New A2 milk clinical trial with children has big implications both for child nutrition and also for the dairy industry

New A2 milk clinical trial with children has big implications both for child nutrition and also for the dairy industry

A new paper relating to A2 milk has been published this month in the Journal of Pediatric Gastroenterology and Nutrition (JPGN). The paper provides strong evidence from a clinical trial with pre-school children in China that A1 beta-casein relative to A2 beta-casein has negative effects on both digestion and cognitive performance.

The evidence is sufficiently strong that those who have argued until now that A2 milk is just a marketing gimmick will find it increasingly difficult to sustain that argument.  This has major implications for the mainstream dairy industry which continues to downplay the A1 versus A2 issue.

For those new to the debate, A2 milk comes from A2 cows, with these cows naturally producing milk free of A1 beta-casein. As background, there is no A1 beta-casein in human milk or goat milk or sheep milk. Cows are the only species that produce A1 beta-casein, and it is found in a high proportion of cows of European origin.

The strength of this latest paper is not just what is new but how it builds on prior research. Through confirmation, it provides credibility to that prior research.

The paper also gains credibility from where it is published. The JPGN, where this latest paper is published, is the official journal of the European and North American Societies of Pediatric Gastroenterology, Hepatology and Nutrition.  

The authors of this new paper come from Shanghai Jiao Tong and Peking Universities in China, together with an Australian collaborator. Peking University is ranked by Times Higher Education as the Number One university in China and Jiao Tong as number 7.

The trial was with 80 pre-school-age children. The trial compared ordinary milk containing a mix of A1 and A2 beta casein (hereafter called ‘A1’) with a milk product where all of the beta-casein was A2.  Most of the children were showing early signs of intolerance to conventional milk prior to the study.

It was a crossover trial, with all of the children having five days of consuming one milk product and then, following a nine-day washout, another five days of the other milk. The children, their parents, and the supervising staff were all blinded as to which milk was which. Half the children had the A1 milk first and the other half had the A2 milk first.

The trial provided exceptionally strong evidence across a wide range of measures. When the children were consuming the A1 milk, they had more digestive discomfort, their faeces were of a different consistency, they produced less of the desirable fatty acids in their digestive system, they had elevated  beta-casomorphin in their blood, they had increased inflammatory markers in their blood, and their cognitive performance on a  standardised computerised test of response times was inferior. The paper is available here.

For those who are statistically minded, many of the results were at significance levels of p<.001. This is much higher – more than 50 times – what is normally required to provide acceptance of a genuine effect. The crossover design is the ideal method for reducing chance effects, and double-blinding of both participants and scientific supervisors is also best practice.

None of the results came as a surprise. All results were hypothesised based on prior research and with the biochemical pathways increasingly understood. However, this trial has tested those hypotheses in a rigorous setting and with pre-school children. This was the first time such a trial had been undertaken with children of any age.

I had been waiting for the publication of this paper for two years. The trial itself was in 2016. It is the third of three major related pieces of research conducted in China.

It has been a frustrating wait for publication. When I inquired, all I could find out was that a key researcher was very ill and this was causing the delay.  I had to hope that the health issue would be solved and that this was indeed the full story. It now seems that it was.

The first of these Chinese studies, which I call ‘China1’, was published in April 2016 with Jianqin Sun from Shanghai’s Fudan University as the lead author. It provided very powerful evidence, also from a crossover design, that A1 beta-casein slowed down the transit of food through the digestive system, that it caused inflammation, and that there were cognition effects using the computerised test of response rates and response accuracy.

Unfortunately, the China1 paper is not easy to read. Even scientists can get confused and misinterpret the strength of the results unless they spend many hours exploring the detail. Also, although the design was very strong, those who did not understand the strength of the crossover design were always going to be sceptical because the trial only involved 45 people.  Hence, I always knew that trial would not have the public impact that it deserved.

As a consequence, although I have written about ‘China1’ for scientific audiences, and discussed it at seminars, I have never discussed it in the mainstream media. I decided to wait for ‘China2’ and ‘China3’.

China2, also known as the ‘Three Cities Study’ involved more than 600 people in Beijing, Shanghai and Guangzhou who were tested for intolerance for A1 versus A2 beta-casein. The paper is available here.

China2, like China 1, provided strong evidence of intolerance but given the number of people involved, the design was much simpler and only limited measurements were taken. It had more impact in the public arena than China1, in part because it was easy to understand, and also because people were impressed by the large number of participants. But there was less science.

Despite studying and writing about the science behind A1 and A2 milk for fifteen years, I still chose to say nothing in public about China2. I wanted to wait for China3 with its in-depth study of pre-school children.

In the meantime, there was another published paper from the China-based studies. Blood samples from China1 were sent to American researchers who analysed them for their beta-casomorphin7 content and also their levels of antioxidant glutathione. Once again, they found important differences that gave scientific insights beyond the immediate clinical effects. That paper is available here.

Taking all of the China studies together, I now have the confidence to say publicly that this is a very impressive body of evidence from a range of scientists from top-level Chinese institutions and international collaborators. The combined effect will be to influence all Chinese dairy companies and also international dairy companies with a China-focus to commit themselves to A2 dairy products. Their success in China now depends on it.

In Western countries, there will still be scepticism, with more evidence required from studies undertaken in Western countries before the sceptics are convinced. However, while that debate will continue, there are now increasing quantities of A2 dairy products in supermarkets of the world. That includes all across Australia, much of the USA and the United Kingdom, increasingly in New Zealand and even in Moscow.

Of course, the evidence for dairy products free of A1 beta-casein goes well beyond the clinical effects investigated in the China studies. It is now well over 20 years since Professor Bob Elliott from Auckland University and Professor Robert Cade from Florida started writing independently about the effects of the A1-derived beta-casomorphin7 on wide ranging medical conditions.  Back in 2007, I wrote a book about their work and that of other scientists who followed, which I called ‘Devil in the Milk’. At least now, when I write about the ‘milk devil’, I know that people in many Western countries do have the opportunity to buy A2 dairy products should they wish to. Until recently that was not the case.


*Keith Woodford is a retired academic who now holds an honorary position of Professor of AgriFood Systems at Lincoln University, NZ. He now consults through his own company AgriFood Systems Ltd. He has been writing about the A1 and A2 issue since 2004. Articles written since 2010 are archived at https://keithwoodford.wordpress.com. He can be contacted at kbwoodford@gmail.com

We welcome your help to improve our coverage of this issue. Any examples or experiences to relate? Any links to other news, data or research to shed more light on this? Any insight or views on what might happen next or what should happen next? Any errors to correct?

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. .. these results were predicted by everyone , except the board of Fonterrible ...

A2 Milk Corp were 100 % right ... and their share price is up 15 times since listing ... whereas Fonterrible were 0 % right about the benefits of A2 milk , they were in complete denial , and their share price is down by a third since listing ...

Curious that an Academic such as Keith Woodford fails to disclose the obvious bias.

THE PAPER WAS FUNDED BY THE A2 MILK COMPANY AND "HAD INSIGHT INTO DRAFTING THE MANUSCRIPT" (That is more involvement than the average drug company :-) )

"Conflicts of Interest and Source of Funding
Dr Greg Yelland is co-director of NeuroTest Pty. Ltd., the company that owns and distributes the Subtle Cognitive Impairment Test. The other authors have no conflicts of interest to declare. This study was funded by The a2 Milk Company.
The a2 Milk Company provided funding for the study and had insight into drafting the manuscript, but the authors had full responsibility for, and decided about, manuscript content."

Anyway - as Trump knows - if people hear something often enough they will end up believing it whether it is true or not. I am not saying that A2 isn't better I am just saying that this is not definitive evidence!!!!

Nice post.

The fact that this highly relevant fact was not disclosed is telling. A bit like an Exxon Mobil-sponsored study denying climate change. Maybe there is something to A2 milk but this is definitely not irrefutable evidence.

Jmmyback and others
The disclosures were easy to find – I provided the links. There were also a lot of other things left unsaid in my article about this research and I may well write more in another article. But in this article, I used my usual self-imposed limit when writing for the general public of around 1200 words.
The key issue in relation to your scepticism is the quality of the data and the statistical analyses, all of which were independent of A2M.
If those data are not valid, then given their strength, it could only mean that there was outright fraud. That would need to involve a conspiracy between the authors of all four papers that I refer to in the article, and for which I provided the links. Personally, I don’t think that is likely.
KeithW

I guess the fact that they picked people who were known to be intolerant to A1 biased the results. Notably Europeans are far less likely to be intolerant of A1. So the devil is in the details.

skudiv
No, they did not select people known to be intolerant to A1. But they did select people who believed they had a moderate intolerance to milk ( as do most Chinese except for very young children). Tests subsequently showed that many of these children had a deficiency of the lactase enzyme indicating a level of lactose intolerance. However, regardless of whether or not there was a lactase deficiency, there were big differences between the results for the A1 and A2. This adds to the evidence that there is an interaction between lactase deficiency and A1 beta-casein. The results also indicated a benefit for those children who had not developed lactase deficiency.
KeithW

Hi Keith,
Perhaps the study did select for subjects known to be A1 intolerant. They screened 835 preschoolers and only 104 were eligible. The study does not say why the other 731 preschoolers were not eligible. They claim to be looking for a representative sample of Chinese Preschoolers but hand picking 12.5% of a preschool population that gives you excellent results suggests ... well we can all figure that out. If the a2 Milk Company did indeed hand pick their population to find these results, they ought to be commended. There is nothing dishonest about what they have written nor can the science itself be criticised. It is just that the population they picked is not representative of the Chinese preschooler population, which they they claim it is ... so actually perhaps that could be interpreted as a bit dishonest aye?
Regards,
James

... whether this study is in A2 Corps best interest or not : We are discussing milk here .... a healthy product ...

So , it's not quite the same red flag as when giant American firms were sponsoring studies to support their own sugary or tobaccery products ...

Ms Market - the ultimate decider of product fates, has already had her Wicked Way with the relative trajectories of Fonterra/A1 and its A2 alternative. Your opinion is clearly worth less than the Wisdom of Crowds, especially Crowds with Investment Pesoes in their pockets....

We are really worried about the wrong stuff these days. When I was at school in England we got given a small bottle of milk to drink every day for free. No point worrying about A2 milk when many kids parents are no longer able to afford even the basic milk and get water on their Weetbix instead. Sad that we think we are going forwards as a species but in reality we are slowly going backwards.

I suspect some of the antis on this site have never owned A2 shares. I started buying them in 2016. One of my better investments. Certainly beat Christchurch rentals. Like Xero you can only see blue sky.

Yes, we are worrying about the wrong stuff these days and it is showing up in more anxiety in our children than in previous generations. We are becoming quite intolerant of people having free choice to eat what they wish. There is a minority percentage of people who can afford to buy ethically/morally etc. Many groceries are bought on price for those with families. Fonterra's free milk in schools programme is now available in 70% of primary schools and around 140,000 children are drinking it. For some it is the only time they get to have dairy. https://fonterramilkforschools.com/about/

Casual Observer,
Given that Fonterra does now produce Anchor A2 milk - we buy it for our household - Fonterra could now also organise for its school milk supply to be A2, if it wanted to. It won't want to do this, because it would focus attention on A2 and most of Fonterra's farmers still have a long way to go in converting their herds. And by doing so, it would put unwelcome attention on the A1 versus A2 issue. But it could do it if it wanted to.
KeithW

.... I suspect that Fonterrible has a bigger issue on its mind than the benefits or not of A2 milk : the balance sheet !

They've been in denial for years that they're over indebted... and are paying out too much to milk suppliers ... not a tip top situation to be in ..

And anyway, they face the rise in veg based milks, 10% per annum at the moment in UK or US.
UK say 25% of milk drinkers prefer veg substitutes.
-sources were Guardian or Global Meat News

The meat & dairy farming industry has bean under the threat of vege-substitutes for many years ...

... but , Muufri Milk , and meatless burgers are yet to gain serious traction in the market place ...

I stood in a small Basel ( Switzerland ) produce market last year . . and nearly fainted for joy at the vast array and aromas of the cheeses on offer... could plain old soy substitutes ever elicit such raptures of pleasure in a connoisseurs heart ?

... I very much doubt it . . .

What caught my eye was the GMN article that valued the veg substitute business at US $4.5 billion with 10% pa growth rates.
Not much money but they seem to want a piece of it.

Dp

This morning while pondering if meat substitutes could scale at a speed that meets the demand I found an article, we may have guessed the labour productivity is high, one plant is producing 750kg per month with a staff of fifteen.
That article said they believed meat substitutes could take 25-50% of what is the manufacturing beef market.
Oh, and they expect to be price competitive in 2-3 years

The Guardian article also states that at 87% standard milk remains the most widely consumed. So while 25% prefer veg substitutes some of those 25% are likely users of both. The Head of Fonterra R&D has stated it is not about one or the other - there is room for both dairy and non dairy. It is about providing choice. Nutritionally, plant based food gram for gram (or whatever weight you want to use) doesn't come near dairy/meat. But it is about choices.
Soy has a dark underside that is not often talked about, deforestation being one, the other from mainland USA - 'Beyond environmental degradation, the spread of industrial soy farms displaces rural farmers and indigenous communities, and facilitates exploitative labor arrangements. Large plantations will continue to be dominant producers in the soy industry, due to their economies of scale.' https://globalforestatlas.yale.edu/land-use/industrial-agriculture/soy-a.... In NZ arable under pivots has a higher environmental cost than dairy, but hey David Parker and mates wants to see more of the latter and less of the former, and some regional councils have made rules making it almost impossible to increase vegetable production.

Casual Observer thats a common misconception; around "70 percent of the world's soy is fed directly to livestock and only six percent of soy is turned into human food, which is mostly consumed in Asia" It is not direct human consumption that is driving deforestation, but cheap meat and dairy production. Go vegan folks ;)

And yet from the FAO:

"Of the plant material fed to livestock, 86 percent would be
inedible by humans directly but is converted into valuable food for
human consumption and contributes greatly to food and nutrition
security."

Hi Doris, Thanks for the reply, however it does not counter my point; it just points out that human only consume the best parts - whereas cows will eat anything. The conversion of energy to produce meat/dairy protein from vegetable protein is a horrendous waste even when they consume the other 80 odd percent! Poultry protein is the most efficient from feed.

Keith they supply UHT milk, and I'm not aware they do an A2 UHT milk. Grandson can access it at school but doesn't - 'It doesn't taste as good as the milk from our farm vat', he says. He also has an intolerance of homogenised milk, so should Fonterra also supply pasteurised only milk to schools? A2 is a niche product just as Zero lactose, Organic, and the various low fat varieties.
a2milk would need to agree to it as the Fonterra-a2 milk agreement is ' is designed to generate returns for both companies'. And as we both know, a2milk puts nothing back in to the NZ community by way of supporting it's young or communities. Heck it doesn't even pay a dividend to its shareholders, they have to rely on what some refer to as the greed factor - capital gains.

Casual Observer,
You are correct. They do not currently produce an A2 UHT. And if they did, then a2 Milk Company (ATM) would clip the ticket just like with the Anchor a2. But I am confident that ATM would go along with a special a2 schools project without clipping the ticket. Fonterra is now collecting A2 milk for its Hautapu factory (starting this season) so they could easily divert some to Waitoa for an A2 UHT. Where you and I might disagree is whether A2 is niche like zero lactose. The evidence elsewhere is that once A2 becomes available it quickly far outstrips products like zero lactose. The current schools program is reduced fat so that lessens but does not eliminate the issue of homogenisation.
KeithW

Keith, yes agree to disagree. Whichever way we see it, it is good to have choice.

Does A2 taste different? I bought a bottle of A2 a few years back and thought it tasted a bit strange, a bit unpleasant.

Yes, the quality of A2 milk produced by two historical NZ franchisees was terrible. Nothing to do with it being A2; everything to do with lack of quality control.
The current Fonterra product (Anchor a2) is good quality - it should taste the same as conventional milk.
Fresha Valley A2 also now seems much better quality than in the past.
KeithW

Our agricultural industries appear forgiving of variable quality, more than the consumers.
I gave up on meat after nicely packaged lamb back straps were unpredictably tough.
Why would you bother.

I was intrigued by the authors claim that the place of publication of the work in the JPGN strengthens its case for acceptance. Scientific journals are ranked according to parameters such as impact factor - scientists typically strive to have their journals published in the best journals they can, with the highest impact factors (which feeds back into things such as their annual review and their standing in their field). The highest ranking journals typically have much more stringent criteria for acceptance than more lowly ranked journals. JPGN ranks well down the list in the Gastroenterology field on the SJR database - a very lowly 36th out of the 50 journals in the field: https://www.scimagojr.com/journalrank.php?category=2715
If the work really was as definitive and important as the author claimed it would/should have gone in a top journal such as Gut or Gastroenterology (which do take papers on Paediatric related issues).
The author also muses on his disappointment that the work has taken 2 years to be published - whilst the reason given that an author was sick is of course plausible, I would suggest that it is also possible that the paper was rejected by higher ranked journals, eventually finding its way down to the lowly JPGN (a scenario which is extremely common in the world of science publishing).

King of the Whiners
If you look more closely at the scimagojr rankings you will see that the JPGN is ranked in the top quartile of journals in gastroenterology - 35/145.
You only looked at the first page. And if you were familiar with the system I am surprised you did not see it was labeled as Quartile 1 ( see the box with green Q1).
Given that the paper covered both pediatric gastroenterology and nutrition, the choice of the journal of the European and North American specialist societies in this combined field would seem to have been an excellent choice. As a general rule, specialist journals do tend to have lower scimagojr rankings and this journal is the highest ranked in that specialist field.
You are correct that citations are important, with author citations being more important than journal citations in ranking the importance of individual papers.
Of course it is too early for this specific paper to have its own ranking but you might like to consider the citations of China1 (48 already since early 2016)) and China2 (15 already since publication in late 2017). You might also like to consider three earlier papers in the stream (which I did not include in my article because of the needs for brevity). These are Barnett et al (including myself as one of the authors) ) with 38, and Ho et al (also including myself as an author) with 40 citations, and Pal et al (also including myself as an author) with 48 citations. You will quickly find those papers if you google the first author name plus Woodford plus beta-casein.
The bottom line of all of this is that the evidence shows that the science community is indeed taking notice and is referencing these papers in their own work. It is indeed high impact work.
KeithW

I notice you did not address my question as to whether the paper had been rejected previously by a higher rated journal? Was this the real reason for the delay in publication? And no, I don't think most people would say a journal ranked 35th in a field is a 'top' journal.

King of the Whiners
Neither you nor I have evidence that it was rejected by another journal.
You do not seem to have a full understanding as to how the ranking system works and how scientists select journals.
Assuming these scientists wanted their work to be read by all other scientists working in the combined field of pediatric gastroenterology and nutrition, then they chose the best journal to be confident of reaching all of those scientists.
KeithW

I don't think you can rely on research sponsored by beneficiary of the research. Few years back red wine industry had been publicising their funded research that drinking red wine is great for health. Only for a recent study published in Lancet that linked any amount of alcohol consumption to cancer.

Anyway A2 as company is doing great, Fonterra should learn from them about marketing and coming up with new value added products.

JP,
I agree with you that beneficiary spin can be a big issue. In the case of wine, the evidence was always modest, although sufficient to give me comfort as I drink my evening glass of wine. In the case of A1 versus A2, The a2 Milk Company has actually said nothing about this research, but allowed the results to do their own talking. The other difference is that with A1 beta-casein there is an increasing body of clinical research relating to those efects which are acute (show up quickly within a trial). In the case of wine (and also cigarettes) there are no such clinical trials because the effects are chronic (take a long time to be evident). Medical ethics can also be hugely important - for example no smokng trial would ever be approved. But these chronic effects can still be very important. That is clearly the case with smoking. With red wine, I think the jury may still be out with both pros and cons. For A1 beta-casein, the pharmacology and biochemistry is still being teased out although becoming increasingly evident. It is the insidious but chronic (long term) effects that are the reason why in my family the grandchildren consume only A2 products. The wider challenge is to create an informed debate.
KeithW

The catch 22 of informed debate is it encourages uninformed debate.
I was intrigued to see discussion in the Guardian that milk make people feel ill, discussion like that was unheard of a decade ago.
While A2 may catch on with the mantra “we dont make you sick”, the US consumption of milk declines at a rate that seems about 1%
per annum.