What were the results of the first randomized controlled study of a dietary intervention for Autism Spectrum Disorder (ASD)?
Gluten-Free, Casein-Free Diets for Autism Put to the Test
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.
The so-called “opioid-excess theory of autism” is that when certain wheat and dairy proteins are ingested, morphine-like protein fragments are created that then leak into the bloodstream, cross into the brain, and cause neurological damage that can manifest as autism. The whole theory started with the apparent discovery of these opioid peptides in the urine of children with autism, but missing from the urine of children who develop normally. But, a decade later, a more specific test failed to find urinary opioid peptides in children with autism. The spectral analysis of urine from autistic children—the pink line here—is practically identical with that of those without autism. And so, the whole theory was called into question…until, a more sensitive test was developed.
“Elevated concentrations of circulating casomorphins…, the exogenous opioid peptides from [bovine] milk casein, may contribute to the [development] of autism in children.” But, “[b]ecause several…studies failed to detect casomorphins in autistic children,” this was called into question. “Here, however, [they] demonstrated…that autistic children [do indeed] have [evidence of] significantly higher levels of urine bovine [casomorphins than normal children]. Furthermore, “[t]he severity of autistic symptoms correlated with [casomorphin] concentrations…” The more casomorphins they had flowing through their body, the worse their autism symptoms tended to be. “Because [casomorphins] interact with opioid and serotonin receptors, the known modulators of synaptogenesis [—the creation of nerve-to-nerve connections within the brain—] maybe “chronic exposure to elevated levels of bovine [casomorphins] may impair early child development, setting the stage for autistic disorders.” But you don’t know, until you put it to the test.
If increasing exposure to casomorphin opioids from cow’s milk is correlated with increasing severity of autism symptoms, why not just try giving kids opioid-blocking drugs? That’s such the medical mentality.
Instead, why not try to treat the cause with a dietary intervention? Not only to see if, indeed, it even is a cause, but if it is, to see if we can actually help these children. It started with case reports like this, where a seven-year-old girl with autistic behavior was described as benefiting from a gluten-free, casein-free diet—a quite remarkable case in which, “[o]ver [a] period of two years, the girl changed from being severely withdrawn to a normally communicating child who enjoy[ed] the company of others.” And, her dramatic improvements seemed to correlate with decreasing urine peptide levels after one year, then two years. Okay. But, maybe this one case was just a fluke.
Some docs figured it was worth a try, and published spectacular results like this—claiming 80% of their autistic children improved after three months of a gluten-free, casein-free diet. Even just specifically cutting out the cow’s milk protein, the casein, appeared to lead to “marked improvement in…behavioural symptoms.” But, none of these studies had a control group. It wasn’t until 2002 when the first “Randomised, Controlled study of [a] Dietary Intervention in Autistic Syndromes” was published. Twenty children with autism, half randomized to a gluten- and casein-free diet for a year, tested before and after. And…those on the diet did better. Did better how?
Here’s where the “resistance to communication and interaction” scores of all 20 kids started out in the diet group and the control group. This is the before. If there was no change after a year for any of the kids, the bars would end up looking like this—the same before and after. The gray is the before; the black is the after. But, the control group actually ended up like this; so, two got better. (Remember this is resistance to communication and interaction; so, the lower the better.) Two got worse, and the rest were just as bad off as they were when they started. But, in the diet group, they all got better.
Social isolation scores. Again, the lower the better. In the control group, half got better; half got worse, or stayed the same. In the diet intervention group, they all got better.
Overall, in terms of total impairment, half got better, and half got worse in the control group, but in the diet group, they all got better.
What does that mean in terms of real-life terms, instead of just numbers? All the kids started out sharing “the most common [autistic] trait”—lack of relationships with their peers, ignoring other children, or “not know[ing] how to interact. Some…had abnormal temper tantrums…or strange emotional [reactions]…, like laughing when other people cried.”
“Extreme anxiety” was noted in some of the children in response to common situations. “These unusual emotions were drastically reduced in the diet group, but not in the control group. Inability to take other people’s perspective and lack of empathy [are] also [other] common [autistic] traits. Some of the children could suddenly hit or bite others, or…[would] make negative comments. Progress was made regarding development of empathy in the diet [group], but not in the control group. Some children also disliked and rejected physical contact, even from their parents. This was no longer a problem [after a year on the diet].”
“While none of the changes were significant in the control group, significant [positive] changes were registered in the diet group, regarding peer relationship[s], anxiety, empathy, and physical contact.”
Please consider volunteering to help out on the site.
- Lucarelli S, Frediani T, Zingoni AM, Ferruzzi F, Giardini O, Quintieri F, Barbato M, D'Eufemia P, Cardi E. Food allergy and infantile autism. Panminerva Med. 1995 Sep;37(3):137-41.
- Roy A, Roy M, Deb S, Unwin G, Roy A. Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review. J Intellect Disabil Res. 2015 Apr;59(4):293-306.
- Sokolov O, Kost N, Andreeva O, Korneeva E, Meshavkin V, Tarakanova Y, Dadayan A, Zolotarev Y, Grachev S, Mikheeva I, Varlamov O, Zozulya A. Autistic children display elevated urine levels of bovine casomorphin-7 immunoreactivity. Peptides. 2014 Jun;56:68-71.
- Cass H, Gringras P, March J, McKendrick I, O'Hare AE, Owen L, Pollin C. Absence of urinary opioid peptides in children with autism. Arch Dis Child. 2008 Sep;93(9):745-50.
- Reichelt KL, Knivsberg AM. Can the pathophysiology of autism be explained by the nature of the discovered urine peptides? Nutr Neurosci. 2003 Feb;6(1):19-28.
- Knivsberg AM, Reichelt KL, Nødland M. Dietary Intervention for a Seven Year Old Girl with Autistic Behaviour. Nutr Neurosci. 1999;2(6):435-9.
- 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.
- Hurwitz S. The gluten-free, casein-free diet and autism: limited return on family investment. Journal of Early Intervention 2013; 35(1): 3-19.
- Knivsberg AM, Reichelt KL, Høien T, Nødland M. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci. 2002 Sep;5(4):251-61.
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.
The so-called “opioid-excess theory of autism” is that when certain wheat and dairy proteins are ingested, morphine-like protein fragments are created that then leak into the bloodstream, cross into the brain, and cause neurological damage that can manifest as autism. The whole theory started with the apparent discovery of these opioid peptides in the urine of children with autism, but missing from the urine of children who develop normally. But, a decade later, a more specific test failed to find urinary opioid peptides in children with autism. The spectral analysis of urine from autistic children—the pink line here—is practically identical with that of those without autism. And so, the whole theory was called into question…until, a more sensitive test was developed.
“Elevated concentrations of circulating casomorphins…, the exogenous opioid peptides from [bovine] milk casein, may contribute to the [development] of autism in children.” But, “[b]ecause several…studies failed to detect casomorphins in autistic children,” this was called into question. “Here, however, [they] demonstrated…that autistic children [do indeed] have [evidence of] significantly higher levels of urine bovine [casomorphins than normal children]. Furthermore, “[t]he severity of autistic symptoms correlated with [casomorphin] concentrations…” The more casomorphins they had flowing through their body, the worse their autism symptoms tended to be. “Because [casomorphins] interact with opioid and serotonin receptors, the known modulators of synaptogenesis [—the creation of nerve-to-nerve connections within the brain—] maybe “chronic exposure to elevated levels of bovine [casomorphins] may impair early child development, setting the stage for autistic disorders.” But you don’t know, until you put it to the test.
If increasing exposure to casomorphin opioids from cow’s milk is correlated with increasing severity of autism symptoms, why not just try giving kids opioid-blocking drugs? That’s such the medical mentality.
Instead, why not try to treat the cause with a dietary intervention? Not only to see if, indeed, it even is a cause, but if it is, to see if we can actually help these children. It started with case reports like this, where a seven-year-old girl with autistic behavior was described as benefiting from a gluten-free, casein-free diet—a quite remarkable case in which, “[o]ver [a] period of two years, the girl changed from being severely withdrawn to a normally communicating child who enjoy[ed] the company of others.” And, her dramatic improvements seemed to correlate with decreasing urine peptide levels after one year, then two years. Okay. But, maybe this one case was just a fluke.
Some docs figured it was worth a try, and published spectacular results like this—claiming 80% of their autistic children improved after three months of a gluten-free, casein-free diet. Even just specifically cutting out the cow’s milk protein, the casein, appeared to lead to “marked improvement in…behavioural symptoms.” But, none of these studies had a control group. It wasn’t until 2002 when the first “Randomised, Controlled study of [a] Dietary Intervention in Autistic Syndromes” was published. Twenty children with autism, half randomized to a gluten- and casein-free diet for a year, tested before and after. And…those on the diet did better. Did better how?
Here’s where the “resistance to communication and interaction” scores of all 20 kids started out in the diet group and the control group. This is the before. If there was no change after a year for any of the kids, the bars would end up looking like this—the same before and after. The gray is the before; the black is the after. But, the control group actually ended up like this; so, two got better. (Remember this is resistance to communication and interaction; so, the lower the better.) Two got worse, and the rest were just as bad off as they were when they started. But, in the diet group, they all got better.
Social isolation scores. Again, the lower the better. In the control group, half got better; half got worse, or stayed the same. In the diet intervention group, they all got better.
Overall, in terms of total impairment, half got better, and half got worse in the control group, but in the diet group, they all got better.
What does that mean in terms of real-life terms, instead of just numbers? All the kids started out sharing “the most common [autistic] trait”—lack of relationships with their peers, ignoring other children, or “not know[ing] how to interact. Some…had abnormal temper tantrums…or strange emotional [reactions]…, like laughing when other people cried.”
“Extreme anxiety” was noted in some of the children in response to common situations. “These unusual emotions were drastically reduced in the diet group, but not in the control group. Inability to take other people’s perspective and lack of empathy [are] also [other] common [autistic] traits. Some of the children could suddenly hit or bite others, or…[would] make negative comments. Progress was made regarding development of empathy in the diet [group], but not in the control group. Some children also disliked and rejected physical contact, even from their parents. This was no longer a problem [after a year on the diet].”
“While none of the changes were significant in the control group, significant [positive] changes were registered in the diet group, regarding peer relationship[s], anxiety, empathy, and physical contact.”
Please consider volunteering to help out on the site.
- Lucarelli S, Frediani T, Zingoni AM, Ferruzzi F, Giardini O, Quintieri F, Barbato M, D'Eufemia P, Cardi E. Food allergy and infantile autism. Panminerva Med. 1995 Sep;37(3):137-41.
- Roy A, Roy M, Deb S, Unwin G, Roy A. Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review. J Intellect Disabil Res. 2015 Apr;59(4):293-306.
- Sokolov O, Kost N, Andreeva O, Korneeva E, Meshavkin V, Tarakanova Y, Dadayan A, Zolotarev Y, Grachev S, Mikheeva I, Varlamov O, Zozulya A. Autistic children display elevated urine levels of bovine casomorphin-7 immunoreactivity. Peptides. 2014 Jun;56:68-71.
- Cass H, Gringras P, March J, McKendrick I, O'Hare AE, Owen L, Pollin C. Absence of urinary opioid peptides in children with autism. Arch Dis Child. 2008 Sep;93(9):745-50.
- Reichelt KL, Knivsberg AM. Can the pathophysiology of autism be explained by the nature of the discovered urine peptides? Nutr Neurosci. 2003 Feb;6(1):19-28.
- Knivsberg AM, Reichelt KL, Nødland M. Dietary Intervention for a Seven Year Old Girl with Autistic Behaviour. Nutr Neurosci. 1999;2(6):435-9.
- 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.
- Hurwitz S. The gluten-free, casein-free diet and autism: limited return on family investment. Journal of Early Intervention 2013; 35(1): 3-19.
- Knivsberg AM, Reichelt KL, Høien T, Nødland M. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci. 2002 Sep;5(4):251-61.
Motion graphics by Avocado Video
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Gluten-Free, Casein-Free Diets for Autism Put to the Test
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Content URLDoctor's Note
This is the third in a six-video series on the role of gluten- and dairy-free diets in the treatment of autism. In case you missed the first two, see Autism and Casein from Cow’s Milk and Does A2 Milk Carry Less Autism Risk?.
The other videos in this autism series are:
- 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 will continue to produce videos on autism. Catch all of the latest here.
Casomorphins—breakdown products of casein, a milk protein, with opiate-like activity—may also play a role in sudden infant death syndrome (SIDS), also known as crib death. See:
- Cow’s Milk-Induced Infant Apnea
- Cow’s Milk Casomorphin and Crib Death
- Cow’s Milk Casomorphin and Autism
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