What is L-Methylfolate? Uses, warnings & side effects

Updated May 14, 2025  •  Published Dec 30, 2020

L-methylfolate is the active form of folate (vitamin B9). Other versions of vitamin B9 such as folic acid have to be metabolized by the body into l-methylfolate before they can be used. Because l-methylfolate is the “ready-to-use” version of vitamin B9, manufacturers sell it as a better low-dose dietary supplement than other folate supplements. L-methylfolate is included in many prenatal vitamins and even in some birth control pills where it’s used as a backup prenatal supplement just in case the pill doesn’t work. In addition to low-dose dietary supplementation, research has shown that high-dose l-methylfolate can improve depression symptoms when added to antidepressants for treatment-resistant depression.

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L-Methylfolate overview

BRAND NAMES:

  • Deplin, Elfolate, Extrafolate-S, Metafolin, MethylPro, Quatrefolic

Generic Names:

  • L-methylfolate, methylfolate, 5-MTHF, active folate, methylated folate, L-5-MTHF, L-MTHF, 5-methyltetrahydrofolate, l-methylfolate calcium, calcium 5-methyltetrahydrofolate, glucosamine salt 5-methyltetrahydrofolate, levomefolate, levomefolic acid

Uses:

  • Used as a dietary supplement, an adjunct treatment for depression, folate deficiency, or high homocysteine levels in people with schizophrenia.

Therapeutic Classes:

  • Dietary supplement, nutriceutical, antidepressant adjunctive

Forms:

  • Tablet, capsule, chewable tablet, orally disintegrating tablet, lozenge, liquid drops

How it’s taken:

  • By mouth

What is L-Methylfolate used for?

Low-dose l-methylfolate is a vitamin B9 dietary supplement for people who have low vitamin B9 levels, who are pregnant or breastfeeding, or who want to improve their health. Healthcare providers may also prescribe higher doses of l-methylfolate for folate deficiency, anemia, schizophrenia, or other conditions related to folate loss or metabolism. At very high doses, l-methylfolate is sometimes used as an add-on treatment with antidepressants for depression. 

What form(s) does L-Methylfolate come in?

  • Tablet

    • 400 mcg

    • 800 mcg

    • 1 mg

    • 7.5 mg

    • 15 mg

  • Capsule

    • 400 mcg

    • 800 mcg

    • 1 mg

    • 2 mg

    • 2.5 mg

    • 5 mg

    • 10 mg

    • 7.5 mg

    • 15 mg

  • Chewable tablet

    • 800 mcg

    • 1 mg

    • 2.5 mg

    • 5 mg

    • 10 mg

  • Orally disintegrating tablet

    • 1 mg

  • Gummies

    • 1 mg

    • 15 mg

  • Lozenge

    • 800 mcg

  • Liquid drops

    • 1 mg

    • 15 mg

What are common L-Methylfolate dosages?

  • Recommended daily intake:

    • For adults and adolescents 14 years of age and older: 400 mcg/day

    • For pregnant women: 600 mcg/day 

    • For lactating women: 500 mcg/day 

    • For children 9–13 years: 300 mcg/day

    • For children 4–8 years: 200 mcg/day

    • For children 1–3 years: 150 mcg/day

    • For children 7–12 months: 80 mcg/day 

    • For newborns to children up to the age of 6 months: 65 mcg/day

  • For treatment-resistant depression along with antidepressants: 7.5 mg or 15 mg taken once daily

  • For high homocysteine levels in people with schizophrenia: 7.5 mg or 15 mg taken once daily

  • For folate deficiency: 400 mcg–1 mg taken daily

  • For megaloblastic anemia (folate deficiency without vitamin B12 deficiency): 1 mg daily

  • To prevent folate deficiency due to methotrexate chemotherapy: 5 mg taken once weekly

  • To prevent folate deficiency due to chronic hemodialysis: 1–5 mg taken once weekly

1,000 mcg = 1 mg

Find more detailed information about folic acid dosage, forms, and strengths here.

L-Methylfolate images - What does L-Methylfolate look like?

  • L-Methylfolate
    15mg tablet

  • L-Methylfolate
    7.5mg tablet

How to take L-Methylfolate

  • L-methylfolate can be taken with or without a doctor’s advice or prescription.

  • For self-administration, follow all the instructions on the product label.

  • When taking l-methylfolate under the direction of a healthcare professional, follow all the prescriber’s instructions. 

  • The package directions or the prescriber will tell you how much to take each day. Do not use more than directed.

  • L-methylfolate doses can be taken with or without food.

  • Store l-methylfolate products at room temperature protected from heat and light.

What to do if you miss a dose of L-Methylfolate

  • Take a dose as soon as you remember. 

  • If it’s the next day, skip the missed dose and resume the regular dosing schedule.

  • Do not take extra doses to make up for a missed dose.

L-Methylfolate contraindications - Who shouldn't take L-Methylfolate?

  • Do not use any l-methylfolate product if you have had an allergic reaction to the product or have a known allergy to any ingredient in the product.

L-Methylfolate warnings

  • Self-administering l-methylfolate supplements at doses lower than one milligram daily should not cause problems other than allergic reactions to ingredients in the product.

  • If self-administering l-methylfolate supplements, do not take high doses until talking to a doctor. Taking high doses of vitamin B9 can hide a vitamin B12 deficiency.

  • Before starting high-dose l-methylfolate (more than 1 mg daily), tell a doctor if you are pregnant, breastfeeding, or have:

    • A vitamin B12 deficiency

    • History of bipolar disorder (when used with an antidepressant)

  • When prescribed high-dose l-methylfolate, the doctor will need to check on the progress of treatment and occasionally perform blood tests. Keep all appointments.

  • Side effects are minimal even at high doses. The most commonly reported side effects are allergic reactions to ingredients in the product.

L-Methylfolate interactions & what to avoid when taking L-Methylfolate

  • Folate supplements interact with many medications. 

  • Before taking high-dose l-methylfolate, talk to a doctor first. Tell that doctor about all the prescription drugs, over-the-counter drugs, supplements, and remedies you take, particularly Prozac (fluoxetine), phenytoin, or capecitabine.

  • Other drugs lower folate levels in the body or interfere with folate metabolism. Some may not affect high-dose l-methylfolate. If you are taking prescription folate supplements, make sure the prescribing healthcare provider knows if you’re taking:

    • Drugs that treat seizures

    • Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen

    • Oral contraceptives

    • Pancreatic enzymes

    • Commonly prescribed drugs such as the acne medication isotretinoin, the diabetes drug metformin, or methylprednisolone

    • Aminopterin, capecitabine, methotrexate, pentamidine, pyrimethamine, triamterene, trimethoprim, warfarin

  • Tell other healthcare providers who treat you that you are taking high-dose vitamin B9 before they prescribe new medications.

L-Methylfolate side effects - How does L-Methylfolate make you feel?

Serious side effects

Stop taking l-methylfolate and talk to a doctor if you notice any signs or symptoms of an allergic reaction including:

  • Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing

Less serious side effects (high dose l-methylfolate)

  • Sleep problems

  • Increased anxiety

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