Effect Of Folic Acid Fortification Research Articles

Gestational palmitic acid suppresses embryonic GATA-binding protein 4 signaling and causes congenital heart disease

Dysregulated maternal fatty acid metabolism increases the risk of congenital heart disease (CHD) in offspring with an unknown mechanism, and the effect of folic acid fortification in preventing CHD is controversial. Using gas chromatography coupled to either a flame ionization detector or mass spectrometer (GC-FID/MS) analysis, we find that the palmitic acid (PA) concentration increases significantly in serum samples of pregnant women bearing children with CHD. Feeding pregnant mice with PA increased CHD risk in offspring and cannot be rescued by folic acid supplementation. We further find that PA promotes methionyl-tRNA synthetase (MARS) expression and protein lysine homocysteinylation (K-Hcy) of GATA4 and results in GATA4 inhibition and abnormal heart development. Targeting K-Hcy modification by either genetic ablation of Mars or using N-acetyl-L-cysteine (NAC) decreases CHD onset in high-PA-diet-fed mice. In summary, our work links maternal malnutrition and MARS/K-Hcy with the onset of CHD and provides a potential strategy in preventing CHD by targeting K-Hcy other than folic acid supplementation.

Dataset on the folic acid uptake and the effect of sonication-based fortification on the color, pasting and textural properties of brown and milled rice

The data included in this article are related to research paper entitled “Efficient fortification of folic acid in rice through ultrasonic treatment and absorption”. These datasets compile the folic acid uptake expressed in concentration and the effects of folic acid fortification on the physical properties of brown and milled rice. We reported the folic acid uptake of rice in increasing fortificant concentration through soaking, one-step, and stepwise fortification protocols. In addition, the data on the effects of fortification on the color, pasting, and textural properties of brown and milled rice were also presented.

Fortification of wheat and maize flour with folic acid for population health outcomes.

Fortification of wheat and maize flour with folic acid for population health outcomes.

Effects of folic acid fortification on orofacial clefts prevalence: a meta-analysis.

Orofacial clefts (OFC) are the most prevalent craniofacial birth defect. Folic acid (FA) supplementation has been demonstrated as an effective intervention to reduce risk of OFC occurrence. However, the effect of mandatory FA fortification of wheat and/or maize flour on OFC prevalence has shown controversial results among countries adopting this policy. Thus, we performed a meta-analysis to synthesize the available evidence evaluating the global impact of this mandatory policy on OFC occurrence. Literature search in conventional and grey medical/scientific databases showed fifteen studies considering OFC prevalence in pre- and post-fortification periods with FA. The effect of this policy was evaluated by computing relative risk (RR) and separating samples into total OFC, non-syndromic forms, cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO). We found a significant effect of FA fortification only on non-syndromic CL/P (RR=0·88; 95 % CI 0·81, 0·96), whereas neutral effects were detected for total OFC (syndromic plus non-syndromic) and CPO. Our results may reflect the different aetiology of syndromic OFC with respect to non-syndromic forms and the CL/P related to CPO. Although the number of non-syndromic CL/P samples was lower than that for total OFC, the absence of both between-study heterogeneity and publication bias leads us to conclude that FA fortification may have beneficial effects on non-syndromic CL/P.

Periconceptional folic acid fortification for the risk of gestational hypertension and pre-eclampsia: a meta-analysis of prospective studies.

Published literatures report controversial results about the association of folic acid-containing multivitamins with gestational hypertension and pre-eclampsia. A comprehensive search was performed to identify related prospective studies to assess the effect of folic acid fortification on gestational hypertension and pre-eclampsia. The Q test and I(2) statistic were used to examine between-study heterogeneity. Fixed or random effects models were selected based on study heterogeneity. A funnel plot and modified Egger linear regression test were used to estimate publication bias. Eleven studies conformed to the criteria. Pooled results indicated that folic acid fortification alone was not associated with the occurrence of gestational hypertension [relative risk (RR) = 1.03, 95% confidence interval (CI): 0.98-1.09, P = 0.267] and pre-eclampsia (RR = 0.99, 95% CI: 0.90-1.08, P = 0.738). However, supplementation of multivitamins containing folic acid could prevent gestational hypertension (RR = 0.57, 95% CI: 0.43-0.76, P < 0.001) and pre-eclampsia (RR = 0.64, 95% CI: 0.48-0.84, P = 0.001). The difference between folic acid fortification alone and multivitamins containing folic acid was significant. This meta-analysis suggests that periconceptional multivitamin supplementation with appropriate dose, not folic acid alone, is an appropriate recommendation for pregnant women. The effect should be further confirmed by conducting large-scale randomised controlled trials.

Associations between Folate Biomarker Levels and Renal Function among Adults in the U.S.

Since the kidneys are highly involved in maintaining folate homeostasis, the effect of folic acid fortification of grain products may be affected by reduced kidney function. However, it is unclear what the impact of renal insufficiency is on folate status. This study investigated the associations of renal function with levels of serum and red blood cell (RBC) folate, plasma homocysteine and the presence of serum unmetabolized folic acid (UMFA) in U.S. adults. Data of participants of the National Health and Nutrition Examination Survey (NHANES) 1999–2002 aged 蠅 40 years were used in this study. Associations between levels of folate biomarkers and homocysteine and the presence of UMFA and three estimated glomerular filtration rate (eGFR) categories (&lt; 60, 60–90 and 蠅 90 mL/min/1.73 m2) were assessed using multivariable regression models, controlled for confounders. The Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) formula was used to estimate eGFR. In men and women, RBC folate and plasma homocysteine levels were significantly higher among individuals with eGFR &lt; 60 ml/min/1.73 m2 compared with those with eGFR 蠅 90 ml/min/1.73 m2; serum folate levels were not significantly different between eGFR groups. In women but not in men, UMFA was significantly more likely to appear in the blood of individuals with eGFR &lt; 60 ml/min/1.73 m2 than those with GFR 蠅 90 ml/min/1.73 m2 (OR: 2.2, 95% CI: 1.2–4.0). Reduced renal function may be implicated in the increased blood folate concentrations. Caution should be taken in consumption of folic acid‐enriched foods and supplements among individuals with renal insufficiency.

Is folic acid supplementation to food benefit or risk for human health?

Abstract The need for sufficient quantities of folic acid for normal embryogenesis and fetal development is well known. Women of childbearing age must be sure to have an adequate intake of folic acid periconceptionally prior to and during pregnancy. Folate plays an essential role in the biosynthesis of RNA and DNA, phospholipid and neurostransmitters synthesis, using S-adenosylmethionine (SAM) as the primary methyl group donor. In some countries, the knowledge that folic acid is preventable for the reduction of the risk for neural tube defects (NTD) and in lowering the high amount of homocysteine (Hcy) led to the recommendation that all women capable of becoming pregnant should consume 400 µg of folic acid daily. Later, in 1998, folic acid fortification of all enriched cereal grain product flour was implemented in some countries. In addition to careful monitoring of adverse effects, the studies are warranted in order to determine the potentially positive and deleterious effects of folic acid fortification and supplementation on the human health or human diseases. To further understand the metabolic action of folates we asked ourselves the question: Is the intake of a sufficient amount of this vitamin a benefit or risk for human health?

One-Carbon Vitamins, Epigenetic/Genetic Integrity and Colon Cancer: Research is Needed to Understand the Effect on Tumorigenic Signaling Pathways

Copyright: © 2012 Liu Z. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Evidence has established the protective effect of folic acid fortification and periconceptional supplementation on neural tube defects. A large and growing body of compelling evidence from both epidemiological and pre-clinical studies also indicates that adequate folate status, and possibly in combination with other one-carbon nutrients, is associated with a decreased risk of colorectal carcinogenesis [1,2]. Evidence is still accumulating in support of these claims, but some recent studies raise warnings in regard to the safety for use folate as a chemopreventive component. Not to mention some null observations [3,4], it is important to point out that some studies suggest that overly abundant intake of folate may paradoxically promote tumor progression if administered in an inopportune time when an individual already has harbored foci of precancerous or cancerous cells [5-8]. To fully take advantage of this chemopreventive agent and avoid its cancer-promoting effect (though more studies are needed to confirm), research is urgently needed to understand specific molecular mechanisms by which these paradoxical effects are mediated.

Pros and cons of increasing folic acid and vitamin B12 intake by fortification.

There is no doubt that folic acid fortification can be effective for reducing the incidence of neural tube defects. The degree of efficacy depends on both the level of folate depletion and other, yet to be fully characterized, genetic and/or environmental factors. This article summarizes briefly data on neural tube defect reduction and other benefits of folic acid fortification as these have been reviewed in more detail elsewhere. More attention is drawn to questions that have been raised about the possible adverse effects of folic acid fortification including the incidence of colorectal cancer and immune function. The main question addressed here is whether folic acid fortification can exacerbate the adverse effects of vitamin B12 deficiency. Most analyses of this question have been conducted in wealthier countries based on data from elderly populations - which have the highest prevalence of vitamin B12 deficiency. However, of potentially greater concern is the increasingly common practice of folic acid fortification in developing countries, where folate status is probably often adequate even prior to fortification, and vitamin B12 depletion or deficiency is common. To add to this information, data from a group of Chilean elderly with a range of vitamin B12 status and exposed to high levels of folic acid fortification will be presented.

Pre- and postfortification intake of folate and risk of colorectal cancer in a large prospective cohort study in the United States

A higher folate intake is associated with a decreased colorectal cancer risk in observational studies, but recent evidence suggests that excessive folate supplementation may increase colorectal cancer risk in some individuals. Therefore, mandatory folic acid fortification of grain products in the United States may have unintended negative consequences. We examined the association between folate intake and colorectal cancer risk, including 8.5 y of postfortification follow-up. We examined the association between folate intake and colorectal cancer in the NIH-AARP Diet and Health Study-a US cohort study of 525,488 individuals aged 50-71 y initiated in 1995-1996. Dietary, supplemental, and total folate intakes were calculated for the pre- and postfortification periods (before and after 1 July 1997) based on a baseline food-frequency questionnaire. HRs and 95% CIs were calculated by using multivariable Cox proportional hazards regression models. During follow-up through 31 December 2006 (mean follow-up: 9.1 y), 7212 incident colorectal cancer cases were identified. In the postfortification analysis (6484 cases), a higher total folate intake was associated with a decreased colorectal cancer risk (HR for ≥900 compared with <200 μg/d: 0.70; 95% CI: 0.58, 0.84). The highest intakes specifically from supplements (HR: 0.82; 95% CI: 0.72, 0.92) or from diet (HR: 0.81; 95% CI: 0.67, 0.97) were also protective. The pattern of associations was similar for the prefortification period, and no significant differences between time periods were observed. In this large prospective cohort study that included 8.5 y of postfortification follow-up, folate intake was associated with a decreased colorectal cancer risk. Given that the adenoma-carcinoma sequence may take ≥10 y, additional follow-up time is needed to fully examine the effect of folic acid fortification.

Effects of folic acid fortification on spina bifida prevalence in Brazil

To assess spina bifida birth prevalence changes after folic acid fortification of wheat and maize flours began in Brazil in June 2004. Cross-sectional study of Brazilian live births in 2004 and 2006. Spina bifida birth prevalence from the Live Births Information System (SINASC: Sistema de Informações sobre Nascidos Vivos) in a prefortified period was compared to a period fortified with folic acid in each state. Observed prevalence rates in 2004 were used to calculate the expected prevalence rates in 2006 under the null hypothesis that both were similar. The observed/expected (O/E) ratios were tested by two-tailed Z-test. To minimize ascertainment differences among states, the O/E ratio of each one of the 27 Brazilian states was adjusted for the number of births with the Mantel-Haenszel statistic. RESULTS The reduction in spina bifida birth prevalence in 2006 was 39% (O/E = 0.61; 95% confidence interval [CI], 0.55-0.67), and 40% (O/E = 0.60; 95% CI, 0.53-0.68), after adjusting for state birth number. This reduction was significant (p < 0.0001), and heterogeneous among states (χ(2) = 72.96; p < 0.0001). Using SINASC data, there was a significant reduction in spina bifida birth prevalence in Brazil, probably related to the folic acid food fortification program.

The effect of folic acid, protein energy and multiple micronutrient supplements in pregnancy on stillbirths

BackgroundPregnancy is a state of increased requirement of macro- and micronutrients, and malnourishment or inadequate dietary intake before and during pregnancy, can lead to adverse perinatal outcomes including stillbirths. Many nutritional interventions have been proposed during pregnancy according to the nutritional status of the mother and baseline risk factors for different gestational disorders. In this paper, we have reviewed three nutritional interventions including peri-conceptional folic acid supplementation, balanced protein energy supplementation and multiple micronutrients supplementation during pregnancy. This paper is a part of a series to estimate the effect of interventions on stillbirths for input to Live Saved Tool (LiST) model.MethodsWe systematically reviewed all published literature to identify studies evaluating effectiveness of peri-conceptional folic acid supplementation in reducing neural tube defects (NTD), related stillbirths and balanced protein energy and multiple micronutrients supplementation during pregnancy in reducing all-cause stillbirths. The primary outcome was stillbirths. Meta-analyses were generated where data were available from more than one study. Recommendations were made for the Lives Saved Tool (LiST) model based on rules developed by the Child Health Epidemiology Reference Group (CHERG).ResultsThere were 18 studies that addressed peri-conceptional folic acid supplementation for prevention of neural tube defects (NTDs). Out of these, 7 studies addressed folic acid supplementation while 11 studies evaluated effect of folic acid fortification. Pooled results from 11 fortification studies showed that it reduces primary incidence of NTDs by 41 % [Relative risk (RR) 0.59; 95 % confidence interval (CI) 0.52-0.68]. This estimate has been recommended for inclusion in the LiST as proxy for reduction in stillbirths. Pooled results from three studies considered to be of low quality and suggest that balanced protein energy supplementation during pregnancy could lead to a reduction of 45% in stillbirths [RR 0.55, 95 % CI 0.31-0.97]. While promising, the intervention needs more effectiveness studies before inclusion in any programs. Pooled results from 13 studies evaluating role of multiple micronutrients supplementation during pregnancy showed no significant effect in reducing stillbirths [RR = 0.98; 95% CI: 0.88 – 1.10] or perinatal mortality [RR = 1.07; 95% CI: 0.92 – 1.25; random model]. No recommendations have been made for this intervention for inclusion in the LiST model.ConclusionsPeri-conceptional folic acid supplementation reduces stillbirths due to NTDs by approximately 41%, a point estimate recommended for inclusion in LiST.

Effect of folic acid fortification on the incidence of neural tube defects

In a few countries enriched cereal grains have been fortified with folic acid to reduce the incidence of neural tube defects. The objective of this study was to analyse the effect of folic acid fortified foods on the incidence of neural tube defects in live newborns at Princess Badea Teaching Hospital, in the north of Jordan, before and after the national food fortification with folic acid was implemented. For the 7-year period from 1 January 2000 to 31 December 2006, we retrospectively extracted the total number of births at Princess Badea Hospital, as well as the number of pregnancies affected by spina bifida and anencephaly, per 1000 births during the periods before (2000-01), during (2002-04) and after (2005-06) folic acid fortification of grain products, was implemented. Neural tube defects were defined in accordance with the International Classification of Diseases, 10th revision (ICD-10): anencephaly, encephalocele and spina bifida. A total of 78 subjects with neural tube defects were recorded among 61 447 births during the study period. The incidence of neural tube defects decreased from 1.85 per 1000 births before fortification [95% confidence interval (CI) 1.2, 2.4] to 1.07 per 1000 births during the fortification period [95% CI 0.7, 1.5], and 0.95 after full fortification [95% CI 0.5, 1.5], a 49% reduction. The difference between incidence of neural tube defects in the periods before and after food fortification with folic acid was statistically significant. We conclude that food fortification with folic acid was associated with a significant reduction in the rate of neural tube defects in north Jordan.

Circulating folic acid in plasma: relation to folic acid fortification

BackgroundThe implementation of folic acid fortification in the United States has resulted in unprecedented amounts of this synthetic form of folate in the American diet. Folic acid in circulation may be a useful measure of physiologic exposure to synthetic folic acid, and there is a potential for elevated concentrations after fortification and the possibility of adverse effects. ObjectiveWe assessed the effect of folic acid fortification on circulating concentrations of folic acid and 5-methyltetrahydrofolate in the Framingham Offspring Cohort. DesignThis is a cross-sectional study that used plasma samples from fasting subjects before and after fortification. Samples were measured for folate distribution with the use of an affinity-HPLC method with electrochemical detection. ResultsAmong nonsupplement users, the median concentration of folic acid in plasma increased from 0.25 to 0.50 nmol/L (P < 0.001) after fortification, and among supplement users the median increased from 0.54 to 0.68 nmol/L (P = 0.001). Among nonsupplement users, the prevalence of high circulating folic acid (≥85th percentile) increased from 9.4% to 19.1% (P = 0.002) after fortification. Among supplement users, the prevalence of high circulating folic acid increased from 15.9% to 24.3% (P = 0.02). Folic acid intake and total plasma folate were positively and significantly related to high circulating folic acid after adjustment for potential confounding factors (P for trend < 0.001). ConclusionsFolic acid fortification has resulted in increased exposure to circulating folic acid. The biochemical and physiologic consequences of this are unknown, but these findings highlight the need to understand the effects of chronic exposure to circulating folic acid.

Long-term Effects of Folic Acid Fortification and B-vitamin Supplementation on Total Folate, Homocysteine, Methylmalonic Acid and Cobalamin in Older Adults

To investigate the long-term effects of the Canadian folic acid fortification program in older adults' whole blood cell folate (folate) and cobalamin (Cbl) status, including homocysteine (tHcy) and methylmalonic acid (MMA), with and without voluntary B-vitamin intake, from 1997 to 2004. Cohort of community-dwelling volunteer older adults. Clinical and biochemical data, including intake of B-vitamin supplements, were obtained at 2- to 2.5-year intervals and divided in 4 periods. Random coefficients (mixed effects) models were used to estimate the linear trend in folate and to compare levels of biochemical parameters between periods. All models were estimated by restricted maximum likelihood as implemented in PROC MIXED of SAS V8.2. Folate levels increased continuously at a yearly rate of 234 ng/mL (95% CI 213-254; p < 0.001) and had not plateaued by the last period when 84% of subjects without B-vitamins had elevated folate. Homocysteine did not remain suppressed. Elevated tHcy was as prevalent in the last study period as in the first. No significant deficits of Cbl or increases of MMA were observed, but MMA levels tended to increase with time in subjects without B-vitamins. B-vitamin supplements significantly affected all results, reducing tHcy and MMA levels. In this population, fortification with folic acid has resulted in cumulative increases of folate with no long-term reduction in tHcy or changes in Cbl or MMA. Possible deleterious effects of cumulative increases of folate, and beneficial effects of B-vitamin supplements in reducing tHcy and MMA, should be investigated.

Folic Acid Fortification and Supplementation-Good for Some but Not So Good for Others

Evidence has established the protective effect of folic acid (FA) fortification and periconceptional supplementation on neural tube defects (NTDs). Folic acid fortification and periconceptional supplementation of women may reduce the risk of certain childhood cancers in their offspring. However, recent human studies have suggested that FA supplementation and fortification may promote the progression of already existing, undiagnosed, preneoplastic and neoplastic lesions, thereby corroborating earlier observations from animal and in vitro studies. Following the success of mandatory FA fortification on the reduction of NTD rates in the United States and Canada, several countries are currently considering whether or not, and at what dose, to institute FA fortification. Future debates and decisions regarding FA fortification should take into consideration all potential adverse effects and dose-responses of such a measure because it may be associated with very serious consequences for many generations. In addition to careful monitoring of adverse effects, preclinical and population-based studied are warranted in order to determine the efficacy, safety, and potential deleterious effects of FA fortification and supplementation on cancer risk and other health outcomes.

A High Prevalence of Biochemical Evidence of Vitamin B12 or Folate Deficiency does not Translate into a Comparable Prevalence of Anemia

Based on biochemical evidence, a high prevalence of biochemical evidence of vitamin B12 or folate deficiency has been reported in a number of areas in the world. The evidence that these biochemical abnormalities lead to a comparable prevalence of anemia is reviewed. The overall contribution of vitamin B12 deficiency to the global burden of anemia is probably not significant, except perhaps in women and their infants and children in vegetarian communities. In developed countries, folate-deficiency anemia is uncommon. In some developing countries, this anemia is still seen, but there are no comprehensive data on the relative prevalence compared with anemia due to malaria, iron-deficiency, hemoglobinopathy, and HIV disease. It seems unlikely that folate deficiency makes a major contribution to the burden of anemia in developing countries. Iron-deficiency anemia may coexist with vitamin B12 and especially folate deficiency, and may confound the hematological features of the vitamin deficiencies whose prevalence would then be underestimated. Supplementation of the diet of pregnant women with folic acid can virtually eliminate folate-deficiency anemia in these women. There are very few data on the hematological effect of vitamin B12 supplementation or fortification at the population level. The addition of vitamin B12 to the supplementation of the diet of pregnant women with iron and folic acid does not produce an increased hematological response, at least in nonvegetarian populations. There are numerous reports of the effect of folic acid fortification of food on tests of folate status, but only a single published report on the hematological response was found.

Prevalence of anemia is lower in post‐folic acid fortification period compared to pre‐fortification period

It is not known whether improved folate status from folic acid fortification has had any impact on the prevalence of anemia in the US. Trends in indices and prevalence of anemia and macrocytosis with a focus on comparing pre‐fortification data (1988–1994) with post‐fortification data (1999–2004) were investigated (n=26596). In men, from 1988–1994 to 2003–2004, hemoglobin and hematocrit values slightly but significantly improved from 15.1 to 15.5 g/dL (2.6%) (P&lt;.0001) and from 44.5 to 45.7% (2.6%) (P&lt;.0001), respectively. In women, the improvement was from 13.3 to 13.7 g/dL in hemoglobin (3%) (P&lt;.0001) and from 39.5 to 40.4% in hematocrit (2.3%) (P&lt;.0001). There was a modest but significant increase in MCV from 1998–1994 to 2003–2004 in men (P=0.0001). MCV increased significantly in both older (&gt;60 years) men (P=.0105) and women (P=.0141). In women but not in men, prevalence of anemia was significantly lower in 1999–2004 (10.4%) relative to 1988–1994 (7.5%, a 27.9% reduction, P=.0005). In general, prevalence of macrocytosis did not change significantly from 1988–1994 to 2003–2004. In US women, folic acid fortification may be indirectly responsible for the reduction of prevalence of anemia from 1988–1994 to 1999–2004. In the post‐fortification period, increased MCV in non‐target populations such as men and older persons may suggest an adverse effect of folic acid fortification.

Effect of folic acid fortification on the characteristics of lemon yogurt

Development of dairy products with new flavors and health benefits helps the dairy industry increase sales of products as well as provide consumers with products they enjoy. Folic acid is used in the prevention of neural tube defects, heart defects, facial clefts, urinary tract abnormalities, and limb deficiencies. The objective of this study was to determine the effect of different concentrations and stage of addition of folic acid on the physico-chemical and sensory characteristics of lemon yogurt over a storage period. Lemon yogurts were manufactured with 0%, 25%, 50%, 75%, and 100% of the RDA of 400 μg folic acid per 224 ml cup. Folic acid was added before and after pasteurization of yogurt mix. Moisture, ash, fat, and protein concentrations were measured at week 1 only. Folic acid concentration was measured at weeks 1 and 5. Viscosity, pH, TA, syneresis, color, and sensory analysis were measured at weeks 1, 3, and 5. Mean folic acid content values were higher when folic acid was added post-pasteurization. Average mean viscosity values were lower when folic acid added post-pasteurization. Greater syneresis was seen in samples where folic acid was added post-pasteurization. Less viscous yogurts had more free whey resulting in higher syneresis values. Level of folic acid impacted flavor scores. As level of folic acid increased, flavor scores decreased.

Unmetabolized folic acid in plasma: Effect of folic acid fortification

Unmetabolized folic acid in plasma: Effect of folic acid fortification