Methylation & Mood

Folic acid is converted to monoglutamate entites by the enzyme alpha-L-glutamyl transferase in the intestinal wall as they are absorbed. Once absorbed, monoglutamate entities are converted to methylenetetrahydrofolate (MTHF), the fat soluble form of folate that passes into the brain and is utilized by trimonoamine neurons to facilitate neurotransmitter synthesis or dopamine, epinephrine and norepinephrine. Normally, ingesting folate from dihydrofolate in the diet or from folic acid in synthetic supplements will result in adequate delivery of MTHF levels to the brain, especially in those individuals with the more efficient methylation genotype (C677C) producing up to 100% of the methylenetetrahydrofolate reductase and who do not have depression.

However, in patients with methylation deficiencies, the level of MTHF produced is limited, therefore limiting dopamine production. Thus, administration of folinic acid, has significant advantages over administration of folic acid as a trimonoamine modulator to depressed or anxious patients or depressed patients who do not respond adequately to their antidepressant treatment. These patients may not be folate deficient on standard blood work.