Evidence supporting the use of: Folinic acid
For the health condition: Schizophrenia

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Synopsis

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

Folinic acid (also known as leucovorin) has been studied as an adjunctive treatment in schizophrenia, primarily due to its role in one-carbon metabolism and methylation processes, which are often disrupted in psychiatric disorders. Some individuals with schizophrenia exhibit low folate levels or genetic polymorphisms (such as MTHFR mutations) that impair folate metabolism. Several small-scale clinical trials and open-label studies have investigated folinic acid supplementation, particularly in patients with low serum folate or those who are non-responsive to standard antipsychotic therapy. Results suggest that folinic acid may offer modest improvement in negative symptoms and overall functioning, especially in genetically defined subgroups (e.g., those with certain folate pathway gene variants). However, the overall evidence base remains limited. Most published studies have small sample sizes, short durations, and methodological constraints. Meta-analyses and systematic reviews conclude that while there is a biologically plausible rationale and some preliminary positive findings, the data are insufficient to recommend routine use of folinic acid in all patients with schizophrenia. Instead, its use may be considered in select cases—particularly when folate deficiency or relevant genetic polymorphisms are present. Larger, well-controlled trials are needed to establish efficacy, optimal dosing, and which patients are most likely to benefit.

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Products containing folinic acid

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