Casein is the chief component of the milk proteins of which about 30-35 percent is beta-casein. The major beta- casein variants are A1 and A2. A2 beta-casein possesses proline at 67th position of its 229 amino acid chain while A1 beta casein has histidine at the respective position owing to a mutation that occurred in due course of time. Breeds like Jerseys, Asian and African cows produce A2 milk while Holsteins and Ayrshire predominantly produce A1 milk. Beta-casomorphin-7 (BCM-7) is a bioactive seven-amino peptide released by digestive enzymes exclusively from the A1-beta-casein protein. Several researchers have reported BCM-7 interacts with the human gastrointestinal tract, internal organs and brainstem. BCM7 adversely affects the immune response and is also considered as a risk factor for type 1diabetes. A2 milk is considered safe for human consumption. However, several other studies have found no relationship between A1 milk and the etiology of these diseases. Hence the present picture on A1vs A2 milk in concern to their health impacts is still unclear.
Since time immemorial milk has been considered as perfect food because it is an important source of nutrients and micronutrients. Milk consists of about 87 percent water and 13 percent of milk solids constituting fat, lactose, minerals and protein. Casein is the chief component of the milk proteins of which about 30-35 percent is beta-casein. Beta- casein may be of different types based on genetic background of the animals but the major types are A1 and A2 (Swinburn, 2004). Beta-casein consist a chain of 229 amino acids. Milk having proline at 67th position of beta- casein amino acid chain is regarded as A2 milk and with histidine amino acid at this position is A1 milk (Cowan, 2009; Woodford, 2007). Cows producing A2 milk are known as A2 cows while those producing A1 milk are called A1 cows. Cows like Jerseys, Guernsey, Asian and African cows produce A2 milk while Holstein and Ayrshire cattle breeds predominantly produce A1 milk (Woodford, 2007; Cowan, 2009; www.snowvillecreamery.com). Sheep, goat, yaks, buffalo, camels, donkeys and Asian cows naturally contain more A2 beta casein protein (Briden, 2013).
Genetics behind A1 and A2 Milk
Production of A1 or A2 milk by cows is governed by beta casein gene which is located on chromosome number 6. Since long back, cows have been producing A2 milk which is regarded as safe and nutritious. Around five thousand years back beta-casein gene was mutated and 67th amino acid was changed from proline (A2 allele) to histidine (A1 allele). A cow carries only two copies of the beta-casein gene. Hence, possibly she can be of A2A2 homozygous genotype or A1A2 heterozygous genotype or A1A1 homozygous genotype. The alleles do not have dominant – recessive relationship i.e., both the alleles are co-dominant in nature. Thus, an A1A2 cow will produce both A1 and A2 beta casein alleles in equal proportion. An A2A2 genotype cow will only produce A2 beta-casein and an A1A1 cow will only produce A1 beta-casein. A cow of A2A2 genotype will transmit the A2 allele to her progeny while an A1A1 cow will pass on the A1 allele and for A1A2 cow there is an equal chance of transmitting either allele. Breeding for A2A2 cows can be done by using semen from bulls of A2A2 genotype.
Table 1: Breeding designs and offspring genotype
(Woodford, 2007; snowvillecreamery.com; www.zoetis.com; Indian Dairymen, 2017)
With the continuous use of the European breeds in selective breeding to increase milk production, improve reproduction gradually A1 allele have propagated through the breeding programme. It has been shown by several surveys that A1 / A2 frequency is area-specific rather than breed-specific. Example, A1 gene frequency in Holstein Friesen of North America and North Europe cow is very high (above 90%) but in German Holstein Frisian A2 gene frequency is very high (around 97 %). In other countries, frequency of A1 in Holstein Friesian is in the range of 40 – 65%. Guernsey breed from USA or Europe has high A2 frequency in cows and breeding bulls even more than 98 % which is almost equal to Indian breeds. A2 gene frequency is usually higher in Jersey (60-80%) globally (Vet Helpline India, 2015, www.downtoearth.org.in, snowvillecreamery.com). Genotyping of bulls for A1 and A2 allele is a good method for lowering the risk of A1 allele in human health and increase milk and protein yield (Olenski et al., 2009)
The Devil in A1 Milk
Digestive enzymes act differently upon A1 and A2 beta-casein proteins during digestion process. Beta-casomorphin-7 (BCM-7) is a bioactive seven-amino peptide is released by digestive enzymes from the A1-beta-casein protein but these enzymes cannot split the A2 protein due to presence of proline at that location. So BCM-7 is not released from A2 proteins digestion. BCM-7 interacts with the human gastrointestinal tract, internal organs, and brainstem and is regarded as the “devil” in A1 milk (snowvillecreamery.com, Trustwell, 2005).
Fig.1: A2 and A1 beta casein differ only by one amino acid at 67th position in 229 amino acid chain (www.drjockers.com)
Fig. 2: Release of BCM 7 from A1 beta casein during digestion (www.rawfoodlife.com)
Health Hazards of A1 Milk
Several research workers have reported about the health hazards associated with A1 milk consumption. Elliot (1992) observed that children in Polynesian islands consuming only to A2 type milk were at lesser risk to Diabetes type 1 than Polynesian children in Auckland who were accessing A1 type of milk. An in vivo experiment on non-obese diabetic mice further scientifically authenticated the observation. Elliot et al. (1999) found a positive correlation between consumption of the β-casein A1 variant and incidence of diabetes mellitus. BCM-7 can affect many opioid receptors in the nervous, endocrine and immune system. Infants are more vulnerable because they have more chance of absorption of BCM-7 because of comparatively less developed gastro-intestinal tract than the adults. BCM-7 may act as an immunosuppressant and may increase the risk of Type 1 Diabetes, Coronary Heart Disease, Arteriosclerosis, and Sudden Infant Death Syndrome. It is also related with some neurological disorders like Autism or Schizophrenia (Pattanayak, 2013).
Bovine BCM-7 has been associated with the possible risk of human ischemic heart diseases (McLachlan, 2001). Kamiński et al. (2007) claimed a probable linkage between consumption of beta-casein A1 and occurrence of ischemic heart disease, sudden infant death syndrome, neurological disorders like autism and schizophrenia in New Zealand. Beta-casein A1 is more atherogenic than beta-casein A2 (Tailford et al., 2003). Moreover, Laugesen and Elliot (2003) also found a strong correlation between consumption of A1 bovine milk and incidence of ischemic heart disease (IHD) and Type 1 Diabetes Mellitus. High intake of milk with A1 β-casein increases the chance of different diseases likes Diabetes Mellitus-1, Ischemic Heart Disease, Schizophrenia and Autism (Swinburn, 2004). Laugesen and Elliott analyzed food consumption data from 19 ‘health care affluent’ developed countries to study correlations between food consumption and the rates of Type 1 diabetes. Strong correlations (r = 0.92) were identified between the consumption of A1 β-casein and the incidence of type 1 diabetes. Incidence was found to be highest in Finland and Sweden (countries with the highest A1 β-casein consumption/per capita) and lowest in Venezuela and Japan (countries with the lowest A1 β-casein consumption/per capita). Padberg et al. (1999) in one human study to investigate the differences in antibody responses to A1 and A2 β-casein reported that the ratio of A1 to A2 β-casein antibodies was significantly higher in those with Type 1 diabetes than in controls (P<0.001).
Benefits of A2 Milk
A2 milk is free from the devil in milk BCM-7 and hence is safe for consumption (Pattanayak, 2013). The populations consuming milk having more beta-casein A2 exhibit a lower occurrence of cardiovascular disease and Type 1 diabetes (Sodhi et al., 2012). People consuming A2 milk had better stool consistency, less incidence of bloating and less abdominal pain (Ho et al., 2014).
A2 Milk Production- Indian Context
In India, most of the native cows produce A2 milk which is very much safe for consumption. Several research workers have attempted to study the A1 or A2 milk status in our indigenous breeds. Mishra et al. (2009) examined 15 zebu cattle breeds (Kangayam, Nimari, Red Kandhari, Malnad Gidda, Kherigarh, Malvi, Amrit Mahal, Kankrej, Gir, Sahiwal, Hariana, Tharparker, Rathi, Mewati and Red Sindhi) and 8 river buffalo breeds (Murrah, Mehsana, Marathwada, South Kanara, Manipur, Assamese Swamp, Nili Ravi and Pandharpuri) and reported the absence of A1A1 genotype. A2 gene was nearly at fixation (0.987) in zebu cattle. Indian cattle and buffalo breeds are reported to have 99 to 100% of the A2 /A2 genotype and A1 /A1 genotype is almost absent or very rare among them. Therefore, it can be said that our native cows and buffaloes produce safer milk than European cattle breeds (Pattanayak, 2013). Ganguly et al. (2013) reported genotypic frequency A1A1 (0.15), A1A2 (0.41) and A2A2 (0.44) in Frieswal cattle and genotype frequency of A2A2 genotype (0.89), A1A1 (0.00) and A1A2 (0.11) in Ongole cows. Malarmathi (2014) reported A2 gene frequency among Holstein Friesian crossbred to be 0.595 and 1.0 in pure Kangeyam cows.
Opportunity for Commercialization of A2 Milk
There is vast scope for commercialization of A2 milk worldwide since demand for safe A2 milk is ever-increasing. In New Zealand, a company named A2 Corporation Ltd. (A2C) presently renamed as a2 Milk Company Ltd has been launched to commercialize A2 milk. This company has started huge scale marketing of A2 milk and milk products in the name of A2TM in New Zealand, Australia, United States and Asia (http://www.a2corporation.com). A subsidiary of A2 Corporation Limited known as A2 Milk Uk (Ltd) produces and markets milk containing A2 protein in UK and Ireland ( www.a2milk.co.uk). Demand for Indian cattle (A2 milk) is rising globally in many countries like Australia, South America, Africa, Brazil and Southeast Asia (De et al., 2015). So there is an opportunity to collect A2 milk from A2 genotyped herds separately and market at premium price. A2 milk can be used to prepare baby food. Therefore, India has a prospect to become world leader in A2 infant food supply. (www.suruchiconsultants.com).
The Non-Conclusive Opinion on A1/A2 Milk
As stated above, there are many research reports reflecting the negative health impacts of A1 milk. However, several other studies have found possible evidence of A1 milk as a factor for causing diabetes and coronary heart disease. European food safety authority also could not find any relationship between oral intake of BCM-7 and etiology of such diseases (Hills, 2009). The Australian and New Zealand food safety Authorities have also reported no relation between A1 or A2 milk and diabetes and Coronary Heart Disease incidence. Thus, there is no conclusive remark on A1 milk being the risk factor for these diseases. Hence, need of the present era is to carry forward for research to establish the association between A1 or A2 milk with the etiology of the above said diseases (Indian Dairymen, 2017).
India is fortunately bestowed with a large number of dairy cattle and buffaloes producing the healthy A2 milk. Time has come to pay attention for improvement and conservation of our indigenous germplasm. However, to establish the advantages and disadvantages of A1 vs A2 milk, more research should be conducted to draw conclusion on the hypothesis.