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PubMed1982

Effect of insulin on folic-acid transport in cultured fibroblasts.

Uptake of folic acid was measured in secondary cultures of skin fibroblasts from fetal rats. The cultures were made quiescent by 24 hours preincubation in medium containing 1% serum and subsequent 3 hours preincubation in phosphate buffered saline. The uptake of 3H-folic acid was linear with time during 15 seconds and reached a plateau level at 2-3 minutes. There was no further increase in the intracellular radioactivity until the end of the experiments at 10 minutes. The uptake of folic acid in fibroblasts was not concentrative and proceeded until equilibration with the extracellular concentration. Intracellular metabolic conversion of folic acid was not significant during the time of experiments (up to 10 minutes). Insulin caused a two-fold increase in the initial rate of folate uptake as determined from the 15 second uptake values. The dose response curves for the insulin effect showed that 85% of the maximal effect was exerted by 1 microM insulin. A lag period of 7-10 minutes was observed after the addition of insulin and before the effect on folic acid uptake was manifested. Thereafter the effect increased with the time of preincubation with insulin. The concentration dependence of folate uptake yielded non homogeneous curves. At low concentrations of substrate, saturable components were observed while at high concentrations (above 5 X 10(-6) M) a linear component was observed. Insulin increased the slope of the linear component and the Vmax of the saturable component while the Km remained unaltered.

Animals↗
PubMed2003

High prevalences of vitamin B12 and folic acid deficiency in elderly subjects in Israel.

The prevalences of vitamin B12 and folic acid deficiency in the general Israeli population of elders has not been assessed. We measured plasma cobalamin and folic acid concentrations in 418 subjects from four institutions for the aged, 749 subjects attending 19 geriatric day centres and 104 healthy controls. Methylmalonic acid (MMA) and/or homocysteine concentrations were determined in subjects who had a cobalamin concentration <221 pmol/l or folic acid concentration <11 nmol/l respectively. The prevalences of vitamin B12 deficiency (cobalamin <147 pmol/l and MMA > or =0.24 micromol/l), and folic acid deficiency (folic acid <11 nmol/l and homocysteine of >15 micromol/l) in subjects from day centres were 12.6% and 16.4% respectively, and in subjects from institutions 1.2% and 2.2% respectively (P < 0.001). Multiple logistic regression analysis indicated that the relative risk of living at home versus institutions for the aged was highly significant, with odds ratios (OR) of 6.8 [95% confidence interval (CI) 2.6-18.0] for vitamin B12 deficiency and 6.6 (95% CI 2.9-13.1) for folic acid deficiency. Analysis of data for day centre patients showed that folic acid deficiency was a significant risk factor of vitamin B12 deficiency (adjusted OR 3.68, 95% CI 2.27-5.98), and vitamin B12 deficiency was a significant risk of folic acid deficiency (adjusted OR 3.69, 95% CI 2.27-6.01). These data suggest that malnutrition is a major cause of the highly prevalent deficiencies of vitamin B12 and/or folic acid in elderly Israeli subjects dwelling at home.

Aged↗
PubMed2003

Folic acid awareness in Michigan, 1996-1999.

OBJECTIVE: To evaluate the prevalence and trend of folic acid awareness among Michigan mothers during 1996-1999 and to identify maternal characteristics predictive of folic acid awareness. METHODS: We analyzed data from the Michigan Pregnancy Risk Assessment Monitoring System, a population-based survey of women with recent live births. A positive response to the question, "Before you became pregnant, did you know that folic acid could help prevent some birth defects?" was used as an indicator of folic acid awareness. Logistic regression was used to evaluate trends in folic acid awareness prevalence and the association between folic acid awareness and certain maternal characteristics. RESULTS: Of the women invited to participate, 7252 responded (67.3%). Overall, folic acid awareness increased from 1996 to 1999 (60.3-71.4%; P < .001). However, folic acid awareness decreased for women with no high school education from 1997 to 1999 (59.3-13.8%, P = .05). In addition, folic acid awareness was lower among black women (adjusted odds ratio [OR] 0.43; 95% confidence interval [CI] 0.4, 0.5, versus other races), women with unplanned pregnancies (adjusted OR 0.6; 95% CI 0.5, 0.8, versus those with planned pregnancies), and those with no high school education (adjusted OR 0.08; 95% CI 0.03, 0.2, versus women with college education). CONCLUSION: Although folic acid awareness has increased among Michigan mothers overall during 1996-1999, it has decreased among women with less than a high school education, and substantial gaps exist among socioeconomic subgroups. Continued efforts are needed to improve folic acid awareness and consumption of folic acid among women of reproductive age, with special attention focused on populations experiencing gaps or declines in folic acid awareness.

Adult↗
PubMed2002

Interventional study of high dose folic acid in gastric carcinogenesis in beagles.

BACKGROUND: A decrease in folic acid and subsequent DNA hypomethylation may be involved in gastric carcinogenesis. Epidemiological and nutritional studies have indicated that folate status modulates the risk of developing cancers. AIMS: To investigate whether folic acid plays an important role in the chemoprevention of gastric carcinogenesis induced by N-ethyl-N-nitrosoguanidine (ENNG) in beagles. METHODS: Sixteen male beagles were randomly divided into two groups: folic acid treated group and control group. In both groups beagles were fed ENNG 75 mg per day for eight months and in the treated group 20 mg folic acid was given to beagles for 15 months. Gastroscopy and biopsies were performed before and every 2-3 months after administration of ENNG until the end of the experiment. Histopathological lesions were diagnosed with regard to the criteria for human gastric mucosal biopsies. Serum and gastric mucosal tissue folic acid concentrations were measured. RESULTS: In the control group, all beagles developed gastric cancer (8/8) compared with only 3/8 in the folic acid treated group (p<0.05). Moreover, serum and gastric mucosal tissue folic acid concentrations were markedly elevated 15 months after folic acid administration. The difference was statistically significant between the two groups (p<0.05). CONCLUSIONS: Our results indicate that high dose folic acid plays an important role in the chemoprevention of gastric carcinogenesis induced by a chemical carcinogen ENNG in beagles.

Animals↗
PubMed2001

Randomized trial of folic acid supplementation and serum homocysteine levels.

BACKGROUND: Lowering serum homocysteine levels with folic acid is expected to reduce mortality from ischemic heart disease. Homocysteine reduction is known to be maximal at a folic acid dosage of 1 mg/d, but the effect of lower doses (relevant to food fortification) is unclear. METHODS: We randomized 151 patients with ischemic heart disease to 1 of 5 dosages of folic acid (0.2, 0.4, 0.6, 0.8, and 1.0 mg/d) or placebo. Fasting blood samples for serum homocysteine and serum folate analysis were taken initially, after 3 months of supplementation, and 3 months after folic acid use was discontinued. RESULTS: Median serum homocysteine level decreased with increasing folic acid dosage, to a maximum at 0.8 mg of folic acid per day, when the homocysteine reduction (placebo adjusted) was 2.7 micromol/L (23%), similar to the known effect of folic acid dosages of 1 mg/d and above. The higher a person's initial serum homocysteine level, the greater was the response to folic acid, but there were statistically significant reductions regardless of the initial level. Serum folate level increased approximately linearly (5.5 nmol/L for every 0.1 mg of folic acid). Within-person fluctuations over time in serum homocysteine levels, measured in the placebo group, were large compared with the effect of folic acid, indicating that monitoring of the reduction in an individual is impractical. CONCLUSIONS: A dosage of folic acid of 0.8 mg/d appears necessary to achieve the maximum reduction in serum homocysteine level across the range of homocysteine levels in the population. Current US food fortification levels will achieve only a small proportion of the achievable homocysteine reduction.

Adult↗
PubMed1995

Does folic acid harm people with vitamin B12 deficiency?

Oral folic acid given before and during pregnancy can prevent about 75% of fetal neural tube defects. Even in large dose (20 mg daily) folic acid has never been shown to harm normal people, but it has acquired a bad reputation in pernicious anaemia. Before 1930, if untreated patients survived the anaemia, they succumbed to peripheral neuritis, subacute combined degeneration of the spinal cord, and death. The speed of this progression was extremely variable. From 1947 onwards, there were many reports of rapid neurological deterioration during administration of folic acid as sole therapy to people with pernicious anaemia. However, a review of clinical studies published before the introduction of liver and vitamin B12 therapy shows that neurological deterioration was often quite as rapid and severe in untreated patients. Oral folic acid can usually correct or prevent the anaemia of pernicious anaemia. Thus it could mask the underlying disease, and allow the development or progression of neurological deterioration, if diagnosis depended on the presence of anaemic symptoms. This possibility can readily be overcome by adequate education of doctors, so that a macrocytic anaemia is not regarded as a necessary accompanying sign of the neurological disorder. The hypothetical and avoidable side-effects of food fortification with folic acid have to be balanced against the certain benefit of preventing neural tube defects in unplanned pregnancies, and also against the probability that adults may be spared the neuropsychiatric and other ill-effects which result from inadequate dietary folic acid.

Aged↗
PubMed2006

[Uncertain effects of folic acid on disorders other than neural-tube defects].

Periconceptional supplemention with folic acid prevents neural-tube defects in infants. However, contrary to expectations, clinical trials found no beneficial effect of folic acid on the recurrence of cardiovascular disease. Trial evidence on folic acid and cognitive decline or dementia is scarce, though observational studies suggest that high folate intake may prevent these disorders. In contrast, animal studies suggest that high doses of folic acid enhance the growth of existing tumours. However, recent clinical trials failed to show significant effects of folic acid on cancer incidence and mortality. There are also speculations that folic-acid fortification may increase the number of newborns with the thermolabile variant of methylene tetrahydrofolate reductase. There appears to be little evidence that folic-acid supplementation may mask vitamin-B12 deficiency. In view of these controversies, it is unlikely that The Netherlands will mandate folic-acid fortification of staple foods in the near future. Therefore, women who are planning a pregnancy should be urged to take folic-acid supplements.

Animals↗
PubMed2004

Evidence for suboptimal use of periconceptional folic acid supplements globally.

OBJECTIVE: To systematically summarise the available evidence concerning the rate of folic acid supplement use pre- and periconceptionally, to identify those characteristics associated with low rates of use and to assess whether folic acid public awareness campaigns are associated with higher folic acid use. DESIGN: Systematic overview. SETTING: Survey studies. POPULATION: Women of reproductive age, most of whom were currently or recently pregnant. METHODS: Two investigators searched MEDLINE, Embase and Nutriotiongate databases between 1990 and 2003. Bibliographies of retrieved references were scanned for other relevant publications, and authors were contacted if necessary. Studies were included that evaluated the rate of folic acid supplement use either before conception or in early pregnancy. MAIN OUTCOME MEASURES: Rate of preconceptional and/or periconceptional folic acid use, rate of planned pregnancy in each study, as well as significant characteristics differentiating non-users from users of folic acid, including the effect of folic acid awareness campaigns. RESULTS: A total of 52 studies were included. In 34 studies, reported preconceptional folic acid use varied from 0.9% to 50%. In 49 studies, the reported rate of periconceptional supplement use ranged from 0.5% to 52%. Significant predictors of reduced periconceptional folic acid use were a low level of formal education, immigrant status, young maternal age, lack of a partner and an unplanned pregnancy. Four studies examined the effect of mass media campaigns on periconceptional folic acid use; the reported rates increased significantly, by a factor of 1.7 to 7.2, but in no study was the post-campaign rate above 50%. CONCLUSIONS: In many countries, fewer than 50% of women take periconceptional folic acid supplements. Consideration should be given to the practical advantages of folic acid fortification of centrally processed foods, such as wheat, corn and rice flour, while further promoting vitamin tablet supplement use and planned pregnancy.

Dietary Supplements↗
PubMed2006

Which mothers take folic acid and folate containing foods?

This study documented the prevalence (proportion) of mothers taking folic as supplements or as fortified foods and explored the factors that determined whether folic acid was taken. A cross sectional analysis of the baseline data of mothers who participated in the Perth Infant Feeding Study was performed. A total of 587 mothers who delivered at the two hospitals in the study completed baseline questionnaires. The factors associated with the decision to take folic acid supplements or fortified foods were investigated using multivariate logistic regression. Main outcome measures were the percentage of mothers taking folic acid or folic acid fortified foods. A total of 455 (78%) mothers stated that they took folic acid supplements before or during the first three months of their pregnancy. Of the 132 who did not take folate supplements only 35 (6% of all participating mothers) claimed to have taken folate fortified food or beverages. In the highest income group, 87% of mothers took folic acid supplements compared to 64% in the poorest group. The significant factors independently associated with not taking folic acid supplements or fortified food were " years of education " (OR ' 10 years or less' 0.45 (0.23-0.88)), " family income " (OR < $ 25000 0.40(0.20-0.80)), and for taking folic acid "the timing of the pregnancy. "(OR'actively trying'2.01 (0.1.04-0.3.87)). There was a significant proportion of mothers who did not take folic acid periconceptually. The mothers who were not taking folic were less educated, from lower socio-economic groups and were not actively trying to fall pregnant at the time they became pregnant. The results suggest that in order to reach all Australian mothers, mandatory fortification of foods with folic acid should be required.

Adolescent↗
PubMed2004

Folic acid: neurochemistry, metabolism and relationship to depression.

The associations of folic acid and its derivatives with depressive disorder are reviewed. Derivatives of folic acid such as biopterins and the synthesis of S-adenosyl methionine (SAM) are known either to be associated with improvement or to have a direct therapeutic effect in depressive disorder. Studies investigating plasma and red cell folic acid levels in depressed patients have used differing assay methodologies which make comparison difficult, although there is substantial evidence of the association between depressive disorder (particularly severe depression) and low folic acid levels. The few studies available suggest folic acid has either antidepressant properties or can act as an augmenting agent for standard antidepressant treatment. A recently discovered genetic variant (5,10 MTHFR) leading to altered folic acid metabolism may explain why some individuals are vulnerable to the effects of folic acid deficiency, despite adequate intake. The links of 5,10 MTHFR to the presence of depressive disorder in the community are being investigated.

Brain↗
PubMed2005

L-folic acid supplementation in healthy postmenopausal women: effect on homocysteine and glycolipid metabolism.

CONTEXT: Hyperhomocysteinemia as well as alterations of glycemic and lipidic metabolism are recognized as risk factors for cardiovascular diseases. OBJECTIVE: The aim of this study was to examine the effect of L-folic acid supplementation on homocysteine (Hcy) and related thiols, such as cysteine (Cys) and Cys-glycine (Cys-Glyc) pathways and their relationship to glucose, insulin, and lipidic metabolism in normoinsulinemic postmenopausal women. DESIGN: This study was a randomized placebo, not double-blind, trial. SETTING: The study was performed in an academic research center. PATIENTS OR OTHER PARTICIPANTS: Twenty healthy postmenopausal women were selected. No patient was taking drugs known to affect lipid or glucose metabolism. INTERVENTION(S): Patients underwent two hospitalizations before and after 8 wk of L-acid folic (7.5 mg/d) or placebo administration. The glycemic metabolism was studied by an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Hcy metabolism was studied by a standardized oral methionine-loading test. MAIN OUTCOME MEASURE(S): Hcy, Cys, and Cys-Glyc, basally and after a methionine loading test, were measured. Basal insulin, glucose, and peptide C levels as well as area under the curve for insulin, area under the curve for peptide, hepatic insulin extraction, and metabolic index were assayed. The total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels and the cholesterol/HDL and LDL/HDL ratios were also measured. RESULTS: The total basal Hcy concentration and the plasma postmethionine loading Hcy values were significantly decreased (P < 0.01) in L-folic acid-treated patients, whereas postmethionine loading Cys-Glyc levels were markedly increased (P < 0.02). Furthermore, L-folic acid intake induced a significant improvement in carbohydrate metabolism through an increase in fractional hepatic insulin extraction (P < 0.05) and peripheral insulin sensitivity (P < 0.02) in normoinsulinemic women. HDL levels considerably increased, inducing an improvement in other atherosclerotic indexes, such as cholesterol/HDL and LDL/HDL ratios (P < 0.03). CONCLUSIONS: These results show that folic acid supplementation lowers plasma Hcy levels and improves insulin and lipid metabolism, reducing the risk of cardiovascular disease.

Blood Glucose↗
PubMed2001

Folic acid supplementation and risk for imperforate anus in China.

Maternal consumption of folic acid before pregnancy and during early pregnancy is associated with a reduced risk for some birth defects. Whether folic acid can reduce the risk for imperforate anus is unknown. As part of a public health campaign conducted in China from 1993 through 1995, the outcomes of pregnancies of > or =20 weeks' gestation were evaluated among women using folic acid supplements. The women were asked to take one pill containing 400 microg of folic acid (without other vitamins) every day from the time of their premarital examination until the end of their first trimester of pregnancy. Rates of imperforate anus and risk ratios for imperforate anus among the offspring of these women were calculated according to folic acid use. Among the offspring of women who took folic acid and women who did not take folic acid, 20 and 30 infants with imperforate anus were identified, respectively. The rate of imperforate anus was 3.1 per 10,000 among the offspring of women who did not take folic acid and 1.6 per 10,000 among the offspring of women who took folic acid; adjusted for maternal age, the risk ratio was 0.59 (95% confidence interval: 0.33, 1.07). Daily maternal consumption of 400 microg of folic acid before and during early pregnancy may reduce the risk for imperforate anus.

Adult↗
PubMed1983

The effect of folic acid on cAMP-elicited cAMP production in Dictyostelium discoideum.

In Dictyostelium discoideum, folic acid serves as a chemoattractant, accelerates the appearance of several developmentally regulated enzymes, alters the phase of spontaneous light-scattering oscillations, and elicits increases in cGMP and cAMP. The effect of folic acid and pteridine analogs on rates of [3H]cAMP secretion, monitored by rapid perfusion, was studied. At low cell densities folic acid elicited only minimal [3H]cAMP secretion. At high cell densities, folic acid elicited greater increases in cellular cAMP and rates of [3H]cAMP secretion than did maximally effective doses of cAMP. Following pretreatment with 10(-8) M cAMP for 10 min or 10(-6) M cAMP for 2 min, no [3H]cAMP was secreted in response to folic acid. Conversely, pretreatment with folic acid did not impair subsequent responsiveness to 5 X 10(-9) M cAMP. Simultaneous addition of folic acid and cAMP increased the release of [3H]cAMP two- to threefold compared to control stimuli of the same concentration of cAMP. Pretreatment with a mixed stimulus attenuated the response to a subsequent increment in the cAMP concentration only if the higher cAMP stimulus did not include folic acid. The effects of folic acid are mimicked by the pteridine ring alone; analogs substituted at the 2- or 5-position are ineffective; non-reducible analogs are partially active. The observations presented here suggest significant differences in the mechanisms by which cAMP and folic acid stimulate cAMP production. Rather than there being separate receptors for each chemoattractant that interact in the same way with an intracellular pathway, it appears that folic acid and pteridine analogs potentiate the response to cAMP.

Adaptation, Physiological↗
PubMed1999

How many pregnant women in Christchurch are using folic acid supplements in early pregnancy?

AIMS: To determine the proportion of pregnant women in Christchurch using folic acid supplements in early pregnancy. To evaluate the level of current knowledge relating to folic acid amongst pregnant women. To determine the main sources from which this information was gained. METHODS: A short questionnaire was administered to 191 pregnant women in Christchurch during antenatal visits with their lead maternity carer. The survey contained questions relating to knowledge about folic acid and use together with sources of information regarding folic acid. Obstetric and demographic details were also collected. RESULTS: The response rate was 95.5%. Ninety-one per cent (174/191) of participants had heard of folic acid and, of these, 63% knew that folic acid reduces the risk of spina bifida. Of the 191 participants in the study, 118(62%) took folic acid supplements at some stage of their pregnancy, however, only 33(17%) had taken periconceptual folic acid supplements. Of the 44% of all women in the study with a planned pregnancy, only 35% had taken folic acid supplements periconceptually. Of those women with an unplanned pregnancy (55%), only 2.8% had taken a folic acid supplement periconceptually. The main sources of advice for women relating to folic acid were general practitioners (48%) or media advertising, either in the form of a magazine, or health pamphlet or television promotion (20%). CONCLUSIONS: The results of this study indicate that the level of knowledge amongst women of child-bearing age relating to folic acid is relatively high compared with other countries. Despite this high level of knowledge, only a small percentage of women are actually consuming a folic acid supplement during the recommended periconceptual period due in part to the high proportion of unplanned pregnancies. These results emphasize the need for an effective public health strategy to ensure that all women of child-bearing age have access to an adequate folic acid intake.

Female↗
PubMed2005

Randomized trial of a physician-based intervention to increase the use of folic acid supplements among women.

OBJECTIVE: Fewer than one third of American women take folic acid daily, although many women report that they would take folic acid if their physicians advised them to do so. This study determined the impact of a physician intervention during routine gynecologic visits on folic acid supplementation. STUDY DESIGN: Patients were assigned randomly to receive brief folic acid counseling, a reminder phone call, and 30 folic acid tablets (n = 162 women; intervention group) or to receive counseling about other preventive health behaviors and a folic acid informational pamphlet (n = 160 women; control group). Self-reported folic acid use was compared at baseline and at 2 months. RESULTS: Of the 279 patients who completed the study, weekly folic acid intake increased in the intervention group by 68%, compared with 20% in the control group ( P =.008). No significant differences were found in daily intake. The women who were most influenced by the intervention were black and lower income and not planning pregnancies. CONCLUSION: With little effort expended to encourage folic acid use, gynecologists could potentially reduce the risk of folate-preventable birth defects among their patients by as much as 11%.

Adolescent↗
PubMed1979

Folic acid supplement and intrauterine growth.

The effect of a folic acid supplment on birth weight and placental weight in women delivering in the early summer in Denmark was investigated. Thirty-six women with normal pregnancy and expected delivery in the first half of June were selected consecutively. They were paired two and two, and allotted to two groups, one of which was supplied daily with 5 mg folic acid, and the second with tablets without folic acid, from the 23rd week of pregnancy. A significant correlation was found between erythrocyte folic acid and birth weight. The infants in the folic acid group were 12.7 per cent heavier than those in the control group (p less than 0.01). A similar difference was found with regard to placental weight and the number of placental cells.

Birth Weight↗