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Proper Methylfolate Dosage for MTHFR Treatment

Proper Methylfolate Dosage for MTHFR Treatment

Finding the Right Methylfolate Dosage for MTHFR

Demand for methyl-folate has surged in recent years as more and more people learn they are affected by low folate levels.

Low folate can result from certain medications, diet, alcohol, drugs, gastrointestinal disorders, or—in many cases—an MTHFR genetic mutation. In all these cases, prescription folic acid is often recommended. Doctors will also prescribe folic acid for pregnant or nursing women or to patients with treatment-resistant depression. Read on to learn why this approach does not improve health.

Folate deficiency can not only lead to depression but also hinder recovery from it. Recent studies show that folate deficiency, especially caused by genetic variability in folate metabolism, is a causative factor in resistance to antidepressant treatment.

However, folic acid is not a suitable option because the MTHFR genetic enzyme deficiency prevents the proper conversion of folate to 5-MTHF. The best option for those with MTHFR is methylfolate. 

Bioactive L-methylfolate has been shown to significantly increase blood serum folate levels when compared to folic acid.

As with any supplement, there are proper dosage levels for methylfolate.

There are many dosage guidelines for folic acid online. However, methylfolate is absorbed much more quickly than folic acid, often allowing for a lower dose. Folic acid’s effectiveness is influenced by the MTHFR genetic variants in the folate pathway that impairs conversion to its active form.

Although it is unlikely you will suffer adverse effects from taking too much methylfolate, the dosage that accompanies a particular product is there for a reason. Taking the proper dosage will ensure that you enjoy the maximum benefits.

This article will explain the proper dosage for methylfolate and how much methylfolate you should take. We’ll also discuss how to determine the right dosage for you and why people take methylfolate at all.

How Much Methylfolate Should You Take?

Understanding the general dosage for methylfolate can help you determine what is best for your own needs.


Prescription methylfolate (known as Deplin®) is available in dosages of 7.5 mg and 15 mg. The recommended dosage for adjunctive treatment to antidepressant medication is 7.5 - 15 mg per day. The greatest effects of high-dose methylfolate in treatment-resistant depression are seen from taking 15 mg/day of methylfolate.

The dosage for treating megaloblastic anemia is also 7.5 - 15 mg per day, while the dosage for renal and hepatic disorders (moderate) is not to exceed 40 mg per day.

It’s important to note that doses greater than 0.1 mg/day may mask pernicious anemia. Doctors advise that this may cause normal blood cell count to show up in blood tests while “irreversible nerve damage” continues.

Everyone is different, and everyone metabolizes supplements differently. For some people, determining the right dose of methylfolate may be a matter of trial and error. Many Naturopaths will suggest you start low and go slow to increase your dosage amounts. However, a doctor’s prescription for Methylfolate will usually be prescribed based on the patient’s specific health problems.

How to Determine the Right Dosage of Methylfolate for You

How to Determine the Right Dosage of Methylfolate for You

Determining the right dosage of methylfolate begins with assessing the degree of your symptoms. For some people, symptoms of folate deficiency are their first clue that they are in need of supplementation.

Symptoms of folate deficiency typically include:

● Tiredness, fatigue, lethargy (1-4 mg of L-methylfolate)

● Muscle weakness

● Neurological signs: pins and needles, tingling, or burning, or peripheral neuropathy (numbness in the extremities) - 3 mg of L-methylfolate

● Psychological issues: depression (7.5-15 mg of L-methylfolate)

● Cognitive symptoms: poor memory, brain fog, impaired judgment and understanding, dementia/Alzheimer’s (5-6 mg of L-methylfolate)

● Gastrointestinal signs: nausea, vomiting, abdominal pain, weight loss, diarrhea, irritable bowel syndrome (IBS) (if symptoms are due to low serotonin levels, consider 7.5-15 mg of L-methylfolate)

● Headache and dizziness

● Pallor

● Shortness of breath

However, because symptoms of mild folate deficiency are often mild, testing is often a much more accurate means of determining your folate status. This can provide a better picture of how depleted you may be. In addition, some of the symptoms mentioned above (headache, dizziness, shortness of breath) are also symptoms of anemia, so it may be necessary to test for Vitamin B12 deficiency as well.

A plasma test can measure the amount of folate in the liquid portion of your blood. This can help show how much folate you’re getting from supplements and your diet. The folate blood test will also measure your levels of folic acid (which is also known as unmetabolized folic acid), tetrahydrofolate (THF), folinic acid, and methylfolate.

However, a more accurate way to measure folate levels is to test the amount in your red blood cells. This will show the amount of folate in your body when the cell was made, which can indicate your levels over the past four months. Unlike the plasma test, the red blood cell test is not usually affected by the amount of folate and folic acid you are consuming each day.

Why Use L-Methylfolate for MTHFR Treatment?

L-methylfolate plays a crucial role in many bodily processes. It is necessary for DNA synthesis and various methylation reactions, including the conversion of homocysteine to methionine. It is also required for repairing DNA, turning genes on and off, and creating neurotransmitters.

Low levels can lead to a range of health conditions, including megaloblastic anemia, pancytopenia, glossitis, angular stomatitis, oral ulcers, neuropsychiatric disorders(depression, irritability, insomnia, cognitive decline, fatigue, and psychosis).

However, ordinary folic acid supplements may not provide the full spectrum of effects for those who are unable to convert folate to its biologically active form due to an MTHFR mutation. Instead, folic acid must be broken down and methylated through a complicated four-step process.

In addition, folic acid supplements can result in intakes above the Tolerable Upper Intake Level.

L-5-Methyltetrahydrofolate(L-methylfolate, or 5-MTHF) is the preferred form of the nutrient as it is the predominant active form in the body. L-methylfolate is the only folate that can cross the blood-brain barrier, which means it is suitable for those with the MTHFR polymorphism, vegans, vegetarians, the elderly, or those with malabsorption issues.

Taking methylfolate alongside antidepressants can significantly boost the effectiveness of the medication. This form is able to bypass the conversion step mediated by the MTHFR enzyme(methylenetetrahydrofolate reductase). This means that L-methylfolate supplements can be given as a means of improving serum and Central Nervous System (CNS) folate levels, particularly in assisting with the response to antidepressant medication.

One study involving patients with schizophrenia measured the benefits of L-methylfolate over folic acid. After receiving 15 mg of L-methylfolate for 12 weeks, L-methylfolate significantly increased plasma methylfolate levels compared to placebo. The patients also showed improvements in many cognitive tasks.

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Why Use L-Methylfolate for MTHFR Treatment

Best L-Methylfolate Supplements

Supporting your body’s needs for folate begins with taking the right form of the nutrient and in the correct dose. This can be determined by first assessing your level of deficiency and then by beginning a supplement regime and monitoring your response.


Taking bioactive folate (5-MTHF) has been shown to significantly increase blood serum folate levels compared with folic acid supplementation. This form of folate is vital for people who have the MTHFR genetic enzyme deficiency because it requires no conversion to become metabolically active.


Those who cannot convert folic acid to its biologically active form (5-methyltetrahydrofolate [5-MTHF] or L-Methylfolate) well are much less likely to benefit from folic acid supplements.


Some of the best methylfolate supplements for those with MTHFR mutations (or folate deficiency caused by other factors) include Methyl-Life® products (B-Methylated II, Methylated Multivitamin, Methylfolate 5,  Methylfolate 7.5+ or Methylfolate 15+.) This product range has been created by a team of natural health experts and used successfully by thousands of people all over the world. The form of L-methylfolate used in Methyl-Life® products is the purest, most stable, and most potent when compared to four of the world’s industry-leading, patented L-methylfolates.

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    Written By,
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