Trace element dysregulation and detoxification dysfunction in autism spectrum disorder : a urinary biomarker study with element ratio analysis

Osredkar, Joško (author), Godnov, Uroš (author), Jekovec-Vrhovšek, Maja (author), Osredkar, Damjan (author), Avguštin, Gorazd (author), France Štiglic, Alenka (author), Fabjan, Teja (author), Kumer, Kristina (author)

Background: Autism spectrum disorder (ASD) arises from complex gene–environment interactions. While trace element abnormalities have been studied, associations with autism severity remain inconsistent. Ratios indicating detoxification balance, rather than single toxic elements, may better reflect severity. Objective: To examine the relationships between urinary trace element levels, detoxification-related element ratios, and autism severity measured by the Childhood Autism Rating Scale (CARS). Methods: In a crosssectional study of 168 participants (103 ASD, 65 controls), thirty urinary trace elements were quantified by ICP-MS. ASD patients were stratified by CARS into subthreshold ASD (n = 29), mild–moderate ASD (n = 36), and severe ASD (n = 38). Analyses included Mann–Whitney U, Kruskal–Wallis, and Spearman correlation tests, focusing on Li/Pb, Cu/Pb, and Cr/Pb ratios. Results: Individual elements showed weak associations with CARS; lead correlated positively (ρ = 0.209, p = 0.035) and lithium inversely (ρ = −0.194, p = 0.051). In contrast, element ratios showed stronger links: Li/Pb (ρ = −0.349, p = 0.0003), Cu/Pb (ρ = −0.320, p = 0.0011), and Cr/Pb (ρ = −0.209, p = 0.035). Severe ASD exhibited modest 90th-percentile elevations for toxic elements but high heterogeneity. Conclusions: Single-element levels showed limited associations with ASD severity. Element ratios, particularly Li/Pb, showed stronger statistical associations than individual elements in this cross-sectional dataset; however, these findings should be interpreted as candidate correlates rather than causal or clinically validated biomarkers.

• Language: English
• Keywords: autism spectrum disorder, trace elements, lead, llithium, detoxification, biomarkers, CARS, element ratios, environmental toxins, metallothionein
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; FMF - Faculty of Mathematics and Physics; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 23 str.
• Numbering: Vol. 16, iss. 11, art. 5332
• PID: 20.500.12556/RUL-182880
• UDC: 615.874.24:616.896
• ISSN on article: 2076-3417
• DOI: 10.3390/app16115332
• COBISS.SI-ID: 279467011
• Publication date in RUL: 27.05.2026

Record is a part of a journal

• Title: Applied sciences
• Shortened title: Appl. sci.
• Publisher: MDPI
• ISSN: 2076-3417
• COBISS.SI-ID: 522979353

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: elementi v sledovih, svinec, litij, biomarkerji, CARS, razmerja elementov, okoljski toksini, metalotionein, motnje avtističnega spektra, razstrupljanje

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P3-0124
• Name: Metabolni in prirojeni dejavniki reproduktivnega zdravja, porod III

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: J3-1756
• Name: Okoljski in genetski dejavniki pri motnjah avtističnega spektra