Zn/Cu Levels in the Field of Autism Disorders: A Systematic Review and Meta-analysis




How to Cite This Article: Sayehmiri F, Babaknejad N, Bahrami S, Sayehmiri K, Darabi M, Rezaei-Tavirani M. Zn/Cu Levels in the Field of Autism Disorders: A Systematic Review and Meta-analysis. Iran J Child Neurol. Autumn 2015;9(4):1-9.

There is probably a relationship between zinc/cupper concentration in individuals
with autism. The present review was written to estimate this probability by using meta-analysis method.

Martials & Methods
In this meta-analysis of Fixed Effect Model, by searching PubMed, Scopus
and Google scholar databases, 11 articles were selected and verified published
in 1978 to 2012. I² statistics were calculated to examine heterogeneity. The
information was analyzed by R and STATA Ver. 11.2.

Due to non-uniform measurement methods of Zn/Cu concentrations, the
concentration of these elements was measured in various subgroups (plasma,
hair and general) in both study cases and controls. There was a significant
statistical difference between plasma OR=0.252 (95% CI: -0.001-0.504) and
hair OR=0.27(95% CI: 0.059-0.481, P=0.01) concentrations of Zn/Cu statuses
between controls and autistic patients. Using a Fixed Effects Model, the overall integration of data from the two groups was significant as risk factor
OR=0.31(95% CI:0.16-0.46, P=0.001).

Significant correlation existed between Zn/Cu levels and the development of
autistic disorders in general analysis. Therefore, Zn/Cu levels could be mentioned as a pathogenesis reason of autism spectrum disorders.


Zinc; Cupper; Concentration; Autism spectrum disorders; Metaanalysis

Full Text:




Arnold LE, Farmer C, Kraemer HC et al. Moderators, Mediators, and Other Predictors of Risperidone Response in Children with Autistic Disorder and Irritability. J Child Adolesc Psychopharmacol 2010;20(2):83-92.

Karimzadeh P. Recent finding about etiology of autism. Rehabilitation 2000; 1(2):58-63.

American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV. 4th ed. Washington, DC: American Psychiatric Association; 2000. ISBN 0-89042-025-4. OCLC 768475353.

Diagnostic criteria for 299.00 Autistic Disorder. 4. Levy SE, Mandell DS, Schultz RT. Autism. Lancet 2009;374 (9701):1627–38.

Abrahams BS, Geschwind DH. Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 2008;9(5):341–55.

Arndt TL, Stodgell CJ, Rodier PM. The teratology of autism. Int J Dev Neurosci 2005;23(2–3):189–99.

Rutter M. Incidence of autism spectrum disorders: changes over time and their meaning. Acta Paediatr 2005;94(1):2-15.

Gerber JS, Offit PA. Vaccines and autism: a tale of shifting hypotheses. Clin Infect Dis 2009;48(4):456-61.

Newschaffer CJ, Croen LA, Daniels J, et al. The epidemiology of autism spectrum disorders. Ann Rev

Public Health 2007; 28:235–58.

Kinney DK, Munir KM, Crowley DJ, Miller AM. Prenatal stress and risk for autism. Neurosci Biobehav

Rev 2008;32(8):1519–32.

Cornish E. Gluten and casein free diets in autism: a study of the effects on food choice and nutrition. J Hum Nutr Dietet 2002; 15:261-268.

De Palma G, Catalani S, Franco A, Brighenti M, Apostoli P, et al. Lack of Correlation Between Metallic Elements Analyzed in Hair by ICP-MS and Autism. J Autism Dev Disord 2012; 42(3):342–353.

Halsted JA, Hackley BM, Smith JC. Plasma zinc and copper in pregnancy and after oral contraceptives. Lancet 1968; 2:278.

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 2011;70(12):1046-51.

Blaurock-Busch E, Amin OR, Dessoki HH, Rabah T. Toxic Metals and Essential Elements in Hair and Severity of Symptoms among Children with Autism. Maedica (Buchar) 2012;7(1):38-48.

Russo AJ. Increased Copper in Individuals with Autism Normalizes Post Zinc Therapy More Efficiently in Individuals with Concurrent GI Disease. Nutrition and Metabolic Insights 2011;4: 49–54.

Russo AJ, Bazin AP, Bigega R, et al. Plasma Copper and Zinc Concentration in Individuals with Autism Correlate with Selected Symptom Severity. Nutr Metab Insights 2012;28(5):41–7.

Van Weyenbergh J, Santana G, Oliveira DA, et al. Zinc/ copper imbalance reflects immune dysfunction in human leishmaniasis: and ex vivo and in vitro study. BMC Infect Dis 2004; 4: 50.

Al-Farsi, Waly MI, Al-Sharbati MM, et al. Levels of Heavy Metals and Essential Minerals in Hair Samples of Children with Autism in Oman: a Case–Control Study. Biol Trace Elem Res 2013;151(2):181-6.

Aschner M, Syversen T, Souza DO, Rocha JBT. Metallothioneins: mercury species-specific induction and their potential role in attenuating neurotoxicity. Exp Biol Med 2006; 231: 1468–1473.

Geir Bjørklund. The role of zinc and copper in autism spectrum disorders. Acta Neurobiol 2013;73: 225–236.

Faber S, Zinn GM, Kern JC, Kingston HM. The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders. Biomarkers 2009;14(3):171-80.

Jackson MJ, Garrod PJ. Plasma zinc, copper and Amino acids levels in the blood of autistic children. J Autism Child Schizophr 1978;8(2):203-8.

Russo AJ. Decreased Serum Cu/Zn SOD in Children with Autism. Nutr Metabol Insights 2009, 2, 27-35.

Shearer TR, Larson k, Neuschwander, Gedney B. Minerals in the hair and nutrient intake of autistic children. J Autism Develop Disord 1982;12:1.

Wecker L, SHifra B, Miller S, et al. Trace element concentrations in hair from autistic children. J Ment Defic Res 1985; 29:15-22.

Xia W, Zhou Y, Sun C, Wang J, Wu L. A preliminary study on nutritional status and intake in Chinese children with autism. Eur J Pediatr 2010;169(10):1201-1205.

Adam JB, Holloway CE, George F, Quig D. Analyses of Toxic Metals and Essential Minerals in the Hair of Arizona Children with Autism and Associated Conditions, and Their Mothers. Biol Trace Element Res 2006;110:193-209.

Lakshmi Priya MD, Geetha A. Level of Trace Elements (Copper, Zinc, Magnesium and Selenium) and Toxic Elements (Lead and Mercury) in the Hair and Nail of Children with Autism. Biol Trace Elem Res 2011;142:148–158.

Elsheshtawy E, Tobar S, Sherra KH, Atallah S, Elkasaby R. Study of some biomarkers in hair of children with autism. Middle East Current Psychiatr 2011; 18:6–10.

Busch EB, Amin OR, Rabah T, et al. Heavy Metals and Trace Elementsn in Hair and Urine of a Sample of Arab Children with Autistic Spectrum Disorder. J Clin Med 2011;6(4):247-57.

DOI: https://doi.org/10.22037/ijcn.v9i4.6780


  • There are currently no refbacks.

Copyright (c) 2015 Iranian Journal of Child Neurology