Is L-Methylfolate safe?
Pro Research Analysisby 
Searched over 200M research papers
Consensus Meter
Safety of L-Methylfolate: A Comprehensive Review
Introduction to L-Methylfolate Safety
L-Methylfolate, a bioavailable form of folate, is often used as an adjunctive treatment for various neuropsychiatric conditions, including major depressive disorder (MDD) and schizophrenia. This article synthesizes findings from multiple studies to evaluate the safety profile of L-Methylfolate across different populations and conditions.
Safety in Adults with Major Depressive Disorder
Long-Term Safety and Tolerability
A 12-month open-label study assessed the long-term safety and tolerability of L-Methylfolate calcium 15 mg as an adjunctive therapy with selective serotonin reuptake inhibitors (SSRIs) in adults with MDD. The study found that L-Methylfolate was well-tolerated, with no significant adverse events reported. Additionally, 38% of participants achieved full recovery without recurrence of MDD, indicating sustained efficacy and safety over the long term.
Efficacy and Adverse Events in Short-Term Trials
Two randomized, double-blind trials also evaluated the safety of L-Methylfolate as an adjunctive treatment for SSRI-resistant MDD. The trials demonstrated that L-Methylfolate at 15 mg/day was well-tolerated, with adverse event rates comparable to those of the placebo group. These findings suggest that L-Methylfolate is a safe augmentation strategy for patients with partial or no response to SSRIs .
Safety in Pediatric and Adolescent Populations
Retrospective Analysis in Psychiatry Clinics
A retrospective chart review of pediatric and adolescent patients (ages 7-20) prescribed L-Methylfolate calcium revealed that the supplement was well-tolerated. Adverse events were less frequent in the treated population compared to the comparator group, with the most common issues being impaired sleep and increased anxiety. The study concluded that L-Methylfolate calcium is safe for use in younger populations with neuropsychiatric conditions .
Case Series on Treatment-Resistant Depression
A case series involving adolescents with treatment-resistant depression found that L-Methylfolate was well-tolerated and led to improvements in depression, anxiety, and irritability in 80% of the patients. This further supports the safety and potential efficacy of L-Methylfolate in younger populations.
Safety in Infants
Randomized-Controlled Trial in Infant Formula
A randomized-controlled trial assessed the suitability of L-5-methyltetrahydrofolate, a form of L-Methylfolate, as a folate source in infant formula. The study found no significant differences in tolerance or adverse events between infants fed formula containing L-5-methyltetrahydrofolate and those fed formula with folic acid. This indicates that L-Methylfolate is safe for use in infant nutrition.
Meta-Analysis and Systematic Reviews
Comprehensive Safety Assessment
A systematic review and meta-analysis of L-Methylfolate augmentation in depressive disorders concluded that adjunctive L-Methylfolate is associated with modest efficacy and a favorable safety profile. The meta-analysis found no significant increase in adverse events compared to antidepressant monotherapy, reinforcing the safety of L-Methylfolate in treating depressive disorders.
Conclusion
The collective evidence from multiple studies indicates that L-Methylfolate is a safe and well-tolerated treatment option across various populations, including adults, adolescents, and infants. Its use as an adjunctive therapy in neuropsychiatric conditions, particularly major depressive disorder, shows promise with minimal adverse effects. Further controlled studies are warranted to continue evaluating its long-term safety and efficacy.
Sources and full results
Most relevant research papers on this topic