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5-Methyltetrahydrofolate (5-MTHF) is the most active form of folic acid


5-Methyltetrahydrofolate (5-MTHF) is the most active form of folic acid, the B group vitamin, also known generically as folate. Folate deficiencies have been linked with such health conditions as cancer, cardiovascular diseases and neurological abnormalities.

What Does 5-MTHF Do?

5-MTHF (together with vitamin B12) functions as a methyl group donor in a range of metabolic and nervous system processes, making it vital to numerous metabolic pathways in the body. 5-MTHF plays an essential role in methylation, it enables the conversion of homocysteine to methionine, the production of serotonin and melatonin, and it is indirectly involved in the synthesis of DNA.

There is a well researched link between low folate status and an increased risk of neural tube defects, miscarriages and premature births in pregnant women. This is why folate supplementation, in conjunction with increased consumption of folate rich foods, is now recommended before and during pregnancy.

5-MTHF is the strongest type of dietary folate. It is the only form naturally found in our circulation, and is therefore the type of folate normally transported into peripheral tissues to be used for cellular metabolism. Many people are not aware that folic acid is a synthetic form of the vitamin, which means it is only found in fortified foods, supplements and pharmaceuticals. It is the most oxidised form of folate and does not possess the coenzyme activity needed by the body. Because of this it must be reduced and methylated to become metabolically active in the body. Within the cell folic acid is reduced to the metabolically active “tetrahydrofolate” form.

What Studies Have Shown

Many studies have been conducted over the years comparing supplementation of 5-MTHF with that of folic acid and the two main advantages (of 5-MTHF) that have been found are...

  1. 5-MTHF reduces the potential for masking the haematological symptoms of vitamin B12 deficiency, and
  2. 5-MTHF may be associated with a reduced interaction between drugs that inhibit dihydrofolate reductase.

Overall conclusions which have been drawn are that “the two compounds have comparable physiological activity, bioavailability and absorption at equimolar doses...” and that “5-MTHF is at least as effective as folic acid in improving folate status, as measured by blood concentrations of folate and by functional indicators of folate status, such as plasma homocysteine.”

However, there is an exception to the above conclusions. Recent studies have uncovered that approximately half the European population appear to have a mutation in the methylenetetrahydrofolate reductase gene, which leads to inactivation, or impaired function of the methylenetetrahydrofolate reductase (MTHFR) enzyme.

The MTHFR enzyme is responsible for the formation of 5-MTHF. Therefore a mutation in this gene can result in moderately elevated levels of homocysteine in the blood, among other problems, and for women there is an increased risk of having a miscarriage or a baby with neural tube defects. Supplementation with 5-MTHF over folic acid in these situations gives you the opportunity to deliver the reduced (activated) folate that does not need to be converted by the reductase enzyme. Furthermore, it avoids the build up of free folic acid in the circulation.

5-MTHF is available at Kingsway Compounding. We can make it up in capsule form, with or without vitamin B12. For more details on these products or anything else I have discussed please feel free to give us a call on 1300 564 799.



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  3. Fenech M, Wang X. A comparison of folic acid and 5-methyltetrahydrofolate for prevention of DNA damage and cell death in human lymphocytes in vitro. Oxford J. 2002; 18(1): 81-86
  4. Bailey L, Piettzik K, Shane B. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharma. 2010; 49(8): 535-48.
  5. Ames BN, Crott JW, Fenech MF, Mashiyama ST. Methylenetetrahydrofolate reductase C677T polymorphism does not alter folic acid deficiency-induced uracil incorporation into primary human lymphocyte DNA in vitro. Carcinogenesis
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  7. Medical Genetics Summaries - Methylenetetrahydrofolate Reductase Deficiency (Laura Dean, MD). (Created: March 2012, visited: September 2013)


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