Folates: what is important to know?

Folates (vitamin B9) are essential nutrients for metabolic processes in the body that are involved in the division of all types of cells. This vitamin is necessary for the health of the reproductive system, heart and blood vessels, thyroid gland, and blood system. Folates are the natural form of B9, while the well-known folic acid is an artificially synthesized substance that is much less easily absorbed. Vitamin B9 deficiency occurs in 90% of the population and is especially dangerous for women who are planning to become pregnant or are carrying a child.

Folate metabolism and genetic mutations

Folates are not produced in the body. They come from outside sources, such as food or vitamin supplements. They are found in the highest quantities in green vegetables, leafy greens, legumes, and citrus fruits. Such foods make up a small proportion of most people's diets, so B9 hypovitaminosis is a natural occurrence.

Several risk factors for folate deficiency have been identified:

• impaired food absorption in chronic gastrointestinal diseases;
• diabetes mellitus;
• hypothyroidism;
• smoking and alcohol abuse;
• use of hormonal contraceptives, cytostatics, anticonvulsants, sulfonamides.

For a complete folate metabolism cycle, it is important not only to have sufficient folate in blood, but also to have a number of enzymes working properly. One form of folate, 5-methyltetrahydrofolate (5-MTHF) monoglutamate, is absorbed into the bloodstream and participates in metabolic processes. Other forms of vitamin B9 are converted by enzymes into 5-MTHF and are also involved in metabolism.
Problems often arise at this stage of metabolism, as more than 60% of the population has defects in the main enzyme of the folate cycle, methylenetetrahydrofolate reductase (MTHFR). It is this substance that converts inactive forms of the vitamin into 5-MTHF.

There are two main types of mutations in the gene that encodes the MTHFR enzyme:

• the heterozygous form, which occurs in 40-60% of the population and causes a moderate decrease in folate conversion reactions;
• homozygous form - found in 15-20% of people, causes a sharp suppression of the folate cycle and severe hypovitaminosis.

MTHFR mutations reduce enzyme activity by 30-70% and are a key risk factor for hypovitaminosis of vitamin B9.

Folic acid - what are its disadvantages?

The role of synthetic folic acid is discussed separately, as its structure differs from natural folates. When this substance enters the body, part of it undergoes a complex series of transformations and is converted into active 5-MTHF. However, when consumed in doses exceeding 200 mcg/day, it enters the bloodstream unchanged and negatively affects the folate cycle.

An excessive intake of folic acid reduces the activity of other forms of folate and leads to a relative vitamin deficiency (‘folic acid paradox’) [2,3].
Another problem with synthetic folic acid is related to its side effects on pregnant women and their unborn children. New research shows that irrational use of synthetic supplements increases the risk of cancer, obesity, glucose metabolism disorders, and mental retardation in children [4]. Therefore, natural forms of folate are recommended to compensate for vitamin deficiency.

Multizan Folate is the best source of folates

Multizan Folate tablets contain L-methylfolate (5-MTGF) - an active and bioavailable form of folate. This dietary supplement is suitable for people with any type of genetic mutation of the MTHFR enzyme, as Multizan Folate is absorbed unchanged in the gastrointestinal tract and does not require complex biochemical transformations. 

One Multizan Folate tablet contains 400 mg of methylfolate. This dosage covers 100% of the daily requirement of vitamin B9 and is considered ideal for pregnant women and women planning to conceive. Convenient once-daily intake with food, no side effects and guaranteed effectiveness make Multizan Folate the ideal drug for correcting vitamin B9 deficiency.

The benefits of folate supplements

Folate plays a key role in male and female reproductive health. Vitamin B9 promotes proper development of all organs in the embryo and foetus, reduces the risk of neural tube defects by 70-92% and reduces the likelihood of heart defects by 26-40% [7]. Folates are essential for healthy pregnancy, proper placental function and maintaining  health of expectant mother. Across men, vitamin B9 improves spermatogenesis and ejaculate quality, and reduces the number of spermatozoas with genetic mutations.

In addition to role in reproductive health, folates have the following positive effects:

• regulation of serotonin and dopamine metabolism, improving mood state and supporting psycho-emotional well-being;
• reduce the likelihood of intellectual disorders and Alzheimer's disease;
• participate in formation of red blood cells, increase the haemoglobin content in blood and prevent the development of macrocytic anaemia;
• promote muscle tissue regeneration;
• participate in DNA replication processes during cell division;
• reduce the risk of malignant tumours in digestive system, mammary glands, female reproductive organs and prostate gland.

Folates and hypercystinemia

The most important role of folates is participation in the biochemical conversion of homocysteine to methionine. With sufficient intake of vitamin B9, the concentration of homocysteine in blood does not exceed 10 μmol/L. When the level of this substance increases, it damages inner lining of blood vessels, increases thrombus formation and formation of lipid plaques. Elevated homocysteine levels are associated with the risk of the following pathologies:

• stroke;
• myocardial infarction;
• ischaemic heart disease;
• venous thromboembolism.

Regular intake of folates at a dose of more than 200 mcg/day reduces the amount of homocysteine in blood and reduces mortality from cardiovascular diseases [8].

List of sources:

1. Pustotina, O. A. ‘Achievements and risks of folate use outside and during pregnancy.’ Medical Council 9 (2015).
2. Muggli E.E., Halliday J.L. Folic acid and risk of twinning: a systematic review of the recent literature, July 1994 to July 2006. Med. J. Aust. 2007; 186(5): 243–8.
3. Pietrzik K., Bailey L., Shane B. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin. Pharmacok. 2010; 49(8): 535–48. DOI: 10.2165/11532990-000000000-00000
4. Cantarella C.D., Ragusa D., Giammanco M. et al. Folate deficiency as a predisposing factor for childhood leukaemia: a review of the literature. Genes Nutr. 2017; 12: 14. DOI: 10.1186/s12263-017-0560-8
5. Clinical protocol of the Russian Society of Obstetricians and Gynaecologists for normal pregnancy for 2019.
6. Order of the Ministry of Health of the Russian Federation No. 572n dated 01.11.2012.
7. Gromova O.A., Serov V.N., Torshin I.Yu. et al. The role of vitamin and mineral complexes with folic acid in the prevention of congenital heart defects and neural tube defects. Effective pharmacotherapy. Obstetrics and gynaecology. 2015; 4(36): 4–15.
8. Djuric D, Jakovljevic V, Rasic-Markovic A, Djuric A, Stanojlovic O. Homocysteine, folic acid and coronary artery disease: possible impact on prognosis and therapy. Indian J Chest Dis Allied Sci. 2008 Jan-Mar;50(1):39-48. PMID: 18610689.