Why can some people tolerate dairy and others not?
I’ll give you a big reason.
It’s because of the type of casein the milk has.
A1, A2 beta-casein and beta-casomorphins
Milk proteins consist mainly of casein and whey, of which there are different kinds.
The main casein proteins are A1 and A2 beta-casein. There is A2 milk, which contains only A2 beta-casein, but there is no A1 milk, which contains only A1 beta-casein. If it’s not specified as A2 milk, the milk is most likely a blend between A1 and A2 beta-casein (different breeds produce different ratios).
A1 and A2 beta-casein are 209 amino acid proteins, but with different amino acids at the 67 position. Namely, A1 has a histidine and A2 has a proline at that position. The proline makes it much harder to break down at that point. So the A1 beta-casein can easily be broken at the histidine amino acid, yielding beta-casomorphin-7 (BCM7).
In contrast to A1, A2 beta-casein, the amino acid at position 67 is proline, leading to preferential cleavage of the longer peptide BCM9 (R). “Although bBCM9 is itself also an opioid with consequent potential pharmacologic properties, these properties are fundamentally different, and bBCM9 is considered a potential beneficial bioactive carrying both antihypertensive properties  and antioxidant properties . Additionally, in contrast to A1 beta-casein and bBCM7, no digestive differences have been recorded when A2 beta-casein digests containing bBCM9 are tested with and without naloxone .” (R)
BCM7 starts with a tyrosine proline, which gives it its opioid receptor (specifically the μ-opioid) binding properties. As you can see from the illustration above, there are 3 total proline amino acids in BCM7, which makes the peptide very difficult to break down further.
Milk is not the only food with opioids though. Wheat also contains strong opioid agonists, namely gliadorphin peptides. Barley and rye have homologous proteins to the gluten proteins found in wheat. These barley and rye proteins release opioid hordein peptides and opioid secalin peptides, respectively (R). Non-homologous opioid peptides can also be released from soy as soymorphins and from spinach as rubiscolins.
But back to milk. It turns out that a lot of people are sensitive to the A1 casein and not the A2 casein. This is thought to be due to the formation of BCM7.
Side effects of A1 milk and BCM7
Milk consumption, due to the BCM7 has been associated with coronary heart disease, arteriosclerosis, fractures, sudden infant death syndrome, autism, schizophrenia and type 1 diabetes may be attributed to an opioid peptide, beta-casomorphin-7 (BCM-7), derived from A1 beta-casein. BCM-7 exerts its function by binding to the μ-opioid receptors in the body (R, R).
However, this paper has a great critique section that discusses (debunks) all the studies showing negative effects of milk on type I diabetes and coronary heart disease (R).
Although there is no evidence that BCM7 is actually found in the bloodstream or crosses the blood-brain barrier (R, R), it can bind to opioid receptors in the gut, which can influence the brain and other organs as well.
It is also hypothesized that activation of the μ-opioid receptors in the gut can alter the gut microbial composition, impair gut barrier integrity and bile acid metabolism, in addition to increasing gastrointestinal transit time and gut inflammation (R).
Morphine, for example, has shown a dysbiotic effect on the bacterial microbiota in addition to inducing an increase in intestinal permeability facilitating bacterial translocation. Additionally, certain components of bacteria can modify the expression of opioid receptors at the central level increasing sensitivity to pain. (R)
Furthermore, there is evidence that A1 beta-casein can upregulate the endotoxin receptors (TLR2 and TLR4 mRNA) and enhance inflammation (R) and act as a serotonin 5-HT2 receptor antagonist (R; in vitro; which might actually be a good thing).
Gut inflammation, constipation and transit time
In multiple human studies, switching from A1/A2 milk to A2 milk lowers intestinal inflammation (lowers calprotectin), bloating and abdominal pain, prevents constipation and brain fog and improves lactose tolerance and a bunch of other symptoms as well (R, R, R, R).
Keep in mind that not everyone improves by switching to A2 milk, however, a big percentage do. Almost everyone that I spoke to that didn’t tolerate cow milk very well did much better (and were even symptom-free) on goat milk.
Any inflammation can inhibit brain function. It makes the blood-brain barrier leaky, which allows toxins to enter and damage the brain and give you brain fog (R). The gut can be a major source of toxins that promote inflammation. “Elevated levels of circulating inflammatory markers have been linked to significant impairments in memory, attention, executive function and processing speed, even after controlling for age and other health-related factors“. (R)
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Benefits of dairy protein
So now that we have talked enough about the potential side effects, let’s talk about the benefits.
“Dairy bioactive compounds can be classified as antihypertensive, anti-oxidative, immmunomodulant, anti-mutagenic, antimicrobial, opoid, anti-thrombotic, anti-obesity, and mineral-binding agents, depending upon biological functions.” (R)
“Dose-response analyses indicated that an increment of 200 ml (approximately 1 cup) milk intake per day was associated with a lower risk of cardiovascular disease, stroke, hypertension, colorectal cancer, metabolic syndrome, obesity and osteoporosis. Beneficial associations were also found for type 2 diabetes mellitus and Alzheimer’s disease. Conversely, milk intake might be associated with higher risk of prostate cancer, Parkinson’s disease, acne and Fe-deficiency anaemia in infancy.” (R)
“Our results suggest that genetically predicted milk intake is associated with a decreased risk of MS and AD but with an increased risk of PD.” (R)
Contrary to the meta-analysis above, people who consume a lot of dairy don’t have a higher risk of prostate cancer (R, R) or anemia (anemia is unlikely if you eat enough iron in general (milk is very low in iron)). Chronic low-grade inflammation, which A1 milk can cause in some people, can contribute to the progression of Parkinson’s disease.
Finally, it’s notable that bovine BCM7 stimulates mucin biosynthesis, with this likely to be a protective response (R).
I also wrote an article on the great benefits of dairy fat specifically.
Milk sources and A1, A2 ratios
It’s speculated that around 5000 years ago, cows from Europe started producing A1 beta-casein.
A1 beta-casein is a major variant of beta-casein in the milk of the common dairy cows of north European origin: Friesian, Ayrshire, British Shorthorn, and Holstein. However, there are European niche breeds such as Guernsey and Fleckvieh which tend to carry higher levels of the A2 allele.
Apart from those cows, most other animals and cows produce A2 milk.
Predominantly A2 beta-casein is found in the milk of Channel Island cows, Guernsey and Jersey, in Southern French breeds, Charolais and Limousin, and in the Zebu original cattle of Africa (R).
The beta-caseins of sheep, goats, horses, camels, yaks, buffalo, pure African cattle, pure Asian cattle, and even human milk are all classified as being exclusive of the A2 type, with no reliable evidence of exceptions even at low levels. However, some cattle classified as African or Asian types may have a small hidden proportion of European-breed ancestry due to crossbreeding within the last 200 years, leading to low levels of A1 beta-casein (R).
Milk containing A1 beta-casein has a higher risk of causing intestinal inflammation, gas, bloating, water retention, immune reactions, brain fog, constipation, etc.
But this is not in all people. I and many others tolerate A1/A2 milk perfectly fine, whereas others don’t.
If you struggle to digest milk, give A2 milk a shot. I always suggest people try A2 cows milk or goat milk if they have trouble digesting normal milk and almost always they report that they feel better.
So whether it’s the BCM7 causing it or not, if you get side effects from A1 milk, try A2. If you still get issues, try low-fat or even cheese or strained yogurt.
Always go with what you do best with.
Other things to look out for:
- Fortification with vitamin A and D
Theory as to why some people have problems with A1
I think it’s because they have low strains of certain bifidobacteria.
“All strains tested showed some level of dipeptidyl peptidase activity, which is thought to be involved in the degradation of food-derived opioid peptides. However, this activity was higher in bifidobacterial strains that are commonly found in the intestines of human infants, such as Bifidobacterium longum subsp. longum, B. longum subsp. infantis, Bifidobacterium breve and Bifidobacterium bifidum, than in those of other species, such as Bifidobacterium animalis and Bifidobacterium pseudolongum.” (R)