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Mercury and Autism: Is there a Link ?

(12.11.2017)


Background:
Mercury is a potent neurotoxin. Depending on the species looked at, it may stay in the human body (e.g. in the brain) for decades (see EVISA News below). Therefore, also small amounts should be avoided because they can be accumulated during life, causing cumulative adverse effects. The Agency for Toxic Substances and Disease Registry (ATSDR) affirms that young children and fetuses are particularly sensitive to harmful mercury-related effects such as “brain damage, mental retardation, incoordination, blindness, seizures and inability to speak. While the level of toxicity of mercury strongly depends on the species, all mercury species are strongly toxic.  

Humans are exposed to different mercury species by several pathways: inorganic mercury is present in the environment, may be a risk factor in special working environments (e.g. chlor-alkali industry, mining) and may be released from dental amalgam. Organic mercury is present in the form of methylmercury in fish and in the form of ethylmercury as a component that makes up 50% of the vaccine preservative thimerosal. Organic mercury compounds are even more dangerous in comparison to inorganic species, since they can cross the blood-brain barrier causing numerous neurological problems. Numerous studies (see some references below) have found exposure to organic mercury being a strong risk factor for neurodevelopmental disorders such as Autism spectrum disorder (ASD), tic disorders, delayed language and attention-deficit/hyperactivity disorder (ADHD).

Despite this toxicological profile of mercury compounds, the Centers for Disease Control and Prevention (CDC) refuses to admit that mercury in vaccines is an ASD risk factor and is discouraging researchers to continue to focus attention on the compelling relationship between mercury and ASD.

New studies:
Two new studies by Iranian teams, have validated the link between autism and mercury. A team of researchers investigated the relationship between ASD and mercury levels in hair, urine, blood, red blood cells (RBC), and brain through a meta-analysis of published studies. A key benefit of such meta-analysis, which is a quantitative systematic review, is its capability to consolidate “a large, and often complex, sometimes apparently conflicting, body of literature.”

Case-control studies evaluating concentration of total mercury in different tissues of ASD patients and comparing them to the healthy subjects (control group) were identified in several databases. A total of 44 studies were identified that met the necessary criteria for meta-analysis. The mercury level in whole blood, RBC, and brain tissue was significantly higher in ASD patients than healthy subjects, whereas mercury level in hair was significantly lower in ASD patients than healthy subjects. The mercury level in urine was not significantly different between ASD patients and healthy subjects. The authors conclude that their results of the current meta-analysis revealed that mercury is an important causal factor in the etiology of ASD. The authors also offer an explanation by suggesting that the detoxification and excretory mechanisms are impaired in ASD patients which lead to accumulation of mercury in the body.

The second study (published in Progress in Neuropsychopharmacology and Biological Psychiatry by Amene Saghazadeh and Nima Rezaei at the Tehran University of Medical Sciences) examines mercury along with other heavy metals. The included 52 observational studies were related to the metals antimony, arsenic, cadmium, lead, manganese, mercury, nickel, silver, and thallium in different body fluids and tissues such as whole blood, plasma, serum, red cells, hair and urine. The meta-analysis revealed that the hair concentrations of antimony and lead in ASD patients were significantly higher than those of control subjects. Also ASD patients had higher erythrocyte levels of lead and mercury. There were
significantly higher blood lead levels in ASD patients.

Both teams used a variety of techniques to mitigate the potential weaknesses of meta-analyses. These included using multiple databases, search terms and search strategies to identify relevant studies; following established guidelines to assess the quality of each study; investigating sources of and (where appropriate) adjusting for heterogeneity; analyzing subgroup differences (i.e., the distinction between developed and developing countries); and screening for publication bias. The substantial overlap in the individual studies included in each meta-analysis and the comparability of the two teams’ findings offer a further degree of confidence in the results.

Unfortunately, the majority of published studies only measure total mercury, and very few have examined brain tissue. Therefore, future additional studies on mercury levels in different tissues of ASD patients should be undertaken.



The original studies

Tina Jafari, Noushin Rostampour, Aziz A. Fallah, Afshin Hesami, The association between mercury levels and autism spectrum disorders: A systematic review and meta-analysis, J. Trace Elements Med. Biol., 44 (2017) 289–297. doi: 10.1016/j.jtemb.2017.09.002

Amene Saghazadeh, Nima Rezaei, Systematic review and meta-analysis links autism and toxic metals and highlights the impact of country development status: Higher blood and erythrocyte levels for mercury and lead, and higher hair antimony, cadmium, lead, and mercury, Progr. Neuro-Psychopharmacol. Biol. Psych.,  79/Part B (2017) 340-368. doi: 10.1016/j.pnpbp.2017.07.011



Related studies (newest first)

H. Li, H. Li, Y. Li, Y. Liu, Z. Zhao, Blood mercury, arsenic, cadmium, and lead in children with autism spectrum disorder, Biol. Trace Elem. Res. (2017), doi: 10.1007/s12011-017-1002-6.

A.V. Skalny, N.V. Simashkova, T.P. Klyushnik, A.R. Grabeklis, G. Bjørklund, M.G. Skalnaya, et al., Hair toxic and essential trace elements in children with autism spectrum disorder, Metab. Brain Dis., 32/1 (2017) 195–202. doi: 10.1007/s11011-016-9899-6

A.V. Skalny, N.V. Simashkova, T.P. Klyushnik, A.R. Grabeklis, I.V. Radysh, M.G. Skalnaya, A.A. Tinkov, Analysis of hair trace elements in children with autism spectrum disorders and communication disorders, Biol. Trace Elem. Res., 177/2 (2017) 215–223. doi: 10.1007/s12011-016-0878-x

A.V. Skalny, N.V. Simashkova, T.P. Klyushnik, A.R. Grabeklis, I.V. Radysh, M.G. Skalnaya, A.A. Nikoronov, A.A. Tinkov, Assessment of serum trace elements and electrolytes in children with childhood and atypical autism, J. Trace Elem. Med. Biol., 43 (2016) 9-14. doi: 10.1016/j.jtemb.2016.09.009

D.A. Geier, J.K. Kern, M.R. Geier, Increased risk for an atypical autism diagnosis following thimerosal-containing vaccine exposure in the United States: a prospective longitudinal case control study in the vaccine safety datalink, J. Trace Elem. Med. Biol., 42 (2017) 18–24. doi: 10.1016/j.jtemb.2017.03.005

D.A. Geier, J.K. Kern, K.G. Homme, M.R. Geier, Abnormal brain connectivity spectrum disorders following thimerosal administration: a prospective longitudinal case–control assessment of medical records in the vaccine safety datalink, Dose Response, 15/1 (2017) 1–12. doi:10.1177/1559325817690849

A. El-Ansary, G. Bjørklund, A.A. Tinkov, A.V. Skalny, H. Al Dera, Relationship between selenium, lead, and mercury in red blood cells of Saudi autistic children, Metab. Brain Dis., 32/4 (2017) 1073–1080. doi: 10.1007/s11011-017-9996-1

Janet K.Kern, David A. Geier, Lisa K. Sykes, Boyd E. Haley, Mark R.Geier, The relationship between mercury and autism: A comprehensive review and discussion, J. Trace Elements Med. Biol., 37 (2016) 8-24. doi: 10.1016/j.jtemb.2016.06.002

E.M. Khaled, N.A. Meguid, G. Bjørklund, A. Gouda, M.H. Bahary, A. Hashish, et al., Altered urinary porphyrins and mercury exposure as biomarkers for autism severity in Egyptian children with autism spectrum disorder, Metab. Brain Dis., 31/6 (2016) 1419–1426. doi: 10.1007/s11011-016-9870-6

V.F. Domingues, C. Nasuti, M. Piangerelli, L. Correia-Sá, A. Ghezzo, M. Marini, P.M. Abruzzo, P. Visconti, M. Giustozzi, G. Rossi, R. Gabbianelli, Pyrethroid pesticide metabolite in urine and microelements in hair of children affected by autism spectrum disorders: a preliminary investigation, Int. J. Environ. Res. Pub. Health, 13/4 (2016) 388. doi:10.3390/ijerph13040388

G.A. Mostafa, G. Bjørklund, M.A. Urbina, L.Y. A.L-Ayadhi, The levels of blood mercury and inflammatory-related neuropeptides in the serum are correlated in children with autism spectrum disorder, Metab. Brain Dis., 31/3 (2016) 593–599. doi: 10.1007/s11011-015-9784-8

K.N. Kim, H.J. Kwon, Y.C. Hong, Low-level lead exposure and autistic behaviors in school-age children, Neurotoxicology, 53 (2016) 193-200. doi: 10.1016/j.neuro.2016.02.004

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S.J. McKean, S.M. Bartell, R.L. Hansen, G.H. Barfod, P.G. Green, I. Hertz-Picciotto, Prenatal mercury exposure, autism, and developmental delay, using pharmacokinetic combination of newborn blood concentrations and questionnaire data: a case control study, Environ. Health, 14 (2015) 62. doi: 10.1186/s12940-015-0045-4

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Mohammad H. Rahbar, Maureen Samms-Vaughan, Aisha S. Dickerson, Katherine A. Loveland, Manouchehr Ardjomand-Hessabi, Jan Bressler, Sydonnie Shakespeare-Pellington, Megan L. Grove, Deborah A. Pearson,  Eric Boerwinkle, Blood Lead Concentrations in Jamaican Children with and without Autism Spectrum Disorder, Int. J. Environ. Res. Public Health, 12 (2015) 83-105. doi: 10.3390/ijerph120100083 

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V.M. Yau, P.G. Green, C.P. Alaimo, C.K. Yoshida, M. Lutsky, G.C. Windham, G. Delorenzo, M. Kharrazi, J.K. Grether, L.A. Croen, Prenatal and neonatal peripheral blood mercury levels and autism spectrum disorders, Environ. Res., 133 (2014) 294–303. doi: 10.1016/j.envres.2014.04.034

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N.W. Hodgson, M.I. Waly, Y.M. Al-Farsi, M.M. Al-Sharbati, O. Al-Farsi, A. Ali, A. Ouhtit, T. Zang, Z.S. Zhou, R.C. Deth, Decreased glutathione and elevated hair mercury levels are associated with nutritional deficiency-based autism in Oman, Exp. Biol. Med., 239/6 (2014) 697–706. doi:10.1177/1535370214527900

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Related information

Wikipedia: Thiomersal controversy
U.S. Food and Drug Administration: Information about Thimerosal in Vaccines
Centers for Disease Control and Prevention (CDC): Frequently asked questions about Thimerosal
NIAID Research on Thimerosal
Toxic Exposure Study Trust (TEST) Foundation: Toxicity of Thimerosal
EVISA Link Database: Thimerosal
Board on Health Promotion and Disease Prevention, Institute of Medicine. 2004. Immunization Safety Review: Vaccines and Autism. Washington, D.C.: National Academies Press. Available at http://www.nap.edu/books/030909237X/html/.
Prisonplanet.com, September 28, 2007: How Mercury Kills the Brain (set of videos)
Translating Autism: Informational blog intended to rapidly disseminate the latest scientific findings related to the nature, causes, & treatments of autism spectrum disorders.




 Related EVISA Resources

Link Database: Toxicity of Organo-mercury compounds
Link Database: Mercury exposure through the diet
Link Database: Environmental cycling of methylmercury
Link Database: Environmental cycling of inorganic mercury
Link Database: Environmental pollution of methylmercury
Link Database: Environmental pollution of inorganic mercury
Link Database: Toxicity of mercury



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