Concern about autism is growing as the number of affected individuals has surged in recent years, either due to an actual increase, an expanded definition or a greater awareness and thus more frequent diagnosis. Often a debilitating condition, autism is the most common syndrome among a group of related conditions, known as autism spectrum disorders (ASDs). ASDs are characterized by fundamental impairments in social interactions, severe communication and language deficits, and the presence of restricted or repetitive behaviors, and are now thought to be as prevalent as 0.6 to 1.2 percent.(1) Some autistic children are not able to make significant progress, and may always remain non-verbal and socially withdrawn, and most remain dependent on parents or others through adulthood.(2) This may be improving somewhat, however, and a small number of those with ASDs are able to live independently and establish relationship and educational goals, particularly those without severe intellectual disabilities.(3)
Given the complexity and heterogeneous expression of ASDs, it is not surprising that the contributing factors are multi-factorial, and although there are some common themes, they are likely to be very specific to each individual. An approach which emphasizes identifying and correcting underlying physiological dysfunction, as advocated by organizations such as Defeat Autism Now! may bring about improvement in many of the symptoms of ASDs, and increase the potential for more significant recovery in some children. The most important factors for those with ASDs appear to be impaired mitochondrial function, genetic predisposition combined with environmental exposure and poor detoxification, immune and gastrointestinal dysfunction, and nutritional imbalances.
Impaired Mitochondrial Function
Mitochondria are the organelles responsible for producing most of the energy used by our bodies, and a subset of individuals with ASDs have mutations in mitochondrial DNA, as well as markers in the blood for mitochondrial disease.(4) In a recent study evaluating individuals with both ASD and mitochondrial dysfunction, abnormalities were found frequently in complexes I and V of the mitochondria. Surprisingly, this report also indicated that fever may have been a contributing factor for autism development in these individuals.(4) Poor function of mitochondrial complexes may explain why restoring mitochondrial function through nutrients such as riboflavin, carnitine and CoQ10 (which improve efficiency of mitochondrial complexes) may be of benefit, although limited clinical evidence is available. I have one ASD patient who is symptom free as long as he takes the high levels of nutrients needed for his mitochondria to function. Whenever he stops taking them, his symptoms and dysfunction immediately return.
Genes, Detoxification and Environmental Exposure
The evidence for a role of genes in ASDs is quite strong. Twin studies found that monozygotic twins (identical) had up to a 90 percent chance of having ASDs if one of the twins did, while dizygotic siblings had only a 10 percent chance, indicating a very strong relationship to genetic factors. Although mutations in one specific gene can’t explain ASDs, genetic variations in multiple genes appear to play a role in most cases.(5)
As is the case for most genetic mutations though, having a mutation may not be enough to cause the disorder, i.e. it may be necessary, but not sufficient. Researchers have long looked for environmental causes of ASDs, but now they are looking at the way genetic predispositions might interact with environmental exposures to trigger a problem. For example, a key dysfunction in many individuals with ASDs is increased oxidative (free radical) stress. Glutathione, for instance, is a critical antioxidant and detoxifier of many environmental chemicals, and a deficiency of this compound may render individuals with ASDs more susceptible to environmental insults.(6) (Also, a recent study found that the severity of autistic symptoms could be correlated with the amount of glutathione found in red blood cells, as well as with heavy metal burden.(7)) Genetic analyses of individuals with ASDs have found polymorphisms (variants) for genes involved in glutathione metabolism, such as glutathione peroxidase, which may render them more susceptible.(8) So although someone with plenty of glutathione could detoxify harmful chemicals without difficulty, an individual with a genetic predisposition affecting glutathione status may be harmed more significantly by the same toxins. Although very controversial, this also may point to the risk of more seemingly benign compounds such as acetaminophen (which binds to glutathione and reduces its availability) to those with a genetic mutation in glutathione metabolism.(9)
Similarly, polymorphisms have been found in genes related to lead and organophosphate pesticide detoxification, suggesting that those with ASDs are more susceptible to the toxicity of these substances.6 Indeed, a recent review published in Current Opinion in Pediatrics found that among the environmental risks for autism (during pregnancy), there was very strong evidence for the organophosphate insecticide chlorpyrifos (among other risk factors) increasing the risk of ASDs.(10) This strongly suggests we should support healthy detoxification pathways, and avoid potentially damaging exposures, particularly in those most susceptible. Folic acid and vitamin B12, for example, have been used to restore glutathione (as well as methylation) status in children with autism,(11) and DMSA (Dimercaptosuccinic acid) use among those with high heavy metal excretion has been found to be safe as well as effective in increasing glutathione red blood cell levels and improving symptoms of autism.(12,13)
Immune and Gastrointestinal Dysfunction
A number of immune and gastrointestinal disturbances have been reported in individuals with ASDs, including multiple immune abnormalities such as signs of autoimmunity, increased intestinal permeability, food intolerances and malabsorption. Very recent research has also documented the presence of maternal autoantibodies directed toward fetal brain proteins, which may be one of the most specific markers for autism.(14) Additionally, abnormalities in immunoglobulin IgG4 (a type of antibody often associated with food allergy) and inflammation in the central nervous system has been documented. We have learned in recent years about the many connections between immune and gastrointestinal health, and although not all the immune abnormalities are connected to diet and GI health, some appear to be.
For example, one of the most common nutritional interventions recommended to individuals with ASDs is a gluten/casein free (GFCF) diet. A recent study published in the Journal of Pediatric Gastroenterology and Nutrition found that increased intestinal permeability was found in nearly 40 percent of those with autism (and 21 percent among family members), a rate nearly eight-fold higher than in controls. Additionally, they found that those on a GFCF diet had a significantly lower degree of permeability, suggesting that evaluation of intestinal integrity could help identify those patients most likely to benefit from dietary changes.(15) What’s more is that previous research suggests that a GCFC diet affects a ”gut-brain axis,” with adoption of this diet showing significant benefit to autistic children.(16) In fact, at least one case study was reported in which a boy diagnosed with severe autism had all his symptoms resolved when he was correctly diagnosed with celiac disease, and adopted a GFCF diet.(17) Although gluten and casein have particular significance for autistic individuals, the identification and avoidance of other food allergies is also likely to be of benefit, as are strategies aimed at restoring healthy intestinal permeability.
About 20 years ago, I tested all 30 of the children living in a home in Seattle for autistic children. I found that every one of them had a large number of food allergies. Although none were cured, all improved when they went on a diet avoiding their major allergens.
Nutritional and Other Potential Therapies
Although this brief review is not meant to be comprehensive for existing therapies, a few more are worth mentioning. Vitamin D deficiency is becoming more widely recognized as being both common and critical, and recent evidence suggests that deficiency during pregnancy may be a risk factor for autism and affect fetal brain development.(18) A study comparing the use of a broad-spectrum vitamin/mineral combination was found to have less adverse effects than medication, and also to have greater efficacy in improving many symptoms of autism.(19) Other treatments that will benefit some individuals with ASDs include Applied Behavioral Analysis (ABA), melatonin, music therapy, speech and vision therapy, massage, neurofeedback and oxytocin.(20,21,22,23,24)
1. Levy SE, et al. Autism. Lancet. Nov2009;374(9701):1627-38. Epub 2009 Oct 12.
2. Howlin P, et al. Adult outcome for children with autism. J Child Psychol Psychiatry. Feb2004;45(2):212-29.
3. Marriage S, et al. Autism spectrum disorder grown up: a chart review of adult functioning. J Can Acad Child Adolesc Psychiatry. Nov2009;18(4):322-8.
4. Shoffner J, et al. Fever plus mitochondrial disease could be risk factors for autistic regression. J Child Neurol. Apr2010;25(4):429-34.
5. El-Fishawy P, State MW. The genetics of autism: key issues, recent findings, and clinical implications. Psychiatr Clin North Am. Mar2010;33(1):83-105.
6. Herbert, MR. J. Toxicol. 2009;2009:532640. Epub 2009 Aug 26. Curr Opin Neurol. 2010 Apr;23(2):103-10.
7. Adams JB, et al. The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels. J Toxicol. 2009;2009:532640. Epub 2009 Aug 26.
8. Ming X, et al. Genetic variant of glutathione peroxidase 1 in autism. Brain Dev. Feb2010;32(2):105-9. Epub 2009 Feb 4.
9. Schultz ST, Klonoff-Cohen HS, Wingard DL, et al. Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey. Autism 2008;12:293–307.
10. Landrigan PJ. What causes autism? Exploring the environmental contribution. Curr Opin Pediatr. Apr2010;22(2):219-25. Review.
11. James SJ, et al. Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr. Jan2009;89(1):425-30. Epub 2008 Dec 3.
12. Adams JB, et al. Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A—medical results. BMC Clin Pharmacol. Oct2009;9:16.
13. Adams JB, et al. Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: part B – behavioral results. BMC Clin Pharmacol. Oct2009;9:17.
14. Goines P, Van de Water J. The immune system’s role in the biology of autism. Curr Opin Neurol. Apr2010;23(2):111-7. Review.
15. de Magistris L Alterations of the Intestinal Barrier in Patients With Autism Spectrum Disorders and in Their First-degree Relatives. J Pediatr Gastroenterol Nutr. Jul2010. [Epub ahead of print]
16. Reichelt KL, Knivsberg AM. The possibility and probability of a gut-to-brain connection in autism. Ann Clin Psychiatry. Oct2009;21(4):205-11.
17. Genuis SJ, et al. Celiac disease presenting as autism. J Child Neurol. Jan2010;25(1):114-9.
18. Grant WB, Soles CM. Epidemiologic evidence supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism. Dermatoendocrinol. Jul2009;1(4):223-8.
19. Mehl-Madrona L, et al. Micronutrients versus standard medication management in autism: a naturalistic case-control study. J Child Adolesc Psychopharmacol. Apr2010;20(2):95-103.
20. Virués-Ortega J. Applied behavior analytic intervention for autism in early childhood: meta-analysis, meta-regression and dose-response meta-analysis of multiple outcomes. Clin Psychol Rev. Jun2010;30(4):387-99. Epub 2010 Feb 11.
21. Rossignol DA. Novel and emerging treatments for autism spectrum disorders: a systematic review. Ann Clin Psychiatry. Oct2009;21(4):213-36.
22. Silva LM, et al. Am J Occup Ther. Qigong massage treatment for sensory and self-regulation problems in young children with autism: a randomized controlled trial. Am J Occup Ther. Jul2009;63(4):423-32.
23. Coben R et al. Neurofeedback for autistic spectrum disorder: a review of the literature. Appl Psychophysiol Biofeedback. Mar2010;35(1):83-105.
24. Guastella AJ, et al. Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry. Apr2010;67(7):692-4. Epub 2009 Nov 7.
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