L-methylfolate recommended daily dosage

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L-methylfolate Recommended Daily Dosage for Depression and Related Conditions

Recommended Dosage for Major Depressive Disorder (MDD)

Research consistently shows that the most effective recommended daily dosage of L-methylfolate for adults with major depressive disorder, especially those who do not respond well to selective serotonin reuptake inhibitors (SSRIs), is 15 mg per day. Multiple clinical trials found that 15 mg/day of L-methylfolate, when used as an adjunct to SSRIs, led to significant improvements in depression symptoms compared to placebo, while a lower dose of 7.5 mg/day did not show the same benefit 1235.

Dosage for Patients with Specific Genetic or Biological Markers

Patients with certain genetic markers (such as MTHFR polymorphisms) or biological markers (like high body mass index or elevated inflammatory biomarkers) may particularly benefit from the 15 mg/day dosage. These groups showed greater improvements in depression symptoms when treated with L-methylfolate at this dose 35.

Dosage for Sleep Disturbance in MTHFR Polymorphism

For individuals with sleep disturbances and known MTHFR gene polymorphisms, a daily dose of 5 mg of L-methylfolate has been used and shown to improve sleep quality over several weeks . This is a lower dose than what is typically used for depression, but it was effective in this specific context.

Safety and Tolerability of L-methylfolate Dosage

Across studies, L-methylfolate at 15 mg/day was well tolerated, with side effects and discontinuation rates similar to placebo. This suggests that the 15 mg/day dosage is not only effective but also safe for most patients 1235.

Conclusion

The recommended daily dosage of L-methylfolate for adults, particularly as an adjunctive treatment for major depressive disorder resistant to SSRIs, is 15 mg. Lower doses, such as 7.5 mg, are less effective for depression, but a 5 mg dose may be considered for sleep disturbances in patients with MTHFR polymorphisms. L-methylfolate at these dosages is generally safe and well tolerated.

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Most relevant research papers on this topic

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.

RCTHighly Cited

2012·

247citations

·G. Papakostas et al.

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.

RCT

2011·

4citations

·G. Papakostas et al.

Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients who were stratified by biomarker levels and genotype: results from a randomized clinical trial.

Adjunctive L-methylfolate 15 mg may be effective in treating SSRI-resistant depression in patients with specific biomarkers and genetic markers.

RCTHighly Cited

2014·

113citations

·G. Papakostas et al.

Effect of L-Methylfolate Supplementation on Sleep for Patients with Reduced Methylenetetrahydrofolate Reductase Activity

L-methylfolate supplementation may improve sleep disturbances in patients with MTHFR polymorphisms, potentially benefiting their overall health.

Non-RCT

2024·

0citations

·Alex S. Carmon et al.

A Review of l-Methylfolate as Adjunctive Therapy in the Treatment of Major Depressive Disorder.

L-methylfolate is effective as an adjunctive treatment for major depressive disorder, particularly benefiting patients with higher BMI and inflammation.

Systematic Review

2023·

6citations

·V. Maletić et al.

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.

Case Report

2020·

2citations

·Rubens Pitliuk et al.

Association of obesity and inflammatory marker levels on treatment outcome: results from a double-blind, randomized study of adjunctive L-methylfolate calcium in patients with MDD who are inadequate responders to SSRIs.

L-methylfolate calcium significantly improves treatment outcomes in patients with major depressive disorder and inadequate response to SSRIs, particularly for those with BMI 30 and elevated inflammatory markers.

RCT

2015·

43citations

·R. Shelton et al.

L-Methylfolate For Bipolar I depressive episodes: An open trial proof-of-concept registry.

L-methylfolate combined with treatment as usual shows potential in treating bipolar depression, with 6/10 patients showing at least 50% improvement and 4/10 patients exhibiting remission.

Non-RCTRigorous Journal

2017·

20citations

·A. Nierenberg et al.

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.

Observational StudyVery Rigorous Journal

2018·

3citations

·M. Rainka et al.

Caveat emptor: Folate in unipolar depressive illness, a systematic review and meta-analysis

Folate at a dose of 5 mg/day or methylfolate at 15 mg once daily as an adjunct to selective serotonin reuptake inhibitor therapy shows a significant benefit compared to placebo in unipolar depression.

Meta-AnalysisVery Rigorous Journal

2018·

29citations

·Emmert Roberts et al.

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