Introduction Parents of children diagnosed with autism spectrum disorders (ASD), tend to opt for alternative intervention for their children, for example, the use of a gluten-free, casein-free diets, which they perceived as risk free, to improve the cognitive-behavioural function of their children with ASD. The main focus of this essay is to discuss the most recent advances in gluten-free research and the evidences that argued for or against the use of a gluten-free, casein-free diets, especially for children who are diagnosed with ASD. It also critically explored the strategies used, the challenges encountered, and the emotional impact experienced by people who followed a gluten-free diet, as evidenced by past research studies. A systematic review of research papers published from 1970 to date indicated that most studies conducted on children with ASD who are following a gluten-free diet were mostly tested on randomized controlled trials, with small sample sizes. Hence, it lacks validity and sound scientific evidence to conclude the effectiveness of adopting a gluten-free diet as a form of intervention. Future research on a larger scale is recommended (O’Shea, Arendt, & Gallaghar, 2014; Zarkadas, Dubois, McIsacc, Cantin, Rashid, Roberts, La Vieille, Godefroy, & Pulido, 2013; Mari-Bauset, Zazpe, Mari-Sanchis, Llopis-Gonzalez, & Morales-Suarez-Varela, 2014).Description and Definition Autism spectrum disorders (ASD) has been on the rise for the past 30 years and is becoming prevalent, affecting 1 in every 68 persons in United States. It is a highly complex disorder with multiple causes and various treatment approaches to treat only the symptoms as autism is not curable. Children with autism are characterised by a spectrum of neurological developmental disorders that manifest in early childhood. They include persistent deficits in social communication and social interaction, along with restricted, repetitive patterns of behaviour, interests, or activities, such as stereotyped or repetitive speech, motor movements or fixative interest in certain object or task. A variety of genetic, environmental and immunological factors could also affect multiple systems, especially the cognitive-behavioural function of the person with ASD. In past epidemiological studies of prenatal development, metabolic and nutritional factors have been identified as one of the contributing risks of autism for the newborn babies (Matelski, & Van de Water, 2016).The ‘opioid excess theory’ could best explain ‘gluten and casein intolerance’ in persons diagnosed with ASD. According to Lange, Hauser & Reissmann (2015), when gluten (from wheat) and casein (from dairy products) are consumed into the body, they are metabolized to ‘gluteomorphine’ and ‘casomorphine’. These ‘peptides’ then bind to ‘opiate receptors’ in the ‘central nervous system’ and to imitate the effects of ‘opiate drugs’. During digestion, ‘opioid peptides’ are formed which then led to an increased activity in the ‘endogenous opioid system’ and resulted in the symptoms of autism. Hence, a diet low in gluten and casein is believed to improve the cognitive-behavioural function of persons with ASD (Lange, Hauser, & Reissmann, 2015, n.p).Children diagnosed with autism tend to also suffer from comorbid problems which cause gastrointestinal symptoms and affect their concentration and attention span. Past research studies also associated gluten intolerance with ASD and indicated the relationship between ASD and celiac disease, an autoimmune disease that causes gastrointestinal syndrome (Lange, Hauser, & Reissmann, 2015; Jackson, Eaton, Cascella, Fasano, & Kelly, 2012, pp 95-96).Intervention’s Definition of Improving Quality of Life The purpose of choosing a non-invasive intervention or therapy is to improve the quality of life for the diseased. A Gluten Free Diet (GFD) tends to be the preferred intervention used by parents of children with ASD because it is not a form of medication, non-evasive in nature, as compared to other form of therapy, such as stem cell therapy. Currently, GFD is widely used by individuals with celiac disease and by parents who have children diagnosed with ASD to improve their children’s quality of life. However, due to misinformation circulating online or by ill advice from unqualified sources regarding the benefits or harmful effects of GFD, it is legitimate to examine the accuracies or inaccuracies, the fact and fiction of using GFD, as a form of intervention. With the growing popularity of parents putting their children on a GFD, in the belief that it is a risk free intervention to relieve their children’s autistic symptoms, it might pose important implications for them (Reilly, 2016). A recent UK survey indicated that 80% of parents of children with autism spectrum disorders tend to use some form of dietary intervention for their child, out of which 29% of the parents placed their child on a gluten-free and casein-free diet (GFCFD). On examining the effects of using GFCFD on their children, 20–29% of the parents reported significant improvements on the cognitive-behavioural function. The findings also suggested that a gluten-free and casein-free diet did help to relieve comorbid problems such as gastrointestinal symptoms, and improve the concentration, and attention span of these children. Although parents in the studies gave positive effects of GFCFD on their children, most scientific evaluations have failed to confirm its therapeutic effects. Using parents as informants on their children’s autistic symptoms can be a bias source of information. Perhaps, in future case studies, we need to include clinicians as informants and assessors of the effects, to introduce standardized test procedures and observational parameters. It will then complement the measures and give a more complete picture of dietary effects of GFCFD on children with ASD (Lange, Hauser & Reissmann, 2015).The use of GFCFD by parents on their children might have some loop holes that need to be addressed. For example, some parents may go ahead to place their child on GFCFD without testing their child for celiac disease or consulting a dietician. Some children with celiac disease may be asymptomatic from the start and thus was not noticed for having the condition. Furthermore, information on the health and social consequences of starting a child on GFCFD are not adequate online or in books, for parents to make an informed choice (Reilly, 2016).Research studies behind Intervention and Evaluations According to Lange, et al. (2015), GFCFD trials evaluating the effects of a GFCFD on autistic symptoms have so far been questionable and inconclusive. The authors also mentioned that research studies investigating the efficacy of a GFCFD in the treatment of autism are seriously flawed and the therapeutic value of this diet appeared to be weak and restricted. A systematic review of research papers published from 1970 to date also indicated that most research studies conducted on children with ASD who are placed on a gluten-free diet were mostly tested on randomized controlled trials and with a small sampling size. Hence, it lacks validity and reliability and is unable to provide a sound scientific evidence to conclude the effectiveness of adopting a gluten-free diet as a form of intervention.Recent research studies indicated that gluten sensitivity (GS) is an illness distinct from celiac disease. This new discovery gave rise to new understanding and knowledge of the disease. Both celiac disease and GS may present with a variety of neurologic and psychiatric co-morbidities. However, for those with GS, the prime symptoms are extra-intestinal problems. It was found that those with celiac disease have villous atrophy or antibodies present in their bodies, unlike those with GS who do not have the antibodies. Hence, GS if remained untreated, can lead to psychiatric and neurologic manifestations in persons with ASD (Jackson, et al., 2012).Jackson, et al. (2012) also cited a few research studies indicating an increased risk of ASDs in children with a ‘maternal history of rheumatoid arthritis’, ‘celiac disease’ and ‘irritable bowel syndrome’. Another study used a control group to make comparison. It was found that persons with ASDs and their family members have a high percentage of people with ‘abnormal intestinal permeability’ as compared to the group without ASDs. Another control group study of GFCFD used on patients with ASD have found ‘a better intestinal permeability’ as compared to patients on a non-GFCFD. As most of the research studies tend to focus on the use of GFCFD rather than eliminating GFCFD on persons with ASDs, it makes it dif?cult to determine whether there is additional bene?cial effects if a non-GFCFD is used (p. 95).The beneficial effects of a GFCFD on autistic symptoms have so far been contradictory and remained debatable to date and there is not enough data to support its benefits (Mari-Bauset,et al.,2014; Gaesser & Angadi, 2012, p. 1330). In fact, recent evidence suggested that a gluten-free diet might reduce beneficial gut bacteria in the intestines. Other reports also indicated that patients who are obese tend to put on even more weight after being placed on a gluten-free diet. It could be due to better absorption of nutrients or healing of intestinal lining following a gluten-free diet (Gaesser & Angadi, 2012). This might have an implication on obese children with ASD to put on more weight if they were to use a gluten-free diet as a form of intervention.Reilly (2016) asserted that there is not enough evidence to support the health benefits of a gluten-free diet. On the contrary, a gluten-free diet may have negative effects if it is not prescribed or approved by a registered dietician or physician.Gluten-free packaged food also tend to have higher sugar and fat content as compared to non-gluten-free food. Intake of too much sugar and fat may increase the risks of obesity. There are emerging evidences to show that a strictly rice flour gluten-free diet without other varieties of gluten-free products may lead to toxicity due to ‘arsenic’,found in inorganic form in most rice-based gluten-free products. A gluten-free diet may also result in deficiencies in vitamin B, folate and iron. Hence, it is a myth to think that eating a gluten-free diet is a healthier choice (Reilly, 2016, pp. 206-207).A recent research study was conducted by Hyman, Stewart, Foley, Cain, Peck, Morris, Wang, & Smith (2016), on the safety and ef?cacy of the gluten-free/casein-free (GFCF) on a group of 14 children (age 3–5 years) with autism. They were put on GFCF diet for 4–6 weeks and followed by placebo controlled challenge study for 12 weeks while continuing the diet, with a 12-week follow-up. Children were given weekly snacks that contained gluten, casein, gluten and casein, or placebo during the dietary challenges with nutritional counselling. The findings indicated that the GFCF diet was safe and well-tolerated. However, the limitation of this study was that it was unable to track the signi?cant effects on physiologic functioning, behaviour problems, or autism symptoms. Due to the small sampling size, the ?ndings must be interpreted with caution and has to be replicated on a larger scale to validate the findings.The scienti?c community has all along tried to establish alternative ways of intervention. To date, there is no pharmacological treatment that is available to gluten-intolerant patients. Placing patients on a strict, life-long gluten-free diet appeared to be the only safe solution although it is still not conclusive regarding its effectiveness. A research study was conducted by Caputo, Marilena, Stefania & Esposito (2010) on the use of enzymes as additives or as processing aids in the food biotechnology industry to detoxify gluten. The recent development of ‘enzyme therapy’ is a new alternative intervention that focused on inactivating immunogenic gluten epitopes and is administered orally to patients. For people with ASD, it might spell new hope and be a new strategy to relieve their autism symptoms and improve cognitive-behavioural functions. Persons undergoing this therapy are administered doses of ‘Flavobacterium meningosepticum’, ‘Sphingomonas capsulate’, and ‘Myxococcus xanthus’. These enzymes are believed to help ‘degrading proline-containing peptides’ that are otherwise resistant to degradation by ‘proteases’ in the gastrointestinal tract. A lifelong gluten-free diet may not be easy to maintain and does cause a negative impact on the quality of life. It is also a costly affair to stick to a gluten-free diet whereas a non-gluten-free diet is commonly available and cheaper to maintain (Caputo, Marilena, Stefania & Esposito, 2010, pp.4-5; Zarkadas, et al., 2013). A systematic review of the medical literature related to GFCFD was conducted by Mari-Bauset, et al. (2014).The researchers tracked databases dating back from the 1970s to September, 2013 on published research articles or written reports on the use of GFCFD on children with ASD as an intervention. The systematic review evaluated the findings and reported that none of the studies identified provided conclusive evidence of GFCFD effectiveness as an intervention for ASD because they were poorly validated. The studies are mostly tested on randomized controlled trials, with a small sample size thus cannot be conclusive or represented.A recent research study conducted in 2008 by Zarkadas, et al.,(2013) investigated the effects of gluten-free diet among Canadians with coeliac disease. A questionnaire was mailed to all 1,0693 members of both the Canadian Celiac Association and the Fondation québécoise de la maladie cœliaque. A total of 5912 (age?18 years) responded which is equivalent to 72% of the response rate. The findings reflected the difficulties encountered, the strategies used and the emotional impact of following a gluten-free diet. For example, a significantly higher percentage of women than men reported often feeling frustrated and isolated during both time periods of treatment. As there is lack of research studies on gender response in regards to GFCFD’s intervention on persons with ASD, it is worth investigating this aspect. Future Directions and ConclusionPast research studies and evidences regarding the effectiveness of a GFCFD as an intervention therapy for persons with autism are still inconclusive and lack robust evidences. Despite the diet’s popularity and the positive feedbacks from parents regarding its effects, most scientific evaluations have failed to confirm therapeutic effects. Adhering to a GFCFD is highly complex, costly and impacts on all activities involving food, making it difficult to maintain in the long term and may be perceived as a negative impact on the quality of life. Cross-sectional study of these nature are challenging to evaluate the emotional impact of following a gluten-free diet and the difficulties faced by users or the effectiveness of the strategies used (Lange et. al., 2015; Zarkadas, et al., 2013). Perhaps in future dietary studies, it should include longitudinal studies on single case or group study. As a GFCFD can be costly, more research studies could be done to explore potentially cheaper options and a more functional alternative. Other than rice, corn, and potato starch products, the use of chestnut flour and flours developed from fruit by-products, for example, OP and defatted strawberry seeds could be explored (O’Shea, 2014). Apart from parents as informants of the effectiveness of the GFCFD, clinical expert ratings should also be sought and behavioural observations be gathered from various sources, to give a more complete picture of the dietary effects of GFCFD on children with ASD.