Skip to main content

Advertisement

Log in

Evaluation of whole blood zinc and copper levels in children with autism spectrum disorder

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Zinc (Zn) and copper (Cu) are important trace elements for cognitive development and normal neurological functioning. Autism spectrum disorder (ASD) is a common neurological disorder, which has previously been associated with the levels of some trace elements in the blood. However, clinical data regarding the potential implication of Zn and Cu in patients with ASD are still insufficient. Therefore, the aim of the present study was to investigate the whole blood levels of Zn and Cu in a cohort of 28 children with ASD and 28 age- and gender-matched healthy controls. Whole blood Zn and Cu levels were assessed using inductively-coupled plasma-sector field mass spectrometry. Both in the control and in the ASD group, the values of whole blood Cu and Zn were characterized by a Gaussian distribution. The results indicate that the ASD children were characterized by ~10 % (p = 0.005) and ~12 % (p = 0.015) lower levels of whole blood Zn and Zn/Cu ratio, respectively, in comparison to controls. No significant difference in whole blood Cu was observed. However, Cu/Zn ratio was ~15 % (p = 0.008) higher in ASD children than that in the control ones. The results of the present study may be indicative of Zn deficiency in ASD children. Taking into account Zn-mediated up-regulation of metallothionein (MT) gene expression, these findings suggest a possible alteration in the functioning of the neuroprotective MT system. However, further investigations are required to test this hypothesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • ADDM Network - Autism and Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators (2014) Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2010. MMWR Surveill Summ 63(2):1–21

  • APA - American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders: DSM-IV-TR. American Psychiatric Association, Washington, DC

    Google Scholar 

  • APA - American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders: DSM-5. American Psychiatric Association Publishing, Arlington

    Book  Google Scholar 

  • Bjørklund G (2013) The role of zinc and copper in autism spectrum disorders. Acta Neurobiol Exp 73:225–236

    Google Scholar 

  • Böckerman P, Bryson A, Viinikainen J, Viikari J, Lehtimäki T, Vuori E, Keltikangas-Järvinen L, Raitakari O, Pehkonen J (2015) The serum copper/zinc ratio in childhood and educational attainment: a population-based study. J Public Health (Oxf). doi:10.1093/pubmed/fdv187

    Google Scholar 

  • Cuajungco MP, Lees GJ (1997) Zinc metabolism in the brain: relevance to human neurodegenerative disorders. Neurobiol Dis 4:137–169

    Article  CAS  PubMed  Google Scholar 

  • Endreffy I, Bjørklund G, Dicső F, Urbina MA, Endreffy E (2016) Acid glycosaminoglycan (aGAG) excretion is increased in children with autism spectrum disorder, and it can be controlled by diet. Metab Brain Dis 31:273–278

  • Essa MM, Braidy N, Vijayan KR, Subash S, Guillemin GJ (2013) Excitotoxicity in the pathogenesis of autism. Neurotox Res 23:393–400. doi:10.1007/s12640-012-9354-3

    Article  CAS  PubMed  Google Scholar 

  • Faber S, Zinn GM, Kern JC 2nd, Kingston HM (2009) The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders. Biomarkers 14:171–180. doi:10.1080/13547500902783747

    Article  CAS  PubMed  Google Scholar 

  • Iyengar V, Woittiez J (1988) Trace elements in human clinical specimens: evaluation of literature data to identify reference values. Clin Chem 34:474–481

    CAS  PubMed  Google Scholar 

  • Kern JK, Geier DA, Audhya T, King PG, Sykes LK, Geier MR (2012) Evidence of parallels between mercury intoxication and the brain pathology in autism. Acta Neurobiol Exp (Wars) 72:113–153

    Google Scholar 

  • Kern JK, Geier DA, Deth RC, Sykes LK, Hooker BS, Love JM, Bjørklund G, Chaigneau CG, Haley BE, Geier MR (2015) Systematic assessment of research on autism spectrum disorder and mercury reveals conflicts of interest and the need for transparency in autism research. Sci Eng Ethics. doi:10.1007/s11948-015-9713-6

    PubMed  Google Scholar 

  • Kozlowski H, Luczkowski M, Remelli M, Valensin D (2012) Copper, zinc and iron in neurodegenerative diseases (Alzheimer’s, Parkinson’s and prion diseases). Coord Chem Rev 256:2129–2141

    Article  CAS  Google Scholar 

  • Kumar S, Awasthi S, Jain A, Srivastava RC (2004) Blood zinc levels in children hospitalized with severe pneumonia: a case control study. Indian Pediatr 41:486–491

    PubMed  Google Scholar 

  • Li SO, Wang JL, Bjørklund G, Zhao WN, Yin CH (2014) Serum copper and zinc levels in individuals with autism spectrum disorders. Neuroreport 25:1216–1220

    Article  CAS  PubMed  Google Scholar 

  • Macedoni-Lukšič M, Gosar D, Bjørklund G, Oražem J, Kodrič J, Lešnik-Musek P, Zupančič M, France-Štiglic A, Sešek-Briški A, Neubauer D, Osredkar J (2015) Levels of metals in the blood and specific porphyrins in the urine in children with autism spectrum disorders. Biol Trace Elem Res 163:2–10

    Article  PubMed  Google Scholar 

  • Matelski L, Van de Water J (2016) Risk factors in autism: thinking outside the brain. J Autoimmun 67:1–7

  • Mostafa GA, Bjørklund G, Urbina MA, AL-Ayadhi, LY (2016) The levels of blood mercury and inflammatory-related neuropeptides in the serum are correlated in children with autism spectrum disorder. Metab Brain Dis doi:10.1007/s11011-015-9784-8

  • Rodushkin I, Ödman F, Olofsson R, Axelsson MD (2000) Determination of 60 elements in whole blood by sector field inductively coupled plasma mass spectrometry. J Anal At Spectrom 15:937–944

    Article  CAS  Google Scholar 

  • Saad K, Abdel-Rahman AA, Elserogy YM, Al-Atram AA, Cannell JJ, Bjørklund G, Abdel-Reheim MK, Othman HA, El-Houfey AA, Abd El-Aziz NH, Abd El-Baseer KA, Ahmed AE, Ali AM (2015a) Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Nutr Neurosci. doi:10.1179/1476830515Y.0000000019

    PubMed  Google Scholar 

  • Saad K, Eltayeb AA, Mohamad IL, Al-Atram AA, Elserogy Y, Bjørklund G, El-Houfey AA, Nicholson B (2015b) A randomized, placebo-controlled trial of digestive enzymes in children with autism spectrum disorders. Clin Psychopharmacol Neurosci 13:188–193

    Article  PubMed  PubMed Central  Google Scholar 

  • Sakulsak N (2012) Metallothionein: an overview on its metal homeostatic regulation in mammals. Int J Morphol 30:1007–1012

    Article  Google Scholar 

  • Smith TJ, Temple AR, Reading JC (1976) Cadmium, lead, and copper blood levels in normal children. Clin Toxicol 9:75–87

    Article  CAS  PubMed  Google Scholar 

  • Srinivasan P (2009) A review of dietary interventions in autism. Ann Clin Psychiatry 21:237–247

    PubMed  Google Scholar 

  • Stelmashook EV, Isaev NK, Genrikhs EE, Amelkina GA, Khaspekov LG, Skrebitsky VG, Illarioshkin SN (2014) Role of zinc and copper ions in the pathogenetic mechanisms of Alzheimer’s and Parkinson’s diseases. Biochemistry (Mosc) 79:391–396

    Article  CAS  Google Scholar 

  • Stewart-Knox BJ, Simpson EE, Parr H, Rae G, Polito A, Intorre F, Meunier N, Andriollo-Sanchez M, O’Connor JM, Coudray C, Strain JJ (2005) Zinc status and taste acuity in older Europeans: the ZENITH study. Eur J Clin Nutr 59(Suppl 2):S31–S36

    Article  CAS  PubMed  Google Scholar 

  • Takeda A, Tamano H (2009) Insight into zinc signaling from dietary zinc deficiency. Brain Res Rev 62:33–44

    Article  CAS  PubMed  Google Scholar 

  • Valko M, Morris H, Cronin MT (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12:1161–1208

    Article  CAS  PubMed  Google Scholar 

  • Vergani L, Cristina L, Paola R, Luisa AM, Shyti G, Edvige V, Adriana V (2011) Metals, metallothioneins and oxidative stress in blood of autistic children. Res Autism Spectr Disord 5:286–293

    Article  Google Scholar 

  • Zablotsky B, Black LI, Maenner MJ, Schieve LA, Blumberg SJ (2015) Estimated prevalence of autism and other developmental disabilities following questionnaire changes in the 2014 National Health Interview Survey. Natl Health Stat Report 87:1–20

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Geir Bjørklund.

Ethics declarations

Conflict of interest

The authors declare no potential conflicts of interest with respect to the authorship, and/or publication of this paper.

Ethical approval

All procedures were in accordance with the ethical standards of the institutional and/or national research committee/s and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Crăciun, E.C., Bjørklund, G., Tinkov, A.A. et al. Evaluation of whole blood zinc and copper levels in children with autism spectrum disorder. Metab Brain Dis 31, 887–890 (2016). https://doi.org/10.1007/s11011-016-9823-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-016-9823-0

Keywords

Navigation