Human clinical trial demonstrates digestive differences in A1 and A2 beta-casein

The results of a human trial comparing A1 and A2 beta-casein have been published recently in the European Journal of Clinical Nutrition, which is a high ranking journal of the Nature Publishing Group. The trial demonstrated statistically significant differences in faecal consistency, with the faeces on A1 being overall looser. Also, for those people who on the A1 milk had the looser and runnier faeces, there was very strong evidence (p=.001) that this was associated with more stomach pain, whereas this relationship did not hold on the A2.

The trial was undertaken at Curtin University and led by Associate Professor Sebely Pal. I was part of the analysis and writing team, and I am listed as a co-author.

Prior to this trial there was already conclusive evidence that A1 and A2 beta-casein digest differently in animals. For example, an earlier paper by Barnett et al (discussed here) had demonstrated with rats that A1 beta-casein slows down transit of food through an opioid effect, increases the level of an enzyme DPP4 which amongst other things influences insulin metabolism (a non-opioid effect) , and causes inflammation in the colon (an opioid effect). I was also a co-author on that paper. Similarly, a trial with mice (discussed here) also showed an increase in inflammatory markers in the intestines, and also demonstrated a raft of immunological effects in the digestive system. However, until now, no-one had undertaken a clinical trial looking at digestion differences in humans.

We called this trial a pilot trial because we had no prior knowledge as to the sample size we would probably need to obtain statistically significant results. We started with 41 people, most of whom normally drink milk and considered themselves prior to the trial to have no problems with digesting ordinary milk.

From the initial 41, there were 36 who completed the eight week trial. Each person spent two weeks on each treatment, and they did not know which milk they were drinking at which time. Half had the A1 milk first (randomly assigned), and the others had the A2 milk first. Before and between the treatments they had a two week ‘washout’ period using rice milk and no cow milk.

We hoped that the number of people in the trial would be enough to get statistically significant results and that is how it turned out both for the key measure of faecal consistency, and also the relationship between looser faeces and stomach pain on A1. Although not specifically reported in the paper, there were 14 of the 36 people who completed the trial who had a mean faecal consistency on the A1 milk that was looser than is considered normal, and these were predominantly the ones who had the greater stomach pain.

The faecal consistency differences between A1 and A2 were more pronounced for women than for men. Personally, I doubt whether there is any fundamental A1 versus A2 difference between women and men; I suspect that it is probably just that the women take more care when asked to ‘grade’ their faeces.

For a small group of people who self-defined before the trial as being intolerant to milk, we were also able to show considerable differences in bloating, pain, wind and voiding difficulty between the two arms of the trial, with all values higher on A1. But our group size there was insufficient to show statistical significance (i.e. conclusive proof). We only started with 10 people who considered themselves intolerant, and of these two pulled out during the A1 arm of the trial, and so we could not use the data for those two. The message there is that for people who already know they are intolerant to ordinary milk, we need a bigger sample size. To encourage these people to engage in any future trial, we will need to keep the period of milk drinking much shorter.

The power of this paper has two elements.
1. It has demonstrated at levels which in science are considered conclusive that in humans there are indeed differences in digestive symptoms between A1 and A2 beta-casein.
2. The results are consistent with conclusive prior evidence from animals.

The mainstream dairy industry will not be pleased with these results. The PR folk will undoubtedly try and counter the message with spin. However, there is more evidence in the pipeline. They should not sleep easy.

What the mainstream industry now needs to do is urgently start thinking about converting the mainstream herds to A2. In New Zealand, there are no constraints to this occurring but it will take time. In many other parts of the world there are patent issues which restrict the selection of A2 herds. However, these herd selection patents now run out in less than two years.

There is much more in the paper than what I have discussed here. A copy of the paper is therefore attached here as a pdf for those who wish to dig a little deeper. (Ho et al ejcn)

About Keith Woodford

Keith Woodford is an independent consultant, based in New Zealand, who works internationally on agri-food systems and rural development projects. He holds honorary positions as Professor of Agri-Food Systems at Lincoln University, New Zealand, and as Senior Research Fellow at the Contemporary China Research Centre at Victoria University, Wellington.
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13 Responses to Human clinical trial demonstrates digestive differences in A1 and A2 beta-casein

  1. Pingback: Rural round-up | Homepaddock

  2. Lyn Haycock says:

    It irritates me soooo much that the Health system of which I was once part off continues to do much hand wringing about obesity, diabeties and heart disease, not to mention those other conditions along the way that have been identified as most likely connected to A1 milk, the answer is right ther under their noses!!! If they do not like the European countries results do their own trials here. There are plenty of potential candidates for a very simple trial.
    It would be such a simple short trial to run in comparison with a complex drug trial. The risks are much less,the benefits to the nation as a whole are great. Relatively inexpensive to run as well maybe HRC grant trial there

  3. farmerbraun says:

    ” who(m) normally drink milk and considered themselves prior to the trial to have no problems with digesting ordinary milk.”

    and then:-
    ” these were predominantly the ones who had the greater stomach pain.”

    I don’t understand.
    They had pain from drinking normal milk before the trial, and considered that it was no problem?
    Or, they had no problem(pain) from drinking normal milk before the trial , but during the trial they did get pain from A1 (conventional) milk?

    Which is it?

    • Keith Woodford says:

      First the grammar: I think I was correct.
      Prior to the trial, if they did experience pain they did not associate it with the milk.
      When on the A1 arm of the trial, there were 14 of the 36 who had mean stool values (Bristol stool) greater than the normal range of 3 to 4. And yes, the results show this was associated with more pain. In general, the amount of milk they were drinking during the trial would have been greater than their normal consumption.
      The key message from this particular trial is that in humans there are indeed differences between the A1 and A2 treatments. It demonstrates that the mainstream mantra that ‘there is no difference’ is incorrect. The full implications of the differences has yet to be elucidated, The evidence for that lies in animal trials and human epidemiology which have been and are coming forth.
      Keith W

    • Keith Woodford says:

      You have misunderstood the trial.
      Prior to the trial most of these people had not self identified as having a problem with milk. But when they were on the A1 arm of the trial there were 14 of the 36 participants who had faeces with a mean consistency above the normal Bristol stool figure of 4, and these people were the ones who predominantly had the greater pain. The relationship was statistically highly significant. There was no such relationship on the A2 arm of the trial.
      Keith W

  4. ed765 says:

    I believe the people who reported pain with A1 milk were getting not normal milk, but milk which was only A1 beta casein. This, combined with drinking more milk would be a much greater exposure to A1 beta casein than they normally had.

    Also being in a trial they would have been more conscious of their consumption of milk, and likely to attribute it to the milk, while in ordinary life where milk was frequently drunk (or casein consumed in another product), the occasional pains might not be associated with milk.

    I hope the subjects were informed of the results of the study, and what they drank when. Some might then reasonably conclude their occasional pains could be attributed to milk, or casein in other products. They might then choose to avoid milk, and casein containing products, or to use A2 brand milk which I believe is available in Perth.

  5. ed765 says:

    Besides using a short milk drinking period in any future studies (which I hope will be carried out), it is possible I presume to pay subjects. Paid subjects endure fairly serious side effects in drug trials. (see the book, Chasing Medical Miracles: The Promise and Perils of Clinical Trials by Alex O’Mearasee).

    I hope further studies will be done to pin these effects down. It would also be nice to know how to best do a test to determine whether you were sensitive to A1 beta casein. Some people may wish to just try drinking large quantities of supermarket milk, possibly along with casein containing products (say ice cream made from milk, not cream), and seeing what happened. They might then try drinking the same quantity of A2 brand milk to see if there was an effect.

    The question is would a one day trial work, two days, a week, two weeks (as in this study).
    Ideally they would use milk with only A1 beta casein in the trial, but I do not know if that is readily available. It might be in the interest of A2 Corporation to make this available (but I do not know the legalities, and whether making it available for such testing would make it subject to expensive testing usually done before marketing a medical test).

    Developing such procedures could be in the interest of A2 Corporation, and I would hope they would fund such studies. I suspect they would sell a certain amount of milk to those doing the test, and probably acquire some new customers, ones whose health (or at least intestinal comfort levels) would be improved by using their milk.

  6. Peter says:

    In the Sydney Morning Herald this week, Rosemary Stanton (a very popular veteran nutritionist with a good reputation) criticised the Curtin study at:
    Do you think her comments have any validity? Would it be a good idea for you to contact the Herald journo to clarify? There’s a link to his email near the top of the article.

    • Keith Woodford says:

      Peter, I did write very politely to Rosemary Stanton suggesting she had misinterpreted the paper and suggesting that I would like to discuss with her the trial, and also broader issues of A1 beta-casein. But she has not acknowledged my email. I am advised that Rosemary approached the media herself, rather than being sought out by the media, which suggests that it is indeed an issue she feels strongly about. I think we just have to accept that there are a lot of people who have sung the praises of milk for a long time, and it can be very hard to get them to look objectively at these matters.
      Keith W

  7. Peter says:

    (off-topic) A week ago, this appeared in the Sydney Morning Herald:

    “There are institutional investors and then there are investors who are an institution.

    The fifth-biggest shareholder of New Zealand dairy company, a2 Milk, is none other than her majesty, Queen Elizabeth II.

    The Crown owns just over 6 per cent of the company, which is worth a princely sum of about $NZ25 million ($22.2 million),

    But not is all what it seems.

    Although the shares were bought through the New Zealand Superannuation Fund, which her majesty owns, it is name only.

    The sovereign wealth fund was created under the New Zealand Superannuation and Retirement Act in 2001. Its purpose was to provide universal superannuation to people over 65 sometime in the 2020s, by which time a state-paid pension would become a little heavy for taxpayers to bear.

    But the New Zealand government suspended its contributions to the fund, which have totalled about $NZ14.88 billion, in 2009 – opting to repay debt instead.

    So one is yet to know if her majesty does indeed “feel the difference”, as the company says, of using a2 Milk on her morning porridge to improve her digestive wellbeing.”

    • Keith Woodford says:

      Peter, It is always nice to see some humour! a2 milk is indeed available in the UK but it is very much a niche product and I doubt that Her Majesty has come across it.
      Keith W

  8. Jock campbell says:

    The Queen’s dairy herd ar Windsorwhich provides milk for the Palace etc is a Jerseyherd sois probably A2

    • Keith Woodford says:

      It will probably be higher in A2 than most herds in England, but it will still have a considerable proportion of A1 in the herd.
      Keith W

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