In relation to depression few people assume that it might be linked to the lack of a micronutrient, however, with folate that’s exactly the case. Of vitamin B9’s countless biological functions we can only suspect which one is responsible for the development of depression but research unequivocally verifies that vitamin B9 deficiency proves to be a significant factor. 

In a 2007 meta-analysis it was established based on the analysis of the data of 11 studies and 15315 persons that in the case of insufficient folate supplies the risk of depression becomes 42% higher. (1) Those who have the MTHFR-gene mutations – it decreases the transformation of folates into methylfolate – also experience depression 36% more often than people without this gene mutation, probably owing to lowered folate levels. (2) 

How does this happen? 

One important task of vitamin B9 is to transform homocysteine back into methionine. A by-product of this metabolic process is a molecule called SAMe which is important because it acts as an antidepressant. The low level of SAMe most likely presents the main problem in connection with depression because it’s not only linked to MTHFR mutations but it’s an effective antidepression therapy on its own. (3) This means that low folate intake and MTHFR mutations can lower the SAMe level which might lead to low serotonine levels and depression symptoms. (4) Luckily we have several possibilities to prevent that. 

Unfortunately supplementing micronutrients is rarely considered in the treatment of psychiatric illnesses, however, folate has been tested as complementary therapy to alleviate the symptoms of depression. Folic acid supplementation led to mixed results but the methylfolate form proved more promising and resulted in significant improvement complementing traditional treatment in a study. (5) 

Folate can provide effective treatment 

The results of three clinical trials were analysed in a 2003 review study. In two of the trials participants were given 15 mg methylfolate while 500 mcg folic acid in the third. In all three trials folate supplementation brought positive results, but supplementing methylfolate led to better results. Meta-analysis established that folate supplementation alleviated symptoms of depression and might be a promising treatment for the illness. (6) It’s important to note, however, that the participants for the trials were chosen expressly because of their folate deficiency. It’s probably the most important aspect since if somebody already obtains enough folate – as we’ll soon see – it’s ineffective to supplement more. 

In a 2014 randomized controlled trial participants got 5 mg folic acid daily along with their antidepressant medication. (7) In this study, by contrast, only participants with no folate deficiency were chosen. Perhaps the outcome will not come as a shock: folic acid supplementation didn’t lead to significant results. 

In a study published in 2012 two consecutive clinical trials tested methylfolate’s antidepressant effect. It was used to complement traditional therapy for people who didn’t respond to antidepressant medication. In the first trial methylfolate supplementation wasn’t more effective than traditional therapy. In the second, however, it was; the decrease in depression symptoms was double in the case of participants taking methylfolate as opposed to those following only the traditional antidepressant therapy. (8) 

What to look out for based on this 

In order to have ample folate supplies you should eat vitamin B9-rich foods although folate absorption from food is not always effective. In a study where the effects of supplementing equal amounts of dietary folate, folic acid and methylfolate the amount of dietary folate absorbed was only a third of how much folic acid or methylfolate supplements were absorbed. (9) There is also MTHFR-mutation for many which hinders folate’s transformation into methylfolate. To eliminate this you sholud pay particular attention to vitamin B2 and B12 intake because MTHFR-mutations only cause a problem if you have a deficiency of these vitamins. (10) 

It’s also worth paying attention to the intake of choline, betaine and other methyl group-providing nutrients since similarly to folate they decrease homocysteine levels and they support the same biological processes as folate. Adequate proteine intake is also important because it supplies methionine amino acid. However, be careful not to take too much of the latter because that’s not beneficial. So it’s worth giving a try to methylfolate or SAMe supplementation for those who experience similar symptoms after consulting their doctor.