Udderly New Insight About Milk and Autism: An Emerging New Hypothesis on A1 and A2 Beta-Casein

Reposted from December 31, 2008, NourishingHope.com

By Julie Matthews, Certified Nutrition Consultant

As an autism nutrition consultant, I’ve been supporting clients following the Gluten-Free Casein-Free (GFCF) diet for years.  Some of my clients would report that their child could handle goat’s milk or raw milk without allergic reactions. I began to wonder if all milk was created equally.

I conjured various theories: could the protein in goat’s milk be different than cow milk, was it the pasteurization process (absent in raw milk) that made the difference, was it something else, or a combination of factors?  Then, one of my clients introduced me to A1 and A2 beta-casein.

There are various types of casein.  Goat’s milk, as well as sheep and buffalo milk, contain A2 beta-casein. Raw milk, while often from cows, is typically produced from small herds of Jersey and Gernsey cows, both of which contain a high percentage of A2 beta-casein compared to most dairies that use mainly Holstein cow’s that produce a majority of A1 beta-casein.  Here’s what I have learned through my research about casein and A1 versus A2 beta-casein.

Beta-casein is a protein that contains bioactive peptides and opioids. Bioactive peptides are important for protecting the undeveloped immune system of newborns, and stimulate the growth and development of organs like the gastrointestinal tract and gut. Bioactive peptides have also been shown to kill bacteria that normally cause immune system infections. Opioids have pain-killing effects, sedative properties, induce sleep, and play a role in the control of food intake. Opioids can be produced by the body in the form of endorphins, or be absorbed from digested food, such as milk and wheat, in the form of casomorphins and gluteomorphins (opioid proteins). Several forms of beta-casein exist and make up 25-30% of the proteins in cow’s milk. There are approximately 13 beta-casein variants, with A1 and A2 variants being the most commonly occurring. A1 beta-casein contains the amino acid histidine at position 67 in the protein, while A2 beta-casein instead contains the amino acid proline at the same position. Studies have shown that when digested, A1 beta-casein breaks down to a casomorphin protein called beta-casomorphin-7 (BCM7). This is a direct result of the histidine amino acid that A1 beta-casein contains, as A2 beta-casein does not form BCM7 (1).

Several enzymes in the digestive tract process beta-casein including DPPIV, (dipeptidyl peptidase IV) and cause the break down of bioactive peptides and opioids. Studies suggest that the digestion of cow’s milk (containing A1 beta-casein), leads to the release of opioids, such as BCM7, and can cause harmful effects in children with autism (2) where DPPIV function may be impaired.  As this amino acid structure is more difficult to breakdown, those with compromised or weak digestion may accumulate opioids more readily. Additionally, when the gut is “leaky” (referring to increased gut permeability), these opioids end up in the blood stream in much greater concentrations than in those people with a healthy gut wall that does not leak. BCM7 is not produced when A2 beta-casein is digested, so goat’s, buffalo’s, and sheep’s milk that contain A2 beta-casein but not A1 beta-casein should not cause these harmful effects. There are other opioids that may also be formed; however, BCM7 appears to be the strongest.

As Jon Pangborn, Ph.D. describes, the enzyme DPPIV, which is also called CD26, has several other functions in the body, including involvement in signal transmission via lymphocyte receptors, and assisting the enzyme, ADA, in processing adenosine as an ADA binding protein. DPPIV is impaired by toxic heavy metals like mercury, lead and cadmium, a milk allergy, organophosphate insecticides, and yeast. Children with autism have greater toxic metal burdens, and one theory is that these heavy metals knock out this DPPIV enzyme, and the impaired DDPIV leads to improper processing of dairy and wheat. A supplemented plant analog version of DPPIV cannot substitute for the animal version completely, but it can certainly help.

While it is possible that A2 milk may also release opioids, Japanese and German scientists were unable to release BCM7 from A2 milk (1, 3). It appears that human breast milk may not release BCM7 either. Interestingly, this may explain why breastfeeding does not seem to cause a casein reaction to sensitive babies when dairy is avoided in a mother’s diet. In addition to affecting autism, research suggests that BCM7 may lead to the onset of several diseases, such as heart disease, diabetes, and schizophrenia (4).

Studies have also shown that wheat products, which contain gluten, also cause health problems for children with autism (5)  Gluten has long been established as a problematic protein for many individual, most well studied in celiac patients, causing inflammation in the gut, diarrhea, constipation, abdominal pain, digestive problems, and the improper absorption of nutrients.  Similar responses are seen in many children with autism (that are not diagnosed with celiac).  Gluten, along with an autistic person’s already compromised digestive system, can exacerbate the ability of the body to break down beta-casein.

Scientists believe that opioids like gliadomorphin (a gluten opioid) and BCM7 (a casein opioid) are toxic for children with autism due to the fact that these children have an abnormal, leaky, gastrointestinal tract (6). Instead of completely digesting and excreting these opioid proteins, some of the partially digested gluten and casein proteins leak out of the gut and are transported to other parts of the body before they can be completely digested. These opioid proteins travel through the bloodstream, cross the blood brain barrier (the barrier between the brain and the rest of the body), enter the brain, and stimulate morphine-like effects. Casein proteins (BCM7) negatively affect the brain by causing inattentiveness, unclear thinking, and irregular sleeping and eating patterns (7).

In children with autism, gliadomorphin and BCM7 can also cause the release of histamine, a chemical that regulates immune cell communication. Histamines are normally released in the body in response to an allergic reaction. This mis-regulation of immune cells weakens the immune system’s ability to ward off harmful viruses and bacteria that cause diseases.  This is consistent with the experience that many children with autism get frequent infections and illness.

Antibodies are also released to help target and remove unwanted opioid proteins. IgA is an antibody that can be found in blood, saliva, tears, and mucous membranes of the respiratory system and gastrointestinal tract. IgG antibodies are the most common antibodies in the body, and can be located in all bodily fluids. IgG antibodies are the only form of antibody that can cross the placenta in pregnant woman to protect a fetus (unborn baby). IgG antibodies also play a major role in fighting viral and bacterial infections. When the immune system detects foreign particles such as viruses, bacteria, fungi, or cancer cells it stimulates the production and release of antibodies. These antibodies attach to the foreign particles, labeling them as hazardous so that they can be destroyed and removed from the body (8). So while the peptides from casein or gluten trigger an IgG immune response, the opioids trigger an IgA immune response. So it is not just opioids that trigger an immune response, casein and gluten protein can do so also, just using different types of antibodies.

Studies have shown that in autistic and schizophrenic patients, large amounts of gliadomorphin and BCM7 can be detected outside the gut (8). This further indicates that their bodies are not able to properly break down and utilize these opioid proteins. These studies also showed that in 86% of schizophrenic patients, IgA antibodies that were targeting gluten were released into the body, and 67% had IgA antibodies that were targeting casein. In patients with autism, approximately 30% of the patients had IgA antibodies targeting gluten and casein present in the body. The release of IgG antibodies targeting gluten and casein were also detected in these patients. More than 80% of the autistic and schizophrenic patients had elevated levels of IgG antibodies in their blood.

In recent years, the adverse
effects of gluten and casein led researchers and to believe that autistic and schizophrenic patients should be placed on a gluten-free/casein-free diet, and this has become a widespread treatment for both diseases (9). Case studies that involved putting patients with schizophrenia and autism on a gluten-free/casein-free diet normally lead to some improvement of symptoms, but more clinical trials need to be performed to get a better picture of why this is the case. There is not enough data yet to understand all of the complexity behind gluten and casein and the challenges with them, but the experience of thousands of patients support the science we know so far: that a gluten-free/casein-free diet helps. And of course implementing the diet always depends on the patient’s needs, the caregiver’s willingness to try it, and professional supervision (10).

Schizophrenic patients who were put on a gluten-free/casein-free diet or treated with dialysis, a process that cleans the blood in order to rid the body of gliadomorphin and BCM7, were relieved of their symptoms, and low levels of the opioid proteins were detected. Approximately 81% of patients with autism who were put on a gluten-free/casein-free diet for at least 3 months were also relieved of their symptoms. A few parents, who stated that their child with autism had seizures before going on the diet, noticed that the frequency of the seizures either decreased or ceased all together. As previously stated, opioid proteins can cause an allergic response in the body, which leads to the release of histamines. Histamines have a direct effect on immune cell regulation. The disturbed immune response leads to a higher production of antibodies, such as IgA and IgG, as a means of further breaking down and excreting harmful gliadomorphin and BCM7 particles. In other words, the high levels of antibodies that are detected in patients with autism are a direct result of complications that occur when gluten and A1 beta-casein are consumed (8).

A vast majority of children that consume dairy consume cow milk products so removal of dairy on the GFCF diet would be the removal of A1 beta-casein in most instances. This may be the reason the GFCF diet is so successful for children on the autism spectrum.  I’d like to pose a new hypothesis, maybe it is not ALL casein but the A1 beta-casein that is actually the primary problem with milk for children with autism.

With that said, there are most likely are other reactions and problems with dairy for some (if not many) individuals, so I do not think this preliminary information justifies abandoning the GFCF diet.  (In fact, I hesitated writing and talking about this topic for a long time, as I did not want to confuse parents new to diet.)  I have seen many wonderful results from GFCF and know many clients that cannot seem to tolerate goat or raw dairy.  I don’t want children to miss out of the full benefit from diet by not trying a GFCF diet.

Through my clinical experience, I have found that it is very important to give the GFCF diet a complete trial, free of any infractions.  Once a child has been on this diet for 3-6 months and you see what progress can be made with it, then and only then, do I feel that a parent may experiment with diet and try adding goat’s milk or some other A2 milk back.  It seems that for some children, their casein sensitivity is mild and A2 milk works well.  For others, once the gut is healed, they are able to consume small amounts of A2 milk.  I often hear that as a child’s digestive systems improve, they are able to handle goat’s milk yogurt or raw milk. It is possible that the BCM7 issue is a primary factor for some people, and that A2 milk may provide an option for some individuals.

While milk is not “necessary” in the diet, dairy has health benefits when the individual is not intolerant to it.  (Note that when people are intolerant, it can be very harmful regardless of the “benefits.”)  If there is a way to include some dairy in some children’s diets, there can be a positive benefit to having this flexibility and nutrition in the diet.  Dairy makes wonderful probiotic-rich fermented foods such as yogurt and kefir to support a healthy intestinal tract—and often nuts, nut milk and coconut-based fermentations are not tolerated.  Dairy contains essential fatty acids, fat-soluble vitamins A, D, and K, and calcium.  Additionally, as I describe in Nourishing Hope for Autism, butyrate, (also butyric acid), found in dairy, “has been shown to clear ammonia and nitrogen, modulate local electrolyte flux, supports the reduction of diarrhea and improves very large, hard stools. Butyric acid also supports and fuels the intestinal walls to support a healthy gut and is used as an anti-candida substance.”   Raw dairy contains phosphatase (an enzyme important for calcium absorption), probiotics, unadulterated protein, and higher nutritional content (because of what is normally destroyed during pasteurization and because they are pasture-grazed).  This new A1 and A2 information may allow some children with autism to receive the benefits of milk without the problems it can cause.

Please share your experience with A2 milk.

References

1. Jinsmaa Y, Yoshikawa M. (1999) Enzymatic release of neocasomorphin and beta-casomorphin from bovine beta-casein. Peptides, 20:957-962.

2. Reichelt KL, Knivsberg AM, Lind G, Nodland M: Probable etiology and possible treatment of childhood autism. Brain Dysfunction 1991; 4: 308-319.

3. Hartwig A, Teschemacher H, Lehmann W, Gauly M, Erhadt G. (1997) Influence of genetic polymorphism in bovine milk on the occurence of bioactive peptides. In: Milk Protein Polymorphism, International Dairy Federation Special Publication, Brussels, Belgium. 9702 :459-460.

4. Kamiński S, Cieslińska A, Kostyra E. (2007) Polymorphism of bovine beta-casein and its potential effect on human health. The Journal of Applied Genetics, 48(3):189-198.

5.  Jyonouchi H, Geng L, Ruby A, Reddy C, Zimmerman-Bier B. (2005) Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. J Pediatr. May;146(5):582-4.

6. Shattock P, Whiteley P. (2002) Biochemical aspects in autism spectrum disorders: updating the opioid-excess theory and presenting new opportunities for biomedical intervention. Expert Opin Ther Targets. Apr;6(2):175-83

7. Sun Z, Zhang Z, Wang X, Cade R, Elmer Z, Fregly M. (2003) Relation of beta-casomorphin to apnea in sudden infant death syndrome. Peptides, 24:937–943.

8. Cade R, Privette R, Fregly M, Rowland N, Sun Z, Zele V. (2000) Autism and schizophrenia: intestinal disorders. Nutritional Neuroscience, 3: 57–72.

9. Knivsberg AM, Reichelt KL, Nodland M. (2001) Reports on dietary intervention in autistic disorders. Nutritional Neuroscience, 4(1):25-37.

10. Knivsberg AM, Reichelt KL, Hoien T, Nodland M. (2002) A randomised, controlled study of dietary intervention in autistic syndromes. Nutritional Neuroscience, 5(4):251-61.

Originally published December 31, 2008.  Republished February 2011.

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26 Comments

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  1. sz May 30, 2009 at 6:34 pm #

    what about the dangers of unpasturized milk?

  2. barry jennings June 1, 2010 at 1:20 pm #

    I have a daughter who is ADHD and she is very tiny for a 10 year old, so i am always looking for diet tip info like you have here on your site,thanks!

  3. Michelle August 1, 2011 at 10:42 pm #

    Wow! You just summed up the past 3 1/2 years of learning about the diet and trying to explain to friends why it works! The GFCF diet has been a miracle worker for our son. He was not speaking much, and after just 3 days started talking!!! We tested the theory a few weeks later and sure enough, went back to almost silence when given Gluten and Casein. I just wish more parents were willing to do the work to heal their children. Don’t get me wrong…there are many causes of Autism, but for those with the food sensativities…it changes lives and their future!
    Thank you!!!!

    • Julie Matthews August 1, 2011 at 11:20 pm #

      Thanks for your comments Michelle! It’s so helpful for other parents to hear your experience and the possibilities for children with autism.

  4. Steve August 4, 2011 at 4:07 pm #

    Thank you for elucidating the mechanisms that contributed (or directly caused) my sister-in-law’s early demise.

    I researched and found info on casomorphins almost ten years ago, prompted by Trish’s milk addiction….she would be uneasy if there was less than two gallon jugs of industrial grade milk in the fridge.

    I pointed her to notmilk.com, and other info, but to no avail, like other true addicts…..I got the “you’re not a doctor” treatment.
    Dead at 62 (stroke), outlived by both father and mother. A tragedy.
    Industrial milk kills!

  5. AnnabethK June 3, 2012 at 9:08 pm #

    I realize that I’m a little late seeing this article and maybe you have since discovered what I am about to write. I have been on a gluten-free, cow’s milk-free diet for some time, due to a severe case of hyperthyroidism. My condition is an immune disorder, as are other allergic conditions. I am currently able to eat goat’s milk and sheep’s milk cheese.

    I have been working with a practitioner of Clinical Kinesiology, which is a very advanced version of Applied Kinesiology. The field of Applied Kinesiology allows the practitioner to assess whether an individual food causes adverse reactions in an individual, using an assessment tool called “muscle testing”.

    Using Clinical Kinesiology, my doctor is able to assess which foods I am allergic to. This way, I do not need to try the foods out myself and risk experiencing a debilitating allergic reaction. Over time, we can re-assess whether my immune system can handle foods it was previously unable to tolerate.

    Allopathic medicine does not acknowledge the value of this assessment process but each patient can decide for him or herself. The process is safe and has no risk.

    If a patient cannot find a practitioner of Clinical Kinesiology, I suggest at least finding a health care practitioner who practices Applied Kinesiology.

  6. Snow Shoes For Zebra August 15, 2012 at 6:03 pm #

    Thanks so much for this article Julie,

    It’s a delight for me to read.

    I can’t help but wonder how many Udder Nazi’s will be totally outraged by the mere suggestion of what you are saying here. Not that I think they would ever go anywhere near an artcle like this. I’m sure they would need to be force fed it.

    I am a mother that recovered 2 children from Autism while using A2 and raw organic dairy. I was actually kicked off a popular Aussie Biomed forum (they know who they are) for saying that I had used those specific kinds of dairy for my children all along the biomed journey. I did not suggest anyone else use it, just told of my experience with it. Oh boy did it get nasty!

    So glad someone with your credability in the biomed community came out and mentioned that this may be a possibility for some children.

    LOL

    Snow Shoes For Zebra

  7. Leila December 14, 2012 at 10:45 am #

    Thank you for very informative article. My son suffers from milk protein intolerance/ digestive issues and eczema and I may try him on A2 milk or raw milk in the future to see if he can digest them better and benefit from the live enzymes and good bacteria which he is missing ….

  8. MimiLee February 3, 2013 at 8:13 am #

    While not autistic, I am unable to tolerate A1 caseine containing milk OR raw milk, but goat and sheep milk, cheese and yogurt don’t seem to bother me. I get extremely tired, immobilized, heavy, and peaceful (for a time that leads to anxiety later) after consuming regular cow dairy, a definite opiate reaction! I also get an uncomfortable feeling of irritation in my gut which isn’t pleasant!

    • Chris February 23, 2013 at 8:32 pm #

      Wow, that’s crazy, I get the exact same opiate reaction from cow milk, I basically feel strung out for some hours and my gut doesn’t like it. After I had been on goat milk/cheese for a few weeks and then went back to cow milk I noticed how strong this effect is on me, and was shocked I had been drinking the stuff since childhood. I also noticed cow milk has a weird after taste compared to goat milk, kinda sharp and a little bitter, not pleasant at all

  9. Kathryn March 6, 2013 at 4:11 am #

    I was a leaky gut case with lactose intolance until I lived in Europe, where I learned to drink raw, unpasteurized milk. Thank you for the clear explanation of th white-cow/brown -cow story.

  10. Anonymous April 12, 2013 at 2:42 pm #

    “Scientists believe that opioids like gliadomorphin (a gluten opioid) and BCM7 (a casein opioid) are toxic for children with autism due to the fact that these children have an abnormal, leaky, gastrointestinal tract (6).”

    Well scientists know that gluten/gliadin causes leaky gut in the first place, and is one of the only things known to do so.

    Look up zonulin on pubmed and wikipedia for more information.

    • Julie Matthews April 12, 2013 at 5:13 pm #

      Great point! Not only in gluten a problem when the gut is leaky – it can CAUSE leaky gut. Thanks for mentioning it and reminding us of this great point.

  11. Luana April 30, 2013 at 1:06 pm #

    Do we have to check our autism children IgA and IgG levels before we decide keep allow them drink milk (A1 or A2 or replace it to soy milk that she unwanted for sure)? I don’t see differences between when my daughter drink/eat dairy products and when she’s not. But my colleague said perhaps better if she stop dairy products and gluten free. What test should she do, to know more about her better diet?
    many thanks

  12. Monica Harris May 26, 2013 at 2:11 pm #

    I would like to fully disclose my background and then give my opinion on the A2 milk question. I am a Speech Language Pathologist with Asperger’s and work exclusively with kindergarten through high school ASD students. My husband has a small (very small) raw milk business that provides A2 milk to persons with ASD, the Mennonite Community in our area and other health conscious people in our area. We did not start the dairy for the A2 aspect, but got interested when a friend gave us Keith Wood ford’s book, THE DEVIL IN THE MILK. With that and other research in hand I convinced my husband to test our Jerseys ($25 a cow was not cheap!). All but one was A2/A2. We have had reports from people that have children with allergies, “suspected” lactose intolerance, those with ASD and me that they can drink our milk without digestive or behavioral effects that commercial A1 milk produces. We all know that “if you have seen one person with Autism, you have seen one person with Autism”. I have seen first hand the changes in students that are on a strict CFGF diet and sadly those that are not. There is a marked difference in focus, tolerance levels with sensory issues and skills acquisition in these students on a CFGF diet. A2 milk is not medicine. A2 milk is not a cure all. But it is not snake oil. There is a real difference in the make-up of the milk produced in the large commercial diaries and what an exclusively A2 dairy can provide. I would try to find a farmer that has a Jersey or Guernsey cow and try the milk. Those breeds are typically A2. If the farmer will let you, the cow can be tested by sending tail hairs to a certified lab. If you are interested I can give you that information off line. I am not trying to sell our milk here. I am trying to broaden the awareness of the real health and behavioral changes that occur when the opiod producing beta-casomorphin-7 found in A1 milk is removed from the diet.

    • Jeff Knight August 25, 2013 at 4:03 am #

      Dear Monica,

      We are a small raw milk dairy in Idaho and milk Ayrshire cows. I would be interested in the link to test for A2 cows. We are also pature based program.

      I had a customer ask me about raw milk and autism today at the farmers market today.

      Thanks
      Jeff Knight

    • CHIKA27 August 29, 2013 at 6:17 pm #

      Thanks this article in general has made me more confortable with trying raw milk. We have been GFDF since March and I go back to dairy myself from time to time. My Daughter was diagnosed with autism then and we have seen great improvements. My children have never been able to handle dariy well and have been on rice or almond milk. I am excited to have an option for me and my kids that I can feel like I am not harming them.

  13. Lynn August 10, 2013 at 8:32 pm #

    Thank you for this very clear explanation. My son has been on the diet for 3 1/2years. He also takes several supplements , probiotics and digestive enzymes. Yes it is not easy and expensive but if there is anything I can do to improve his quality of life and relieve him of some of his symptoms I’m doing it. It has helped tremendously with his behavior and tantrums (which are pretty much nonexistent now). His is nonverbal and although his language hasn’t come yet it is emerging and I am confident if we stay the course it will come. I agree with the other mom that said she wishes more parents would try it for their kids. I see kids that I know would be helped by going on the diet but the parent’s response is that it is too hard….it breaks my heart.

  14. Pam October 9, 2013 at 5:55 pm #

    Thank you for this article. Going to change my daughters diet ASAP. She has Triple X and is a Fragile X carrier. I am dealing with behavioral and discipline issues……..ADHD, sensory, OCD, Dyslexia, etc. I am praying this change will have the great affect on her that your article implies. Would only make sense that it would. Sure couldn’t hurt. Anything will be better than all of the meds that have been subscribed to my poor eight year old over the past several years. I am so excited. Sorry I didn’t find this sooner. :(

  15. Marcelo February 10, 2014 at 6:44 pm #

    Please,
    I was giving pasteurized cow milk kefir to my son, 1,5yr, and it was not just fine, it was improving something, I was feeling he was great. But After read about casein A1, I stop to gave. The only difficulty he show with digestion was a little reflux, he used to show that he was full even hours after the last food. For sure when I took of the infant milk formulas it almost finish. As he is almost not talking I decide to try GFCF…
    Sorry for my english!

  16. kathi February 19, 2014 at 2:11 pm #

    Julie,
    i would love to know if in your practice you’ve used raw milk w/ autistic children adn how they reacted (good and bad). also if any of those kids had major reflux/ftt as an infant toddler due to using formula/processed milk.
    thanks kathi

  17. Sandra Prazeres March 6, 2014 at 2:02 pm #

    Definitely ever since, I put my daughter, which has autism on GF/CF/SF diet, I could see HUGE difference on her behavior and learning. I heard about raw goat cheese has also casein, that drove me crazy, once that is the only cheese I thought she was able to eat. I noticed, every time I give to her piece of raw cheese, her uncomfortable reaction. WOW. I’m thankful for that explanation.

  18. Don R. April 8, 2014 at 1:09 am #

    Dear Julie,
    your article is helping so many people thanks to your outstanding explanation of the problem.
    I just wanted to add that (GFCF) diet is also very effective for many other illnesses.
    In a rare case if it will not completely eliminate symptoms of autism some parents should consider parasite cleansing since parasites also can be one of the major causes of autism.

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