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Methylfolate vs. Folic Acid vs. Folate: What’s the Difference?

Methylfolate vs. Folic Acid vs. Folate: What's the Difference?

Methylfolate vs. Folic Acid vs. Folate: What’s the Difference?

Folate is an essential vitamin that can be replaced by folic acid in individuals who do not consume enough folate naturally. However, folic acid is not an ideal option for people with MTHFR. Here is an overview of the importance of folate and your options for replacing it if you are not getting enough.

Folate vs. Folic Acid vs. Folinic Acid

Folate, folic acid, and folinic acid are all forms of vitamin B9, but they are not exactly the same thing or serve exactly the same purpose. Folate is vitamin B9 in its natural form, while folic acid is a synthetic version of vitamin B9. Folate is found naturally in vitamin-rich whole foods, particularly leafy vegetables, and folic acid is used to add vitamin B9 to processed foods and vitamin supplements.

Like the seven other variations of vitamin B, vitamin B9 is used to convert food into fuel and support healthy skin, eyes, hair, and blood cells. Folic acid is used to replace folate to obtain these benefits if enough folate cannot be consumed naturally. During pregnancy, some form of vitamin B9 is needed to ensure the baby's proper brain, skull, and spinal cord development to prevent birth defects.

Folinic acid, as well as methylfolate, is an active form of folate. This means that the body can use folinic acid's nutrients as soon as it is consumed, rather than having to convert it through the liver. Active folates are the most ideal forms of vitamin supplements when the body is not able to efficiently convert or absorb enough of the vitamin on its own.

Folate vs. Methylfolate

Like folate and folic acid, folate and methylfolate are used to obtain similar end goals in slightly different ways. Methylfolate is a reduced form of folate that can be found in certain dietary supplements. This means it’s the already-converted, most active form of folate the body can use. Like folic acid, it also serves as a synthetic replacement for natural folate.

It can be used as a superior folate supplement in many situations, as well as as a medication for anemia, depression, diabetes, dementia, and other disorders. Methylfolate is a particularly common substitute for folate in individuals with MTHFR, a type of gene mutation that prohibits them from converting and using natural folate efficiently.

The MTHFR gene helps to produce an enzyme that converts a portion of folate and folic acid into folinic acid. Folinic acid is then converted into the active form methylfolate, which is used by cells to perform the functions.

Folic Acid vs. Methylfolate

Folic Acid vs. Methylfolate

Methylfolate is active folate, which is the precise enzymatic form available for immediate cellular absorption and energy release. Although it has a similar end function to folic acid, choosing this efficient and ready-to-use form is a much more effective option for people who have difficulty converting food into fuel. 

Which Is the Best for MTHFR?

Methylenetetrahydrofolate reductase (MTHFR) is a type of gene mutation that lowers the efficiency of the MTHFR enzyme. Individuals with this mutation cannot properly convert folate into methylfolate. By disrupting the natural metabolic pathway, MTHFR blocks usable methylfolate from reaching the cells.

Inadequate methylfolate levels can have a wide variety of negative effects on the body, particularly those that affect the cardiovascular and nervous systems. During pregnancy, a lack of methylfolate can also have serious impacts on healthy fetal development.

Fortunately, there are several folate replacements available that can largely make up for deficiencies that are caused by MTHFR. Folic acid and folate can be cheap, but methylfolate tends to be the most effective option when it comes to treating the unique needs of MTHFR and giving the body an enzyme it can directly act upon.

L-methylfolate (chemically (6S)-5-Methyltetrahydrofolate) is the most pure, active form of methylfolate you can buy. Methylfolate and folic acid can sometimes perform similarly in individuals without MTHFR, but completely eliminating folic acid from the diet is recommended to allow methylfolate to obtain the most benefits in patients with MTHFR.

Because folic acid is synthetic and requires 4 conversions before it can be fully utilized in the body, it can cause health complications for patients with MTHFR and should be avoided in favor of methylfolate.

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Best Methylfolate Supplement

Best Methylfolate Supplement

There are several types of methylfolate supplements available, and the best methylfolate product for you largely depends on the specific benefits you would like to get from it.

Plain methylfolate supplements are available, which can be taken on their own or in combination with other supplements you are currently taking that do not contain folic acid. There are also several products that combine methylfolate with other vitamins and nutrients that were formulated to treat a specific condition.

Methyl-Life's® MTHFR Newbies guide provides an overview of several of the most common types of L-methylfolate supplements on the market, many of which are only available with a prescription.

Depending on the specific amount of methylfolate you need, your supplements may come in the form of chewable tablets, pills, or medical food products.

Some common prescription L-methylfolate supplements are used as treatments that target specific health problems. Cerefolin NEC is typically used to treat dementia, Alzheimer's, and other concerns related to brain health (5.6 mg of L-methylfolate), while Metanx is used for neuropathy and conditions related to the nervous system (3 mg of L-methylfolate). Deplin 7.5 and Deplin 15 (7.5 mg and 15 mg) are different strengths of L-methylfolate used to treat depression by increasing serotonin production within the body.

Women with MTHFR must be especially cautious about taking the proper supplements during pregnancy because the mutation can have a significant impact on the development of the baby or lead to miscarriage. Prenatal methylfolate supplements with 1 mg of L-methylfolate can be used to support healthy pregnancies. They can be taken on their own or in combination with certain other types of prenatal vitamins to boost both the baby's development as well as the mother’s health during pregnancy.

Other methylfolate supplements are more general and are used to support and optimize health overall, much like other supplements and multivitamins. These products can be used to boost mood, brain health, and general health without requiring the presence of a specific health problem. These supplements can be purchased without a prescription, though it is always a good idea to consult your doctor before adding supplements to your diet to make sure they will meet your needs.


Methylfolate can be a highly effective folate replacement for a wide variety of people. Folate is an essential vitamin in overall health, and replacing it with a supplement is extremely important if your body is not able to produce or convert enough of it on its own.

Although folic acid is cheap and readily available, and folinic acid can be an appropriate folate supplement for some people, these are not effective options for people with MTHFR. Methyl-Life's® purest L-methylfolate supplements are generally the best option for these individuals.

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