Target intelligence / Profile preview

5-Methyltetrahydrofolate (5-MTHF)

Target
5-MTHF
Molecular classification
Other, Small molecule, Folate vitamer, Metabolite
01

Overview

5-Methyltetrahydrofolate (5-MTHF) is the primary biologically active, methylated form of folate (vitamin B9) found in blood and tissues. It is produced in the body by reduction and methylation of dietary folate or synthetic folic acid, via the enzyme methylenetetrahydrofolate reductase (MTHFR). 5-MTHF serves as the crucial methyl group donor in the remethylation of homocysteine to methionine, a step essential for cellular methylation reactions, DNA synthesis and repair, neurotransmitter production, and fetal development. Deficiency or impaired metabolism of 5-MTHF—particularly due to common polymorphisms in the MTHFR gene—can result in elevated homocysteine, with potential links to cardiovascular, neurodevelopmental, and neuropsychiatric disorders. Supplementation with L-methylfolate is sometimes used therapeutically, particularly in populations with known MTHFR mutations or absorption deficits.

Other names
MethylfolateMethyl-THFL-methylfolate5-methyl-THFN5-methylfolate5-methyltetrahydrofolic acidmethyl-H4FN5-CH3-THFPrefolic A
02

Mechanism of action

Provides methyl groups for conversion of homocysteine to methionine, supporting methylation cycles and DNA synthesis

03

Biological functions

One-carbon metabolismDNA methylationHomocysteine remethylationMethyl group donor for methylation reactionsNeurotransmitter synthesisCell growth and repairPrenatal neural development
04

Disease associations

Cardiovascular disease (due to homocysteine metabolism)Neural tube defects (as deficiency risk)Neuropsychiatric disorders (potential link via methylation deficits)Other (genetic disorders of folate metabolism)
05

Safety considerations

Generally well-tolerated, but excessive or inappropriate supplementation could mask vitamin B12 deficiency or lead to unmetabolized folic acid accumulation in people who cannot efficiently methylate folic acid (especially those with MTHFR mutation)
06

Interacting drugs

L-methylfolate (pharmaceutical/supplemental form)

1 more in the full profile.

07

Biomarkers

Plasma homocysteine (inversely related to 5-MTHF activity/levels)Blood 5-MTHF levels (for folate status assessment)

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