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A Randomized Controlled Dietary Trial for Autism

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What were the results of the first randomized controlled study of a dietary intervention for Autism Spectrum Disorder (ASD)?

At the start of my video Gluten-Free, Casein-Free Diets for Autism Put to the Test, I discuss the so-called opioid-excess theory of autism, which states 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 theory started when opioid peptides were apparently discovered in the urine of children with autism, but missing from the urine of children who develop normally, as you can see at 0:27 in my video. A decade later, however, a more specific test failed to find urinary opioid peptides in children with autism. As shown at 0:41 in my video, the spectral analysis of urine from children with autism is practically identical with that of those without autism, so the whole theory was called into question…until an even more sensitive test was developed.

“Elevated concentrations of circulating casomorphins (CM), the exogenous opioid peptides from [bovine] milk casein, may contribute to the pathogenesis [development] of autism in children. Because several mass spectrometry studies failed to detect casomorphins in autistic children, it was questioned…” until researchers were able to demonstrate that autistic children do indeed have evidence of significantly higher levels of urine bovine casomorphins than children without autism, as you can see at 1:15 in my video. Furthermore, the “severity of autistic symptoms correlated with concentrations of CM-7 [casomorphins] in the urine.” The more casomorphins they had flowing through their body, the worse their autism symptoms tended to be. The researchers continued: “Because CMs [casomorphins] interact with opioid and serotonin receptors, the known modulators of synaptogenesis”—the creation of nerve-to-nerve connections within the brain—“we suggest that chronic exposure to elevated levels of bovine CMs may impair early child development, setting the stage for autistic disorders.” 

If increasing exposure to casomorphin opioids from cows’ milk is correlated with increasing severity of autism symptoms, as you can see at 2:03 in my video, why not just give 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 it even is a cause, but, if it is, to also see if we can actually help these children? 

It started with case reports, such as: “A seven year old girl with autistic behaviour who benefited from a diet without gluten and casein…” Quite remarkably, “over the period of two years the girl changed from being severely withdrawn to a normally communicating child who enjoys the company of others.” What’s more, her dramatic improvements seemed to correlate with decreasing urine peptide levels after one year, then two years, as you can see at 2:54 in my video. 

Could this one case have just been a fluke? Some doctors figured it was worth a try and published spectacular results, claiming 80 percent of their child patients with autism improved after three months of a gluten-free, casein-free diet. Even just cutting out casein, the cow’s milk protein, appeared to lead to “a marked improvement in the behavioural symptoms…” None of these studies had a control group, however. It wasn’t until 2002 when the first randomized controlled study of a dietary intervention in autistic syndromes was published. Twenty children with autism participated in the study, and half were randomized to a gluten- and casein-free diet for a year. They were tested before and after. How did those on the diet do? “The development for the group of children on diet was significantly better than for the controls.” Okay, but did better how? 

At 3:51 in my video, you can see the “resistance to communication and interaction” scores of all 20 kids in the study before and after the year-long experimental period. In the control group, two children got better, two got worse, and the rest were as bad off as they had been when the study started. In the diet group, however, they all got better. “Social isolation” scores were also tested. In the control group, half got better, while the other half got worse or stayed the same. In the diet intervention group, once again, they all got better. Overall, in terms of “total impairment scores for both social isolation and bizarre behaviour,” half got better and half got worse in the control group, but they all got better in the diet group. 

What does all of this mean in real-life terms, rather than just numbers? “All the participants initially shared a most common trait in autistic syndromes, lack of peer relationships. Some ignored other children, while others tried to make contact, but did not know how to interact. Some had abnormal temper tantrums. Paradoxical and strange emotional expressions were displayed by some, like laughing when other people cried…” As well, 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 common traits in autistic syndromes. Some of the children could suddenly hit or bite others, or they could 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 in the diet group after the [year-long] experimental period was over. While none of the changes were significant in the control group, significant [positive] changes were registered in the diet group regarding peer relationship, anxiety, empathy, and physical contact.”

This article discusses the third video in a six-part series on the role of gluten- and dairy-free diets in the treatment of autism. In case you missed the first two, see and Autism and Casein from Cow’s Milk and Does A2 Milk Carry Less Autism Risk?.

Stay tuned for the rest of the series:

Keep abreast of all of my videos on autism 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:

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:


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