Methylfolate dosage for MTHFR

• The amount of methylfolate you need depends on individual factors such as your folate status, genetics, health conditions, symptoms, folate receptor autoantibodies, the medications you’re taking, and surprisingly, maybe less so, your age or weight. 
• Dosages of up to 15mg of methylfolate are generally shown to be effective and safe. 
• Methylfolate is more effective for those with DHFR, SHMT and MTHFR mutations because it is absorbed directly by the body. 
• Healthcare professionals have recommended both high and moderate doses of methylfolate, depending upon symptom-specific needs.

As with many nutrients, there is an RDI (recommended daily intake) dosage amount for folate, but dosage for methylfolate is not usually one-size-fits-all. Methylfolate is absorbed much more quickly than folic acid, which means the same folate dosages may not apply.

Determining your methylfolate dosage requires careful consideration of your unique health needs, what you are trying to treat, your genetic makeup, as well as medications you may be taking. At the end of the day, L-Methylfolate dosage is not a one-size fits all approach, nor is it strictly based on age, size or weight for determining how much is optimal to take.

We are not doctors and cannot provide any medical advice or recommendations. We simply offer our experience (since 2011), research and discovery from the pioneering healthcare professionals who have been making recommendations over the last decade.

Review our Methylation Protocols - different symptom-based protocols based on your specific health needs. These protocols give detailed, step-by-step instructions regarding which nutrients and products to consider. They also detail specific amounts of each nutrient as well as when and in what order to take them.

Because it takes about 18 years for a known medical fact to become a part of the ‘typical medical practice’, most doctors don't know a lot about MTHFR and methylfolate. If you are conducting research on this topic, you are ahead of the curve and may find some early answers to several long-term health challenges you have been fighting.

There seems to be two schools of thought regarding dosages; specifically I have heard them through Dr. Neil Rawlins (MD – Gynecologist) and Dr. Ben Lynch (Researcher/Naturopath).

If you do not have any specific genetics data regarding your MTHFR or other methylation pathway SNP statuses and do not wish to spend the time or money to do a larger genetics test, then you are not alone, many folks are in the same place. After all, this is how doctors have had to "practice medicine" for centuries - it's only recently that we have discovered the genetics data in detail, but science still doesn't yet have a broad knowledge about how to use it all (it's a pretty massive learning curve that the research world has been working to better understand).

You might decide to trial recommended doses of the key nutrients (methylfolate and an active B12 like hydroxocobalamin, methylcobalamin and/or adenosylcobalamin). Or you might want to speak with a healthcare practitioner or Naturopath to determine where you might want to start based on some of your specific medical goals. The things that might affect how well you tolerate the methylated nutrients could be other mutations like COMT, CBS, SUOX, etc.

MTHFR is a genetic mutation that interferes with the activity of the MTHFR enzyme, which is required to activate folic acid. Many people with MTHFR mutations are unable to benefit from folic acid in fortified foods or supplements because folic acid is a synthetic form of folate, and must be activated in order to be used by the body.⁶ In addition, folic acid supplements can result in intakes above the tolerable upper intake level due to poor metabolism in the body.⁷

Methylfolate, however, is an active form of folate, which means it doesn’t require processing with the MTHFR enzyme. Instead, methylfolate is absorbed and available for use in the body almost immediately after it is ingested. 

Taking bioactive folate (5-MTHF) has been shown to significantly increase blood serum folate levels compared with folic acid supplementation.⁸ 

L-methylfolate is the only folate that can cross the blood-brain barrier, which means it is suitable for vegans, vegetarians, the elderly, or those with malabsorption issues. It is also the only form that can bypass the MTHFR mutation.

Research into methylfolate dosage is limited, and it’s important to talk to your doctor first before starting a child on methylfolate supplements. However, one study found that L-methylfolate calcium dosages of 7.5mg and 15mg were well-tolerated and potentially beneficial for a range of neuropsychiatric conditions in children and young people aged 7-20.⁹

Our video above includes a naturopath briefly explaining how to dose a child and you can review more on the MTHFR, Methylfolate & Nutrient Ideas for Kids page.

Everyone metabolizes and responds to supplements differently. This largely depends on individual characteristics, including underlying medical conditions and genetics.

Health conditions and their severity may also necessitate dosage adjustments. For example, a severe folate deficiency may require a higher dose to improve folate levels as quickly as possible. Taking other medications or supplements at the same time must also be considered, as some drugs can affect uptake.  

• 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 folic acid doses greater than 0.1 mg/day may mask pernicious anemia: another reason that doctors recommend L-methylfolate over folic acid. 

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.

When determining the right dosage of methylfolate for you, be sure to consider all of the factors mentioned above: your body’s ability to metabolize folate, other health conditions (if applicable), what you are trying to treat, and your age and weight. 

It’s also important to remember that the dosage for methylfolate is not the same as for folic acid because methylfolate is fully bioavailable. The amount of methylfolate you take will be completely absorbed by the body, while folic acid (as a non-active nutrient) will only be partially absorbed by the time it has been converted to its active form. 

If you have symptoms of folate deficiency, here are some suggestions for dosage according to the severity of your symptoms. Remember, a healthcare professional is the best person to assess your needs.

• Possible anemia (tiredness, fatigue, lethargy, muscle weakness, headaches, dizziness, pale skin, shortness of breath): 1-4 mg of L-methylfolate
• Neurological signs such as pins and needles, tingling, burning, or numbness in the hands and feet: 3 mg of L-methylfolate
• Cognitive symptoms: poor memory, brain fog, dementia, impaired judgment and understanding: 5-6 mg of L-methylfolate
• Psychological issues such as depression and anxiety: 7.5-15 mg of L-methylfolate

If you’re not sure, or if you’re taking other medications, it’s best to consult a healthcare professional, naturopath and/or pharmacist. 

Testing can be an 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 but not distinguish between your levels of folic acid (which is also known as unmetabolized folic acid), tetrahydrofolate (THF), folinic acid and methylfolate. This can make it challenging to determine if you need bioactive and absorbable folate or not.

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.

As with any supplement, the right dosage of methylfolate for your needs will provide the best results. This can be determined by first assessing your level of deficiency and then by beginning a supplement regime and monitoring your response.

While high doses (up to 45 mg L-methylfolate) have been studied without any adverse effects, your personal circumstances will also influence how your body responds to a dosage.¹

Taking too low a dose will not provide the benefits you require.

It doesn’t matter what time of day you take methylfolate as long as you take it at around the same time every day. Consistent dosage is the key to optimal results. 

Many people may take their dose in the morning (as the extra energy stimulation some get can keep them up at night), and others take it at night (as the serotonin production it generates can aid ‘get up’ motivation in the morning). It depends on what’s most comfortable and convenient for you as well as what time you’re most likely to remember. 

Health practitioner Dr. Neil Rawlins recommends taking two half doses (i.e. 7.5 mg at a time) of methylfolate per day (morning and afternoon). Methylfolate has a short half-life in the body, so divided dosing can help to maintain a steady level of folate in the bloodstream throughout the day.

Taking methylfolate in the morning and/or at lunchtime is recommended, as B vitamins can be somewhat energizing. Some people who take methylfolate later in the day may find it difficult to sleep at night. 

Keep your bottle of methylfolate near the items you would usually use at breakfast and lunch, such as your tea and coffee canister or the fridge. This will help you to remember to take it at the same time every day. If you miss a day, don’t double your next dosage: simply take the same dose the next day as usual.