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 (MT) system functioning (1-4, 6). 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).

Saldanha Tschinkel et al. (2018) investigated the plasma concentrations of Cu, Zn, and selenium (Se) in 23 patients with ASD (≤ 18 years old, both sexes) residing in Campo Grande, Brazil (5). No marked difference in the intake of the trace elements related to the residential area, dietary habit, or metabolic state was found.

Meguid et al. (2019) investigated 30 Egyptian ASD children (age range 3-8 years) who received Zn supplementation in 12 weeks (6). The daily dosage of Zn was equal to the body weight in kg plus 15-20 mg. Following Zn supplementation, the cognitive-motor performance and the serum MT concentration increased, and the serum levels of Cu decreased significantly. After Zn therapy, the MT-1 gene expression was higher in the ASD patients than before the treatment.

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 (1-4, 6). Mercury accumulation may occur as a cause or consequence of MT dysfunction in ASD children, which may be one of the causes of Zn deficiency. MTs 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. Saldanha Tschinkel PF, Bjørklund G, Conón LZ, 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.
6. 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.