Biomedical Therapy for Autism and Developmental Delays

A few comments are in order. There have been many changes in the biomedical therapy approach both in terms of testing and treatment. It’s an ongoing process. The great news is that there has been a considerable amount of new scientific validation for many of the initial laboratory tests and just the opposite for some. The same holds true for some of the therapies and….. many new approaches are showing results.

Lab Testing

In the area of laboratory evaluations, the newer methods include a simple urine sample that saturates a paper collection device, expanded salivary panels, using a few drops of blood, think similar to getting a blood sugar level, but that can accurately give multiple results. All of these methods reduce time and discomfort so theirs much less trauma at the collection centers or as an alternative, you can even do it yourself, at home.  As a note, these labs are not the Theranos group, that was unreliable.

Change…

Treatments have been streamlined and it would seem prudent to  also note that we always start with limited changes to one’s lifestyle or supplement intake. Why….because change is difficult and especially in many of the situations we encounter with ASD/PPD patients. We recognize that everyone wants results literally yesterday. It’s not generally possible nor a reasonable expectation. The biomedical approach is intended for long lasting and impactful change. That means we need to find the causes of the disturbed chemistry and slowly adjust it back towards normal.

Chemistry

I would encourage you to read the lengthy article below and get an idea of the complexity of the chemistry, from a physician parent’s point of view.

Don’t go down the route of the shotgun approach and order a number of supplements or a slew of tests, until a good history and physical can be done. It will impede getting good lab information and most of the time is neither cost or time effective.

Our method

At the Center of Health, we see ourselves as your coach, in the process of being a detective and uncovering the clues that need to be followed, while leaving those that don’t get results behind. You and your family will be the best at knowing what changes take place and really keeping track of your family member’s behavioral progress. It’s a team event to get your loved one on track.

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Please call us and arrange for an appointment as the earlier we can make changes the higher the chance for lifelong optimization of one’s health. 541.773.3191

I’ve included an excellent overview of the biomedical treatment of autism, from Dr. Rossignol’s 2009 article below. He describes it as the simplified approach….which it is…. even though it may seem rather overwhelming, hang in there as it’s a powerful means to making changes to your family member. I’ve added highlighted comments in the article for some clarifications.

Diagnosis autism: Now what?

A Simplified Biomedical Approach

By Dan Rossignol, MD, FAAFP

 

In 2002, my older son, Isaiah, was diagnosed with autism. At the time I had been practicing as a family physician for about 12 years. Prior to his diagnosis, Isaiah loved to get down on the floor and spin objects, and I thought it was cool, so I helped him. He also used to shake his hands back and forth in the air for hours. When I tried to shake my hands like him, I tired out in a couple of minutes. I couldn’t figure out how he could do it for hours! He had a significant speech delay and walked very late.

However, despite all of these problems, I did not have a CLUE that he had autism.

 
I remember when my wife and I went to his psychological evaluation to determine what was wrong with him. He was evaluated by a pediatric neurologist and several psychologists, and we spent the morning with him during the testing. We were then told to go to lunch while the team met to determine a diagnosis. I remember as we sat in McDonalds eating French fries and cheeseburgers that my wife and I discussed that maybe the team would say he had “autistic tendencies.” It was quite a shock to us when Isaiah was actually diagnosed with autism! For the first year after his diagnosis, my wife started looking into biomedical treatments, which I considered “quackery.”

I remember as we sat in McDonalds eating French fries and cheeseburgers that my wife and I discussed that maybe the team would say he had “autistic tendencies.”

 
It was quite a shock to us when Isaiah was actually diagnosed with autism! For the first year after his diagnosis, my wife started looking into biomedical treatments, which I considered “quackery.”

I remember asking some developmental disorder-not otherwise specified (PDD-NOS, also called high- functioning autism or mild autism), will generally come from a developmental pediatrician or a neurologist. Most neurologists will perform genetic testing (including chromosomal analysis and checking for fragile X syndrome), a developmental disorder-not otherwise specified (PDD-NOS, also called high- functioning autism or mild autism), will generally come from a developmental pediatrician or a neurologist. Most neurologists will perform genetic testing (including chromosomal analysis and checking for fragile X syndrome), an MRI scan (to exclude some type of brain structural problem), and an EEG (to look for seizure activity). An EEG is especially important because newer studies are reporting that about 60% or more of children with autism have subclinical seizure activity (subclinical means that you are not aware of this seizure activity) 3,4. We find significant improvements, especially in speech, in some children with autism when we treat seizures, with medication.

After the initial diagnosis, there are specific laboratory tests that can be very helpful in either checking for other medical conditions (that could be exacerbating the autistic behavior) or defining underlying biomedical problems. Since autism is diagnosed based upon examination of the child’s behavior, the actual diagnosis does not point to the underlying cause(s) of the disorder.

We find that some of the core problems in autism include toxicity (including elevated levels of heavy metals, pesticides, and other chemicals)5,6, in inflammation (potentially in the gastrointestinal tract and brain)7-9, oxidative stress (damage to tissue caused by free radicals, which are neutralized by antioxidants such as vitamins C and E)10, impaired glutathione production (which is the body’s main natural detoxifier and antioxidant)10, and impaired mitochondrial function (which are responsible for producing ATP, or energy)11.

An in-depth discussion of each of these biomedical problems is beyond the scope of this article, but we will review simple laboratory tests and nutritional supplementation that any parent of a child with autism could start and which could potentially alleviate these problems and improve autistic behaviors. After the initial diagnosis, there are specific laboratory tests that can be very helpful in either checking for other medical conditions (that could be exacerbating the autistic behavior) or defining underlying biomedical problems. Since autism is diagnosed based upon examination of the child’s behavior, the actual diagnosis does not point to the underlying cause(s) of the disorder.

Shortly after this, my second son, Joshua, was also diagnosed with autism. I now realize that God allowed us to have two children with autism to give me a new career (taking care of children with autism) and to give us the ability to help other parents who also have children with autism.

Now that I look back on things, I realize that we (me more so than my wife) wasted precious time because I didn’t know what to do for my child. And I am a physician, and my wife is a nurse practitioner!

 
Fortunately, there are currently many resources available to parents of a child with autism such as websites, books, and conferences. However, navigating through all of these possibilities can be daunting. The purpose of this article is to empower you, as a parent of a child with autism, by providing a starting point for biomedical treatments for your child.
 

Initial laboratory testing:

In many cases, a physician will need to order these tests for you.

The Complete Blood Count (CBC) and Comprehensive Metabolic Panel (CMP) check for anemia, platelet count (a high count is consistent with inflammation), and liver and kidney function.

Thyroid. We find a significant number of children with autism who have hypothyroidism, which can mimic some of the symptoms of autism and impair development. A simple blood test called TSH can check for this problem. (This single test is insufficient to get you the full story)

 

Iron deficiency can cause inattention and concentration problems 12. Low iron is also linked to lowered IQ 13. Iron supplementation in children with attention deficit hyperactivity disorder (ADHD) who have low iron levels has been shown to improve attention compared to a placebo 14, and iron supplementation in children with autism has been shown to improve sleep 15. (A full panel including ferritin is essential to know one’s iron status)

 

Ammonia and lactic acid are initial tests that can help determine if mitochondrial dysfunction exists, which can lead to low energy production and hypotonia (low muscle tone)11 and is potentially treatable with supplements like coenzyme Q10 and L-carnitine. (We use the OATs testing to give a more comprehensive overview of mitochondrial function)

 

Cholesterol. A cholesterol count less than 145 mg/dl in typical children has been shown to increase defiance and irritability and increase the chances of school suspension by three-fold16. Supplementation with cholesterol in some children with autism may be beneficial 17.

 

Cysteine is the precursor to glutathione and is the rate-limiting step for glutathione production. Low levels of cysteine reflect impaired glutathione production or increased glutathione utilization due to oxidative stress18.

 

Lead has been shown in some studies to contribute to autistic behaviors in some children 19,20. An elevated blood lead level reflects ongoing exposure and should prompt an investigation into possible sources of lead in the house or environment.

 

Magnesium has a calming effect, and lower levels have been found in children with ADHD 21 and autism 22. Magnesium supplementation can decrease hyperactivity 23 and improve certain autistic behaviors 22. ( We have found a good tasting set of products that works)

 

Testosterone. A small percentage of children with autism have elevated testosterone 24, which can lead to aggression.

The organic acid panel (OAT) is a specialized test that can measure markers of yeast, Clostridia, and other markers such as vitamin levels and mitochondrial function.

Urinary porphyrin concentrations can reflect increased heavy metal or pesticide levels in the kidney and are markers of the metal burden in the body5.

 

Urinary neopterin is a marker of inflammation and tends to reflect autoimmunity in some children with autism25. Elevated neopterin often predicts positive responses to anti-inflammatory treatments.

Urinary oxidized DNA and RNA are markers of oxidative stress inside the cell 26, and children with elevated levels often have improvements with antioxidants.

Urinary isoprostane is a marker of oxidative stress outside the cell26. Again, antioxidants can be helpful when this is elevated.

 

Stool testing can check for the presence of inflammation, dysbiosis (increased levels of yeast and abnormal bacteria), digestion, and absorption.

 

Initial treatments:

There are certain treatments that parents can use to help improve certain behaviors in children with autism (and ADHD). The ideal treatment would be one that is well- studied, proven to be effective compared to a placebo, not too expensive, safe and tolerable, and can be done at home. Not many nutritional supplements fit into this category, but several do. Many of these supplements are antioxidants that help to lower oxidative stress, which is a common finding in both ADHD27 and autism18. With the use of an evidence-based medicine approach, parents can get started with some simple biomedical treatments based upon the above laboratory testing and/or the child’s behaviors. For example, if oxidative stress is elevated, then antioxidants can be added. If a child has an attention problem, then supplements or dietary changes could be made that have been shown to improve attention.

With the use of an evidence-based medicine approach, parents can get started with some simple biomedical treatments based upon the above laboratory testing and/or the child’s behaviors.

 
For example, if oxidative stress is elevated, then antioxidants can be added. If a child has an attention problem, then supplements or dietary changes could be made that have been shown to improve attention.
 

Diet: Several studies have shown improvements in certain autistic behaviors, such as social isolation, communication, and overall behavior, with the use of a gluten-free/casein-free diet1,2,28. Food additives, colorings, and preservatives can increase hyperactivity in typical children 29, so avoiding these products can be helpful. In children with autism, testing for food allergies and eliminating reactive foods has been shown to improve certain autistic behaviors 30. An organic diet can be helpful in eliminating pesticide exposures in children 31.BIOMEDICALA ketogenic diet can be helpful in some children with autism32. It should be noted that the use of specialized diets should be closely monitored by a physician or nutritionist.

 

Sleep: If this is a problem, I usually start with trying to improve sleep because autistic behaviors are usually worsened with sleep deprivation33. One recent study revealed a defect in the ASMT gene that resulted in less melatonin production in some children with autism (this defect was also found in some of the parents)34. Several studies have shown improvement in sleep with the use of melatonin in autism35,36 and ADHD37. Melatonin at doses of 1-3 mg at bedtime is safe.

 

Multivitamin: A general moderate-dose multivitamin has been shown to improve sleep and gastrointestinal problems in children with autism when compared to a placebo 38. (Not all supplements are created equal in quality or contents, don’t just go for price or best advertisement)

 

Vitamin C: In a double-blind, placebo- controlled study, vitamin C (about 100 mg/kg) was shown to reduce stereotypical behavior (stimming) in individuals with autism compared to a placebo 39.

Methylcobalamin and folinic acid: Two studies have reported some improvements in certain autistic behaviors with the use of subcutaneous methylcobalamin injections (75 mcg/kg, requires a prescription) and oral supplementation of folinic acid (400 mcg twice a day)10-40. Methylcobalamin can also be given orally. (Always get tested before begining these very useful therapies)

 

Zinc: Deficiency has been correlated with inattention in children with ADHD41. Zinc deficiency has also been reported in autism42. In one study of 400 children, the use of zinc sulfate (150 mg/day that provided 40 mg/day of elemental zinc) was shown to improve ADHD symptoms compared to a placebo 43. (This is the too much is no better than too little. There is a simple oral test to know if you need more or less.)

 

Magnesium and vitamin B-6: The use of these (given together) has been shown to improve autistic behaviors, including social interaction, communication, and stereotypical behaviors22, and improve hyperactivity in some children 44. Typical doses are: magnesium at 6 mg/kg/day and vitamin B-6 at 0.6 mg/kg/day 22; sometimes higher doses are used under physician supervision.

 

Pycnogenol: This has been shown to increase glutathione levels in children with ADHD 45, decrease oxidative stress46, and improve attention, coordination, concentration, and hyperactivity compared to a placebo 47. A typical dose is 1-2 mg/kg/day.

 

Carnitine: Deficiency has been described in some children with autism48 and can impair mitochondrial function 11. In one study of children with Rett syndrome, L-carnitine significantly improved sleep efficiency, energy level, and communication 49. Carnitine has also been shown to improve attention and aggression in children with ADHD50 as well as lessen hyperactivity51. Generally, we use 50-100 mg/kg/day of L-carnitine or Acetyl-L-carnitine (preferring the latter as it penetrates into the brain better).

 

Carnosine: This has strong antioxidant properties and also has been shown to decrease seizure activity. In one study, L-carnosine (400 mg twice a day) improved speech and social behavior compared to a placebo in children with autism52.

 

Omega-3 fatty acids: Deficiency has been shown to increase hyperactivity, conduct problems, anxiety, and temper tantrums in typical children53. Infants not receiving omega-3 fatty acid supplementation in breast milk or infant formula are about 2-4 times more likely to develop autism54. Several studies have demonstrated improvements, with the use of omega-3 fatty acids in children with developmental coordination disorder55, ADHD56, and autism57,58. Omega-3 fatty acids can also have anti-seizure effects[59]. I usually recommend about 800 mg of EPA and 800 mg of DHA (sometimes higher), which is the approximate dose used in a recent double-blind placebo-controlled study of children with autism showing improvements in hyperactivity and stereotypical behavior 58. I also generally recommend starting antioxidants before omega-3 fatty acid supplementation. (There are a number of sources of omega-3’s with a wide variance between doses, cost and quality…. ask before buying.)

 

Even though these treatments are available without a prescription, it is best to be under a physician’s supervision when using these supplements and implementing significant dietary changes. Furthermore, a physician may be required to obtain certain laboratory tests and methylcobalamin injections. However, the supplements listed in this article are generally well-tolerated and can be helpful in improving certain behaviors in children with autism and ADHD. I would recommend sitting down with your child’s physician to discuss these potential treatment options.

 

References

 

1 Whiteley, P., et al., A gluten-free diet as an intervention for autism and associated spectrum disorders: preliminary ndings. Autism, 1999. 3(1): p. 45.

2 Knivsberg, A.M., et al., A randomized, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci, 2002. 5(4): p. 251-61.

3 Lewine, J.D., et al., Magnetoencephalographic patterns of epileptiform activity in children with regressive autism spectrum disorders. Pediatrics, 1999. 104(3 Pt 1): p. 405-18.

4 Chez, M.G., et al., Frequency of epileptiform EEG abnormalities in a sequential screening of autistic patients with no known clinical epilepsy from 1996 to 2005. Epilepsy Behav, 2006. 8(1): p. 267-71.

5 Nataf, R., et al., Porphyrinuria in childhood autistic disorder: implications for environmental toxicity. Toxicol Appl Pharmacol, 2006. 214(2): p. 99-108.

6 Geier, D.A., et al., Biomarkers of environmental toxicity and susceptibility in autism. J Neurol Sci, 2009. 280(1-2): p. 101-8.

7 Vargas, D.L., et al., Neuroglial activation and neuro inflammation in the brain of patients with autism. Ann Neurol, 2005. 57(1): p. 67-81.

8 Li, X., et al., Elevated immune response in the brain of autistic patients. J Neuroimmunol, 2009.

9 Torrente, F., et al., Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism. Mol Psychiatry, 2002. 7(4): p. 375-82, 334.

10 James, S.J., et al., Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr, 2004. 80(6): p. 1611-7.

11 Rossignol,D.A.andJ.J.Bradstreet,Evidence of mitochondrial dysfunction in autism and implications for treatment. American Journal of Biochemistry and Biotechnology, 2008. 4(2): p. 208-217.

12 Konofal,E., etal.,Iron deficiency in children with attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med, 2004. 158(12): p. 1113-5.

13 Lozoff,B., etal.,Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev, 2006. 64(5 Pt 2): p. S34-43; discussion S72-91.

14 Konofal,E., etal.,Effectsofironsupplementation on attention de cit hyperactivity disorder in children. Pediatr Neurol, 2008. 38(1): p. 20-6.

15 Dosman,C.F. ,etal.,Children with autism:effect of iron supplementation on sleep and ferritin. Pediatr Neurol, 2007. 36(3): p. 152-8.

16 Zhang,J., etal.,Associationofserumcholesteroland history of school suspension among school-age children and adolescents in the United States. Am J Epidemiol, 2005. 161(7): p. 691-9.

17 Aneja,A.andE.Tierney,Autism:the role of cholesterol in treatment. Int Rev Psychiatry, 2008. 20(2): p. 165-70.

18 James,S.J.,etal.,Metabolic end phenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet, 2006. 141(8): p. 947-56.

19 Lidsky,T.I.andJ.S.Schneider, Autism and autistic symptoms associated with childhood lead poisoning. J Applied Research, 2005. 5(1): p. 80-87.

20 Accardo,P.,etal.,Autismandplumbism.A possible association. Clin Pediatr (Phila), 1988. 27(1): p. 41-4.

21 Kozielec,T.andB.Starobrat-Hermelin,Assessment of magnesium levels in children with attention de cit hyperactivity disorder (ADHD). Magnes Res, 1997. 10(2): p. 143-8.

22 Mousain-Bosc,M.,etal.,Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism. Magnes Res, 2006. 19(1): p. 53-62.

23 Starobrat-Hermelin, B. and T. Kozielec, The effects of magnesium physiological supplementation on hyperactivity in children with attention de cit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test. Magnes Res, 1997. 10(2): p. 149-56.

24 Geier, D.A. and M.R. Geier, A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders. Neuro Endocrinol Lett, 2006. 27(6): p. 833-8.

25 Sweeten, T.L., D.J. Posey, and C.J. McDougle, High blood monocyte counts and neopterin levels in children with autistic disorder. Am J Psychiatry, 2003. 160(9): p. 1691-3.

26 Ming, X., et al., Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins Leukot Essent Fatty Acids, 2005. 73(5): p. 379-84.

27 Ross, B.M., et al., Increased levels of ethane, a non- invasive marker of n-3 fatty acid oxidation, in breath of children with attention de cit hyperactivity disorder. Nutr Neurosci, 2003. 6(5): p. 277-81.

28 Millward,C., etal .,Gluten-and casein-free diets for autistic spectrum disorder. Cochrane Database Syst Rev, 2008(2): p. CD003498.

29 McCann, D., et al., Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomized, double-blinded, placebo- controlled trial. The Lancet, 2007. 370(9598): p. 1560-7.

30 Lucarelli, S., et al., Food allergy and infantile autism. Panminerva Med, 1995. 37(3): p. 137-41.

31 Lu, C., et al., Organic diets significantly lower children’s dietary exposure to organophosphorus pesticides. Environ Health Perspect, 2006. 114(2): p. 260-3.

32 Evangeliou, A., et al., Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol, 2003. 18(2): p. 113-8.

33 Schreck, K.A., J.A. Mulick, and A.F. Smith, Sleep problems as possible predictors of intensi ed symptoms of autism. Res Dev Disabil, 2004. 25(1): p. 57-66.

34 Melke, J., et al., Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry, 2008. 13(1): p. 90-8.

35 Andersen, I.M., et al., Melatonin for insomnia in children with autism spectrum disorders. J Child Neurol, 2008. 23(5): p. 482-5.

36 Garstang,J.andM.Wallis,Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child Care Health Dev, 2006. 32(5): p. 585-9.

37 VanderHeijden,K.B., etal.,Effectofmelatoninon sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad Child Adolesc Psychiatry, 2007. 46(2): p. 233-41.

38 Adams, J.B. and C. Holloway, Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. J Altern Complement Med, 2004. 10(6): p. 1033-9.

39 Dolske, M.C., et al., A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry, 1993. 17(5): p. 765-74.

40 James, S.J., et al., Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr, 2009. 89: p. 1-6.

41 Arnold,L.E., etal.,Serumzinccorrelateswith parent- and teacher- rated inattention in children with attention-de cit/hyperactivity disorder. J Child Adolesc Psychopharmacol, 2005. 15(4): p. 628-36.

42 Yorbik, O., et al., Zinc status in autistic children. J Trace Elem Exp Med, 2004. 17(2): p. 101-107.

43 Bilici, M., et al., Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention de cit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry, 2004. 28(1): p. 181-90.

44 Mousain-Bosc,M., etal.,MagnesiumVitB6intake reduces central nervous system hyperexcitability in children. J Am Coll Nutr, 2004. 23(5): p. 545S-548S.

45 Dvorakova, M., et al., The effect of polyphenolic extract from pine bark, Pycnogenol on the level of glutathione in children suffering from attention de cit hyperactivity disorder (ADHD). Redox Rep, 2006. 11(4): p. 163-72.

46 Chovanova,Z., et al.,Effectofpolyphenolicextract, Pycnogenol, on the level of 8-oxoguanine in children suffering from attention de cit/hyperactivity disorder. Free Radic Res, 2006. 40(9): p. 1003-10.

47 Trebaticka, J., et al., Treatment of ADHD with French maritime pine bark extract, Pycnogenol. Eur Child Adolesc Psychiatry, 2006. 15(6): p. 329-35.

48 Filipek,P.A., etal.,Relative carnitine deficiency in autism. J Autism Dev Disord, 2004. 34(6): p. 615-23.

49 Ellaway,C.J., etal.,Medium-term open label trial of L-carnitine in Rett syndrome. Brain Dev, 2001. 23 Suppl 1: p. S85-9.

50 VanOudheusden,L.J.andH.R.Scholte,Efficacy of carnitine in the treatment of children with attention- de cit hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids, 2002. 67(1): p. 33-8.

51 Torrioli, M.G., et al., A double-blind, parallel, multicenter comparison of L-acetylcarnitine with placebo on the attention de cit hyperactivity disorder in fragile X syndrome boys. Am J Med Genet A, 2008. 146(7): p. 803-12.

52 Chez, M.G., et al., Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol, 2002. 17(11): p. 833-7.

53 Stevens, L.J., et al., Omega-3 fatty acids in boys with behavior, learning, and health problems. Physiol Behav, 1996. 59(4-5): p. 915-20.

54 Schultz, S.T., et al., Breastfeeding, infant formula supplementation, and Autistic Disorder: the results of a parent survey. Int Breastfeed J, 2006. 1: p. 16.

55 Richardson, A.J. and P. Montgomery, The Oxford- Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder. Pediatrics, 2005. 115(5): p. 1360-6.

56 Sinn, N., J. Bryan, and C. Wilson, Cognitive effects of polyunsaturated fatty acids in children with attention de cit hyperactivity disorder symptoms: a randomized controlled trial. Prostaglandins Leukot Essent Fatty Acids, 2008. 78(4-5): p. 311-26.

57 Meguid, N.A., et al., Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clin Biochem, 2008.

58 Amminger, G.P., et al., Omega-3 fatty acids supplementation in children with autism: a double- blind randomized, placebo-controlled pilot study. Biol Psychiatry, 2007. 61(4): p. 551-3.

59 Schlanger, S., M. Shinitzky, and D. Yam, Diet enriched with omega-3 fatty acids alleviates convulsion symptoms in epilepsy patients. Epilepsia, 2002. 43(1): p. 103-4.

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