Folate Nutrigenetics: A Convergence of Dietary Folate Metabolism, Folic Acid Supplementation, and Folate Antagonist Pharmacogenetics

AbstractObjective:To investigate the hypothesis that folic acid supplementation and dietary folate intake before conception and during pregnancy reduce the risk of small for gestational age (SGA) and to examine the joint effect of folic acid supplementation and dietary folate intake on the risk of SGA.Design:Participants were interviewed by trained study interviewers using a standardized and structured questionnaire. Information on birth outcomes and maternal complications was abstracted from medical records and dietary information was collected via a semi-quantitative FFQ before conception and during pregnancy.Setting:A birth cohort data analysis using the 2010–2012 Gansu Provincial Maternity and Child Care Hospital.Participants:Women (n 8758) and their children enrolled in the study.Results:Folic acid supplementation was associated with a reduced risk of SGA (OR = 0·72, 95 % CI 0·60, 0·86), with the reduced risk seen mainly for SGA at ≥37 weeks of gestational age (OR = 0·70, 95 % CI 0·58, 0·85) and nulliparous SGA (OR = 0·67, 95 % CI 0·54, 0·84). There was no significant association between dietary folate intake and SGA risk.Conclusions:Our study suggested that folic acid supplementation was associated with a reduced risk of SGA and the risk varied by preterm status and parity.

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Maternal Folic Acid Intake and Risk of Nonsyndromic Orofacial Clefts: A Hospital-Based Case–Control Study in Bangalore, India

The Cleft Palate-Craniofacial Journal ◽

10.1177/1055665619893214 ◽

2019 ◽

Vol 57 (6) ◽

pp. 678-686

Author(s):

Vivienne J. Mendonca

Keyword(s):

Folic Acid ◽

Case Control Study ◽

Folic Acid Supplementation ◽

Folic Acid Intake ◽

Orofacial Clefts ◽

Dietary Folate ◽

Acid Supplementation ◽

Folic Acid Supplements ◽

Periconceptional Period ◽

Control Study

Background: Orofacial clefts are the most common congenital anomaly worldwide. Cleft etiology appears to be multifactorial, with genetic and environmental components. Although periconceptional folic acid supplementation has been shown to be protective for neural tube defects, current evidence for its role in cleft prevention is mixed with few studies from low- and middle-income countries. Aim: To investigate the association between periconceptional folic acid intake and incidence of nonsyndromic orofacial clefts among infants in Bangalore, India. Methods: A hospital-based case–control study (106 cases, 212 controls) utilizing a questionnaire to collect data on prenatal supplements, dietary folate, and potentially confounding factors. Multivariate logistic regression analysis was used to assess relationships between folic acid supplementation and all nonsyndromic clefts, and in separate analyses for cleft lip and/or palate (CL/P) and cleft palate (CP), adjusting for statistically significant variables. Results: A statistically significant protective association was found for separate folic acid supplements (not combined with iron or multivitamins) taken in the periconceptional period and all clefts combined (adjusted odds ratio [OR]: 0.62, 95% confidence interval [CI], 0.45-0.86) and CL/P (adjusted OR: 0.57; 95% CI, 0.38-0.86). Higher levels of dietary folate were found to be associated with a reduced risk for all clefts (adjusted OR: 0.98, 95% CI, 0.96-0.99), CL/P (adjusted OR: 0.98, 95% CI, 0.96-0.99), and CP (adjusted OR: 0.96, 95% CI, 0.93-0.99). Conclusion: This study provides limited evidence for a protective association of periconceptional folic acid supplementation with nonsyndromic orofacial clefts. The low proportion of mothers taking folic acid supplements in the periconceptional period highlights the need for increased education and awareness regarding prenatal nutrition.

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Maternal Folic Acid Supplementation, Dietary Folate Intake and Low Birth Weight: A Birth Cohort Study

10.21203/rs.3.rs-163378/v1 ◽

2021 ◽

Author(s):

LiPing Yang ◽

Wenjuan Wang ◽

Baohong Mao ◽

Jie Qiu ◽

Huaqi Guo ◽

...

Keyword(s):

Folic Acid ◽

Folic Acid Supplementation ◽

Folate Intake ◽

Care Hospital ◽

Folic Acid Supplement ◽

Dietary Folate ◽

Acid Supplementation ◽

Dietary Folate Intake ◽

Reduced Risk ◽

Joint Associations

Abstract ObjectivesTo investigate the independent and collective effects of maternal folic acid supplementation or dietary folate intake upon the risk of low birth weight (LBW), and to further comprehensively examine the joint associations of folic acid supplementation and dietary folate intake with LBW by various clinical subtypes.DesignParticipants were recruited in Gansu Provincial Maternity and Child Care Hospital. A standardized and structured questionnaire was distributed to collect demographic factors, reproductive and medical history, occupational and residential history, physical activity and diet. Data on pregnancy-related complications and birth outcomes were extracted from medical records. Unconditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (95%CI) for single and joint associations of folic acid supplementation and dietary folate intake with LBW. SettingA birth cohort data analysis using the 2010–2012 Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China.Participants9231 pregnant women and their children were enrolled in the study. ResultsCompared to non-users, folic acid supplementation was associated with a reduced risk of LBW (OR: 0.80, 95%CI: 0.66-0.97), and the reduced risk was mainly seen for term-LBW (OR: 0.59, 95%CI: 0.41-0.85), and multiparous-LBW (OR: 0.72, 95%CI: 0.54-0.94). For dietary folate intake, there were no significant associations with LBW, and there was no interaction of folic acid supplement and dietary folate intake on LBW.ConclusionsOur study results indicated that folic acid supplementation was associated with a reduced risk of LBW, and there was not interaction of folic acid supplement and dietary folate intake on LBW.

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ZIP-5/bZIP transcription factor regulation of folate metabolism is critical for aging axon regeneration

10.1101/727719 ◽

2019 ◽

Author(s):

Vanisha Lakhina ◽

Melanie McReynolds ◽

Daniel T. Grimes ◽

Joshua D. Rabinowitz ◽

Rebecca D. Burdine ◽

...

Keyword(s):

Transcription Factor ◽

Folic Acid ◽

Axon Regeneration ◽

Folic Acid Supplementation ◽

Folate Metabolism ◽

Bzip Transcription Factor ◽

General Strategy ◽

Invasive Approach ◽

Acid Supplementation ◽

Regenerative Ability

AbstractAging is associated with reduced capacity for tissue repair, perhaps the most critical of which is a decline in the ability of aged neurons to recover after injury. Identifying factors that improve the regenerative ability of aging neurons is a prerequisite for therapy design and remains an enormous challenge, yet many of the genes that play a role in regeneration of youthful axons do not regulate axon regeneration in older animals2,9, highlighting the need to identify aging-specific regeneration mechanisms. Previously, we found that increased DAF-16/FOXO activity enhances the regenerative ability of mechanosensory axons in aged animals9. Here we show that DAF-16/FOXO mediates its pro-regenerative effects by upregulating folate metabolism genes via the ZIP-5 bZIP transcription factor. Remarkably, dietary folic acid supplementation improves the regeneration of aging C. elegans axons. Enzymes regulating folate metabolism are also up-regulated in regenerating zebrafish fins, and we show that dietary folic acid supplementation post-amputation enhances fin regrowth in aging zebrafish. Our results demonstrate that boosting folate metabolism is a conserved and non-invasive approach to increase the regenerative capacity of aging neurons and tissues. Given that lower folate status has been linked with reduced cognition in the elderly17, maintaining optimal folate metabolism may be a general strategy to achieve healthy brain aging.

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Folate Supplementation during Oocyte Maturation Positively Impacts the Folate-Methionine Metabolism in Pre-Implantation Embryos

10.21203/rs.3.rs-552700/v1 ◽

2021 ◽

Author(s):

Sikander Saini ◽

Vishal Sharma ◽

Shama Ansari ◽

Amit Kumar ◽

Abhishek Thakur ◽

...

Keyword(s):

Folic Acid ◽

Production Rate ◽

Oocyte Maturation ◽

Folic Acid Supplementation ◽

Folate Metabolism ◽

Acid Supplementation ◽

Maturation Medium ◽

Metabolism Enzymes ◽

Methionine Cycle ◽

Folate Transporters

Abstract Folic acid is vital for DNA synthesis and methylations through one-carbon (C1) metabolism. Thus, it is essential for cell division during embryonic development. The present study investigated the effect of folic acid supplementation on oocyte maturation, blastocyst development and the expression of folate transporters as well as folate metabolism enzymes in oocytes and pre-implantation embryos of goat. Immature goat oocytes, matured in maturation medium comprising different folic acid concentrations (0, 10, 50, 100 and 150 µM), were in vitro fertilized and cultured. Cumulus expansion markers (Ptx3 and Ptgs2) in cumulus cells were highly upregulated after 50 µM folic acid supplementation indicating higher degree of maturation. Supplementation of 50 µM folic acid during oocyte maturation resulted in significantly higher blastocyst production rate, reduction in intracellular ROS levels as well as upregulation of the transcripts for folate transporters and key folate-methionine cycle enzymes in comparison to control. The present study demonstrates the existence of active folate-methionine cycle in oocytes and pre-implantation goat embryos. Supplementation of 50 µM folic acid in maturation medium increases the blastocyst production rate, improves oocyte maturation, reduces ROS production as well as upregulate the expression of Folr1 and folate metabolism enzyme, Mtr.

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Effects of folic acid supplementation on growth performance and hepatic folate metabolism-related gene expressions in weaned piglets

Frontiers of Agriculture in China ◽

10.1007/s11703-010-1047-1 ◽

2010 ◽

Vol 4 (4) ◽

pp. 494-500 ◽

Cited By ~ 3

Author(s):

Bing Yu ◽

Guangbo Yang ◽

Jingbo Liu ◽

Daiwen Chen

Keyword(s):

Folic Acid ◽

Growth Performance ◽

Folic Acid Supplementation ◽

Folate Metabolism ◽

Related Gene ◽

Weaned Piglets ◽

Gene Expressions ◽

Acid Supplementation

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Maternal folic acid supplementation and dietary folate intake and congenital heart defects

PLoS ONE ◽

10.1371/journal.pone.0187996 ◽

2017 ◽

Vol 12 (11) ◽

pp. e0187996 ◽

Cited By ~ 14

Author(s):

Baohong Mao ◽

Jie Qiu ◽

Nan Zhao ◽

Yawen Shao ◽

Wei Dai ◽

...

Keyword(s):

Folic Acid ◽

Congenital Heart Defects ◽

Congenital Heart ◽

Heart Defects ◽

Folic Acid Supplementation ◽

Folate Intake ◽

Dietary Folate ◽

Acid Supplementation ◽

Dietary Folate Intake

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Precise Dose of Folic Acid Supplementation Is Essential for Embryonic Heart Development in Zebrafish

Biology ◽

10.3390/biology11010028 ◽

2021 ◽

Vol 11 (1) ◽

pp. 28

Author(s):

Xuhui Han ◽

Bingqi Wang ◽

Dongxu Jin ◽

Kuang Liu ◽

Hongjie Wang ◽

...

Keyword(s):

Folic Acid ◽

Heart Development ◽

Cardiac Development ◽

Folic Acid Supplementation ◽

Mthfr Gene ◽

Folate Metabolism ◽

Marker Genes ◽

Zebrafish Embryos ◽

Cardiovascular Development ◽

Acid Supplementation

Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. Moreover, we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid and mthfr−/− mutant all gave rise to early pericardial edema and cardiac defect at 3 days post fertilization (dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5 dpf. The expression levels of cardiac marker genes hand2, gata4, and nppa changed in the abnormality of folate metabolism embryos and mthfr−/− mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. Furthermore, our results reveal that folic acid has a dose-dependent effect on early cardiac development. Precise dosage of folic acid supplementation is crucial for the embryonic development of organisms.

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