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. 

Stay tuned for: 

Keep abreast of all of my videos on autism here.

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.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live presentations:

Do Casomorphins from Cow’s Milk Contribute to Autism?

Casomorphins—breakdown products of casein, a milk protein, with opiate-like activity—may help explain why autism symptoms sometimes improve with a dairy-free diet.

In my last video series on autism and diet, I talked about the benefits of broccoli sprouts, but the most commonly studied nutritional and dietary interventions for autism and diet involve variations of gluten-free and casein-free diets. Why?

In the 1980s, a team of respected Norwegian researchers reported a peculiar finding. They were comparing the urine of children with and without autism in the hopes of teasing out any differences that could lead to hints to the cause of autism. As you can see at 0:42 in my video Autism and Casein from Cow’s Milk, a urine profile shows spikes for each of the various components. Normally, the urine’s peptides region is pretty quiet. Peptides are like small pieces of proteins, and, normally, we shouldn’t be peeing out much protein. But, in the urine profiles from children with autism, there were all sorts of peptide spikes.

This difference raised a question: “Can the pathophysiology”—that is, the dysfunction—“of autism be explained by the nature of the discovered urine peptides?” But, first: “Where do the peptides come from?” They didn’t know, but there was a clue: Most of the parents of kids with autism reported that their children’s disorder got worse when they were exposed to cow’s milk. In fact, two proteins—gluten, a protein in wheat, and casein, a protein in milk—break down not only into peptides, but also into exorphins.

Exorphins, opioid peptides derived from food proteins, “are called exorphins because of their exogenous [that is, from outside of the body] origin and morphine-like activity,” as opposed to endorphins, which are morphine-like compounds we produce inside our bodies. Perhaps some of these food peptides represent a new class of hormones?

Well, is that what the kids were peeing out? Apparently so, as some of those peptides had opioid activity. Maybe the researchers were on to something. 

Two types of opioids have been found in milk: casomorphins, “in view of their morphine-like activity and their origin—they represent fragments of the milk protein β-casein,” and the actual opiate, morphine. There appears to be actual morphine in milk. This can’t just be a coincidence. “It is difficult to believe that these, or other types of opioids found in the milk, can be devoid of physiological, or nutritional, significance.” If you think about it, it makes total sense. “Morphine and the opioid peptides may also have an important role in the mother-infant bonding mechanism, because the infants may be ‘addicted’ to their own mother’s milk.” But, what about the milk of another species?

“Human milk is markedly different from that of other mammalian species” in that it has the lowest casein content. Further, human casein is a markedly different protein in terms of its sequence of amino-acid building blocks.

As you can see at 3:40 in my video, human breastmilk has about 15 times less casein than cow’s milk and differs in its amino acid sequence by about half, so it breaks down into peptides differently. “Twenty-one peptides were identified from cow casein proteins,” including multiple casomorphins, compared to only five active peptides identified in human milk and just one casomorphin. What’s more, “those [casomorphins] from bovine casein are more potent than β-casomorphins from human milk.” At 4:08 in my video, you can see a graph of opioid activity, where lower means more potent. Bovine casomorphin was shown to be significantly more potent than the weak opioid peptide from gluten, a substance more comparable to the casomorphin from human breastmilk.

Indeed, when you expose human nerve tissue to bovine casomorphin, it acts more like morphine than the casomorphin from human breastmilk in terms of epigenetic changes, changes in gene expression, not only providing “a molecular rationale for the recommendation of breastfeeding vs. [cows’ milk] formula feeding,” but also providing a possible explanation why “casein-free, gluten-free diets have been reported to mitigate some of the inflammatory gastrointestinal and behavioral traits associated with autism…” 

“What is good for the goose may be good for the gander, but what is good for the cow could be harmful to the human.” 

This article discusses the first video in a series on the role of gluten- and dairy-free diets in the treatment of autism. Stay tuned for the other five videos in this six-part series: 

My previous series on autism explored the amazing story of broccoli sprouts put to the test for the treatment of autistic boys. See: 

Keep abreast of all of my videos on autism here.

You may also be interested in these videos on milk and child and infant health:

In health, 

Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live presentations:

Should You Get an Annual Physical Exam?

What are the risks and benefits of getting a comprehensive annual physical exam and routine blood testing?

The model of getting an annual physical exam dates back nearly a century in American medicine, but recently, many health authorities “have all agreed that routine annual checkups for healthy adults should be abandoned”—yet, the majority of the public still expects not only a comprehensive annual physical exam, but also extensive routine blood testing. “Given the gap between patients’ enthusiasm for and [the new] guidelines’ skepticism about annual head-to-toe examinations, what are physicians to do?” As I discuss in my video Is It Worth Getting an Annual Physical Exam?, “first, we must educate patients about preventive practices of proven and unproven benefit.” For example, the only routine blood test currently recommended by the USPSTF, the official preventive medicine guidelines setting body, is cholesterol.

The reason “why many physicians continue to perform annual examinations of patients’ hearts, lungs, abdomens and even reflexes and continue to order some of the tests that have been proven ineffectual or even harmful” is because, otherwise, the patient might leave unsatisfied with the visit. “Evidence suggests that the more thorough physicians are (that is, the more physical and laboratory examinations they perform), the better patients feel about their health and their physicians.” So, they are like “placebo clinical manoeuvers…But rather than performing unnecessary (and sometimes contraindicated) physical exams and laboratory tests during an annual visit, perhaps physicians should spend some of the time saved by telling their patients why they are not examining their abdomens, hearts and lungs”—that is, why are aren’t just going to go through the motions like some witch doctor. 

“Most important, we need to educate ourselves about the dangers of overdiagnosis….There will always remain a small possibility that our examination might detect some silent, potentially deadly cancer or aneurysm. Unfortunately for our patients, these serendipitous, life-saving events are much less common than the false-positive findings that lead to invasive and potentially life-threatening tests,” wrote a doctor from the Cleveland Clinic. He went on to share a story about his own father who went in for a checkup. Can’t hurt, right? His dad’s physician thought he felt what might have been an aortic aneurism, so he ordered an abdominal ultrasound. Can’t hurt, right? His aorta was fine, but something looked suspicious on his pancreas, so a CT scan was ordered. Well, that can hurt—it’s a lot of radiation—but thankfully, his pancreas looked fine. But…what’s that on his liver? It looked like cancer, which made a certain amount of sense since his dad had worked in the chemical industry. Realizing how ineffective the treatments were for liver cancer, he realized he was going to die.

His daughter was not ready to give up on him, though, and convinced him to see a specialist. Maybe if they cut it out, he could live a few more years. But first, they had to do a biopsy. The good news was he didn’t have cancer. The bad news, though, was that it was a benign mass of blood vessels, so when they stuck a needle in it to biopsy, he almost bled to death. He required ten units of blood—and ten units is about all you have! This resulted in pain, thus morphine, thus urinary retention, and thus a catheter, yet, thankfully, no infection. Just a bill for $50,000. 

The frustrating thing is that there wasn’t any malpractice or anything in the whole horrible sequence. Every step logically led to the next. “The only way to have prevented this [life-threatening] outcome would have been to dispense with the initial physical examination”—the “checkup” that couldn’t hurt, right?

“Why, then, do we continue to examine healthy patients? First of all, we get paid to do it.” His dad’s initial doctor only received a hundred bucks or so, but just think about all that “downstream revenue” for the hospital and all the specialists. Overdiagnosis is big business.

“Too many patients bear the costs and harms of unneeded tests and procedures,” but without annual check-ups, we doctors would miss out on all those opportunities for “open communication and interpersonal continuity…” Is that so? In that case, replied one physician, if you want communication, why not just take your patients out to lunch? 

“Of course, such lunches should fairly and ethically be preceded by an informed consent discussion that allows prospective diners to understand the risk that they will be infantilized, made dependent, and may well receive unnecessary and injurious diagnostic and therapeutic interventions as a consequence of that grilled cheese and soup”—particularly, I would add, if you’re feeding your patients grilled cheese, having already chalked up your first such “unnecessary and injurious” act!

So, if you don’t have any symptoms or issues, should you even have an annual check-up? That was the subject of my last video, Is It Worth Getting Annual Health Check-Ups?.

Should All Children Have Their Cholesterol Checked, too? Watch the video to find out!

Check out this video to Find Out If Your Doctor Takes Drug Company Money.

I sometimes stumble across these peripheral issues and fall down various rabbit holes. For example, I’ve got a whole series of videos on various diagnostic tests such as mammograms. I don’t want to get too far away from nutrition, but whenever I learn something new and interesting—particularly if there are conflicts of interest trying to muddy the waters—I feel compelled to try to share to help set the record straight.

In health,

Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live presentations: