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Diet and autism: no gluten, no casein, no difference?

Gluten and casein are two food components often linked with autism spectrum disorder symptoms. Hence the prevalance of wheat and dairy free diets. But will they work in a rigorously controlled trial?

Study under review: The Gluten-Free/Casein-Free Diet: A Double-Blind Challenge Trial in Children with Autism


Interest surrounding gluten-free/casein-free (GFCF) diets for children with autism spectrum disorder (ASD) has been growing for decades. The first trial to test a gluten-free diet on children with ASD was published in 1971[1]. A few years later, a 1977 case study[2] from The Johns Hopkins University School of Medicine was the first to eliminate both milk and gluten products from the diet, in this case of a 9-year-old boy with ASD.

Since then, GFCF diets have become one of the most popular dietary treatments chosen by parents who have children with ASD. Many surveys have attempted to determine the prevalence of GFCF diets as an alternative treatment, but results have been wide ranging[3]. An average of these rates gives us an estimated 35% prevalence of GFCF diets, including both current and previous use. Parents with ASD children on a GFCF diet often report seeing improvements[4] in behavior.

The prevailing concept in support of a GFCF diet is the ‘opioid-excess theory’ of ASD, depicted in Figure 1. This theory states that the incomplete breakdown of gluten and casein proteins into excess opioid peptides can trigger symptoms in people with ASD. Gluten proteins are found in products like wheat, barley, and rye, while casein proteins are found in dairy products. When ingested, gluten and casein are broken down into peptides (short chains of amino acids) such as gluteomorphin/gliadorphin or beta-casomorphin. These peptides could potentially cross through[5] an abnormally permeable intestinal border, often referred to as a ‘leaky gut’, fully intact and undigested. If sufficient quantities were produced, these peptides could theoretically cross the blood-brain barrier[5], affecting the central nervous system and interfering with brain development, attention span, learning capacities, and cognitive function in people with ASD. It is therefore hypothesized that removal of these proteins from the diet could cause the behavioral symptoms of ASD to improve.

Figure 1: The opioid excess theory of ASD

Like any theory, the opioid-excess theory of ASD does have its weak points. The biggest issue is a lack of consistent results. For example, some studies[6] have noted an increased presence of gut permeability[7] in people with ASD, while others have seen no difference[8]. Further trials have seen increased gut permeability, but only in a specific subset of children[9] with ASD. Additional doubt has been cast on this theory due to the consistent lack of detectable concentrations[10] of opioid peptides in urine samples[11] of patients with ASD using highly-sensitive measurement techniques. If significant amounts of opioid peptides were making it past the gut and into the bloodstream, urine tests would reveal their high levels as the body worked to eliminate them.

Regardless of the points for or against the opioid-excess theory, the biggest question is: does the dietary elimination of casein and gluten actually help to alleviate symptoms in people with ASD? The present rigorously-controlled study aims to shed further light on that matter.

Gluten-free/casein-free (GFCF) diets are a popular alternative treatment among parents who have a child with autism spectrum disorder (ASD). Many parents have reported seeing behavior improvements when their child is on a GFCF diet. The opioid-excess theory of ASD proposes that the opioid peptides produced from incomplete breakdown of gluten and casein proteins cross into the body and alter brain functions, causing the symptoms of ASD. The study under review uses rigorous methodology to test if a GFCF diet can provide ASD symptom relief.

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