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Folate and vitamin B12 supplementation in patients with schizophrenia and low serum folate level: A 24-week randomized, double-blind, placebo-controlled study.

  • 2026-01
  • Journal of the Formosan Medical Association = Taiwan yi zhi 125(1)
    • Chun-Hsin Chen
    • Chih-Chiang Chiu
    • Yi-Hang Chiu
    • Chin-Hao Chang
    • Yu-Han Chang
    • Ming-Chyi Huang
    • Mong-Liang Lu
    • Po-Yu Chen

Study Design

Type
Randomized Controlled Trial (RCT)
Sample size
n = 36
Population
55 schizophrenia patients with serum folate levels lower than 6 mg/L
Methods
randomized in a 2:1 ratio to supplementation with 5 mg of folate and 500 μg of vitamin B12 per day (the folate group, n = 36) or placebo (the placebo group, n = 19) for 24 weeks
Duration
24 weeks

Purpose

We aimed to evaluate the effects of folate and vitamin B12 on psychopathology in patients with schizophrenia and low serum folate levels.

Methods

Fifty-five schizophrenia patients with serum folate levels lower than 6 mg/L were randomized in a 2:1 ratio to supplementation with 5 mg of folate and 500 μg of vitamin B12 per day (the folate group, n = 36) or placebo (the placebo group, n = 19) for 24 weeks. We evaluated patients' symptomatology with the Positive and Negative Symptom Scale (PANSS) and cognitive functions with Cogstate.

Results

During the 24-week intervention, serum folate and vitamin B12 levels significantly increased, and homocysteine level significantly decreased in the folate group, but these markers did not significantly change in the placebo group. There were no significant changes in scores of total and each subscale of PANSS, and Cogstate between the folate and placebo groups. A subgroup analysis within the folate groups revealed no significant differences in the changes of psychotic symptoms severity or cognitive functions among patients with different degrees of folate level increments.

Conclusion

Our finding suggested that the extent of increased folate levels did not exert a notable impact on the changes of psychotic symptoms severity or cognitive function in our patients. It may also due to the relatively stable condition in our recruited patients, so supplementation of folate cannot show its effectiveness. Whether folate can improve psychopathology in moderate to severe patients with schizophrenia should be evaluated with a larger sample size in the future.

Research Insights

  • Vitamin B12→Improved Cognitive Function

    There were no significant changes in scores of total and each subscale of PANSS, and Cogstate between the folate and placebo groups.

    Effect
    Neutral
    Effect size
    Small
    Dose
    500 μg/day
  • Vitamin B12→Reduced Psychotic Symptom Severity

    There were no significant changes in scores of total and each subscale of PANSS, and Cogstate between the folate and placebo groups.

    Effect
    Neutral
    Effect size
    Small
    Dose
    500 μg/day
  • Vitamin B9→Improved Cognitive Function

    There were no significant changes in scores of total and each subscale of PANSS, and Cogstate between the folate and placebo groups.

    Effect
    Neutral
    Effect size
    Small
    Dose
    500 μg/day
  • Vitamin B9→Reduced Psychotic Symptom Severity

    There were no significant changes in scores of total and each subscale of PANSS, and Cogstate between the folate and placebo groups.

    Effect
    Neutral
    Effect size
    Small
    Dose
    500 μg/day
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