 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. OK, 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 behaviors 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 towards 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 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 they'd 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 families' 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, it'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-free 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 food 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 six 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. The 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 market improvements in language and decreased hyperactivity, 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 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 videotape showed no improvement, so again did not support the efficacy of a gluten-free casein-free diet from proving 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 in 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 doesn't work, given the relatively shorter duration of dietary intervention. The same issue cropped up years later in a 2014 study in Texas. The whole study design put everyone on a gluten-free casein-free diet, and then randomized 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-in-casein-free and no meaningful changes were found in either diet group. OK, but this study only lasted four weeks, and diet proponents suggest it may take months of gluten-in-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.