Karolina Banyś, Monika Knopczyk, Barbara Bobrowska-Korczak

Znaczenie kwasu foliowego dla zdrowia organizmu człowieka
2020-03-15

Kwas foliowy jest niezbędny do właściwego funkcjonowania organizmu i zachowania homeostazy. Uczestniczy w metabolizmie kwasów nukleinowych, aminokwasów, syntezie pirymidyn i puryn. Syntetyczna postać kwasu foliowego nie wykazuje aktywności biologicznej. Przekształcana jest w szeregu reakcji do postaci folianów (L-5-MTHF), które transportowane są do komórek, gdzie bierze udział w ważnych procesach biologicznych. Gen MTHFR odpowiedzialny jest za katalizę reakcji enzymatycznej – redukcję 5,10-metylenotetrahydrofolianu do aktywnej formy. Mutacja genu MTHFR 677C>T występuje nawet u 53% populacji, czego konsekwencją jest zmniejszenie aktywności reduktazy – MTHFR nawet o 70%. Metafolina (aktywna forma) w przeciwieństwie do kwasu foliowego, aby zostać włączona do procesów metabolicznych w komórce, nie ulega redukcji, katalizowanej przez DHFR oraz MTHFR. Jest to istotne w szczególności dla osób, które mają mutację genu MTHFR oraz DHFR. Przyjmowanie niektórych leków osłabia wchłanialność kwasu foliowego. Kwas foliowy jest niezbędny do prawidłowego funkcjonowania organizmu człowieka, a jego niedobór może indukować różne procesy chorobowe w organizmie, do których zaliczamy powstawanie wad cewy nerwowej, zaburzenia w układzie nerwowym, niedokrwistość megaloblastyczną, negatywny wpływ na funkcjonowanie układu sercowo-naczyniowego oraz rozwój miażdżycy i nowotworów. Witamina ta bierze udział w powstawaniu ważnych neuroprzekaźników, takich jak: adrenalina, dopamina i noradrenalina, dlatego jej niedobór może prowadzić do powstania zaburzeń neuropsychiatrycznych. Niedobór kwasu foliowego sprzyja aktywacji protoonkogenów do onkogenów. Badania kliniczne i dostępna literatura potwierdzają funkcję kwasu foliowego jako niezbędnego związku o wielokierunkowym działaniu biologicznym, pełniacego istotną rolę w tkankach. Suplementacja metafoliną omija wieloetapowy proces metaboliczny, w przeciwieństwie do nieaktywnej postaci kwasu foliowego.

Słowa kluczowe: kwas foliowy, MTHFR, niedobór, mutacja, aktywny kwas foliowy

© Farm Pol, 2020, 76 (2): 79–87

The importance of folic acid for the health of the human body

A well-balanced diet is undoubtedly a key factor to maintain your body’s normal state of health. Folic acid is one of the elements of the diet, which is often supplied in insufficient quantities. This vitamin and its derivatives participate in the metabolism of amino acids and nucleic acids. Therefore, it is necessary for the proper functioning of the body’s cells and for maintaining homeostasis, especially of the nervous, circulatory and cardiovascular systems. The biological activity of folic acid and its derivatives essentially affects the metabolism of important amino acids, such as methionine, homocysteine, serine, glycine, pyrimidine and purine synthesis and DNA methylation.

The synthetic form of folic acid (most oxidized), which can be found in fortified foods, dietary supplements or pharmaceuticals, does not show biological activity. It is transformed in a series of reactions with the participation of many enzymes to form folates, which differ in the number of glutamic acid residues and the degree of oxidation. The actively biological form is reduced folate (L-5-MTHF), which is transported together with the blood to cells where it undergoes biological processes important for our health.

The MTHFR gene, coding for the enzyme protein of the same name – methylene tetrahydrofolate reductase, is located on chromosome 1 at the 1p36.3 locus. This protein is responsible for the catalysis of the enzymatic reaction, which is the reduction of 5,10-methylenetetrahydrofolate to L-5-methyltetrahydrofolate, i.e. the active form of folate. This form is necessary in the process of homocysteine degradation, in the aftermath remethylation to methionine. This form is necessary in the process of homocysteine degradation, in the aftermath remethylation to methionine. However, according to available literature, mutation of the MTHFR 677C> T gene occurs in even 53% of the population. Among carriers of the TT genotype, it can cause about 70% reduction of MTHFR reductase activity. It is especially dangerous for people who do not provide adequate amounts of folic acid along with their diet and for those who need a high amount of this vitamin, e.g. due to taking medications that reduce its absorption. Many people metabolize folic acid on insufficient levels. For medical reasons, not the mutation itself is a problem, but too low the folate levels. In recent years, there is more and more discussion about the active form of folic acid and the possibility of effective supplementation with metapholine, which is a combination of calcium with L-5-MTHFR. It is a natural and reduced form of folate, which hydrolized and then transforms into L-5-MTHFR. Metapholine, in comparison to folic acid, is not reduced to be incorporated into metabolic processes in the cell, which is catalyzed by DHFR and MTHFR enzymes. Looking at the numerous clinical studies, available literature and the function of folic acid, it can be stated that it is an essential compound with multidirectional biological action, which is involved in the synthesis of amino acids and nucleic acids important for health. It plays an important role in tissues, such as: the fetus, hematopoietic system and gastrointestinal epithelium, in which cell divisions occur. For this reason, the presence of folic acid in the right amounts, ensures the proper functioning of our body. A deficiency of folic acid in the diet leads to a reduced concentration of folate in plasma and red blood cells. It is a condition that contributes to the formation of many serious diseases in our body and congenital neural tube defects in the fetus. As clinical studies have shown, the optimal concentration of folates in the blood reduces the risk of cardiovascular, circulatory, central nervous system diseases and certain types of cancer.

To reduce the risk of diet-related diseases caused by folic acid deficiency, daily diet should be optimally balanced and contain products rich in natural folates. If diet is an insufficient source of folic acid, its supplementation should be considered, with the possible inclusion of its active form. Supplementation is recommended, in particular, for people with: megaloblastic anemia, diabetes mellitus, malabsorptions (e.g. Crohn’s disease), alcoholism, malnutrition, neurodegenerative diseases (e.g. Alzheimer’s disease), cardiovascular diseases, elevated homocysteine levels and using certain medications (e.g. oral contraceptives, metformin, methotrexate). It is also worth mentioning that metapholine supplementation bypasses the multistage metabolic process before incorporating folates into the cell cycle, as opposed to the inactive form of folic acid. This is particularly important for patients with the DHFR and MTHFR mutation, which depending on the polymorphism, may occur in up to 53% of the Caucasian population. Consequently, MTHFR reductase activity is reduced by up to 70%.

Keywords: folic acid, MTHFR, mutation, deficiency, active folic acid.

© Farm Pol, 2020, 76 (2): 79–87