Does Vitamin D Deficiency Increase the Risk of Autism Spectrum Disorder? Linking Evidence with Theory—A Narrative Review
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Linking Vitamin D with Autism
3.2. Evidence of the Relationship Between Vitamin D Deficiency and ASD
3.3. Evidence of Improvement with Vitamin D Supplementation
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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First Author/Year | Study Design | Sample Size | Trimester | Sample and Assessment Method | Vitamin D Levels ng/mL | Diagnosis | Outcome |
---|---|---|---|---|---|---|---|
Chen et al. (2016) [48] | Case–control China | ASD: 68 Controls: 68 | 11–13 weeks | Serum | <25—deficiency >50—sufficient | DSM-5 | Significant association (p—0.001 and OR: 3.99 (2.58–7.12) |
Magnuss et al. 2016 [49] | Register-based total population study Sweden | N = 509 4–17 years | - | Serum | <25—deficiency | ICD-10 | Significantly increased offspring risk of ASD OR = 2.51, (95% CI 1.22–5.16) |
Lee et al. (2019) [51] | Nested case–control Sweden | ASD: 449 Controls: 574 | 10.9 (9.3–13.0) weeks | Dried blood spot LC-MS | <25—deficiency >50—sufficient | ICD-10 and DSMIV | VD deficiency was associated with 1.58 times higher odds of ASD (95% CI: 1.00, 2.49) as compared with controls. |
Windham, et al. (2020) [52] | Case–control California | ASD—534 Controls—421 | Mid-pregnancy | Serum LC-MS | <50—deficiency >75—sufficient | DSMIV-TR | No association OR-0.79 (95% CI 0.49–1.3) |
Souranderetal 2021 [53] | Nested case–control study Finland | ASD—1558 Controls—1558 | First and early second trimester | Serum CMI | <30—deficiency | ICD-10 | Increased risk of ASD in VD deficiency (1.44, 95% CI 1.15–1.81, p = 0.001 |
First Author/Year | Study Design | Sample Size | Trimester | Sample and Assessment Method | Vitamin D Levels ng/mL | Diagnosis | Outcome |
---|---|---|---|---|---|---|---|
Vinkhuyzen et al. (2018) [50] | Prospective cohort Netherland | ASD: 62 Controls: 3895 | Mid-gestation: 18.1–24.9 weeks Neonatal serum | Serum LC-MS | <25—deficiency >50—sufficient | SRS | Significantly high SRS scores (p = 0.001) |
Dowd et al. (2022) [54] | Prospective cohort study UK | Mothers: 7689 | Midpoint of each trimester: 7 weeks, 20 weeks, and 34 weeks | Serum LC-MS | <25—deficiency >50—sufficient | ICD-10 SCDC | No asssociation [OR = 0.9895% CI = 0.90–1.06),] Mendelian randomization suggested no causal effect [OR = 1.08, 95% CI = 0.46–2.55)] |
First Author/Year | Study Design | Sample Size (Both Boys and Girls) | Sample and Assessment Method | Vitamin D Levels ng/mL | Diagnosis/Outcome Measure | Outcome |
---|---|---|---|---|---|---|
Fernell et al. (2015) [55] | Case–control Sweden | ASD: 58 Controls: 57 | Dried blood Spot LC-MS | ASD: 24.0 ± 19.6 Controls: 31.9 ± 27.7 | DSM-5 | Significantly low VD levels in a group of newborn children, who later developed ASD. |
Lee et al. (2019) [51] | Nested case–control Sweden | ASD: 449 Controls: 574 | Dried blood spot LC-MS | ASD: 10.28 ± 5.96 Controls: 10.64 ± 6.31 | ICD-10 and DSM-IV | VD deficiency was associated with 1.33 (CI 1.01, 1.74) times higher odds of ASD as compared with controls. |
Schmidt et al. (2019) [57] | Case–control USA | ASD: 357 Controls: 234 | Dried blood Spot LC-MS/MS | ASD: 32.04 ± 14.96 Controls: 33.08 ± 15.72 | ADOS-2, ADI-R | No significant association OR: 0.98 (0.63–1.51). |
Windham et al. (2019) [58] | Case–control | ASD: 563 Controls: 436 | Dried blood Spot LC-MS/MS | ASD: 34.04 ± 14.1 Controls: 33.72 ± 11.85 | DSM-IV-TR | No significant association OR: 0.96 (0.65–1.43). |
First Author/Year | Study Design | Sample Size (Both Boys and Girls) | Sample and Assessment Method | Vitamin D Levels ng/mL | Diagnosis/Outcome Measure | Outcome |
---|---|---|---|---|---|---|
Vinkhuyzen et al. (2017) [50] | Prospective cohort Netherland | ASD: 62 Controls: 3895 | Serum LC-MS | - | SRS | VD-deficient individuals had significantly high SRS scores p = 0.001 |
Ali et al. (2019) [56] | Prospective study cohort Canada | ASD: 26 Controls: 2500 | Serum: A two-step chemiluminescence assay | - | ADOS-2/DSM-IV/ DSM-5 | No increase in risk of ASD RR: 1.06 (0.95–1.18) |
First Author | Study Design | Sample Size/Age | Sample and Assessment Method | Vitamin D Levels ng/mL | Diagnosis/Outcome Measure | Outcome |
---|---|---|---|---|---|---|
Saad et al. (2016) [59] | Case–control cross-sectional Egypt | ASD: 122 Controls: 100 Age ASD: 5.09 ± 1.42 year Controls: 4.88 ± 1.30 year | Serum ELISA | ASD: 18.02 ± 8.75 Controls: 42.51 ± 9.48 | DSM-IV-TR | Significantly low VD in ASD children (p ≤ 0.0001) |
Coşkun et al. (2016) [60] | Case–control Turkey | ASD: 85 Controls: 82 Age ASD: 43.4 ± 25.3 month Controls: 47.1 ± 14.2 month | Serum ELISA | ASD: 79.5 ± 25.9 Controls: 65.1 ± 23.9 | DSM-5 | Significantly low VD in ASD children (p ≤ 0.0001) |
Basheer et al. (2017) [61] | Case–Control India | ASD: 40 Controls: 30 Age ASD: 3–12 year control: 3–12 year | Serum LC-MS/MS | ASD: 13.5 ± 4.7 Controls: 12.7 ± 4.7 | DSM-5 ADI-R | No significant difference between groups p = 0.462 OR: 0.88 (0.14–5.63) |
Desoky et al. (2017) [62] | Case–control cross-sectional Egypt | ASD: 60 Controls: 40 Age ASD: 7.03 ± 2.34 year Controls: 7.91 ± 3.21 year | Serum ELISA | ASD: 18.63 ± 10.8 Controls: 45.9 ± 8.85 | - | Significantly low VD in ASD children (p = 0.001) |
Altun et al. (2018) [63] | Cross-sectional Turkey | ASD: 60 Controls: 45 Age ASD: 5.8 ± 2.7 year Controls: 6.7 ± 2.5 year | Serum ELISA | ASD: 13.79 ± 1.03 | DSM-IV-TR | Significantly low VD in ASD children (p < 0.001) |
Arastoo et al. (2018) [64] | Cross-sectional Iran | ASD: 31 Controls: 31 Age ASD: 9.17 ± 2.11 year Controls: 9.31 ± 2.09 year | Serum ELISA | ASD: 9.03 ± 4.14 Controls: 15.25 ± 7.89 | DSM-IV ADI-R | Significantly low VD in ASD children (p = 0.001) OR: 12.273 (1.447–104.101) |
El-Ansary et al. (2018) [65] | Cross-sectional Saudi Arabia | ASD: 28 Controls: 27 Age ASD: 7.0 ± 2.34 year Controls: 7.2 ± 2.14 year | Plasma ELISA | ASD: 95.63 ± 26.63 Controls: 140.43 ± 17.68 | DSM-IV-TR | Significantly low VD in ASD children (p < 0.001) |
Alzghoul et al. (2018) [66] | Case–control cross-sectional Jordan | ASD: 83 Controls: 106 Age ASD: 5.08 year Controls: 5.02 year | Serum LC-MS/MS | ASD: 23.4 Controls: 37.5 | DSM-5 | Significantly low VD in ASD children OR: 9.896 (4.605–21.264) |
Chtourou et al. (2019) [67] | Case–control Tunisia | ASD: 40 Controls: 43 Age Controls: 4.76 ± 1.08 year | Serum - | ASD: 17.13 ± 9.65 Controls: 21.34 ± 8.1 | DSM-5 | No significant difference between groups (p = 0.03) |
Petruzzelli et al. (2020) [68] | Case–control Italy | ASD: 54 Controls: 36 Age ASD: 6.87 (±3.92) year Controls: 11.28 (±4.44) year | Serum CMI | ASD: 35 (64.8) Controls: 12 (33.3) | DSM-5 ADI-R ADOS-2 | A significant association between ASD and VD deficiency (p = 0.006) |
Sengenc¸ et al. 2020 [69] | Case–control Turkey | ASD: 100 Controls: 100 Age ASD: 5.95, 3.13 year Controls: 6.68, 3.8 year | Serum ELISA | ASD: 42.86, 19.84 Controls: 48.57, 22.36 | DSM-5 | Significantly low VD in ASD children (p = 0.037) |
First Author | Study Design | Population Characteristics | Serum Vitamin D Estimation Method | Diagnosis | Result |
---|---|---|---|---|---|
Wang T et al. 2015 [70] | 11 case–control | 870 ASD patients and 782 healthy controls | Serum plasma ELISA, RIA, LC-MS/MS HPLC | DSM IV(TR) | Significant difference between the ASD group and control group (WMD = −8.63; 95% CI (−13.17, −4.09), p = 0.0002). |
Wang Z et al. 2020 [71] | 34 studies | Total participants = 20,580 (Asia, America, Europe, Africa) | Serum, plasma, or dried blood spot ELISA, RIA, LC-MS/MS HPLC | DSM-IV, DSM-IV-TR, ADOS, ADIR, DSM-V, ICD-9, ICD-10, ICD-F84.0 | Vitamin D concentration of the ASD group was 7.46 ng/mL lower than that of the control group (95% CI: −10.26; −4.66 ng/mL, p < 0.0001. |
26 case–control studies | Assessing Vitamin D in children 1792 ASDs 1969 controls | ||||
3 case–control studies and 2 nested case–control studies of neonates | Assessing Vitamin D in neonates (2687 ASDs 3574 controls) | ||||
1 nested case–control | Maternal vitamin D concentration of the ASD and control groups (517 ASDs, 642 controls) | ||||
2 cohort studies | Investigated the OR/RR for ASD incidence after being exposed to early-life vitamin D deficiency (5442 neonates, 3957 pregnant women) |
First Author/Year | Study Design | Type of Participants Age/Gender | Treatment Details and Duration | Change in Level of Vitamin D | ASD Severity Measure (M) | Result | |
---|---|---|---|---|---|---|---|
Before- After the Change | Between-Group Comparison | ||||||
Azzam (2015) [74] | Prospective, case–control | n = 21 Age: 2–12 year M:F: 16:5 | 2000 IU/day of vitamin D3 for 6 months (n = 10) No supplement (n = 11) for cases | 47 ± 20 to 71 ± 35 (nmol/L) 69 ± 41 to 70 ± 36 (nmol/L) | CARS ATEC | Decrease Decrease | NS |
Kerley 2017 [75] | RDBPC | n = 38 Age: <18 year M:F: 33:5 | 2000 IU vitamin D3 (n = 18) for 20 weeks Placebo (n = 20) | 58.4 ± 17.9 to 86.1 (nmol/L) | ABC SRS | Decrease Decrease | NS |
Mazahery (2019) a New Zealand [76] | RDBPC | Age: 2.5–8 year M:F: 60:13 | 2000 IU/day (n = 28) Omega 3 (n = 28) Placebo (n = 30) 12 months | - | ABC | Decrease in hyperactivity and irritability | Significant reduction in irritability and hyperactivity (−5.2 ± 6.3 vs. −0.8 ± 5.6, p = 0.047). |
Mazahery (2019) [77] | RDBPC | n = 73 Age: 2.5–8 year M:F: 60:13 | 2000 IU/day vitamin D3 (n = 19) omega-3 (n = 23) Vitamin D3 and omega 3 (n = 15) Placebo (n = 16) For 12 months | 68 ± 21 to an increase by 95 ± 14 (nmol/L) | SRS SPM | Decrease Decrease | NS |
Javadfar (2020) [78] | RDBPC | n = 43 children with ASD Age: 3–13 year M:F: 36:7 | 300 IU/kg/day (Max. 6000 IU/day) of vitamin D3 for 15 weeks (n = 22) Placebo n = 21 | 8.19 ± 6.78 to 39.10 | CARS ATEC ABC-C subscale | Decrease Decrease Decrease | Significant decrease in CARS AND ATEC scores No significant difference in ABC domains |
Moradi (2020) [79] | RDBPC | n = 100 Age: 6–9 year M:F: 100:0 | 300 IU/kg/day (max. 5000 IU/day) of vitamin D3 (n = 25) Perceptual-motor exercises (n = 25) Exercises and vitamin D3 (n = 25) Placebo (n = 25) 3 months | 12.6 to 24.36 | SS-GARS-2 | Decrease | Significant decrease in stereotypes (p = 0.01) |
Ansari et al., 2020 [80] | RDBPC | n = 40 Age: 6–14 year M:F: 100:0 | 50,000 IU/week or 50,000 IU/2 weeks (vitamin D3) for 10 weeks (n = 10) Placebo (n = 10) | 11.12 to 31.60 | GARS-2 | Significant decrease in stereotypes |
First Author | Study Design | Population Characteristics | Vitamin D Supplementation | Outcome Measure | Result |
---|---|---|---|---|---|
Song et al., 2020 [84] | 4 RCTs 3 included in meta-analysis | - (New Zealand, China, Ireland) Age 2–10 years Both male and female | Dose range 800 IU/day to 2000 IU/day Duration 20 weeks–12 months | ABC SRS CARS DD-CGAS | No significant improvement (SMD = −0.46, 95% CI: −0.87 to −0.05; p = 0.03 |
Li et al., 2020 [85] | 5 RCTs 3 included in meta-analysis | 349 participants New Zealand Age 2–12 years Both male and female | Dose: 2000 IU/day Duration = 5–12 months | ABC SRS CARS SPM ATEC DD-CGAS SSGARS-2 | Social interaction: No difference (pooled MD: −1.54; 95% CI: [−4.09, 1.01]; p = 0.24) Communication: No difference (pooled MD: −0.05; 95% CI: [−1.79, 1.69]; p = 0.96) Repetitive restrictive behavior: No difference (pooled MD: 0.85; 95% CI: [−0.33, 2.02]; p = 0.16) Hyperactivity: A significant difference (pooled MD: −3.20; 95% CI: [−6.06, −0.34]; p = 0.03) Irritability: No difference (pooled MD: −2.31; 95% CI: [−6.08, 1.46]; p = 0.23), |
Zhang 2023 [86] | 8 RCTs 6 included in meta-analysis | 266 participants (New Zealand, Iran, China, Ireland) Age 2.5−14 years Both male and female | Dose range: 800 IU/day to 50,000 IU/week and 2000 IU/day Duration 10 weeks to 12 months | ABC SRS CARS | No difference in core symptoms (pooled MD: −8.74; 95% CI: −17.45, −0.03; p = 0.05) Social interaction: No difference (pooled MD: −0.07; 95% CI: −1.70, 1.57; p = 0.93) Communication: No difference (pooled MD: −0.04; 95% CI: −1.19, 1.10; p = 0.94), Stereotypes: Significant difference between the intervention and placebo groups (pooled MD: −1.39; 95% CI: −2.7, −0.07; p = 0.04) Irritability: No difference (pooled MD: −1.79; 95% CI: −4.42, −0.85; p = 0.18) Hyperactivity: No difference (pooled MD: −1.35; 95% CI: −4.37, 1.67; p = 038) |
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Sultan, S.; Alhejin, N.; Serafi, R.; Abu Alrahi, M.; Afifi, G.; Al-Adawi, L.; Serafi, M.; El Madhoun, N. Does Vitamin D Deficiency Increase the Risk of Autism Spectrum Disorder? Linking Evidence with Theory—A Narrative Review. Psychiatry Int. 2025, 6, 22. https://doi.org/10.3390/psychiatryint6010022
Sultan S, Alhejin N, Serafi R, Abu Alrahi M, Afifi G, Al-Adawi L, Serafi M, El Madhoun N. Does Vitamin D Deficiency Increase the Risk of Autism Spectrum Disorder? Linking Evidence with Theory—A Narrative Review. Psychiatry International. 2025; 6(1):22. https://doi.org/10.3390/psychiatryint6010022
Chicago/Turabian StyleSultan, Sadia, Noor Alhejin, Raed Serafi, Manar Abu Alrahi, Gehad Afifi, Layan Al-Adawi, Mohammed Serafi, and Nada El Madhoun. 2025. "Does Vitamin D Deficiency Increase the Risk of Autism Spectrum Disorder? Linking Evidence with Theory—A Narrative Review" Psychiatry International 6, no. 1: 22. https://doi.org/10.3390/psychiatryint6010022
APA StyleSultan, S., Alhejin, N., Serafi, R., Abu Alrahi, M., Afifi, G., Al-Adawi, L., Serafi, M., & El Madhoun, N. (2025). Does Vitamin D Deficiency Increase the Risk of Autism Spectrum Disorder? Linking Evidence with Theory—A Narrative Review. Psychiatry International, 6(1), 22. https://doi.org/10.3390/psychiatryint6010022