Gluten-free, casein-free diet
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A gluten-free casein-free diet (GFCF diet) or gluten-free dairy-free diet (GFDF diet) eliminates dietary intake of the naturally occurring proteins gluten (found most often in wheat, barley, rye, and commercially available oats), and casein (found most often in milk and dairy products).
Background and theory
In the 1960s, Curtis Dohan speculated that the low incidence of schizophrenia in certain South Pacific Island societies was a result of a diet low in wheat and milk-based foods. Dohan proposed a genetic defect wherein individuals are incapable of completely metabolizing gluten and casein as a possible etiology for schizophrenia. Dohan hypothesized that elevated peptide levels from this incomplete metabolism could be responsible for schizophrenic behaviors. In 1979, Jaak Panksepp proposed a connection between autism and opiates, noting that injections of minute quantities of opiates in young laboratory animals induce symptoms similar to those observed among autistic children.
The possibility of a relationship between autism and the consumption of gluten and casein was first articulated by Kalle Reichelt in 1991. Based on studies showing correlation between autism, schizophrenia, and increased urinary peptide levels, Reichelt hypothesized that some of these peptides may have an opiate effect. This led to the development of the Opioid excess theory, expounded by Paul Shattock and others, which speculates that peptides with opioid activity cross into the bloodstream from the lumen of the intestine, and then into the brain. These peptides were speculated to arise from incomplete digestion of certain foods, in particular gluten from wheat and certain other cereals and from casein from milk and dairy produce. Further work confirmed opioid peptides such as casomorphines (from casein) and gluten exorphines and gliadorphin (from gluten) as possible suspects, due to their chemical similarity to opiates.
Reichelt hypothesized that long term exposure to these opiate peptides may have effects on brain maturation and contribute to social awkwardness and isolation. On this basis, Reichelt and others have proposed a gluten-free casein-free (GFCF) diet for sufferers of autism to minimize the buildup of opiate peptides. Reichelt has also published a number of trials and reviews concluding that this diet is effective.
GFCF and GFDF diets as a treatment for autism spectrum disorder
One of the most visible advocates for the GFCF/GFDF diet is the Autism Research Institute. The ARI recommends the GFCF/GFDF diet as a treatment for autism and related conditions. The organization believes that, "Dietary intervention is a cornerstone of a evidence-based medical approach, and there is convincing empirical evidence that special diets help many with autism." The ARI lists two studies: Knivsberg, Wiig, et al. “Dietary Interventions in Autistic Syndromes" in the journal Brain Dysfunctions 3 and Knivsberg, Reichelt, et al. “A Randomised, Controlled Study of Dietary Intervention in Autistic Syndromes” in Nutritional Neuroscience as scientific publications that support their theories.
- American Academy of Pediatrics - Clinical Report (2007)
In their report, the AAP found that they could not recommend the use of special diets for children with autism spectrum disorder because of inadequate evidence. The report stated, "Although use of the gluten/casein-free diet for children with ASDs is popular, there is little evidence to support or refute this intervention, and reviewers have determined that meaningful conclusions cannot be drawn from the existing literature." 
- Cochrane Library - Gluten and Casein-free diets in autism spectrum disorder (2008)
A 2008 systematic review from the Cochrane Library indicates that a gluten-free and/or casein-free diet has not been shown to have any effect on the behavior or functioning of individuals with autism. Likewise, research on adverse outcomes and disbenefits is lacking. Two randomized trials were included in the review. The first included ten individuals, was single blind (with parents aware of allocation), and reported reduced autistic traits; the second included fifteen individuals, was double blind, and found no significant differences in outcomes. The first study has been criticized for its small sample size and single-blinding; both factors are associated with positive outcomes bias.
- Research in Autism Spectrum Disorders - Gluten-free and casein free diets in the treatment of autism spectrum disorders: A systematic review (2009)
The systematic review, conducted in 2009, concluded that the results "reveal that the current corpus of research does not support the use of GFCF diets in the treatment of ASD. Given the lack of empirical support, and the adverse consequences often associated with GFCF diets (e.g. stigmatization, diversion of treatment resources, reduced bone cortical thickness), such diets should only be implemented in the event a child with ASD experiences acute behavioral changes, seemingly associated with changes in diet...and/or a child has allergies or food intolerances to gluten and/or casein."  The review identified 14 studies testing the effects of GFCF diet on autism. Both of the papers ARI references were included in this study. Out of 14 studies, 7 reported positive results, 2 reported mixed results, and 4 reported negative results (that is, absence of statistically significant effects). Among the four studies reporting negative results, none were longer than 6 weeks, with two out of four studying effects of the diet for 4 days and 9 days. Only two double-blind studies were identified, and both of these produced negative results.
- Vanderbilt Evidence-based Practice Center - Therapies for Children with Autism Spectrum Disorder (2011)
The review, commissioned by the Agency for Healthcare Research and Quality, examined 159 unique studies on therapies for children ages 2 to 12 with ASDs. The review included articles published in English from January 2000 to May 2010. Out of the 159 studies, the Vanderbilt Evidence-based Practice Center examined 14 studies of gluten-free and/or casein-free diets.
The studies covered 188 participants, who ranged in age from 2 to 17. The review rated 11 of the 14 studies as suggestive. The investigators' methodological concerns included, "use of measurements subject to bias, lack of blinding and control groups, use of only post-treatment measures, short intervention durations, and failure to control for the effects of maturation." The remaining 3 studies were considered as, "providing a level of certainty of evidence for the lack of effectiveness of GFCF diets." The investigators concluded that, "the evidence supporting GFCF diets in ASD is limited and weak." 
- Clinical Therapeutics - The relationship of autism to gluten (2013)
This review, authored by Timothy Buie, a gastroenterologist at Harvard Medical School, found one double-blind study, which did not find any benefit from the gluten-free diet, and concluded that "Currently, there is insufficient evidence to support instituting a gluten-free diet as a treatment for autism."
- Journal of Child Neurology - Evidence of the Gluten-Free and Casein-Free Diet in Autism Spectrum Disorders: A Systematic Review (2014)
This review found that "...the evidence on this topic is currently limited and weak," and noted that only a few randomized trials had been conducted on the efficacy of gluten-free diets as an autism treatment. The review also noted that even these trials were of questionable scientific merit because they were based on small sample sizes.
The diet may have a negative effect on bone health, although there is debate over whether this is actually due to the diet or caused by eating habits or bowel issues associated with autism.
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The implementation of a GFCF diet involves removing all sources of gluten and casein from a person's diet. Gluten is found in all products containing wheat, rye, and barley. Many gluten-free breads, pastas, and snacks are available commercially. Gluten-free cookbooks have been available for decades. Casein is found in dairy products such as milk, butter or cheese, but is also present in smaller amounts in many substitute dairy products such as vegetarian cheese substitutes and whipped cream topping, which use casein to provide texture. Although advocates of the GFCF diet often recommend total elimination of dairy from the diet, whey protein is a different milk protein from casein.
- Gluten sensitivity
- Opioid excess theory
- Autism therapies
- List of diets
- List of alternative therapies for developmental and learning disabilities
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- "Curtis Dohan, M.D., A.B., Associate Professor, The University of Tennessee Health Science Center".
- Dohan, F. C. (1966). "Cereals and schizophrenia data and hypothesis". Acta Psychiatrica Scandinavica 42 (2): 125–132. doi:10.1111/j.1600-0447.1966.tb01920.x. PMID 5335008.
- Panksepp, Jaak (1979). "A neurochemical theory of autism". Trends in Neurosciences 2: 174–177. doi:10.1016/0166-2236(79)90071-7.
- Reichelt KL, Knivsberg A-M, Lind G, Nødland M. (1991). "Probable etiology and possible treatment of childhood autism". Brain Dysfunction 4 (6): 308–19.
- Reichelt, K. L.; Hole, K; Hamberger, A; Saelid, G; Edminson, P. D.; Braestrup, C. B.; Lingjaerde, O; Ledaal, P; Orbeck, H (1981). "Biologically active peptide-containing fractions in schizophrenia and childhood autism". Advances in biochemical psychopharmacology 28: 627–43. PMID 7010949.
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- Knivsber, A. M.; Reichelt, K. L.; Nødland, M (2001). "Reports on dietary intervention in autistic disorders". Nutritional neuroscience 4 (1): 25–37. PMID 11842874.
- Knivsberg, A.M.; Reichelt, K.L.; Høien, T.; Nødland, M. (2002). "A Randomised, Controlled Study of Dietary Intervention in Autistic Syndromes". Nutritional Neuroscience 5 (4): 251–61. doi:10.1080/10284150290028945. PMID 12168688.
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- Marí-Bauset, S; Zazpe, I; Mari-Sanchis, A; Llopis-González, A; Morales-Suárez-Varela, M (2014-04-30). "Evidence of the Gluten-Free and Casein-Free Diet in Autism Spectrum Disorders: A Systematic Review". Journal of child neurology 29 (12): 1718–27. doi:10.1177/0883073814531330. PMID 24789114.
- Whiteley, P; Shattock, P; Knivsberg, Ann-Mari; Seim, Anders; Reichelt, Karl L.; Todd, Lynda; Carr, Kevin; Hooper, Malcolm (2012). "Gluten- and casein-free dietary intervention for autism spectrum conditions". Front Hum Neurosci 6: 344. doi:10.3389/fnhum.2012.00344. PMC 3540005. PMID 23316152.