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PubMed1994

Vitamins, folic acid and the cause and prevention of neural tube defects.

Primary prevention of neural tube defects has been demonstrated in humans by maternal therapy with multivitamins and folic acid or folic acid alone. It has also been shown in several animal models of neural tube defects. One of these, the curly tail mouse, has been used extensively to study which agents will prevent neural tube defects in embryos when administered to the mother in early pregnancy. Prevention is achieved with retinoic acid, inositol and the DNA inhibitors hydroxyurea, mitomycin C, 5-fluorouracil and cytosine arabinoside. In no case were neural tube defects prevented in every embryo. A possible preventive effect was seen with riboflavin, vitamin C and vitamin D2. Despite the use of a variety of dose levels, no prevention was achieved with folic acid, folinic acid, Pregnavite Forte F tablets, pyridoxine or vitamin B12, or triamcinolone and cycloheximide (inhibitors of mRNA and protein synthesis, respectively), zinc, homocysteine, methionine and thymidine. Various studies have investigated whether there is a biochemical lesion in folate metabolism in women who have had children with neural tube defects. While there is no difference in their dietary intake of folate compared with control patients, the correlation between their dietary folate and the level of folate in both serum and red blood cells is distorted. Also they are less efficient at raising their folate levels after a folate load. The effects are minor but may hint at a lesion which, if identified, could act as a marker for 'at risk' women.

Animals↗
PubMed1998

Increasing awareness of and behaviour towards periconceptional folic acid consumption in The Netherlands from 1994 to 1995.

OBJECTIVE: In November 1993, Dutch health authorities advised that women planning a pregnancy should take folic acid in the periconceptional period to reduce the risk of fetal neural tube defects. In the autumn of 1995 a national campaign was organized to inform women and health care professionals in a systematic way. METHODS: We assessed the awareness and behaviour of women at their first or second antenatal visit in two surveys in the spring of 1994 and the autumn of 1995, in order to evaluate the impact of non-systematic information during that period, and to collect baseline data to evaluate the effect of the national folic acid campaign. The two surveys were carried out in the north and the west of The Netherlands. RESULTS: The proportion of women who had heard of folic acid increased from 28% to 78%. The proportion that used folic acid during any period in pregnancy increased from 7.8% to 26%. The proportion that took folic acid tablets during the whole of the recommended period increased from 0.8 to 4.4%. In the group of women who did not take folic acid, the proportion who did "not like to use anything during pregnancy" decreased, as did the proportion who did "not think it is useful". CONCLUSION: In the Netherlands, non-systemic information about periconceptional folic acid use has already led to significant changes in awareness and behaviour before the start of the national folic acid campaign.

Adult↗
PubMed2004

The impact of folic acid fortification of enriched grains on an elderly population: the New Mexico Aging Process Study.

Fortification of enriched grains with synthetic folic acid is a potential concern for the elderly population who is at higher risk for Vitamin B12 deficiency. Consuming excess amounts of naturally occurring folate or synthetic folic acid can precipitate a deficiency of Vitamin B12, resulting in neurological damage. The purpose of this study was to determine the increase in folate intake in an elderly population due to the fortification of enriched grains. Three-day diet records of 320 participants (average age 76.8 years) were evaluated for total folate intake from food and supplements before and after the fortification of enriched grains. There was a significant mean daily folate intake increase of 63.8 microg due to fortification (p < 0.0001), raising the intake of total folate to 359 microg (89.8% of RDA). Supplements containing folic acid were consumed by 66% of the participants, raising the average total folate intake of supplement users to 793 microg per day. Only 5 participants exceeded the UL of 1,000 microg folic acid per day, with all 5 of these individuals consuming more than 1,000 microg folic acid per day from supplements alone. Folic acid fortification of grains does not appear to have increased the risk of excess folic acid in this population.

Aged↗
PubMed1981

Chemoresponsiveness to cAMP and folic acid during growth, development, and dedifferentiation in Dictyostelium discoideum.

Chemoresponsiveness to cAMP and to folic acid are monitored in growing, developing, and dedifferentiating amebae of the cellular slime mold Dictyostelium discoideum. Two semiquantitative assays are employed, one measuring the directed movement of cells up a gradient of chemoattractant ('chemotaxis' assay) and the other measuring the outward spreading of cells in response to a chemical stimulant distributed equally throughout the substratum ('spreading' assay). Vegetative amebae possess relatively insignificant levels of chemotactic responsiveness to cAMP. Six h after the initiation of development, at approximately the same time as the onset of aggregation, cells rapidly acquire chemotactic responsiveness to cAMP. During 'erasure', a dedifferentiation induced by resuspending aggregating cells in fresh nutrient medium, chemotactic responsiveness to cAMP is lost just after the erasure event. By the same chemotactic assay, it is demonstrated that vegetative amebae possess a significant level of chemotactic responsiveness to folic acid. Two h after the initiation of development, cells completely lose chemotactic responsiveness to folic acid. During erasure, cells reacquire chemotactic responsiveness to folic acid at approximately the same time that they lose responsiveness to cAMP. Dramatically different results are obtained by the spreading assay. When cells lose chemotactic responsiveness to folic acid early in development and when erasing cells lose chemotactic responsiveness to cAMP, they retain the spreading response to the two stimulants, respectively. The different results obtained for chemoreception employing the two assays are discussed in terms of molecular mechanisms, and a testable hypothesis is proposed for the possible roles of chemoresponsiveness and erasure in late morphogenesis.

Chemotaxis↗
PubMed2002

Efficacy of methylcobalamin on lowering total homocysteine plasma concentrations in haemodialysis patients receiving high-dose folic acid supplementation.

BACKGROUND: Hyperhomocysteinaemia, which is considered to be induced by impairment of the remethylation pathway in patients with chronic renal failure (CRF), cannot be cured solely by folic acid therapy. In the present study, we investigated the additional benefit of administration of methylcobalamin, which is a co-enzyme in the remethylation pathway, on lowering total homocysteine (tHcy) plasma concentrations in haemodialysis (HD) patients receiving high-dose folic acid supplementation. METHODS: In order to assess the efficacy on lowering plasma tHcy levels (fasting concentration), 21 HD patients, were randomly assigned and provided folic acid supplementation: 15 mg/day orally (group I, n=7); methylcobalamin 500 mg intravenously after each HD, in addition to folic acid (group II, n=7); or vitamin B(6) (B(6)), 60 mg/day orally, in addition to folic acid and methylcobalamin (group III, n=7). All patients were treated for 3 weeks. A methionine-loading test was conducted before and after supplementation. The following measurements were also made before and after supplementation for each group: serum folic acid, B(6), and vitamin B(12) (B(12)) concentrations (including measurement of proportion of methylcobalamin fraction). Twelve HD patients receiving methylcobalamin alone served as the HD control group and seven healthy volunteers served as the normal control group for this study. RESULTS: In our randomized HD patients the proportions of methylcobalamin fraction (48.3+/-7.5%) and plasma vitamin B(6) concentration (2.9+/-1.1 ng/ml) were significantly lower than in the normal controls (methylcobalamin 58.7+/-2.2%, P<0.01; B(6) 20.1+/-10.8 ng/ml, P<0.01), while folic acid and vitamin B(12) were not significantly different from the normal controls. Mean percentage reduction in fasting tHcy was 17.3+/-8.4% in group I, 57.4+/-13.3% in group II, 59.9+/-5.6% in group III, and 18.7+/-7.5% in HD controls. The power of the test to detect a reduction of tHcy level was 99.6% in group II and 99.9% in group III when type I error level was set at 0.05. Groups II and III had normal results for the methionine-loading test after treatment. Treatment resulted in normalization of fasting tHcy levels (<12 ng/ml) in all 14 patients treated by the combined administration of methylcobalamin and supplementation of folic acid regardless of whether there was supplementation of vitamin B(6). CONCLUSION: The benefit of methylcobalamin administration on lowering plasma tHcy levels in HD patients was remarkable. Our study suggested that both supplementations of high-dose folic acid and methylcobalamin are required for the remethylation pathway to regain its normal activity. This method could be a therapeutic strategy to combat the risk associated with atherosclerosis and cardiovascular disease in patients with chronic renal failure.

Adult↗
PubMed1995

A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes.

OBJECTIVES: To determine the risk of elevated total homocysteine (tHcy) levels for arteriosclerotic vascular disease, estimate the reduction of tHcy by folic acid, and calculate the potential reduction of coronary artery disease (CAD) mortality by increasing folic acid intake. DATA SOURCES: MEDLINE search for meta-analysis of 27 studies relating homocysteine to arteriosclerotic vascular disease and 11 studies of folic acid effects on tHcy levels. STUDY SELECTION AND DATA EXTRACTION: Studies dealing with CAD, cerebrovascular disease, and peripheral arterial vascular disease were selected. Three prospective and six population-based case-control studies were considered of high quality. Five cross-sectional and 13 other case-control studies were also included. Causality of tHcy's role in the pathogenesis of vascular disease was inferred because of consistency across studies by different investigators using different methods in different populations. DATA SYNTHESIS: Elevations in tHcy were considered an independent graded risk factor for arteriosclerotic vascular diseases. The odds ratio (OR) for CAD of a 5-mumol/L tHcy increment is 1.6 (95% confidence interval [CI], 1.4 to 1.7) for men and 1.8 (95% CI, 1.3 to 1.9) for women. A total of 10% of the population's CAD risk appears attributable to tHcy. The OR for cerebrovascular disease (5-mumol/L tHcy increment) is 1.5 (95% CI, 1.3 to 1.9). Peripheral arterial disease also showed a strong association. Increased folic acid intake (approximately 200 micrograms/d) reduces tHcy levels by approximately 4 mumol/L. Assuming that lower tHcy levels decrease CAD mortality, we calculated the effect of (1) increased dietary folate, (2) supplementation by tablets, and (3) grain fortification. Under different assumptions, 13,500 to 50,000 CAD deaths annually could be avoided; fortification of food had the largest impact. CONCLUSIONS: A 5-mumol/L tHcy increment elevates CAD risk by as much as cholesterol increases of 0.5 mmol/L (20 mg/dL). Higher folic acid intake by reducing tHcy levels promises to prevent arteriosclerotic vascular disease. Clinical trials are urgently needed. Concerns about masking cobalamin deficiency by folic acid could be lessened by adding 1 mg of cobalamin to folic acid supplements.

Arteriosclerosis↗
PubMed1999

Preconception counseling and women's compliance with folic acid supplementation.

QUESTION: I am counseling patients to take folic acid when they plan pregnancy and during early pregnancy. Is there any proof that counseling really causes women to comply? ANSWER: A recent Motherisk study showed that counseling women who were planning pregnancy about folic acid use is very effective: 71% of those counseled took folic acid, compared with only 17% of those who were not counseled.

Adult↗
PubMed1999

Achieving a public health recommendation for preventing neural tube defects with folic acid.

OBJECTIVES: This study examined 3 approaches to achieving the public health recommendation that all women of child-bearing age ingest 0.40 mg of folic acid per day to reduce the occurrence of neural tube defects (NTDs). METHODS: A total of 1136 mothers of infants with major malformations from the Boston and Philadelphia areas, whose pregnancies began from 1993 to 1995, were interviewed within 6 months of delivery about vitamin supplementation, dietary intakes, and other factors. RESULTS: Seventy-one percent of the 1136 women in the study did not take folic acid--containing supplements daily before conception, but the proportion decreased over the years of the study. Women not taking supplements consumed an average of 0.25 mg of naturally occurring folates daily. On the basis of dietary intakes reported by women not taking folic acid supplements, a simulation of cereal grain fortification with folic acid at the level required by the US Food and Drug Administration showed that an average of only 0.13 mg of folic acid would be ingested daily. CONCLUSIONS: With consumption of folic acid only through dietary intake, sizeable portions of the childbearing population would receive less than the level of folic acid recommended for preventing NTDs. Even with food fortification, women of childbearing age should be advised to take folic acid--containing supplements on a daily basis.

Adult↗
PubMed2006

Folic acid treatment of Zambian children with moderate to severe malaria anemia.

Whether administration of folic acid to children with malaria anemia is helpful is controversial. Therefore, we conducted a randomised, placebo-controlled trial of 14 days of treatment with folic acid (1 mg/d) in Zambian children with malaria anemia treated with either sulfadoxine/pyrimethamine (SP) or atovaquone/proguanil (AP). Among children who received SP, the prevalence of parasitemia was higher in children treated with folic acid than among those given placebo at days 3, 7, and 14 after the start of treatment, and the difference at day 3 was statistically significant (P = 0.013). Folic acid treatment had no effect on parasitemia in children treated with AP. Administration of folic acid led to a small increase in packed cell volume over that seen in the placebo group at days 14 and 28 after the start of treatment.

Anemia↗
PubMed2006

[The treatment of hyperhomocysteinemia in patients on dialysis: folic acid or the high-flow polysulphonic membrane?].

AIM: The aim of the study was to determine the effects of high-flow and low-flow hemodialysis (HD), with simultaneous treatment with folic acid and vitamin B12, on total homocysteine (tHcy) concentration in plasma of dialyzed patients. METHODS: The planned clinical observation included 46 patients of both sexes, aged 21-82, treated with bicarbonate dialysis for a mean of 4.7 years. The patients were divided into group A, subsequently dialyzed by use of high-flow polysulphonic membrane (AN 69ST, Nephral 300), and group B that continued to be dialyzed by use of low-flow diacetate membrane (Diacepal 14 and 16). The subjects in both groups received 30 mg of folic acid at the end of each dialysis (3 times a week), and 500 g of vitamin B12 at the end of every other dialysis. The method of stable isotopic dilution mass spectrometry was used to measure tHcy. Folic acid was determined by the test based on ion capture technology. Vitamin B12 was determined by MEIA. RESULTS: An increase in the concentration of tHcy was observed in 39/46 (85%) patients with a mean concentration of 24.76 +/- 11.04 micromol/L. The mean concentration of folic acid and vitamin B12 was within the normal limits. In the group dialyzed by high-flow dialyzer, the values of tHcy and folic acid decreased (18.74 +/- 2.95 micromol/L and 13.90 +/- 6.78 pmol/L) after hemodialysis, which was significant compared to the initial value (p<0.01 and p<0.05, respectively). At four weeks of treatment, tHcy concentration before HD showed a significant decrease both in the group dialyzed by high-flow dialyzer (15.10 +/- 4.26 mmol/L, p<0.01) and in the group dialyzed by low-flow dialyzer (12.54 +/- 3.87 micromol/L, p<0.01) compared to the measure before HD and before the treatment. There was no statistically significant difference (z -0.40, p>0.68) in the percentage of tHcy change between the group treated by high-flow dialyzer and the group treated by low-flow dialyzer in the measurements before HD and before the treatment with folic acid and vitamin B12, and after the treatment. DISCUSSION: There is a literature report on the concentration increase by 26 micromol/L, which is very similar to our result. The absence of long-term effect on predialysis concentration of tHcy in HD by high-flow membrane has also been described, because the decrease of tHcy is mantained until the uremic toxins, enzyme inhibitors that are necessary for the process of remethylation of Hcy, accumulated again. During high-flow HD, the folic acid concentration decreased by 23.05% on an average, consistent with other literature reports. Some reports support our observation that the dosage of folic acid required for tHcy decrease is 15-30 mg, and that the dosage higher than 60 mg does not significantly decrease tHcy concentration. Our study confirmed the reported observations that treatment with folic acid and vitamin B12 rather than high-flow dialyzer contributes to tHcy decrease. CONCLUSION: The study confirmed the high prevalence of hyperhomocysteinemia in patients on dialysis. The treatment with folic acid and vitamin B12 results in a significant decrease of tHcy. After individual HD by high-flow dialyzer, there is a significant, but temporary decrease of tHcy concentration in plasma. There is no significant difference in the efficiency on pre-dialysis tHcy concentration between the high-flow and low-flow dialyzer membrane. Because of the atherogenic effect of hyperhomocysteinemia, the treatment with folic acid and vitamin B12 should be accepted as an options to lower the risk factors for the rapid atherosclerosis in patients on dialysis, thus reducing the occurrence and fatality of cardiovascular diseases.

Adult↗
PubMed2004

Birth defects in Arkansas: is folic acid fortification making a difference?

BACKGROUND: Since 1998, fortification of grain products with folic acid has been mandated in the United States, in an effort to reduce the prevalence of neural tube defects (NTDs). Published reports have shown a reduction in the prevalence of spina bifida since fortification was mandated, but no published studies have reported a reduction in birth defects, other than NTDs, that are postulated to be associated with folic acid deficiency. This study was performed to determine if fortification has reduced the prevalence of NTDs and other birth defects in Arkansas. METHODS: Using data from the Arkansas Reproductive Health Monitoring System, prevalences were computed for thirteen specific birth defects with prior evidence supporting a protective effect of folic acid or multivitamins. Prevalences were calculated using data for live births to Arkansas residents for 1993-2000. Exposure to folic acid fortification was classified by birth year as "pre-fortification" (1993-1995), "transition" (1996-1998) or "post-fortification" (1999-2000). Logistic regression analysis was used to compute crude and adjusted prevalence odds ratios comparing the identified time periods. RESULTS: Prevalences decreased between the pre- and post-fortification periods for spina bifida, orofacial clefts, limb reduction defects, omphalocele, and Down syndrome, but only the decrease in spina bifida was statistically significant (prevalence odds ratio 0.56; 95% confidence interval, 0.37, 0.83). CONCLUSION: In Arkansas, the prevalence of spina bifida has decreased since folic acid fortification of foods was implemented. Similar studies by other birth defects surveillance systems are needed to confirm a preventive effect of fortification for malformations other than spina bifida.

Adult↗
PubMed2005

Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample.

BACKGROUND: Case control studies have supported a relationship between low folic acid and vitamin B112 and high homocysteine levels as possible predictors of depression. The results from epidemiological studies are mixed and largely from elderly populations. METHOD: A random subsample of 412 persons aged 60-64 years from a larger community sample underwent psychiatric and physical assessments, and brain MRI scans. Subjects were assessed using the PRIME-MD Patient Health Questionnaire for syndromal depression and severity of depressive symptoms. Blood measures included serum folic acid, vitamin B12, homocysteine and creatinine levels, and total antioxidant capacity. MRI scans were quantified for brain atrophy, subcortical atrophy, and periventricular and deep white-matter hyperintensity on T2-weighted imaging. RESULTS: Being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables. CONCLUSIONS: Low folic acid and high homocysteine, but not low vitamin B12 levels, are correlates of depressive symptoms in community-dwelling middle-aged individuals. The effects of folic acid and homocysteine are overlapping but distinct.

Aged↗
PubMed1995

Folic acid improves phenytoin pharmacokinetics.

Phenytoin (PHT) therapy to control seizures decreases serum folate levels in half of epileptic patients, thus increasing the risk of folate depletion. Supplementation with folic acid prevents deficiency but also changes PHT pharmacokinetics. Kinetic monitoring of PHT when folic acid is provided as a supplement has not been reported in women of child-bearing age. This study of six fertile women examined the interdependence of PHT and folic acid in a randomized crossover study of two treatments: treatment 1 consisted of 300 mg sodium PHT per day and treatment 2 consisted of 300 mg sodium PHT plus 1 mg folic acid per day. Dietary folic acid intake was calculated daily. During treatment 1, serum folate level decreased 38.0 +/- 18.6% (mean +/- standard deviation) and serum PHT concentration was in the low therapeutic range (43.92 +/- 14.52 mumol/L). During treatment 2, serum folate level increased 26.0 +/- 33.4%, and serum PHT level (39.04 +/- 14.16 mumol/L) was similar to that in treatment 1. Only one subject attained PHT steady state during treatment 1, but four subjects achieved steady state during treatment 2. Dietary folate intakes during treatments 1 and 2 were not significantly different. This study suggests an interdependence between PHT and folic acid and supports the observation that fertile women treated with PHT require folic acid supplementation to maintain a normal serum folate level.

Adult↗
PubMed1999

The influence of folic acid supplement on the outcome of pregnancies in the county of Funen in Denmark. Part III. Congenital anomalies. An observational study.

OBJECTIVE: The effect of folic acid supplement on the prevalence of congenital anomalies was studied in a Danish population. MATERIAL AND METHODS: From 1983 to 1986 all Danish women resident in the county of Funen were offered free folic acid when pregnant or planning a pregnancy. Data concerning the starting time of folic acid supplement and congenital anomalies were recorded on close to all pregnancies. Children of folic acid supplemented mothers were subdivided as to start of supplement with dividing lines at week 7 and week 11 calculated from the last menstrual period. Structural malformations were subdivided into an early group with malformation development in the first 7 weeks from the last menstrual period and a late group where malformations develop in weeks 8 to 11. RESULTS: In a total of 14,021 pregnancies 10,494 pregnant women (74.8%) had folic acid supplement. No folic acid was taken by 2721 women (19.4%) and in 806 cases (5.8%) information was lacking. The prevalence of congenital anomalies was 380 in 14,185 children (26.7/1000). Children whose mothers started folic acid supplement before the 7th week of pregnancy showed a significantly lower prevalence of the malformations which develop in the first 7 weeks, when compared to pregnancies with a later start of supplement. The result was interpreted as a clearcut trend.

Congenital Abnormalities↗
PubMed2005

Hyperhomocysteinemia in children treated with antiepileptic drugs is normalized by folic acid supplementation.

PURPOSE: To assess the prevalence of hyperhomocysteinemia in pediatric patients treated with antiepileptic drugs (AEDs) and to evaluate the effect of folic acid supplementation on plasma total homocysteine (tHcy) concentrations in hyperhomocysteinemic patients. METHODS: 123 patients from three regional hospitals participated in the study. Patients with hyperhomocysteinemia were included in a 3-month double-blind randomized trial testing oral folic acid supplementation (1 mg/day) versus placebo. RESULTS: Hyperhomocysteinemia (tHcy >10.4 micromol/L) was present in 19 of 123 patients. Patients with hyperhomocysteinemia were older (13.7 +/- 4 vs. 11.0 +/- 3.9 years) and had significantly lower folate and cobalamin concentrations. Multidrug (two or more) AED treatment and duration of therapy correlated significantly with elevated total homocysteine (tHcy) and low folate. In contrast, polymorphisms in the methylene tetrahydrofolate reductase gene (MTHFR 677 C-->T, 1298 A-->C, 1793 G-->A) had no significant impact on tHcy. Nine of 19 patients with hyperhomocysteinemia were randomized to placebo, whereas the remaining 10 patients received folic acid supplementation. Folic acid supplementation resulted in a significant increase of folate and decrease of tHcy, whereas both parameters remained unchanged in the placebo group. CONCLUSIONS: Hyperhomocysteinemia is present in 15.5% of children receiving long-term AED treatment. Multidrug treatment and long duration of therapy enhance the risk for hyperhomocysteinemia. Folic acid supplementation significantly reduces tHcy. We recommend assessment of serum folate and plasma tHcy in children receiving AEDs.

Anticonvulsants↗
PubMed2001

A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease.

OBJECTIVES: This study was designed to determine the effects of folic acid therapy on endothelial function in patients with coronary artery disease (CAD). BACKGROUND: Hyperhomocysteinemia, a risk factor for CAD, may cause atherosderosis by oxidative endothelial injury. Folic acid reduces plasma homocysteine, but the effect on adverse vascular events is unknown. METHODS: In a double-blind placebo-controlled trial, 90 patients (mean age [range] 63 [46 to 79] years, 79 men) with CAD were randomized to either folic acid 5 mg or placebo daily for 12 weeks. Endothelial function was assessed by measuring: 1) flow-mediated endothelium-dependent dilation (EDD) of the brachial artery; 2) combined serum nitrite/nitrate (NOx) concentrations and; 3) plasma von Willebrand factor (vWF) concentration. RESULTS: At the end of the study, plasma homocysteine was lower in the folic acid group compared with the placebo group (mean [95% confidence interval] 9.3 (8.5 to 10.1) vs. 12.3 [11.3 to 13.4] micromol/l, p < 0.001). Although there were no significant differences in EDD, serum NOx or plasma vWF between the two groups, there was a greater increase in EDD from baseline in the folic acid group compared to placebo (1.2 [0.7 to 1.8] vs. 0.4 [-0.3 to 1.1]%, p = 0.07). CONCLUSIONS: Folic acid reduced plasma homocysteine and was associated with a trend toward improved endothelial function in patients with CAD. The absence of an unequivocally positive result may have been due to inadequate sample size or chance. This reinforces the need for the results of large randomized controlled trials before the implementation of routine folic acid supplementation.

Aged↗