Introduction

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. In recent years there has been evidence indicating that nutrition could play a significant role in the etiology of this disorder. Furthermore, it has been reported that it plays an active role in the treatment of this disorder by alleviating its symptoms, since an association has been reported between nutrition and both the severity and the frequency of the symptoms. This interest has been based on the well documented observation regarding the importance of nutrition in brain development and health, and the suggestion that several nutrients ( e.g. amino acids, fatty acids, vitamins, trace elements and minerals) are important for the proper neural development and functioning of the central nervous system. This has led the scientific community to research the intake of macro and micronutrients in individuals with ASD.

Although, to date, the information from the available literature is not conclusive, there are studies that have observed decreased severity of the core ASD symptoms such as repetitive behavior, social and communicative difficulties, self-harm, and aggression, as the outcome of various nutritional approaches in individuals with ASD. Notably, an issue that highlights the importance of nutrition in these individuals is the observation that there is a variety of factors affecting their nutritional intake. In particular, these individuals are nutritionally vulnerable because they exhibit several nutritional related issues. Evidence has shown that individuals with autism  show unusual dietary patterns, low appetite, low range of preferred foods, selective (picky) eating pattern, intolerance in specific nutrients and digestive disorders of the autonomic nervous system compared to the general healthy population. In addition, food allergies, metabolic disorders, nutritional deficiencies, eating disorders, gastrointestinal problems, a refusal to eat, and a sensory sensitivity have been reported. All these factors predisposes them to restricted intakes and their nutrient intake is hindered. It should be mentioned here that there are reports showing that  30–80% of children with ASD have gastrointestinal dysfunction. The significance of the latter is high since in humans the gastrointestinal tract is tasked with the digestion of food and absorption of nutrients and this dysfunction could more probable result in nutritional deficiencies that could even affect the physiological function of their body.

Since nutrition is suggested to be related and/or linked to ASD a lot of research has been devoted to discover medical nutrition therapies and strategies for individuals with autism. In this context an subtractive and an additive nutritional approach has been developed.

Nutritional Approaches

  1. Regarding the subtractive approachseveral diets have been examined as medical nutrition therapies. These involve:
  2. The Glutein Free Casein Free (GFCF) diet

The gluten free / casein free diet is one of the many alternative treatments for children with autism. With this restrictive diet, all foods containing gluten (found in wheat, barley and rye) and casein (found in milk and dairy products) are removed from the daily diet of the individual.  Although, so far, there has not been enough evidence to show that certain dietary changes reduce the symptoms of autism, its popularity has increased as many parents report an improvement in the autism symptoms with this diet. Among the benefits mentioned are the improvements in certain symptoms and/or behavioral problems, in communication skills, a decrease in  hyperactive behavior, improvement in sleep, speech, attention, focus and behavior.

  1. Ketogenic diet (kcal: 90% fat, 7% protein, 3% carbohydrates))

This dietary intervention is high in fat, low in carbohydrates and contains carefully-regulated  but sufficient protein levels. This diet has been designed for individuals who suffer from seizures. Since many individuals with ASD do suffer from seizures,  treatment with this diet has been employed aiming to  control their symptom. This diet can play a role in managing ASD, since it has been suggested that it has the potential to alleviate certain symptoms related to this disorder. Regarding the latter, evidence indicates that individuals who have followed this diet showed improvement in the Childhood Autism Rating Scale (CARS) and Autism Treatment Evaluation Test (ATEC) score. In addition, a recent study has reported  that children with ASD who followed the ketogenic diet showed better cognition and sociability scores compared to those in the gluten free casein free diet group. However, this diet should be followed with caution and should be undertaken only with close medical supervision. Individuals that choose to follow this dietary regime should be highly motivated and so should be the rest of the family. There are some common proposed complications that include poor growth, poor weight gain, and hypercholestrolemia (high cholesterol ). In addition individuals should be continuously and  meticulously monitored for growth and nutritional deficiencies.

  1. High Fat Diet (kcal: 60% fat, 20% protein, 20% carbohydrates)

This diet is different from the ketogenic diet as seen in the percentage of the included nutrients. There is evidence suggesting that there is a general deterioration in autism-related symptoms  and more  specifically in cognitive and social behavior. This is based on the observed link between the High Fat Diet-induced changes and the dopamine mechanism to reward sensitivity, learning and memory, anxiety-related behaviors, social interaction, and motivation, symptoms that are ASD-related behaviors. However, despite the fact that this dietary intervention looks promising, there is a need for more evidence to justify its use.

  1. Feingold Diet

With the implementation of the Feingold diet, improvement in behavior, attention and intestinal disturbances are evident, indicating that it can be beneficial for individuals with ASD. This intervention is characterized by removing artificial colors, artificial aromatics, aspartame and artificial preservatives (cause hyperactivity and behavioral disorders) from the dietary intake. However, no systematic research exists linking ASD and the Feingold diet.

  1. Regarding the additive approachthe available literature suggests:
  2. Camel milk

Recent scientific evidence suggests that the camel milk improve the clinical results of ASD. Its administration in individuals with ASD have resulted in significant positive changes on the Childhood Autism Rating Scale (CARS). As a nutrient contains a variety of nutrients such as calcium, iron, magnesium, copper, zinc, potassium, vit A, vit E, vit B2, vit  C, and also protective proteins and enzymes with antibacterial, antiviral, antioxidant, and immunological properties. In addition, it has been found that it contains less fat, less cholesterol, and less lactose compared to cow milk.  Recent research reported that camel milk has mitigated autism symptoms or caused great amelioration in basic symptom and improved the obtained provided CARS, SRS, and ATEC scores in individuals with ASD. Although these findings seem indeed exciting more research is needed to determine its effects.

  1. Probiotics

It has been suggested that probiotics may be helpful in alleviating some of the gastrointestinal symptoms individuals with ASD face. In these individuals in general  gastrointestinal dysfunctions have been linked with increased irritability, sleep disturbances, and even aggressive behavior. To date, there is evidence suggesting that probiotics may result in enhanced ability to concentrate, improve behavioral abnormalities (such as improved destructive and antisocial behavior), as well as in anxiety and communication problems to follow instructions However, research on probiotics is insufficient. Furthermore, it has been reported that although they are suggested to be included in the quest for the nutritional interventions and therapies in autistic individuals,  those with compromised immune systems should avoid them.

  1. Vitamin D

In recent years the role of this pro-hormone has been well demonstrated to be nearly related with all the physiological systems of the human body, being involved in a great variety of functions. Studies report decreased concentrations of vitamin  D ( vitamin D (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) in individuals with ASD. Notably, among the physiological function of this secosteroid,  several studies have reported it to be related with various immune-related conditions such autoimmunity that has been suggested to play a role in the pathogenesis of ASD. In addition, the observation that ASD occurs with higher frequency in areas of impaired ultraviolet B penetration that is of major importance for vitamin D production, further suggests a role between this vitamin and ASD. Although, to date, the data regarding interventions with vitamin D on ASD symptoms is limited, the available literature indicates that it might be beneficial to individuals with ASD, since its supplementation has been found to result in significant improvements of the ASDs core symptoms.

  1. Vitamin A

Vitamins A is well demonstrated  to be beneficial in cell growth and maintenance of epithelial integrity. The importance of these mechanism relies on the fact that improved gut epithelial integrity results in enhanced digestion and assimilation of nutrients. In addition, despite the limited evidence, it has been suggested that its supplementation results in improved visual contact, social skills, and sleep in individuals with ASD. Notably, extremely caution  should be taken regarding the supplemented dosage due to the risk of heavy metal poisoning. In this context, it is suggested that in children with ASD liquid fish oil may be safer compared to cod liver oil which could be potentially dangerous since it has been associated with a risk of heavy metal poisoning.

  1. Vitamin B

Vitamin B12 is a key element in methylation and has been shown to improve oxidative stress. Recent evidence suggests that treatment with its methyl form can result in improving the symptoms in autistic children. However, more evidence is needed to support this suggestion.

Vitamin B6 is an important co-factor for metabolic processes which involve several important neurotransmitters. In particular, it is involved in more than 60 biological processes in the human body and it is required for brain development and function.  Some studies have observed that when provided in combination with magnesium it results in  positive effects in ASD symptoms, including improvements in the behavioral parameters. However, more studies are needed to confirm these findings.

  1. Vitamin C

It is an important vitamin as it has well demonstrated antioxidant actions that protects the body against the free radicals, and also anti-inflammatory effects. In addition, it has been related in neurotransmitter syntheses and is involved in the brain excitatory signaling. However, scarce evidence exists regarding its association with ASD. One study has reported that high doses of vitamin C in children with autism had significant positive effects on behavior, as shown by their behavior scores. Other evidence shows it reduces the level of oxidative stress in children with ASD. However, since some issues regarding its tolerance in individuals with ASD have been evident, caution should be taken with its supplementation.

  1. Vitamin E

Although there is limited evidence regarding its association with the ASD syndrome, it has been suggested that the combination of vitamin E that serves as an antioxidant, with Omega-3 fatty acids could treat the speech disorder verbal apraxia. This finding is important for individuals with autism since approximately 50% of them have been found to suffer from this disorder. Notably, more research in needed on this topic to justify these suggestions.

  1. Omega-3 fatty acids

Omega-3 fatty acids are needed for optimal brain development. Although there is some evidence supporting its benefits on ASD, others have failed to support its importance. More research is needed to justify its need. In addition, their supplementation should be monitored since high dosages might result in health related issues.

  1. Melatonin

The interest regarding melatonin have risen due to the well documented finding of it being a neurohormone that regulates circadian rhythms, including sleep patterns. Melatonin levels have been found to be low in individuals with ASD. Research has shown that its supplementation could result in increased sleep duration, and even improved day time behavior in autistic individuals.

Conclusions

The aim of the present paper is to provide the available evidence of the literature regarding the importance and the possible associations of nutrition with ASD.  To date, more than a hundred techniques have been presented aiming to help individuals with ASD with the several issues they face. In this context various medical nutrition approaches have been examined, and been discussed, and there is an on-going research on the roles of nutrition in ASD pathogenesis and management. However, despite the fact that there is data indicating beneficial effects, no clear consensus can be made since these is no conclusive  evidence, and further research is needed.   

References

Hande Cekici & Nevin Sanlier (2017): Current nutritional approaches in managing autism spectrum disorder: A review, Nutritional Neuroscience, DOI: 10.1080/1028415X.2017.1358481

Olakunle James Onaolapo & Adejoke Yetunde Onaolapo (2018 )Nutrition in autism spectrum disorders: A review of evidences for an emerging central role in aetiology, expression, and management. AIMS Medical Science, 5(2): 122–144. DOI: 10.3934/medsci.2018.2.122

Sathe N. Andrews JC, McPheeters ML, Warren ZE (2017) Nutritional and Dietary Interventions for Autism Spectrum Disorder: A Systematic Review. Pediatrics. 2017 Jun;139(6). pii: e20170346. DOI: 10.1542/peds.2017-0346.

Ng QX, Loke W, Venkatanarayanan N, Lim DY, Soh AYS, Yeo WS (2019)A Systematic Review of the Role of Prebiotics and Probiotics in Autism Spectrum Disorders. Medicina (Kaunas). May 10;55(5). pii: E129. DOI:10.3390/medicina55050129. Review.

Hajar Mazahery , Carlos A. Camargo Jr , Cathryn Conlon , Kathryn L. Beck , Marlena C. Kruger and Pamela R. von Hurst (l 2016) Vitamin D and Autism Spectrum Disorder: A Literature Review. Nutrients. 2016 Apr 21;8(4):236. DOI:10.3390/nu8040236.