L-5-methylfolate and Depression

The role of L-5-methylfolate in the treatment of patients with depression has once again been highlighted by an article published in the American Journal of Psychiatry in 2016.

After successfully treating treatment resistant depression in a patient deficient in cerebrospinal fluid (CSF) tetrahydrobiopterin with sapropterin, investigators searched for this and other potential metabolic abnormalities in 33 patients with treatment resistant depression.
Depression and L-5-methylfolate
The study found that a very high proportion of teenagers and young adults with well documented treatment resistant depression had some kind of CSF metabolite abnormality and by far the most common abnormality was normal serum folate and a low L-5-methylfolate level, suggesting a functional deficit in the active form of folate that is involved in the production of the monoamine neurotransmitters that seem to be closely tied to depression.

The researchers then treated these patients in an open label fashion and found some evidence that reversing this apparent deficiency improved depression.


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