Bioactive Folate in the Treatment of Depression

Published on December 30, 2014 by Dr. Colin O'Brien

Depression is a mood disorder that approximately 1 in 8 Canadians will experience at some point during their lifetime. Symptoms vary but often include feelings of sadness, sleep difficulties, fatigue, lack of motivation, loss of interest and withdrawal from friends and family. As you can imagine, depression can have quite a negative impact on an individual’s quality of life.
Unfortunately, there are not great solutions for treating depression. Selective serotonin reuptake inhibitors (SSRI’s) are a class of pharmaceutical drugs that have been used for decades to manage depression, although often with unsatisfactory results and a wide spectrum of side effects. In fact, much research has shown that patients taking an SSRI for mild or moderate depression do not find significant improvement. Moreover, a recent study found that mice with a complete inability to synthesize serotonin did not exhibit depressive behaviors as expected, questioning the idea that serotonin is the sole neurotransmitter affected in this mood disorder.

Perhaps it makes more sense to provide nutrients and co-factors that the body uses in multiple physiological pathways, thereby affecting numerous neurotransmitters instead of artificially elevating only one? One of these key nutrients for treating depression is folic acid; more specifically, the bioactive form that can enter the central nervous system called 5-methyltetrahydrofolate (5-MTHF).

Low levels of 5-MTHF in the bloodstream have long been found in populations of depressed individuals. This led researchers to test the hypothesis that low levels of 5-MTHF may contribute to the incidence of depression. Studies since have confirmed that 5-MTHF is a viable and extremely safe treatment option for depression as a stand-alone therapy, and also in combination with SSRI drugs. In fact, for individuals that respond poorly to SSRI’s, 5-MTHF is particularly indicated and has been shown to increase the drug’s effectiveness.

Why 5-MTHF instead of regular folic acid?
Research has found that a certain percentage of the population has a suboptimal ability to convert regular folic acid into 5-MTHF because of a genetic variation. In fact, up to 20% of Caucasians have two copies of this gene while 40%-50% of the same population has one copy. With two copies, the body’s ability to convert folate to 5-MTHF is reduced by 60% (!) and studies have shown that people with two copies of the variant are more likely to suffer from depression. The latter group containing only one copy of the gene has their conversion ability reduced by 35%. The high prevalence of these genetic modifications suggests that 5-MTHF is the necessary form for supplementation in all individuals. Quite simply, by giving folic acid instead of 5-MTHF, there is a significant risk that the body cannot convert or activate the vitamin at an efficient rate to keep up with the body’s demand.

The take home message here is that if you or someone you know suffer from depression, folic acid in the form of 5-MTHF should be considered as a safe and effective option. Speak with your health care practitioner about 5-MTHF, its dosage, and other nutrients that may be helpful for treating mood disorders.

Images by © 2014 Iain Campbell and 2012 themalni via DollarPhotoClub


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Public Health Agency of Canada. Accessed on Dec. 14th, 2014 at