A1 & A2 Casein Milk: The Evidence

Although the Jury is still deliberating on the strength of the evidence, Research as well as clinical experience are empirically corroborating more and more that A1 milk and its products are deleteriously inflammatory and immune-compromising while A2 milk is not (Section B). But first, an introductory review of the facts and some Milk Science (Section A)

Section A

Introduction

More than 95% of cow milk proteins are constituted by caseins and whey proteins. Among the caseins, beta casein is the second most abundant protein and has an abundance of amino acids, over two hundred i recall.

With the passage of time, different mutations in bovine beta casein gene have led to 12 genetic variants and out of these A1 and A2 are the most common, the historical emergence of which may have occurred aroung ten thousand years ago when agricultural neolithic communities were beginning to mushroom.

Biochemically, the difference between the two caseins are minor. The A1 and A2 variants of beta casein differ precisely at amino acid position 67 with histidine (CAT) in A1 and proline (CCT) in A2 milk as a result of single nucleotide differences. (1)

The above-mentioned polymorphism led to a key conformational change in the secondary structure of expressed β-casein protein, one consequence of which spurred gastrointestinal proteolytic digestion of A1 variant of β-casein (raw/processed milk) to generate a troublesome bioactive peptide, beta casomorphin 7 (BCM7). (Ibid.)

As a result, infants can readily absorb BCM-7 due to an immature gastrointestinal tract whereas adults are more protected. In hydrolysed milk with variant A1 of beta-casein, BCM-7 level is 4-fold higher than in A2 milk. Initial studies on indigenous cow (Zebu type), buffalo and exotic cows (taurine type) have shown that A1 allele is more frequent in exotic cattle while French, African and Indian native dairy cow and buffalo have only A2 allele. (1)

In this context, a relationship between disease risk and consumption of a specific bovine β-casein fraction has been identified. BCM7, which is more prevalent in A1 milk, has been associated as a risk factor for human health hazards as it can potentially affect numerous opioid receptors in the nervous, endocrine and immune system.

Section B

 Comparison between A1 an A2 milk: the Evidence

A 1 Casein has been shown to an oxidant for low dietary lipoproteins (LDL) (oxidation of LDL is believed to be important in formation of arterial plaque). Epidemiological evidence confirmed that consumption of beta-casein A1 milk has been associated as a risk factor for type-1 diabetes, coronary heart disease, arteriosclerosis, sudden infant death syndrome, autism, schizophrenia etc.[3,4]

A broad range of studies from American and European investigations has shown reduction in autistic and schizophrenic symptoms with decrease in A1 milk intake.[5]

Furthermore, animal trials have also supported the linking of type-1 diabetes to A1 beta-casein in. (See Exhibits below)

Milk’s other Constitutents & Milk’s Benefits

Are there other deleterious molecules in cow milk for humans ?  While some studies have shown that milk can be anti-cancer (Source) and generally healthy when taken in the context of a mediterranean meal (Source),  other studies have suggested the opposite. One has to look closely at who financed these studies in order to better understand why the evidence can be ambiguous.

Some studies have shown for example that ovulation and a woman’s period health is favored with an abundance amount of dairy fat. Full-fat dairy may thus help to promote ovulation and fertility.

Other studies have shown that lactose  (the sugar in dairy) is a problem for those who don’t make enough lactase (lactose-digesting enzyme). Lactose intolerance causes diarrhea and digestive bloating.

Still other studies have shown that milk naturally contains small amounts of over sixty different hormones including testosterone, progesterone, insulin, and a potent growth hormone called IGF-1 and that these hormones can compete with human ones in a way that may not always be healthy. There’s still as scientific debate about how much humans are affected by these animal hormones. Different cancer experts believe that dairy hormones can lead to an increased risk of breast and inter alia, prostate cancer as well as acne.

Genetic variation or SNPs

While humans are genetically different from ruminants and cows, some humans are genetically closer to  ruminants in that their immune system recognizes these animal molecules as friendly. But for an important group of humans,  the evidence shows that A1 casein cleaves in the digestive tract to form a potent opiate-type molecule (called casomorphin or BCM7) that stimulates inflammatory cytokines, mast cells, and histamine.

Discussion

Clinical Experience

For some people, A1 milk (normal cow’s milk) is devastating to health. We cannot get around the fact that one of the proteins in milk—A1 casein—is highly inflammatory for some people.  In susceptible individuals, A1 casein is cleaved to form a powerful inflammatory opiate called casomorphin.

Casomorphin’s drug-like effect explains why it worsens anxiety and mood disorders and causes  addictive cravings for dairy. Also why it causes withdrawal symptoms when it’s stopped.

The inflammation from A1 casein also causes lymphatic congestion, metabolic suppression, and weight gain. Contrarily to A2 milk, A1 milk can worsen acne, eczema, upper respiratory infections, asthma, and allergies.

It causes digestive problems, and not because of the lactose. It’s because of the massive histamine release from casomorphin.

Women’s Health Issues

Because there’s a high number of mast cells in the uterine lining, these cells may play a role in heavy periods by releasing heparin as well as histamine.

Histamine also plays a role in PMS and PMDD. Histamine and inflammation can profoundly disturb periods. And that’s why dairy can cause period problems.

The Happiness Medicine Institute’s experience confirms that A1 casein can drive many inflammatory diseases, including, but not limited to cancer,  endometriosis, diabetes and other conditions.

We at the Institute believe in the evdience that shows that this type of milk tends to have an inflammatory, immune-disrupting effect for many people, in particular women. Women have their own milk, it indeed doesn’t make physiological nor evolutionary sense for women  to drink milk past their infant phase.

Stopping A1 milk can improve period pain, heavy periods (especially in. teenagers), fibroids, endometriosis, acne, and PMS.  Some women are ok with any milk, as they seem to be genetically protected in terms of the BCM7 break-down.

Who is affected by A1 milk and dairy products?

Some people are fine with A1 casein (they safely deactivate and eliminate the casomorphin). The problem occurs in people who lack the digestive enzymes to deactivate casomorphin, or have intestinal permeability which allows casomorphin to enter the body.

There is no effective test that can show who can have A1 milk. At least not yet or not to my knowledge. I’ve heard that there may be a new urine test for BCM7, but it doesn’t seem to be available as of yet. So the clinician has to assess the situation clinically.

A clinical sign that can confirm the need to avoid A1 casein is a history of recurrent upper respiratory infections in childhood.  Either ear infections, bronchitis or tonsillitis. Immune disruption by A1 casein can worsen those childhood conditions, and then in adulthood, the same immune disruption can drive other inflammatory conditions

Fortunately, A1 casein is not inflammatory for everyone. Some people don’t have the digestive enzyme that cleaves A1 casein, so they don’t form BCM7.

To assess for a casein problem, I look for the tell-tale childhood symptoms of recurring tonsillitis, chest or ear infections.  They were signs of casein immune disruption in childhood. They were outgrown but that doesn’t mean the underlying casein problem was outgrown. The casein symptoms merely changed to adult problems like recurring chest infections and period pain.

To detect a dairy sensitivity, apply the Elimination Diet Technique

The best way to detect a casein problem is to avoid A1 milk or all dairy for at least three months. That’s how long it takes for the hormonal system to recover from dairy’s inflammatory effects.

Which Ruminant is more human-friendly in terms of Casein nutrition

Not all cows produce A1 casein.  This protein comes from Holstein and Friesian cows who are the dominant breeds in western Europe, (except France and parts of Italy, Greece and Spain) North America, and Australia. Dairy cows in Africa, Asia, Iceland and parts of southern Europe make milk with mostly A2 casein. Those A2 areas have a lower incidence of the conditions discussed above. Goat’s  and sheep’s milk is A2. And so is milk from Jersey and Guernsey cows. And France is full of those types of ruminants.

On the other hand,  Holstein (Friesian) cows are the cash-breed for the US, Canada, Australia, and the UK. These cows produce more milk, so more cash.  There is no A1 casein in the milk from pure Jersey-Gernesey  cows, goats, and sheep. Unless the cow got impure by breeding with an A1 cow.

Is raw and organic milk better?

Certain types of pasteurization increase the amount of casomorphin in A1 dairy. So raw is usually better, if only because the milk’s enzymes help to predigest the casein and fats. But in the US, raw dairy is illegal.  Except for aged cheese. And organic is obviously better because dairy farmers still give their animals multiple drugs including antibiotics and synthetic hormones, as well as loads of pesticides via omega 6 inflammatory grains.

Is Cow Milk Calcium really an indispensable nutrient as claim conventional medicine and it’s Big-Pharma-financed Governmental Representatives ?

A Harvard study concluded that “humans have no nutritional requirement for animal milk.”  Another  large meta-analysis showed that milk-drinkers do not have better bones. In fact, some research suggests that milk-drinkers may actually have worse bones. That makes sense when we consider that dairy is inflammatory, and that inflammation is a major cause of osteoporosis.

Years ago, when i read Campbell’s China study, i confirmed the evidence that supported a causal relationship between milk and osteoporosis. Because milk is acidic, the body gets calcium from the bones in order to restore the PH balance. Over time, this process leaches bone calcium. In Asia where dairy is not a staple food, human bones are usually stronger than in the West. So it may be wise to get one’s calcium directly from Greens and nuts. And for those who eat cheese, to have quality A2 cheese in moderation with wine and lots of greens so that there is no bone shrinkage

What about A2 ruminants

As shown in the Exhibits below, A2 milk does not produce the deleterious effects of A1 milk. The best appear to be the smaller mammals like goat and sheep, full fat. They are also rich in a rare vitamin, K2 that helps to distribute calcium in tissues.

Consumption of milk containing A1 β-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 β-casein attenuated these effects, some symptoms of lactose intolerance may stem from inflammation it triggers, and can be avoided by consuming milk containing only the A2 type of beta casein. (Source)

Trying alternatives is also a healthy option, like almond milk, (homemade), coconut and rice milk, and even soy milk, though non pasteurized, home made, raw.

Tentative Conclusion

Today, among the health-conscious consumers, A 2 milk products are starting to take the stores by storm. (Source)

The totality of the evidence does show that those who consume β-casein A2 variant have a lower incidence of cardiovascular disease, cancer, type-1 diabetes and other inflammatory disorders.

The A1/A2 hypothesis is both intriguing and potentially very important for public health if it continues to be proven correct. It should be taken seriously as we wait for more decisive evidence from human RCT clinical trials.

Pending the final determination of this question, Reason commands that it is best to apply the precautionary principle. Which means to avoid A 1 milk product in favor of A 2 milk. Unless the consumer has a serious chronic inflammatory condition like cancer, auto-immunity, autism, inflammatory bowel syndrome, fibroid or endometriosis, in which case it may be wise to abstain from all  dairy, at least until the chronic illness is fully resolved.

Pr Joubert (HM Institute director)

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Exhibit A

Adv Nutr. 2017 Sep 15;8(5):739-748. doi: 10.3945/an.116.013953. Print 2017 Sep.
Systematic Review of the Gastrointestinal Effects of A1 Compared with A2 β-Casein.
Abstract
This is the first systematic review, to our knowledge, of published studies investigating the gastrointestinal effects of A1-type bovine β-casein (A1) compared with A2-type bovine β-casein (A2). The review is relevant to nutrition practice given the increasing availability and promotion in a range of countries of dairy products free of A1 for both infant and adult nutrition. In vitro and in vivo studies (all species) were included. In vivo studies were limited to oral consumption. Inclusion criteria encompassed all English-language primary research studies, but not reviews, involving milk, fresh-milk products, β-casein, and β-casomorphins published through 12 April 2017. Studies involving cheese and fermented milk products were excluded. Only studies with a specific gastrointestinal focus were included. However, inclusion was not delimited by specific gastrointestinal outcome nor by a specific mechanism. Inclusion criteria were satisfied by 39 studies. In vivo consumption of A1 relative to A2 delays intestinal transit in rodents via an opioid-mediated mechanism. Rodent models also link consumption of A1 to the initiation of inflammatory response markers plus enhanced Toll-like receptor expression relative to both A2 and nonmilk controls. Although most rodent responses are confirmed as opioid-mediated, there is evidence that dipeptidyl peptidase 4 stimulation in the jejunum of rodents is via a nonopioid mechanism. In humans, there is evidence from a limited number of studies that A1 consumption is also associated with delayed intestinal transit (1 clinical study) and looser stool consistency (2 clinical studies). In addition, digestive discomfort is correlated with inflammatory markers in humans for A1 but not A2. Further research is required in humans to investigate the digestive function effects of A1 relative to A2 in different populations and dietary settings.
https://www.ncbi.nlm.nih.gov/pubmed/28916574

Exhibit B

Nutr J. 2016 Apr 2;15:35. doi: 10.1186/s12937-016-0147-z.
Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows’ milk.
Abstract
BACKGROUND:
Cows’ milk generally contains two types of β-casein, A1 and A2 types. Digestion of A1 type can yield the peptide β-casomorphin-7, which is implicated in adverse gastrointestinal effects of milk consumption, some of which resemble those in lactose intolerance. This study aimed to compare the effects of milk containing A1 β-casein with those of milk containing only A2 β-casein on inflammation, symptoms of post-dairy digestive discomfort (PD3), and cognitive processing in subjects with self-reported lactose intolerance.
METHODS:
Forty-five Han Chinese subjects participated in this double-blind, randomized, 2 × 2 crossover trial and consumed milk containing both β-casein types or milk containing only A2 β-casein. Each treatment period was 14 days with a 14-day washout period at baseline and between treatment periods. Outcomes included PD3, gastrointestinal function (measured by smart pill), Subtle Cognitive Impairment Test (SCIT), serum/fecal laboratory biomarkers, and adverse events.
RESULTS:
Compared with milk containing only A2 β-casein, the consumption of milk containing both β-casein types was associated with significantly greater PD3 symptoms; higher concentrations of inflammation-related biomarkers and β-casomorphin-7; longer gastrointestinal transit times and lower levels of short-chain fatty acids; and increased response time and error rate on the SCIT. Consumption of milk containing both β-casein types was associated with worsening of PD3 symptoms relative to baseline in lactose tolerant and lactose intolerant subjects. Consumption of milk containing only A2 β-casein did not aggravate PD3 symptoms relative to baseline (i.e., after washout of dairy products) in lactose tolerant and intolerant subjects.
CONCLUSIONS:
Consumption of milk containing A1 β-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 β-casein attenuated these effects, some symptoms of lactose intolerance may stem from inflammation it triggers, and can be avoided by consuming milk containing only the A2 type of beta casein.
TRIAL REGISTRATION:
ClinicalTrials.gov/NCT02406469.
https://www.ncbi.nlm.nih.gov/pubmed/27039383

 Exhibit C

Nutr J. 2017 Oct 25;16(1):72. doi: 10.1186/s12937-017-0275-0.
Effects of cow’s milk beta-casein variants on symptoms of milk intolerance in Chinese adults: a multicentre, randomised controlled study.
Abstract
BACKGROUND:
A major protein component of cow’s milk is β-casein. The most frequent variants in dairy herds are A1 and A2. Recent studies showed that milk containing A1 β-casein promoted intestinal inflammation and exacerbated gastrointestinal symptoms. However, the acute gastrointestinal effects of A1 β-casein have not been investigated. This study compared the gastrointestinal effects of milk containing A1 and A2 β-casein versus A2 β-casein alone in Chinese adults with self-reported lactose intolerance.
METHODS:
In this randomised, crossover, double-blind trial, with a 3-day dairy washout period at baseline, subjects were randomised to consume 300 mL of milk containing A1 and A2 β-casein (ratio 58:42; conventional milk) or A2 β-casein alone; subjects consumed the alternative product after a 7-day washout period. Urine galactose was measured at baseline after a 15 g lactose load. Subjects completed 9-point visual analogue scales for gastrointestinal symptoms (borborygmus, flatulence, bloating, abdominal pain, stool frequency, and stool consistency) at baseline and at 1, 3, and 12 h after milk consumption.
RESULTS:
A total of 600 subjects were included. All six symptom scores at 1 and 3 h were significantly lower after consuming A2 β-casein versus conventional milk (all P<0.0001). At 12 h, significant differences remained for bloating, abdominal pain, stool frequency, and stool consistency (all P<0.0001). Symptom scores were consistently lower with A2 β-casein in both lactose absorbers (urinary galactose ≥0.27 mmol/L) and lactose malabsorbers (urinary galactose <0.27 mmol/L).
CONCLUSION:
Milk containing A2 β-casein attenuated acute gastrointestinal symptoms of milk intolerance, while conventional milk containing A1 β-casein reduced lactase activity and increased gastrointestinal symptoms compared with milk containing A2 β-casein. Thus, milk-related gastrointestinal symptoms may result from the ingestion of A1 β-casein rather than lactose in some individuals.
TRIAL REGISTRATION:
NCT02878876 , registered August 16, 2016. Retrospectively registered.
https://www.ncbi.nlm.nih.gov/pubmed/29070042

Exhibit D

Eur J Clin Nutr. 2014 Sep;68(9):994-1000. doi: 10.1038/ejcn.2014.127. Epub 2014 Jul 2.
Comparative effects of A1 versus A2 beta-casein on gastrointestinal measures: a blinded randomised cross-over pilot study.
Abstract
BACKGROUND/OBJECTIVES:
At present, there is debate about the gastrointestinal effects of A1-type beta-casein protein in cows’ milk compared with the progenitor A2 type. In vitro and animal studies suggest that digestion of A1 but not A2 beta-casein affects gastrointestinal motility and inflammation through the release of beta-casomorphin-7. We aimed to evaluate differences in gastrointestinal effects in a human adult population between milk containing A1 versus A2 beta-casein.
SUBJECTS/METHODS:
Forty-one females and males were recruited into this double-blinded, randomised 8-week cross-over study. Participants underwent a 2-week dairy washout (rice milk replaced dairy), followed by 2 weeks of milk (750 ml/day) that contained beta-casein of either A1 or A2 type before undergoing a second washout followed by a final 2 weeks of the alternative A1 or A2 type milk.
RESULTS:
The A1 beta-casein milk led to significantly higher stool consistency values (Bristol Stool Scale) compared with the A2 beta-casein milk. There was also a significant positive association between abdominal pain and stool consistency on the A1 diet (r=0.520, P=0.001), but not the A2 diet (r=-0.13, P=0.43). The difference between these two correlations (0.52 versus -0.13) was highly significant (P<0.001). Furthermore, some individuals may be susceptible to A1 beta-casein, as evidenced by higher faecal calprotectin values and associated intolerance measures.
CONCLUSIONS
These preliminary results suggest differences in gastrointestinal responses in some adult humans consuming milk containing beta-casein of either the A1 or the A2 beta-casein type, but require confirmation in a larger study of participants with perceived intolerance to ordinary A1 beta-casein-containing milk.
https://www.ncbi.nlm.nih.gov/pubmed/24986816

References

1. Elliott RB, Harris D P, Hill JP, Bibby NJ, Wasmuth HE. Type I (insulin-dependent) diabetes mellitus and cow milk: casein variant consumption. Diabetologia. 1999;42:292–6. [PubMed]
2. Mishra BP, Mukesh M, Prakash B, Monika S, Kapila R, Kishore A, et al. Status of milk protein, b-casein variants among Indian milch animals. Indian J Anim Sci. 2009;79:72–5.
3. Laugesen M, Elliott R. Ischaemic heart disease, type 1 diabetes, and cow milk A1 beta-casein. N Z Med J. 2003;116:U295. [PubMed]
4. Tailford KA, Berry CL, Thomas AC, Campbell JH. A casein variant in cow’s milk is atherogenic. Atherosclerosis. 2003;170:13–19. [PubMed]
5. Cade R, Privette M, Fregly M, Rowland N, Sun Z, Zele V, et al. Autism and schizophrenia: Intestinal disorders. Nutr Neurosci. 2000;3:57–72. [PubMed]

Additional Evidence from the Peer-reviewed Literature

New Zealand Professor Keith Woodford’s book Devil in the Milk: Illness, Health, and the Politics of A1 and A2 Milk.
2014 peer-reviewed animal study in the European Journal of Nutrition:  Comparative evaluation of cow β-casein variants (A1/A2) consumption on Th2-mediated inflammatory response in mouse gut. (Evidence that A1 beta-casein (but not A2 casein) generates inflammatory markers including myeloperoxidase (MPO) and interleukin-4 (IL-4).)
2014 human study: Comparative effects of A1 versus A2 beta-casein on gastrointestinal measures: a blinded randomised cross-over pilot study.
2015 study: Epigenetic effects of casein-derived opioid peptides in SH-SY5Y human neuroblastoma cells.
2016 study: Clinical evaluation of glutathione concentrations after consumption of milk containing different subtypes of β-casein: results from a randomized, cross-over clinical trial.
2017 study: “Strikingly different pattern” of digestive symptoms in people identified as lactose intolerant after drinking A2 Milk compared to conventional milk.

 Other Sources

 Green VA, Pituch KA, Itchon J, Choi A, O’Reilly M, Sigafoos J (2006). “Internet survey of treatments used by parents of children with autism” (PDF). Res Dev Disabil. 27 (1): 70–84. doi:10.1016/j.ridd.2004.12.002. PMID 15919178.
Lucarelli S, Frediani T, Zingoni AM, et al. (September 1995). “Food allergy and infantile autism” (PDF). Panminerva Med. 37 (3): 137–41. PMID 8869369.
Rao MB, Tanksale AM, Ghatge MS, Deshpande VV (1 September 1998). “Molecular and biotechnological aspects of microbial proteases”. Microbiol Mol Biol Rev. 62 (3): 597–635. PMC 98927. PMID 9729602.
Engel RW, Copeland DH (1 December 1952). “The influence of dietary casein level on tumor induction with 2-acetylaminofluorene”. Cancer Res. 12 (12): 905–8. PMID 13009679.
Manninen, A.H. (2002). “Protein metabolism in exercising humans with special reference to protein supplementation. Master thesis” (PDF). Department of Physiology, Faculty of Medicine, University of Kuopio, Finland.
Robert H. Demling; Leslie DeSanti (2000). “Effect of a Hypocaloric Diet, Increased Protein Intake and Resistance Training on Lean Mass Gains and Fat Mass Loss in Overweight Police Officers” (PDF). Annals of Nutrition & Metabolism. 44 (1): 21–29. doi:10.1159/000012817.
Healing Thresholds – summarizes scientific evidence on casein-free diets and other therapies for autism
Eating without Casein a practical guide to eating and living without casein
Caseins at the US National Library of Medicine Medical Subject Headings (MeSH)
Time magazine, Monday, December 6, 1936 Lanital
Time magazine, Monday, August 29, 1938 Wool from Cows
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