Folate vs folic acid

Folate is a generic term used to describe a large family of chemically similar compounds including methylfolate (5-MTHF), folic acid, folinic acid and vitamin B9. 5-MTHF is the active form of folate whereas folic acid is an inactive, synthetic form of folate that is metabolised to folate in the body.

5-MTHF is the biologically active form of folate in the body and accounts for approximately 98% of folates in human plasma. 5-MTHF is also the predominant form of dietary folate. After ingestion, both dietary folate and synthetic folic acid need to undergo a complex conversion in the liver to their active form. Folate from animal sources is present in a ‘free-form’ and is readily absorbed. Folate from plant sources is present in a ‘bound-form’ which requires liberation by zinc-dependent enzymes in the gastrointestinal tract prior to absorption.

Supplemental 5-MTHF is directly available and does not need to be metabolised. Quatrefolic®, a fourth-generation folate, comes in the form of a glucosamine salt that provides high solubility in water which facilitates absorption by mucosal cells for further circulation in the blood.

Folic acid
Folic acid is an inactive, synthetic form of folate that relies on the enzyme methylene-tetrahydrofolate reductase (MTHFR) to convert it to the active form of 5-MTHF. Several gene variations exist which can affect folate metabolism and significantly increase the risk of folate deficiency in affected individuals, even when meeting the recommended daily intakes.

The most common mutation is the MTHFR C677T mutation. Individuals who are heterozygote (one copy of the gene) for the MTHFR C677T mutation have a 40% reduction in activity of the MTHFR enzyme. Individuals who are homozygote (two copies of the gene) have about a 70% reduction in activity. Lower levels of MTHFR enzyme activity reduces the production of 5-MTHF and is the most common risk factor for elevated homocysteine.

High doses of folic acid may mask a vitamin B12 deficiency so 5-MTHF may be more beneficial as it does not mask a vitamin B12 deficiency and therefore a vitamin B12 deficiency is more likely to be detected earlier.

5-MTHF vs folic acid
Studies comparing 5-MTHF and folic acid supplementation have found the two compounds to be comparable in physiological activity, bioavailability and absorption at equal doses. However, there is some evidence that methylfolate may be more effective than folic acid in improving folate status and in people with MTHFR polymorphisms, methylfolate appears to be the supplement of choice as it does not require conversion. See Activated Folate 500.

Methionine, an amino acid from dietary protein, is converted to homocysteine in the body. Homocysteine is a toxic metabolite that the body neutralises as soon as possible by remethylating it back to methionine. This enzyme requires 5-MTHF as the methyl donor and vitamin B12 as a cofactor. 5-MTHF helps to reduce homocysteine.

Foetal development
Current recommendations state that women of childbearing age should ensure a daily intake of at least 400mcg of folic acid for at least four weeks before conception and during pregnancy. To-date, there are no studies on 5-MTHF for prevention of neural tube defects, however, general scientific opinion supports its use based on the fact that supplemental studies have found comparable effects for 5-MTHF and folic acid in improving folate biomarkers, including serum or red blood cell folate concentrations.

Benefits of folate

  • Supports blood health
  • Assists healthy red blood cell production
  • Supports brain health
  • Maintains cognitive and mental function
  • Supports memory
  • Supports emotional wellbeing
  • Helps reduce homocysteine
  • Supports cardiovascular system health 
  • Supports healthy foetal development
  • Helps prevent dietary folate deficiency
  • Supports general health and wellbeing

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