Double-Blind Clinical Trial of Diet for Autism

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The first randomized, controlled study of a gluten-free, casein-free diet for autism found that parents in the diet group reported their kids did “significantly better.” But, that could just be the placebo effect—where parents attribute changes to the diet, particularly since they’re putting so much work into it that they may be “biased towards seeing evidence of success” that may not actually be there.

Okay; so, what if you don’t just rely on parental report? What if you do a blinded study of a gluten- and casein-free diet? The parents know what the kids are eating, but you don’t just ask the parents how the kids are doing; you have investigators objectively assess all the kids, without knowing who was in which group—the diet group or the control group. And, they found “a significant beneficial…effect at 8, 12, and 24 months…on core autistic…behaviours” with a gluten- and casein-free diet. And, this was one of the largest such studies ever done—starting out with 73 children. But, they didn’t end up with 73, since about a fifth dropped out—mostly from the diet group.

“If a family didn’t feel their child was making strides on the diet, they may have been more likely to drop out of the study, thereby skewing the analysis toward those” in which the diet appeared to work better. And so, the remarkable results they got in terms of improved social interaction and fewer ADHD-type symptoms may have ended up exaggerating the effects of the diet, since the kids for which it didn’t help may have been, gotten kind of, disproportionately weeded out. Also, because the parents were very much aware whether they were in the diet group versus the control group—because they were the ones cooking the meals—they may have changed their own behavior towards their children.

Like in that famous sugar study where mothers were lied to, and told their children had just received a whopping dose of sugar (even though they hadn’t). Not only did the mothers rate their children “as significantly more hyperactive”; they inadvertently changed their own behavior. They were videotaped, and the mothers who falsely believed their kids just got a load of sugar “exercised more control” and were more critical. So, their expectation of an effect may have actually ended up having an actual effect in changing their children’s behavior. So, in these autism studies, here the parents are upending their family’s diet, hoping, expecting that their child will get better, and maybe unconsciously treating them differently—such that they end up behaving differently when assessed later by the blinded investigators.

That’s why we need double-blind studies, where no one knows who’s in the diet group, who’s in the control group—not the parents, not the kids. So, why didn’t the researchers do it? Why didn’t they secretly sneak some gluten or casein into their diets to see if they got worse again? Same excuse as before; it wouldn’t be “ethical.” But, that’s pre-deciding the outcome; that’s like circular logic. We can’t test to see if it really works, because it may really work—but we can’t test that.

Finally, however, researchers at the University of Florida broke through the impasse by performing a double-blind study. Now, this is not an easy thing to do. I mean, you have to provide “all meals and snacks,” so that the families remain clueless as to whether they were randomized into the gluten- and casein-free diet group, or were actually in the control group getting the same foods, but with gluten and casein slipped in. Then, after six weeks, they switched the foods, so the gluten-free, casein-free group started getting wheat and dairy, and the wheat and dairy control group were covertly switched to gluten- and casein-free.

Before they broke the codes to see who was in which group, the “parents were asked [as to] whether they thought their child was on the [special] diet during the first or second 6 weeks.” And: “Five [got it right], two had ‘‘no idea’’, and six [got it wrong].” In other words, no better than a flip-of-a-coin chance. About half pretty much thought their kids got better on the casein and gluten; so, “no statistically significant findings”—though several parents did report an “improvement…in their children,” claiming “marked improvements in…language, decreased hyperactivity and decreased tantrums”—so much so that a bunch of the parents “decided to keep the children on the…diet,” even though the researchers just told them that it didn’t work.

Look; you don’t want to miss anything, though. Some of the parents claimed significant improvement. So, what the researchers did was to go back and examine the videotapes they made of the kids before and after and showed them to blinded examiners. Did their language really get better? Apparently not. The videotapes showed no improvement, so again, did “not support the efficacy of [a gluten-free, casein-free diet]” for improving some of the core symptoms of autism—or, at least, within six weeks’ time. The non-double-blind studies that showed an effect had kids on the diet for a year or two. And so, the failure to find an effect in the double-blind study “should not necessarily be interpreted to mean that [diet] does not work,” given “the relatively shorter duration of [dietary] intervention…”

The same issue cropped up years later in a 2014 study in Texas. Simple study design: put everyone on a gluten-free, casein-free diet, and then randomize parents to get baggies each week filled with either gluten-free, casein-free brown rice flour—thereby sticking to the diet—or, an identical-looking powder with gluten and milk mixed in. So, no one knew until the end who really remained gluten- and casein-free, and…no, meaningful changes were found in either diet group. Okay, but this study only lasted four weeks, and diet proponents suggest it may take months off gluten and casein to properly assess a response.

The problem is there hadn’t been any double-blind studies that lasted that long…until, now. We’ll find out what they found, next.

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Image credit: CMRF Crumlin. Image has been modified.

Motion graphics by Avocado Video

• autism
• brain health
• casein
• casomorphins
• children
• dairy
• gluten
• infants
• milk
• placebo effect
• protein
• sugar
• wheat