Synopsis

Source of validity: Scientific
Rating (out of 5): 3

5-Methyltetrahydrofolate glucosamine (5-MTHF) is a bioactive form of folate, and its use in supporting or treating schizophrenia is scientifically motivated, primarily due to the role of folate metabolism in psychiatric disorders. Some individuals with schizophrenia exhibit low folate levels or genetic polymorphisms (such as MTHFR C677T) that impair their ability to convert folic acid to the active form, 5-MTHF. Folate is involved in one-carbon metabolism, which is essential for neurotransmitter synthesis and methylation processes in the brain—both of which may be disrupted in schizophrenia.

Several randomized controlled trials have investigated adjunctive folate supplementation (often using L-methylfolate, which is similar to 5-MTHF glucosamine) in schizophrenia, particularly in patients with low serum folate or relevant genetic variants. These studies have shown modest improvements in negative symptoms—such as apathy and social withdrawal—when folate is added to standard antipsychotic treatment, especially in genetically predisposed individuals. However, not all studies have found benefit, and improvement appears limited to subgroups rather than the general population with schizophrenia.

Overall, while there is scientific rationale and some supportive clinical evidence for using 5-MTHF in schizophrenia, particularly in patients with folate deficiency or relevant genetic backgrounds, the strength of evidence is moderate (rated 3/5). Use is generally as an adjunct to, not a replacement for, standard treatments.

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