scholarly journals Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study

2019 ◽  
Author(s):  
Kelsey M Cochrane ◽  
Chantal Mayer ◽  
Angela M Devlin ◽  
Rajavel Elango ◽  
Jennifer A Hutcheon ◽  
...  
Keyword(s):  
Small Intestine ◽  
Folic Acid ◽  
Blood Cell ◽  
Pregnant Women ◽  
Neural Tube ◽  
Red Blood Cell ◽  
Neural Tube Closure ◽  
Serum Folate ◽  
Proof Of Concept ◽  
Natural Form

Abstract Background: Health Canada recommends 0.4 mg/day folic acid before conception and throughout pregnancy to reduce the risk of neural tube defects. Folic acid is a synthetic form of folate that must be reduced by dihydrofolate reductase and then further metabolized in the small intestine. Recent evidence suggests that the maximal capacity for this process is limited and unmetabolized folic acid has been detected in circulation. The biological effects of unmetabolized folic acid are not fully understood. A natural form of folate, (6S)-5-methyltetrahydrofolic acid (Metafolin®), may be a superior alternative because it does not need to be reduced in the small intestine. Metafolin® is currently used in some prenatal multivitamins, however it has yet to be evaluated during pregnancy. Methods: This double-blind randomized trial will recruit 60 pregnant women aged 19-42 years. Women will receive either 0.6 mg/day folic acid or an equimolar dose (0.625 mg/day) of (6S)-5-methyltetrahydrofolic acid for 16-weeks. The trial will be initiated at 8-21 weeks gestation (after neural tube closure) to reduce the risk of harm should (6S)-5-methyltetrahydrofolic acid prove less effective. All women will also receive a prenatal multivitamin (not containing folate) to ensure adequacy of other nutrients. Baseline and endline blood samples will be collected to assess primary outcome measures, including serum folate, red blood cell folate and unmetabolized folic acid. Change in primary outcomes from baseline to endline in each group will be calculated using a paired-t-test. Discussion: This proof-of-concept trial is needed to obtain estimates of the effect of (6S)-5-methyltetrahydrofolic acid compared to folic acid on circulating biomarkers of folate status during pregnancy. These estimates will inform the design of a definitive trial which will be powered to assess whether (6S)-5-methyltetrahydrofolic acid is as effective as folic acid in raising blood folate concentrations during pregnancy. Ultimately, these findings will inform folate supplementation policies for pregnant women.

scholarly journals Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study

2020 ◽  
Author(s):  
Kelsey M Cochrane ◽  
Chantal Mayer ◽  
Angela M Devlin ◽  
Rajavel Elango ◽  
Jennifer A Hutcheon ◽  
...  
Keyword(s):  
Folic Acid ◽  
Blood Cell ◽  
Pregnant Women ◽  
Neural Tube ◽  
Red Blood Cell ◽  
Biological Effects ◽  
Neural Tube Closure ◽  
Serum Folate ◽  
Proof Of Concept ◽  
Natural Form

Abstract Background: North American health authorities recommend 0.4 mg/day folic acid before conception and throughout pregnancy to reduce the risk of neural tube defects. Folic acid is a synthetic form of folate that must be reduced by dihydrofolate reductase and then further metabolized. Recent evidence suggests that the maximal capacity for this process is limited and unmetabolized folic acid has been detected in circulation. The biological effects of unmetabolized folic acid are unknown. A natural form of folate, (6S)-5-methyltetrahydrofolic acid (Metafolin®), may be a superior alternative because it does not need to be reduced in the small intestine. Metafolin® is currently used in some prenatal multivitamins, however it has yet to be evaluated during pregnancy. Methods: This double-blind randomized trial will recruit 60 pregnant women aged 19-42 years. Women will receive either 0.6 mg/day folic acid or an equimolar dose (0.625 mg/day) of (6S)-5-methyltetrahydrofolic acid for 16-weeks. The trial will be initiated at 8-21 weeks gestation (after neural tube closure) to reduce the risk of harm should (6S)-5-methyltetrahydrofolic acid prove less effective. All women will also receive a prenatal multivitamin (not containing folate) to ensure adequacy of other nutrients. Baseline and endline blood samples will be collected to assess primary outcome measures, including serum folate, red blood cell folate and unmetabolized folic acid. The extent to which the change in primary outcomes from baseline to endline differs between treatment groups, controlling for baseline level, will be estimated using linear regression. Participants will have the option to continue supplementing until 1-week postpartum to provide a breastmilk and blood sample. Exploratory analyses will be completed to evaluate breastmilk and postpartum blood folate concentrations. Discussion: This proof-of-concept trial is needed to obtain estimates of the effect of (6S)-5-methyltetrahydrofolic acid compared to folic acid on circulating biomarkers of folate status during pregnancy. These estimates will inform the design of a definitive trial which will be powered to assess whether (6S)-5-methyltetrahydrofolic acid is as effective as folic acid in raising blood folate concentrations during pregnancy. Ultimately, these findings will inform folate supplementation policies for pregnant women.

scholarly journals Estimating the Serum Folate Concentration Associated With the Red Blood Cell Folate Threshold for Optimal Neural Tube Defects Prevention: A Population Based Biomarker Survey

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 644-644
Author(s):  
Amy Fothergill ◽  
Charles Rose ◽  
Krista Crider ◽  
Beena Bose ◽  
Heather Guetterman ◽  
...  
Keyword(s):  
Blood Cell ◽  
Vitamin B12 ◽  
Neural Tube ◽  
Red Blood Cell ◽  
Vitamin B12 Deficiency ◽  
Population Based ◽  
World Health ◽  
Serum Folate ◽  
Total Vitamin ◽  
B12 Deficiency

Abstract Objectives To estimate the serum folate insufficiency threshold (sf-IT) corresponding to the red blood cell (RBC) folate insufficiency threshold for optimal neural tube defect (NTD) prevention. Methods Participants were 977 women of reproductive age (WRA; 15–40y; not pregnant or lactating) from a population-based biomarker survey in Southern India. Venous blood samples were collected at enrollment. Plasma, serum, and red blood cells were centrifuged, processed, and stored < -80°C until batch analysis. Total vitamin B12 concentrations were measured via chemiluminescence; RBC and serum folate concentrations were measured using the World Health Organization-recommended microbiological assay. Vitamin B12 deficiency was defined as total vitamin B12 < 148 pmol/L. Folate insufficiency was defined as RBC folate < 748 nmol/L, the recommended calibrator-adjusted equivalent of the threshold for population optimal NTD prevention. A previously developed Bayesian model and the RBC and serum folate distributions in this population were used to estimate the sf-IT corresponding to the RBC folate insufficiency threshold for optimal NTD prevention, overall and by age, body mass index (BMI) category, HbA1c, anemia, and vitamin B12 status. Results The overall estimated median sf-IT was 37.8 nmol/L (95% credible interval [33.8–43.3]). This threshold was lower in overweight WRA (BMI: ≥25.0 kg/m2: 32.0 nmol/L [27.3–40.2] vs. BMI < 25.0 kg/m2: 36.2 nmol/L [32.2–43.3]), and varied by age (< 25y: 61.3 nmol/L [44.3–111.8]; 25 to 35y: 35.7 nmol/L [30.8–43.5]; ≥35y: 30.8 nmol/L [26.9–37.2]). The sf-IT was lower in anemic WRA (32.9 nmol/L [28.5–40.1]) compared to non-anemic WRA (42.0 nmol/L [36.1–51.3]), and lower in WRA with elevated HbA1c (≥5.7% to < 6.5: 32.4 nmol/L [27.3–41.6]; ≥6.5%: 20.9 nmol/L [17.8–25.6]) vs. WRA with HbA1c < 5.7% (43.8 nmol/L, [37.5–53.7]). The median sf-IT was higher in WRA with vitamin B12 deficiency (72.1 nmol/L [52.0–126.0]), compared to women who were not vitamin B12 deficient (28.1 nmol/L [25.6–31.5]). Conclusions The estimated sf-IT is dependent on anemia, elevated HbA1c, BMI, age, and vitamin B12 status. Funding Sources Centers for Disease Control and Prevention; AF was supported by the National Institutes of Health #5 T32 HD087137.

scholarly journals Validation of a Semi-Quantitative Food-Frequency Questionnaire for Dutch Pregnant Women from the General Population Using the Method or Triads

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1341 ◽  
Author(s):  
Trudy Voortman ◽  
Régine P.M. Steegers-Theunissen ◽  
Nienke E. Bergen ◽  
Vincent W. V. Jaddoe ◽  
Caspar W. N. Looman ◽  
...  
Keyword(s):  
Fatty Acids ◽  
General Population ◽  
Blood Cell ◽  
Vitamin B12 ◽  
Pregnant Women ◽  
Red Blood Cell ◽  
Food Frequency Questionnaire ◽  
Serum Folate ◽  
Food Frequency ◽  
Folate And Vitamin B12

Objective: We aimed to validate a food-frequency questionnaire (FFQ) for Dutch pregnant women, against three 24 h-recalls and blood concentrations of B-vitamins and fatty acids, using the method of triads. Methods: We included 83 pregnant women from the general population of Rotterdam, the Netherlands, at a median gestational age of 15.6 weeks. Participants completed three non-consecutive 24 h-recalls, and subsequently filled out the 293-item FFQ. Participants provided blood samples from which we analyzed serum folate and vitamin B12, as well as red blood cell folate, linoleic acid, and total saturated, monounsaturated, and polyunsaturated fatty acids. Results: Estimated energy intake did not differ between the FFQ and 24 h-recalls. Deattenuated Pearson’s correlation coefficients, between energy-adjusted nutrient intake estimates from the FFQ and the 24 h-recalls, ranged from 0.41 (fat) to 0.88 (fiber) for macronutrients, and were around 0.6 for most micronutrients, except for vitamin E (0.27). Using the triad method, we obtained validity coefficients of 0.86 (95% Confidence Interval (CI) 0.36, 1.00) for serum folate, 0.86 (95% CI 0.18, 1.00) for red blood cell folate, and 1.00 (95% CI 0.42, 1.00) for vitamin B12. Validity coefficients for serum fatty acids ranged from 0.22 to 0.67. Conclusion: This FFQ is a reliable tool for estimating intake of energy, macronutrients, folate and vitamin B12 among women in mid-pregnancy.

scholarly journals Effect of different dosage and administration schedules of folic acid on blood folate levels in a population of Honduran women of reproductive age

2008 ◽  
Vol 11 (8) ◽  
pp. 822-830 ◽  
Author(s):  
J Rosenthal ◽  
G Milla ◽  
A Flores ◽  
M Yon ◽  
C Pfeiffer ◽  
...  
Keyword(s):  
Folic Acid ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Folic Acid Supplementation ◽  
Conclusive Evidence ◽  
Reproductive Age ◽  
Serum Folate ◽  
Folate Supplementation ◽  
Double Blind ◽  
Supplementation Period

AbstractBackgroundObservational studies and clinical trials have shown conclusive evidence that periconceptional folic acid supplementation prevents up to 70 % of neural tube defects (NTD). The Honduran government wanted to implement a supplementation programme of folic acid but needed to assess the relative effects of two dosages of folic acid.ObjectiveTo determine the effect of two dosages of folic acid on blood folate levels in Honduran female factory workers aged 18 to 49 years.DesignThis was a randomized, double-blind control supplementation trial conducted in Choloma, Honduras. A total of 140 eligible women were randomly assigned to two dosage groups and followed up for 12 weeks. One group received a daily dosage of 1 mg folic acid and the other a once weekly dosage of 5 mg. Serum folate and red blood cell folate levels were determined by radioassay at baseline, 6 weeks and 12 weeks.ResultsSerum folate levels increased from 6·3 (se 0·2) to 14·9 (se 0·6) ng/ml (P < 0·0001) in women assigned to the 1 mg/d group and from 6·9 (se 0·3) to 10·1 (se 0·4) ng/ml (P < 0·0001) in those assigned to the 5 mg/week group. Red blood cell folate concentrations also increased significantly in both groups, albeit more slowly. Educational level, age and BMI were not associated with the changes in serum and red blood cell folate levels during the supplementation period. However, a differential effect on serum folate levels by dosage group and time was observed.ConclusionsAlthough both folate supplementation regimens increased serum and red blood cell folate levels significantly among the women studied, blood folate levels that are considered to be protective of NTD were reached faster with the daily dosage of 1 mg folic acid.

A Reassessment of the Red Blood Cell Folate Assay

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3209-3209 ◽  
Author(s):  
James Hoyer ◽  
Jennifer Oliveira ◽  
Nikola Baumann ◽  
Amy Saenger
Keyword(s):  
Folic Acid ◽  
Alcohol Abuse ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Previous History ◽  
Folate Deficiency ◽  
Folic Acid Supplementation ◽  
Serum Folate ◽  
Acid Supplementation ◽  
History Of

Abstract Abstract 3209 Background: The red blood cell folate (RCF) assay has historically been recommended as a more reliable indicator of tissue folate stores compared to the serum folate (SF) assay, as it is not affected by recent ingestion of food. However, the RCF assay suffers from inherent problems with imprecision and accuracy, which are not encountered with SF measurements. Furthermore, following the advent of required folic acid supplementation of many foods by the Food and Drug Administration (FDA) in 1992, folate deficiency is increasingly rare. Very few studies have looked at the value of the RCF versus the SF. We undertook a 10 year retrospective analysis of RCF and SF results to determine the clinical utility of RCF beyond that of SF. Methods: We retrieved all RCF and SF results from the laboratory information system at Mayo Clinic (Rochester, MN) ordered on inpatients and outpatients between 1999–2009. Data for patients who had concurrent orders for SF and RCF were analyzed and chart reviews were conducted on those patients with normal SF but low RCF. Abnormal values were defined by the National Health and Nutrition Examination Surveys (NHANES)/Center for Disease Control (CDC) criteria for folate deficiency (SF< 3.0 ng/ml, RCF < 140 ng/ml). Results: A total of 152,166 SF and 15,708 RCF were performed over the decade of the study. The prevalence of folate deficiency using only SF values was 0.39% and 0.27% using only RCF values. There were 1082 patients in which SFA and RCFA were ordered concurrently (Table 1). Only 1 patient (0.09%) had both abnormal SF and RCF. Chart reviews of the 4 patients with a normal SF but low RCF were as follows: 1) a 6 year old (yo). male with known folic acid transporter deficiency treated with Leucovorin. 2) a 58 yo male with history of gout, hypertension, psoriasis, and hyperlipidemia with normal hemoglobin (Hb) and MCV. 3) a 65 yo male with chronic diarrhea and suspected alcohol abuse; slight macrocytosis (MCV=100.3 fL) but normal Hb. 4) a 51 yo male with multifactorial gait disorder and alcohol abuse. There was a previous history of vitamin B12 deficiency but B12 levels were normal at this time. The CBC was notable for macrocytosis (MCV=115.1 fL) without anemia. Only in patient 4 did the RCF value result in the institution of folic acid supplementation. Conclusions: The RCF provides no additional information beyond that provided by the SF in virtually all situations. Thus SF alone is sufficient for assessment of folate stores. However, there is no evidence to support routine ordering of either SF or RCF, as true folate deficiency in the current era of FDA mandated folic acid supplementation is exceedingly rare. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Kelsey M. Cochrane ◽  
Chantal Mayer ◽  
Angela M. Devlin ◽  
Rajavel Elango ◽  
Jennifer A. Hutcheon ◽  
...  
Keyword(s):  
Folic Acid ◽  
Pilot Study ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Proof Of Concept

scholarly journals Knowledge and intake of folic acid to prevent neural tube defects among pregnant women in urban China: a cross-sectional study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mingming Cui ◽  
Xiao-Lin Lu ◽  
Yan-Yu Lyu ◽  
Fang Wang ◽  
Xiao-Lu Xie ◽  
...  
Keyword(s):  
Folic Acid ◽  
Pregnant Women ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Rural Women ◽  
Rural Areas ◽  
Urban Areas ◽  
Unplanned Pregnancy ◽  
Urban China ◽  
Cross Sectional

Abstract Background The prevalence of neural tube defects (NTDs) in China declined during 2000–2017 with periconceptional folic acid (FA) supplementation, which is effective in reducing the risk of birth defects. We aimed to assess the knowledge and actual use of FA among Chinese pregnant women and to explore factors associated with FA use before pregnancy. Methods All data were collected in face-to-face interviews during health visits among pregnant women. We collected information about knowledge and use of FA supplements and demographic, socioeconomic, and health status. One maternity and childcare hospital was chosen in each of four cities: Beijing, Huaibei, Kunming, and Haikou. In total, 435 pregnant women were randomly recruited for interviews conducted from June to December 2016. Results A total of 428 pregnant women were included in this survey. Of these, 82.0% (351/428) knew that FA can prevent NTDs, and 75.9% (325/428) knew the correct time to take FA. Overall, 65.9% (282/428) of women knew both that FA can prevent NTDs and the recommended time to take FA before pregnancy. Approximately 95.1% (407/428) of women reported having ever taken FA, only 46.3% (198/428) had begun to take FA supplementation before conception, and 64.5% (109/169) of women from rural areas failed to take FA before pregnancy. Women living in northern China (odds ratio [OR] = 1.81, 95% confidence interval [CI], 1.18–2.77), those with unplanned pregnancy (OR = 1.99, 95% CI 1.30–3.04), and highly educated women (OR = 2.37, 95% CI 1.45–3.88) were more likely to know about FA. Women who were homemakers (OR = 1.94, 95% CI 1.21–3.11) and had unplanned pregnancy (OR = 6.18, 95% CI 4.01–9.53) were less likely to begin taking FA before pregnancy. Conclusions Our survey showed that most pregnant women knew about FA. Although preconception intake of FA can help to reduce NTDs, improving the rate of FA intake before pregnancy is needed in urban areas of China, especially among homemakers and women from rural areas or with unplanned pregnancy. Campaigns are needed to increase awareness about FA and FA use before pregnancy among rural women, homemakers, and those with unplanned pregnancy and lower education levels.

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