What Is Deplin?

What Is Deplin?

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Methylfolate 15 mg

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Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Dr. Conor Sheehy - PharmD, BCPS

Medical Reviewer:

Dr. Conor Sheehy - PharmD, BCPS
Kari Asadorian - BSN, RN

Edited By:

Kari Asadorian - BSN, RN
Last updated:
Demystifying Deplin | MTHFR | Methyl-Life® Supplements Source: YouTube.com

What is Deplin®?

Deplin® is a prescription medication designed to be taken alongside antidepressants. It works by improving the brain’s ability to make serotonin, norepinephrine, and dopamine, which enhances the effects of antidepressant medication.
Deplin® is classified as a “medical food” rather than a drug. Medical foods are products that are specially formulated to manage conditions with specific nutritional needs and cannot be fulfilled by diet alone. 


Deplin® contains a form of folate that has already been converted to its bioactive form, L-methylfolate, which allows it to be immediately absorbed by the body. Deplin® is available in 7.5 mg and 15 mg dosages.

What is Deplin® Used For?

Deplin® medication is used to treat people who have depression, schizophrenia, or hyperhomocysteinemia due to folate deficiency. 

Folate is required for the synthesis of neurotransmitters such as serotonin, norepinephrine, and dopamine. Low levels of these chemicals are implicated in major depression and other psychiatric disorders, which is why folate deficiency is linked with depression. As the active form of folate, L-methylfolate can pass through the “blood-brain barrier” and enter the central nervous system, where it can increase levels of these neurotransmitters.
For people with an MTHFR mutation (around half the world's population), dietary folate or folic acid supplements will be ineffective because their body cannot convert it into active folate.  This is why L-methylfolate supplements may help those with mood disorders. 

Research has shown that taking L-methylfolate with an antidepressant is more effective in improving depressive symptoms and function than taking an antidepressant alone. The antidepressant therapy was also better tolerated along with the L-methylfolate. 1 Other studies have shown that patients managed with L-methylfolate achieved statistically significant improvements in their self-reported depression symptoms and functioning as well as greater satisfaction with their medication treatment. 2

Deplin® side effects

Deplin® is generally reported to be safe and well-tolerated. 3

Some people have reported allergic reactions to L-methylfolate calcium. Consult your health professional if you have a skin rash, itching, swelling of the face, or hives.

Agitation, anxiety, and gastrointestinal issues have also been reported.

Deplin® dosage

The standard adult dosage is one Deplin® 7.5mg capsule twice a day. Deplin® can be taken with or without food.

When not to take Deplin®

If you are allergic to Levomefolate, folic acid, other medicines, dyes, preservatives, milk or soy, talk to your health professional before taking Deplin®. You should also tell your health professional if you are deficient in B12, have a low red blood cell count, or if you are pregnant, breastfeeding, or trying to conceive.

How to take Deplin®

Deplin® should be swallowed whole with water. It can be taken with or without food.


If you miss a dose, take it as soon as you can. But if it’s nearly time for your next dose, skip the missed dose to avoid doubling up or overdosing.


If you want to know more about alternatives to Deplin®, and how L-methylfolate can help in managing your depression, check out Methyl-Life’s® supplement range. Methyl-Life® is a leading brand of L-methylfolate supplements specifically formulated to support mood, cognitive function, and overall well-being. Methyl-Life’s® methylfolate products can be an affordable over-the-counter alternative to Deplin®.

Deplin compared to other products

Deplin Algal Oil

Deplin is a combination of Metafolin® (L-methylfolate) and Algae-S powder [Schizochytrium]. Schizochytrium is made from marine algae and is a vegetarian source of omega-3 fatty acids, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which have important benefits for cognitive function, mood, and overall health. Numerous studies and meta-analyses support the use of omega-3s for the prevention and treatment of major depressive disorder and depressive symptoms.4 Algae powder is used in foods and as a medicine.

EnLyte® vs Deplin®

Like Deplin®, EnLyte® is an FDA-regulated prescription medical food containing L-methylfolate, the active dietary form of the vitamin B9 (folate).


EnLyte® also meets the FDA USP for dissolution and degradation of folates, which means that it meets the FDA’s standards for how effectively folate dissolves and breaks down in the body. This is an FDA standard claimed by only about a third of folate supplements.


Deplin® contains L-methylfolate calcium, while EnLyte® contains L-methylfolate magnesium (a salt of levomefolic acid) and folinic acid (leucovorin).
EnLyte® is considered a multivitamin as it also contains active B vitamins, vitamin C, zinc, and magnesium. EnLyte® is prescribed for treating anemia and nutritional deficiencies, including iron deficiency. It is also prescribed as prenatal nutrition.

Deplin® vs Metanx®

Metanx is a medical food prescribed for managing diabetic peripheral neuropathy and diabetic ulcers. It contains L-methylfolate, methylcobalamin (B12) and pyridoxal 5'-phosphate (B6). Metanx® is designed to support nerve repair in diabetic patients by providing nutrients to improve blood flow.

Deplin® vs generic folate

Generic folate includes folic acid, a synthetic (man-made) form of vitamin B9. Folic acid is cheaper to produce than L-methylfolate, which is why it is used in many supplements, prenatal vitamin formulas, and fortified foods. However, folic acid must be converted to its active form in the body before it can be used, which can be difficult for people with the MTHFR genetic mutation.


Natural dietary folate from foods such as spinach, kale, eggs, legumes, and citrus also must be properly metabolized in the body before it can be used.5

Product Recommendations

L Methylfolate 15 mg - A Mood-Boosting Supplement

L Methylfolate 15 mg - A Mood-Boosting Supplement

$76.00

  • Professional Strength - Ask Your Doctor
  • High-Dose L Methylfolate 15 Mg for Natural Mood Support²
  • 3rd-Party Tested for Purity, Potency & Safety
  • 90 Vegan, Non-GMO, Chewable Mint Tablets

Understanding Deplin® & L-Methylfolate

Frequently Asked Questions about Deplin®

What does the drug Deplin® do?

Deplin® contains a high dose of L-methylfolate, the bioavailable form of vitamin B9. L-methylfolate is essential for supporting healthy mood, DNA production, cognitive function, and much more. Methylfolate helps the brain to produce serotonin, dopamine, and norepinephrine. These neurotransmitters play an important role in mood management. Low levels of neurotransmitters have been associated with mental health disorders such as depression, schizophrenia, and bipolar disorder.4

Many people who are diagnosed with depression will be prescribed antidepressants. Antidepressants are prescription drugs designed to enhance the availability of neurotransmitters such as serotonin in the brain, which can reduce symptoms of depression. However, people who already have low levels of these neurotransmitters are less likely to benefit from antidepressants such as selective serotonin reuptake inhibitors (SSRIs). By increasing neurotransmitter levels, L-methylfolate improves the effectiveness of antidepressant medication and the symptoms of depression in patients who are otherwise treatment-resistant. 5

Why is Deplin® so expensive?

Deplin® requires a doctor’s prescription, which can make it unaffordable for those who don't have health insurance. Many insurance companies don’t cover this medical food and it can be quite expensive. Talk to your medical professional to determine if Deplin® would be a good addition to your health needs.

A Deplin® generic formulation is available over-the-counter from Methyl-Life®. These L-methylfolate calcium supplements are chemically identical to Deplin®, and include dosages of 15mg, 7.5mg, 5mg, and 2.5mg.

Is Deplin® a controlled substance?

Deplin® is classed as a vitamin or “medical food”, and it is not a controlled substance. It has not been classified as a risk during pregnancy, however it is recommended that you consult with your doctor before taking Deplin® during pregnancy.

Can you buy Deplin® over the counter?

Deplin® can only be prescribed by a healthcare professional, so it cannot be purchased over the counter. It should only be used under the direction of a physician.

Is Deplin® covered by insurance?

Every insurance plan is different, but most will not cover Deplin®. Check with your insurance provider for specific details regarding drug coverage and copayment.

References

  1. Lawrence D Ginsberg, Alondra Y Oubre, Yahya A DaouD; "L-methylfolate Plus SSRI or SNRI from Treatment Initiation Compared to SSRI or SNRI Monotherapy in a Major Depressive Episode"; Innovations In Clinical Neuroscience; 2011 Jan

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036555/

  2. Richard C Shelton, J Sloan Manning, Lori W Barrentine, Eleanor V Tipa; "Assessing Effects of l-Methylfolate in Depression Management: Results of a Real-World Patient Experience Trial"; The Primary Care Companion CNS Disorders; 2013 Aug

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869616/

  3. Alfasigma USA, Inc.; "DEPLIN® is Safe and Well Tolerated"; Deplin.com; 2024

    https://www.deplin.com/hcp/safety-and-tolerability

  4. James J DiNicolantonio, James H O’Keefe; "The Importance of Marine Omega-3s for Brain Development and the Prevention and Treatment of Behavior, Mood, and Other Brain Disorders"; Nutrients; 2020 Aug

    https://pmc.ncbi.nlm.nih.gov/articles/PMC7468918

  5. Maša Vidmar Golja, Alenka Šmid, Nataša Karas Kuželički, Jurij Trontelj, Ksenija Geršak, Irena Mlinarič-Raščan; "Folate Insufficiency Due to MTHFR Deficiency Is Bypassed by 5-Methyltetrahydrofolate"; Journal of Clinical Medicine; 2020

    https://pmc.ncbi.nlm.nih.gov/articles/PMC7564482/

  6. Jun-Xi Pan, Jin-Jun Xia, Feng-Li Deng, Wei-Wei Liang, Jing Wu, Bang-Min Yin, Mei-Xue Dong, Jian-Jun Chen, Fei Ye, Hai-Yang Wang, Peng Zheng, Peng Xie; "Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters: a targeted metabolomics study"; Translational Psychiatry Vol. 8 Article #130; 2018 Jul

    https://www.nature.com/articles/s41398-018-0183-x

  7. Matthew Macaluso; "L-Methylfolate in Antidepressant Non-responders: The Impact of Body Weight and Inflammation"; Frontiers In Psychiatry; 2022 Mar

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968318

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Katie Stone - Naturopath

About the Author

Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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