Folic Acid Group Research Articles

The Folic Acid and Creatine Trial: Treatment effects on arsenic metabolite concentrations in blood

Background and Aim. Arsenic exposure is a global issue. Inorganic As (InAs) undergoes methylation to monomethyl (MMAs) and dimethyl-arsenical species (DMAs); full methylation to DMAs facilitates urinary excretion and can reduce risk of adverse health outcomes. Folate and creatine influence one-carbon metabolism which provides methyl groups for As methylation. We investigated the effects of folic acid (FA) and/or creatine supplementation on As metabolites and primary (PMI: MMAs/InAs) and secondary (SMI: DMAs/MMAs) methylation indices in blood in Bangladeshi adults. Methods. In this double-blind, placebo-controlled trial, 622 participants (20% folate deficient) were randomized to receive FA (400 or 800 μg/day), 3 g creatine/day, 3 g creatine+400 μg FA/day, or placebo for 12 weeks. For the following 12 weeks, half of the FA participants received placebo. All participants received As-removal water filters. Results. Blood As metabolite concentrations decreased in all groups due to filter use. After 1 week, the mean within-person increase in SMI for the creatine+400FA group exceeded the placebo group. The mean decreases in blood concentrations of MMAs (bMMAs) between baseline and week 12 was greater for all treatment groups compared to placebo, and the increase in bDMAs concentrations for the FA treated groups exceeded that of placebo. The decrease in PMI and increase in SMI in all FA groups at week 12 exceeded placebo. Data from week 24 showed evidence of rebound from week 12, with decreases in SMI in those who switched from 800FA to placebo, whereas for those who remained on 800FA, PMI and bMMAs concentrations continued to decline. Conclusions. FA supplementation lowered bMMAs and increased bDMAs in adults in Bangladesh. Evidence of rebound in As methylation capacity following FA cessation suggests short-term benefits of supplementation and underscores the importance of long-term interventions such as FA fortification and As mitigation in drinking water. Keywords: Arsenic, Nutritional Intervention

Association between Folic Acid Supplementation and Hypertensive Disorder Complicating Pregnancy in Jiangsu Province: A Cross-Sectional Study

Objectives To investigate the association of folic acid (FA) supplementation with hypertensive disorder complicating pregnancy (HDCP) and preeclampsia in Jiangsu Province, China. Materials and Methods In this cross-sectional study, a total of 10,662 women with infants born between January 2017 and December 2018 were enrolled in Jiangsu Province, China. Maternal women with and without FA supplement intake were compared in this study. FA supplementation included 0.4 mg FA (0.4 FA), multivitamins with 0.4 mg FA (multivitamin (MV)+0.4 FA), and multivitamins with 0.8 mg FA (MV + 0.8 FA). Associations between FA intake, FA supplement dose or duration, (MV + FA) dosage per weight, and HDCP were analysed using ANOVA, the chi-square test, and logistic regression analysis. Results Over the study follow-up period, the incidences of HDCP and preeclampsia were 3.5%, 1.4%, and 2.2%, 0.6% in the non-FA supplementation and FA supplementation groups, but only 1.5% and 0.1% in the MV + 0.8 FA group in early pregnancy. Compared with the non-FA group, HDCP and preeclampsia had the lowest risk in the MV + 0.8 FA group among the seven FA supplementation groups (HDCP: RR = 0.42, 95% CI = 0.27-0.68, P=0.001; preeclampsia: RR = 0.09, 95% CI = 0.03–0.33, P=0.001) in early pregnancy. Compared with the 0.4 FA alone group, the risk of HDCP and preeclampsia in women taking MV + 0.8 FA was significantly reduced (RR = 0.60, 95% CI = 0.41–0.87, P=0.008; preeclampsia: RR = 0.18, 95% CI = 0.06–0.60, P=0.005) in early pregnancy. (MV + FA)/BMI supplementation was associated with the risk of HDCP in early pregnancy (P trend = 0.002). Conclusions MV supplement with 0.8 mg FA during early pregnancy may be effective in reducing HDCP and preeclampsia risk. The study provided the viewpoint that (MV + FA)/BMI could be used as a reference for FA intake in pregnant women of different weights.

Amino-functionalized cross-linked cellulosic fabric with antibacterial, UV protection, and coloring effects using folic acid

The amino-functionalized cellulose with folic acid, via an esterification reaction between carboxylic acid of folic acid and hydroxyl groups of cellulose, can develop multifunctional products with new chemical and physical properties. Folic acid contains two carboxylic groups as well as an amine group that can be used as a coupling agent and provide suitable conditions for coupling hydroxyl-based compounds to cellulose. Also; the multi-functionalized cellulose with folic acid has no effects on the physical and mechanical properties and also has benefits such as antibacterial, UV protection, and wrinkle resistance. The FTIR-ATR and Raman analysis confirmed the amino functionalized-cellulosic fabric via an esterification reaction between cellulose and folic acid. The cell viability of L929 fibroblast (NCBI C161) and MCF-7 (NCBI C135) cancer cells indicated more effectiveness on MCF-7 cancer cells. Therefore; folic acid can be used as a biocompatible natural cross-linker to modify cellulose fabrics for apparel and medical applications.

Effect of folic acid supplementation on diminished ovarian reserve: study protocol of a single-centre, open-label, randomised, placebo-controlled clinical trial

IntroductionThe prevalence of diminished ovarian reserve (DOR), a common gynaecological disorder, is approximately 10% across the world. Failure in early diagnosis and treatment may result in continuous decreases in ovarian...

Serum L-Carnitine Levels Are Associated With First Stroke in Chinese Adults With Hypertension.

This study aimed to evaluate the association of serum L-carnitine with first stroke and explore potential effect modifiers. This is a nested, case-control study drawn from the China Stroke Primary Prevention Trial among rural Chinese adults with hypertension, including 557 first stroke cases and 557 age-matched, sex-matched, treatment group-matched, and residence-matched controls. Serum L-carnitine was measured by liquid chromatography with tandem quadrupole mass spectrometry. Multiple conditional logistic regression models were used to evaluate the association between L-carnitine and first stroke. The mean level of serum L-carnitine in the stroke population was 4.7 μg/mL, which was significantly lower than that of the control group (5.7 μg/mL). When L-carnitine was assessed as quintiles, compared with the reference group (quintile 1, <3.3 μg/mL), the odds of stroke were 0.62 (95% CI, 0.39-1.00) in quintile 2, 0.66 (95% CI, 0.40-1.10) in quintile 3, 0.47 (95% CI, 0.28-0.81) in quintile 4, and 0.50 (95% CI, 0.30-0.84) in quintile 5. The trend test was significant (P=0.01). When quintiles 2 to 5 were combined, the adjusted odds ratio of first stroke was 0.58 (95% CI, 0.38-0.87) compared with quintile 1. Similar associations were found for ischemic stroke and hemorrhagic stroke. In subgroup analysis, a significant L-carnitine-stroke association was only observed in the normal folate group (P interaction, 0.039) and in the MTHFR CC genotype group (P interaction, 0.047). In this study of rural Chinese adults with hypertension, serum L-carnitine had an inverse but nonlinear association with first stroke. Folate status and the MTHFR C677T variant were significant effect modifiers of the association.

Folic Acid Preconditioning Alleviated Radiation-Induced Ovarian Dysfunction in Female Mice.

Radiological therapy/examination is the primary source of artificial radiation exposure in humans. While its application has contributed to major advances in disease diagnosis and treatment, ionizing radiation exposure is associated with ovarian damage. The use of natural products, either alone or as an adjunct, has become increasingly common for reducing the side effects of radiological therapy during disease treatment. Herein, we explored the protective effect of folic acid (FA), a widely used B vitamin, against radiation-induced ovarian injury and its mechanism of action. Female mice with normal ovarian function were randomly divided into control, FA, radiation, and radiation + FA groups. The intervention strategy included daily intragastric administration of FA (5 mg/kg) for 3 weeks prior to radiation exposure. Mice in the radiation and radiation + FA groups received a single dose of 5 Gy X-ray irradiation. Changes in the estrous cycle were then recorded, and ovarian tissues were collected. Pathophysiological changes as well as reproductive and endocrine-related indexes were determined via H&E staining, immunohistochemistry, Western blot, and ELISA. The reproductive performance and emotional symptoms of animals were also monitored. Our results indicated that FA intervention effectively alleviated ovarian damage, leading to more regular estrous cycles, lesser impairment of follicular morphology and endocrine status, as well as greater germ cell preservation. Reduced levels of oxidative stress, inflammation, and enhanced DNA repair were associated these changes. FA pre-administration improved the reproductive performance, leading to higher pregnancy rates and greater litter sizes. Further, the anxiety levels of animals were significantly reduced. Our results indicate that FA pre-administration significantly alleviates radiation-induced ovarian damage in rodents, highlighting its potential as a protective strategy against radiation exposure in the female population.

Folic acid effect on homocysteine, sortilin levels and glycemic control in type 2 diabetes mellitus patients

AimThe present study aimed to determine the folic acid supplement (FAS) effects on serum homocysteine and sortilin levels, glycemic indices, and lipid profile in type II diabetic patients.MethodA double-blind randomized controlled clinical trial have been performed on 100 patients with T2DM randomly divided into two groups that received either placebo or folic acid 5 mg/d for 12 weeks.ResultsFAS caused a significant decrease in homocysteine and sortilin serum levels (28.2% and 33.7%, P < 0.0001, respectively). After 3 months of intervention, 8.7% decrease in fasting blood glucose (P = 0.0005), 8.2% in HbA1c (P = 0.0002), 13.7% in serum insulin (P < 0.0001) and 21.7% in insulin resistance (P < 0.0001) were found in the folic acid group, however no significant difference was observed in the placebo group. Serum hs-CRP level showed significant positive associations with sortilin (r = 0.237, P = 0.018), homocysteine (r = 0.308, P = 0.002) and fasting blood glucose (r = 0.342, P = 0.000). There were no significant changes in lipid profile in both groups after 12 weeks.ConclusionFAS might be beneficial for reducing homocysteine and sortilin levels, enhancing glycemic control, and improved insulin resistance in patients with T2DM.

Resveratrol: A new approach to ameliorate hyperhomocysteinaemia-induced renal dysfunction.

Hypertension is a common cause of kidney injury and renal damage occurs earlier and is more serious in patients with hypertension and hyperhomocysteinaemia (HHCY). Folic acid (FA) is widely used to ameliorate the organ damage caused by HHCY. However, the effective dose of FA remains controversial and certain studies have suggested that FA increases the risk of cancer. Therefore, it is necessary to identify a safe, effective drug. Resveratrol (RSV) is a natural polyphenol antioxidant. Therefore, the present study explored the effects of RSV on renal damage in spontaneously hypertensive rats (SHRs) with HHCY and its potential underlying mechanism. SHRs were divided randomly into control, HHCY, HHCY + FA and HHCY + RSV groups. Blood pressure, plasma homocysteine, indexes of oxidative stress [serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels] and indexes of renal function [glomerular filtration rate (GFR) and urinary albumin creatinine ratio (UACR)] were assessed. The mRNA and protein expression levels of nephrin and NAPDH oxidase (NOX)2 and NOX4 were detected via reverse transcription-quantitative PCR and western blotting. The results demonstrated that there was no significant difference in BP (blood pressure) among the groups, while the levels of homocysteine (HCY) in the HHCY intervention groups were significantly increased compared with the control. Both FA and RSV decreased the level of HCY, but the decrease was more obvious in the HHCY + FA group. Compared with the control the serum SOD levels and GFR were significantly decreased in the HHCY group, whereas the serum MDA levels and UACR were significantly increased. Moreover, the NOX2 and NOX4 expression levels were significantly increased, whereas those of nephrin were significantly decreased in the HHCY group. The changes caused by HHCY were significantly counteracted in both the HHCY + FA and HHCY + RSV groups and the antioxidant effect was markedly stronger in the HHCY + RSV group. In conclusion, RSV, like FA, potentially improved the renal function damage aggravated by HHCY in SHRs. Furthermore, RSV improved renal function mainly via the inhibition of oxidative stress. RSV may be a potential safe and effective treatment for HHCY-induced hypertensive renal damage.

DAPAGLIFLOZIN’S EFFECT ON SERUM HOMOCYSTEINE IN PATIENTS WITH HYPERTENSION COMPLIACTED WITH INSULIN RESISTANCE

Objective: Most patients with hypertension complicate with insulin resistance (IR), which is one of risk factors of hypertension and can increase the level of serum homocysteine (hcy) by affecting hcy metabolic enzyme and insulin. Investigations in recent years have shown that hcy is an independent risk factor of cardiovascular diseases. At present, folic acid is the main drug used to reduce hcy, but its effection for hcy has obvious individual difference, which is closely related to individual genes. Moreover, folic acid (FA) is mostly used in patients with hcy beyond 15 mol/l, but hcy beyond 10 mol/l has had an adverse effect for cardiovascular system. Animal studies have shown that dapagliflozin can improve insulin resistance. Therefore, whether it can reduce hcy has become a new direction. Design and method: This study is a retrospective case-control study. Patients with highly serum hcy and hypertension complicated with insulin resistance are divided into two groups: dapagliflozin group and FA group. Before and after 12 weeks of treatment, the changes in serum hcy and IR index are measured and compared. Results: (1) The IR index and serum hcy levels are clearly lower in the dapagliflozin group after therapy, and the changement of IR index and the level of serum hcy has a significant relativity. (2) The IR index reduction is more noticeable in the dapagliflozin group than in FA group. (3) In dapagliflozin group, the standard deviation (SD) of serum hcy is lower than in the FA group. Conclusions: Dapagliflozin can reduce the serum hcy level of patients with hypertension and insulin resistance in a certain extent, also having an important effection in reducing IR. The lowering of serum hcy in the dapagliflozin group is more balanced than in the FA group. Dapagliflozin could be a viable option for these patients.

Association of Plasma Folate, Vitamin B12, and Betaine With Total Homocysteine in Pregnancy, and Effect Modification Due to Folic Acid Versus Natural Folate Supplementation

ObjectivesElevated circulating total homocysteine (tHcy) is associated with numerous pregnancy complications. Determinants of circulating tHcy include folate, vitamin B12, and betaine status, which catalyze the remethylation of homocysteine to methionine. In countries with folic acid food fortification, vitamin B12 and betaine are reported as stronger predictors of tHcy than folate. We evaluated the association between plasma folate, vitamin B12, and betaine with plasma tHcy in pregnancy, and any effect modification due to supplementation with folic acid versus 5-methyltetrahydrofolate (natural folate; 5-MTHF).MethodsPregnant women (n = 60) in Vancouver, BC, were randomized to 0.6 mg folic acid or 5-MTHF for 16 weeks, starting at 8–21 weeks gestation. Dietary folate intake was recorded at baseline. A 3-hour fasting blood sample was collected at baseline and endline for quantification of plasma folate (LC-MSMS), vitamin B12 (immunoanalyzer), betaine and tHcy (HPLC-MSMS). Linear regression was used to assess the association of endline plasma folate, vitamin B12, and betaine with endline tHcy, with folate group as an interaction term, adjusting for baseline tHcy, weeks gestation, and dietary folate intake. As the trial is not yet unblinded, groups are presented as “A” and “B”.ResultsThe median [IQR] concentrations of plasma analytes at endline in groups “A” and “B” were: folate 58 [54, 65] and 66 [61, 82] nmol/L; vitamin B12 204 [159,239] and 206 [166,300] pmol/L; betaine 15 [13, 16] and 14 [12, 17] µmol/L; tHcy 4.9 [4.5, 5.6] and 5.2 [4.7, 5.8] µmol/L, respectively. Folate group did not significantly modify the association of tHcy with folate (p = 0.39), vitamin B12 (p = 0.42), or betaine (p = 0.56). Overall, there was no association (β, 95% CI) of endline plasma folate, vitamin B12, or betaine with the outcome tHcy (µmol/L): folate −0.002 (−0.01 to 0.009); tB12 −0.0005 (−0.002 to 0.0005); betaine 0.02 (−0.04 to 0.07). Baseline tHcy was the most significant predictor of endline tHcy in each model (β = 0.8, 95% CI 0.6 to 1.0).ConclusionsFolate, vitamin B12, and betaine concentrations were not associated with tHcy, nor was the effect modified by supplementation with folic acid versus 5-MTHF. In this group of n = 60 healthy pregnant women, baseline tHcy was the most important predictor of tHcy in later pregnancy.Funding SourcesHealthy Starts Catalyst Grant (BCCHR).

Effects of high-dose folic acid on protein metabolism in breast muscle and performance of broilers

Attaining the optimal feed conversion ratio is the unaltered goal for poultry breeding, meat yield is one of the vital reference indexes for that. Folic acid is involved in protein metabolism by acting as a transmitter of one carbon unit, and the detail mechanism for the high-dose folic acid on growth of broiler skeletal muscle is still unclarified. The present study was conducted to investigate the effect and regulatory mechanism of folic acid on deposition and metabolism of protein in broiler breast muscle. A total of 196 one-day-old AA broilers were randomly assigned to 2 treatment groups. The chicks were fed corn-soybean diet with folic acid levels of 1.3 mg/kg (CON) or 13 mg/kg (FA), respectively. The results showed that high dose of folic acid significantly increased the body weight gain, average daily gain, average daily feed intake, and feed conversion ratio of broilers during 1 to 42 d. Compared with control group, folic acid statistically augmented the breast muscle ratio of broilers at 42 d, abdominal fat percentage was also decreased in FA group. Folic acid significantly increased the gene expression of folate receptor (FR) in duodenum and jejunum at 21 d, and its relative expression in jejunum of broilers at 42 d. Furthermore, relative expression of myogenin in broiler breast muscle was upregulated in folic acid group. Folic acid supplementation significantly enhanced the protein expression of phosphorylated serine/threonine kinase (AKT) and ribosomal protein S6 kinase 1 (S6K1) in the breast muscle of broilers at 21 d and 42 d. In conclusion, the results proved that high-dose folic acid activated the AKT/mammalian target of rapamycin (mTOR) pathway and increased the activity of phosphorylation of S6K1, thereby regulating the protein deposition in breast muscle. Meanwhile, the gene expression of the myogenic determinant factor was upregulated by folic acid and then promoted the growth of breast muscle. Consequently, the growth performance, meat production and feeding efficiency were improved of broilers by adding folic acid at 13 mg/kg.

Effects of folate supplementation on recurrence and metabolic status of cervical intraepithelial neoplasia grade 2/3 in overweight and obese women: a randomized double-blind placebo-controlled trial.

Inconsistent evidence showed that folate supplementation may be associated with reduced risk of cancer due to improved metabolic profiles and reduced markers of oxidative stress and inflammation. The aim of this investigation was to quantify the effects of folate supplementation on the recurrence and other metabolic factors of women with cervical intraepithelial neoplasia grade 2/3 (CIN2/3). This randomized, double-blind, placebo-controlled clinical trial was performed among 60 overweight/obese women with CIN2/3. Definitive CIN2/3 confirmation was done via biopsy, pathological diagnosis, as well as colposcopy. Participants were randomly assigned to the intervention group to take 5 mg/day folate supplements or placebo group (n = 30 in each group) for 12 weeks. The results of the current study showed a non-significant decrease in recurrence of CIN2/3 in the folate group in comparison with the placebo group (3.3% vs. 16.7%, P = 0.08). Compared with the placebo, folate supplementation significantly decreased plasma homocysteine (Hcy) levels (P < 0.001), serum insulin values (in the crude model) (P = 0.01), and homeostasis model assessment of insulin resistance (P = 0.01). Also, folate supplementation resulted in a significant improvement in the quantitative insulin sensitivity check index (P = 0.002) and total antioxidant capacity (P = 0.04) and a significant reduction in high-sensitivity C-reactive protein (P = 0.015) in comparison with the placebo group. In conclusion, folate supplementation for 12 weeks among overweight/obese women with CIN2/3 showed a non-significant decrease in its recurrence and had beneficial effects on insulin sensitivity, inflammation, and oxidative stress markers.

Folic acid alleviates lead acetate-mediated cardiotoxicity by down-regulating the expression levels of Nrf2, HO-1, GRP78, and CHOP proteins.

The purpose of this study was to explore the interventional effects of folic acid on the heart damage caused by lead acetate exposure. Twenty-four 60-day-old male Sprague-Dawley (SD) rats were randomly divided into 4 groups with 6 rats in each group. The control group (C group) was normal rats; the lead exposure group (L group) rats drank 0.2% lead acetate solution freely for 14days. The rats in the intervention group (T group) were given 0.2% lead acetate solution for 14days, respectively, and 0.4mg/kg BW folic acid solution was given to the rats by gavage on the 7th day of lead administration. The rats in the folic acid group (group E) were given 0.4mg/kg BW folic acid solution by gavage. To weigh rat body weight and heart weight, calculate heart index, and observe the expression level of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase 1(HO-1), glucose-regulated protein 78/binding immunoglobulin protein (GRP78), and C/EBP-homologous protein (CHOP) by immunofluorescence method. The results showed that compared with group C, serum lead levels in group L and T were significantly increased (P < 0.05); superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX) levels in group L were significantly decreased (P < 0.05), and malondialdehyde (MDA) content was significantly higher increased (P < 0.05), and the GSH-PX content in group T were significantly increased in group L (P < 0.05), and the MDA content in group T was significantly lower than that in group L (P < 0.05). Compared with group C, the expression of Nrf2, HO-1, GRP78, and CHOP in group L increased significantly, and the difference was statistically significant (P < 0.05). Compared with the L group, the expression of Nrf2, HO-1, GRP78, and CHOP in the T group was reduced. Therefore, folic acid has a certain protective effect on the oxidative damage of lead-exposed rat heart tissue. Lead exposure will increase ROS, NO, MDA, and other oxidizing substances and reduce the level of GSH, SOD, CAT, GPx, and other antioxidant factors, which will lead to cardiac hypertrophy, cardiac index increase, oxidative stress, Nrf2, and HO-1. The expression of stress-related proteins such as GRP78 and CHOP also increased, leading to cardiomyocyte apoptosis. After a folic acid intervention, these changes can be significantly reversed.

Edible folic acid and medicinal folinic acid produce cardioprotective effects in late-stage triple-transgenic Alzheimer's disease model mice by suppressing cardiac hypertrophy and fibrosis.

Some clinical studies have indicated the patients with Alzheimer's disease (AD) display an increased risk of cardiovascular disease (CVD). Here, to examine the relationship between AD and CVDs, we investigated the changes in heart function in triple-transgenic late-stage AD model mice (3× Tg-AD; APPSwe, PS1M146V, and tauP301L). We fed the AD mice folic acid (FA) or folinic acid (FN) and analyzed the protective effects of the compounds on the heart; specifically, 20-month-old triple-transgenic AD mice, weighing 34-55 g, were randomly allocated into three groups-the AD, AD + FA, and AD + FN groups-and subject to gastric feeding with FA or FN once daily at 12 mg/kg body weight (BW) for 3 months. Mouse BWs were assessed throughout the trial, at the end of which the animals were sacrificed using carbon dioxide suffocation. We found that BW, whole-heart weight, and left-ventricle weight were reduced in the AD + FA and AD + FN groups as compared with the measurements in the AD group. Furthermore, western blotting of excised heart tissue revealed that the levels of the hypertrophy-related protein markers phospho(p)-p38 and p-c-Jun were markedly decreased in the AD + FA group, whereas p-GATA4, and ANP were strongly reduced in the AD + FN group. Moreover, the fibrosis-related proteins uPA, MMP-2, MEK1/2 and SP-1 were decreased in the heart in both AD + FN group. In summary, our results indicate that FA and FN can exert anti-cardiac hypertrophy and fibrosis effects to protect the heart in aged triple-transgenic AD model mice, particular in FN.

Comparing the Effects of Folic Acid and Cyproheptadine on Appetite, Weight, and ADHD Symptoms in Children with ADHD: A Randomized Clinical Trial

Background: Children with Attention Deficit Hyperactivity Disorder (ADHD) treated with methylphenidate may lose their appetite and body weight. In this study, an attempt was to compare the effects of folic acid with cyproheptadine on appetite, weight, and symptoms of attention deficit and hyperactivity in children with ADHD who are taking methylphenidate. Methods: This was a randomized clinical trial performed on 7-12 year old children who were diagnosed with ADHD, treated with methylphenidate, and complained of appetite loss. In the first visit, anthropometric measurements were performed and then mothers completed the ADHD rating scale, Sleep Disturbance Scale for Children, and visual analogue scale for appetite. Then, the participants were randomly assigned to receive either cyproheptadine (4 mg/day), or folic acid (1 mg/day). All assessments were repeated after 8 weeks. Results: Twenty-four children in the cyproheptadine group and 23 in the folic acid group (19 boys in each group) completed the study and statistical analyses were performed. The hyperactivity score significantly decreased in the folic acid group compared with the cyproheptadine group (p=0.035). However, the change in attention deficiency scores between groups was not significant. During the study, only girls in the folic acid group had significant body weight increase in contrast to other subgroups. Conclusion: Improving hyperactivity symptoms in the folic acid group along with better growth especially in girls reveals the clinical superiority of folic acid over cyproheptadine.

Small-Quantity Lipid-Based Nutrient Supplements Increase Infants’ Plasma Essential Fatty Acid Levels in Ghana and Malawi: A Secondary Outcome Analysis of the iLiNS-DYAD Randomized Trials

IntroductionSmall-quantity (SQ) lipid-based nutrient supplements (LNSs) may influence infants’ plasma fatty acid (FA) profiles, which could be associated with short- and long-term outcomes. ObjectivesWe aimed to determine the impact of SQ-LNS consumption on infants’ plasma FA profiles in Ghana and Malawi. MethodsGhanaian (n = 1320) and Malawian (n = 1391) women ≤20 weeks pregnant were assigned to consume 60 mg iron and 400 μg folic acid daily until delivery [iron and folic acid (IFA) group], multiple-micronutrient supplements (MMNs) until 6 months postpartum (MMN group), or SQ-LNSs (∼7.8 linoleic acid:α-linolenic acid ratio) until 6 months postpartum (LNS group). LNS group infants received SQ-LNS from 6 to 18 months of age. We compared infant plasma FAs by intervention group in subsamples (n = 379 in Ghana; n = 442 in Malawi) at 6 and 18 months using ANOVA and Poisson regression models. Main outcomes were mean percentage compositions (%Cs; percentage of FAs by weight) of α-linolenic acid (ALA), linoleic acid (LA), EPA, DHA, and arachidonic acid (AA). ResultsAt 6 months, LNS infants had greater mean ± SD ALA %Cs in Ghana (0.23 ± 0.08; IFA, 0.21 ± 0.06; MMN, 0.21 ± 0.07; P = 0.034) and Malawi (0.42 ± 0.16; IFA, 0.38 ± 0.15; MMN, 0.38 ± 0.14; P = 0.034) and greater AA values in Ghana (6.25 ± 1.24; IFA, 6.12 ± 1.13; MMN, 5.89 ± 1.24; P = 0.049). At 18 months, LNS infants had a tendency towards greater ALA (0.32 ± 0.16; IFA, 0.24 ± 0.08; MMN, 0.24 ± 0.10; P = 0.06) and LA (27.8 ± 3.6; IFA, 26.9 ± 2.9; MMN, 27.0 ± 3.1; P = 0.06) in Ghana, and greater ALA (0.45 ± 0.18; IFA, 0.39 ± 0.18; MMN, 0.39 ± 0.18; P < 0.001) and LA (29.7 ± 3.5; IFA, 28.7 ± 3.3; MMN, 28.6 ± 3.4; P = 0.011) in Malawi. The prevalence of ALA below the population-specific 10th percentile was lower in the LNS group compared to the MMN group, but not the IFA group. Groups did not differ significantly in plasma EPA or DHA levels. ConclusionsSQ-LNS increased infants’ plasma essential FA levels in Ghana and Malawi, which may have implications for health and developmental outcomes. These trials were registered at clinicaltrials.gov as NCT00970866 and NCT01239693.

Correlation of MTHFR Gene Polymorphism with Male Infertility

Background: Folate is present in Vitamin B, which is not present in the body, and one has to consume it from outside. Its functions are to help in the production of RBCs, helps in the production of genes, DNA, RNA, and protein, helps in the metabolism of homocysteine, and is also the main component which is required for the process of methylation. For the metabolism of the folate group, the MTHFR gene is responsible. When there is a problem occurs in the MTHFR gene such as SNP, then it can create a problem with many allied metabolisms and other biological reactions or processes in the body of human body and deficiency of folate in the body may lead to affect various processes such as it can increase the homocysteine level in the body and can cause hyperhomocysteinemia, which has been linked with many diseases along with causing male infertility.&#x0D; Objectives:&#x0D; &#x0D; To identify nucleotide polymorphism in cases and control group.&#x0D; To correlate polymorphism status with male infertility.&#x0D; To correlate MTHFR polymorphism with abnormal semen parameters.&#x0D; To correlate BMI with male infertility.&#x0D; &#x0D; Methodology: For this study, we will use various collective methods to conduct the study which includes the recording of treatment history and the indications of infertile patients visiting WARDHA TEST TUBE CENTRE and counselling them. After that semen collection and analysis will be done along with blood collection, DNA extraction, DNA quantification with nanodrop and agarose gel, PCR, and RFLP. We have also made use of PubMed for getting related articles.&#x0D; Results and Conclusion: We have done many searches on PubMed and NCBI sites (http://www.ncbi.nlm.nih.gov/pubmed/) with keyword MTHFR gene, polymorphism in MTHFR gene, methylation, folate methylation, methylenetetrahydrofolate reductase, methylenetetrahydrofolate reductase, and primer for MTHFR gene and retrieved many articles related to primers for MTHFR gene and will design our primer for forward and reverse annealing with the help of Amplify software (Engels, 1993). With the help of our study, we will analyze the MTHFR genomic sequence along with analysis of RFLP, in which we will design an amplicon of 513bps in which we will find restriction site for Hinf I and will check that if polymorphism is there then it will cut the DNA amplicon into two and will confirm it with electrophoresis.

Studying the mechanism of sperm DNA damage caused by folate deficiency.

Sperm DNA injury is one of the common causes of male infertility. Folic acid deficiency would increase the methylation level of the important genes, including those involved in DNA double‐strand break (DSB) repair pathway. In the early stages, we analysed the correlation between seminal plasma folic acid concentration and semen parameters in 157 infertility patients and 91 sperm donor volunteers, and found that there was a significant negative correlation between seminal folic acid concentration and sperm DNA Fragmentation Index (DFI; r = −0.495, p < 0.01). Then through reduced representation bisulphite sequencing, global DNA methylation of sperm of patients in the low folic acid group and the high folic acid group was analysed, it was found that the methylation level in Rad54 promoter region increased in the folic acid deficiency group compared with the normal folic acid group. Meanwhile, the results of animal model and spermatocyte line (GC‐2) also found that folic acid deficiency can increase the methylation level in Rad54 promoter region, increased sperm DFI in mice, increased the expression of γ‐H2AX, that is, DNA injury marker protein, and increased sensitivity of GC‐2 to external damage and stimulation. The study indicates that the expression of Rad54 is downregulated by folic acid deficiency via DNA methylation. This may be one of the mechanisms of sperm DNA damage caused by folate deficiency.

Biology of Perseverative Negative Thinking: The Role of Timing and Folate Intake.

Past-oriented rumination and future-oriented worry are two aspects of perseverative negative thinking related to the neuroticism endophenotype and associated with depression and anxiety. Our present aim was to investigate the genomic background of these two aspects of perseverative negative thinking within separate groups of individuals with suboptimal versus optimal folate intake. We conducted a genome-wide association study in the UK Biobank database (n = 72,621) on the “rumination” and “worry” items of the Eysenck Personality Inventory Neuroticism scale in these separate groups. Optimal folate intake was related to lower worry, but unrelated to rumination. In contrast, genetic associations for worry did not implicate specific biological processes, while past-oriented rumination had a more specific genetic background, emphasizing its endophenotypic nature. Furthermore, biological pathways leading to rumination appeared to differ according to folate intake: purinergic signaling and circadian regulator gene ARNTL emerged in the whole sample, blastocyst development, DNA replication, and C-C chemokines in the suboptimal folate group, and prostaglandin response and K+ channel subunit gene KCNH3 in the optimal folate group. Our results point to possible benefits of folate in anxiety disorders, and to the importance of simultaneously taking into account genetic and environmental factors to determine personalized intervention in polygenic and multifactorial disorders.

Synthesis and characterization of fluorescent magnetic Fe3O4/CdTe@SiO2-NH-FA nanoprobe

In this study, fluorescent magnetic Fe3O4/CdTe@SiO2-NH-FA (FCSN-FA) nanoprobe was synthesized by a simple method. First, Fe3O4 nanoparticles and TGA-stabilized CdTe QDs formed Fe3O4/CdTe core, and the Fe3O4/CdTe core was coated with amorphous silica. Amino groups (–NH2) of 3-aminopropyltriethoxysilane (APTES) was modified on the surface of the amorphous silica, forming Fe3O4/CdTe@SiO2-NH2 (FCSN) nanocomposite. The carboxyl group (–COOH) of folic acid (FA) can covalently conjugate with the –NH2 to form Fe3O4/CdTe@SiO2-NH-FA nanoprobe. The results show that the FCSN-FA nanoprobes have a uniform size, excellent fluorescent and superparamagnetic properties, indicating that the FCSN-FA nanoprobes have potential biomedical applications.