scholarly journals Intake and status of folate and related B-vitamins: considerations and challenges in achieving optimal status

2008 ◽  
Vol 99 (S3) ◽  
pp. S48-S54 ◽  
Author(s):  
Helene McNulty ◽  
John M. Scott
Keyword(s):  
Folic Acid ◽  
Folic Acid Supplementation ◽  
B Vitamins ◽  
Natural Food ◽  
Vitamin B ◽  
High Dose ◽  
Folic Acid Fortification ◽  
Younger Women ◽  
Folate Status ◽  
The Uk

Folate and the metabolically related B-vitamins, vitamin B12and riboflavin, have attracted much scientific and public health interest in recent years. Apart from a well established role in preventing neural tube defects (NTDs), evidence is emerging to support other potential roles for folate and/or related B-vitamins in protecting against cardiovascular disease (especially stroke), certain cancers, cognitive impairment and osteoporosis. However, typical folate intakes are sub-optimal, in that although adequate in preventing clinical folate deficiency (i.e. megaloblastic anaemia) in most people, they are generally insufficient to achieve a folate status associated with the lowest risk of NTDs. Natural food folates have a limited ability to enhance folate status as a result of their poor stability under typical cooking conditions and incomplete bioavailability when compared with the synthetic vitamin, folic acid (as found in supplements and fortified foods). Current folate recommendations to prevent NTDs (based primarily on folic acid supplementation) have been found to be ineffective in several European countries. In contrast, in North America and Chile, the policy of mandatory folic acid-fortification has proven itself in terms of lowering the prevalence of NTD, but remains controversial because of concerns regarding potential risks of chronic exposure to high-dose folic acid. In the case of vitamin B12, the achievement of an optimal status is particularly difficult for many older people because of the common problem of food-bound B12malabsorption. Finally, there is evidence that riboflavin status is generally low in the UK population, and particularly so in younger women; this warrants further investigation.

scholarly journals Folate and vitamin B12status in relation to cognitive impairment and anaemia in the setting of voluntary fortification in the UK

2008 ◽  
Vol 100 (5) ◽  
pp. 1054-1059 ◽  
Author(s):  
Robert Clarke ◽  
Paul Sherliker ◽  
Harold Hin ◽  
Anne M. Molloy ◽  
Ebba Nexo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Folic Acid ◽  
Older People ◽  
Serum Folate ◽  
Vitamin B ◽  
Cross Sectional ◽  
Folic Acid Fortification ◽  
Folate Status ◽  
Cross Sectional Studies ◽  
The Uk

Concerns about risks for older people with vitamin B12deficiency have delayed the introduction of mandatory folic acid fortification in the UK. We examined the risks of anaemia and cognitive impairment in older people with low B12and high folate status in the setting of voluntary fortification in the UK. Data were obtained from two cross-sectional studies (n2403) conducted in Oxford city and Banbury in 1995 and 2003, respectively. Associations (OR and 95 % CI) of cognitive impairment and of anaemia with low B12status (holotranscobalamin < 45 pmol/l) with or without high folate status (defined either as serum folate >30 nmol/l or >60 nmol/l) were estimated after adjustment for age, sex, smoking and study. Mean serum folate levels increased from 15·8 (sd14·7) nmol/l in 1995 to 31·1 (sd26·2) nmol/l in 2003. Serum folate levels were greater than 30 nmol/l in 9 % and greater than 60 nmol/l in 5 %. The association of cognitive impairment with low B12status was unaffected by highv.low folate status (>30 nmol/l) (OR 1·50 (95 % CI 0·91, 2·46)v.1·45 (95 % CI 1·19, 1·76)), respectively. The associations of cognitive impairment with low B12status were also similar using the higher cut-off point of 60 nmol/l for folate status ((OR 2·46; 95 % CI 0·90, 6·71)v.(1·56; 95 % CI 1·30, 1·88)). There was no evidence of modification by high folate status of the associations of low B12with anaemia or cognitive impairment in the setting of voluntary fortification, but periodic surveys are needed to monitor fortification.

scholarly journals High-dose folic acid supplementation in rats: effects on gestation and the methionine cycle

2000 ◽  
Vol 83 (2) ◽  
pp. 177-183 ◽  
Author(s):  
M. Achón ◽  
E. Alonso-Aperte ◽  
L. Reyes ◽  
N. Úbeda ◽  
G. Varela-Moreiras
Keyword(s):  
Folic Acid ◽  
Dietary Supplementation ◽  
Folic Acid Supplementation ◽  
Serum Folate ◽  
Vitamin B ◽  
High Dose ◽  
Acid Supplementation ◽  
Folate Status ◽  
Methionine Cycle ◽  
Acid Administration

There is new evidence that a good folate status may play a critical role in the prevention of neural-tube defects and in lowering elevated homocysteine concentrations. This adequate folate status may be achieved through folic acid dietary supplementation. Folate is a water-soluble vitamin with a low potential toxicity. However, the possible consequences of long-term high-dose folic acid supplementation are unknown, especially those related to the methionine cycle, where folate participates as a substrate. With the aim of evaluating such possible effects, four groups of Wistar rats were classified on the basis of physiological status (virgin v. pregnant) and the experimental diet administered (folic-acid-supplemented, 40 mg/kg diet v. control, 2 mg folic acid/kg diet). Animals were fed on the diets for 3 weeks. Results showed that gestation outcome was adequate in both groups regardless of the dietary supplementation. However, there were reductions (P < 0·001) in body weight and vertex-coccyx length in fetuses from supplemented dams v. control animals. Folic acid administration also induced a higher (P < 0·01) S-adenosylmethionine : S-adenosylhomocysteine value due to increased S-adenosylmethionine synthesis (P < 0·01). However, hepatic DNA methylation and serum methionine concentrations remained unchanged. Serum homocysteine levels were reduced in supplemented dams (P < 0·05). Finally, pregnancy caused lower serum folate, vitamin B6 and vitamin B12 levels (P < 0·05). Folic acid administration prevented the effect of pregnancy and raised folate levels in dams, but did not change levels of vitamins B12 and B6. These new findings are discussed on the basis of potential benefits and risks of dietary folic acid supplementation.

scholarly journals Addressing optimal folate and related B-vitamin status through the lifecycle: health impacts and challenges

2019 ◽  
Vol 78 (3) ◽  
pp. 449-462 ◽  
Author(s):  
Helene McNulty ◽  
Mary Ward ◽  
Leane Hoey ◽  
Catherine F. Hughes ◽  
Kristina Pentieva
Keyword(s):  
Folic Acid ◽  
Methylenetetrahydrofolate Reductase ◽  
Folic Acid Supplementation ◽  
B Vitamins ◽  
Food Sources ◽  
Natural Food ◽  
Vitamin B ◽  
Genetic Characteristics ◽  
Increased Risk ◽  
B Vitamin

The functional effects of folate within C1 metabolism involve interrelationships with vitamin B12, vitamin B6 and riboflavin, and related gene–nutrient interactions. These B vitamins have important roles throughout life, from pregnancy, through childhood, to middle and older age. Achieving optimal nutritional status for preventing folate-related disease is challenging, however, primarily as a result of the poor stability and incomplete bioavailability of folate from natural food sources when compared with the synthetic vitamin form, folic acid. Thus, in European countries, measures to prevent neural tube defects (NTD) have been largely ineffective because of the generally poor compliance of women with folic acid supplementation as recommended before and in early pregnancy. In contrast, countries worldwide with mandatory folic acid fortification policies have experienced marked reductions in NTD. Low vitamin B12 status is associated with increased risk of cognitive dysfunction, CVD and osteoporosis. Achieving optimal B12 status can be problematic for older people, however, primarily owing to food-bound B12 malabsorption which leads to sub-clinical deficiency even with high dietary B12 intakes. Optimising B-vitamin intake may be particularly important for sub-populations with impaired folate metabolism owing to genetic characteristics, most notably the 677C→T variant in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR). This common folate polymorphism is linked with several adverse health outcomes, including stroke, however, recent evidence has identified its novel interaction with riboflavin (the MTHFR cofactor) in relation to blood pressure and risk of developing hypertension. This review addresses why and how the optimal status of folate-related B vitamins should be achieved through the lifecycle.

scholarly journals Health behaviours in 131,182 UK women planning pregnancy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Beth McDougall ◽  
Kimberley Kavanagh ◽  
Judith Stephenson ◽  
Lucilla Poston ◽  
Angela C. Flynn ◽  
...  
Keyword(s):  
Folic Acid ◽  
Health Behaviours ◽  
Folic Acid Supplementation ◽  
Preconception Health ◽  
Younger Women ◽  
Healthy Pregnancy ◽  
Folic Acid Supplements ◽  
Weekly Physical Activity ◽  
The Uk ◽  
Changes Over Time

Abstract Background A woman’s health at the time of conception lays the foundation for a healthy pregnancy and the lifelong health of her child. We investigated the health behaviours of UK women planning pregnancy. Methods We analysed survey data from the ‘Planning for Pregnancy’ online tool (Tommy’s, UK). We described all women planning pregnancy and compared the frequency of non-adherence to preconception recommendations in women who had already stopped contraception (active planners) and those who had not (non-active planners). Results One hundred thirty-one thousand one hundred eighty-two women from across the UK were included, of whom 64.8% were actively planning pregnancy. Of the whole cohort, twenty percent were smokers and less than one third took folic acid supplements (31.5%). Forty two percent engaged in less than the recommended 150 min of weekly physical activity and only 53.3% consumed five portions of fruit or vegetables 4 days a week. Smokers were 1.87 times more likely to be active planners than non-smokers (95% CI 1.79–1.94), and women who took folic acid were 7 times more likely to be active planners (95% CI 6.97–7.59) compared to women who did not. Smoking, drug use and lack of folic acid supplementation were common in younger women and those who were underweight. Conclusions This unique survey of UK women has identified poor adherence to preconception recommendations in those planning pregnancies and supports the need for a greater public health focus on preconception health. This study provides a contemporary basis from which to inform preconception health advice and a benchmark to measure changes over time.

scholarly journals B vitamins for stroke prevention

2018 ◽  
Vol 3 (2) ◽  
pp. 51-58 ◽  
Author(s):  
Graeme J Hankey
Keyword(s):  
Clinical Trials ◽  
Folic Acid ◽  
Stroke Prevention ◽  
Stroke Risk ◽  
Folic Acid Supplementation ◽  
Adverse Outcomes ◽  
B Vitamins ◽  
Vitamin B ◽  
Folate Supplementation ◽  
Acid Supplementation

Supplementation with B vitamins (vitamin B9(folic acid), vitamin B12 and vitamin B6) lowers blood total homocysteine (tHcy) concentrations by about 25% and reduces the relative risk of stroke overall by about 10% (risk ratio (RR) 0.90, 95% CI 0.82 to 0.99) compared with placebo. Homocysteine-lowering interventions have no significant effect on myocardial infarction, death from any cause or adverse outcomes. Factors that appear to modify the effect of B vitamins on stroke risk include low folic acid status, high tHcy, high cyanocobalamin dose in patients with impaired renal function and concurrent antiplatelet therapy. In regions with increasing levels or established policies of population folate supplementation, evidence from observational genetic epidemiological studies and randomised controlled clinical trials is concordant in suggesting an absence of benefit from lowering of homocysteine with folic acid for prevention of stroke. Clinical trials indicate that in countries which mandate folic acid fortification of food, folic acid supplementation has no significant effect on reducing stroke risk (RR 1.05, 95% CI 0.90 to 1.23). However, in countries without mandatory folic acid food fortification, folic acid supplementation reduces the risk of stroke by about 15% (RR 0.85, 95% CI 0.77 to 0.94). Folic acid alone or in combination with minimal cyanocobalamin (≤0.05 mg/day) is associated with an even greater reduction in risk of future stroke by 25% (RR 0.75, 95% CI 0.66 to 0.86), whereas the combination of folic acid and a higher dose of cyanocobalamin (≥0.4 mg/day) is not associated with a reduced risk of future stroke (RR 0.95, 95% CI 0.86 to 1.05). The lack of benefit of folic acid plus higher doses of cyanocobalamin (≥0.4 mg/day) was observed in trials which all included participants with chronic kidney disease. Because metabolic B12 deficiency is very common and usually not diagnosed, future randomised trials of homocysteine-lowering interventions for stroke prevention should probably test a combination of folic acid and methylcobalamin or hydroxocobalamin instead of cyanocobalamin, and perhaps vitamin B6.

Folate, vitamin B12, and vitamin B6status of a group of high socioeconomic status women in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort

2014 ◽  
Vol 39 (12) ◽  
pp. 1402-1408 ◽  
Author(s):  
Faiqa Fayyaz ◽  
Flora Wang ◽  
René L. Jacobs ◽  
Deborah L. O’Connor ◽  
Rhonda C. Bell ◽  
...  
Keyword(s):  
Folic Acid ◽  
Pregnancy Outcomes ◽  
First Trimester ◽  
Folic Acid Supplementation ◽  
Nutritional Deficiencies ◽  
Vitamin B ◽  
Folate Status ◽  
Plasma Folate ◽  
Child Bearing ◽  
Upper Level

Folic acid supplementation and food fortification policies have improved folate status in North American women of child bearing age. Recent studies have reported the possible inadequacy of vitamin B12and B6in the etiology of neural tube defects in folate-fortified populations. The aims of this study were to describe folate status and its relationship to supplementation and to assess vitamin B12and B6status in a cohort of pregnant women. Supplement intake data were collected in each trimester from the first cohort (n = 599) of the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Red blood cell folate (RBCF) and plasma folate, holotranscobalamin, and pyridoxal 5-phosphate were measured. Overt folate deficiency was rare (3%) but 24% of women in their first trimester had suboptimal RBCF concentration (<906 nmol·L−1). The proportion of the cohort in this category declined substantially in second (9%) and third (7%) trimesters. High RBCF (>1360 nmol·L−1) was observed in approximately half of the women during each pregnancy trimester. Vitamin B12and B6deficiencies were rare (<1% of the cohort). Women consuming folic acid supplements above the upper level had significantly higher RBCF and plasma folate concentrations. In conclusion, the prevalence of vitamin B12and B6deficiency was very low. A quarter of the women had suboptimal folate status in the first trimester of pregnancy and over half the women had abnormally high RBCF, suggesting that supplementation during pregnancy is not appropriate in a cohort of women considered to be healthy and a low risk for nutritional deficiencies.

Meta-analysis of folic acid efficacy trials in stroke prevention

Neurology ◽  
2017 ◽  
Vol 88 (19) ◽  
pp. 1830-1838 ◽  
Author(s):  
Min Zhao ◽  
Guangliang Wu ◽  
Youbao Li ◽  
Xiaobin Wang ◽  
Fan Fan Hou ◽  
...  
Keyword(s):  
Folic Acid ◽  
Fixed Effects ◽  
Stroke Risk ◽  
Meta Analysis ◽  
Folic Acid Supplementation ◽  
Vitamin B ◽  
Fixed Effects Model ◽  
Folic Acid Fortification ◽  
Acid Supplementation ◽  
Low Dosage

Objective:To examine the efficacy and effect modifiers of folic acid supplementation in the prevention of stroke in regions without folic acid fortification based on relevant, up-to-date published randomized trials.Methods:Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of stroke using a fixed effects model.Findings:Overall, folic acid supplementation significantly reduced the stroke risk by 11% (22 trials, n = 82,723; RR 0.89, 95% confidence interval [CI] 0.84–0.96). The effect was greater in low folate regions (2 trials, n = 24,020; Asia, 0.78, 0.67–0.90) compared to high folate regions (7 trials, n = 14,655; America, 1.05, 0.90–1.23), and among patients without folic acid fortification (11 trials, n = 49,957; 0.85; 0.77–0.94) compared with those with folic acid fortification (7 trials, n = 14,655; 1.05, 0.90–1.23). In further stratified analyses among trials without folic acid fortification, a larger beneficial effect was found in those trials that used a low dosage of folic acid (≤0.8 mg: 0.78, 0.69–0.88) or low baseline vitamin B12 levels (<384 pg/mL: 0.78, 0.68–0.89). In the corresponding comparison groups, the effect sizes were attenuated and insignificant (p for interaction <0.05 for both). Although the interaction tests were not significant, there might be a higher benefit in trials with a low dosage of vitamin B12, a low prevalence of statin use, but a high prevalence of hypertension.Conclusions:Folic acid supplementation could reduce the stroke risk in regions without folic acid fortification, particularly in trials using a relatively low dosage of folic acid and with low vitamin B12 levels.

scholarly journals Folate and vitamin B12: friendly or enemy nutrients for the elderly

2007 ◽  
Vol 66 (4) ◽  
pp. 548-558 ◽  
Author(s):  
Geraldine J. Cuskelly ◽  
Kathleen M. Mooney ◽  
Ian S. Young
Keyword(s):  
Folic Acid ◽  
Serum Vitamin ◽  
The Elderly ◽  
Megaloblastic Anaemia ◽  
Vitamin B ◽  
Folic Acid Fortification ◽  
The Usa ◽  
Criteria For Diagnosis ◽  
Folate And Vitamin B12 ◽  
The Uk

In the UK vitamin B12deficiency occurs in approximately 20% of adults aged >65 years. This incidence is significantly higher than that among the general population. The reported incidence invariably depends on the criteria of deficiency used, and in fact estimates rise to 24% and 46% among free-living and institutionalised elderly respectively when methylmalonic acid is used as a marker of vitamin B12status. The incidence of, and the criteria for diagnosis of, deficiency have drawn much attention recently in the wake of the implementation of folic acid fortification of flour in the USA. This fortification strategy has proved to be extremely successful in increasing folic acid intakes pre-conceptually and thereby reducing the incidence of neural-tube defects among babies born in the USA since 1998. However, in successfully delivering additional folic acid to pregnant women fortification also increases the consumption of folic acid of everyone who consumes products containing flour, including the elderly. It is argued that consuming additional folic acid (as ‘synthetic’ pteroylglutamic acid) from fortified foods increases the risk of ‘masking’ megaloblastic anaemia caused by vitamin B12deficiency. Thus, a number of issues arise for discussion. Are clinicians forced to rely on megaloblastic anaemia as the only sign of possible vitamin B12deficiency? Is serum vitamin B12alone adequate to confirm vitamin B12deficiency or should other diagnostic markers be used routinely in clinical practice? Is the level of intake of folic acid among the elderly (post-fortification) likely to be so high as to cure or ‘mask’ the anaemia associated with vitamin B12deficiency?

scholarly journals Folate bioavailability

2004 ◽  
Vol 63 (4) ◽  
pp. 529-536 ◽  
Author(s):  
Helene McNulty ◽  
Kristina Pentieva
Keyword(s):  
Folic Acid ◽  
Methodological Approach ◽  
Relative Bioavailability ◽  
Food Sources ◽  
Future Research ◽  
Natural Food ◽  
Limiting Factor ◽  
Folic Acid Fortification ◽  
Folate Status ◽  
Folate Bioavailability

The achievement of optimal folate status to prevent neural-tube defects, and possibly other diseases, is hindered by the well-recognised incomplete bioavailability of the natural folates found in foods compared with the synthetic vitamin, folic acid. Folate bioavailability from different foods is considered to be dependent on a number of factors, including the food matrix, the intestinal deconjugation of polyglutamyl folates, the instability of certain labile folates during digestion and the presence of certain dietary constituents that may enhance folate stability during digestion. There is conflicting evidence as to whether the extent of conjugation of polyglutamyl folate (in the absence of specific inhibitors of deconjugation in certain foods) is a limiting factor in folate bioavailability. Estimates of the extent of lower bioavailability of food folates compared with folic acid (relative bioavailability) show great variation, ranging anywhere between 10 and 98%, depending on the methodological approach used. The lack of accurate data on folate bioavailability from natural food sources is of particular concern in those countries in which there is no mandatory folic acid fortification, and therefore a greater reliance on natural food folates as a means to optimise status. Apart from the incomplete bioavailability of food folates, the poor stability of folates in foods (particularly green vegetables) under typical conditions of cooking can substantially reduce the amount of vitamin ingested and thereby be an additional factor limiting the ability of food folates to enhance folate status. A recent workshop convened by the Food Standards Agency concluded that gaining a better understanding of folate bioavailability in representative human diets is a high priority for future research.

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