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)