Effect Of Folic Acid Supplementation Research Articles

Effects of folic acid supplementation on C-reactive protein: A systematic review and meta-analysis of randomized controlled trials

Background and aimGiven the contradictory results of previous randomized controlled trials (RCTs), we performed a systematic review and meta-analysis to quantify and summarize the effects of folic acid supplementation on C-reactive protein (CRP). Methods and resultsWe performed a systematic search of all available RCTs conducted up to October 2018 in the following databases: PubMed, Scopus, and Cochrane. RCTs that investigated the effect of folate on CRP were included in the present study. Data were combined with the use of generic inverse-variance random-effects models. Statistical heterogeneity between studies was evaluated using Cochran's Q-test. Ten RCTs (1179 subjects) were included in the present meta-analysis. Pooled analysis results showed that folate supplementation significantly lowered the serum CRP level (weighted mean difference (WMD): −0.685 mg/l, 95% CI: −1.053, −0.318, p < 0.001). However, heterogeneity was significant (I2 = 96.7%, p = 0.000). Stratified analyses indicated that sex, intervention period, and type of study population were sources of heterogeneity. Following analysis, results revealed that the greatest impact was observed in women (WMD: −0.967 mg/l, 95% CI: −1.101, −0.833, p = 0.000), patients with type 2 diabetes mellitus (WMD: −1.764 mg/l, 95% CI: −2.002, −1.526, p = 0.000), and intervention period less than 12 weeks (WMD: −0.742 mg/l, 95% CI: −0.834, −0.650, p = 0.000). ConclusionThis meta-analysis suggested that folic acid supplementation could significantly lower the serum CRP level. Folic acid leads to greater CRP lowering effect in women, patients with T2DM, and those with less than 12-week intervention.

Maternal Folic Acid Supplementation and the Risk of Oral Clefts in Offspring.

There is controversial evidence from the literature regarding the protective effect of folic acid supplementation during pregnancy against orofacial clefts. The authors undertook this meta-analysis to assess whether folate supplementation during pregnancy can reduce the risk of nonsyndromic cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO) in infants. Eligible articles were identified by searching databases, including PubMed, Medline, Scopus, ISI (Web of Knowledge) to September 2017. A meta-analysis was performed to evaluate the effects of maternal supplementation on oral clefts. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using Stata software. Publication bias was assessed by the Begg and Egger test. (Registration ID: CRD42018083922) RESULTS:: Out of the 1630 articles found in the authors' initial literature searches, 6 cohort studies, and 31 case-control studies were included in the authors' final meta-analysis. The results of the main analysis revealed that maternal folate supplementation was associated with a modest but statically significant decreased risk of all cleft subtypes (OR = 0.69, 95% CI: 0.60, 0.78). Folic acid intake alone was inversely associated with CL/P (OR = 0.73, 95% CI: 0.62-0.85,) but to a lesser extent than CPO (OR = 0.75, 95% CI = 053-1.04). Multivitamin intake had a significant protective effect for CL/P (OR = 0.65 95% CI = 0.55-0.80) as well as CPO (OR = 0.69, 95% CI = 0.53-0.90). Our results indicate that maternal supplementation in early pregnancy reduces the risk of nonsyndromic CL/P and CPO in infants. These data can serve to reassure women planning a pregnancy to consume multivitamins during the periconception period to protect against oral clefts.

Verbal abilities in children of mothers with epilepsy: Association to maternal folate status.

ObjectiveTo examine the effect of maternal folic acid supplementation and maternal plasma folate and antiepileptic drug (AED) concentrations on language delay in AED-exposed children of mothers with epilepsy.MethodsChildren of mothers with and without epilepsy enrolled from 1999 to 2008 in the Norwegian Mother and Child Cohort study were included. Information on medical history, AED use, and folic acid supplementation during pregnancy was collected from parent-completed questionnaires. Maternal plasma folate and maternal plasma and umbilical cord AED concentrations were measured in blood samples from gestational weeks 17 to 19 and immediately after birth, respectively. Language development at 18 and 36 months was evaluated by the Ages and Stages Questionnaires.ResultsA total of 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy were surveyed. For those with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratio (OR) for language delay in AED-exposed children compared to the controls at 18 months was 3.9 (95% confidence interval [CI] 1.9–7.8, p < 0.001) and at 36 months was 4.7 (95% CI 2.0–10.6, p < 0.001). When folic supplementation was used, the corresponding ORs for language delay were 1.7 (95% CI 1.2–2.6, p = 0.01) and 1.7 (95% CI 0.9–3.2, p = 0.13), respectively. The positive effect of folic acid supplement use on language delay in AED-exposed children was significant only when supplement was used in the period from 4 weeks before the pregnancy and until the end of the first trimester.ConclusionFolic acid use early in pregnancy may have a preventive effect on language delay associated with in utero AED exposure.

Folic acid supplementation improves vascular endothelial function, yet not skin blood flow during exercise in the heat, in patients with heart failure.

Heart failure (HF) patients are susceptible to heat strain during exercise, secondary to blunted skin blood flow (SkBF) responses, which may be explained by impaired nitric oxide (NO)-dependent vasodilation. Folic acid improves vascular endothelial function and SkBF through NO-dependent mechanisms in healthy older individuals and patients with cardiovascular disease. We examined the effect of folic acid supplementation (5 mg/day for 6 wk) on vascular function [brachial artery flow-mediated dilation (FMD)] and SkBF responses [cutaneous vascular conductance (CVC)] during 60 min of exercise at a fixed metabolic heat production (300 ẆHprod) in a 30°C environment in 10 patients with HF (New York Heart Association Class I-II) and 10 healthy controls (CON). Serum folic acid concentration increased in HF [preintervention (pre): 1.4 ± 0.2; postintervention (post): 8.9 ± 6.7 ng/ml, P = 0.01] and CON (pre: 1.3 ± 0.6; post: 5.2 ± 4.9 ng/ml, P = 0.03). FMD improved by 2.1 ± 1.3% in HF ( P < 0.01), but no change was observed in CON postintervention ( P = 0.20). During exercise, the external workload performed on the cycle ergometer to attain the fixed level of heat production for exercise was similar between groups (HF: 60 ± 13; CON: 65 ± 20 external workload, P = 0.52). Increases in CVC during exercise were similar in HF (pre: 0.89 ± 0.43; post: 0.83 ± 0.45 au/mmHg, P = 0.80) and CON (pre: 2.01 ± 0.79; post: 2.03 ± 0.72 au/mmHg, P = 0.73), although the values were consistently lower in HF for both pre- and postintervention measurement intervals ( P < 0.05). These findings demonstrate that folic acid improves vascular endothelial function in patients with HF but does not enhance SkBF during exercise at a fixed metabolic heat production in a warm environment.

Folic Acid Supplementation Attenuates Chronic Hepatic Inflammation in High-Fat Diet Fed Mice.

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide. Hepatic inflammation is an important pathogenic mediator of NAFLD. There is currently no pharmacological agent approved for the treatment of NAFLD. Folic acid is a water-soluble B vitamin that has been shown to have lipid-lowering and antioxidant effects. The objective of this study was to investigate the effect of folic acid supplementation on hepatic inflammation and to identify the underlying mechanisms. Male C57BL/6 J mice were fed a control diet (10% kcal fat), a high-fat diet (HFD) (60% kcal fat), or a HFD supplemented with folic acid (26 mg/kg diet) for 8 weeks. HFD feeding led to increased body mass gain, lipid accumulation, activation of transcription factor nuclear factor-κB (NF-κB), and elevation of inflammatory cytokine gene expression in the liver. Folic acid supplementation attenuated hepatic lipid accumulation and aggregation of inflammatory foci induced by HFD feeding. This was associated with a significant reduction of NF-κB activation and inflammatory cytokine expression. These results suggest that the hepatoprotective effect of folic acid in NAFLD may be attributed, in part, to its anti-inflammatory action.

Folic acid supplementation does not attenuate thermoregulatory or cardiovascular strain of older adults exposed to extreme heat and humidity.

What is the central question of this study? Does folic acid supplementation alleviate thermoregulatory and cardiovascular strain of older adults during exposure to extreme heat and humidity? What is the main finding and its importance? Folic acid supplementation for 6weeks did not affect whole-limb blood flow/vasodilatation, core and skin temperatures, heart rate, blood pressure and cardiac output. Thus, 6weeks of folic acid supplementation does not alleviate thermoregulatory or cardiovascular strain of healthy older adults exposed to extreme heat and humidity. Folic acid supplementation reverses age-related reductions in cutaneous vasodilatation during passive heating. However, it is unknown if folic acid supplementation alleviates thermoregulatory and cardiovascular strain experienced by older adults during heat exposure. We evaluated the effect of folic acid supplementation on thermoregulatory and cardiovascular responses of nine healthy older adults (61-72years, 3 males/6 females) exposed to extreme heat and humidity. Participants rested at 42°C while relative humidity was increased from 30% to 70% in 2% increments every 5min. The protocol was performed before (CON) and after (FOLIC) 6weeks of folic acid supplementation (5mgday-1 ). Local cutaneous vascular conductance (CVC, laser-Doppler flowmetry), forearm vascular conductance (FVC, Doppler ultrasound), mean skin and oesophageal temperatures, heart rate, blood pressure and cardiac output were measured. Folic acid supplementation increased fasting serum folate concentrations (P<0.01). Absolute CVC was greater throughout the protocol following supplementation (CON: 1.29±0.16unitsmmHg-1 vs. FOLIC: 1.65±0.24unitsmmHg-1 , P<0.01). However, normalized CVC (CON: 54±8% vs. FOLIC: 59±7%, P=0.22), FVC (CON: 3.47±0.76mlmmHg-1 vs. FOLIC: 3.40±0.56mlmmHg-1 , P=0.93), mean skin (P=0.81) and oesophageal (CON: 36.87±0.28°C vs. folic: 36.90±0.25°C, P=0.98) temperatures, heart rate (CON: 83±10beatsmin-1 vs. FOLIC: 84±8beatsmin-1 , P=0.64), blood pressure (P=0.71) and cardiac output (P=0.20) were unaffected by folic acid supplementation. These results demonstrate that 6weeks of folic acid supplementation does not alleviate thermoregulatory or cardiovascular strain of healthy older adults exposed to extreme heat and humidity.

A bacterial route for folic acid supplementation

BackgroundTo prevent folate deficiencies, many countries supplement various foodstuffs with folic acid. This compound is a synthetic oxidised folate that differs from naturally occurring reduced folates in its metabolism and uptake. Notably, safety reviews of folic acid supplementation have not considered interactions with gut bacteria. Here, we use the Caenorhabditis elegans – Escherichia coli animal– microbe model to examine a possible bacterial route for folic acid uptake. It has been assumed that supplements are taken up directly by the worm, especially because E. coli is unable to take up folates. However, E. coli, like many other bacteria, can transport the folate breakdown product, para-aminobenzoate-glutamate (PABA-glu), via AbgT and use it for bacterial folate synthesis. This pathway may impact host health because inhibition of bacterial folate synthesis increases C. elegans lifespan.ResultsFolic acid supplementation was found to rescue a C. elegans developmental folate-deficient mutant; however, a much higher concentration was required compared to folinic acid, a reduced folate. Unlike folinic acid, the effectiveness of folic acid supplementation was dependent on the E. coli gene, abgT, suggesting a bacterial route with PABA-glu uptake by E. coli as a first step. Surprisingly, we found up to 4% PABA-glu in folic acid preparations, including in a commercial supplement. Via breakdown to PABA-glu, folic acid increases E. coli folate synthesis. This pathway restores folate synthesis in a bacterial mutant defective in PABA synthesis, reversing the ability of this mutant to increase C. elegans lifespan.ConclusionsFolic acid supplementation in C. elegans occurs chiefly indirectly via bacterial uptake of breakdown products via E. coli AbgT, and can impact C. elegans development and longevity. Examining how folic acid supplementation affects bacterial folate synthesis in the human gut may help us to better understand the safety of folic acid supplementation.

PR074: The effects of folic acid supplementation on novel biomarkers of the endothelial function in rats with experimental periodontitis

PR074: The effects of folic acid supplementation on novel biomarkers of the endothelial function in rats with experimental periodontitis

Effects of maternal folic acid supplementation on airway remodeling and allergic airway disease development

Objective: Maternal folic acid supplementation has been recommended prior to and during the first trimester of pregnancy to reduce the risk of infant neural tube defects. However, an uncertain relationship between folic acid supplementation during pregnancy and development of childhood asthma exists. Recent data show a methyl donor-rich diet could increase the risk of developing allergic airway disease through DNA methylation and aberrant gene transcription. This study evaluated the effect of folic acid supplementation during pregnancy on airway remodeling and allergic airway disease vulnerability in a mouse asthma model.Methods: BALB/c mice were divided into four groups according to gestational folic acid supplementation and postnatal ovalbumin (OVA) exposure: Group 1 (whole pregnancy folic acid supplementation + OVA-exposed group), Group 2 (first gestational week folic acid supplementation + OVA-exposed group), Group 3 (no folic acid supplementation + OVA-exposed group), and Group 4 (control group). Offspring were sacrificed on day 45 for immunohistological and ultrastructural tests.Results: In OVA challenged groups, folic acid supplementation led to a thicker epithelial and subepithelial smooth muscle layer than in the unsupplemented group. Moreover, folic acid supplementation during whole pregnancy (Group 1) was associated with a thicker epithelial and subepithelial smooth muscle layer than folic acid supplementation during the first week of pregnancy (Group 2), suggesting a duration–response relationship. Electron microscopic imaging revealed that structural changes including the loss of epithelial integrity, thickening of basement membrane, and subepithelial fibrosis were more prominent in the folic acid supplementation groups.Conclusions: This study suggested that maternal folic acid supplementation during pregnancy affects airway remodeling and increases the allergic responses induced by ovalbumin challenge in offspring. In addition, the effect size increased as the duration and cumulative dose increased.

Folic Acid Supplementation throughout pregnancy: psychological developmental benefits for children.

To test the effect of folic acid supplements taken throughout pregnancy on children's psychosocial development. A randomised controlled trial of folic acid supplementation in pregnancy, with parental rating using the Resiliency Attitudes and Skills Profile (RASP), the Strengths and Difficulties Questionnaire (SDQ) and the Trait Emotional Intelligence Questionnaire Child Short Form (TEIQue-CSF). Children aged 6-7 whose mothers received folic acid throughout pregnancy (n = 22) were compared to those whose mothers only received it during the first trimester (n = 17). Children whose mothers received the full-term supplement scored significantly higher on emotional intelligence and resilience. Hierarchical multiple regression analysis identified folate level at 36th gestational week as an important predictor of emotional intelligence (EI) and resilience. Although conclusions must be drawn with caution, this research presents a number of potential implications, the main one being a proposed policy recommendation for women to take folic acid for the duration of pregnancy rather than stopping at the end of the first trimester. The second is the potential for future research to explore the possible psychological and social development benefits and in line with this to try and identify the explanatory mechanism involved.

The effect of vitamin B12 and folic acid supplementation on routine haematological parameters in older people: an individual participant data meta-analysis.

Low vitamin B12 and folate levels in community-dwelling older people are usually corrected with supplements. However, the effect of this supplementation on haematological parameters in older persons is not known. Therefore, we executed a systematic review and individual participant data meta-analysis of randomised placebo-controlled trials (RCTs). We performed a systematic search in PubMed, EMBASE, Web of Science, Cochrane and CENTRAL for RCTs published between January 1950 and April 2016, where community-dwelling elderly (60+ years) who were treated with vitamin B12 or folic acid or placebo. The presence of anaemia was not required. We analysed the data on haematological parameters with a two-stage IPD meta-analysis. We found 494 full papers covering 14 studies. Data were shared by the authors of four RCTs comparing vitamin B12 with placebo (n = 343) and of three RCTs comparing folic acid with placebo (n = 929). We found no effect of vitamin B12 supplementation on haemoglobin (change 0.00 g/dL, 95% CI: -0.19;0.18), and no effect of folic acid supplementation (change -0.09 g/dL, 95% CI: -0.19;0.01). The effects of supplementation on other haematological parameters were similar. The effects did not differ by sex or by age group. Also, no effect was found in a subgroup of patients with anaemia and a subgroup of patients who were treated >4 weeks. Evidence on the effects of supplementation of low concentrations of vitamin B12 and folate on haematological parameters in community-dwelling older people is inconclusive. Further research is needed before firm recommendations can be made concerning the supplementation of vitamin B12 and folate.

Correction: The Effects of Folate Supplementation on Diabetes Biomarkers Among Patients with Metabolic Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Correction: The Effects of Folate Supplementation on Diabetes Biomarkers Among Patients with Metabolic Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The Effects of Folate Supplementation on Diabetes Biomarkers Among Patients with Metabolic Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Although several studies have evaluated the effect of folate supplementation on diabetes biomarkers among patients with metabolic diseases, findings are inconsistent. This review of randomized controlled trials (RCTs) was performed to summarize the evidence on the effects of folate supplementation on diabetes biomarkers among patients with metabolic diseases. Randomized-controlled trials (RCTs) published in PubMed, EMBASE, Web of Science and Cochrane Library databases up to 1 September 2017 were searched. Two review authors independently assessed study eligibility, extracted data, and evaluated risk of bias of included studies. Heterogeneity was measured with a Q-test and with I2 statistics. Data were pooled by using the fix or random-effect model based on the heterogeneity test results and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). A total of sixteen randomized controlled trials involving 763 participants were included in the final analysis. The current meta-analysis showed folate supplementation among patients with metabolic diseases significantly decreased insulin (SMD -1.28; 95% CI, -1.99, -0.56) and homeostasis model assessment of insulin resistance (HOMA-IR) (SMD -1.28; 95% CI, -1.99, -0.56). However, folate supplementation did not affect fasting plasma glucose (FPG) (SMD -0.30; 95% CI, -0.63, 0.02) and hemoglobin A1C (HbA1c) (SMD -0.29; 95% CI, -0.61, 0.03). The results of this meta-analysis study demonstrated that folate supplementation may result in significant decreases in insulin levels and HOMA-IR score, but does not affect FPG and HbA1c levels among patients with metabolic diseases.

Effect of Folic Acid Supplementation and/or its Absence on Body Weight of Wistar Rats in Pregnancy and in their Offspring

Introduction: Foetal birth weight is the best predictor of pregnancy outcome as the growth restriction has been associated with high morbidity and mortality. The need of Folic Acid (FA) supplementation is essential during the period of pregnancy to prevent untoward effects on pregnancy related complication in mother and to prevent birth defects in foetus. Aim: To compare the effects of FA supplementation and FA absent diets during the pregnancy on maternal and their offspring body weight. Materials and Methods: This was a prospective study comprising of 18 Wistar albino rats procured from the Animal house, Manipal Academy of Higher Education, Karnataka, India, after the institutional ethical committee clearance. Rats were randomly divided into three groups and given different diets: Control group with normal diet, group with FA supplementation diet, and group with FA absent diet (with added succinyl sulfathiazole) for five weeks. Later the female adult Wistar rats could mate with male rats of their own strain and allowed the female to complete their pregnancy. After the delivery, delivered pups were counted for each rat and gross malformation in each pup were noted. Immediately after the delivery, all the pups born to each rat were weighed individually in digital weighing machine. Results: Among the pregnant dams the body weight gain was observed more in control group with an average weight of 40.56 gm, followed by diet with absent FA (32 gm) and least in rats fed with FA supplementation diets (31 gm). Average number of pups born to pregnant dams fed with FA supplementation, FA absent diet, and in normal diet was found to be 8, 8, and 9 respectively. Regarding the birth weight of pups born to pregnant dams fed with FA supplementation the average weight was found to be 6.01-5.09 gm, with normal diet it was 5.51-5.08 gm, and least weight was observed in pups born with FA absent diet (4.74-3.31 gm). Conclusion: The present study concluded that the FA status in pregnancy is inversely proportional to the prenatal death in pups but in offspring’s born to mothers fed with FA supplementation, average body weight was more than those born to mothers fed with FA absent diet and with control groups. However, this needs further confirmation as the tests were done on limited samples.

Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial.

Observational studies have frequently reported that low blood folate concentrations are associated with poor cognitive performance. Our previous studies have shown the potential beneficial effect on the metabolite levels of methionine cycle and peripheral blood inflammatory cytokines from 6- and 12-month folic acid supplementation on cognitive function in mild cognitive impairment (MCI). This study aims to continue exploring the effect of 24-month folic acid supplementation on cognitive function and pathological mechanism in MCI. 180 individuals with MCI were identified and randomly divided into intervention (folic acid 400µg/day, n = 90) and convention (n = 90) groups. Cognitive function (WAIS-RC) and blood Aβ-related biomarkers were measured at baseline and at 6, 12, 18, and 24 months. Data were analyzed using generalized estimating equation. This trial has been registered with Trial Number: ChiCTR-TRC-13003227. During the follow-up, scores of full scale IQ, verbal IQ, and subdomains of Information and Digit Span were significantly higher in the intervention group than those in the convention group (P < 0.05). In the intervention group, blood homocysteine, S-adenosylhomocysteine (SAH), Aβ-42, and the expression of APP-mRNA were decreased (P < 0.05), while S-adenosylmethionine (SAM), SAM/SAH ratio, and the expression of DNA methyltransferase mRNA were increased (P < 0.05). Folic acid supplementation appears to improve cognitive function and reduce blood levels of Aβ-related biomarkers in MCI. Larger-scale double-blind placebo-controlled randomized trials of longer duration are needed.

170 Effect of Folic Acid Supplementation on In Vitro Maturation of Oocytes and Folate Cycle

Folic acid (vitamin B9) is the principal component of one-carbon (C1) metabolism in mammalian cells. It acts as a coenzyme in C1 unit transfer during nucleotide and amino acid metabolism. Therefore, it is unquestionably essential for the formation of thymidylate (TMP) for DNA synthesis and methylation, which is in turn crucial for post-implantation embryonic brain and nerve chord development. However, the role of folic acid in maturation of oocytes and subsequent blastocyst production is largely ambiguous in different mammalian species. The aim of this study was to investigate the effect of folic acid supplementation on expression of oocyte maturation markers and folate cycle enzymes in cumulus cells in addition to blastocyst development rate in goat. Immature oocytes were isolated from ovaries, and 1600 oocytes were matured in maturation medium (medium-199) supplemented with 0 (control), 50, 100, or 150 µM folic acid (Sigma Aldrich, India), comprising total 400 oocytes in each group in 5 replicates. The oocytes were in vitro fertilized and embryos were cultured for 7 days. Blastocyst rate was calculated in all 4 groups. Cumulus cells from matured oocytes from each group were analysed for the differential expression of oocyte maturation markers: PTX3, PTGS2, CTSB, and CTSS, and folate cycle enzyme transcripts MTR, MAT2A, ACHY, DHFR, and SLC19A1, by qRT-PCR. For statistical analysis, one-way ANOVA was used. The results of present study show that blastocyst rate was significantly higher (P ≤ 0.05) at 50 µM folic acid (21.4 ± 1.2%) compared with control (13.6 ± 0.4%), 100 µM (10.4 ± 0.34%), and 150 µM (7.4 ± 0.54%). However, there was no effect on the number of cleaved embryos among control (72 ± 0.21%), 50 µM (70.6 ± 0.58%), 100 µM (73.75 ± 0.31%), and 150 µM (73.02 ± 0.04%). The expression of the oocyte maturation markers PTX3 and PTGS2 was up-regulated, whereas that of CTSS and CTSSB was down-regulated (P ≤ 0.05), in the 50 µM group, but did not change (P ≤ 0.05) among the other groups. The expression of these genes did not change significantly among the other groups. The expression of genes of the folate cycle, MTR, MAT2A, ACHY, and DHFR, increased (P ≤ 0.05) by 5.7-, 3.6-, 2.2-, and 1.7-fold, respectively, at 50 µM, but did not change (P ≤ 0.05) among the other groups. The expression of SLC19A1 did not change significantly among all the groups. The results of present study show that the supplementation of 50 µM folic acid to the maturation medium results in increased maturation of oocytes, making them more competent for the blastocyst development. Up-regulation of transcripts of folate cycle enzymes at 50 µM might explain the increase in the blastocyst production rate, which further needs to be validated.

Effect of Folate Supplementation on Inflammatory Markers in Individuals Susceptible to Depression: A Systematic Review

Folate has been proposed to be an efficacious treatment strategy for depression. The mandatory fortification of flour with synthetic folic acid (FA) in over 80 countries has yielded improvements in folate intake; however, depression is still a considerable public health concern. While there are established benefits of FA fortification in reducing risk of neural tube defects, the implications regarding depression are unclear, especially in individuals with certain genetic polymorphisms. Therefore, a systematic review was conducted to examine the effects of folate to treat depression. Following PRISMA guidelines, a systematic review was conducted of electronic databases (PUBMED, Scopus, CINAHL, and Cochrane Library) to identify human clinical trials examining the effects of folate (including FA) supplementation in the management or prevention of depression, the impact on inflammatory markers and if genetic polymorphisms were considered. Ten trials met the inclusion criteria. Seven trials examined effects of either adjunctive FA or L-methylfolate (L-MTHF) supplementation with antidepressants in the management of depression and three examined effects of FA supplementation alone for prevention of depression. No benefit of FA was found compared to placebo (all, p > 0.05). The single L-MTHF trial that explored the interplay of genetic polymorphisms and methylation status found benefit in the Hamilton depression rating scale from adjunctive treatment with 15 mg/day of L-MTHF compared with placebo (−6.8 ± 7.2 vs. −3.7 ± 6.5; p = 0.017) and improvement with L-MTHF for most genetic markers. Currently, there is no evidence to support FA supplementation for the management or prevention of depression. More research is required to determine the efficacy of L-MTHF and folinic acid in certain clinical populations.

Effect of supplementation with folic acid and B vitamins on cardiovascular outcomes: a meta-analysis of randomised controlled trials

BackgroundThere is an increasing amount of data over the effect of folic acid and B vitamins (vitamin B6 and B12) on cardiovascular disease, but whether supplementation with folic acid and B vitamins can reduce the risk of cardiovascular disease among middle-aged and elderly patients remains unclear. We conducted this meta-analysis to assess the efficacy of folic acid supplementation in the prevention of cardiovascular disease. MethodsWe searched PubMed and Web of Science for randomised controlled trials published between Jan 1, 1980, and Sept 1, 2015. We used relative risk (RR) with 95% CIs as a measure of effect of folic acid supplementation on the risk of cardiovascular disease. Data were independently extracted and sorted by two investigators to assess their quality. The results were pooled with a randomised-effects model using Stata 12.0 software. We used forest plots to analyse the effect of B vitamins as well as folic acid. FindingsWe included 22 randomised controlled trials reporting data on 79 564 participants. All participants were aged 45 years or older (ie, middle-aged or elderly). Supplementation with both folic acid and B vitamins together was not associated with any significant reduction in the risk of cardiovascular events (RR 0·98, 95% CI 0·92 to 1·03, p=0·353), myocardial infarction (1·00, 0·93 to 1·08, p=0·940), or total mortality (1·00, 0·94 to 1·06, p=0·778). However, a beneficial effect was observed for stroke, with supplementation with folic acid and B vitamins reducing the risk by 12% (RR 0·88, 95% CI 0·80 to 0·97, p=0·001). Moreover, we found that folic acid only could reduce the risk of cardiovascular events by 11% (RR 0·89, 95% CI 0·80 to 0·98, p=0·016) and the risk of stroke by 20% (0·80, 0·69 to 0·93, p=0·003). The level of homocysteine was reduced by 0·72 μmol/L (95% CI −1·00 to −0·44, p<0·0001). InterpretationSupplementation with folic acid with or without B vitamins is more beneficial for stroke than for other cardiovascular outcomes in middle-aged and elderly patients. Funding2012 Chinese Nutrition Society Nutrition Research Foundation—DSM Research Fund (2014-014); the Research Program of Shaanxi Soft Science (2015KRM117); the National High-Level Talents Special Support Plan (“Thousands of People Plan”); Shaanxi Provincial Youth Star of Science and Technology in 2016; and the Basic Scientific Research Funding of Xi'an Jiaotong University (SK2015007).

Effect of folate supplementation during 10 weeks of HIIT on serum levels of ghrelin and leptin in male Wistar rats

Effect of folate supplementation during 10 weeks of HIIT on serum levels of ghrelin and leptin in male Wistar rats

Folic acid modulates cancer-associated micro RNAs and inflammatory mediators in neoplastic and non-neoplastic colonic cells in a different way.

Scientific evidence suggests that folic acid (FA) supplementation protects the healthy colonic mucosa from neoplastic transformation but may promote the progression of precancerous lesions. The underlying molecular mechanisms are not fully understood. Therefore, we explored, if high physiological FA doses provoke changes in (i) promoter-specific DNA methylation (ii) expression of cancer-associated micro RNAs (miRNAs) and (iii) inflammatory mediators in human neoplastic and non-neoplastic colonic cell lines. The malignant and the non-malignant colonic cell lines HT29 and HCEC were adapted to different near-physiological FA concentrations. Using DNA methylation and pathway specific PCR arrays, high-physiological FA concentrations revealed no relevant impact on promoter methylation but a number of differences between the cell lines in the expression of miRNAs and inflammatory mediators. In the HCEC cell line pro-inflammatory genes were repressed and the miRNA expression remained nearly unaffected. In contrast, in the HT29 cell line tumour-suppressive miRNAs were predominantly down-regulated and the expression of genes involved in chemotaxis and immunity were modulated. The different effects of high-physiological FA concentrations in malignant and non-malignant colonic cell lines regarding cancer-associated miRNAs and inflammatory mediators may contribute to the different effects of FA supplementation on colonic carcinogenesis.