Is L-Methylfolate safe?

L-Methylfolate is a form of folate, a B vitamin that is essential for various bodily functions, including DNA synthesis and repair, methylation, and the production of certain neurotransmitters. It has been studied for its potential benefits in treating conditions such as major depressive disorder and its safety profile in different populations, including infants and children.

Key Insights from Research Papers

L-Methylfolate at a dose of 15 mg/day may be an effective and well-tolerated adjunctive treatment for major depressive disorder in patients with an inadequate response to selective serotonin reuptake inhibitors (SSRIs), with no significant difference in adverse event rates compared to placebo .
L-Methylfolate is suitable for use in infant and follow-on formula, with no indications of untoward effects, and is well-tolerated with no significant differences in growth, tolerance, or adverse events compared to folic acid .
In pediatric and adolescent populations, L-Methylfolate supplementation was generally well-tolerated and may provide benefits for patients with a range of neuropsychiatric conditions, with adverse events occurring less frequently compared to a comparator population .
While there is some evidence of potentially harmful effects of folate supplementation, such as masking B12-deficiency anemia or promoting early-stage tumor growth, L-Methylfolate may be less likely to cause these issues than folic acid, and the overall consequences of unmetabolized folic acid in the serum are unknown.
A single case report suggests a possible association between L-Methylfolate supplementation and psoriasis relapse, indicating that individual responses to supplementation can vary and potential side effects should be monitored.

Conclusion

The research suggests that L-Methylfolate is generally safe and well-tolerated as an adjunctive treatment for major depressive disorder in adults and as a folate source in infant formula. It also appears to be beneficial and well-tolerated in pediatric and adolescent populations for various neuropsychiatric conditions. However, individual responses can vary, and there may be specific cases where supplementation could be associated with adverse effects, such as a potential relapse of psoriasis. Overall, L-Methylfolate is considered safe for use under the studied conditions and dosages.

Is L-Methylfolate safe?

Summary

Consensus Meter

Key Insights from Research Papers

Conclusion

Sources and full results

L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials.

Adjunctive L-methylfolate at 15 mg/day may be an effective, safe, and well-tolerated treatment strategy for patients with major depressive disorder who have partial or no response to SSRIs.

Suitability and safety of L-5-methyltetrahydrofolate as a folate source in infant formula: A randomized-controlled trial

L-5-methyltetrahydrofolate is suitable for use in infant and follow-on formula, with no indications of untoward effects.

Calcium l‐methylfolate as a source of folate added for nutritional purposes to infant and follow‐on formula, baby food and processed cereal‐based food

Calcium l-methylfolate is a safe and bioavailable folate source for infant and young children, with no need for additional toxicological studies.

L-methylfolate augmentation of selective serotonin reuptake inhibitors (SSRIS) for major depressive disorder: Results of two randomized, double-blind trials

L-methylfolate 15 mg/d may be a safe and effective augmentation strategy for inadequate response to SSRIs in treating major depressive disorder.

L-methylfolate Augmentation to Antidepressants for Adolescents with Treatment-Resistant Depression: A Case Series.

L-methylfolate supplementation may be a safe and effective strategy for managing treatment-resistant depression in adolescents.

Long-term efficacy, safety, and tolerability of L-methylfolate calcium 15 mg as adjunctive therapy with selective serotonin reuptake inhibitors: a 12-month, open-label study following a placebo-controlled acute study.

Adjunctive L-methylfolate 15 mg/d may be an early option for patients who fail to adequately respond to antidepressant monotherapy, demonstrating sustained remission and recovery.

L-Methylfolate Calcium Supplementation in Adolescents and Children: A Retrospective Analysis

L-methylfolate calcium supplementation is well-tolerated in pediatric and adolescent patients and may provide benefits for a range of neuropsychiatric conditions.

L-Methylfolate Calcium in Adolescents and Children: A Retrospective Analysis (P5.337)

L-methylfolate calcium shows potential in treating a range of psychiatric and neurologic conditions in children and adolescents, with potential benefits for MTHFR mutations and folate metabolism.

Folate supplementation: is it safe and effective?

Folate supplementation may not be safe and effective for treating depression, with potential harmful effects and potential cognitive decline.

L-methylfolate, a new option in psychiatric treatment, would it be linked to psoriasis relapse?

L-methylfolate may be linked to psoriasis relapse in patients with MTHFR gene polymorphism, suggesting its potential as an adjuvant treatment for depression.

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