Vitamin D2 & Suicide Risk: What the Research Says

Key Findings

This retrospective cohort study found that Vitamin D2 supplementation was associated with a 48% lower risk of suicide attempts or intentional self-harm in U.S. veterans (HR = 0.512, 95% CI: 0.457–0.574), compared to untreated controls. Vitamin D3 showed a similar but slightly smaller association (45% risk reduction; HR = 0.552). Black veterans and those with baseline serum levels <20 ng/ml experienced the greatest benefits, with ~64% lower risk (Black veterans: HR = 0.362; 0–19 ng/ml: HR = 0.359). Higher average daily dosages correlated with greater risk reductions (HR per log dosage = 0.837, 95% CI: 0.779–0.900).

Study Design

The study analyzed a retrospective cohort of U.S. veterans who received Vitamin D prescriptions (D2 or D3) between 2010–2018 via the Department of Veterans Affairs (VA). Researchers matched supplemented veterans 1:1 with untreated controls based on demographics, medical history, and mental health diagnoses. Cox proportional hazards regression modeled time to first suicide attempt or intentional self-harm. While the study included over 100,000 veterans (exact numbers unspecified), the design limits causal inference due to its observational nature.

Dosage & Administration

The study evaluated any prescription fill for Vitamin D2 (ergocalciferol) or D3 (cholecalciferol), with dosages stratified into average daily intake categories. However, specific dosage ranges (e.g., IU/day) were not reported in the provided summary. Administration occurred via VA pharmacy records, implying oral supplementation, but formulation details (e.g., capsules, frequency) were unspecified. Stratified analyses considered "log average dosage," suggesting a dose-response relationship but without quantifying thresholds.

Results & Efficacy

• Overall risk reduction: Vitamin D2 supplementation reduced suicide attempt/self-harm risk by 48% (HR = 0.512, 95% CI: 0.457–0.574).
• Race-specific effects: Black veterans supplemented with D2 had a 63.8% lower risk vs. controls (HR = 0.362, 95% CI: 0.298–0.440).
• Serum level correlation: Veterans with baseline D levels 0–19 ng/ml saw a 64.1% risk reduction (HR = 0.359, 95% CI: 0.215–0.598).
• Dose-response: Higher average daily dosages were linked to incremental risk reductions (HR per log dosage = 0.837, 95% CI: 0.779–0.900).
  All associations were statistically significant (CIs excluded null values), though the study did not directly compare D2 vs. D3 efficacy.

Limitations

1. Observational design: Cannot establish causality; unmeasured confounders (e.g., socioeconomic factors, concurrent mental health treatments) may influence results.
2. Population specificity: Findings are limited to veterans, who may have unique risk factors (e.g., PTSD, trauma history) affecting generalizability.
3. Dosage heterogeneity: No explicit dosage thresholds (e.g., 1,000 vs. 2,000 IU/day) were provided for D2, complicating clinical interpretation.
4. Serum level variability: Blood tests were not standardized for timing or frequency, potentially misclassifying baseline D status.
5. Lack of direct D2-D3 comparison: The study assessed both forms separately against controls but did not compare D2 vs. D3 directly.

Clinical Relevance

These findings suggest Vitamin D2 supplementation may benefit veterans with low serum levels (<20 ng/ml) or those identifying as Black, who showed the strongest associations. However, as an observational study, it cannot confirm causality or optimal dosing. Clinicians might consider screening veterans for D deficiency and recommending supplementation, particularly in high-risk subgroups. Further research, including randomized controlled trials (RCTs), is needed to validate these links and clarify whether D2 and D3 have comparable protective effects. Users should not interpret this as a standalone treatment for mental health conditions but as a potential adjunct to comprehensive care.

Study URL | PubMed