A recent paper published in the European Journal of Nutrition provides particularly strong evidence that A1 beta-casein causes gut inflammation and associated immune effects relative to A2 beta-casein. The trials were conducted with mice and, using normal scientific criteria, the results are sufficiently strong that the differences under these research conditions can be described as ‘conclusive’.
This research has the potential to give a great boost to the campaign against A1 beta-casein. Milks that are free of A1 beta casein include all goat milk, all sheep milk, all pure Asian cattle, and all ‘A2 milk’ from cattle. Human milk is also free of A1 beta-casein. It is only the milk from a large proportion of European-origin cattle that produce the mutant A1 beta-casein.
The work was conducted at the Animal Biochemistry Division at the National Dairy Research Institute in India. The lead author is Dr Mohammad Raies Ul Haq.
The trial had four groups of mice. The control group were fed a standard diet of mice chow. The other groups were fed the same chow but in addition were dosed each day with 85 mg (less than one tenth of a gram) of beta-casein of either the A1 type (written as A1A1), or the A2 type (written as A2A2) or an A1A2 mix. The control group were dosed with a saline fluid to maintain comparability of handling.
In all, the trial produced statistically significant difference for eleven different measures of digestive function. These include a range of inflammation markers, various types of antibodies, and immunity regulators.
In the interests of brevity, in this post I will present the figures for just two of the measures, these being intestinal myeloperoxidase (MPO) and interleukin-4 (IL-4). Other physiological measures for which statistically significant differences were found, but which I don’t present here, include monocyte chemotactic protein-1, IgE, IgG, IgG1, IgG2a, IgA, TLR-4, and TLR-2.
MPO is an enzyme contained within neutrophils, which are a type of white blood cell. MPO is widely regarded as a classic marker of inflammation. Elevated levels of MPO are also associated with increased risk of heart disease and there is an extensive medical literature on this.
In the figure below taken from the Ul Haq paper, it is evident that whereas there is no difference between the control and A2A2 treatment, the MPO levels are considerably higher for both the A1A2 and the A1A1 treatments. The common letter ‘a’ for the control and A2A2 treatments indicates that any apparent differences between the control and the A2A2 treatment are statistically non-significant. However, because the other treatments have different letters above them, this indicates that the MPO levels for the A1A2 and A1A1 treatments are statistically significantly different both to the other treatments and to each other. The small lines above each treatment are called ‘error bars’ and provide to those trained in statistics a visual indication of the confidence that can be held in the apparent differences being real and repeatable. Within the text of the paper, it is reported that “feeding of A1A1 and A1A2 beta-casein variants increased MPO activity in murine [mouse] intestine (p<0.01) by 204.20 and 43.54% respectively, compared to control group mice”
Interleukin-4 (Il-4) leads to development of a particular type of T cells called Th2 cells. An increase in Th2 production is an immune response; i.e. the body is reacting against a foreign substance. Overproduction of IL-4 is also associated with some allergies, including eczema, asthma and urticaria (hives).
In the graph below it is evident that there is no difference between interleukin-4 production between the control and A2A2 treatments. (They both have a common letter ‘a’.) However the values for the A1A1 and A1A2 treatments are both much higher. The text states that “the current study revealed an increase (p<0.01) in IL-4 levels in murine intestinal fluid on consumption of A1A1 and A1A2 beta-casein variants by 266.12 and 277.41% compared to control group mice”. (Remember that dealing in percentages can sometimes be a little confusing. An increase of 266% means that the levels had been increased by a factor of 3.66 times.)
So what does this mean?
For quite some time the science has been very clear that A1 beta-casein digests differently than A2 beta-casein , i.e. that beta-casomorphin-7 (BCM-7) is released from the A1 but not the A2 beta-casein. However, it has not previously been proven in a trial situation that this leads to physiological responses by the immune system. What Ul Haq and colleagues have shown is that not only do such differences occur but they are profound. In summary, the results of this study show unequivocally that ‘there is a difference’.
These proven differences in relation to physiological functioning do not in themselves prove that the A1 beta casein causes any particular disease. However, where there is smoke there is almost certainly going to be fire. The results fit perfectly with prior claims relating to digestive function, a range of auto immune conditions, and heart disease.
Is there a counter argument?
It is inevitable that the mainstream dairy industry will try to downplay these results. What else can they do in the battle for survival? However, the challenge for those who wish to argue against this paper is that:
a) The research protocol is very strong
b) The results are very strong from a statistical perspective.
c) The paper has been through peer review and is published in a highly rated international journal.
Nevertheless, my expectation is that the paper will be attacked on multiple grounds, to all of which there is a counter.
- The attack: This work was undertaken in mice. How do we know the same effects will occur in humans?
The answer: For obvious reasons, many trials can only be done with animals. Mice are an accepted model for investigating intestinal conditions. The structure of the intestines of mice and humans is fundamentally very similar, as are the enzymes and immune systems.
- The attack: This research needs to be repeated in a Western country before we can place credence on the results.
The answer: Undertaking similar trials in other countries would and will reinforce the very strong messages of this trial. Indeed I am aware of a trial in a Western country, which has been completed but not yet published, that will confirm key results of the Ul Haq study.
- The attack: The amounts of beta-casein used in this trial were high. Many substances if fed in high enough doses will have nasty effects.
The answer: The dose rate of beta-casein appears to be broadly similar to what a mouse might eat on an all milk diet, given that mice are voracious eaters. But the key issue is that the effect only occurs with the A1 beta-casein and not the A2 beta-casein. Even if the differences are much less for humans on human diets, this would still be very worrying in terms of the long-term effects.
So in summary, the Ul Haq et al paper is a significant step forward in relation to the ongoing scientific debate about A1 versus A2 beta-casein. I know which side of the debate I want to be on.
Ul Haq MR, Kapila R, Sharma R, Saliganta V, Kapila S. 2013 “Comparative evaluation of cow β-casein variants (A1/A2) consumption on Th2-mediated inflammatory response in mouse gut”. European Journal of Nutrition. DOI 10.1007/s00394-013-0606-7 [Epub ahead of print].
The Abstract of this paper is shown below (click once on the Abstract for larger view).
Disclosure: Keith Woodford consults as an independent adviser to A2 Corporation.