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Folic Acid Supplementation: A Review of the Known Advantages and Risks
Abstract
Folate is required for metabolic processes and neural development. The aim of this paper was to review the effects of folic acid supplementation before and throughout pregnancy on fetal development, summarize research needs with a focus on studying the effects of correct dosage folic acid. Methods: Related publications were reviewed to determine and quantify associations of maternal use of folic acid before conception and during pregnancy as risk factor for Neural Tube Defects (NTD), Orofacial Clefts, ischemic heart diseases, Unmetabolised folic acid, Masking of B12 Deficiency Anemia and cancer. Evidence on maternal drug use before conception and during pregnancy as risk factor for developmental defect from epidemiological studies is still very limited. This review showed that a high prevalence of malformations and diseases that affect fetus could be related to the mother folic acid supplementation before and during pregnancy. Challenges in global prevalence estimation include quality of surveillance methods, geographic and socioeconomic factors, availability and use of folic acid, racial-ethnic and genetic factors, and limitations in education and access to care. For primary prevention of NTD in women with no prior affected pregnancy, 0.4 mg daily dose of folic acid was recommended and 4.0 mg daily dose was effective in preventing NTD in women with a prior affected pregnancy. Also Maternal supplementation in early pregnancy reduces the risk of oral cleft in infants, evidence from the literature serve to reassure women planning a pregnancy to consume folic acid during the periconception period to protect against oral clefts. Several studies have confirmed that folic acid supplementation before pregnancy was associated with a reduced risk of ischemic heart diseases, lower dietary folate intake during pregnancy was associated with increased risk. Folic acid may prevent or promote cancer development and progression depending on the timing of intervention In conclusion and based on the evidence evaluated, caution regarding under and/or over folic acid supplementation is warranted.
... Prescribing folic acid as a prophylactic measure to prevent adverse outcomes in live births is widely endorsed and substantiated in the literature. Beyond its role in preventing neural tube defects (Martinez et al., 2021;van Gool et al., 2018), there are reports of its potential in averting early placental rupture, prematurity, reducing low birth weight, preventing cardiac anomalies, brain tumors, and even mitigating autism risk in early childhood (Al-mashhadane and Amer, 2018;Sampaio et al., 2021;van Gool et al., 2018). However, a cohort of researchers aims to discern potential adverse effects of folic acid supplementation during preconception and pregnancy. ...
... It's important to note that these studies often lack robust evidence, methodological rigor, and comprehensive analysis. Nevertheless, some studies suggest an association between folic acid supplementation and respiratory diseases in newborns and children, encompassing conditions like wheezing, asthma, respiratory allergies, and bronchitis (Al-mashhadane and Amer, 2018;Guo et al., 2019;Nasir et al., 2020). Given the limitations of relying solely on increased flour with added iron and folic acid in the diet, as it cannot precisely measure the dose consumed, antianemic supplementation remains a crucial strategy. ...
Anemia during pregnancy is a significant risk factor for adverse maternal and fetal outcomes, including preterm birth, low birth weight, and maternal mortality. In Brazil, anemia prevention and treatment programs are available, but regional variations in prevalence and factors associated with antianemic drug use remain understudied. The objective was to identify the prevalence of gestational anemia and the factors associated with the use of antianemic drugs during pregnancy in a cross-sectional population-based study carried out in Rio Branco, AC. To do so, we planned a cross-sectional, population-based study with a total of 1190 postpartum women who gave birth between April 6 and July 10, 2015, were interviewed about demographic, socioeconomic, reproductive, and prenatal care factors. The prevalence of anemia during pregnancy was found to be 13.8 %, with 93.2 % of women using antianemic drugs, such as ferrous sulfate and folic acid. Factors positively associated with antianemic drug use were higher education (elementary school II RCajust = 2.46; 95 %, CI: 1.01–6.13; high school RCajust = 2.61; 95 %, CI: 1.11–6.12), primiparity (ACadjust = 1.69; 95 %, CI: 0.98–3.74), 6 to 8 prenatal consultations (ACjust = 2.16; 95, CI%: 1.15–4.05), and planned pregnancy (ARjust = 1.94; 95 %, CI: 1.05–3.74). Food security during pregnancy was inversely associated. These findings suggest that while anemia prevention and treatment programs exist, more targeted strategies are needed, particularly for women with lower socioeconomic status, to improve maternal and fetal health outcomes.
... However, there is limited evidence on the correlation between folic acid intake after the frst trimester of pregnancy and fetal malformations. Some studies have shown that continued folic acid supplementation during pregnancy may still have benefts in reducing the risk of certain birth defects, while others found no signifcant correlation [30,31]. ...
Methods:
A 17-week-old female neonate with a history of prenatal diagnosis of congenital heart anomaly was admitted to Ayatollah Mousavi Hospital in Zanjan, Iran. For the diagnosis of thoracic ectopia, cordis fetal echocardiography and ultrasonography were performed. Moreover, the noninvasive prenatal testing (NIPT) genetic test performed in the 10th week of pregnancy was evaluated.
Results:
The neonate was diagnosed with thoracic ectopia cordis, with the heart located outside the thoracic cavity and covered by a thin membrane. The Z scores of the analyzed maternal venous blood chromosomes were between +6 and -6, and all chromosomes had a low risk in terms of the risk of birth defects. The results of this study revealed that genetic test analysis is not enough to diagnose and predict congenital anomalies and defects. Furthermore, the findings showed that the fetus's mother continued to take folic acid after the first 3 months of pregnancy. This can be one of the risk factors involved in causing this heart defect.
Conclusion:
One of the important results of this study was that the diagnostic findings of ultrasound were normal, but the findings of echocardiography were reported as abnormal. This shows that fetal echocardiography is better than ultrasound imaging in diagnosing ectopia cordis. In addition, it is recommended that pregnant women should avoid taking folic acid after the first trimester of pregnancy.
... For the sake of reducing the risk of NTDs, supplementation of folic acid has been recommended before and during the first three months of pregnancy (McStay et al., 2017). The recommended daily dose of folic acid depends on the patient's history of birth abnormalities; the recommended preventative daily allowance of folic acid for women with no prior history of birth defects dose is 4.0 mg per day starting at least 30 days before conception and continuing throughout the first trimester of pregnancy (Al-Mashhadane et al., 2018). ...
There is a recent rise in the number of birth defects. This could be related to folic acid deficiency. Folic acid, as an antioxidant, is an important factor in preventing birth defects during embryonic development. This study, via content uniformity measurements and medical history, aimed to investigate the role of folic acid before and during pregnancy and to measure the content uniformity of different brands of folic acid tablets. The statistical study aimed to determine the relationship between folic acid consumption, miscarriage, and anomalies in newborn babies. The study studied a sample of 300 women based on their medical records. There was no significant effect (p-value = 0.143) of folic acid consumption on the frequency of anomalies. On the other hand, there was a high significant relation (p-value = 0.003) between folic acid consumption and miscarriage. The correlation, principally with miscarriage, coincides with previous studies and highlights the importance of folic acid supplementation before and during gestation. Content uniformity measurements were made on three famous folic acid brands (Folic Acid-Nile, Folicum-Julphar and Wockhardt-UK) available at local pharmacies. Measurements on the three folic acid brands were conducted in compliance with the British Pharmacopoeia (BP) (2010) test for content uniformity. Ten tablets from each brand were tested using the UV spectrophotometric method. The results showed that only the first brand name passed the content uniformity test, while the other two brands did not comply with the standards. This result highlights the problem of under-dosing in commercially available folic acid dosage forms, and identifies the need for taking action towards the implementation of quality control on all medical drugs.
... Folic acid is a small water-soluble molecule that is present in artificially enriched foods and pharmaceutical vitamins [20]. Among the benefits of folic acid is the prevention of the development of cancer and the prevention of megaloblastic anemia during pregnancy [21]. Folic acid also plays an important role in DNA synthesis and cell division [22]. ...
Levothyroxine (LT4) is known for its use in various conditions including hypothyroidism. LT4 interaction with serum albumin may be influenced by the presence of vitamins. For this reason, we investigated the effect of vitamin C, vitamin B12, and folic acid on the complex of Bovine Serum Albumin with LT4 (BSA-LT4). UV-Vis spectroscopy was used to monitor the influence of vitamins on the BSA-LT4 complex. Fluorescence spectroscopy revealed a static quenching mechanism of the fluorescence of BSA-LT4 complex by the vitamin C and folic acid and a combined mechanism for vitamin B12. The interaction of vitamin C and folic acid with BSA-LT4 was moderate, while the binding of vitamin B12 was much stronger, extending the storage time of LT4 in blood plasma. Synchronous fluorescence found that the vitamins were closer to the vicinity of Trp than to Tyr and the effect was more pronounced for the binding of vitamin B12. The thermal stability of the BSA-LT4 complex was more evident, but no influence on the stability of BSA-LT4 complex was obtained for vitamin C. Molecular docking studies showed that vitamin C and folic acid bound the same site of the protein, while vitamin B12 bonded to a different site.
... Folate is required for metabolic processes and neural development. The necessity of folic acid supplementation before and throughout pregnancy on fetal development is known (Al-Mashhadane, Al-Mashhadane, & Taqa, 2018). ...
Since deltamethrin (DM) is hydrophobic and lipophilic, it easily accumulates in the body, causing increased ROS production and DNA damage. Therefore, mitochondrial energy depletion, DNA fragmentation and apoptosis develop in the cell. The aim of our study is to investigate the effect of deltamethrin administered to rats during pregnancy on cellular adhesion in the gingiva. It was divided into two groups as control and Delthametrin groups. The control group was fed with physiological saline, water and feed. The experimental group was given 30 mg/kg deltamethrin in 0.5 ml saline orally. After the animals were mated, vaginal smears were taken and detected on the first day of pregnancy. After the 6th day, DTM was given by oral gavage between 6-21 days. At the end of pregnancy, a gingival fragment was removed from the anterior incisors and stained with H.E after routine histological follow-up. E-cadherin antibody was used for immunohistochemistry. Significant changes in the gingival epithelium were observed in the comparison of the control group and the group administered deltamethrin. In epithelial cells close to the basement membrane, degenerative cell structure and pycnotic nuclei were found with hyperplasia. The underlying blood vessels were dilated and congested, with a marked thickening of the basement membrane. E-Cadherin expression increased in the delthametrin group in the control group, and cell adhesion was significantly affected. It is thought that deltamethrin, which is an effective insecticide by ingestion, especially used in vegetables and fruits, is a toxic substance that affects cell adhesion in the gingiva and may have a negative effect on tooth development with significant bleeding in the gingiva when contaminated during pregnancy.
Besin Takviyesi ve Sağlıklı Beslenmenin Besin Takviyeleri ile İlişkisi Şenol YILDIZ A, D, E, K Vitaminleri Ayşegül FİDANCI C Vitamini Emel UNUTMAZ DUMAN B1, B2 ve B3 Vitaminleri Kübra YİĞİT B5, B6, B7 Vitaminleri Muteber Gizem KESER Folik Asit Gizem Ece DERİCİ B12 Vitamini (Kobalamin) Ekin BAL EPA, DHA, DPA Feyza Nur PAKSOY Konjuge Linoleik Asit Elif YILDIRIM Selenyum Ece KUTSAL İyot Gözde ERGENE Çinko Hatice Ece AKGÜN Kalsiyum Serap ANDAÇ ÖZTÜRK Pınar ÇAĞLAYAN URAL Demir Selin UÇAK Magnezyum Büşranur AKPINAR Kurkumin ve Ginkgo Biloba Esin Zekiye ERGİN Sarı Kantaron (St John’s Wort), Resveratrol ve Ginseng Rumeysa ÇEKER Glukozamin ve Kolajen Kübra YİĞİT Probiyotikler Hümeyra GÜNGÖR
Today, public organizations as well as private enterprises are expected to attach
importance to efficiency, economy and performance indicators in management processes. Universities, like other institutions, should measure the extent to which they have achieved their strategic goals and plan their management processes according to their performance results. These measurements can only be made with performance management models. With the Balanced Scorecard, which is one of the most widely used performance management models, universities can measure their performance from four dimensions: financial (resources), customer (public), internal processes, learning and growth (development). The Balanced Scorecard uses two tools; One of the tools is the strategy map. The strategy map is a diagram that graphically depicts managers' views on the organization's strategy and the cause-effect relationship between objectives in terms of four outcome cards. The second tool is the result cards for each objective in the strategy map, which include measurement, target and current performance data.
In this study, it is explained how to develop the Balanced Scorecard, how to apply it
to universities based on the example of Adiyaman University in Turkey and explains the
application results. Thus, the aim of the study is to provide a performance model that can
help management activities in universities. In this respect, hypothesis of this study is that ―performance management implementation in universities will facilitate participation, transparency and accountability. To reach the necessary scientific data, indirect research method is employed in the study. The most important result achieved from the study is that ―utilizing performance management models increases institutional effectiveness and productivity, and consequently institutional performance in a university.
Keywords: Performance Management, Balanced Scorecard, Performance Management in Universities
COVID-19 has left the world in a condition of uncertainty. Physical as well as the human resources (HR) of an organization were adversely affected during the lockdown. To mitigate the COVID-19’s consequences many organisations accepted the challenges and developed a new remote work modality on an emergency basis, to enhance employee productivity and engagement. The objective of the current study is to examine the impact of “Work from Home” (WFH) on Employees Productivity (EP) and Employee Engagement (EE). Questionnaires were collected from Multi-National Companies in India with a sample size of 110. SPSS analyses were conducted to test the proposed hypotheses. Results revealed that WFH has implications on employee’s productivity and engagement. This current study has provided suggestions and practical implications for further developing employee’s productivity and engagement. The findings also suggest key issues for organizations that need to adapt to the changing business environment, employee engagement, and hybrid work arrangements. The current study contributes to the extant literature of organizational behaviour body of knowledge.
Background:
Although low levels of folate leads to disturbances in DNA replication, DNA methylation and DNA repair, the association between dietary folate intake and head and neck cancer (HNC) risk remains unclear.
Methods:
We evaluated the association between folate intake and HNC risk using prospective cohort data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. This study included 101 700 participants and 186 cases with confirmed incident HNC. The median follow-up was 12.5 years. We estimated hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) using Cox proportional hazard model including age, sex, body mass index, education, race, tobacco smoking, alcohol drinking and total fruit and vegetable intake.
Results:
Higher intake of food folate and fortified folic acid in foods was associated with a decreasing HNC risk in a dose-response manner. The HRs of highest vs the lowest quartile of intake were 0.35 (95%CI: 0.18-0.67) for food folate, and 0.49 (95%CI: 0.30-0.82) for fortified folic acid. Intakes of total folate, natural folate and supplemental folic acid were not associated with the risk of HNC and its subsites. We did not detect any interaction between smoking, drinking and food folate intake on HNC risk.
Conclusions:
These findings provide evidence of the protective role of dietary folate intake on HNC risk.British Journal of Cancer advance online publication, 21 November 2017; doi:10.1038/bjc.2017.383 www.bjcancer.com.
Folate is required for metabolic processes and neural development. Insuring its adequate levels for pregnant women through supplementation of grain-based foods with synthetic folic acid (FA) in order to prevent neural tube defects has been an ongoing public health initiative. However, because women are advised to take multivitamins containing FA before and throughout pregnancy, the supplementation together with natural dietary folates has led to a demographic with high and rising serum levels of unmetabolized FA. This raises concerns about the detrimental effects of high serum synthetic FA, including a rise in risk for autism spectrum disorder (ASD). Some recent studies have reported a protective effect of FA fortification against ASD, but others have concluded there is an increased risk for ASD and other negative neurocognitive development outcomes. These issues are accompanied by further health questions concerning high, unmetabolized FA levels in serum. In this review, we outline the reasons excess FA supplementation is a concern and review the history and effects of supplementation. We then examine the effects of FA on neuronal development from tissue culture experiments, review recent advances in understanding of metabolic functional blocks in causing ASD and treatment for these with alternative forms such as folinic acid, and finally summarize the conflicting epidemiological findings regarding ASD. Based on the evidence evaluated, we conclude that caution regarding over supplementing is warranted.
Viral bronchiolitis affects 20%-30% of infants; because there is no known effective treatment, it is important to identify risk factors that contribute to its pathogenesis. Although adequate folate intake during the periconceptional period prevents neural tube defects, animal data suggest that higher supplementation may be a risk factor for child respiratory diseases. Using a population-based retrospective cohort of 167,333 women and infants, born in 1995-2007 and enrolled in the Tennessee Medicaid program, we investigated the association between the filling of folic acid-containing prescriptions and infant bronchiolitis. We categorized women into the following 4 groups in relation to the first trimester: "none" (no prescription filled), "first trimester only," "after first trimester," and "both" (prescriptions filled both during and after the first trimester). Overall, 21% of infants had a bronchiolitis diagnosis, and 5% were hospitalized. Most women filled their first prescriptions after the fifth to sixth weeks of pregnancy, and most prescriptions contained 1,000 µg of folic acid. Compared with infants born to women in the "none" group, infants born to women in the "first trimester only" group had higher relative odds of bronchiolitis diagnosis (adjusted odds ratio = 1.17, 95% confidence interval: 1.11, 1.22) and greater severity (adjusted odds ratio = 1.16, 95% confidence interval: 1.11, 1.22). This study's findings contribute to an understanding of the implications of prenatal nutritional supplement recommendations for infant bronchiolitis.
Health authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. The objective of this study was to examine the association of folic acid supplementation during different periods of pregnancy and of dietary folate intake with the risk of spontaneous preterm delivery (PTD).
The Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 65,668 women with singleton pregnancies resulting in live births in 1999--2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until week 24 during pregnancy. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4--5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,628).
The median total folate intake was 266 mug/d (interquartile range IQR 154--543) in the overall population and 540 mug/d (IQR 369--651) in the supplement users. Eighty-three percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while 42% initiated folic acid supplementation before their pregnancy. Cox regression analysis showed that the amount of folate intake from the diet (hazard ratio HR 1.16; confidence interval 95% CI 0.65-2.08) and from the folic acid supplements (HR 1.04; CI 0.95-1.13) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for PTD (HR 1.19; CI 1.05-1.34) compared to no folic acid supplementation pre-conception. There was no significant association with PTD when supplementation was initiated within 8 weeks pre-conception (HR 1.01; CI 0.88-1.16). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables.
Our findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Pre-conceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.
Background:
Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted.
Methods/design:
This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4 mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings.
Discussion:
The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women. CLINICALTRIALS.GOV IDENTIFIER: NCT00397917.
Cleft palate only (CPO) is one of the most common congenital malformations worldwide. The etiopathogenesis of CPO is not completely understood. Environmental factors, such as smoking, alcohol consumption, intake of drugs during pregnancy, advanced paternal age, have been demonstrated to be a risk of CPO, but conflicting results have also been published. Insufficient intake of folic acid during the pregnancy has been suggested to increase the risk for CPO. The demonstrated risk for siblings and the higher risk for monozygotic twins suggest a genetic etiopathogenesis for CPO. In some cases of CPO a prevalent mode of inheritance has been reported, but oligogenic models with reduced penetrance, and the risk related to environmental factors have also been proved. One of the first manifestations associated with CPO is difficulty with feeding. Aerophagia is a problem in these infants with CPO and requires more frequent burping and slower feeding. The inability to generate intraoral breath pressure due to nasal air emission in CPO children frequently manifests as articulation difficulties, particularly consonant weakness, and unintelligible speech. Hearing disorders are prevalent among individuals with CPO, as a result of chronic otitis media with effusion due to eustachian tube dysfunction. A multidisciplinary team is essential to manage the many aspects of CPO. In treating CPO, the reconstructive surgeon works in cooperation with otolaryngologists, dentists and orthodontists, speech pathologists, audiologists, geneticists, psychiatrists, maxillofacial surgeons, social workers, and prosthodontists. CPO can be considered a genetically complex disease, but new knowledge and new therapeutic approaches have greatly improved the quality of life of these children. Prenatal diagnosis is an important step in the treatment of this disease.
Previous epidemiological studies of circulating folate concentration and colorectal cancer have reported inconsistent results. We evaluated associations of pre-diagnostic plasma folate concentration with colorectal cancer risk in a case-control study nested within the Shanghai Men's Health Study (2002-2010). Included herein are 288 cases who were diagnosed with incident colorectal cancer and 575 controls who were individually matched to cases on baseline characteristics. Folate concentrations in plasma were measured by microbiological assay. Multivariate conditional logistic regression was used to assess associations of plasma folate concentrations with colorectal cancer risk. Plasma folate was non-significantly but positively associated with colorectal cancer risk. Odds ratios (OR) and 95% confidence intervals (CI) were 1.38 (0.95-2.02) for the middle tertile of plasma folate concentrations and 1.33 (0.90-1.98) for the highest compared with the lowest tertile. The positive association reached statistical significance for the highest tertile of folate concentrations for men with late-stage colorectal cancer (OR=2.66; 95% CI=1.03-6.86) and for the middle tertile for cases diagnosed within the first 4 years after blood collection (OR=1.72; 95% CI=1.02-2.92) and for men in the high BMI group (OR=1.88; 95% CI=1.14-3.11). In our study population, where folic acid fortification of the food supply and vitamin supplement use are uncommon, plasma folate concentration was positively associated with colorectal cancer risk among men who may have had preneoplastic lesions. These findings need to be confirmed in studies with specific assessment of preneoplastic lesions and repeated measurements of folate level over time. © 2014 Wiley Periodicals, Inc.
Folate was identified as an essential micronutrient early in the twentieth century and anti-folate chemotherapy such as 5-fluorouracil (5-FU) has been central to the medical management of solid tumours including colorectal cancer for more than five decades. In the intervening years, evidence has been gathered which shows that folate deficiency leads to many human diseases throughout the life-course. However, we still do not know all of the mechanisms behind functional folate deficiency, or indeed its rescue through supplementation with natural and particularly synthetic folates. There is growing evidence that one adverse effect of folic acid fortification programmes is an increased risk of colorectal cancer within populations. The complexity of folate-dependent, one-carbon metabolism and the heterogeneity that exists between individuals with respect to the enzymes involved in the anabolic pathways, and the catabolism of 5-FU, are explored in this review. The enzyme products of some genes such as MTHFR exert multiple and perhaps unrelated effects on many phenotypes, including cancer development. We describe this pleiotropy and the common genetic variants that affect folate metabolism; and discuss some of the studies that have investigated their potential as predictive biomarkers.
Folic acid-containing multivitamins have been associated with a reduced risk of preterm birth. We examined whether periconceptional use of folic acid alone reduced this risk.
Data were derived from a large population-based cohort study conducted in China to evaluate the prevention of neural tube defects with folic acid supplementation. The sample comprised 207 936 singleton live births delivered at gestational ages of 20-42 weeks to women from two provinces in southern China. Healthcare workers recorded folic acid intake prospectively each month. Gestational age calculation was based on the first day of the last menstrual period. Preterm births were categorized into three clinical subtypes: iatrogenic preterm birth, preterm premature rupture of membranes (PPROM) and spontaneous preterm birth. Logistic regression was used to evaluate the association between folic acid use and the risk of preterm birth, adjusting for potential confounders.
The incidence of preterm birth was significantly lower among folic acid users (5.28%) than among non-users (6.10%). Folic acid use showed a 14% risk reduction for preterm birth overall [adjusted risk ratio (RR) = 0.86, 95% confidence interval (CI) 0.82-0.90]. This association was strongest for spontaneous preterm birth (adjusted RR = 0.81, 95% CI 0.78-0.86) and was not significant for iatrogenic preterm birth (adjusted RR = 0.97, 95% CI 0.88-1.07) or PPROM (adjusted RR = 1.07, 95% CI 0.93-1.23).
Daily intake of 400 μg folic acid alone during the periconceptional period was associated with a reduced risk of spontaneous preterm birth.
Folic acid is a water-soluble B-complex vitamin. Increasing evidence demonstrates that physiological supply of folic acid during pregnancy prevents from folic acid deficiency-related neural tube defects (NTDs). Previous studies showed that maternal lipopolysaccharide (LPS) exposure caused NTDs in rodents. The aim of this study was to investigate the effects of high-dose folic acid supplementation during pregnancy on LPS-induced NTDs. Pregnant mice were intraperitoneally injected with LPS (20μg/kg/d) from gestational day (GD) 8 to GD12. As expected, a five-day LPS injection resulted in 19.96% of fetuses with NTDs. Interestingly, supplementation with folic acid (3mg/kg) during pregnancy significantly alleviated LPS-induced NTDs. Additionally, folic acid significantly attenuated LPS-induced fetal growth restriction and skeletal malformations. Additional experiment showed that folic acid attenuated LPS-induced glutathione (GSH) depletion in maternal liver and placentas. Moreover, folic acid significantly attenuated LPS-induced expression of placental MyD88. Additionally, folic acid inhibited LPS-induced c-Jun NH2-terminal kinase (JNK) phosphorylation and nuclear factor kappa B (NF-κB) activation in placentas. Correspondingly, folic acid significantly attenuated LPS-induced tumor necrosis factor (TNF) -α, interleukin (IL) -1β and IL-6 in placentas, maternal serum and amniotic fluid. In conclusion, supplementation with high-dose folic acid during pregnancy protects against LPS-induced NTDs through its anti-inflammatory and anti-oxidative effects.