Modifiable Nutritional Biomarkers in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis of Vitamin D, B<sub>12</sub>, and Homocysteine Exposure Spanning Prenatal Development Through Late Adolescence.

This elevation was highly significant ( p < 0.001) but moderately heterogeneous (I 2 ~52%), with larger case-control gaps in studies from regions with prevalent folate/B 12 deficiencies (e.g., South Asia).

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The overall heterogeneity, while moderate, approached significance with Cochran’s Q-test (Q = 15.08, df = 8, p = 0.06) and an I 2 statistic of 47% ( Supplementary Materials, Tables S27 and S28 ).

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Pooled analysis of two placebo-controlled B 12 trials did not reach statistical significance for core symptom improvement overall (pooled SMD ~–0.30, 95% CI: −0.80 to 0.20, p = 0.24), reflecting the mixed outcomes [ 12 , 25 ].

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The pooled estimate across all comparisons was OR = 0.39 (95% CI: 0.06–1.00), suggesting a borderline significant protective effect of vitamin B12 on ASD-related symptomatology, albeit with wide confidence intervals reflecting the limited sample size and lack of replication.

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