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The effectiveness of daily supplementation with 400 or 800 µg/day folate in reaching protective red blood folate concentrations in non-pregnant women: a randomized trial.

ABSTRACT: Folate required to achieve desirable red blood cell (RBC) folate concentrations within 4-8 weeks pre-pregnancy is not known. We studied the effect of supplementation with 400 or 800 µg/day folate in achieving RBC-folate ?906 nmol/L.Non-pregnant women were randomized to receive multinutrient supplements containing 400 µg/day (n = 100) or 800 µg/day (n = 101) folate [folic acid and (6S)-5-CH3-H4folate-Ca (1:1)]. The changes of folate biomarkers were studied after 4 and 8 weeks in the 198 women who returned at least for visit 2.At baseline, 12 of the 198 participants (6.1%) had RBC-folate <340 nmol/L, but 88% had levels <906 nmol/L. The RBC-folate concentrations increased significantly in the 800 µg/day (mean ± SD = 652 ± 295 at baseline; 928 ± 330 at 4 weeks; and 1218 ± 435 nmol/L at 8 weeks) compared with the 400 µg/day [632 ± 285 at baseline (p = 0.578); 805 ± 363 at 4 weeks (p < 0.001); 1021 ± 414 nmol/L at 8 weeks (p < 0.001)]. The changes of RBC-folate were greater in the 800 µg/day than in the 400 µg/day at any time (changes after 8 weeks: 566 ± 260 vs. 389 ± 229 nmol/L; p < 0.001). Significantly more women in the 800 µg group achieved desirable RBC-folate concentrations at 4 weeks (45.5 vs. 31.3%; p = 0.041) or 8 weeks (83.8 vs. 54.5%; p < 0.001) compared with the 400 µg group. RBC-folate levels below the population median (590 nmol/L) were associated with a reduced response to supplements.88% of the women had insufficient RBC-folate to prevent birth defects, while 6.1% had deficiency. Women with low RBC-folate were unlikely to achieve desirable levels within 4-8 weeks, unless they receive 800 µg/day. The current supplementation recommendations are not sufficient in countries not applying fortification.The trial was registered at The German Clinical Trials Register: DRKS-ID: DRKS00009770.

SUBMITTER: Obeid R

PROVIDER: S-EPMC6060806 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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The effectiveness of daily supplementation with 400 or 800 µg/day folate in reaching protective red blood folate concentrations in non-pregnant women: a randomized trial.

Obeid Rima R Schön Christiane C Wilhelm Manfred M Pietrzik Klaus K Pilz Stefan S

European journal of nutrition 20170426 5

<h4>Purpose</h4>Folate required to achieve desirable red blood cell (RBC) folate concentrations within 4-8 weeks pre-pregnancy is not known. We studied the effect of supplementation with 400 or 800 µg/day folate in achieving RBC-folate ≥906 nmol/L.<h4>Methods</h4>Non-pregnant women were randomized to receive multinutrient supplements containing 400 µg/day (n = 100) or 800 µg/day (n = 101) folate [folic acid and (6S)-5-CH<sub>3</sub>-H<sub>4</sub>folate-Ca (1:1)]. The changes of folate biomarkers ...[more]

PMID: 28447203

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Project description:It is not known whether folate metabolism is altered during pregnancy to support increased DNA and RNA biosynthesis. By using a state-of-the-art LC tandem mass spectrometry technique, the aim of this study was to investigate differences in RBC folate forms between pregnant and nonpregnant women and between nonpregnant women consuming different concentrations of supplemental folic acid. Forms of folate in RBCs were used to explore potential shifts in folate metabolism during early erythropoiesis. Total RBC folate and folate forms [tetrahydrofolate; 5-methyltetrahydrofolate (5-methyl-THF); 4α-hydroxy-5-methyl-tetrahydrofolate (an oxidation product of 5-methyl-THF); 5-formyl-tetrahydrofolate; and 5,10-methenyl-tetrahydrofolate] were measured in 4 groups of women (n = 26): pregnant women (PW) (30-36 wk of gestation) consuming 1 mg/d of folic acid, and nonpregnant women consuming 0 mg/d (NPW-0), 1 mg/d (NPW-1), and 5 mg/d (NPW-5) folic acid. The mean ± SD RBC folate concentration of the NPW-0 group (890 ± 530 nmol/L) was lower than the NPW-1 (1660 ± 350 nmol/L) and NPW-5 (1980 ± 570 nmol/L) groups as assessed by microbiologic assay (n = 26, P < 0.0022). No difference was found between the NPW-1 and NPW-5 groups. We detected 5-methyl-THF [limit of detection (LOD) = 0.06 nmol/L] in all groups and tetrahydrofolate (LOD = 0.2 nmol/L) in most women regardless of methylenetetrahydrofolate reductase genotype. Most women consuming folic acid supplements had detectable concentrations of 5,10-methenyl-tetrahydrofolate (LOD = 0.31 nmol/L). However, there was no difference in the relative distribution of 5-methyl-THF (83-84%), sum of non-methyl folates (0.6-3%), or individual non-methyl folate forms in RBCs across groups. We conclude that although folic acid supplementation in nonpregnant women increases RBC total folate and the concentration of individual folate forms, it does not alter the relative distribution of folate forms. Similarly, distribution of RBC folate forms did not differ between pregnant and nonpregnant women. This trial was registered at clinicaltrials.gov as NCT01741077.

Project description:For treatment of multidrug-resistant tuberculosis (MDR-TB), there is a scarcity of antituberculosis drugs. Co-trimoxazole is one of the available drug candidates, and it is already frequently coprescribed for TB-HIV-coinfected patients. However, only limited data are available on the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of co-trimoxazole in TB patients. The objective of this study was to evaluate the PK parameters and in vitro PD data on the effective part of co-trimoxazole: sulfamethoxazole. In a prospective PK study in patients infected with drug-susceptible Mycobacterium tuberculosis (drug-susceptible TB patients) (age, >18), sulfamethoxazole-trimethoprim (SXT) was administered orally at a dose of 960 mg once daily. One-compartment population pharmacokinetic modeling was performed using MW\Pharm 3.81 (Mediware, Groningen, The Netherlands). The area under the concentration-time curve for the free, unbound fraction of a drug (ƒAUC)/MIC ratio and the period in which the free concentration exceeded the MIC (fT > MIC) were calculated. Twelve patients received 960 mg co-trimoxazole in addition to first-line drugs. The pharmacokinetic parameters of the population model were as follows (geometric mean ± standard deviation [SD]): metabolic clearance (CLm), 1.57 ± 3.71 liters/h; volume of distribution (V), 0.30 ± 0.05 liters · kg lean body mass(-1); drug clearance/creatinine clearance ratio (fr), 0.02 ± 0.13; gamma distribution rate constant (ktr_po), 2.18 ± 1.14; gamma distribution shape factor (n_po), 2.15 ± 0.39. The free fraction of sulfamethoxazole was 0.3, but ranged between 0.2 and 0.4. The median value of the MICs was 9.5 mg/liter (interquartile range [IQR], 4.75 to 9.5), and that of theƒAUC/MIC ratio was 14.3 (IQR, 13.0 to 17.5). The percentage of ƒT > MIC ranged between 43 and 100% of the dosing interval. The PK and PD data from this study are useful to explore a future dosing regimen of co-trimoxazole for MDR-TB treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT01832987.).

Dataset Information

The effectiveness of daily supplementation with 400 or 800 µg/day folate in reaching protective red blood folate concentrations in non-pregnant women: a randomized trial.

Publications

The effectiveness of daily supplementation with 400 or 800 µg/day folate in reaching protective red blood folate concentrations in non-pregnant women: a randomized trial.

Similar Datasets

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