Medically Reviewed on 4/11/2022

Generic Name: L-methylfolate

Brand Name: Deplin

Drug Class: Food, supplements

What is L-methylfolate, and what is it used for?

L-methylfolate is the active form of vitamin B9, also known as folate that naturally occurs in many foods. L-methylfolate is a prescription medical food used to supplement folate deficiency in people with major depressive disorder or schizophrenia, and megaloblastic anemia, a form of anemia caused because the bone marrow produces large, immature and structurally abnormal red blood cells.

L-methylfolate is a water-soluble vitamin crucial for several cellular functions including DNA synthesis, amino acid synthesis and growth of healthy cells, particularly, red blood cells. L-methylfolate is a cofactor in the production of chemicals (neurotransmitters) in the brain including serotonin, dopamine and norepinephrine. L-methylfolate is the more effective form of folate that can cross the blood-brain barrier and is more readily available for cellular functions.

L-methylfolate is naturally available as folate from many foods, including leafy green vegetables, legumes, eggs, beef liver, fruits and vegetables. People also take folic acid, the synthetic form of folate, as a supplement. Folic acid and l-methylfolate cannot be used interchangeably because folic acid or folate must be converted by the body into L-methylfolate for the cells to be able to use it, and some people may have genetic conditions that affect this ability.


  • Do not take if you have hypersensitivity to L-methylfolate or any of its components
  • L-methylfolate must not be used as a monotherapy for megaloblastic or pernicious anemia if the patient also has vitamin B12 deficiency
  • Doses of L-methylfolate greater than 0.1 mg/day may mask B12 deficiency pernicious anemia while irreversible nerve damage continues to progress
  • L-methylfolate must be taken only under a physician’s supervision
  • L-methylfolate therapy for a prolonged period of time may cause a decrease in vitamin B12 levels

What are the side effects of L-methylfolate?

Common side effects of L-methylfolate include:

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

What are the dosages of L-methylfolate?


  • 7.5mg
  • 15mg



  • Adjunctive treatment to antidepressant medication
  • 7.5 – 15 mg orally every day

Megaloblastic Anemia

  • 7.5 – 15 mg orally every day

Renal and hepatic impairment

  • Moderate-to-severe renal or hepatic impairment: Not to exceed 40 mg/day


  • Safety and efficacy not established


  • Overdose of L-methylfolate is unlikely to cause life-threatening symptoms; may cause mood changes.
  • In case of overdose or if you develop severe hypersensitivity symptoms, seek medical help immediately or contact Poison Control.


Depression is a(n) __________ . See Answer

What drugs interact with L-methylfolate?

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

L-methylfolate may interact with the following drugs:

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

Pregnancy and breastfeeding

  • Adequate l-methylfolate during conception and early pregnancy is essential and the requirement is greater in pregnant women. Supplemental L-methylfolate intake during pregnancy is likely to be beneficial for the health of the mother and the fetus. Studies suggest that improving folate levels in pregnancy reduces the risk of neural tube defects that can affect the brain and spinal cord in the newborn.
  • L-methylfolate is a beneficial nutrient to the breastfeeding infant and is present in breast milk in adequate amounts required for the infant.

What else should I know about L-methylfolate?

  • Take L-methylfolate exactly as prescribed
  • Keep L-methylfolate out of reach of children
  • Seek medical help immediately if you have severe allergic reactions


L-methylfolate is the active form of vitamin B9, also known as folate, used to supplement folate deficiency in people with major depressive disorder or schizophrenia, and megaloblastic anemia. Common side effects of L-methylfolate include allergic reactions, flatulence, abdominal distention, nausea, bitter or bad taste, loss of appetite (anorexia), impaired judgment, overactivity, excitement, difficulty concentrating, confusion, irritability, and changes in sleep patterns. Folic acid and l-methylfolate cannot be used interchangeably. Supplemental L-methylfolate intake during pregnancy and while breastfeeding is likely to be beneficial.

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You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 4/11/2022