Autism And The Paleo Diet

A gluten-free, casein-free diet is popular for autism.1 In individuals with leaky gut syndrome, it could be possible that peptides derived from milk and gluten proteins may pass into the systemic circulation. Indeed, autistic children present a variety of gastrointestinal symptoms, and a significant percentage of these children have increased intestinal permeability (the so called leaky gut).2-4

Some of these peptides that are derived from milk and gluten proteins have opiate-like activity,5 which means that if they could access circulation and pass the blood-brain barrier, they would have the capacity to influence a variety of neurotransmitter systems that regulate behaviour.2-5 Since some studies2-6 (but not all)7 have reported abnormal levels of peptides in the urine and cerebrospinal fluid of children with autism, a gluten-free, casein-free diet has been widely promoted for these children.

Nevertheless, current evidence for efficacy of these diets remains poor, and there is an urgent need for large scale, randomized controlled trials.6

Yet, evidence is increasing that autism may be autoimmune in nature,8-17 and that casein and gluten may be implicated through this mechanism.10-13 As readers are aware, we believe that gluten, dairy and other Neolithic foods, such as legumes, potatoes and tomatoes are suspected environmental triggers in various autoimmune diseases. Furthermore, a class of proteins in wheat gluten called gliadins upregulates a protein called zonulin,18 which increases tight junction diameter. This increases gut permeability in virtually all people, and a leaky gut is a common phenomenon in multiple autoimmune diseases,19-39 and in autism.2-4

Therefore, it is our opinion that any dietary intervention study should include the multiple dietary factors implicated in autism, and not just gluten and casein. One such diet is the Paleo diet with its avoidance of grains, dairy, legumes, tomatoes, potatoes or other factors that increase intestinal permeability, such as hot peppers40,41 and alcohol.42

In addition, correcting zinc and vitamin D deficiency is extremely important because such deficiencies may increase intestinal permeability.43,44 Recent evidence appears to show that vitamin D deficiency may be directly implicated in autism.45

References:

1.  Elder JH. The gluten-free, casein-free diet in autism: an overview with clinical implications. Nutr Clin Pract. 2008;23(6):583-588

2.  Kidd PM. Autism, an extreme challenge to integrative medicine. Part: 1: The knowledge base. Altern Med Rev. 2002 Aug;7(4):292-316

3. Kidd PM. Autism, an extreme challenge to integrative medicine. Part 2: medical management. Altern Med Rev. 2002 Dec;7(6):472-99

4.  White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49

5.  Gardner MLG. Exorphins and other biologically active peptides derived from diet. In Brostoff J, Challacombe SJ. Food Allergy and Intolerance 2nd Edition. Saunders, 2002, pgs 465-478

6. Millward C, Ferriter M, Calver S, Connell-Jones G. Gluten- and casein-free diets for autistic spectrum disorder. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD003498

7. Cass H, Gringras P, March J, McKendrick I, O’Hare AE, Owen L, Pollin C. Absence of urinary opioid peptides in children with autism. Arch Dis Child. 2008 Sep;93(9):745-50

8. Singh VK et al. Antibodies to myelin basic protein in children with autistic behavior. Brain, Behavior and Immunity 1993;7:97-103

9.  Warren RP et al. Strong association of the third hypervariable region of HLA-DR beta 1 with autism. J Neuroimmunol 1996;67:97-102

10.  Vojdani A, O’Bryan T, Green JA, Mccandless J, Woeller KN, Vojdani E, Nourian AA, Cooper EL. Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism. Nutr Neurosci. 2004 Jun;7(3):151-61

11. Vojdani A, Bazargan M, Vojdani E, Samadi J, Nourian AA, Eghbalieh N, Cooper EL. Heat shock protein and gliadin peptide promote development of peptidase antibodies in children with autism and patients with autoimmune disease. Clin Diagn Lab Immunol. 2004 May;11(3):515-24

12. 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-Dec;16(3):189-99

13. Vojdani A, Campbell AW, Anyanwu E, Kashanian A, Bock K, Vojdani E. Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A. J Neuroimmunol. 2002 Aug;129(1-2):168-77

14.  Enstrom AM, Van de Water JA, Ashwood P. Autoimmunity in autism. Curr Opin Investig Drugs. 2009 May;10(5):463-73

15. Castellani ML, Conti CM, Kempuraj DJ, Salini V, Vecchiet J, Tete S, Ciampoli C, Conti F, Cerulli G, Caraffa A, Antinolfi P, Galzio R, Shaik Y, Theoharides TC, De Amicis D, Perrella A, Cuccurullo C, Boscolo P, Felaco M, Doyle R, Verrocchio C, Fulcheri M. Autism and immunity: revisited study. Int J Immunopathol Pharmacol. 2009 Jan-Mar;22(1):15-9

16.  Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral D, Van de Water J. Autoantibodies in autism spectrum disorders (ASD). Ann N Y Acad Sci. 2007 Jun;1107:79-91

17. Zimmerman AW, Connors SL, Matteson KJ, Lee LC, Singer HS, Castaneda JA, Pearce DA. Maternal antibrain antibodies in autism. Brain Behav Immun. 2007 Mar;21(3):351-7

18.  Drago S, El Asmar R, Di Pierro M, Grazia Clemente M, Tripathi A, Sapone A, Thakar M, Iacono G, Carroccio A, D’Agate C, Not T, Zampini L, Catassi C, Fasano A. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006 Apr;41(4):408-19

19. Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Br J Nutr. 2000 Mar;83(3):207-17

20. Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol. 2008 Nov;173(5):1243-52

21. Teshima CW, Meddings JB. The measurement and clinical significance of intestinal permeability. Curr Gastroenterol Rep. 2008 Oct;10(5):443-9

22. Meddings JB, Jarand J, Urbanski SJ, Hardin J, Gall DG. Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat. Am J Physiol. 1999 Apr;276(4 Pt 1):G951-7

23. Harrison LC, Honeyman MC. Cow’s milk and type 1 diabetes: the real debate is about mucosal immune function. Diabetes. 1999 Aug;48(8):1501-7

24.  Watts T, Berti I, Sapone A, Gerarduzzi T, Not T, Zielke R, Fasano A. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2916-21

25. Neu J, Reverte CM, Mackey AD, Liboni K, Tuhacek-Tenace LM, Hatch M, Li N, Caicedo RA, Schatz DA, Atkinson M. Changes in intestinal morphology and permeability in the biobreeding rat before the onset of type 1 diabetes. J Pediatr Gastroenterol Nutr. 2005 May;40(5):589-95

26. Vaarala O. Is type 1 diabetes a disease of the gut immune system triggered by cow’s milk insulin? Adv Exp Med Biol. 2005;569:151-6

27. Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, Lampis R, Kryszak D, Cartenì M, Generoso M, Iafusco D, Prisco F, Laghi F, Riegler G, Carratu R, Counts D, Fasano A. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006 May;55(5):1443-9

28. Bosi E, Molteni L, Radaelli MG, Folini L, Fermo I, Bazzigaluppi E, Piemonti L, Pastore MR, Paroni R. Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia. 2006 Dec;49(12):2824-7

29.  Simpson MD, Norris JM. Mucosal immunity and type 1 diabetes: looking at the horizon beyond cow’s milk. Pediatr Diabetes. 2008 Oct;9(5):431-3

30. Vaarala O. Leaking gut in type 1 diabetes. Curr Opin Gastroenterol. 2008 Nov;24(6):701-6

31. Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A, Goldblum SE. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000 Apr 29;355(9214):1518-9

32 . Drago S, El Asmar R, Di Pierro M, Grazia Clemente M, Tripathi A, Sapone A, Thakar M, Iacono G, Carroccio A, D’Agate C, Not T, Zampini L, Catassi C, Fasano A.  Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006 Apr;41(4):408-19

33. Lammers KM, Lu R, Brownley J, Lu B, Gerard C, Thomas K, Rallabhandi P, Shea-Donohue T, Tamiz A, Alkan S, Netzel-Arnett S, Antalis T, Vogel SN, Fasano A. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology. 2008 Jul;135(1):194-204.e3

34.  Smecuol E, Sugai E, Niveloni S, Vázquez H, Pedreira S, Mazure R, Moreno ML, Label M, Mauriño E, Fasano A, Meddings J, Bai JC.  Permeability, zonulin production, and enteropathy in dermatitis herpetiformis. Clin Gastroenterol Hepatol. 2005 Apr;3(4):335-41

35. Yacyshyn B, Meddings J, Sadowski D, Bowen-Yacyshyn MB.  Multiple sclerosis patients have peripheral blood CD45RO+ B cells and increased intestinal permeability. Dig Dis Sci. 1996 Dec;41(12):2493-8

36.  Vaile JH, Meddings JB, Yacyshyn BR, Russell AS, Maksymowych WP. Bowel permeability and CD45RO expression on circulating CD20+ B cells in patients with ankylosing spondylitis and their relatives. J Rheumatol. 1999 Jan;26(1):128-35

37. Wyatt J, Vogelsang H, Hübl W, Waldhöer T, Lochs H. Intestinal permeability and the prediction of relapse in Crohn’s disease. Lancet. 1993 Jun 5;341(8858):1437-9

38. D’Incà R, Annese V, di Leo V, Latiano A, Quaino V, Abazia C, Vettorato MG, Sturniolo GC. Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn’s disease. Aliment Pharmacol Ther. 2006 May 15;23(10):1455-61

39. Collett A, Higgs NB, Gironella M, Zeef LA, Hayes A, Salmo E, Haboubi N, Iovanna JL, Carlson GL, Warhurst G. Early molecular and functional changes in colonic epithelium that precede increased gut permeability during colitis development in mdr1a(-/-) mice. Inflamm Bowel Dis. 2008 May;14(5):620-31

40.  Jensen-Jarolim E, Gajdzik L, Haberl I, Kraft D, Scheiner O, Graf J. Hot spices influence permeability of human intestinal epithelial monolayers. J Nutr. 1998 Mar;128(3):577-81

41.  Tsukura Y, Mori M, Hirotani Y, Ikeda K, Amano F, Kato R, Ijiri Y, Tanaka K. Effects of capsaicin on cellular damage and monolayer permeability in human intestinal Caco-2 cells. Biol Pharm Bull. 2007 Oct;30(10):1982-6

42.  Purohit V, Bode JC, Bode C, Brenner DA, Choudhry MA, Hamilton F, Kang YJ, Keshavarzian A, Rao R, Sartor RB, Swanson C, Turner JR. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Alcohol. 2008 Aug;42(5):349-61

43.  Kong J, Zhang Z, Musch MW, Ning G, Sun J, Hart J, Bissonnette M, Li YC. Novelole of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G208-16

44.  Finamore A, Massimi M, Conti Devirgiliis L, Mengheri E. Zinc deficiency induces membrane barrier damage and increases neutrophil transmigration in Caco-2 cells. J Nutr. 2008 Sep;138(9):1664-70

45. Cannell JJ. Autism and vitamin D. Med Hypotheses. 2008;70(4):750-9

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3 Responses to “Autism And The Paleo Diet”

  1. Jen Says:

    really like this!! I used to work one on one with a child with autism! I want to pass this along to his mother! Thank you so much!

    • dochand Says:

      You are quite welcome! Thanks for visiting the blog. And please keep us posted as to this special child’s progress with the Paleo Diet.

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