Did You Know These Methylfolate Benefits Can Help with Mood?
Medically Reviewed by Dr. Nicole Avena

Perhaps you’ve heard of the essential vitamin folate (aka vitamin B9).

But what’s the difference between folate and methylfolate? And what’s folic acid?

It can be a bit confusing, so let’s unpack each of these and see how they relate to each other.

What’s the Difference Between Folate, Folic Acid, and Methylfolate?


Folate is a group of chemically complicated substances that supply the body with chemically simple methyl groups. The body can’t make folate from scratch, so we must get it from foods or dietary supplements.

Folate is vital at every stage of life, from early development in the womb through birth, and all the way through adulthood. But for many people, lifestyle factors, some medications, and common gene mutations can deplete their folate stores.

Folic Acid

To help consumers maintain good nutritional folate status, many foods are being “fortified” with folic acid (FA). Also, dietary supplements that include folate typically provide it as FA.

But FA doesn’t occur in plants or in any of our foods and is so chemically different from natural folates that it gunks up our folate enzymes and impairs our natural folate utilization. The body must produce an enzyme to make FA usable, and this enzyme’s conversion capacity is limited. As a result, some people may have unconverted FA in their bloodstream, which may lead to negative health effects such as nausea, diarrhea, irritability, and behavior changes.


Methylfolate (technically methyltetrahydrofolate) is the pre-activated and most readily utilized form of the folate vitamin. The body has enzymes that rely on methylfolate (MF) specifically for its methyl groups, which are crucial for a broad range of brain and body functions.

Methylfolate is the folate form most naturally preferred by the body, which is why the intestinal lining has “transport proteins” that bind to it and selectively absorb it into the blood. Similar proteins also move MF from the circulation into the brain tissue.

The methyl chemical groups that come from folate are fundamental to practically all our life processes. It’s essential for all our cells, tissues, and organs to survive, grow, function, and maintain their structural integrity. MF also supports the entire array of functions in the bone marrow, liver, and all the other organs.

All our cells need methylfolate to make their DNA, package it into genes, repair it when damage occurs, and regulate their overall gene activity (epigenetics). The brain’s nerve cells also need it to make their electrical insulation (myelin) and to make dopamine and serotonin. MF also works with vitamin B6 and B12 in the detoxication of homocysteine.

Methylfolate promotes smooth and efficient folate metabolism for those who need it most: women of reproductive age, the elderly, the high proportion of individuals who carry folate enzyme mutations. For these individuals, and for the rest of us, methylfolate is the best dietary form of folate.

Methylfolate Benefits

Here are just a few methylfolate benefits:

  • Fundamental to the growth, renewal, and functioning of our cells, tissues, and organs.
  • Helps support a healthy mood, memory, cognition, and behavior.
  • Enhances the clinically proven mood benefits of SAMe (s-adenosyl-methionine).
  • Essential for the brain to make the key neurotransmitters serotonin, dopamine, and norepinephrine.
  • Promotes the brain’s healthy production of melatonin, our major sleep hormone.
  • Enhances the body’s regulation of homocysteine, a potentially toxic human metabolic product.
  • Promotes healthy pregnancy and birth outcomes.

While considering these impressive methylfolate benefits, it’s also important to be aware of the potential dangers of not taking methylfolate.

Folate Mutations

When consumed, methylfolate doesn’t need to be converted into active folate – as the body’s most active folate form, it can be immediately used by our folate enzyme systems. One of the most common human gene mutations is the C677T mutation in the enzyme MTHFR (Methylene Tetrahydrofolate Reductase), whose function is to produce MF.

More than 40 percent of individuals in some ethnic groups have this mutation, which is associated with impaired folate utilization from food. Taking MF by mouth bypasses this mutation: as premade, authentic MF, it doesn’t need to be produced by MTHFR. For people with C677T or various other, less common MTHFR mutations, methylfolate is a health breakthrough!

Methylfolate Benefits for Mood

Among its many positive actions in the brain and body, methylfolate can help support emotional balance. Methylfolate is a cofactor in the production of monoamines dopamine, norepinephrine, and serotonin.

In one study, patients struggling with low mood reported significant improvements in their symptoms when using methylfolate. The results of two randomized, double-blind, parallel-sequential trials found that MF may help those with medication-resistant mood issues. The trial concluded that MF may be an effective, safe, and well tolerated treatment for patients with major mood problems.

So, where can you get an ultra-pure source of this mood-, memory-, and cognitive-supporting vitamin?

Methylfolate for Mood | Benefits of Methylfolate | BrainMD

BrainMD’s MethylFolate

Methylfolate is a form of the folate vitamin that’s better utilized than folic acid or other folates. BrainMD’s MethylFolate is essential for mood, cognition, behavior, and overall brain and body health.

Methylfolate is the body’s most fully active form of folate, a vitamin that provides methyl groups (-CH3) which are crucial for a broad range of brain functions, including healthy mood. In clinical trials, MF corrected methyl deficiency while promoting a positive mood and overall brain health.

Highly Bioavailable Source of Methyl Groups

To be utilized by the body, dietary folates from foods or supplements must first be converted to methylfolate. But the enzymes involved in this conversion process often carry mutations that can interfere with their activity. High-quality MF supplements bypass these enzymes, directly supplying methyl to make SAMe and other methyl cofactors that manage the body’s extensive networks of methyl metabolism.

Promotes Metabolic Recycling of Homocysteine

Homocysteine (HCy) is a byproduct of SAMe production from MF and the amino acid methionine. If allowed to build up in the blood and other tissues, HCy can become toxic. MF facilitates the recycling of HCy to methionine, which helps curb its toxic potential.

Supports Brain Health and DNA

Methyl from MF is needed from the moment of fertilization of the human egg, through the development of the brain, heart and other organs, to birth, and across the lifespan. All our cells need methyl groups to make their DNA, repair ongoing DNA damage, and regulate their utilization of DNA.

Put the Methyl in Your Folate

Though folate is an effective vitamin, methylfolate is better utilized in the body than folate and synthetic folic acid.

Taking folate as MethylFolate can help provide nutritional support for your brain and body. This versatile supplement is also fundamental to the growth and renewal of our cells, helps regulate potentially harmful homocysteine, promotes healthy pregnancy, and much more.

You can enjoy all the methylfolate benefits in BrainMD’s MethylFolate supplement.

Try it today!

At BrainMD, we’re dedicated to providing the highest purity nutrients to improve your physical health and overall well-being. For more information about MethylFolate and our full list of brain healthy supplements, please visit us at BrainMD.

Keith Rowe