Until May 15 of this year, there had been a lack of new scientific evidence about A1 milk for almost a year. The reason it was quiet is because no-one had been funding the next studies that needed to be undertaken. However, new evidence has now come forward from India, somewhat out of left field.
Prior to this, there had been multiple strands of evidence demonstrating that A1 beta-casein and hence A1 milk is pro-inflammatory and linked to auto-immune conditions. However, the new research published by Nature Research in the journal ‘Scientific Reports’ is the first to explore these pro-inflammatory and immune-related effects of A1 beta-casein in the airway and lungs.
For those new to the A1 versus A2 milk issue, or needing a refresher course, the A1 versus A2 milk issue relates to whether or not the beta-casein in the milk is of the A1 or the A2 type. A lot of milk from European breeds of cows is of the A1 type whereas Asian cattle, sheep, goats, all humans and many other species of animal produce milk where the beta-casein is exclusively of the A2 type. The A1 milk, when digested, releases a protein fragment called beta-casomorphin which has opioid characteristics. This opioid can have a myriad of effects.
As to why the funding of A1 beta-casein science has gone a little quiet recently, the answers are that it is a consequence of global dairy-industry politics and commercial positioning. That is a story for another time. However, in the meantime most of the big international dairy companies have been positioning themselves with A2 product offerings, particularly in the infant-formula category. Infant formula is the most profitable dairy category for those who manage to get a foothold in a very crowded field.
Anyone who follows the stock exchange will know that ‘The a2 Milk Company’, which is the New Zealand registered but dominant global company in the A2 category, has grown to have a market capitalisation more than twice that of Fonterra. It has been a huge success, based on original science undertaken in New Zealand, but with most of the company now owned by overseas investors. Oh dear!
The science journey started with investigations by Professor Bob Elliott, who has in recent days been awarded a knighthood in the latest Queen’s Birthday Honours. It was Elliott, now ‘Professor Sir Robert Elliott’ who identified A1 milk as a risk factor for Type 1 diabetes. From there, the A1 versus A2 beta-casein research spread into many other health fields.
Returning here to the latest research, the paper published by Nature Research investigates whether prolonged use of A1 milk predisposes for asthma and other lung conditions through breathing-passage constriction and pro-inflammatory effects. The short answer is that it does, and the evidence is powerful with high statistical significance.
There is a lot of health research, particularly relating to foodstuffs, where it is extremely difficult to conduct the research directly in humans. That is a key reason why nutrition research is typically controversial and contested. Results often take a long time to show up, which makes clinical trials exceedingly difficult, even if ethics approval is granted.
For many trials, ethics approval is impossible. So, for cause and effect questions that need proof and not just epidemiological correlations, the work is often done with animals.
In this case, the research was done with mice that were fed the equivalent of one glass of milk per day for thirty weeks (210 days), with this being squirted down their throats. Then the mice were treated with methacholine which is a standard method in humans for testing whether someone is susceptible to asthma. At that point the mice had to make the supreme sacrifice so that all the measurements could be taken.
Of course, if this research had been undertaken with only A1 milk, then it would have proved nothing. Other groups of mice, all housed individually, were fed either A2 milk, or a 1:1 ratio of A1 and A2 milk. There was also a control group that were drenched with distilled water.
The results were very clear. The mice that had been on a diet of A1 milk were much more susceptible to asthma when dosed with methacholine. This was caused through both airway constriction and inflammation in the lungs.
The mechanism behind the result was also very clear, being what scientists call Th-2 driven. This means that the immune system becomes unbalanced and there is overproduction of cytokines such that the body is damaged by its own actions. Specific cytokines that were over-produced include interleukin-4 and interleukin-5.
The term ‘cytokine’ is well known to immunologists but has only recently entered the general lexicon, largely through its association with COVID-19. When people die suddenly from COVID-19, it is typically from a cytokine storm which leads to organ failure through lack of oxygen. Coincidentally or not, the mechanism is essentially the same – an immune over-reaction leading to excessive cytokine production.
The evidence from the current study is that the A1 milk itself is not the final trigger. Rather, long-term exposure to A1 beta-casein creates an immune environment more susceptible when the trigger gets pulled by some other factor, in this case methacholine. Conversely, in the absence of A1 beta-casein, the trigger, which can be either be a specific foodstuff or a virus, is much more likely to either fire a blank or a low-powered half-shot.
With humans, the susceptibility to various diseases including asthma and pneumonia-type conditions varies between individuals. This is because of genetic variation between individuals. Some people have weak immune systems, others have overactive immune systems in response to specific situations. However, all humans have the same Th-2 and cytokine driven immune systems. It is the sensitivity that varies between individuals.
With the specially inbred mice, all were similarly susceptible to specific environmental conditions and triggers. This is what made them a good animal model to test out the Th-2 and cytokine driven mechanism, in this case set-up by the A1-milk environment.
With hindsight, the results should come as no surprise. It was already known both for humans and animals that A1 beta-casein is pro-inflammatory through these same Th-2 and cytokine mechanisms. It was just that no-one had done a trial to prove it in relation to asthma and the lungs.
When trying to evaluate the credibility of a study, most people ask several questions. Are the results statistically significant? Is there evidence for the mechanism? Is the mechanism plausible for humans? Who published the study? Who authored the study and did they have conflicts of interest?
The first three questions have already been answered as a strong ‘yes’. The fourth question has also been answered – the study was published by pre-eminent Nature Research. The answer to the fifth question is that the six authors are scientists employed by various governmental research institutes and universities in India, and they all declared that they had no competing interests. India has considerable interest in A2 milk because their native cattle are A2.
For those who want to dig deeper, the article is open access at nature.com. Here is the full link. A gentle warning is that the paper does assume some prior knowledge of immunology.
*Keith Woodford is a retired professor from Lincoln University (NZ) and retains an honorary position there as Professor of Agri Food Systems. As one element of broad-ranging scientific interests, he has been writing about A1 and A2 beta-casein for many years. This includes a book ‘Devil in the Milk’ on the science and politics of the issue, first published in 2007 in NZ, and with subsequent American and Russian editions. More recently he has co-authored five research papers with medical colleagues in international nutrition and medical journals on further research into A1 and A2 beta-casein. Articles for non-scientists are archived here.