Evidence supporting the use of: Vitamin B9 (folinic acid)
For the health condition: Schizophrenia

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Synopsis

Source of validity: Scientific
Rating (out of 5): 2

Vitamin B9, specifically in the form of folinic acid (as opposed to folic acid), has been investigated for its potential role in supporting the treatment of schizophrenia. The scientific rationale stems from observations that some individuals with schizophrenia have lower folate levels and that folate plays a role in neurotransmitter synthesis and methylation processes in the brain. Several studies, including randomized controlled trials, have examined whether folate supplementation could improve symptoms, particularly in patients with a genetic variant (MTHFR polymorphism) that impairs folate metabolism.

The evidence base is limited but suggestive. A 2013 randomized trial (Roffman et al., JAMA Psychiatry) found that supplementation with folinic acid and vitamin B12 led to modest improvements in negative symptoms of schizophrenia, but these effects were most pronounced in patients with specific genetic markers related to folate metabolism. Other meta-analyses and systematic reviews note that while there is a biological plausibility, the clinical impact is relatively small and not consistent across all patients. Folinic acid may be preferable to folic acid due to better bioavailability, particularly in those with metabolic impairments.

Overall, while there is some scientific validation for the adjunctive use of folinic acid in select individuals with schizophrenia—especially those with demonstrated folate deficiency or relevant genetic variants—the strength of evidence is moderate at best, and it is not considered a primary therapy.

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