Does Methylfolate Make You Depressed?

Does Methylfolate Make You Depressed?

A common question surrounding methylfolate is whether it will make you depressed or not. The short answer is no, methylfolate won’t make you depressed. In fact, some studies and research have shown methylfolate to have positive effects on people with depression symptoms.   

A majority of these studies focus on people suffering from treatment-resistant depression (TRD), which is a fancy word for those who see no improvement with antidepressants. While this can make the treatment process much more difficult, methylfolate has shown the ability to spur the production of mood-related neurotransmitters like serotonin, dopamine, and norepinephrine.

Furthermore, methylfolate can cross the blood-brain barrier, unlike folate or folic acid. This makes it that much more effective when regulating your mood, among other functions inside the body. 

Depression and Folate Deficiency

The use of methylfolate for depression is a rather new concept. For a while, many people believed supplementation of folate or folic acid could help alleviate depression symptoms -- especially since depression is often linked to a folate deficiency. 

In some people, the problem isn’t that they aren’t getting enough folate. The problem is that their body is struggling to convert that folate or folic acid into methylfolate. Since our bodies can’t utilize folate or folic acid until this conversion happens, the lack of methylfolate will start to cause negative side effects. 

This conversion is due to a process called methylation, which occurs when the MTHFR gene interacts with folate. Studies report that nearly half of the population will suffer from one or two mutations of the MTHFR gene, which is the root cause of the conversion struggle. 

Are There Side Effects to Methylfolate?

While methylfolate isn’t known to cause depression, there have been cases where the body reacts negatively to the methylfolate. Methylfolate may cause a wide range of side effects to occur, some more serious than others. 

Let’s take a look at some of the most common side effects with methylfolate supplementation:

  1. Flu-like symptoms
    a) Fatigue
    b) Body aches
    c) Headaches
    d) Reactions from detoxification (i.e. rashes, blisters, red skin) 

  2. Feeling like you’ve had too much caffeine (heart palpitations, amped up)
  3. Upset stomach
  4. Burning & Tingling Sensations

Taking too much methylfolate could also cause acne or allergic reactions (i.e. difficulty breathing or swallowing - if this happens, seek emergent care as soon as possible). 

Do You Need Methylfolate?

Methylfolate is still new to most people, but the alarming amount of people suffering from MTHFR mutations is sure to continue spiking interest in this supplement. Your doctor may suggest getting tested for it, but it’s something you can ask for if you’re interested or curious. 

If a mutation is found, there’s a good chance your body isn’t receiving enough methylfolate -- meaning the folate or folic acid you consume on a daily basis is going to waste. Adding a methylfolate supplement to your diet can help your body get what it needs without needing the MTHFR gene. 

If your doctor has recommended you give methylfolate a try, Methyl-Life’s version, the purest on the planet, we have several different supplements you can try. Whether you’re looking for methylfolate with added nutrients or methylfolate by itself, check out our shop to see what we have to offer! Don’t hesitate to contact us with any questions, comments, or concerns.


LeBano, Lauren. “L-Methylfolate: A Promising Therapy for Treatment-Resistant Depression?” Psychiatry & Behavioral Health Learning Network, 8 May 2013,



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