Tetrahydrofolic acid (THF) is a molecule that plays an important role in human health. It serves as the active form of folate, also known as vitamin B9. This molecule is involved in various essential bodily processes.
What is Tetrahydrofolic Acid
Tetrahydrofolic acid is the biologically active form of vitamin B9, or folate. Folate is a water-soluble B vitamin.
Dietary folate, found naturally in foods, and synthetic folic acid must undergo conversion within the body to become THF. This conversion process is multi-step and involves specific enzymes. Folic acid is first reduced to dihydrofolate (DHF) and then to THF, a process that relies on the enzyme dihydrofolate reductase (DHFR).
Once THF is formed, it can be further converted into other active forms, such as 5,10-methylenetetrahydrofolate (5,10-CH2-THF) and 5-methyltetrahydrofolate (5-MTHF). These transformations are facilitated by various enzymes for diverse metabolic reactions. The ability of THF to carry different one-carbon groups makes it a versatile cofactor in these biochemical pathways.
Key Roles in the Body
Tetrahydrofolic acid is a central component in one-carbon metabolism, biochemical reactions involving single-carbon unit transfer. These one-carbon groups are attached to THF and then donated to various molecules. This process is important for several physiological functions, including detoxification, energy production, immune function, and the regulation of gene expression.
One of the most recognized functions of THF is its involvement in DNA synthesis and repair. Specifically, 5,10-methylenetetrahydrofolate, a derivative of THF, donates a methyl group to convert uracil into thymine, a nucleotide essential for DNA replication and repair. A sufficient supply of THF ensures the proper formation of DNA precursors, which is important for cell division and growth.
THF also plays an important role in amino acid metabolism, particularly in the conversion of homocysteine to methionine. 5-methyltetrahydrofolate, another active form of folate, provides a methyl group to homocysteine, transforming it into methionine in a reaction catalyzed by methionine synthase. This process helps regulate homocysteine levels, which is important for various bodily functions.
THF is also involved in the formation of healthy red blood cells. THF’s role in DNA synthesis supports the rapid division and maturation of these cells, which are responsible for transporting oxygen throughout the body.
Sources and Conversion
Folate is found in a variety of natural dietary sources. These include:
Leafy green vegetables like spinach, kale, and broccoli
Legumes such as beans, peas, and chickpeas
Citrus fruits
Eggs
Beef liver
Adults typically require around 200 micrograms of folate daily.
Both natural dietary folate and synthetic folic acid, found in fortified foods like cereals and breads, undergo a conversion process to become the active THF form in the body. Dietary folates are absorbed and then reduced to THF.
Synthetic folic acid needs to be converted through a multi-step enzymatic process, with dihydrofolate reductase (DHFR) being a key enzyme in the initial steps. A subsequent step involves the enzyme methylenetetrahydrofolate reductase (MTHFR), which converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a primary circulating form of folate. Variations in the MTHFR gene can affect the efficiency of this conversion, with about 40% of the global population having genetic variations that may reduce enzyme activity.
Consequences of Deficiency
Insufficient levels of tetrahydrofolic acid, or folate, can lead to several health problems. One of the most common consequences is megaloblastic anemia. This condition is characterized by the production of abnormally large, immature, and dysfunctional red blood cells, which are fewer in number. This occurs because impaired DNA synthesis, due to folate deficiency, prevents red blood cells from dividing properly, leading to their enlarged size and reduced ability to carry oxygen.
Symptoms associated with megaloblastic anemia and folate deficiency include:
Fatigue
Weakness
Shortness of breath
Pale skin
Changes in the tongue, such as redness or soreness
Gastrointestinal issues like diarrhea or loss of appetite
Neurological issues, such as tingling in the hands and feet, can also arise from prolonged deficiency.
The role of folate is particularly important during pregnancy to prevent neural tube defects (NTDs) in developing fetuses. These are birth defects of the brain and spine that occur early in pregnancy due to incomplete development. Adequate folate intake before and during early pregnancy can significantly reduce the risk of these defects.
Therapeutic Uses and Supplementation
In situations where the body’s ability to convert folic acid to its active forms is reduced, such as with certain genetic variations like those in the MTHFR gene, direct supplementation with active folate forms may be considered. L-methylfolate, also known as 5-MTHF, is a biologically active form of folate that the body can readily absorb and use without needing further conversion. This can be particularly beneficial for individuals with MTHFR enzyme variations, as it bypasses the conversion step that might be impaired.
L-methylfolate is used therapeutically to address folate deficiencies that may contribute to conditions like megaloblastic anemia, and it may also be used for other conditions, especially when associated with folate deficiency or elevated homocysteine. While folic acid is widely recommended, especially for pregnancy, L-methylfolate is gaining recognition as an alternative due to its immediate bioavailability and its potential to avoid the accumulation of unmetabolized folic acid in the bloodstream. However, it is always advisable to consult with a healthcare professional to determine the most appropriate form and dosage of folate supplementation for individual needs.