The pharmacokinetic advantage of 5-methyltetrahydrofolate for minimization of the risk for birth defects

Abstract

Despite efforts to increase folic acid (FA) intake, even within countries mandating FA fortification, there remain pregnant women with folate levels inadequate to minimize congenital disorders (e.g., of the neural tube, heart, and lip/palate). The pharmacokinetics of FA and [6S]-5-methyltetrahydrofolate (5-MTHF) were examined to find a reliable and minimal dose for rapidly rescuing folate status prior to critical periods of embryonic development. Serum total folate increased much more rapidly over the first four days in insufficient women given 7.5 mg doses of 5-MTHF than the same regimen of FA (P for trend <0.0001). Nearly all women given 7.5 mg 5-MTHF (every 12 hours, five doses total) almost immediately reached 50 nM serum total folate. Moreover, this level could be maintained by subsequent administration of 0.4 mg/d of folic acid. Thus, 5-MTHF enables repletion of folate stores more quickly and uniformly than FA and without exposure to unmetabolized FA.

Micronutrients in support to the one carbon cycle for the modulation of blood fasting homocysteine in PCOS women

“…A total of 33 PCOS ladies (mean age 26.8, range [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] were enrolled between June 2017 and October 2018, and one patient withdrew her participation for personal reasons after the basal visit. Out of 32 patients randomized, 22 entered the active treatment group, and 10 the no treatment group.…”

“…Our treatment included instead a standard dose of the physiologic, natural form of activated folate, i.e., 5-methyl-tetrahydrofolate. This does not need activation by DHFR and MTHFR and has been shown to be better effective than folic acid in the repletion of folate stores independently of the genetic background [23]. In addition, plain folic acid treatment supports only one of the three pathways for Hcy detoxification and may not work properly anytime the other pathways are concerned.…”

Periconceptional folic acid (FA) supplementation among pregnant women in Bosnia and Herzegovina: A cross-sectional study

“…One possible solution to this scenario was already suggested by Amitai and Koren, who recommended 5000 g/day of FA for two months, from pregnancy recognition (typically week 5 of pregnancy) throughout the first trimester (13). Another regime was proposed by Bailey and Ayling: short term (five doses, every 12 hours) supplementation with 7500 g of the bioactive form of folate, 5-methyltetrahydrofolate (5-MTHF) and subsequent supplementation with 800 g/day of 5-MTHF (28). This dosing regimen was shown to reach the target serum folate level almost immediately in nearly all tested women and to maintain it adequate throughout the study period of 19 days.…”

[6S]-5-Methyltetrahydrofolic Acid and Folic Acid Pregnancy Diets Differentially Program Metabolic Phenotype and Hypothalamic Gene Expression of Wistar Rat Dams Post-Birth

“…SAM is the universal methyl donor involved in cellular methylation reactions of which regulates dynamic changes in gene expression [ 22 ]. However, the conversion of FA to 5-MTHF is limited by common polymorphisms as well as high FA-induced enzyme inhibitions [ 23 ]. High concentrations of serum [ 24 ] and maternal cord blood [ 25 ] unmetabolized FA have been detected and predicted to affect the metabolism, intracellular transport and/or regulatory functions of bioactive folates [ 26 , 27 ].…”

“…As a result, the replacement of FA with the reduced bioactive form of folate in dietary supplements has been proposed [ 9 , 23 , 28 ]. Many prescribed and over-the-counter prenatal supplements now incorporate the naturally occurring calcium salt, [6 S ]-5-methyltetrahydrofolic acid (MTHF), at a dose that is equivalent to those containing FA (1000 µg) [ 9 , 28 ].…”