The folate status of reproductive-aged women in a randomised trial of a folate-fortified oral contraceptive: dietary and blood assessments

Abstract

Objective: To assess the folate status of US women in a study of a folate-fortified oral contraceptive (OC) using the Short Folate Food Frequency Questionnaire and plasma and red blood cell (RBC) folate samples. Design: Sub-analysis from a multi-centre, randomised, double-blind, controlled contraceptive trial with assessments at baseline and 6 months. We calculated dietary folate equivalents (DFE) consumed and the proportion of participants meeting folate adequacy benchmarks. Setting: Eight centres in the USA. Subjects: Healthy women aged 18-40 years requesting contraception with no contraindications for OC use. Results: Overall, 385 participants were randomised to either a novel folatefortified OC or a marketed OC. The 262 (68 %) participants compliant with the protocol were included in the analysis set. Baseline daily DFE consumption was 529?8 (SD 342?1) mg and similar in both groups. At follow-up, the fortified OC group had higher intake than the conventional OC group (1225?9 (SD 346?2) mg compared with 500?6 (SD 361?2) mg). Mean plasma folate level increased from 44?5 (SD 17?2) to 55?8 (SD 21?1) nmol/l. Mean RBC folate level increased from 996?7 (SD 369?8) to 1311?9 (SD 436?0) nmol/l. The proportion meeting selected folate adequacy benchmarks increased in the fortified OC group (P , 0?001). Conclusions: Lack of adequate folate intake in reproductive-aged women from dietary sources or supplements alone suggests the need for novel approaches. Use of folate-fortified OC ensures adequate folate levels and meeting of folate benchmarks.

The Effectiveness of Folate-Fortified Oral Contraceptives in Maintaining Optimal Folate Levels to Protect Against Neural Tube Defects: A Systematic Review

“…Ultimately, five articles met the final inclusion criteria. [8][9][10][11][12] The five studies presented in this category are summarized in the Table. Bioequivalence studies Wiesinger et al 9 conducted a randomized, open-label, threeperiod, crossover study at a single centre in Germany to evaluate the bioequivalence of a new folate-supplemented oral contraceptive preparation (containing ethinyl estradiol, drospirenone, and levomefolate calcium) with its nonsupplemented counterpart (containing ethinyl estradiol and drospirenone) and levomefolate calcium (5-methyl-THF) separately. Within this intra-individual crossover design, each participant was randomized to a treatment sequence that included: Each treatment commenced between the third and sixth days of the participant's menstrual cycle, and each treatment was administered as a single dose orally, along with extensive dietary restrictions that were standardized across all participants.…”

“…Thus, in the event of an unplanned pregnancy it provides blood folate levels that are optimally protective against NTDs. 8,11 Even without pregnancy, it provides the appropriate daily folate dose for women to maintain good health.…”

“…6 A novel folate-fortified oral contraceptive preparation (Yaz Plus) containing ethinyl estradiol 0.02 mg, drospirenone 3 mg, and levomefolate calcium 0.451 mg in each tablet, was approved by Health Canada in 2010 for the purpose of raising serum folate levels in women who are using it as a method of contraception. 7,8 The objective of this study was to systematically review the data available on this preparation in order to evaluate its potential as an alternative to current folic acid supplementation therapy.…”

A Review of the Effects of Oral Contraceptives on Nutrient Status, with Especial Consideration to Folate in UK

“…A recent meta-analysis and systematic review concluded "Because of the reduction in blood folate concentrations associated with the use of oral contraceptives, it is critical for women of childbearing age to continue folate supplementation during oral contraceptive use" [48]. In 2012, in recognition of this, an oral contraceptive fortified with folate was made available in some markets as a means of lowering the hazard of neural tube defects (NTDs) in females who might become pregnant during OC use or shortly after discontinuation [49,50]. Evidence also suggests that OCs might enhance the rate of progression of cervical dysplasia to cervical cancer, and folic acid may be able reverse or reduce the rate of progression of this dysplasia [51,52].…”

Obesity and reproductive function of women: epigenetic and somato-psychological features

“…Целевая аудитория этих препаратов -наиболее нуждающиеся в фолиевой кислоте женщины детородного возраста, и данная стратегия имеет огромные преимущества в отличие от широкого применения диетического обогащения фолатами. Таким образом, в случае незапланированной беременности КОК с фолатами обеспечивает их оптимальный уровень для профилактики ДНТ [52]. Независимо от того, планирует женщина беременность или нет, препараты обеспечивают необходимой ежедневной дозой фолата для поддержания здоровья.…”