L-methylfolate for Depression? “Never heard of it!”

When was the last time you had the audacity to tell your primary care physician or psychiatrist what you wanted to try? L-methylfolate for depression might make your list.

L-methylfolate (MTHF), a medical food, is being used for the treatment of depression. It’s especially effective as an antidepressant add-on in the early stages of treatment.

Let’s dig in.

Updates!!! When you’re finished reading the article, be sure to click here for an important update. Actually, by now (June 8, 2011), there are several informative updates in the comment section – especially if you’re a European reader. Click the link!

What the Heck is L-methylfolate?

Folic acid is a form of Vitamin B9. Naturally occurring, it’s known as folate. Folic acid itself is not biologically active. It’s the products of its conversion to dihydrofolic acid that are crucial to our functioning.

Interestingly, folic comes from the Latin, folium, meaning leaf. It makes sense, then, that leafy vegetables are a primary source, along with fortified cereals and breads.

L-methylfolate (actually, L-methylfolate2) is a form of folate. And it’s the only form that crosses the blood-brain barrier.

By the way, the blood-brain barrier is a need-to-know kind of thing. I wrote an article not long ago on melatonin, which included a nice explanation of the blood-brain barrier. Click here for a look-see.

In the USofA, MTHF (aka Deplin) is marketed under the FDA classification, medical food. It’s available by prescription only, and it’s thought to be safe with very few side effects, if any.

And it’s sure a lot less expensive that the add-on meds Big Pharma would like you to use.

And This is Important Because?

Some of us come into this world with a genetic boo-boo that leaves us at high-risk for a folate deficiency. A folate deficiency may increase the risk of depression, as well as reduce the action of antidepressants. And that’s because folate provides regulatory assistance to the neurotransmitters associated with depression.

Guess what? Approximately 70% of those enduring major depressive disorder have a genetic error that results in an imbalance of L-methylfolate2.

So Why Don’t I Pop Folic Acid Tabs?

Folate is an essential vitamin, which means we need it, but can’t produce it naturally. Folic acid is the synthetic form of folate found in vitamin supplements. It’s also the synthetic form found in prescriptions for higher doses for medical use. Under normal circumstances, folic acid has problems delivering adequate MTHF levels to the brain.

Using MTHF solves that problem.

Confirmed by Research

The results of a study, authored by Dr. Lawrence D. Ginsberg of Red Oak Psychiatry in Houston, were published last month in Innovations in Clinical Neuroscience.

The study confirmed that L-methylfolate (Deplin) is a powerful supplement. When used in combination with antidepressants in the early treatment of depression, major and more rapid improvement was noted – versus using an antidepressant alone.

And it was especially helpful with treatment resistant cases.

Ever see those Abilify and Seroquel TV ads? They’re atypical antipsychotics being touted as antidepressant add-ons for use in treatment resistant depression. Hopefully, Dr. Ginsberg’s findings will kick a dent in that effort.


I wanted to accomplish two things in this piece. Certainly, I wanted to make you aware of L-methylfolate. But I also want to encourage you to take such subjects to your primary care physician and/or psychiatrist for discussion. It’s an integral part of managing our health care.

I mean, we’re all likely comfortable that our physician and/or psychiatrist knows about, say, desvenlafaxine (Pristiq) for the treatment of depression. But would any of us bet he/she would know about L-methylfolate? Hard to say.

So there they are – L-methylfolate and taking command of our health care. Nice.

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