What to Know About Deplin (L-methylfolate)

A Prescription Medical Food Used to Treat Folate Deficiency

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Deplin (L-methylfolate) is a prescription medical food made up of folic acid—a form of vitamin B. Folic acid is the synthetic form of folate, which occurs naturally in our bodies and various foods.

Getting sufficient folate can prevent anemia and other diseases. Deplin is typically used by people who have folate deficiency or conditions related to folate deficiency. 


The active ingredient in Deplin is L-methylfolate, which is a synthetic form of folate. Folate is needed by the body to efficiently produce red blood cells. 

Deplin is used to treat low folate levels and conditions caused by low folate levels.

This medical food is particularly used for the dietary management of people who have major depressive disorder with folate deficiency and people with schizophrenia who have hyperhomocysteinemia related to folate deficiency.

There are other products available commercially online, such as Methylpro, that have the same ingredient and dosing but are far more cost effective.

Major Depressive Disorder

Deplin is made up of L-methylfolate which is an active form of folic acid. Folate has been shown to help naturally improve moods and a folate deficiency has been linked to certain types of depression.

Dietary folic acid must be converted in the body to L-methylfolate in order for it to cross the blood-brain barrier. Once in the brain it undergoes a series of chemical reactions to convert it to its final form, which is used in the synthesis of serotonin, dopamine, and norepinephrine.

Some individuals have variations of the MTHFR gene that lead to reduced conversion of folic acid to L-methylfolate and it is thought that these individuals are likely to benefit most from L-methylfolate augmentation of antidepressants.

Deplin is typically used alongside antidepressants to help treat depression. If your folate levels are low it might be sometimes harder for your antidepressants to work efficiently. Low levels of folate also put you at risk of relapsing into depression after it has been treated. 

In a 2013 study assessing the effects of L-methylfolate in the management of depression, researchers found that when L-methylfolate was used alongside antidepressants in 502 participants with major depressive disorder, they showed significant improvements in their depressive symptoms.

It’s important to know that Deplin is not an antidepressant but can enhance the effects of antidepressants in people with major depressive disorder.

Before Taking

Before prescribing Deplin, your doctor will conduct a thorough investigation into your medical history. If you have any allergies to folate or the other ingredients contained in Deplin, make sure to disclose this to your doctor.

You can ask your doctor for a comprehensive list of active and inactive ingredients to be sure. If you have a history of vitamin B deficiency, you should also share this with your doctor.

If you have epilepsy or a history of seizures, or a family history of manic depression, tell your doctor to make sure Deplin is safe for you.

Precautions and Contraindications 

If you are pregnant or you just had a baby and intend to breastfeed you should let your doctor know before taking Deplin. This is because while Deplin is relatively safe for pregnant and breastfeeding women, the dosage for people in this category might differ from the typical dosage.

At recommended doses, Deplin poses next to no risk for pregnant or breastfeeding women and their children. 


Deplin is a prescription medical food, which means that the dosage is typically outlined by your doctor to fit your specific needs. You shouldn’t increase or reduce the dosage prescribed for you without first consulting your doctor.

This drug is typically prescribed to be taken once a day. To avoid missing any doses, set an alarm for the same time every day to take it. Deplin is available in two dosages: 7.5 milligrams (mg) and 15 milligrams (mg).The manufacturers recommend the following dosages for these conditions. 

  • Depression: 7.5 mg to 15 mg taken once a day 
  • Megaloblastic Anemia: 7.5 mg to 40 mg taken once a day, depending on the severity of the condition. However, no more than 40 mg a day should be prescribed. 

How to Take and Store 

You can either take Deplin with or without food, however it should be swallowed whole and not chewed or split into two. If you miss a dose, take it as soon as you remember.

If it’s close to the time for your next dose, then skip the missed dose to avoid the risk of overdosing. 

Store your medication in a dry place at room temperature away from direct sunlight. Avoid storing it in your bathroom as bathrooms can get very humid and moist. Deplin should be taken regularly to get the most optimal benefits from it. You shouldn’t discontinue Deplin without first consulting your doctor.

You also shouldn’t share Deplin with any family or friends who might have similar symptoms as you, instead refer them to a doctor so a proper prescription for Deplin can be given. 

Deplin is also available in a generic formulation as L-methylfolate calcium (Metafolin) and Algae-S powder (Schizochytrium). However, some research shows that the generic formulations of medical foods like Deplin might not be an effective substitute for the brand name drug.

Side Effects 

Deplin and folic acids in general typically have very few side effects. However, some people might experience an allergic reaction while using this drug. Even though this is very rare, here are the signs of an allergic reaction to look for when using Deplin: 

  • Difficulty breathing 
  • Dizziness 
  • A skin rash 
  • Swelling of the face, tongue or throat

If you notice any of the above symptoms, stop using Deplin and contact your doctor immediately. If you notice any other unusual effects that are not life-threatening but could be bothersome, speak to your doctor about it. 

Some common side effects you might experience while using Deplin include: 

  • Nausea 
  • Weight loss 
  • Gass 
  • Irritability 
  • Overactivity 
  • Bloating 
  • Difficulty concentrating 

Warning and Interactions 

Deplin may interact with other drugs, supplements, or vitamins you are taking in such a way that it may reduce their efficacy or reduce the efficacy of Deplin. Before taking, give your doctor a list of all other drugs, vitamins, or supplements you are currently taking.

If you are already on Deplin and need to start taking another drug, update your doctor to ensure that there’ll be no adverse reactions. However, Deplin has no known severe interactions with any other medications. 

It’s possible to overdose on Deplin, the most telling sign of an overdose include fainting, trouble breathing, and sudden mood changes.

If you suspect you are experiencing an overdose or notice someone has overdosed call 911 or your local poison control center immediately. Deplin may also reduce the effectiveness of anticonvulsants like carbamazepine, valproate, and phenytoin.

3 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Shelton RC, Sloan Manning J, Barrentine LW, Tipa EV. Assessing Effects of l-Methylfolate in Depression Management: Results of a Real-World Patient Experience TrialPrim Care Companion CNS Disord. 2013;15(4):PCC.13m01520. doi:10.4088/PCC.13m01520

  2. University of Michigan Medicine. L-methylfolate.

  3. Cleveland Clinic. Levomefolate tablets and capsules.

By Toketemu Ohwovoriole
Toketemu has been multimedia storyteller for the last four years. Her expertise focuses primarily on mental wellness and women’s health topics.