A2 variants of bovine β-casein differ at amino acid 67th position with histidine in A1 and proline in A2 milk. This polymorphism leads to key conformational changes in the secondary structure of expressed β-casein protein (McLachlan, 2001). Due to presence of histidine at amino acid 67th position, digestion of A1 β-casein milk releases a 7 amino acid bioactive peptide called beta-casomorphin 7 (BCM-7) in small intestine, while proline in A2 milk at 67th position prevents the split at this particular site and generates peptide BCM- 9 (Kostya et al., 2004). It is believed that generation of BCM-7 is the major causative factor associated with A1 milk related health disorders. However, A2 β-casein not been linked to any of such health issues (Kaminski et al., 2007).
Genetic variants in bovine β-casein gene (A1 and B) release a bioactive peptide, β-casomorphin-7(BCM-7) upon digestion, responsible for many human disorders like Type 1 diabetes, autism, schizophrenia and heart diseases but A2 milk does not cause such type of illnesses (Sodhi et al., 2012). Infants may absorb β-CM-7 due to an immature gastrointestinal tract. Adults, on the other hand, appear to reap the biological activity locally on the intestinal brush boarder. Β-CM-7 can potentially affect numerous opioid receptors in the nervous, endocrine, and immune systems. Whether there is a definite health benefit to milk containing the A2 genetic variant is unknown and requires further investigation unlike harmful effects of A1 milk.
Beneficial effects of BCM-7
Apart from negative health impacts of BCM-7, there are certain reports indicating the association of BCM-7 with positive health promoting effects such as
- Antagonist for 5-HT2-scrotonin receptor and found to block serotonin induced platelet aggregation
- Inhibin of epithelial-mesenchymal transdifferentiation during hyperglycemia in NRK-52E cells by BCM-7 preventing, fibrosis in chronic renal failure
- Contribution to mucin production in intestine which has protective function
- Protective role in preventing high glucose induced oxidative stress in both in-vivo and in-vitro model
- Decreased oxidative stress in pancreas of diabetic mice by inhibiting NF-kB-iNOS-NO signalling pathway.
Conclusion
The A1/A2 hypothesis is both intriguing and potentially very important for public health. A few studies indicate that A1 beta casein may have adverse effects in certain individuals. The epidemiological and in-vitro data suggests the potential health hazards of consuming A1 type milk derived BCM-7, but the in-vivo studies of the same are very few to support the findings. Although a clear link between A1 β-casein and a disease state has not yet been confirmed. The hypothesis of A1 milk association with few chronic diseases drawn from a survey done in western countries population not in India. Considering the contribution of buffalo, indigenous cows and crossbred population in India’s milk pool and based on the assumption that β-casein is 45% of total protein and that around 25% of the β-casein may be from A11allele cows, the average consumption of A1 milk in India would be around 0.24g/day; 5-10 times lower than countries surveyed. So there is no cause to panic. If there is demand from consumers for A2 milk as a matter of choice, the government of India and state governments should come up with policy guidelines and entrust the certification powers with the agency that is currently certifying organic milk, otherwise the consumers are likely to be rigged.
Reference
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Sodhi, M., Mukesh, M., Mishra,B.P., Kishore,A., Prakash, B., Kapila, R. and Mclachlan. C.N.S. CNS. Β-casein A1, ischaemic heart disease mortality, and other illnesses. Medical Hypoth 56, 262–272, 2001
