Effect Of Folic Acid Supplementation Research Articles

Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals

Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals

Homocysteine-lowering therapy with folic acid is effective in cardiovascular disease prevention in patients with kidney disease: A meta-analysis of randomized controlled trials

The efficacy of homocysteine-lowering therapy with folic acid to lower homocysteine levels in an effort to reduce cardiovascular disease (CVD) risk in patients with kidney disease remains inconclusive. We conducted a meta-analysis of relevant randomized trials to further examine this issue. This meta-analysis included 8234 patients with kidney disease from nine qualified randomized trials using folic acid therapy, and with CVD reported as one of the endpoints. Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of CVD using a random effects model. When pooling the nine randomized trials, folic acid therapy reduced the risk of CVD by 10%（RR=0.90; 95% CI:0.81-1.00, P=0.046). A greater beneficial effect was observed among those trials without a history of grain fortification with folic acid (0.82; 0.70-0.96, P=0.01), with lower percent baseline diabetes (<30% (median), 0.80; 0.65-0.99, P=0.04), and in patients with end-stage renal disease (ESRD) or advanced chronic kidney disease (ACKD) (0.85; 0.77-0.94, P=0.002). Furthermore, a meta-regression analysis suggested a positive dose-response relationship between percent baseline diabetes and log-RR for CVD risk associated with folic acid supplementation (P=0.007). Most importantly, even the inclusion of three subgroup results did not substantially affect the results (n=11032, RR: 0.93; 95% CI:0.87-0.99, P=0.03). Our meta-analysis indicates that folic acid supplementation may be effective for CVD prevention in patients with kidney disease, particularly in trials among patients without a history of grain fortification with folic acid, with lower percent baseline diabetes, and in patients with ESRD or ACKD.

Molecular mechanisms underlying the potentially adverse effects of folate

The importance of proper consumption of dietary folate for human health has been highlighted by an extensive number of publications over several decades. Fortification of grain products with folic acid was initiated with the specific intent to prevent neural tube defects, and the scope of this endeavor is unique in that its target population (women of the periconceptional period) is many times smaller than the population it affects (everyone who ingests fortified grain products). Folate fortification has been wildly successful in terms of its goal; since its inception, the incidence of neural tube defects has markedly decreased. In the wake of this public health triumph, it is important to catalog both the serendipitous benefits and potential side effects of folic acid supplementation. The vitamin is generally regarded as a harmless nutrient based on studies evaluating the safe upper limits of folate intake. In recent years, however, a concern has been raised with respect to a potential downside to folate supplementation; namely, its proposed ability to enhance proliferation of malignant tumors. The current review summarizes the available literature on the effects of folate supplementation and the molecular mechanisms by which high doses of folate may have negative consequences on human health, especially with regard to cancer.

The dual modulatory effect of folic acid supplementation on indomethacin- induced gastropathy in the rat

Folic acid modulates several disorders in humans. We investigated the effects of folic acid supplementation at varying doses on ulcer formation in the rat. Male Wistar rats were treated with 1 mg/kg, 2 mg/kg and 3 mg/kg diet of folic acid for 21 days. Gastric ulceration was induced by indomethacin, scored, and assayed to determine the concentration of mucus, malondialdehyde, catalase, and superoxide dismutase in homogenized samples. Normal saline- and ranitidine-treated groups served as negative and positive control, respectively. Indomethacin caused severe damage to the glandular portion of the rats' stomachs with increase in malondialdehyde concentration and reduction in mucus, catalase and superoxide dismutase concentration (p < 0.001). Folic acid supplementation at 2 mg/kg diet reduced significantly the formation of gastric lesions by indomethacin, while at 3 mg/kg, potentiation of the lesions was observed (p < 0.05). Malondialdehyde concentration significantly decreased and superoxide dismutase activity increased in the 2 mg/kg folic acid pre-treated group, while 3 mg/kg folic acid significantly increased the malondialdehyde concentration and decreased both catalase and superoxide dismutase. Mucus concentration was increased in the 2 mg/kg folic acid pretreated group, but decreased in the 3 mg/kg folic acid pretreated group when compared with controls. Pre-treatment with 1 mg/kg diet of folic acid produced no significant changes. Histopathological studies underlined differences in the indomethacin-induced alterations in gastric mucosal structure following pre-treatment with a 2 mg/kg or 3 mg/kg diet of folic acid. Folic acid is gastroprotective at the basal requirement supplemental dose; high dose may be dangerous to the integrity of the stomach.

Effects of folic acid supplementation on bone turnover markers in male rats subjected to experimental hyperhomocysteinemia

Objective The objective of this study was to examine whether lowering homocysteine (HCY) with folate has beneficial effects on altered structural and biomechanical properties of bone, induced by experimental hyperhomocysteinemia (HHCY). Methods Thirty adult male Wistar albino rats were randomized into three equal groups: a control group, an HHCY group, and an HHCY+folate group. After 8 weeks of treatment, blood was collected to measure the plasma concentrations of HCY and some bone markers including osteocalcin, bone-specific alkaline phosphatase, and tartrate-resistant acid phosphatase (TRAP5b). Also, histopathological examination of bone was carried out. Results TRAP5b showed higher plasma concentrations, whereas plasma concentrations of osteocalcin and bone-specific alkaline phosphatase were significantly lower in HHCY rats compared with the control rats. Feeding of rats with a folate-enriched diet showed a significant reduction in the plasma HCY level and induced a significant improvement in the disturbances resulting from HHCY on the bone structure and turnover markers. Conclusion The results of this study indicate that HHCY is associated with altered bone turnover. Also, folate supplementation may have beneficial effects to avoid osteoporosis and fractures.

Oral cleft prevention program (OCPP)

BackgroundOral 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/designThis 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 (4mg, 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.DiscussionThe 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 IdentifierNCT00397917

Is there an effect of folic acid supplementation on the coagulation factors and C-reactive protein concentrations in subjects with atherosclerosis risk factors?

Folic acid (FA) may delay the formation of atherosclerotic lesions. Increased plasma levels of von Willebrand factor (VWF) are observed in cardiovascular disease, which leads to higher risk of thrombosis. Fibrinogen (Fb) is a well-documented risk factor of cardiovascular disease. The aim of this study was to analyze the effect of FA supplementation on the Fb, VWF and C-reactive protein (CRP) plasma concentrations in subjects with atherosclerosis risk factors. The study enrolled 124 Caucasian individuals (60 M, 64 F) with atherosclerosis risk factors--family history of premature ischaemic stroke, arterial hypertension, dyslipidaemia, overweight and obesity, cigarette smoking and low physical activity. The participants were asked to take FA in the low dose of 0.4 mg/24 h for three months. After FA supplementation a significant reduction of the VWF concentrations in females (76.6 vs 72.3%; p=0.028) and in males (75.5 vs 66.9%; p=0.001) was observed. Among women and men with dyslipidaemia concentrations of VWF decreased after FA supplementation (76.8% vs 69.6%; p=0.003 and 76.7% vs 67.8%; p=0.001 respectively). Among females and males with BMI ≥25 kg/m² concentrations of VWF decreased only in men (77.6% vs 66.5%; p=0.001). In female and male smokers supplementation of FA decreased VWF concentrations (82.5% vs 74.4%; p=0.012 and 76.6% vs 69.5%; p=0.036 respectively). The results of our study suggest that there is an effect of FA supplementation on VWF concentrations in subjects with atherosclerosis risk factors.

Use of folic acid supplements in early pregnancy in relation to maternal plasma levels in week 18 of pregnancy

Birth cohorts typically measure plasma folate in midgestation, but effects of folic acid supplementation are sometimes specific to the periconceptional period. The relationship between midgestation plasma folate and periconceptional supplementation is not known. We compared plasma folate at week 18 of gestation with self-report use of supplements comtaining folic acid from before pregnancy to week 17 of gestation. The sample comprised 2911 women from The Norwegian Mother and Child Cohort Study. For women reporting continuous supplementation from gestational week -4 to 17 (N = 238), median plasma folate was 15.72 at week 18 (in nmol/L). This was about threefold higher than the median plasma folate of 5.67 for women reporting no supplementation from week -4 to 17 (N = 844), but only slightly higher than the median plasma folate of 13.34 for all women reporting supplementation in weeks 13-17 (N = 1158). Reported supplementation before week 8 was not associated with plasma folate at week 18, in an analysis that adjusted for continued supplementation after week 8. Overall we found a strong and coherent relationship between self-reported folic acid use and plasma folate at week 18. We also found that plasma folate at week 18 did not reflect self-reported supplementation before week 8. For periconceptional supplementation per se, self-report data may offer a better measure.

FOLIC ACID REDUCES ADHESION MOLECULES VCAM-1 EXPRESSION ON ENDOTHELIUM IN RATS WITH HYPERHOMOCYSTEINEMIA

ObjectivesTo investigate the effects of folic acid supplementation on the expression of adhesion molecules VCAM·1 in aortic endothelium of rats with hyperhomocys teinemia (HHCY) induced by ingestion of excess methionine...

EFFICACY OF FOLIC ACID SUPPLEMENTATION IN STROKE PREVENTION: NEW INSIGHT FROM A META-ANALYSIS

ObjectivesThere are growing data and a continuing controversy over the efficacy of folic acid supplementation in stroke prevention. We conducted a meta-analysis based on relevant, up-to-date published randomised trials to...

Effect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation

The beneficial effect of folic acid supplementation before and shortly after conception is well recognized, whereas the effect of supplementation during the second and third trimesters is controversial and poorly documented. Our aims were to systematically review randomized controlled trials (RCTs) investigating the effect of folate supplementation on birth weight, placental weight and length of gestation and to assess the dose–response relationship between folate intake (folic acid plus dietary folate) and health outcomes. The MEDLINE, EMBASE and Cochrane Library CENTRAL databases were searched from inception to February 2010 for RCTs in which folate intake and health outcomes in pregnancy were investigated. We calculated the overall intake-health regression coefficient ( ) by using random-effects meta-analysis on a loge-loge scale. Data of 10 studies from 8 RCTs were analyzed. We found significant dose–response relationship between folate intake and birth weight (P=0.001), the overall was 0.03 (95% confidence interval (CI): 0.01, 0.05). This relationship indicated 2% increase in birth weight for every two-fold increase in folate intake. In contrast, we did not find any beneficial effect of folate supplementation on placental weight or on length of gestation. There is a paucity of well-conducted RCTs investigating the effect of folate supplementation on health outcomes in pregnancy. The dose–response methodology outlined in the present systematic review may be useful for designing clinical studies on folate supplementation and for developing recommendations for pregnant women.

Effect of folic acid supplementation on plasma total homocysteine levels and glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis

AimThe evidences illustrating the effects of folic acid supplementation (FAS) in individuals with type 2 diabetes on plasma total homocysteine (tHcy) levels and glycemic control have been contradictory. The aim of the study was to systematically search and quantitatively analyze the effect of FAS on tHcy levels and HbA1c compared with placebo. MethodsWe searched PubMed, Scopus, and Embase up to March 2012 without language restriction. Key words “folic acid” and “diabetes mellitus” with slight modifications based on the sources for search strategy were used. References of initially identified articles were examined to identify any other relevant studies. A random-effects model was used for estimation the pooled effect estimates (weighted mean different, WMD). ResultsOf 6185 studies identified, 4 studies with 183 patients were included. FAS had statistically significant effect on tHcy levels [WMD, −3.52; 95% confidence interval (CI), −4.44 to −2.60]. However, the effect on HbA1c levels [WMD, −0.37; 95% CI, −1.10 to 0.35] was not significant. ConclusionsFolic acid supplementation in patient with type 2 diabetes mellitus may reduce tHcy levels and have a trend to associate with better glycemic control compared with placebo. Further longitudinal studies on these intervention and outcomes are warranted.

OS040. Effect of folic acid supplementation in pregnancy on preeclampsia– Folic acid clinical trial (FACT)

Observational studies suggest that folic acid supplementation during pregnancy can reduce the risk of preeclampsia (PE). No randomized controlled trial has been conducted to demonstrate the effect of folic acid supplementation on PE. FACT aims to determine efficacy on a new PE prevention strategy of high dose folic acid supplementation from early pregnancy (8(0/7) to 16(6/7)weeks of gestation) until delivery in women with high risk of developing PE. FACT is an international, multi-centre, double-blind, placebo controlled clinical trial of 3656 women. Eligible women will be randomised in a 1:1 ratio to folic acid 4.0mg or placebo. Pregnant women (8(0/7)and 16(6/7) weeks of gestation) ⩾18 years of age, taking ⩽1.1mg of folic acid supplementation who fulfill at least one of the following identified risk factors for PE. Pre-existing hypertension (blood pressure ⩾90mmHg on two separate occasions or at least 4h apart prior to randomization, or use of antihypertensive medication during this pregnancy specifically for the treatment of hypertension prior to randomization), pre-pregnancy diabetes (Type I or Type II DM), twin pregnancy, history of PE in a previous pregnancy, BMI ⩾35kg/m(2) within 3 months prior this pregnancy or during the first trimester of this pregnancy. PE is defined as blood pressure ⩾d90mmHg on two occasions ⩾4 h apart and proteinuria developed in women greater than 20 weeks of gestation. Or HELLP (Haemolysis, Elevated, Liver Enzymes, Low Platelets) syndrome Or superimposed PE, defined as history of pre-existing hypertension (diagnosed pre-pregnancy or before 20 weeks' gestation) with new proteinuria. Proteinuria is defined as: Analysis plan: Intent-to-Treat (ITT) population will be analyzed. Chi-square test will be used in the comparison of incidence of PE between the intervention and placebo groups for analysis of the primary outcome. The Ottawa Hospital randomized the first FACT subject in April 2011. As of February 29th, 2012, 62 subjects have been randomized. There are currently 18 Canadian sites participating in FACT, of which 10 are actively recruiting and 8 are pending site activation. Internationally, Argentina, Australia and the United Kingdom are anticipating first recruits in the late spring of 2012. Israel and Holland are expected to begin enrolment as early as the fall of 2012. Recruitment is on target and expected to end August 2014. Results from this large scale trial will provide a definitive answer to the important question whether folic acid supplementation can prevent PE.

Efficacy of folic acid supplementation in stroke prevention: new insight from a meta-analysis

There are growing data and a continuing controversy over the efficacy of folic acid supplementation in stroke prevention. We conducted a meta-analysis based on relevant, up-to-date published randomised trials to further examine this issue. Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of stroke with a fixed-effects model. Overall, folic acid supplementation reduced the risk of stroke by 8% (n = 55,764; RR: 0.92; 95% CI: 0.86-1.00, p = 0.038). In the 10 trials with no or partial folic acid fortification (n = 43,426), the risk of stroke was reduced by 11% (0.89; 0.82-0.97, p = 0.010). Within these trials, a greater beneficial effect was observed among trials with a lower percent use of statins [≤ 80% (median); 0.77; 0.64-0.92, p = 0.005], and a meta-regression analysis also suggested a positive dose-response relationship between percent use of statins and log-RR for stroke associated with folic acid supplementation (p = 0.013). A daily dose of 0.4-0.8mg folic acid appeared to be adequate for stroke prevention in comparison with larger doses. In the remaining five trials conducted in populations with folic acid fortification (n = 12,338), folic acid supplementation had no effect on stroke risk (1.03; 0.88-1.21, 0.69). Our analysis indicated that folic acid supplementation is effective in stroke prevention in populations with no or partial folic acid fortification. In addition, a greater beneficial effect was observed among trials with a lower percent use of statins. Our findings underscore the importance of identifying target populations that can particularly benefit from folic acid therapy.

Effect of folate supplementation on folate status and health outcomes in infants, children and adolescents: A systematic review

The aim of this systematic review was to collect all available randomized controlled trials on the effect of folate supplementation on folate status and health outcomes within the paediatric age group. The method included a structured search strategy on MEDLINE, Embase and Cochrane databases, with formal inclusion/exclusion criteria and data extraction procedure. We included 26 studies. We conclude that both serum and erythrocyte folate values reflect folate intake; however, serum folate reacts more rapidly to folate intake than erythrocyte folate. As to health outcomes, we found no evidence indicating that additional intake of folate can influence haematological parameters in non-anaemic paediatric patients. We were unable to find evidence of a favourable effect of folate supplementation on the growth of infants. However, the limited data available suggest that supplementing the diet of low-birth-weight infants with folic acid may moderate the rapid fall of serum and red cell folate in the first months of life.

Abstract 5432: The effect of folic acid supplementation on chemosensitivity of colon cancer cells to 5-fluorouracil in a xenograft model

Abstract Background: As a mediator of one-carbon transfer reactions, folate is an essential cofactor in nucleotide biosynthesis. Interruption of intracellular folate metabolism and the consequent inhibition of tumor growth has been the basis for chemotherapy using antifolates and 5-fluorouracil (5FU). A growing body of evidence suggests that folic acid (FA; the synthetic form) may promote the progression of established colorectal (pre)neoplastic lesions. Folate blood levels in North America have dramatically increased over the past decade owing to FA fortification and widespread supplement use. Furthermore, over 50% of newly diagnosed colorectal cancer patients use vitamin supplements containing FA in addition to chemotherapeutic agents whose mechanisms of action are based on interruption of folate metabolism. This study therefore investigated whether FA supplementation can affect chemosensitivity of colon cancer cells to 5FU, the cornerstone of colorectal cancer treatment, in vivo. Methods: Male athymic nude mice were placed on the control diet containing 2 mg FA/kg diet and were inoculated with human HCT116 colon cancer cells. When xenografts were established, the animals were randomized to receive a diet containing 2, 8, or 25 mg FA/kg diet for eight weeks. Within each diet group, the animals were further randomized to receive saline vehicle or 5FU (20 mg/kg) + leucovorin (1 mg/kg) for five days. The primary endpoints were the rate of xenograft growth and the final volume. At necropsy, blood was collected and xenografts were harvested and evidence of metastasis was determined. Results: Plasma folate concentrations of animals on the 2 mg FA diet were significantly lower than those of animals fed the 8 and 25 mg FA diets (p&amp;lt;0.05). Xenograft folate concentrations significantly reflected the supplemental levels of FA in a dose-responsive manner (p=0.002). The effect of dietary levels of FA and 5FU alone were not significant, p=0.907 and p=0.193, respectively, but the interaction effect was significant (p&amp;lt;0.007). 5FU was beneficial only to animals fed the 2 mg FA diet (p&amp;lt;0.0001). In contrast, animals fed the 8 mg FA diet fared worse on 5FU (p=0.048) whereas animals fed the 25 mg FA diet demonstrated no effect of 5FU (p=0.31). All animals exhibited macroscopically evident lymph node involvement, but no distant metastases, irrespective of dietary levels of FA. Conclusion: Our data suggests that FA supplementation may adversely affect chemosensitivity to 5FU chemotherapy, although a dose-responsive relationship was not evident. Results of this study pose a legitimate public health concern given the drastically increased intake of FA from supplements, particularly among recently diagnosed colorectal cancer patients and from mandatory fortification. Further studies are warranted to confirm our findings and to elucidate the underlying mechanisms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5432. doi:1538-7445.AM2012-5432

Effect of folic acid supplementation on hepatic antioxidant function and mitochondrial-related gene expression in weanling intrauterine growth retarded piglets

The aim of the present study was to investigate the effect of dietary folic acid supplementation on antioxidant function and mRNA expression levels of genes involved in mitochondrial biogenesis and function in the liver of piglets affected by intrauterine growth retardation (IUGR). Sixteen piglets at normal birth weight and 16 IUGR piglets were fed either a control diet (C) or a folic acid-supplemented diet (FS, C+5mg/kg folic acid) from 14d of age to 35d of age postnatal. Blood and liver samples were collected at the end of the study. The results showed that body weight was lower for IUGR piglets than that of NBW piglets at 14d of age and 35d of age postnatal (P<0.05). Dietary folic acid supplementation increased plasma folic acid concentrations and hepatic GPx activity, but decreased plasma homocysteine levels (P<0.05). Reduced activities of Mn-SOD and T-AOC, mitochondrial DNA (mtDNA) content, and ATP concentration (P<0.05) were observed in the liver of IUGR pigs fed a control diet. However, the changes in mtDNA content and activities of Mn-SOD and T-AOC were negated in IUGR pigs fed a FS diet (P<0.05). Also, dietary folic acid supplementation decreased protein carbonyls and MDA concentration in the liver of IUGR piglets (P<0.05). Expression levels of genes encoding for PPARγ coactivator-1α (PGC-1α), mammalian silencing information regulator-2α (SIRT-1), nuclear respiratory factor-1 (NRF-1), mt transcription factor A (TFAM), mt single-strand DNA-binding protein (mt SSB), mt polymerase r (mt polr), glucokinase, citrate synthase (CS), ATP synthase (ATPS), and cytochrome c oxidase (CcOX) subunit I and V were decreased in IUGR piglets compared with NBW piglets. However, mRNA levels of PGC-1α, SIRT-1, NRF-1, TFAM, and mt polr in the liver of IUGR pigs fed FS diet were not different from that of NBW pigs. Gene mRNA expression abundance of CcOX IV was enhanced by folic acid supplementation (P<0.05) regardless of birth weight. The present study indicates that IUGR impaired hepatic antioxidant function and mRNA expression levels of genes are involved in mitochondrial biogenesis and function. Dietary folic acid supplementation prevented the harmful effect of IUGR on hepatic antioxidant function and mtDNA biogenesis, but had no effect on mRNA expression levels of genes involved in mitochondrial function.

Influence of a fat-rich diet, folic acid supplementation and a human-relevant concentration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine on the induction of preneoplastic lesions in the rat colon

In the present study, the effect of three controversially discussed risk factors for colorectal cancer, a fat-rich diet (16% raw fat content), dietary folic acid supplementation (50 mg folic acid/kg lab chow) and a human-relevant concentration (0.1 ppm) of the heterocyclic aromatic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), either alone or in combination, on the induction of aberrant crypt foci (ACF) in the colon of male Fischer 344 rats was analyzed. The mean number of ACF per rat in the case of the four groups fed a fat-rich diet tended to be higher than that of the four groups being fed a standard diet. However, the increase in the mean number of ACF per rat only reached statistical significance in the case of the rats receiving a fat-rich lab chow supplemented with 50 mg/kg folic acid. Moreover, a concentration of 0.1 ppm PhIP per se, either in the standard or in the fat-rich lab chow, did not lead to an increase in the mean number of ACF per rat. In conclusion, the present study provides additional evidence for a colon cancer promoting effect of folic acid supplementation when rodents are fed the compound in supraphysiological concentrations.

Folic Acid Effect on Arginase Activity in Human Colostrum and Mature Milk

Abstract Folic acid, or folates are available from a large variety of sources, such as green leafy vegetables (spinach, beans) and liver. The importance of folates is based on their requirement as coenzymes in the transfer and utilization of one-carbon units in a variety of biosynthetic reactions. Folate is an essential cofactor for the de novo biosynthesis of purine nucleotides and thymine, thus influencing RNA and DNA synthesis. Therefore, during periods of rapid cell regeneration and growth, such as pregnancy and infancy, increased amounts of folate are required. Folate has the roles in the prevention of neural tube defects, an important cause of infant mortality and disability. The periconceptional folic acid intake reduces the risk of neural tube defects. Arginase, as part of the urea cycle, detoxifies human body from ammonia. Its activity is important in the production of ornithine, subsequently leading to the production of polyamines (spermine and spermidine), glutamate or proline, and nitric oxide. Arginase is normally present in mother's milk. In the present study, the effect of folic acid supplementation during pregnancy on the dynamics of arginase activity and malondialdehyde concentration in human colostrum and mature milk was studied. The obtained results suggest that in breastfeeding mothers' colostrum and mature human milk samples, supplemented with folic acid during pregnancy (400mg/daily periconceptionaly), the arginase activity increases compared with the enzyme activity in milk samples taken from mothers who did not take folic acid. At the same time, the supplementation with folic acid causes malondialdehyde decrease in colostrum and mature milk.

Folic acid supplementation and colorrectal adenoma recurrence: systematic review

Observational studies show that folate levels may be associated with the development of adenomas and colorectal cancer, suggesting that folic acid supplementation may have a preventive effect. Systematic review of scientific evidence from randomized placebo-controlled clinical studies to identify the effects of folic acid supplementation on the recurrence of colorectal adenomas. Medline via Pubmed systematic review of randomized clinical trials, double-blind and placebo-controlled and references, specifically to evaluate the effect of acid supplementation on the recurrence of colorectal adenomas. Seven randomized clinical trials that met the inclusion criteria were selected and evaluated for analysis based on pre established criteria. The selected studies do not support that folic acid supplementation is beneficial in recurrence of colorectal adenomas. We observed in some studies differences in risk by type of folate suggesting to review the criteria and levels of supplementation in some population subgroups with higher risks.