Folate (Vitamin B9) is a water-soluble nutrient required for numerous biological processes, which the body must obtain through diet. It is necessary for processes involving rapid cell division and growth, such as fetal development and the formation of red blood cells. While “folate” is a broad term for related compounds, only one form is directly usable by cells: 5-methyltetrahydrofolate (5-MTHF). This active form performs the vitamin’s essential functions throughout the body.
Defining the Active Form of Folate
5-MTHF is the biologically active form of Vitamin B9 that circulates in the blood and is transported into cells. Folate is acquired from natural food sources (like leafy greens) or synthetic folic acid (used in fortified foods and supplements). Natural folate must be processed in the digestive tract and liver to become 5-MTHF.
Synthetic folic acid requires a series of enzymatic steps, primarily in the liver, to be converted into usable 5-MTHF. Since 5-MTHF is already in its final, circulating form, it is highly bioavailable. The advantage of 5-MTHF is that it bypasses the entire metabolic conversion pathway required for precursor forms, making it immediately ready for use upon absorption.
The Central Role in Methylation
The primary function of 5-MTHF is its involvement in methylation, a fundamental biochemical process. Methylation is the transfer of a methyl group from one molecule to another, acting as an “on” or “off” switch for countless cellular activities, including gene expression and detoxification.
5-MTHF serves as the direct methyl donor for converting the amino acid homocysteine back into methionine. This reaction is a step in the one-carbon metabolism cycle. Methionine is then converted into S-adenosylmethionine (SAMe), which is the body’s universal methyl donor.
SAMe uses the methyl group supplied by 5-MTHF to regulate essential molecules. Methylation regulates DNA expression, determining which genes are active or dormant. It is also required for synthesizing important neurotransmitters, including serotonin, dopamine, and melatonin, which govern mood and cognitive function.
The conversion of homocysteine is a protective mechanism, as high levels are associated with increased health risks. By recycling homocysteine into methionine, 5-MTHF helps maintain healthy blood vessel function and cardiovascular health. The entire methylation cycle depends on a steady supply of active folate to operate smoothly.
The MTHFR Enzyme Connection
The importance of 5-MTHF is linked to the enzyme Methylenetetrahydrofolate Reductase (MTHFR). This enzyme is responsible for the final, irreversible step in converting inactive folate forms into active 5-MTHF. MTHFR acts as a bottleneck, processing all ingested folate into the usable compound.
The gene for the MTHFR enzyme has common variations, or polymorphisms, such as C677T and A1298C. A single change in the DNA sequence can alter the enzyme’s structure, impairing its ability to function effectively.
Depending on the variation inherited, the MTHFR enzyme’s efficiency in producing 5-MTHF can be significantly reduced, sometimes by 30 to 70 percent. This reduction slows the conversion of common folate sources, leading to less available 5-MTHF, inefficient methylation, and the accumulation of homocysteine.
This enzymatic inefficiency is why 5-MTHF is often a preferred supplemental option. Supplementing with active 5-MTHF bypasses the potentially compromised MTHFR enzyme step. This ensures the active folate is delivered directly into the circulation, overcoming genetic hurdles and supporting methylation pathways.
Dietary and Supplemental Sources
Vitamin B9 is obtained through natural foods and supplements. Natural food folate is abundant in dark leafy green vegetables (spinach, kale), legumes, asparagus, and liver. While these foods contain folate compounds that convert to 5-MTHF, cooking and processing can cause significant nutrient loss.
In supplementation, folate is available as synthetic folic acid or as the active L-Methylfolate (5-MTHF). For the general population with functional MTHFR enzymes, both sources contribute to folate status. However, for individuals with impaired MTHFR function, L-Methylfolate offers a direct and reliable way to ensure the body receives the active nutrient.
L-Methylfolate supplements provide the finished product, ready for immediate use without enzymatic conversion. This active form is stable and highly absorbable. For those with genetic variations or women during pregnancy, supplemental 5-MTHF is often favored to guarantee sufficient levels for rapid cell growth and neurological development.