Life Extension Magazine December 2007
Autism:A Nutraceutical Approach
By Julius G. Goepp, MD
Many people with autism also demonstrate poor absorption of nutrients due to inflammation in the gut.26 Poor nutrient absorption can lead to a host of health problems in growing children, including impaired growth and well-being. Individuals affected by autism also commonly suffer problems with elimination, such as diarrhea or constipation.5 Diarrhea can contribute to dehydration and depletion of vitamins and minerals, while constipation impairs the body’s elimination of toxic wastes.
Additionally, it is not unusual to find that those with autism have fewer beneficial bacteria in the gut to manufacture critical vitamins such as B12, K, and biotin.5,27 Autism has also been linked with a common deficiency in a host of micronutrients such as vitamins A, B1, B3, B5, and biotin, selenium, zinc, magnesium, certain essential amino acids, and essential fatty acids.5,28 In addition, some studies suggest that vitamins B6, B12, and folate, which are critical for healthy mood and cognitive function, are also lacking in autism.5
Research has revealed the use of multivitamin supplementation to be beneficial for children with autism.29,30 A 2004 double-blind, placebo-controlled trial showed that by increasing the levels of vitamins B6 and C, children with autism showed improvements in sleep and bowel patterns.29 Sleep provides crucial healing and mood stabilization for most children, and disturbed sleep can lead to a host of childhood complications. It should be noted that multivitamin-mineral supplements for autistic children should not include copper, because people with autism often have elevated copper:zinc ratios.5
Vitamin B6 and Magnesium
Children with autism may have low levels of the enzyme needed to convert dietary vitamin B6 into its active form, which is required to produce important nerve-signaling chemicals (neurotransmitters) that ensure healthy brain function. 29 For these reasons, having low levels of B6 may reduce levels of neurotransmitters that are critical for the development of language and attention and for optimizing sleep, activity, and alertness. Supplementation with vitamin B6 can increase levels of the vitamin’s active form, and has been found to improve sleep, attention, and language.29,31 Rigorous, placebo-controlled trials with B6 have also demonstrated statistically significant improvements in eye contact, speech, and interactions with the environment in children with autism.32
The combination of B6 with magnesium has been described as a “breakthrough autism intervention,”5 with improvement in about half of the cases studied.33,34 Magnesium is an essential mineral that many enzymes require in order to function properly, particularly the enzyme systems that manufacture brain neurotransmitters.5 Multiple studies of vitamin B6 (75 to 800 mg per day) and magnesium (100 to 700 mg per day) have now shown that this particular nutrient combination is dramatically more effective than either nutrient alone.5,35
One of the most impressive and recent studies of this combination comes from France, where researchers treated 33 children aged 1-10 years with autism, using a daily supplement containing B6 (0.6 mg/kg) and magnesium (6 mg/kg) for six months.36 Supplementation safely improved symptoms in 23 of the 33 children, with the most powerful effects seen in social interactions and communication.
Vitamins A and C
Further improvements in the symptoms of autism have been observed with vitamins A and C. Vitamin A is essential for rapidly growing tissue such as gut, brain, and nerves—systems that malfunction in autism. Deficiencies in vitamin A have been noted in some individuals with autism.5,37 In one study, supplementation with vitamin A for three months or longer produced improvements in eye contact, social skills, and sleep in children with autism.38 Vitamin A is stored in body fat, and high levels can be toxic, so it is best to determine a safe dose in consultation with your physician or nutritionist.
Vitamin C, on the other hand, has dual biochemical and antioxidant roles, as well as being an important co-factor in the production of nerve-signaling chemicals.5,39 A 1993 study of high-dose supplementation with vitamin C (8 grams per 154 pounds of body weight) in 18 autistic children revealed improvements in their measures of social relationship to people, observed emotional responses, and sensory responses. These improvements disappeared when the supplements were replaced by placebo.40
Nutrients to Support Detoxification
Boosting the body’s detoxification system has yielded impressive benefits in combating autism. Children with autism often demonstrate impaired ability to detoxify harmful compounds from food, water, air, and byproducts of the body’s own metabolism. Due to these faulty elimination systems, toxic compounds that would normally be quickly neutralized can linger, damaging the delicate nervous system.
The most important detoxification systems in the body require sulfur in a variety of forms to function effectively.3,24 Sulfur compounds such as glutathione, and sulfur-containing amino acids methionine, cystathionine, and cysteine, are often depleted in autistic children, yet are crucial in the enzymatic destruction of toxins, such as phenolic compounds and tyramine, known to be harmful in autism.41,42
In 2002, Lonsdale reported improvements in behavior, speech, and communication in 8 out of 10 autistic children with the sulfur-containing vitamin B1 derivative, thiamine tetrahydrofurfuryl disulfide (TTFD), at a dose of 50 mg twice daily, which also promoted the excretion of some toxic metals in the urine.43 While not yet widely available, TTFD is beginning to reach the dietary supplement market in specialty products targeted at boosting detoxification.
Another promising approach to enhancing the detoxification capabilities of individuals with autism is supplementation with substances that promote healthy levels of glutathione. This substance occurs abundantly in the livers of healthy people where it facilitates the removal of toxins from the body. Natural glutathione taken orally reduces inflammation in the gut, but is not well absorbed from the gut into the bloodstream.44 As people with autism have lower levels of glutathione, 42 supplementation with nutrients that are converted to glutathione, such as glutamine, N-acetylcysteine, lipoic acid, and glycine, can ensure a ready supply of glutathione for the liver.5
An alternate approach to ensuring healthy glutathione levels is to supplement with folinic acid (an active form of folic acid naturally found in food), betaine, and methyl-cobalamin (vitamin B12), all of which are necessary in converting sulfur-containing compounds to glutathione, making it available for its crucial role in neutralizing toxins that may contribute to the symptoms of autism.42
Other Vitamins and Nutrients that May Benefit Autism
Significant improvements in social interaction, communication, and sleep disturbances in autistic individuals have been seen with folic acid, tetrahydrobiopterin (BH4, a chemical derived from folate), iron, and L-carnosine.
Folic acid is a B vitamin that is critical for nervous system development in children, which has been reported via parent questionnaire responses to improve behavior in autistic children.5 In addition, two small studies have shown that folic acid supplements improve motor skills45 and behavior in children with autism.46
Children with autism often display behavioral problems such as repetitive movements and restlessness, and can occasionally experience psychomotor regression (loss of previously attained motor skills). Supplementing with folic acid may help avert these troubling symptoms.
Furthermore, research suggests that tetrahydrobiopterin (BH4), a folate derivative and an essential co-factor in the synthesis of the neurotransmitters dopamine, epinephrine, and serotonin, may play a role in autism. In 2005, Swedish scientists treated 12 boys aged 4-7 years, who had autistic disorder and low concentrations of tetrahydrobiopterin, with daily doses of BH4 (3 mg/kg body weight) or placebo for six months.47 Using an autism rating scale to assess the boys’ behavior, the researchers noted significant improvement in social interaction, one of the core symptoms of autism, among the treated group compared with controls. While BH4 is not yet widely available as a dietary supplement, folate and S-adenosylmethionine (SAMe) influence its synthesis in the body.48,49
Iron deficiency has also been implicated in autism. A recent study revealed that 77% of a group of children with autism spectrum disorder were deficient in iron. Remarkably, iron supplementation significantly improved sleep disturbances in these children. This finding suggests that all children with autistic disorder should be screened for iron deficiency as part of their regular medical care, and that they should treated with iron as indicated.50
Notable benefits for children with autism have been discovered using L-carnosine, a dipeptide that is a potent antioxidant.39 The nutrient is perhaps best known for protecting against damaging glycation (non-enzymatic binding of a sugar with a protein) reactions, which have been implicated in aging and in the complications of diabetes.51 L-carnosine appears to be highly beneficial in autistic subjects, successfully improving socialization, communication, and vocabulary.52
Essential Fatty Acids
Essential fatty acids, particularly the omega-3 fatty acids known as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are cell membrane components that are crucial in normal nerve and blood cell development and function.5 A number of studies have revealed these omega-3 fatty acids to be deficient in the majority of children with autism.53-55 Supplementation with essential fatty acid-rich fish oils has been shown to correct these deficiencies.56 Many physicians believe that their autistic patients benefit from omega-3 supplementation in terms of behavior control and learning.5 Essential fatty acids are also important in fighting the increased inflammatory response seen in many autistic children.57-59
Most recently, Austrian researchers published a double-blind placebo-controlled pilot study comparing omega-3 fatty acid supplementation with placebo in 13 autistic children aged 5-17 years who had severe tantrums, aggression, or self-injurious behaviors.60 After six weeks of treatment with either placebo or 1.5 g/day of omega-3 fatty acids containing 800 mg of EPA and 700 mg of DHA, the treated group showed noticeable improvement on a behavior-rating scale for hyperactivity and stereotypical behavior. No adverse effects were noted, and the researchers concluded that this study provided “preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism.”
Autism has appropriately been called “an extreme challenge to integrative medicine.”5 At the same time, integrative medicine and nutritional approaches offer tremendous promise for the future of this heartbreaking group of disorders. Autistic children’s quality of life can be greatly improved even with what we now know. We can have high hopes that the growing interest of the scientific community will result in urgently needed research to defeat autism within our lifetimes.
If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.
1. Muhle R, Trentacoste SV, Rapin I. The genetics of autism. Pediatrics. 2004 May;113(5):e472-86.
2. Baker SM. Part II: Notes on treatment options. In: Pangborn JB, Baker SM, editors. Biomedical Assessment Options for Children with Autism and Related Problems. San Diego, CA: Autism Research Institute; 2002.
3. Kidd PM. Autism, an extreme challenge to integrative medicine. Part: 1: The knowledge base. Altern Med Rev. 2002 Aug;7(4):292-316.
4. Lord C, Cook EH, Leventhal BL, Amaral DG. Autism spectrum disorders. Neuron. 2000 Nov;28(2):355-63.
5. Kidd PM. Autism, an extreme challenge to integrative medicine. Part 2: medical management. Altern Med Rev. 2002 Dec;7(6):472-99.
6. Serajee FJ, Nabi R, Zhong H, Huq M. Polymorphisms in xenobiotic metabolism genes and autism. J Child Neurol. 2004 Jun;19(6):413-7.
7. Sogut S, Zoroglu SS, Ozyurt H, et al. Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clin Chim Acta. 2003 May;331(1-2):111-7.
8. Horvath K, Perman JA. Autism and gastrointestinal symptoms. Curr Gastroenterol Rep. 2002 Jun;4(3):251-8.
9. Zilbovicius M, Garreau B, Samson Y, et al. Delayed maturation of the frontal cortex in childhood autism. Am J Psychiatry. 1995 Feb;152(2):248-52.
10. Singh VK, Warren R, Averett R, Ghaziuddin M. Circulating autoantibodies to neuronal and glial filament proteins in autism. Pediatr Neurol. 1997 Jul;17(1):88-90.
11. Chez MG, Chin K, Hung PC. Immunizations, immunology, and autism. Semin Pediatr Neurol. 2004 Sep;11(3):214-7.
12. DeStefano F, Thompson WW. MMR vaccine and autism: an update of the scientific evidence. Expert Rev Vaccines. 2004 Feb;3(1):19-22.
13. Fitzpatrick M. MMR: risk, choice, chance. Br Med Bull. 2004;69:143-53.
14. Bradstreet J, Kartzinel J. Biological interventions in the treatment of autism and PDD. San Diego, CA: Autism Research Institute; 2001.
15. Christison GW, Ivany K. Elimination diets in autism spectrum disorders: any wheat amidst the chaff? J Dev Behav Pediatr. 2006 Apr;27(2 Suppl):S162-71.
16. Elder JH, Shankar M, Shuster J, Theriaque D, Burns S, Sherrill L. The gluten-free, casein-free diet in autism: results of a preliminary double blind clinical trial. J Autism Dev Disord. 2006 Apr;36(3):413-20.
17. Shattock P, Whiteley P. The Sunderland Protocol: A Logical Sequencing of Biomedical Interventions for the Treatment of Autism and Related Disorders. Sunderland, UK: Autism Research Unit, University of Sunderland;2002.
18. Vojdani A, O’Bryan T, Green JA, et al. Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism. Nutr Neurosci. 2004 Jun;7(3):151-61.
19. Shattock P, Hooper M, Waring R. Opioid peptides and dipeptidyl peptidase in autism. Dev Med Child Neurol. 2004 May;46(5):357-8.
20. Vojdani A, Pangborn JB, Vojdani E, Cooper EL. Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes are major instigators of autoimmunity in autism. Int J Immunopathol Pharmacol. 2003 Sep;16(3):189-99.
21. Brudnak MA, Rimland B, Kerry RE, et al. Enzyme-based therapy for autism spectrum disorders -- is it worth another look? Med Hypotheses. 2002 May;58(5):422-8.
22. Kirkman Laboratories. The Kirkman Guide to Intestinal Health in Autism Spectrum Disorders. Lake Oswego, OR: Kirkman Laboratories;2002.
23. Brudnak MA. Probiotics as an adjuvant to detoxification protocols. Med Hypotheses. 2002 May;58(5):382-5.
24. Garvey J. Diet in autism and associated disorders. J Fam Health Care. 2002;12(2):34-8.
25. Song Y, Liu C, Finegold SM. Real-time PCR quantification of clostridia in feces of autistic children. Appl Environ Microbiol. 2004 Nov;70(11):6459-65.
26. Wakefield AJ, Puleston JM, Montgomery SM et al. Review article: the concept of entero-colonic encephalopathy, autism and opioid receptor ligands. Aliment Pharmacol Ther. 2002 Apr;16(4):663-74.
27. Sandler RH, Finegold SM, Bolte ER, et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000 Jul;15(7):429-35.
28. Page T. Metabolic approaches to the treatment of autism spectrum disorders. J Autism Dev Disord. 2000 Oct;30(5):463-9.
29. Adams JB, Holloway C. Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. J Altern Complement Med. 2004 Dec;10(6):1033-9.
30. Rimland B. The use of vitamin B6, magnesium, and DMG in the treatment of autistic children and adults. In: Shaw W, editor. Biological Treatments for Autism and PDD. Lenexa, KS: The Great Plains Laboratory, Inc; 2005.
31. Levy SE, Hyman SL. Use of complementary and alternative treatments for children with autistic spectrum disorders is increasing. Pediatr Ann. 2003 Oct;32(10):685-91.
32. Rimland B, Callaway E, Dreyfus P. The effect of high doses of vitamin B6 on autistic children: a double-blind crossover study. Am J Psychiatry. 1978 Apr;135(4):472-5.
33. Lelord G, Muh JP, Barthelemy C et al. Effects of pyridoxine and magnesium on autistic symptoms--initial observations. J Autism Dev Disord. 1981 Jun;11(2):219-30.
34. Lelord G, Callaway E, Muh JP. Clinical and biological effects of high doses of vitamin B6 and magnesium on autistic children. Acta Vitaminol Enzymol. 1982;4(1-2):27-44.
35. Martineau J, Barthelemy C, Cheliakine C, Lelord G. Brief report: an open middle-term study of combined vitamin B6-magnesium in a subgroup of autistic children selected on their sensitivity to this treatment. J Autism Dev Disord. 1988 Sep;18(3):435-47.
36. Mousain-Bosc M, Roche M, Polge A, Pradal-Prat D, Rapin J, Bali JP. Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism. Magnes Res. 2006 Mar;19(1):53-62.
37. Clark JH, Rhoden DK, Turner DS. Symptomatic vitamin A and D deficiencies in an eight-year-old with autism. JPEN J Parenter Enteral Nutr. 1993 May;17(3):284-6.
38. Megson MN. Is autism a G-alpha protein defect reversible with natural vitamin A? Med Hypotheses. 2000 Jun;54(6):979-83.
39. McGinnis WR. Oxidative stress in autism. Altern Ther Health Med. 2004 Nov;10(6):22-36.
40. Dolske MC, Spollen J, McKay S, Lancashire E, Tolbert L. A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry. 1993 Sep;17(5):765-74.
41. McFadden SA. Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways. Toxicology. 1996 Jul 17;111(1-3):43-65.
42. James SJ, Cutler P, Melnyk S, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004 Dec;80(6):1611-7.
43. Lonsdale D, Shamberger RJ, Audhya T. Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study. Neuro Endocrinol Lett. 2002 Aug;23(4):303-8.
44. No authors. Glutathione, reduced (GSH). Monograph. Altern Med Rev. 2001 Dec;6(6):601-7.
45. Moretti P, Sahoo T, Hyland K, et al. Cerebral folate deficiency with developmental delay, autism, and response to folinic acid. Neurology. 2005 Mar 22;64(6):1088-90.
46. Gillberg C, Wahlstrom J, Johansson R, Tornblom M, Bertsson-Wikland K. Folic acid as an adjunct in the treatment of children with the autism fragile-X syndrome (AFRAX). Dev Med Child Neurol. 1986 Oct;28(5):624-7.
47. Danfors T, von Knorring AL, Hartvig P, et al. Tetrahydrobiopterin in the treatment of children with autistic disorder: a double-blind placebo-controlled crossover study. J Clin Psychopharmacol. 2005 Oct;25(5):485-9.
48. Ortega TM, Andrés P, López-Sobaler A, et al. The role of folates in the diverse biochemical processes that control mental function. Nutr Hosp. 1994 Jul-Aug;9(4):251-6.
49. Available at: http://www.medscape.com/viewarticle/431514_side. Accessed September 27, 2007.
50. Dosman CF, Brian JA, Drmic IE, et al. Children with autism: effect of iron supplementation on sleep and ferritin. Pediatr Neurol. 2007 Mar;36(3):152-8.
51. Alhamdani MS, Al-Kassir AH, Abbas FK, Jaleel NA, Al-Taee MF. Antiglycation and antioxidant effect of carnosine against glucose degradation products in peritoneal mesothelial cells. Nephron Clin Pract. 2007;107(1):c26-34.
52. Chez MG, Buchanan CP, Aimonovitch MC, et al. Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol. 2002 Nov;17(11):833-7.
53. Bell JG, Sargent JR, Tocher DR, Dick JR. Red blood cell fatty acid compositions in a patient with autistic spectrum disorder: a characteristic abnormality in neurodevelopmental disorders? Prostaglandins Leukot Essent Fatty Acids. 2000 Jul;63(1-2):21-5.
54. Vancassel S, Durand G, Barthelemy C, et al. Plasma fatty acid levels in autistic children. Prostaglandins Leukot Essent Fatty Acids. 2001 Jul;65(1):1-7.
55. Ward PE. Potential diagnostic aids for abnormal fatty acid metabolism in a range of neurodevelopmental disorders. Prostaglandins Leukot Essent Fatty Acids. 2000 Jul;63(1-2):65-8.
56. Bell JG, MacKinlay EE, Dick JR, et al. Essential fatty acids and phospholipase A2 in autistic spectrum disorders. Prostaglandins Leukot Essent Fatty Acids. 2004 Oct;71(4):201-4.
57. Jyonouchi H, Sun S, Le H. Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. J Neuroimmunol. 2001 Nov 1;120(1-2):170-9.
58. Grimm H, Mayer K, Mayser P, Eigenbrodt E. Regulatory potential of n-3 fatty acids in immunological and inflammatory processes. Br J Nutr. 2002 Jan;87 Suppl 1S59-S67.
59. De CR, Liao JK, Libby P. Fatty acid modulation of endothelial activation. Am J Clin Nutr. 2000 Jan;71(1 Suppl):213S-23S.
60. Amminger GP, Berger GE, Schafer MR, Klier C, Friedrich MH, Feucht M. Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol Psychiatry. 2007 Feb 15;61(4):551-3.
61. Levy SE, Hyman SL. Novel treatments for autistic spectrum disorders. Ment Retard Dev Disabil Res Rev. 2005;11(2):131-42.
62. Brown MJ, Willis T, Omalu B, Leiker R. Deaths resulting from hypocalcemia after administration of edetate disodium: 2003-2005. Pediatrics. 2006 Aug;118(2):e534-6.
63. Adams JB, Romdalvik J, Ramanujam VM, Legator MS. Mercury, lead, and zinc in baby teeth of children with autism versus controls. J Toxicol Environ Health A. 2007 Jun;70(12):1046-51.
64. Soden SE, Lowry JA, Garrison CB, Wasserman GS. 24-hour provoked urine excretion test for heavy metals in children with autism and typically developing controls, a pilot study. Clin Toxicol (Phila). 2007 Jun;45(5):476-81.
65. Ng DK, Chan CH, Soo MT, Lee RS. Low-level chronic mercury exposure in children and adolescents: meta-analysis. Pediatr Int. 2007 Feb;49(1):80-7.
66. Kirkman Laboratories. Detoxification of heavy metals in the treatment of autism. A Guide to Scientific Nutrition for Autism and Related Conditions. Lake Oswego, OR: Kirkman Laboratories; 2002.
67. Shannon M, Woolf A, Goldman R. Children’s environmental health: one year in a pediatric environmental health specialty unit. Ambul Pediatr. 2003 Jan;3(1):53-6.
68. Geier DA, Geier MR. A case series of children with apparent mercury toxic encephalopathies manifesting with clinical symptoms of regressive autistic disorders. J Toxicol Environ Health A. 2007 May 15;70(10):837-51.
69. Chisolm JJ, Jr. Safety and efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) in children with elevated blood lead concentrations.J Toxicol Clin Toxicol. 2000;38(4):365-75.
70. Graziano JH, Lolacono NJ, Moulton T, Mitchell ME, Slavkovich V, Zarate C. Controlled study of meso-2,3-dimercaptosuccinic acid for the management of childhood lead intoxication. J Pediatr. 1992 Jan;120(1):133-9.
71. Karunasagar D, Krishna MV, Rao SV, Arunachalam J. Removal and preconcentration of inorganic and methyl mercury from aqueous media using a sorbent prepared from the plant Coriandrum sativum. J Hazard Mater. 2005 Feb 14;118(1-3):133-9.
72. Aga M, Iwaki K, Ueda Y, et al. Preventive effect of Coriandrum sativum (Chinese parsley) on localized lead deposition in ICR mice. J Ethnopharmacol. 2001 Oct;77(2-3):203-8.
73. Geier DA, Geier MR. A comparative evaluation of the effects of MMR immunization and mercury doses from thimerosal-containing childhood vaccines on the population prevalence of autism. Med Sci Monit. 2004 Mar;10(3):I33-9.
74. Hornig M, Chian D, Lipkin WI. Neurotoxic effects of postnatal thimerosal are mouse strain dependent. Mol Psychiatry. 2004 Sep;9(9):833-45.
75. Parker SK, Schwartz B, Todd J, Pickering LK. Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published original data. Pediatrics. 2004 Sep;114(3):793-804.
76. Davidson PW, Myers GJ, Weiss B. Mercury exposure and child development outcomes. Pediatrics. 2004 Apr;113(4 Suppl):1023-9.
77. Halsey NA, Hyman SL. Measles-mumps-rubella vaccine and autistic spectrum disorder: report from the New Challenges in Childhood Immunizations Conference convened in Oak Brook, Illinois, June 12-13, 2000. Pediatrics. 2001 May;107(5):E84.