Is Methylfolate the Same as Vitamin B12?

When so many nutrients have similar names, it’s easy to get confused. You may be wondering if there’s a difference between two major B vitamins B9 (folate or methylfolate) and B12, also known as cobalamin (or methylcobalamin).

Both of these vitamins are available in natural and synthetic forms, and they’re both commonly deficient in humans. But although they sound similar and are involved in many of the same biochemical processes in the body, they are distinctively different. 

These nutrients differ not only in their structure and sources but also in the roles they play in the methylation process. Methylation is one of the most important biochemical reactions in the body, occurring billions of times per second. It’s required for proper detoxification, neurotransmitter production, hormone metabolism, histamine metabolism, DNA/genetic expression, amino acid metabolism, and growth and development. 

However, those with an MTHFR polymorphism are unable to properly utilize the inactive forms of folate and B12, which impairs the methylation process. It is important to understand how methylfolate differs from folic acid and how B12 differs from methylcobalamin. 

This article will explain these differences and the importance of the methylation cycle in how these nutrients are used in the body. We will also explain why methylated forms of these vitamins are essential for numerous biochemical processes in the body and the regulation of overall health.

Methylfolate is the methylated form of folate and the preferred form of folate in the body. It is the only form of folate that can cross the blood-brain barrier, and its bioavailability is much higher than that of folic acid.

Methylfolate is vital to health at every age and stage of life. It’s involved in making and repairing DNA and helps cells to grow and regenerate. It’s required in the electrical insulation of nerve cells and the production of monoamines serotonin, dopamine, and norepinephrine, which regulate mood. 

Folic acid is a synthetic form of folate and can be difficult for the body to convert into active folate in the presence of an MTHFR mutation. Folic acid is not metabolically active, so it must be converted to methylfolate in a complicated four-step process before being used in cellular metabolism. 

Like methylfolate, vitamin B12 must be in the active form to be used properly in the body.

Vitamin B12 is available in three natural forms: methylcobalamin (MeCbl), adenosylcobalamin (AdCbl), and hydroxocobalamin (OHCbl). Like methylfolate, these forms are bioidentical to the B12 forms in the body and animal foods.

The most common forms of vitamin B12 used in supplements are methylcobalamin and cyanocobalamin. Although both forms contain a cobalt ion surrounded by a corrin ring, each has a different molecule attached to the cobalt ion. Methylcobalamin contains a methyl group, while cyanocobalamin contains a cyanide molecule. This is because cyanocobalamin is a synthetic form of B12 that is often added to fortified foods or cheaper supplements. It is only present in trace amounts in the body, often due to cyanide intake from cigarette smoke or other sources.

In people with MTHFR mutations, both methylfolate and methyl B12 are essential for bypassing the malfunctioning conversion process and ensuring the methylation cycle functions optimally. 

Methylfolate and methyl B12 are the active forms of folate and B12. It is these forms that are available to be used immediately by the body without further conversion. 

Methylcobalamin is an active form of vitamin B12 essential for the proper synthesis of methionine and S-adenosylmethionine. It is required for supporting the integrity of myelin, proper red blood cell formation,  neuronal function, and DNA synthesis. It works alongside methylfolate to pass the methyl group through the cycle. This occurs via the transfer of the methyl group from methyltetrahydrofolate.

It is also necessary for preventing homocysteine from accumulating in the body. 

People with particular SNPs (single nucleotide polymorphisms) affecting B12 uptake may require methyl B12 to boost their B12 status as efficiently as possible. 

Methyl-B12 and adenosylcobalamin are two forms of B12 that have biological activity to act as cofactors in these many enzymatic reactions. Cyanocobalamin and hydroxocobalamin are synthetic forms of cobalamin.

Folate is the natural form of vitamin B9 present in leafy green vegetables, cruciferous vegetables, and legumes. We cannot synthesize folate and depend on food or supplements to maintain normal levels. 

Low folate status may result from diet and/or poor absorption of folate or compromised folate metabolism due to genetic defects. 

Folate deficiency is a serious condition that should be corrected immediately, as it has been linked to health conditions such as neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction. 

Folate supplements are in the form of folic acid, folinic acid, or methylfolate (5-methyltetrahydrofolate or 5-MTHF). 

Naturally occurring methylfolate is far superior to synthetic folic acid for many reasons. It is well absorbed even when digestive function is poor, and its bioavailability is not affected by metabolic defects. Methylfolate doesn’t mask symptoms of vitamin B12 deficiency, nor does it interact with medications that inhibit dihydrofolate reductase. 

Using methylfolate prevents the potential negative effects of unconverted folic acid in the peripheral circulation.

L-methylfolate has no known severe, serious, moderate, or mild interactions with other drugs.

As a highly bioavailable nutrient, it is the most effective for raising folate levels in the blood.

Over-the-counter (OTC) folic acid, however, is not well absorbed and does not cross the blood-brain barrier. It must be converted to its active form before it can be used, a process that may be compromised in many patients with an MTHFR polymorphism. 

Folic acid (FA) is a synthetic compound with no biological functions unless it is reduced to dihydrofolate and then to tetrahydrofolate. Unmetabolized FA has been shown to appear in the circulation at doses of >200 mcg.

For this reason, methylfolate should not be interchanged with OTC (over the counter) folic acid.

In addition, high doses of folic acid may mask vitamin B12 deficiency and even exacerbate the neurologic effects of vitamin B12 deficiency.

Deficiencies in vitamin B12 and folate are very common due to genetic SNPs, dietary choices, and environmental factors. Those with these deficiencies almost certainly require supplementation - as long as they are supplementing with the most bioavailable form of the nutrient. 

Those with an MTHFR polymorphism cannot metabolize folate or B12 properly, so they would be well advised to take the methylated forms of both of these nutrients: methylfolate (5-MTHF) and methylated vitamin B12 (methylcobalamin/methyl-B12 and adenosylcobalamin). However, methylfolate is the most important of the two for facilitating methylation in the body. 

Unlike folic acid, methylfolate has no tolerable upper intake level and won’t mask a vitamin B12 deficiency. Supplemental methylfolate has been shown to effectively boost folate levels in the body. 

Where possible, supplementing with any of the nature-identical forms of B12 (MeCbl, OHCbl, and/or AdCbl) is preferred instead of the use of cyanocobalamin, owing to their superior bioavailability and safety.

Methylfolate is absolutely essential for normal bodily function due to its involvement in an enormous range of processes - the most important being methylation. Aberrant DNA methylation has been widely observed in many diseases, cancers, and health conditions. 

Deficiencies in methylfolate and B12 are often linked to the MTHFR mutation. 

Some of the most highly recommended methylfolate supplements are in the Methyl-Life® product range, which includes a selection of dosage levels: Methylfolate 7.5+, Methylfolate 10, and Methylfolate 15.

Each of the methylfolate products in the Methyl-Life’s® range contains the internationally-patented Magnafolate® PRO  [(6S)-5-methyltetrahydrofolic acid, Calcium salt, Type C Crystalline molecule (L-Methylfolate)]. These best-selling products are formulated especially for people with a heightened need for bioavailable folate due to MTHFR defects, dietary deficiencies (such as vegans or vegetarians), or other conditions in which nutritional absorption is impaired.  

This unique and internationally-patented L-5-Methylfolate ingredient is crystalline calcium salt-based for superior stability and absorption. Research has revealed that this proprietary form of methylfolate is approximately three times more pure and stable than other L-Methylfolates available on the health supplement market today.