Effect of synthetic and reduced folic acid on methionine metabolism parameters in various experimental models with Wistar rats

Abstract

Introduction. Currently, folic acid preparations are administered during preconception period in an empirical manner. Along with synthetic folic acid, there also exists its reduced counterpart 5-methyltetrahydrofolate (5-MTHF). Manufacturers of the latter claim that 5-MTHF overcomes metabolic defects due to c.665C>T gene polymorphism in the methylenetetrahydrofolate reductase (MTHFR), and therefore it is superior to synthetic folic acid (pteroylmonoglutamic acid, PGA). However, no large-scale studies to confirm this hypothesis have been conducted yet.Aim: to assess an effect of various folic acid preparations on methionine metabolism in experimental models with Wistar rats.Materials and Methods. A chronic hyperhomocysteinemia (HHC) was induced in sexually mature female Wistar rats by daily methionine supplementation. After HHC development, experimental animals were administered PGA or 5-MTHF. Some animals without HHC also received folic acid supplements or water. Blood samples were collected at 3 time points (1, 2 weeks and 1.5 months after folate preparation administration) to quantitate level of homocysteine (HC), plasma folic acid and red blood cell count.Results. It was verified that HHC developed in mature Wistar rats after methionine supplementation, with HC level being significantly higher (p < 0.05) than in control group. Use of folic acid supplements during HHC caused by methionine load did not result in lower HC level. In experimental animals administered PGA or 5-MTHF, blood serum folic acid level and red blood cell count did not change upon longer drug administration. No advantage for 5-MTHF vs. synthetic folic acid on HC levels and erythrocyte folate accumulation was observed. Instead of the expected decline in HC level in HHC models related to the examined folate preparations, the opposite effect was obtained. In case of pre-existing non-folate-dependent chronic HHC, HC level increased from time point 1 to time point 3.Conclusion. Chronic non-folate-dependent HHC, induced by chronic oral methionine was self-limiting in experimental models; additional folate supplementation resulted in sharply increased plasma HC level. Experimental models with Wistar rats showed that no further accumulation of folic acid occurs upon its optimal levels in plasma and red blood cells. The study revealed no advantages for 5-MTHF over synthetic folic acid in lowering blood plasma HC level and folic acid accumulation in erythrocytes.