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:

Are Avocados Associated with Greater Risk or Reduced Risk of Cancer?

Avocado consumption can improve artery function, but what effect might guacamole have on cancer risk?

In my last video about avocados, The Effects of Avocados and Red Wine on Meal-Induced Inflammation, I described their anti-inflammatory effects and cholesterol- and triglyceride-lowering effects, but what about the Are Avocados Good for You? video I did years ago about the chromosome-damaging effects in a petri dish? That goes back to 1975, when a pesticide naturally produced by the avocado tree was discovered, thought to explain why lactating livestock suffer mammary gland damage after nibbling on the leaves. The toxin, named persin, was also found to be damaging to the heart, which is why you should never feed avocado to your pet birds.

But, if persin attacks mammary cells in animals, might it attack breast cancer cells in humans? As you can see at 0:52 in my video Are Avocados Healthy?, it did seem to have the same kind of cellular cytoskeleton-clumping effect in vitro that chemotherapy can have, demonstrating potent cell growth stopping and killing effects of the novel plant toxin among various lines of human breast cancer cells. So, researchers are thinking about how it might one day be used as chemo itself, but I’m thinking, Holy guacamole, Batman! Please tell me it doesn’t have toxic effects on normal cells, too.

We got an answer in 2010 with an evaluation of the genotoxicity—the toxicity to our chromosomes—of avocado extracts on human white blood cells in a petri dish. As you can see at 1:35 in my video, normally, less than 10 percent of our dividing cells have any chromosome abnormalities, but if you drip some avocado fruit extracts on them, up to half come out defective in some way. The researchers concluded that there’s something in avocado fruit that “can potentially induce significant genomic instability and some genetic damage in human lymphocytes in vitro,” that is, in white blood cells in a petri dish. If the same effect occurs in actual people, it could, for example, result in transforming cells into cancer. That is a big if, though. These were blood cells. You don’t inject guacamole into the vein. For something to get into our bloodstream, it first has to survive our stomach acid, get absorbed through our intestines, and then sneak past our liver’s detoxification enzymes. And indeed, persin may be affected, changed by acidic conditions. So, given all the differences between what happens in a petri dish and inside a person, it’s essential to carry out further studies “before making a final remark on the genotoxicity.” Sounds reasonable, but what do you do before these studies come out? I was concerned enough that I provisionally moved avocados from being a don’t-hold-back green-light food to a moderate-your-intake yellow-light food to err on the side of caution until we knew more.

Even if persin were utterly destroyed by stomach acid, what about oral cancer? As you can see at 3:01 in my video, avocado extracts at high enough concentrations can harm the growth of the kinds of cells that line our mouths. This was in a petri dish, though, where the avocado is coming in direct contact with the cells—but that’s also kind of what happens in your mouth when you eat it. However, it harms oral cancer cells even more. At 3:32 in my video, you can see a bunch of oral cancer cells. In the first image, the mitochondria, the power plants of the cells fueling cancer growth, are seen in red. In the second image, you can see they’ve been extinguished by the avocado extract—no more red-colored mitochondria. Since it does this more to cancerous cells than normal cells, the researchers conclude that avocados may end up preventing cancer.

What about the esophagus, which lies between the mouth and the stomach? Researchers similarly found that an avocado fruit extract appeared to inhibit cancer cell growth more than normal cell growth when it came to both colon cancer cells and esophageal cancer cells, as you can see at 3:53 in my video. But, rather than comparing the effects to normal colon and esophagus cells, they compared them to a type of blood cell, which, again, is of limited relevance in a petri dish study of something you eat.

A study I found to be pretty exciting looked at p-cresol, which is a “uremic toxin” and may also be toxic to the liver. “Found to be associated with autism,” it comes from eating high-protein diets, whereas if you eat a more plant-based diet, which is the only source of prebiotics like fiber and resistant starch, your levels go down. See, fermentation of carbohydrates in the colon, like fiber, is considered beneficial, whereas fermentation of protein, which is called putrefaction, is considered detrimental. So, if you switch people to a high-protein diet, within days, the excess protein putrefying in their gut leads to an increase in ammonia as well as p-cresol—in fact, a doubling of levels within a week. But, might phytonutrient-rich plant foods, like apples, cranberries, grapes, or avocados, protect the cells lining our colon “from the deleterious effects of p-cresol…in terms of cell viability, mitochondrial function, and epithelial integrity,” meaning protection against gut leakiness? At 5:12 in my video, I show the data on barrier function integrity. You can see that it is damaged by p-cresol, but rescued by all the cranberry, avocado, grape, and apple extracts. Mitochondrial function, however, was only improved by the cranberries and avocados, which also were the only ones that appeared to prevent the deleterious effect of p-cresol on colon cell viability. The bottom line, though, is that avocados appear to have beneficial effects on colon lining cells. Okay, but enough of these in vitro studies, already. Yes, an avocado extract can inhibit cancer cell growth in a petri dish, but unless you’re doing some unspeakable things to that avocado—like guacamole with benefits—there’s no way that avocado is going to come in direct contact with your prostate cells. So, what does this study mean?

This is why I was so excited to see the first study to actually look for a link between avocado consumption and prostate cancer. Actual human beings eating avocados! So, do avocado eaters have more cancer risk or less cancer risk? Men who ate the most avocado, more than about a third of an avocado a day, had reduced risk of prostate cancer—in fact, less than half the odds. So, with the data on improved artery function, lower cholesterol, and, if anything, an association with decreased cancer risk, I’d suggest moving avocados back up with the other green-light foods.

How Not to Die from Cancer is an overview on dietary approaches to cancer prevention and treatment, and I also have hundreds of videos on all of the common cancers.

What if you’ve already been diagnosed? Even if you already have prostate cancer, for example, it’s not too late to improve your diet. See: 

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: