THF (Tetrahydrofolate)
THF (Tetrahydrofolate) is the central, foundational form of folate used throughout the body for DNA synthesis, amino acid metabolism, and the creation of key folate derivatives involved in methylation. When dietary folate is absorbed, it is first reduced to THF before being converted into other essential forms such as 5-MTHF, 5-Formyl-THF, and 10-Formyl-THF. Because of this, THF serves as the biochemical “hub” of the folate cycle.
In one-carbon metabolism, THF accepts and donates single-carbon units necessary for nucleotide production, detoxification, neurotransmitter balance, and red blood cell formation. Low THF can impair DNA synthesis, cell repair, methylation efficiency, and the body’s ability to recycle homocysteine. Levels can be influenced by diet, intestinal absorption, genetic variants affecting folate enzymes (such as MTHFR, MTHFD1, or DHFR), oxidative stress, chronic inflammation, or liver function.
Elevated THF may reflect increased folate intake, supplementation, or imbalances in the conversion of folate into downstream forms. Because THF interacts closely with other folate derivatives, interpreting this marker in the context of 5-MTHF, 10-Formyl-THF, 5-Formyl-THF, and Active Folate (RBC) provides the clearest view of folate-cycle health. Together with SAM, SAH, and homocysteine, THF helps build a comprehensive picture of methylation capacity and cellular metabolic efficiency.
What does it mean if your THF (Tetrahydrofolate) result is too high?
High THF may result from increased folate intake or supplementation, or from reduced conversion of THF into downstream folate derivatives. Elevated levels can also indicate metabolic bottlenecks elsewhere in the folate cycle. This marker is best interpreted alongside 5-MTHF, 5-Formyl-THF, 10-Formyl-THF, and methylation markers.
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What does it mean if your THF (Tetrahydrofolate) result is too low?
Low THF suggests inadequate availability of foundational folate needed for DNA synthesis, cell repair, and production of other folate derivatives. Common causes include low dietary folate, poor gastrointestinal absorption, chronic inflammation, oxidative stress, or genetic variations affecting folate activation. Low levels may contribute to fatigue, impaired tissue repair, reduced immune function, and elevated homocysteine.
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