CONEM

Council for Nutritional and Environmental Medicine

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Zinc, Copper, and Autism Spectrum Disorder

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Joint Research

Research indicates that children with autism spectrum disorder (ASD) appear to be at risk for zinc (Zn) deficiency, copper (Cu) toxicity, and often disturbed metallothionein system functioning (1-4). Working with international researchers, the following is a summary of our work.

Li et al. (2014) investigated the serum levels of Zn and Cu in 60 Chinese children with ASD (48 boys, 12 girls) and a control group of 60 healthy sex-matched and age-matched individuals (2). The researchers also evaluated the autism severity using the Childhood Autism Rating Scale (CARS) score. The mean serum Zn levels and Zn/Cu ratio in the study were significantly lower in the ASD children compared with the control group (P<0.001). At the same, the serum Cu levels were significantly higher in the ASD children compared with the control group (P<0.001). It was in the study found a significant negative association between the Zn/Cu ratio and CARS scores (r=-0.345, P=0.007) (2).

Macedoni-Lukšič et al. (2015) determined the serum levels of Zn and Cu in a group of Slovenian children with ASD (N = 52, average age = 6.2 years) and a control group of children with other neurological disorders (N = 22, average age = 6.6 years), matched in terms of intellectual abilities (3). Compared to the control group, the ASD group had significantly elevated serum Cu/Zn ratio (95% confidence interval for children with ASD=1.86-2.26; 95% confidence interval for the control group=1.51-1.88) (3).

Crăciun et al. (2016) investigated the levels of Zn and Cu in whole blood, as well as the Cu/Zn ratio in a group of 28 Romanian ASD children. 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 study may be indicative of Zn deficiency in ASD children (4).

Following three months (12 weeks) of Zn supplementation, Meguid et al. (2019) found an increase in cognitive-motor performance, increased serum metallothionein concentration, and a significant lowering in the circulating serum Cu levels in a cohort of 30 Egyptian ASD children aged 3-8 years. Each daily Zn dosage in the study was calculated to equal the body weight in kg plus 15-20 mg. In children with ASD, the genetic expression of metallothionein 1 was higher after Zn therapy than before the treatment (5).

In a cohort of 23 Brazilian ASD children (≤ 18 yrs old, both sexes), Saldanha Tschinkel et al. (2018) did not find a marked difference in the intake of Cu and Zn concerning the geographical area of living, dietary habits, or metabolic state (6). In a study by Skalny et al. (2107), no significant group difference in hair mercury (Hg), Zn, and Cu content was detected between 74 Russian ASD children and 74 sex- and age-matched controls (2-4 and 5-9 years) (7).

In conclusion, our research suggests that providing Zn to ASD children may be an important component of a treatment protocol, especially in children with Zn deficiency (1-5). Mercury accumulation may occur as a cause or consequence of metallothionein dysfunction in ASD children, which may be one of the causes of Zn deficiency. Metallothioneins are proteins with important functions in metal metabolism and protection. It is important to monitor and follow the values for both Cu and Zn together during Zn therapy because these two trace elements are both antagonists in function, and essential for living cells (1).

– Geir Bjørklund

 

References

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

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

3. 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. Levels of metals in the blood and specific porphyrins in the urine in children with autism spectrum disorders. Biol Trace Elem Res 2015; 163: 2-10.

4. Crăciun EC, Bjørklund G, Tinkov AA, Urbina MA, Skalny AV, Rad F, Dronca E. Evaluation of whole blood zinc and copper levels in children with autism spectrum disorder. Metab Brain Dis 2016; 31: 887-890.

5. Meguid NA, Bjørklund G, Gebril OH, Doşa MD, Anwar M, Elsaeid A, Gaber A, Chirumbolo S. The role of zinc supplementation on the metallothionein system in children with autism spectrum disorder. Acta Neurol Belg 2019; 119: 577-583.

6. Saldanha Tschinkel PF, Bjørklund G, Conón LZZ, Chirumbolo S, Nascimento VA. Plasma concentrations of the trace elements copper, zinc and selenium in Brazilian children with autism spectrum disorder. Biomed Pharmacother 2018; 106: 605-609.

7. Skalny AV, Simashkova NV, Klyushnik TP, Grabeklis AR, Bjørklund G, Skalnaya MG, Nikonorov AA, Tinkov AA. Hair toxic and essential trace elements in children with autism spectrum disorder. Metab Brain Dis 2017; 32: 195-202.

Environmental Radiation Exposure and Essential Hypertension in Semey, Kazakhstan

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The Semipalatinsk Test Site (marked in red) was the main site for the nuclear testing of the former Soviet Union. It is situated in northeast Kazakhstan, approx. 150 kilometers west of the city Semey (until 2007 named Semipalatinsk)

In November 2018, a study in collaboration with CONEM Kazakhstan Environmental Health and Safety Research Group was published in the journal Environmental Research (1). The study examined the association between environmental radiation exposure and essential hypertension in a series of investigated geographical districts adjacent to the Semipalatinsk nuclear test site in Kazakhstan. The sample consisted of 2000 volunteers who participated in screening examinations in three administrative districts close to the nuclear test site. The research was a part of the government programs in Kazakhstan on environmental health hazard (1).

In April 2019, this study was quoted in a news article by the US science journalist Wudan Yan in the prestigious journal Nature (2): “Lyudmila Pivina at Semey State Medical University and her colleagues found that long-term, low-dose radiation can lead to cardiovascular problems such as high blood pressure. They looked at health outcomes in approximately 1,800 people, including second- and third-generation Polygon survivors. When they focused on individuals whose parents lived in areas that were exposed to radiation from 1949 to 1989, they found that the risks of hypertension went up in correlation with the amount of radiation someone’s parents received — a discovery that they found surprising”.

 

References

1. Markabayeva A, Bauer S, Pivina L, Bjørklund G, Chirumbolo S, Kerimkulova A, Semenova Y, Belikhina T. Increased prevalence of essential hypertension in areas previously exposed to fallout due to nuclear weapons testing at the Semipalatinsk Test Site, Kazakhstan. Environ Res 2018;167:129-135. https://doi.org/10.1016/j.envres.2018.07.016

2. Yan W. In the shadow of nuclear sins. Nature 2019: 568(4 April):22-24. https://www.nature.com/articles/d41586-019-01034-8