1. Navigating different Diets in Children with Autism
Bariah Dardari, M.D, FAAP
American Hospital Dubai

2. What the diet have to do with it???
Increased prevalence in Autism>>environmental factors>>Diet
Parents survey on ARI list diet as the most successful intervention
Global displacement of traditional foods accompanied by malnutrition and chronic disease
When traditional people adopt modern diets there are increased rates of CVD, diabetes, cancer, hyperlipidemia,hypertension, and obesity.
we face the Dilemma where traditional high-fat foods also contain high amounts of PCBs, mercury, pesticides, and other contaminants.

3. What the diet have to do with it???
Ketogenic diet and seizures
Feingold diet and ADHD : Pesller et al pilot study in Netherland
Celiac disease

4. What the diet have to do with it???
previous reports indicate that the prevalence of GI symptoms ranges widely in individuals with ASD, from 9 to 91% in different study populations
Macroscopic and histological observations in ASD include findings of ileo-colonic lymphoid nodular hyperplasia, enterocolitis, gastritis, and esophagitis
Associated changes in intestinal inflammatory parameters include higher densities of lymphocyte populations, aberrant cytokine profiles, and deposition of immunoglobulin (IgG) and complement C1q on the basolateral enterocyte membrane
Reported functional disturbances include increased intestinal permeability, deficient enzymatic activity of disaccharidases, increased secretin-induced pancreatico-biliary secretion , and abnormal fecal Clostridia taxa
Some children placed on exclusion diets or treated with the antibiotic vancomycin are reported to improve in cognitive and social function. Furthermore, a recent study found a strong correlation between GI symptoms and autism severity

5. Recent Data about the role of Diet
Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with Autism and Gastrointestinal Disturbances. PLoS ONE 2011
Major findings in this study that may shed light on GI morbidity in ASD include the observations that: (1) levels of transcripts for disaccharidases and hexose transporters are reduced in AUT-GI children;
(2) AUT-GI children have microbial dysbiosis in the mucoepithelium;
(3) dysbiosis is associated with deficiencies in host disacharidase and hexose transporter mRNA expression.
propose a model whereby deficiencies in disaccharidases and hexose transporters alter the milieu of carbohydrates in the distal small intestine (ileum) and proximal large intestine (cecum), resulting in the supply of additional growth substrates for bacteria. These changes manifest in significant and specific compositional changes in the microbiota of AUT-GI children .

6. ) Schematic representation of enterocyte-mediated digestion of disaccharides and transport of monosaccharides in the small intestine. Disaccharidases (SI, MGAM, and LCT) in the enterocyte brush border break down disaccharides into their component monosaccharides. The monosaccharides, glucose and galactose, are transported from the small intestinal lumen into enterocytes by the sodium-dependent transporter SGLT1. On the basolateral enterocyte membrane, GLUT2, transports glucose, galactose, and fructose out of enterocytes and into the circulation. The expression levels of disaccharidases and hexose transporters may be controlled, in part, by the transcription factor CDX2. B) In the normal small intestine, where expression of disaccharidases and hexose transporters are high, nearly all disaccharides are efficiently digested and monosaccharides are absorbed from the lumen. C) In the AUT-GI intestine, where expression of disaccharidases and hexose transporters are deficient, mono- and disaccharides accumulate in the lumen of the ileum and cecum resulting in dysbiosis, diarrhea, bloating, and flatulence.

7. Phylum-level comparison of the average relative abundance of bacterial taxa in ileal (A) and cecal (B) biopsies. (C–D) Bacteroidete abundance, obtained from pyrosequencing for ileal (C; Mann-Whitney, p = 0.012) and cecal (D; Mann-Whitney, p = 0.008) biopsies. (E–F) Bacteroidete-specific quantitative real-time PCR analysis of ileal (E; Mann-Whitney, p = 0.003) and cecal (F; Mann-Whitney, p = 0.022) biopsies; copy number values are normalized relative to total bacteria copy numbers. *, p<0.05; **, p<0.01.

9. Nutritional Genomics
The human genome today is virtually unchanged from what it was 50,000 years ago. Yet today’s food supply bears little resemblance to that on which our ancestors evolved.
expectations for this field is to match foods to the individual’s genetically determined ability to digest, absorb, and use the nutrients within. Avoiding foods that are not an appropriate match and focusing on those with a positive impact on health

10. Nutritional Genomics
ex: MTHFR gene encodes enzyme 5,10-methylenetetrahydrofolate reductase that activates folate, which in turn serves as a critical methyl donor as well as being essential to maintaining desirable levels of homocysteine.
Individuals with the 677C>T variation in the MTHFR gene are at risk for impaired MTHFR
enzymatic activity when folate intake is low.
The Role of Nutritional Genomics in Developing an Optimal Diet for Humans Ruth DeBusk, PhD, Nutrition in Clinical Practice December 2010

11. The Gut Brain connection
The first hypothesis:Ketogenic diet and Seizures: glucidic catabolism could cause excess of ketonic products that will initiate comitial seizures. Few studies with ketogenic diet have been conducted but, as it has been described with epileptic subjects, those diets would diminish autistic symptoms.
The second hypothesis: phenylketonuria has been described as being associated with autism. In this case, adapted diet prevents mental retardation and autistic symptoms
The third hypothesis is the amino acid domain. Some autistic children lack some amino acids such as glutamic or aspartic acids and this deficiency would create autistic symptoms. However, these deficits are attributed to nutritional deficits caused by the food selectivity of children

12. The Gut Brain connection
A fourth hypothesis concerning metabolic implication in autism is the suspicion that a food allergy phenomenon could interfere with development, and it has been observed that Ig levels are higher in autistic children than in control children. Autistic children with a positive reaction to food Ig would have a more favorable outcome with diet excluding some kinds of food
The fifth hypothesis is linked with vitamin deficiencies that are a notably important area of research in the treatment of autism. Vitamin B12 or B6 deficiencies have been studied in several articles, and many of them were controlled studies. French teams also emphasize an interest in supplementation with B12 or B6. The two last hypotheses concern auto-immune patterns and the toxic effects of heavy metals like mercury
as evoked by Rimland, 11 controlled placebo-blind studies have been conducted and 50% of autistic children with this supplementation had improved autistic signs.

13. The Gut Brain connection
The opioid-excess hypothesis of autism suggests that autism is the consequence of the incomplete breakdown and excessive absorption of peptides with opioid activity (derived from foods which contain gluten and casein), causing disruption to biochemical and neuroregulatory processes.
Biochemical evidence has indicated the presence of increased levels of peptides in the urine of people with autism
previous behavioral studies have demonstrated a connection between the long term exclusion of gluten and casein from the diet and improvements in the behavior of some children with autism
Accumulating evidence has demonstrated a bidirectional communication between the brain and the gut. Researchers in this field preferentially call this cross-talk the ‘brain–gut axis’ (Aziz & Thompson, 1998). Indeed, it has been shown that a stressful experience can lead to altered gastrointestinal motility, secretions and blood flow; while, in turn, such alteration in gastrointestinal function is transmitted to the brain and can ultimately bring about the perception of visceral events such as nausea, satiety and pain (Drossman, 1998). Interestingly, a number of research papers reported that physical and psychological stress can affect the composition of intestinal microbiota in rodents (Porter & Rettger, 1940; Tannock & Savage, 1974; Suzuki et al. 1983) and primates (Holdeman et al. 1976; Bailey & Coe, 1999). The present results, in which colonizing microbes altered the HPA response to restraint stress, indicate that the interaction of gut bacteria with the brain is also bidirectional, just like the brain–gut axis. To our knowledge, this is the first report that shows commensal microbes affecting the neural network responsible for controlling stress responsiveness.

14. The CF/GF Diet
A Gluten-Free Diet as an Intervention for Autism and Associated Spectrum Disorders: Paul Whiteley Autism Research Unit, University of Sunderland
The introduction of a gluten-free diet to children with autism (n 5 22) was monitored over a 5 month period using a battery of parental and teacher interview/questionnaire sessions, observation reports, psychometric tests and urinary profiling.
Results suggested that participants on a gluten-free diet showed an improvement on a number of behavioral measures
no significant decrease in specific urinary compounds excreted when compared with controls and a gluten challenge group.

15. The CF/GF Diet
Freidman certain ASD subjects deficent in enzyme Dipeptidyl peptidase DPP-IV responsible for breakdown of peptides

16. The specific Carbohydrate Diet
The purpose is to deprive the microbial worlds of the intestine of the food it needs to overpopulate, the sugars from the carbohydrates.
contains predominantly "predigested" carbohydrates allows maximal nourishement without overstimulation of the intestinal microbial population.
As the microbial population decreases due to lack of food (while being balanced by lactobacilli), its harmful by-products also decrease, freeing the intestinal surface of injurious substances. No longer needing protection, the mucus producing cells stop producing excessive mucus, and carbohydrate digestion improved.
many people with IBS and IBD are unable to split disaccharide sugars (lactose, sucrose, maltose, and isomaltose) into single molecule sugars.
The Specific Carbohydrate Diet also eliminates grains, which generally cause inflammation of the intestines in people with IBD. Leo Galland, MD, has found that the Specific Carbohydrate Diet works well for people with IBD."

17. The specific Carbohydrate Diet
many research articles to show that the toxins found in microorganisms play an important role in the suspected causes of ASD, in particular, lipopolysaccharide ( LPS) the bacterial toxins from gram negative bacteria that inhabit the guts of autistic children.
LPS toxicity works synergistically with mercury and other heavy metal poisonings to expand damage. These heavy metals increase harm from LPS.[1] In addition, LPS decreases glutathione levels making it even more difficult for the body to detoxify heavy metals.

18. The GAPS Diet
An altered Abnormal intestinal permeability in children with autism P D'Eufemia JAN 2008 Acta Paediatrica
intestinal permeability was found 43%) autistic patients, but in none of the 40 controls. We speculate that an altered intestinal permeability could represent a possible mechanism for the increased passage through the gut mucosa of peptides derived from foods with subsequent behavioural abnormalities.

19. Elimination Diet
Disruptive behavior: A dietary approach Dan O'Banion, Betty Armstrong The effect of particular foods on levels of hyperactivity, uncontrolled laughter, and disruptive behaviors was studied in an 8- year-old autistic boy.
Data gathered during four phases. During an initial 4-day period the child was fed a normal American diet. A 6-day fasting period followed, during which time only spring water was allowed. The third phase lasted 18 days and involved the presentation of individual foods. During the final phase of the study the child was given only foods that had not provoked a reaction in the third phase. Results showed that foods such as wheat, corn, tomatoes, sugar, mushrooms, and dairy products were instrumental in producing behavioral disorders with this child.

20. Low Oxalate Diet

21. Low phenol Diet
Effects of Phenol-Depleted and Phenol-Rich Diets on Blood Markers of Oxidative Stress Hwa-Young Kim, MSc J AM college of nutrition June 2003
Evidence of difference in phenol metabolism in patients with ASD>>causing oxidative stress in CNS ( Evans 2008, Waring 2000)
Some individuals show reaction to phenol containing foods( spinach, berries, soya, cocoa…) and Salycalate due to Phenolsulfotransferse enzyme which seems to function abnormally in some ASD patients.Waring UK

22. Low Glutamate/ Aspartame diet
Glutamic acid excitatory Neurotransmitter in Brain
Glutamine is found in the following foods: Beans, brewer's yeast, brown rice bran, caseinate, dairy products, eggs, fish, lactalbumin, legumes, meat, nuts, seafood, seeds, soy, whey, whole grains. Hydrolysis of gluten, beet root or other proteins
In 2005 Tebartz et al of Germany reported "increased prefrontal and hippocampal glutamate concentration in schizophrenia".
Reynolds (1991) In 1991 Reynolds of the UK reported glutamate concentrations to be high
Excitotoxicity due to glutamate occurs as part of the ischemic cascade and is associated with stroke2 and diseases like amyotrophic lateral sclerosis, lathyrism, autism, some forms of mental retardation, and Alzheimer's disease.210
Glutamic acid has been implicated in epileptic seizures

23. Serotonin Diet
Dietary increase in Serotonin ( e. g Banana, avocados, pineapple, papaya, walnuts) decreased self injury behavior in Developmentally delayed and Down’s patients
Gedye, A. Biological Psychiatry. 1991: Placebo controlled study: Buspirone was more effective in reducing aggressive/ self injury behavior when combined with serotonin diet.

24. The Body Ecology Diet
Started by Donna Gates no published data about its efficacy
Draws on different dietary approaches ( Macrobiotic diet, D’Adamos Eat for your blood type diet, the Raw food diet..)
Low carbohydrate, low sugar, low dairy, emphasis on raw/ minimally processed foods, fermented foods
Provide high probiotic support, may be beneficial for patients with Dysbiosis.

25. Supplemental Diet
Low urine Calcium level in autistic patients with eye poking behavioral
Clinical pilots Studies showed that ASD and related neurological disorders in adults stems from lack of circulating nutritional neural lipids.
Lipidomics: the function of Vital lipids in embryogenesis preventing ASD. T.Tallberg, J Lipids: 2011
Recommendation of high vital lipids diet for pre and post pregnancy and during BF to secure normal development and enhance IQ in offspring.

26. Supplemental Diet
MIND institute A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins
Children with autism 4–6 years of age (n = 69) were compared to typically developing children A total of 6348 peptide components were
quantified. Of these, five peptide components corresponding to four known proteins had an effect size > 0.99 with a P < 0.05 and a Mascot identification score of 30 or greater for autism
compared to controls. The four proteins were: Apolipoprotein (apo) B-100, Complement Factor H Related Protein (FHR1), Complement C1q and Fibronectin 1 (FN1). In addition, apo B-100 and apo A-IV were higher in children with high compared to low functioning autism.
Apos are involved in the transport of lipids, cholesterol and vitamin E. The complement system is involved in the lysis and removal of infectious organisms in blood, and may be involved in cellular apoptosis in brain.

29. How do I know if my child will benefit?
Hyperactivity, sleep problems
Bloating, constipation, diarrhea
Recurrent OM, Eczema, shiner, AR
Craving food, Pica,
Fatigue, excessive sweating
Family history of Allergies, Celiac Dx, GI diseases.

30. Laboratory Assessment
Casomorphine, Gliadomorphine
Food RAST ( IGG, IGE)
Iron, Ca, Vit D, Oxalate, Zinc, Mg.
Lipid profile
Comprehensive Stool analysis
OAT, AA profile
Celiac disease panel

31. How to assess results Do it with guidance of physician/dietitian
Do it right
But be flexible
Assess every 3 month
Not every diet work for every patient
Keep a food dietary
Remember that it’s only part of the biomedical/ behavioral therapy

32. Avoid pitfalls
CF/GF diet: osteoporosis, lethargy, retinal degeneration, kidney stones.
Low phenol diet: low cholesterol, low antioxidant
Low phenylalanine diet: low Omega 3-6-9
SCD: : osteoporosis, lethargy, retinal degeneration, kidney stones, high copper

33. Books to read Dietary interventions in ASD. By Kenneth Aitken
Food and the Gut Reaction by Elaine Gottschall, B.A., M.Sc.

34. Thank you