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:

Arsenic in Infant Rice Cereal

When it comes to rice and rice-based products, pediatric nutrition authorities have recommended that arsenic intake should be as low as possible.

“The US Food and Drug Administration (FDA) has been monitoring the arsenic content in foods” for decades, yet despite the “well-established science describing the health risks associated with arsenic exposure, no standards have been set limiting the amount of arsenic allowable in foods” in the United States. In 2001, the EPA “adopted a new stricter standard for arsenic in drinking water,” and in 2013, the FDA proposed a legal limit for apple juice. “There are still no standards for arsenic in food products despite the fact that food sources are our main source of exposure.”

Unlike the United States, China has standards. As of 2014, China set a maximum threshold of inorganic arsenic at 150 parts per billion, stricter than the World Health Organization’s limit of 200 ppb. In the United States, a 200 ppb limit wouldn’t change the cancer risk much. If we had China’s safety limits of 150 ppb, though, cancer risk would be reduced up to 23 percent and a maximum threshold of 100 ppb would lower cancer risk up to 47 percent—but that could seriously affect the rice industry. In other words, U.S. rice is so contaminated with arsenic that if a safety standard that really cut down on cancer risk were set, it “would wipe out the U.S. rice market.” However, with no limits, what’s the incentive for the rice industry to change its practices? Setting arsenic limits would not only directly protect consumers but also encourage the industry to stop planting rice paddies on arsenic-contaminated land.

Those cancer estimates are based on arsenic-contaminated water studies. Might the arsenic in rice somehow have a different effect? You don’t know…until you put it to the test. We know rice has a lot of toxic arsenic that urine studies have shown we absorb into our body, but there hadn’t been any studies demonstrating “deleterious health impacts” specific to rice arsenic—until now. Since arsenic causes bladder cancer, the researchers figured they would see what kind of DNA mutations the urine of rice eaters can have on human bladder cells growing in a petri dish. And, indeed, they clearly demonstrated that eating a lot of arsenic-contaminated rice every day can “give rise to significant amounts of genetic damage,” the kind that‘s associated with cancer. Yes, but the study used pretty contaminated rice. However, only about 10 percent of the rice in certain parts of Asia might ever reach those levels of contamination, though a quarter of rice in parts of Europe might and more half in the United States, making for considerable public health implications.

So, “there remains little mystery surrounding the health risks associated with arsenic levels in rice. The remaining mystery is why long-overdue standards for arsenic levels in rice have not been set by the FDA” in the United States, but that may be changing. In 2016, the FDA proposed setting a limit on toxic arsenic—at least in infant rice cereal, which I discuss in my video Arsenic in Infant Rice Cereal.

As you can see at 3:24 in my video, infants and children under four years of age average the highest rice intake, in part because they eat about three times the amount of food in relation to their body size, so there’s an especially “urgent need for regulatory limits” on toxic arsenic in baby food.

Pediatric nutrition authorities have recommended that when it comes to rice and rice-based products, “arsenic intake should be as low as possible,” but how about as early as possible? Approximately 90 percent of pregnant women eat rice, which may end up having “adverse health effects” on the baby.

You can estimate how much rice the mother ate while pregnant by analyzing arsenic levels in the infant’s toenail clippings. “Specifically, an increase of 1/4 cup of rice per day was associated with a 16.9% increase in infants toenail [arsenic] concentration,” which indicates that arsenic in rice can be passed along to the fetus. What might that arsenic do? A quarter cup of rice worth of arsenic has been associated with low birth weight, increased respiratory infections, and, above that, a 5- to 6-point reduction in IQ, among other issues. So, “based on the FDA’s findings, it would be prudent for pregnant women to consume a variety of foods, including varied grains (such as wheat, oats, and barley),” which is code for cut down on rice. Saying eat less of anything, after all, is bad for business.

Once the baby is weaning, “what’s a parent to do?” Asks Consumer Reports, “To reduce arsenic risks, we recommend that babies eat no more than 1 serving of infant rice cereal per day on average. And their diets should include cereals made of wheat, oatmeal, or corn grits, which contain significantly lower levels of arsenic”—that is, rely on other grains, which are much less contaminated than rice. As the American Academy of Pediatrics has emphasized, “there is no demonstrated benefit of rice cereal over those made with other grains such as oat, barley, and multigrain cereals, all of which have lower arsenic levels than rice cereal.” As you can see at 5:28 in my video, reducing consumption of infant rice cereal to just two servings per week could have an even more dramatic effect on reducing risk.

 The proposed limit on toxic arsenic in infant rice cereals would end up removing about half of the products off the shelves. The FDA analyzed more than 500 infant and toddler foods, and the highest levels of toxic arsenic were found in organic brown rice cereals and “Toddler Puffs.” Based on the wording in the report, these puffs appear to be from the Happy Baby brand. Not-so-happy baby if they suffer brain damage or grow up to get cancer. A single serving could expose infants to twice the tolerable arsenic intake set by the EPA for water. I contacted the Happy Baby company and was told they “are not able to provide any comments” on the FDA’s results.

“Eliminating all rice and rice products from the diets of infants and small children up to 6 years old could reduce the lifetime cancer risk from inorganic arsenic in rice and rice products by 6% and 23% respectively.” That is, there would be a 6 percent lower chance of developing lung or bladder cancer later in life if infants stopped, and a 23 percent lower chance if young kids stopped. However, switching to other grains is a move described as “drastic and dramatic,” creating “a huge crisis”—for the rice industry, presumably—and therefore “not feasible at all.”

I was hoping Happy Baby, upon learning of the concerning FDA arsenic toddler puffs data (regardless of whether the data were about its brand or not) would have kicked its own testing and potential remediation into high gear like Lundberg did (see Which Brands and Sources of Rice Have the Least Arsenic?). But, unfortunately, in my email correspondence with the company, I got no sense that it did.

For more videos on this topic, see:

And here are five more:

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: