The casomorphins—breakdown products of casein, a milk protein, with opiate-like activity—in bovine milk appear to have opposite effects than those from human breast milk on infant development, but what about A2 cow’s milk?
Does A2 Milk Carry Less Autism Risk?
4.7/5 - (87 votes)
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
“One of the main sources of [protein fragments with opiate-like activity] in the [diets of] autism patients are dairy products.” The main dairy protein, casein, breaks down into casomorphins, which have been “considered to be factors involved in the [cause] and exacerbation of symptoms in food allergy and [eczema], diabetes, schizophrenia, postpartum psychoses, [crib death],…and autism.”
“According to [this] opioid-excess [idea] the development of autism includes: [a] genetic predisposition, 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.” But, you don’t know, 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 stick tubes down into people’s intestines to find out. And indeed, “[c]onsiderable amounts of…casomorphin…were found.” Okay, but do they get absorbed into the bloodstream? Yes, apparently so. But, this study was on infants, who naturally have leakier guts. Do fully intact casein-protein fragments make it into the bloodstream after infancy? Yes, 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 autistic children may have antibodies in their blood to wheat and dairy proteins, compared to a small minority of normal children. And, based on allergy studies, even if an infant is strictly breastfed, they may still be exposed to bits of bovine milk proteins if the mother drinks milk, as the bovine protein fragments can get into her blood, then her breast, then into her baby’s body. But, does it get into the baby’s brain?
Yeah, those with autism are more likely to suffer from leaky gut, but the so-called “opioid excess theory” depends on casomorphins not only getting into the bloodstream, but up into the central nervous system, the brain. And, there’s something called the blood-brain barrier that helps cordon off the brain. When you examine the brain tissues of those with autism, their blood-brain barrier seems leakier, too. And indeed, evidence for the presence of casomorphins within the brains of infants has since “been confirmed”—which, again, just makes sense. That’s the whole presumed point of casomorphin opioids—to affect the brains of babies, so they crave the milk, cry out for the milk, strengthening the mother-infant bond, the cow-calf bond. That’s what’s supposed to happen; it’s normal, natural. Okay, then, why are casomorphins associated with disease? Well, this is normal and natural. This? Not so much.
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. See, just like bovine casomorphin levels in the baby’s blood appear to rise after feeding cow’s milk formula, human casomorphin levels rise in the baby after breastfeeding, and that’s what’s supposed to happen. “The greatest [baseline human casomorphins] was revealed in breastfed infants with normal psychomotor development and muscle tone. In contrast, elevated [baseline bovine casomorphins] found in [cow’s milk-]formula-fed infants [was associated with] delay[ed] psychomotor development” and stiffened, more rigid, muscle tone.
“The explanation of [the] opposite effects of human [versus] bovine [casomorphins] on infant… development…probably [has to do with] species-specificity.” Cow’s milk is good for calves; breast milk is good for babies. “Indeed, the structure of bovine and human [casein is 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 [more] similar to morphine in its effects.”
A two-amino acid difference doesn’t seem like a lot, but casomorphins are only seven amino acids long! This 30% or so difference “likely defines [the] difference in their biological properties. Both human and bovine [casomorphins]…interact with opioid and serotonin receptors, which are known to be of great importance for [brain] maturation.” But cow casomorphin binds tighter to these receptors and, so, has more of an effect. This can, therefore, help explain not only why breast is best, but 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 so-called “A2” milk? The “A2 [milk] Corporation” points out there are different “variants” of casein. Some cows produce milk with a kind of casein dubbed A1, and other cows produce milk with A2 casein, which differs from A1 casein “by a single amino acid”—but strategically located such that A1 casein breaks down into casomorphin, which acts like morphine, “and is implicated in digestive, immune, and brain development changes.” But, supposedly, A2 milk does not. Put A1 milk in a test tube with some digestive enzymes, and the A1 casein breaks down into casomorphin. But, because of that amino acid difference, the A2 casein breaks down at a different spot. And so, no casomorphin is formed.
But, this was using digestive enzymes from pigs, or cows, which are just cheaper and easier to buy for laboratory experiments. But human digestive juices are different. And so, what happens in a pig’s stomach or cow stomachs may not necessarily be what happens in the human digestive tract. But, the A1 versus A2 breakdown experiment had never been performed with human enzymes before, until…now. Human stomach and intestinal juices were collected, and the devil was in both. The opioid casomorphin was produced from both A1 and A2 milk. So, A2 milk may be better for this Babe, but not necessarily for this one.
Please consider volunteering to help out on the site.
- Park HR, Lee JM, Moon HE, Lee DS, Kim BN, Kim J, Kim DG, Paek SH. A Short Review on the Current Understanding of Autism Spectrum Disorders. Exp Neurobiol. 2016 Feb;25(1):1-13.
- Ly V, Bottelier M, Hoekstra PJ, Arias Vasquez A, Buitelaar JK, Rommelse NN. Elimination diets' efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder. Eur Child Adolesc Psychiatry. 2017 Feb 11.
- Kost NV, Sokolov OY, Kurasova OB, Dmitriev AD, Tarakanova JN, Gabaeva MV, Zolotarev YA, Dadayan AK, Grachev SA, Korneeva EV, Mikheeva IG, Zozulya AA. Beta-casomorphins-7 in infants on different type of feeding and different levels of psychomotor development. Peptides. 2009 Oct;30(10):1854-60.
- Chabance B, Marteau P, Rambaud JC, Migliore-Samour D, Boynard M, Perrotin P, Guillet R, Jollès P, Fiat AM. Casein peptide release and passage to the blood in humans during digestion of milk or yogurt. Biochimie. 1998 Feb;80(2):155-65.
- Cieślińska A, Sienkiewicz-Szłapka E, Wasilewska J, Fiedorowicz E, Chwała B, Moszyńska-Dumara M, Cieśliński T, Bukało M, Kostyra E. Influence of candidate polymorphisms on the dipeptidyl peptidase IV and μ-opioid receptor genes expression in aspect of the β-casomorphin-7 modulation functions in autism. Peptides. 2015 Mar;65:6-11.
- Trivedi MS, Hodgson NW, Walker SJ, Trooskens G, Nair V, Deth RC. Epigenetic effects of casein-derived opioid peptides in SH-SY5Y human neuroblastoma cells. Nutr Metab (Lond). 2015 Dec 9;12:54.
- Cade R, Privette M, Fregly M, Rowland N, Sun Z, Zele V, Wagemaker H, Edelstein C. Autism and Schizophrenia: Intestinal Disorders. Nutr Neurosci. 2000;3(1):57-72.
- Svedberg J, de Haas J, Leimenstoll G, Paul F, Teschemacher H. Demonstration of beta-casomorphin immunoreactive materials in in vitro digests of bovine milk and in small intestine contents after bovine milk ingestion in adult humans. Peptides. 1985 Sep-Oct;6(5):825-30.
- Miller MJ, Witherly SA, Clark DA. Casein: a milk protein with diverse biologic consequences. Proc Soc Exp Biol Med. 1990 Nov;195(2):143-59.
- de Magistris L, Familiari V, Pascotto A, Sapone A, Frolli A, Iardino P, Carteni M, De Rosa M, Francavilla R, Riegler G, Militerni R, Bravaccio C. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr. 2010 Oct;51(4):418-24.
- Fiorentino M, Sapone A, Senger S, Camhi SS, Kadzielski SM, Buie TM, Kelly DL, Cascella N, Fasano A. Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism. 2016 Nov 29;7:49.
- Brondino N, Fusar-Poli L, Rocchetti M, Provenzani U, Barale F, Politi P. Complementary and Alternative Therapies for Autism Spectrum Disorder. Evid Based Complement Alternat Med. 2015;2015:258589.
- Clarke A, Trivedi M. Bovine Beta Casein Variants: Implications to Human Nutrition and Health. IPCBEE. 2014;67(3):11-17.
- Asledottir T, Le TT, Petrat-Melin B, Devold T, Larsen L, Vegarud GE. Identification of bioactive peptides and quantification of β-casomorphin-7 from bovine β-casein A1, A2 and I after ex vivo gastrointestinal digestion. International Dairy Journal. 2017;71:98-106.
Icons created by Mungang Kim, Nook Fulloption, Luis Prado, Pavel N., Alexandr Lavreniuk, and Gan Khoon Lay from The Noun Project.
Image credit: BlackCab (Self-taken) [CC BY-SA 3.0] via Wikimedia Commons. Image has been modified.
Motion graphics by Avocado Video
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
“One of the main sources of [protein fragments with opiate-like activity] in the [diets of] autism patients are dairy products.” The main dairy protein, casein, breaks down into casomorphins, which have been “considered to be factors involved in the [cause] and exacerbation of symptoms in food allergy and [eczema], diabetes, schizophrenia, postpartum psychoses, [crib death],…and autism.”
“According to [this] opioid-excess [idea] the development of autism includes: [a] genetic predisposition, 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.” But, you don’t know, 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 stick tubes down into people’s intestines to find out. And indeed, “[c]onsiderable amounts of…casomorphin…were found.” Okay, but do they get absorbed into the bloodstream? Yes, apparently so. But, this study was on infants, who naturally have leakier guts. Do fully intact casein-protein fragments make it into the bloodstream after infancy? Yes, 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 autistic children may have antibodies in their blood to wheat and dairy proteins, compared to a small minority of normal children. And, based on allergy studies, even if an infant is strictly breastfed, they may still be exposed to bits of bovine milk proteins if the mother drinks milk, as the bovine protein fragments can get into her blood, then her breast, then into her baby’s body. But, does it get into the baby’s brain?
Yeah, those with autism are more likely to suffer from leaky gut, but the so-called “opioid excess theory” depends on casomorphins not only getting into the bloodstream, but up into the central nervous system, the brain. And, there’s something called the blood-brain barrier that helps cordon off the brain. When you examine the brain tissues of those with autism, their blood-brain barrier seems leakier, too. And indeed, evidence for the presence of casomorphins within the brains of infants has since “been confirmed”—which, again, just makes sense. That’s the whole presumed point of casomorphin opioids—to affect the brains of babies, so they crave the milk, cry out for the milk, strengthening the mother-infant bond, the cow-calf bond. That’s what’s supposed to happen; it’s normal, natural. Okay, then, why are casomorphins associated with disease? Well, this is normal and natural. This? Not so much.
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. See, just like bovine casomorphin levels in the baby’s blood appear to rise after feeding cow’s milk formula, human casomorphin levels rise in the baby after breastfeeding, and that’s what’s supposed to happen. “The greatest [baseline human casomorphins] was revealed in breastfed infants with normal psychomotor development and muscle tone. In contrast, elevated [baseline bovine casomorphins] found in [cow’s milk-]formula-fed infants [was associated with] delay[ed] psychomotor development” and stiffened, more rigid, muscle tone.
“The explanation of [the] opposite effects of human [versus] bovine [casomorphins] on infant… development…probably [has to do with] species-specificity.” Cow’s milk is good for calves; breast milk is good for babies. “Indeed, the structure of bovine and human [casein is 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 [more] similar to morphine in its effects.”
A two-amino acid difference doesn’t seem like a lot, but casomorphins are only seven amino acids long! This 30% or so difference “likely defines [the] difference in their biological properties. Both human and bovine [casomorphins]…interact with opioid and serotonin receptors, which are known to be of great importance for [brain] maturation.” But cow casomorphin binds tighter to these receptors and, so, has more of an effect. This can, therefore, help explain not only why breast is best, but 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 so-called “A2” milk? The “A2 [milk] Corporation” points out there are different “variants” of casein. Some cows produce milk with a kind of casein dubbed A1, and other cows produce milk with A2 casein, which differs from A1 casein “by a single amino acid”—but strategically located such that A1 casein breaks down into casomorphin, which acts like morphine, “and is implicated in digestive, immune, and brain development changes.” But, supposedly, A2 milk does not. Put A1 milk in a test tube with some digestive enzymes, and the A1 casein breaks down into casomorphin. But, because of that amino acid difference, the A2 casein breaks down at a different spot. And so, no casomorphin is formed.
But, this was using digestive enzymes from pigs, or cows, which are just cheaper and easier to buy for laboratory experiments. But human digestive juices are different. And so, what happens in a pig’s stomach or cow stomachs may not necessarily be what happens in the human digestive tract. But, the A1 versus A2 breakdown experiment had never been performed with human enzymes before, until…now. Human stomach and intestinal juices were collected, and the devil was in both. The opioid casomorphin was produced from both A1 and A2 milk. So, A2 milk may be better for this Babe, but not necessarily for this one.
Please consider volunteering to help out on the site.
- Park HR, Lee JM, Moon HE, Lee DS, Kim BN, Kim J, Kim DG, Paek SH. A Short Review on the Current Understanding of Autism Spectrum Disorders. Exp Neurobiol. 2016 Feb;25(1):1-13.
- Ly V, Bottelier M, Hoekstra PJ, Arias Vasquez A, Buitelaar JK, Rommelse NN. Elimination diets' efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder. Eur Child Adolesc Psychiatry. 2017 Feb 11.
- Kost NV, Sokolov OY, Kurasova OB, Dmitriev AD, Tarakanova JN, Gabaeva MV, Zolotarev YA, Dadayan AK, Grachev SA, Korneeva EV, Mikheeva IG, Zozulya AA. Beta-casomorphins-7 in infants on different type of feeding and different levels of psychomotor development. Peptides. 2009 Oct;30(10):1854-60.
- Chabance B, Marteau P, Rambaud JC, Migliore-Samour D, Boynard M, Perrotin P, Guillet R, Jollès P, Fiat AM. Casein peptide release and passage to the blood in humans during digestion of milk or yogurt. Biochimie. 1998 Feb;80(2):155-65.
- Cieślińska A, Sienkiewicz-Szłapka E, Wasilewska J, Fiedorowicz E, Chwała B, Moszyńska-Dumara M, Cieśliński T, Bukało M, Kostyra E. Influence of candidate polymorphisms on the dipeptidyl peptidase IV and μ-opioid receptor genes expression in aspect of the β-casomorphin-7 modulation functions in autism. Peptides. 2015 Mar;65:6-11.
- Trivedi MS, Hodgson NW, Walker SJ, Trooskens G, Nair V, Deth RC. Epigenetic effects of casein-derived opioid peptides in SH-SY5Y human neuroblastoma cells. Nutr Metab (Lond). 2015 Dec 9;12:54.
- Cade R, Privette M, Fregly M, Rowland N, Sun Z, Zele V, Wagemaker H, Edelstein C. Autism and Schizophrenia: Intestinal Disorders. Nutr Neurosci. 2000;3(1):57-72.
- Svedberg J, de Haas J, Leimenstoll G, Paul F, Teschemacher H. Demonstration of beta-casomorphin immunoreactive materials in in vitro digests of bovine milk and in small intestine contents after bovine milk ingestion in adult humans. Peptides. 1985 Sep-Oct;6(5):825-30.
- Miller MJ, Witherly SA, Clark DA. Casein: a milk protein with diverse biologic consequences. Proc Soc Exp Biol Med. 1990 Nov;195(2):143-59.
- de Magistris L, Familiari V, Pascotto A, Sapone A, Frolli A, Iardino P, Carteni M, De Rosa M, Francavilla R, Riegler G, Militerni R, Bravaccio C. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr. 2010 Oct;51(4):418-24.
- Fiorentino M, Sapone A, Senger S, Camhi SS, Kadzielski SM, Buie TM, Kelly DL, Cascella N, Fasano A. Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism. 2016 Nov 29;7:49.
- Brondino N, Fusar-Poli L, Rocchetti M, Provenzani U, Barale F, Politi P. Complementary and Alternative Therapies for Autism Spectrum Disorder. Evid Based Complement Alternat Med. 2015;2015:258589.
- Clarke A, Trivedi M. Bovine Beta Casein Variants: Implications to Human Nutrition and Health. IPCBEE. 2014;67(3):11-17.
- Asledottir T, Le TT, Petrat-Melin B, Devold T, Larsen L, Vegarud GE. Identification of bioactive peptides and quantification of β-casomorphin-7 from bovine β-casein A1, A2 and I after ex vivo gastrointestinal digestion. International Dairy Journal. 2017;71:98-106.
Icons created by Mungang Kim, Nook Fulloption, Luis Prado, Pavel N., Alexandr Lavreniuk, and Gan Khoon Lay from The Noun Project.
Image credit: BlackCab (Self-taken) [CC BY-SA 3.0] via Wikimedia Commons. Image has been modified.
Motion graphics by Avocado Video
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Title
Does A2 Milk Carry Less Autism Risk?
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
This is the second in a six-video series on the role of gluten- and dairy-free diets in the treatment of autism. If you missed the first one, see Autism and Casein from Cow’s Milk.
The other videos in this autism series are:
- Gluten-Free, Casein-Free Diets for Autism Put to the Test
- Are Autism Diet Benefits Just a Placebo Effect?
- Double-Blind Clinical Trial of Diet for Autism
- Pros and Cons of Gluten-Free, Casein-Free Diets for Autism
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?.
I will continue to produce videos on autism. Catch all of the latest here.
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