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L-methylfolate
L-methylfolate is the active form of folate that directly participates in one-carbon metabolism and methylation reactions essential for DNA synthesis, repair, and neurotransmitter production.
L-methylfolate is the active form of folate that directly participates in one-carbon metabolism and methylation reactions essential for DNA synthesis, repair, and neurotransmitter production. Used for Depression (adjunctive treatment, particularly in patients with MTHFR polymorphisms), Folate deficiency and megaloblastic anemia, Homocysteinemia.
At a glance
| Generic name | L-methylfolate |
|---|---|
| Also known as | Deplin®, Deplin |
| Sponsor | Queen's University |
| Drug class | Vitamin B supplement / Folate derivative |
| Target | One-carbon metabolism pathway; indirect target of monoamine neurotransmitter synthesis |
| Modality | Small molecule |
| Therapeutic area | Neurology / Psychiatry / Nutritional supplementation |
| Phase | FDA-approved |
Mechanism of action
L-methylfolate (5-methyltetrahydrofolate) is the predominant circulating form of folate and the primary form that crosses the blood-brain barrier. It serves as a methyl donor in critical biochemical pathways, including the remethylation of homocysteine to methionine and the synthesis of neurotransmitters such as serotonin, dopamine, and norepinephrine. By bypassing the enzymatic conversion step (MTHFR), L-methylfolate is particularly beneficial for individuals with MTHFR polymorphisms or deficiencies.
Approved indications
- Depression (adjunctive treatment, particularly in patients with MTHFR polymorphisms)
- Folate deficiency and megaloblastic anemia
- Homocysteinemia
- Cognitive impairment and age-related cognitive decline
Common side effects
- Insomnia or sleep disturbance
- Headache
- Nausea
- Anxiety or agitation
- Gastrointestinal upset
Key clinical trials
- Pharmacokinetic Study of Eicosapentaenoic Acid (EPA) and Calcium L-5-Methyltetrahydrofolate (L-5-MTHF) After Administration of CreNeuroS® CNS Fish Oil Plus Softgels in Healthy Subjects Under Fasting Conditions (NA)
- Optimal Nutrition for Prevention of Hypertension in Pregnancy (NA)
- Use of Ritual Prenatal Multivitamins for Pregnancy (NA)
- Feasibility Test of Folic Acid on Acute Kidney Injury (EARLY_PHASE1)
- Adjunctive Treatment With L-methylfolate for Treatment-Resistant Generalized Anxiety Disorder: a Pilot Study (PHASE4)
- B-Complex: A Nutraceutical SANS Countermeasure (PHASE1)
- Comparison of The Effect of 5-MTHF and Folic Acid Supplementation in Increasing Red Blood Cell Folate in Pregnant Women (NA)
- 5-MTHF Supplementation for Treatment of Type 1 Diabetes Patients (NA)
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- L-methylfolate CI brief — competitive landscape report
- L-methylfolate updates RSS · CI watch RSS
- Queen's University portfolio CI