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Is the Casein in A2 Milk Healthier?

The casomorphins—breakdown products of casein, a milk protein, with opiate-like activity—in bovine milk appears to have opposite effects than those from human breast milk on infant development, but what about A2 cow’s milk?

“One of the main sources of opioid peptides”—that is, protein fragments with opiate-like activity—”in the autism patients diet are dairy products.” As I discuss in my video Does A2 Milk Carry Less Autism Risk?, casein, the main dairy protein, breaks down into casomorphins, which “are considered to be factors involved in etiology [the cause] and exacerbation of symptoms in food allergy and atopic dermatitis [eczema], diabetes, schizophrenia, postpartum psychoses, sudden infant death syndrome (SIDS), and autism.” According to this opioid-excess idea, the development of autism includes a genetic predisposition and early exposure to some kind of environmental stressors that affect the gut, which may cause more of these casomorphins to leak into the blood and then the brain, where they may play a role in the development of autism. You don’t know, though, until you put it to the test.

First of all, do these bovine casomorphins form in the human digestive tract when we drink milk? Researchers decided to insert tubes down into subjects’ intestines to find out and, indeed, “considerable amounts” of casomorphin were found. Do they get absorbed into the bloodstream, though? Yes, apparently so, but the study was on infants who naturally have leakier guts. Do fully intact casein protein fragments make it into the bloodstream after infancy? Yes, as you can see at 1:24 in my video. In fact, they can get into the bloodstream even into adulthood, elevating levels in the blood for at least eight hours after consumption.

And, those with autism may have an especially leaky gut at significantly higher risk for abnormally high intestinal permeability, which may explain why the vast majority of children with autism may have antibodies in their blood to wheat and dairy proteins, compared to a small minority of children without autism, as you can see at 1:44 in my video. And, based on allergy studies, even if infants are strictly breastfed, they may still be exposed to bits of bovine milk proteins if their mothers drink milk, as the bovine protein fragments can get into the mother’s blood, then her breast, and then into her baby’s body. But, do the cow proteins also get into the baby’s brain?

Those with autism are more likely to suffer from leaky gut, but the “opioid excess theory” depends on casomorphins not only getting into the bloodstream, but also up into the central nervous system, which includes the brain. There’s something called the blood-brain barrier, which helps cordon off the brain, but when you examine the brain tissues of those with autism, their blood-brain barrier seems leakier, too. Indeed, evidence for the presence of casomorphins within the brains of infants has since been confirmed. If you think about it, it just makes sense. Presumably, the whole point of casomorphin opioids is to affect the brains of babies so they crave the milk and cry out for the milk, strengthening the mother-infant bond and, similarly, the cow-calf bond. That’s what’s supposed to happen. It’s normal and natural. In that case, why are casomorphins associated with disease? Well, such a bond between a human mother and her human infant is natural, whereas one between a cow and a baby or a human mom and a calf isn’t.

As you can see at 3:24 in my video, human infants with evidence of higher baseline levels of bovine casomorphins in their blood seem more likely to be suffering from psychomotor delay, which is a measure of muscle, language, and mental function development, but the reverse was found for human infant exposure to human casomorphins, meaning human casomorphins appeared to be beneficial in humans. Just as bovine casomorphin levels in human babies’ blood appear to rise after feeding them cow’s milk formula, human casomorphin levels rise in babies after breastfeeding, which is what’s supposed to happen. “The greatest basal irHCM [baseline human casomorphins] was revealed in breastfed infants with normal psychomotor development and muscle tone. In contrast, elevated basal irBCM [baseline bovine casomorphins] was found in [cow’s milk] formula-fed infants showing delay in psychomotor development,” as well as, more rigid, muscle tone.

“The explanation of opposite effects of human and bovine CM [casomorphins] on infants’ psychomotor development and muscle tone probably lay in their species-specificity.” Cow’s milk is good for calves, and  breastmilk is good for babies. Indeed, the structures of bovine casein and human casein are dramatically different, and the bovine and human casomorphins themselves are different molecules, differing by two amino acids, which results in greatly different potencies. Compared to human casomorphin, bovine casomorphin “is highly potent and similar to morphine in its effects.”

A difference of two amino acids may not seem like a lot, but casomorphins are only seven amino acids long. This difference of about 30 percent “likely defines a difference in their biological properties. Both human and bovine CMs [casomorphins]…interact with opioid and serotonin receptors which are known to be of great importance for CNS [central nervous system, including the brain] maturation,” but cow casomorphin binds more tightly to these receptors, so it has more of an effect. As such, this can help explain not only why breast is best, but also why the psychomotor delay linked with higher bovine casomorphin levels in the blood supports this concept that cow casomorphins may play a role in a disease such as autism.

This is why bovine casomorphins have been called “the devil in the milk,” but are they formed from all cow’s milk? What about “A2” milk? The A2 Corporation points out there are different variants of casein: Some cows produce milk with a kind of casein dubbed A1, while other cows produce milk with A2 casein. A2 differs from A1 by only single amino acid, but one that is strategically located such that A1 casein breaks down into casomorphin, which acts like morphine and is “implicated in digestive, immune and brain development changes.” Supposedly, A2 milk does not do the same. As you can see at 6:18 in my video, if you put A1 milk in a test tube with some digestive enzymes, the A1 casein breaks down into casomorphin. But, because of that one amino acid difference, the A2 casein breaks down at a different spot and no casomorphin is formed.

That study, however, used digestive enzymes from pigs or cows, which are cheaper and easier to buy for laboratory experiments. Human digestive juices are different, so what happens in a pig’s stomach or a cow’s stomach may not necessarily be what happens in the human digestive tract. 

When the A1 versus A2 breakdown experiment was finally performed with human enzymes, what was discovered? Human stomach and intestinal juices were collected, and the devil was found in both. The opioid casomorphin was produced from both A1 milk and A2 milk. So, A2 milk may be better for pigs or cow, but not necessarily for humans. 

This article discusses the second video in a six-part series on the role of gluten- and dairy-free diets in the treatment of autism. If you missed the first video, see Autism and Casein from Cow’s Milk. 


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I previously touched on A1 vs. A2 milk in Does Casein in Milk Trigger Type 1 Diabetes? and Does Bovine Insulin in Milk Trigger Type 1 Diabetes?.

In health, 

Michael Greger, M.D.

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