Levomefolate calcium is the calcium salt of L-5-methyltetrahydrofolate (L-5-MTHF), the biologically active, reduced form of folate that directly participates in one-carbon metabolism. Unlike synthetic folic acid, L-5-MTHF does not require enzymatic reduction by dihydrofolate reductase and represents the primary form of folate circulating in human plasma.

In human physiology, L-5-methyltetrahydrofolate functions as a cofactor for methionine synthase, supporting the remethylation of homocysteine to methionine and contributing to downstream methylation capacity. Alterations in folate metabolism have been associated with genetic polymorphisms such as MTHFR variants, making levomefolate calcium a useful reference compound in metabolic and genetic research contexts.

Use in depression research

In neuropsychiatric research, levomefolate calcium has been investigated as an adjunctive compound in studies of depressive disorders, particularly in contexts involving impaired folate metabolism, elevated homocysteine, or reduced monoamine synthesis. Folate availability influences the biosynthesis of neurotransmitters such as serotonin, dopamine, and norepinephrine through its role in tetrahydrobiopterin regeneration and methylation pathways. Research interest in levomefolate calcium stems from its ability to directly supply the active folate form without reliance on upstream metabolic conversion.

The currently marketed formulations include (but is not limited to):

• Deplin (L-methylfolate Ca): 7.5 mg, 15 mg, 30 mg
• and more