Role of Diet with Autism

 

Nutr Neurosci. 2003 Feb;6(1):19-28.

Can the pathophysiology of autism be explained by the nature of the discovered urine peptides?

Reichelt KL, Knivsberg AM.

Institute of Pediatric Research, Univ of Oslo, Rikshospitalet, N-0027, Oslo, Norway. k.l.reichelt@klinmed.uio.no

Opioid peptides derived from food proteins (exorphins) have been found in urine of autistic patients. Based on the work of several groups, we try to show that exorphins and serotonin uptake stimulating factors may explain many of the signs and symptoms seen in autistic disorders. The individual symptoms ought to be explainable by the properties and behavioural effects of the found peptides. The data presented form the basis of an autism model, where we suggest that exorphins and serotonin uptake modulators are key mediators for the development of autism. This may be due to a genetically based peptidase deficiency in at least two or more peptidases and, or of peptidase regulating proteins made manifest by a dietary overload of exorphin precursors such as by increased gut uptake.

Abstract

 

Autism. 2002 Sep;6(3):315-28.

Urinary peptides in Rett syndrome.

Solaas KM, Skjeldal O, Gardner ML, Kase FB, Reichelt KL.

Institute of Pediatric Research, The National Hospital, University of Oslo, Norway.

Rett syndrome is a neuro-developmental disorder related to autistic behavior. Persons with autism have previously been found to have hyperpeptiduria. We here report a significantly higher level of peptides in the first fasting morning urine from 53 girls with Rett syndrome (both classical and congenital) compared with 53 healthy girls. This elevation in urinary peptides was similar to that in 35 girls with infantile autism. As in persons with autism, the individual levels of urinary peptides in the Rett syndrome group varied, and about a fifth were within the normal range. Levels of peptides were lower in girls with classic Rett syndrome than in girls with congenital Rett syndrome. This may be due to different etiological causes or to active and stagnant phases of the disease. Urine from girls with Rett syndrome was found to have higher frequency and higher levels of some urinary peptides that may cause inhibition of brain maturation and epilepsy

Abstract

 

Nutr Neurosci. 2002 Sep;5(4):251-61.

A randomised, controlled study of dietary intervention in autistic syndromes.

Knivsberg AM, Reichelt KL, Hoien T, Nodland M.

Center for Reading Research, Stavanger University College, Norway. ann-mari.knivsberg@slf.his.no

Impaired social interaction, communication and imaginative skills characterize autistic syndromes. In these syndromes urinary peptide abnormalities, derived from gluten, gliadin, and casein, are reported. They reflect processes with opioid effect. The aim of this single blind study was to evaluate effect of gluten and casein-free diet for children with autistic syndromes and urinary peptide abnormalities. A randomly selected diet and control group with 10 children in each group participated. Observations and tests were done before and after a period of 1 year. The development for the group of children on diet was significantly better than for the controls.

Abstract

 

Nutr Neurosci. 2001;4(1):25-37.

Reports on dietary intervention in autistic disorders.

Knivsber AM, Reichelt KL, Nodland M.

Center for Reading Research, Stavanger College, Norway. ann-mari.knivsberg@slf.his.no

Autism is a developmental disorder for which no cure currently exists. Gluten and/or casein free diet has been implemented to reduce autistic behaviour, in addition to special education, since early in the eighties. Over the last twelve years various studies on this dietary intervention have been published in addition to anecdotal, parental reports. The scientific studies include both groups of participants as well as single cases, and beneficial results are reported in all, but one study. While some studies are based on urinary peptide abnormalities, others are not. The reported results are, however, more or less identical; reduction of autistic behaviour, increased social and communicative skills, and reappearance of autistic traits after the diet has been broken.

Abstract

 

Cochrane Database Syst Rev. 2004;(2):CD003498.

Gluten- and casein-free diets for autistic spectrum disorder.

Millward C, Ferriter M, Calver S, Connell-Jones G.

BACKGROUND: It has been suggested that peptides from gluten and casein may have a role in the origins of autism and that the physiology and psychology of autism might be explained by excessive opioid activity linked to these peptides. Research has reported abnormal levels of peptides in the urine and cerebrospinal fluid of persons with autism. If this is the case, diets free of gluten and /or casein should reduce the symptoms associated with autism. OBJECTIVES: To determine the efficacy of gluten- and/or casein- free diets as an intervention to improve behaviour, cognitive and social functioning in individuals with autism. SEARCH STRATEGY: Electronic searching of abstracts from the Cochrane Library (Issue 3, 2003), PsycINFO (1971- May 2003), EMBASE (1974- May 2003), CINAHL (1982- May 2003), MEDLINE (1986- May 2003), ERIC (1965-2003), LILACS (to 2003) and the specialist register of the Cochrane Complementary Medicine Field (January 2004). Review bibliographies were also examined to identify potential trials. SELECTION CRITERIA: All randomised controlled trials involving programmes which eliminated gluten, casein or both gluten and casein from the diets of individuals diagnosed with autistic spectrum disorder. DATA COLLECTION AND ANALYSIS: Abstracts of studies identified in searches of electronic databases were read and assessed to determine whether they might meet the inclusion criteria. The authors independently selected the relevant studies from the reports identified in this way. As only one trial fitted the inclusion criteria, no meta-analysis is currently possible and data are presented in narrative form. MAIN RESULTS: The one trial included reported results on four outcomes. Unsurprisingly in such a small-scale study, the results for three of these outcomes (cognitive skills, linguistic ability and motor ability) had wide confidence intervals that spanned the line of nil effect. However, the fourth outcome, reduction in autistic traits, reported a significant beneficial treatment effect for the combined gluten- and casein- free diet. REVIEWERS' CONCLUSIONS: This is an important area of investigation and large scale, good quality randomised controlled trials are needed.

Abstract

 

Expert Opin Ther Targets. 2002 Apr;6(2):175-83.

Biochemical aspects in autism spectrum disorders: updating the opioid-excess theory and presenting new opportunities for biomedical intervention.

Shattock P, Whiteley P.

Autism Research Unit, School of Sciences (Health), University of Sunderland, Sunderland, SR2 7EE, UK.

Autism is a lifelong condition usually described as affecting social, cognitive and imaginative abilities. For many years, parents and some professionals have observed that in concordance with the behavioural and psychological symptoms of the condition, there are a number of physiological and biochemical correlates which may also be of relevance to the syndrome. One area of interest that encompasses many of these observations is the opioid-excess theory of autism. The main premise of this theory is that autism is the result of a metabolic disorder. Peptides with opioid activity derived from dietary sources, in particular foods that contain gluten and casein, pass through an abnormally permeable intestinal membrane and enter the central nervous system (CNS) to exert an effect on neurotransmission, as well as producing other physiologically-based symptoms. Numerous parents and professionals worldwide have found that removal of these exogenously derived compounds through exclusion diets can produce some amelioration in autistic and related behaviours. There is a surprisingly long history of research accompanying these ideas. The aim of this paper is to review the accompanying evidence in support of this theory and present new directions of intervention as a result of it.

Abstract

 

J Autism Child Schizophr. 1978 Sep;8(3):325-37.

Disruptive behavior: a dietary approach.

O'Banion D, Armstrong B, Cummings RA, Stange J.

The effect of particular foods on levels of hyperactivity, uncontrolled laughter, and disruptive behaviors was studied in an 8-year-old autistic boy. The floor of the child's room was taped off into six equal-sized rectangles to measure general activity level. Frequency data were recorded on screaming, biting, scratching, and object throwing. A time-sample technique was used to record data on laughing. Data were 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.

Abstract

 

J Nutr Health Aging. 2005;9(1):31-8.

Dietary omega-3 Fatty acids and psychiatry: mood, behaviour, stress, depression, dementia and aging.

Bourre JM.

French Academy of Medicine, INSERM department of Neuro-pharmaco-nutrition, Hopital Fernand Widal, 75475 Paris cedex 10. jean-marie.bourre@fwidal.inserm.fr

In view of the high omega-3 poly unsaturated fatty acid content of the brain, it is evident that these fats are involved in brain biochemistry, physiology and functioning; and thus in some neuropsychiatric diseases and in the cognitive decline of ageing. Though omega-3 fatty acids (from fatty fish in the human diet) appear effective in the prevention of stress, their role as regulator of mood and of libido is a matter for discussion pending experimental proof in animal and human models. Dietary omega-3 fatty acids play a role in the prevention of some disorders including depression, as well as in dementia, particularly Alzheimer's disease. Their direct role in major depression, bipolar disorder (manic-depressive disease) and schizophrenia is not yet established. Their deficiency can prevent the renewal of membranes, and thus accelerate cerebral ageing; none the less, the respective roles of the vascular component on one hand (where the omega-3's are active) and the cerebral parenchyma itself on the other, have not yet been clearly resolved. The role of omega-3 in certain diseases such as dyslexia and autism is suggested. In fact, omega-3 fatty acids participated in the first coherent experimental demonstration of the effect of dietary substances (nutrients) on the structure and function of the brain. Experiments were first of all carried out one x-vivo cultured brain cells (1), then on in vivo brain cells(2), finally on physiochemical, biochemical, physiological, neurosensory, and behavioural parameters (3). These findings indicated that the nature of poly unsaturated fatty acids(in particular omega-3) present in formula milks for infants (both premature and term) determines the visual, cerebral,and intellectual abilities, as described in a recent review (4). Indeed,the insufficient dietary supply of omega-3 fatty acids in today's French and occidental diet raises the problem of how to correct dietary habits so that the consumer will select foods that are genuinely rich in omega-3/ the omega-3 family ; mainly rapeseed, (canola) and walnut oils on one hand and fatty fish on the other

Abstract

 

Neuropsychobiology. 2005;51(2):77-85.

Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention.

Jyonouchi H, Geng L, Ruby A, Zimmerman-Bier B.

Department of Pediatrics, New Jersey Medical School, UMDNJ, Newark, NJ 07101-1709, USA. jyanouha@umdnj.edu

OBJECTIVE: Our previous study indicated an association between cellular immune reactivity to common dietary proteins (DPs) and excessive proinflammatory cytokine production with endotoxin (lipopolysaccharide, LPS), a major stimulant of innate immunity in the gut mucosa, in a subset of autism spectrum disorder (ASD) children. However, it is unclear whether such abnormal LPS responses are intrinsic in these ASD children or the results of chronic gastrointestinal (GI) inflammation secondary to immune reactivity to DPs. This study further explored possible dysregulated production of proinflammatory and counter-regulatory cytokines with LPS in ASD children and its relationship to GI symptoms and the effects of dietary intervention measures. METHODS: This study includes ASD children (median age 4.8 years) on the unrestricted (n = 100) or elimination (n = 77) diet appropriate with their immune reactivity. Controls include children with non-allergic food hypersensitivity (NFH; median age 2.9 years) on the unrestricted (n = 14) or elimination (n = 16) diet, and typically developing children (median age 4.5 years, n = 13). The innate immune responses were assessed by measuring production of proinflammatory (TNF-alpha, IL-1beta, IL-6, and IL-12) and counter-regulatory (IL-1ra, IL-10, and sTNFRII) cytokines by peripheral blood mononuclear cells (PBMCs) with LPS. The results were also compared to T-cell responses with common DPs and control T-cell mitogens assessed by measuring T-cell cytokine production. RESULTS: ASD and NFH PBMCs produced higher levels of TNF-alpha with LPS than controls regardless of dietary interventions. However, only in PBMCs from ASD children with positive gastrointestinal (GI(+)) symptoms, did we find a positive association between TNF-alpha levels produced with LPS and those with cow's milk protein (CMP) and its major components regardless of dietary interventions. In the unrestricted diet group, GI(+) ASD PBMCs produced higher IL-12 than controls and less IL-10 than GI(-) ASD PBMCs with LPS. GI(+) ASD but not GI(-) ASD or NFH PBMCs produced less counter-regulatory cytokines with LPS in the unrestricted diet group than in the elimination diet group. There was no significant difference among the study groups with regard to cytokine production in responses to T-cell mitogens and other recall antigens. Conclusion: Our results revealed that there are findings limited to GI(+) ASD PBMCs in both the unrestricted and elimination diet groups. Thus our findings indicate intrinsic defects of innate immune responses in GI(+) ASD children but not in NFH or GI(-) ASD children, suggesting a possible link between GI and behavioral symptoms mediated by innate immune abnormalities. Copyright 2005 S. Karger AG, Basel.

Abstract

 

Cochrane Database Syst Rev. 2004;(2):CD003498.

Gluten- and casein-free diets for autistic spectrum disorder.

Millward C, Ferriter M, Calver S, Connell-Jones G.

BACKGROUND: It has been suggested that peptides from gluten and casein may have a role in the origins of autism and that the physiology and psychology of autism might be explained by excessive opioid activity linked to these peptides. Research has reported abnormal levels of peptides in the urine and cerebrospinal fluid of persons with autism. If this is the case, diets free of gluten and /or casein should reduce the symptoms associated with autism. OBJECTIVES: To determine the efficacy of gluten- and/or casein- free diets as an intervention to improve behaviour, cognitive and social functioning in individuals with autism. SEARCH STRATEGY: Electronic searching of abstracts from the Cochrane Library (Issue 3, 2003), PsycINFO (1971- May 2003), EMBASE (1974- May 2003), CINAHL (1982- May 2003), MEDLINE (1986- May 2003), ERIC (1965-2003), LILACS (to 2003) and the specialist register of the Cochrane Complementary Medicine Field (January 2004). Review bibliographies were also examined to identify potential trials. SELECTION CRITERIA: All randomised controlled trials involving programmes which eliminated gluten, casein or both gluten and casein from the diets of individuals diagnosed with autistic spectrum disorder. DATA COLLECTION AND ANALYSIS: Abstracts of studies identified in searches of electronic databases were read and assessed to determine whether they might meet the inclusion criteria. The authors independently selected the relevant studies from the reports identified in this way. As only one trial fitted the inclusion criteria, no meta-analysis is currently possible and data are presented in narrative form. MAIN RESULTS: The one trial included reported results on four outcomes. Unsurprisingly in such a small-scale study, the results for three of these outcomes (cognitive skills, linguistic ability and motor ability) had wide confidence intervals that spanned the line of nil effect. However, the fourth outcome, reduction in autistic traits, reported a significant beneficial treatment effect for the combined gluten- and casein- free diet. REVIEWERS' CONCLUSIONS: This is an important area of investigation and large scale, good quality randomised controlled trials are needed.

Abstract

 

Panminerva Med. 1995 Sep;37(3):137-41.

Food allergy and infantile autism.

Lucarelli S, Frediani T, Zingoni AM, Ferruzzi F, Giardini O, Quintieri F, Barbato M, D'Eufemia P, Cardi E.

Department of Paediatrics, University of Rome La Sapienza, Italy.

The etiopathogenesis of infantile autism is still unknown. Recently some authors have suggested that food peptides might be able to determine toxic effects at the level of the central nervous system by interacting with neurotransmitters. In fact a worsening of neurological symptoms has been reported in autistic patients after the consumption of milk and wheat. The aim of the present study has been to verify the efficacy of a cow's milk free diet (or other foods which gave a positive result after a skin test) in 36 autistic patients. We also looked for immunological signs of food allergy in autistic patients on a free choice diet. We noticed a marked improvement in the behavioural symptoms of patients after a period of 8 weeks on an elimination diet and we found high levels of IgA antigen specific antibodies for casein, lactalbumin and beta-lactoglobulin and IgG and IgM for casein. The levels of these antibodies were significantly higher than those of a control group which consisted of 20 healthy children. Our results lead us to hypothesise a relationship between food allergy and infantile autism as has already been suggested for other disturbances of the central nervous system.

Abstract

 

J Autism Dev Disord. 2000 Oct;30(5):463-9.

Metabolic approaches to the treatment of autism spectrum disorders.

Page T.

Department of Neurosciences, University of California, San Diego, USA.

Although the exact prevalence of metabolic abnormalities in autism spectrum disorders is unknown, several metabolic defects have been associated with autistic symptoms. These include phenylketonuria, histidinemia, adenylosuccinate lyase deficiency, dihydropyrimidine dehydrogenase deficiency, 5'-nucleotidase superactivity, and phosphoribosylpyrophosphate synthetase deficiency. When the metabolic consequences of an enzyme defect are well defined (e.g., phenylketonuria, 5'-nucleotidase superactivity), treatment with diet, drugs, or nutritional supplements may bring about a dramatic reduction in autistic symptoms. This review evaluates evidence for metabolic etiologies in autism spectrum disorders, as well as for the efficacy of dietary and vitamin treatments. The relationship between gastrointestinal abnormalities and autism spectrum disorders is also considered.

Abstract

 

Biol Psychiatry. 1985 May;20(5):467-78.

Vitamin B6, magnesium, and combined B6-Mg: therapeutic effects in childhood autism.

Martineau J, Barthelemy C, Garreau B, Lelord G.

This article reports the behavioral, biochemical, and electrophysiological effects of four therapeutic crossed-sequential double-blind trials with 60 autistic children: Trial A--vitamin B6 plus magnesium/magnesium; Trial B--vitamin B6 plus magnesium; Trial C--magnesium; and Trial D--vitamin B6. Therapeutic effects were controlled using behavior rating scales, urinary excretion of homovanillic acid (HVA), and evoked potential (EP) recordings. The behavioral improvement observed with the combination vitamin B6-magnesium was associated with significant modifications of both biochemical and electrophysiological parameters: the urinary HVA excretion decreased, and EP amplitude and morphology seemed to be normalized. These changes were not observed when either vitamin B6 or magnesium was administered alone.

Abstract

 
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