scholarly journals Comparison of (6S)-5-methyltetrahydrofolic acidv.folic acid as the reference folate in longer-term human dietary intervention studies assessing the relative bioavailability of natural food folates: comparative changes in folate status following a 16-week placebo-controlled study in healthy adults

2009 ◽  
Vol 103 (5) ◽  
pp. 724-729 ◽  
Author(s):  
Anthony J. A. Wright ◽  
Maria J. King ◽  
Caroline A. Wolfe ◽  
Hilary J. Powers ◽  
Paul M. Finglas

Folic acid (pteroylmonoglutamic acid) has historically been used as the reference folate in human intervention studies assessing the relative bioavailability of dietary folate. Recent studies using labelled folates indicated different plasma response kinetics to folic acid than to natural (food) folates, thus obviously precluding its use in single-dose experiments. Since differences in tissue distribution and site of biotransformation were hypothesised, the question is whether folic acid remains suitable as a reference folate for longer-term intervention studies, where the relative bioavailability of natural (food) folate is assessed based on changes in folate status. Healthy adults aged 18–65 years (n163) completed a 16-week placebo-controlled intervention study in which the relative bioavailability of increased folate intake (453 nmol/d) from folate-rich foods was assessed by comparing changes in plasma and erythrocyte folate concentration with changes induced by an equal reference dose of supplemental (6S)-5-methyltetrahydrofolic acid or folic acid. The relative increase in plasma folate concentration in the food group was 31 % when compared with that induced by folic acid, but 39 % when compared with (6S)-5-methyltetrahydrofolic acid. The relative increase in erythrocyte folate concentration in the food group when compared with that induced by folic acid was 43 %, and 40 % when compared with (6S)-5-methyltetrahydrofolic acid. When recent published observations were additionally taken into account it was concluded that, in principle, folic acid should not be used as the reference folate when attempting to estimate relative natural (food) folate bioavailability in longer-term human intervention studies. Using (6S)-5-methyltetrahydrofolic acid as the reference folate would avoid future results' validity being questioned.

2004 ◽  
Vol 63 (4) ◽  
pp. 529-536 ◽  
Author(s):  
Helene McNulty ◽  
Kristina Pentieva

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.


2008 ◽  
Vol 101 (2) ◽  
pp. 206-212 ◽  
Author(s):  
Leane Hoey ◽  
Helene McNulty ◽  
Elizabeth M. E. McCann ◽  
Kelvin J. McCracken ◽  
John M. Scott ◽  
...  

There are few good sources of natural food folates apart from green leafy vegetables and these may have a limited potential to increase folate status because of substantial losses that can occur during cooking. Fortified foods can overcome this but are controversial because of safety concerns regarding chronic exposure to high-dose folic acid (FA; the synthetic form). The aim of the present study was to develop eggs with an enriched natural folate content and minimal unmetabolised FA. Forty-eight, 30-week-old laying hens were randomised to receive the basal feed (formulated to provide 1 mg folate/kg feed) to which had been added one of the following FA levels (0, 2, 4, 8, 16, 32 mg/kg feed). Total folate was measured in eggs collected throughout the 12-week study period and the FA content estimated at 12 weeks. Results showed that the maximal egg folate content was achieved by adding 16 mg FA/kg feed. At this optimal dose, the total folate content per egg was 75 μg (compared with 32 μg in a regular egg) of which FA represented at most 10 %, a level which would probably be converted into natural folates by humans after ingestion. The results demonstrate that it is possible to use synthetic FA at high doses to produce novel animal foods enriched with natural folates in a cost-efficient process. Such foods may be particularly relevant to European populations without access to FA fortification and therefore dependent on natural food folate sources for the primary prevention of folate-related disease.


2016 ◽  
Vol 19 (16) ◽  
pp. 2897-2905 ◽  
Author(s):  
Kathryn E Bradbury ◽  
Sheila M Williams ◽  
Jim I Mann ◽  
Indrawati Oey ◽  
Cindy Aitchison ◽  
...  

AbstractObjectiveTo estimate the folate status of New Zealand women of childbearing age following the introduction, in 2010, of a new voluntary folic acid fortification of bread programme.DesignThe 2011 Folate and Women’s Health Survey was a cross-sectional survey of women aged 18–44 years carried out in 2011. The survey used a stratified random sampling technique with the Electoral Roll as the sampling frame. Women were asked about consumption of folic-acid-fortified breads and breakfast cereals in a telephone interview. During a clinic visit, blood was collected for serum and erythrocyte folate measurement by microbiological assay.SettingA North Island (Wellington) and South Island (Dunedin) city centre in New Zealand.SubjectsTwo hundred and eighty-eight women, of whom 278 completed a clinic visit.ResultsGeometric mean serum and erythrocyte folate concentrations were 30 nmol/l and 996 nmol/l, respectively. Folate status was 30–40 % higher compared with women of childbearing age sampled as part of a national survey in 2008/09, prior to the introduction of the voluntary folic acid bread fortification programme. In the 2011 Folate and Women’s Health Survey, reported consumption of fortified bread and fortified breakfast cereal in the past week was associated with 25 % (P=0·01) and 15 % (P=0·04) higher serum folate concentrations, respectively.ConclusionsSerum and erythrocyte folate concentrations have increased in New Zealand women of childbearing age since the number of folic-acid-fortified breads was increased voluntarily in 2010. Consumption of fortified breads and breakfast cereals was associated with a higher folate status.


2005 ◽  
Vol 94 (4) ◽  
pp. 602-608 ◽  
Author(s):  
Emma Williams ◽  
Barbara Stewart-Knox ◽  
Ian Bradbury ◽  
Ian Rowland ◽  
Kristina Pentieva ◽  
...  

Evidence suggests that low folate status may be detrimental to mood and associated with depleted cerebrospinal fluid levels of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT). A placebo-controlled trial was carried out to determine the effect of folic acid supplementation (100 μg for 6 weeks followed by 200 μg for a further 6 weeks) upon subjective mood (Positive and Negative Affect Schedule) and biochemical markers of mood (5-HT) in healthy males (n23). Blood samples were obtained at baseline (week 0) and during the intervention at week 6 and week 12. Subjective mood assessments were obtained at week 0 and week 12. The results showed an increase in serum and erythrocyte folate concentrations (P=0·02 andP=0·003, respectively) and a corresponding decrease in plasma homocysteine (P=0·015) in response to the folic acid intervention. Neither subjective mood nor 5-HT levels, however, were significantly altered in response to the change in folate status. Folic acid given at physiological doses did not appear to improve the mood of healthy folate-replete individuals over a 12-week period. Further research is needed to address the effect of folic acid supplementation or of longer duration or increased dose, particularly in the face of sub-optimal folate status.


2021 ◽  
Author(s):  
Jagdish Singh

Folic acid is a B complex water-soluble vitamin that is essential to humans, and its deficiency can cause problems including neural tube defects as well as heart-related diseases. An important feature of such vitamins is that they are generally not synthesized by mammalian cells and therefore must be supplied in sufficient amounts in the diet. Folate is a generic term for compounds, possessing vitamin activity similar to that of pteroylglutamic acid, and is the form of the vitamin, which is naturally present in foods. The main dietary sources of folic acid are dark green and leafy vegetables such as spinach, asparagus, romaine lettuce, broccoli, bok choy, turnip green, beet, dried or fresh beans, and peas. The amount of folate that is absorbed and utilized physiologically varies among different food sources and different chemical forms of the vitamin. About 85% of folic acid is estimated to be bioavailable; however, the bioavailability of food folate is estimated at about 50% of folic acid. Several national health authorities have introduced mandatory food fortification with synthetic folic acid, which is considered a convenient fortificant, being cost efficient in production, more stable than natural food folate, and superior in terms of bioavailability and bio-efficacy. Presently, many countries affected by diseases associated with a lack of folic acid have made it mandatory to supplement foods with the vitamin. Considering the need, several analytical procedures were standardized to determine the presence of folic acid in different food matrices. The reported methods are simple, selective, robust, and reproducible and can be used in routine analyses.


2002 ◽  
Vol 72 (6) ◽  
pp. 351-359 ◽  
Author(s):  
Marcela Gonzalez-Gross ◽  
Reinhild Prinz-Langenohl ◽  
Klaus Pietrzik

Data about folate intake and blood values of the German population, published between 1997 and 2000, have been reviewed. Median folate intake is about 250 mug/day in the adult population, which indicates a high likelihood of inadequate intake when compared to the Estimated Average Requirement (EAR) of 320 mug/day. Only a few studies have evaluated serum and erythrocyte folate or plasma homocysteine as a marker of folate status. The most representative data show that 25% of German women of childbearing age have an inadequate recent folate intake. Only 13.3% of the women have red blood cell folate values above the critical value of 400 mug/day established by Daly et al (1995). Folic acid fortification of food is shown to be responsible for about 25% of folate intake in the German child and adolescent population in one study. If we extrapolate these data to the general population, folic acid fortification could be the explanation for the differences observed between folate intake and blood values. The discrepancy might also be explained by slight inaccuracies in food composition tables. Folate intake from fortified food or from supplements is not taken into account in most of the studies, which is a variable that can lead to confusion. Nutrition surveys should adapt official composition tables for local food patterns, and include fortified commercial foods, in order to make folate intake data more accurate. However, representative serum and erythrocyte folate values are lacking for most age groups. Before taking public health measures concerning folate fortification of food, the real folate status of the German population should be established.


2015 ◽  
Vol 56 (1) ◽  
pp. 247-260 ◽  
Author(s):  
Natalie J. Colson ◽  
Helen L. Naug ◽  
Elham Nikbakht ◽  
Ping Zhang ◽  
Joanna McCormack

2014 ◽  
Vol 39 (3) ◽  
pp. 401-401 ◽  
Author(s):  
Cynthia K. Colapinto

Canada fortifies certain products with folic acid and has periconceptional supplementation guidelines [Formula: see text] policies designed to improve folate status and reduce the incidence of poor birth outcomes. Though optimal folate concentrations have been linked to health benefits, concerns have been raised regarding potential associations with adverse health outcomes. Direct biochemical assessment of the folate status of Canadians based on a nationally representative sample has not been done in more than 40 years. The overall purpose of this research was to investigate the folate status of the Canadian population. All analyses used the nationally representative 2007–2009 Canadian Health Measures Survey (CHMS). Red blood cell (RBC) folate was measured by Immulite 2000 immunoassay. Key findings indicate that folate deficiency (<305 nmol/L) was virtually nonexistent in the Canadian population (6–79 years old). Still, one-fifth of women of childbearing age (WCBA; 15–45 years old) had suboptimal concentrations for the prevention of neural tube defects (<906 nmol/L). Folic acid supplement intake was a primary determinant of WCBA, achieving a RBC folate concentration of ≥906 nmol/L. A distinct shift towards elevated RBC folate concentrations emerged. Three hypothetical cut-offs (1450 nmol/L, 1800 nmol/L and 2150 nmol/L) were examined to create a dialogue since a universal definition of high RBC folate concentration does not exist. Females, participants aged 60–79 years, and those who were overweight or obese had the greatest prevalence of having high RBC folate at each cut-off. We conducted the first national-level comparison of RBC folate concentrations between the United States and Canada. Two different folate assay methods [Formula: see text] microbiologic assay (NHANES) and Immulite 2000 immunoassay (CHMS) [Formula: see text] necessitated the application of a conversion equation. Median Canadian RBC folate concentrations (adjusted to microbiologic assay) were lower than those of Americans but unadjusted Canadian median RBC folate values were higher. Canadian WCBA were less likely than American WCBA to have RBC folate ≥906 nmol/L, though Canadian WCBA with unadjusted RBC folate values were more likely to achieve this cut-off. These results indicate a need for strategies targeting WCBA to improve compliance with folic acid supplement recommendations. The strength and necessity of supplements for the general population should be re-assessed. Further, harmonization of folate measurement procedures in future surveillance efforts would support comparisons and inform policy directions.


2008 ◽  
Vol 99 (S3) ◽  
pp. S48-S54 ◽  
Author(s):  
Helene McNulty ◽  
John M. Scott

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.


2008 ◽  
Vol 108 (12) ◽  
pp. 2090-2094 ◽  
Author(s):  
Aysheh M. Shuaibi ◽  
James D. House ◽  
Gustaaf P. Sevenhuysen

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