Metabolic Brain Disease

, Volume 33, Issue 3, pp 917–931 | Cite as

In the search for reliable biomarkers for the early diagnosis of autism spectrum disorder: the role of vitamin D

  • Afaf El-Ansary
  • John J. Cannell
  • Geir BjørklundEmail author
  • Ramesa Shafi Bhat
  • Abeer M. Al Dbass
  • Hanan A. Alfawaz
  • Salvatore Chirumbolo
  • Laila Al-Ayadhi
Original Article


Autism spectrum disorder (ASD) affects about 1% of the world’s population. Vitamin D is thought to be essential for normal brain development and modulation of the immune system. Worldwide about 1 billion people are affected by vitamin D deficiency. High-sensitivity C-reactive protein (hs-CRP), cytochrome P450 2E1 (CYP2E1) and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) are biomarkers related to inflammation and oxidative stress. In the present study, these biomarkers were together with serum 25-hydroxyvitamin D (25(OH)D3) analyzed in 28 (mean age seven years) Saudi male patients with ASD. The study was conducted to determine if there is any relationship between vitamin D levels, the tested biomarkers and the presence and severity of ASD. The hope was to identify if these biomarkers may be useful for early ASD diagnosis. The Childhood Autism Rating Scale (CARS) and the Social Responsiveness Scale (SRS) were used to measure autism severity. The results of the ASD children were compared with 27 age and gender-matched neurotypical controls. The data indicated that Saudi patients with ASD have significantly lower plasma levels of 25(OH)D3 than neurotypical controls (38 ng/ml compared to 56 ng/ml, respectively; [P = 0.001]). Surprisingly, the levels of CYP2E1 were lower in the children with ASD than the neurotypical controls (0.48 ± 0.08 vs. 69 ± 0.07 ng/ml, respectively; P = 0.001). The ASD children also had significantly higher levels of hs-CRP (0.79 ± 0.09 vs. 0.59 ± 0.09 ng/ml, respectively; P = 0.001) and 8-OH-dG (8.17 ± 1.04 vs. 4.13 ± 1.01 ng/ml, respectively; P = 0.001, compared to neurotypical age and gender-matched controls. The values for hs-CRP and 8-OH-dG did not correlate [P < 0.001] with autism severity. There was found a relationship between autism severity on the CARS scale and the levels of 25(OH)D3 and CYP1B1. But this was not found for SRS. All four biomarkers seemed to have good sensitivity and specificity, but the sample size of the present study was too small to determine clinical usefulness. The findings also indicate that inadequate levels of vitamin D play a role in the etiology and severity of autism. Furthermore, the results of the present study suggest the possibility of using 25(OH)D3, CYP1B1, hs-CRP and 8-OH-dG, preferably in combination, as biomarkers for the early diagnosis of ASD. However, further research is needed to evaluate this hypothesis.


Autism Vitamin D 8-OHdG CYP1B1 High-sensitivity C-reactive protein Autism biomarkers 



This research project was supported by a grant from the Research Center of the Center for Female Scientific and Medical Colleges at King Saud University.

Compliance with ethical standards

Conflict of interest

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

Ethical approval

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


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Afaf El-Ansary
    • 1
    • 2
    • 3
    • 4
  • John J. Cannell
    • 5
  • Geir Bjørklund
    • 6
    Email author
  • Ramesa Shafi Bhat
    • 7
  • Abeer M. Al Dbass
    • 7
  • Hanan A. Alfawaz
    • 8
  • Salvatore Chirumbolo
    • 9
  • Laila Al-Ayadhi
    • 3
    • 4
    • 10
  1. 1.Central Laboratory, Female Centre for Scientific and Medical StudiesKing Saud UniversityRiyadhSaudi Arabia
  2. 2.Medicinal Chemistry Department, National Research CentreCairoEgypt
  3. 3.Autism Research and Treatment CenterRiyadhSaudi Arabia
  4. 4.Shaik AL-Amodi Autism Research ChairKing Saud UniversityRiyadhSaudi Arabia
  5. 5.Vitamin D CouncilSan Luis ObispoUSA
  6. 6.Council for Nutritional and Environmental MedicineMo i RanaNorway
  7. 7.Biochemistry Department, Science CollegeKing Saud UniversityRiyadhSaudi Arabia
  8. 8.Department of Food Science and Human NutritionKing Saud UniversityRiyadhSaudi Arabia
  9. 9.Department of Neurological and Movement SciencesUniversity of VeronaVeronaItaly
  10. 10.Department of Physiology, Faculty of MedicineKing Saud UniversityRiyadhSaudi Arabia

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