Browse/Essential Vitamin
Essential Vitamin

L-Methylfolate (5-MTHF)

01 / OVERVIEW

What this compound does

WHAT IT DOES

L-Methylfolate is a form of vitamin B that helps your body create and repair DNA, which is important for cell growth and function. It also supports the production of brain chemicals that affect your mood and mental clarity. This supplement can be particularly helpful for people who have trouble absorbing regular folate from food.

KEY BENEFITS
Supports healthy brain function
Aids in mood regulation
Promotes heart health
Enhances energy levels
Assists in DNA synthesis
BEST FOR
  • • Individuals with mood disorders
  • • People with elevated homocysteine levels
  • • Pregnant women needing extra folate
  • • Those with absorption issues
  • • Adults over 40 focusing on cognitive health
WHAT TO EXPECT

Users may start to notice improvements in mood and energy levels within a few weeks of consistent use. Some may feel more focused and less fatigued as their body adjusts.

WHO SHOULD AVOID THIS
  • • Individuals with a known allergy to folate
  • • People taking certain medications without doctor supervision
  • • Those with specific metabolic disorders
  • • Pregnant or breastfeeding women without medical advice
MYTHS & FACTS
Myth: L-Methylfolate is the same as regular folate.
Fact: L-Methylfolate is the active form of folate that your body can use directly, while regular folate must be converted into this form.
Myth: All supplements containing folate are equally effective.
Fact: The effectiveness of folate supplements can vary significantly based on their form and how well your body can absorb them.
At a glance
Typical dose
400-1000 mcg/day
Evidence
—
Studies indexed2
How it's made

Production details below.

03 / DOSAGE

How much, when

MAINTENANCE

400-1000 mcg/day

morning with B12

TIMING

L-Methylfolate (5-MTHF) — Morning dose

Standard dosing.

02 / EVIDENCE

Peer-reviewed studies

  • PMID: 23154195

    Depression (adjunct)

    L-Methylfolate as adjunct to antidepressants improved outcomes in MTHFR-variant patients.

    B
  • PMID: 16651297

    Homocysteine reduction

    Active folate reliably reduces elevated homocysteine better than folic acid in MTHFR+.

    A
  • PMID 37526714 · 2023Systematic Review

    Folic Acid Supplementation to Prevent Neural Tube Defects: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

    B
  • PMID 40362912 · 2025Safety Study

    Safety and Efficacy of High-Dose Folinic Acid in Children with Autism: The Impact of Folate Metabolism Gene Polymorphisms

    B
  • PMID 32690472 · 2020RCT

    Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial

    B
  • PMID 31910279 · 2020RCT

    Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial

    B
  • PMID 39703043 · 2025Safety Study

    Folinic acid as a treatment for autism in children: A within-subjects open-label study on safety and efficacy

    B
04 / INTERACTIONS

Medicine interactions

  • Methotrexate· chemotherapy

    L-Methylfolate can counteract the effects of methotrexate, which is designed to inhibit folate metabolism.

    → Avoid concurrent use and consult a healthcare provider.

    DO NOT COMBINE

  • Anticonvulsants· antiseizure

    Some anticonvulsants can lower folate levels, potentially reducing the effectiveness of L-Methylfolate.

    → Monitor levels and adjust dosages as necessary.

    HIGH

  • SSRIs· antidepressants

    L-Methylfolate may enhance the effectiveness of SSRIs by supporting neurotransmitter synthesis.

    → Consult with a healthcare provider for potential adjustments.

    MODERATE

This page is a reference summary, not a prescription. Consult a clinician before starting, stopping, or combining supplements — especially if you take medication or have a medical condition.