L-Methylfolate for Kids & Teens: Is It Safe?

Key Findings

This retrospective study found that L-methylfolate calcium supplementation (15 mg/d or 7.5 mg/d) was well-tolerated in a pediatric/adolescent population (ages 7–20, mean 16 y), with significantly fewer adverse events compared to a comparator group (10% vs. 25%, P = 0.02). Positive subjective treatment experiences were reported by 22.5% of patients, while negative effects occurred in 5.4%. No significant differences in laboratory abnormalities were observed between groups (P = 0.13).

Study Design

An observational, retrospective chart review conducted at a psychiatry clinic in Amherst, NY, analyzing data from patients treated between 2010–2015. The treatment group included 146 individuals (139 on 15 mg/d, 7 on 7.5 mg/d), while 44 patients prescribed but not administered L-methylfolate calcium served as comparators. Demographics: primarily adolescents (mean age 16 y), with anxiety disorders (68%) and mood disorders (57%) being the most common diagnoses.

Dosage & Administration

Two doses were evaluated: 15 mg/day (n=139) and 7.5 mg/day (n=7). L-methylfolate calcium was administered as an adjunct to standard therapies, including antidepressants (69% of treated patients) and mood stabilizers/antiepileptics (63%).

Results & Efficacy

• Adverse events: Treated group experienced fewer adverse events than comparators (10% vs. 25%, P = 0.02). Most common were impaired sleep (n=5) and increased anxiety (n=3).
• Laboratory safety: No significant differences in lab abnormalities between groups (P = 0.13).
• Subjective outcomes: 22.5% of treated patients reported positive experiences, while 5.4% reported negative effects.
• Diagnosis trends: Anxiety disorders were more prevalent in the treated group (68% vs. 50%), suggesting potential utility in this population.

Limitations

• Retrospective design: Relies on historical chart data, limiting control over variables and introducing potential bias.
• Comparator group issues: Patients not administered L-methylfolate may differ systematically (e.g., adherence, severity) from treated groups.
• Small sample: Only 7 patients received 7.5 mg/d, reducing statistical power for lower-dose analysis.
• Subjective reporting: Outcomes based on patient/clinician notes rather than standardized scales, risking recall bias.
• Lack of placebo: Observational nature prevents causal conclusions about efficacy.

Clinical Relevance

This study suggests L-methylfolate calcium may be a safe adjunct for adolescents and children with neuropsychiatric conditions, particularly anxiety and mood disorders, with low adverse event rates. However, the lack of randomization, small comparator group, and subjective reporting limit definitive recommendations. Clinicians might consider it cautiously for patients with inadequate responses to standard therapies, but prospective, controlled trials are needed to confirm benefits. For supplement users, these findings support its tolerability in youth populations but emphasize the importance of medical supervision due to the study’s observational limitations.

Word count: 398