Kinetics of Folate and One-Carbon Metabolism

Gregory, Jesse F.; Silva, Vanessa R. da; Lamers, Yvonne

doi:10.1201/9781420071252-c20

Cited by 16 publications

(22 citation statements)

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“…Because obesity was associated with lower serum folate levels in supplement nonusers, these data suggest that there may be a reduction in the body pool of freely available serum folate owing to changes in tissue distribution. Therefore, obesity may modify folate pharmacokinetics by mechanisms that cannot be explained by these observational data (Gregory et al, 2010). Dietary folate deficiency indicated by serum folate concentrations has been demonstrated to lead to upregulation of transepithelial transport of folic acid, which could lead to higher cellular uptake of the developing erythrocyte, as reflected in the higher concentrations of folate in red blood cells (Said et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Does obesity modify the association of supplemental folic acid with folate status among nonpregnant women of childbearing age in the United States?

Tinker

Hamner

Berry

et al. 2012

Birth Defects Research

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Section: Discussionmentioning

confidence: 99%

Does obesity modify the association of supplemental folic acid with folate status among nonpregnant women of childbearing age in the United States?

Tinker

Hamner

Berry

et al. 2012

Birth Defects Research

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“…If, as we hypothesised, absorbed folic acid leads to the more rapid accumulation of liver folate stores compared with other absorbed natural (food) folates, it could be further inferred that the use of folic acid as a reference in longer-term feeding studies may at the very least lead to a comparatively accelerated change in plasma or serum folate concentration in fasting blood since this is a function of enterohepatic recirculation (estimated at 60-227 nmol/d (15,16) ) which increases in proportion to the magnitude of liver stores (17) . Thus, comparison of the change in fasting plasma or serum folate induced by natural food or nature-identical folate to the change in fasting plasma or serum folate induced by folic acid may result in the significant underestimation of 'relative bioavailability'.…”

mentioning

confidence: 87%

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

et al. 2009

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Comparison of (6S)-5-methyltetrahydrofolic acid v. 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 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 (n 163) 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.Human nutrition: (6S)-5-methyltetrahydrofolic acid: Folic acid: Plasma homocysteine: Folate: Bioavailability: Intervention studies Low folate status is associated with increased risk of neural tube defects in the developing fetus and raising maternal folate status before conception and during pregnancy has been shown to reduce occurrence by approximately 70 %. Additionally, low folate status has been associated with increased risk of other disease states in adults, such as CVD (2) , dementia (3) and some cancers (4) . In the UK, fortification of foods with folate, normally in the form of folic acid, is optional. In some countries, such as the USA, Chile and Canada, a mandatory programme where all flour is fortified with folic acid has been in place for some time (5 -7) , and is currently under consideration in the UK.Folate status can be raised either by supplementation or fortification (usually ...

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“…Supplementation studies with folic acid (100-4 000 µg/day) or [6S]-5-methyl-THF (113-416 µg/day) found that a steady state in serum/plasma folate concentration was achieved after as long as 12 to 14 weeks of supplementation with a constant dose (Venn et al, 2002;Lamers et al, 2006;Hao et al, 2008) and, in that case, serum/plasma folate measurement would reflect the status of the vitamin. This comparatively slow response of serum/plasma folate suggests that it is not just a reflection of dietary intake but it is in equilibrium with and controlled by the cellular folate concentration, with a steady state of plasma folate being reached only upon saturation of cellular folate stores (Gregory and Quinlivan, 2002). Based on the microbiological L. casei subsp.…”

Section: Biomarkers Of Intake and Statusmentioning

confidence: 99%

Scientific Opinion on Dietary Reference Values for folate

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Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for folate. The Panel concludes that an Average Requirement (AR), as well as a Population Reference Intake (PRI) assuming a coefficient of variation (CV) of 15 % to account for the additional variability associated with the higher requirement for folate in individuals with the methylene-tetrahydrofolate reductase (MTHFR) 677TT genotype, can be derived from biomarkers of folate status. Several health outcomes possibly associated with folate intake/status were also considered, but data were found to be insufficient to establish DRVs. For adults, the AR is determined from the folate intake required to maintain folate adequacy characterised by serum and red blood cell folate concentrations of ≥ 10 and 340 nmol/L, respectively. An AR of 250 µg dietary folate equivalents (DFE)/day and a PRI of 330 µg DFE/day are derived. For infants aged 7-11 months, an Adequate Intake (AI) of 80 µg DFE/day is derived by extrapolating upwards from the estimated folate intake in exclusively breast-fed infants. For children, ARs are extrapolated from the AR for adults using allometric scaling and growth factors and considering differences in reference weights. PRIs ranging from 120 µg DFE/day for 1-3 year-old children to 330 µg DFE/day for boys and girls aged 15-17 years are derived. For pregnant women, an AI of 600 µg DFE/day is derived based on a study on maintenance of serum and red blood cell folate concentrations in pregnancy. For lactating women, an additional intake of 130 µg DFE/day is considered to cover folate losses via breast milk; this figure is added to the AR for non-lactating women and a PRI of 500 µg DFE/day is derived.

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Kinetics of Folate and One-Carbon Metabolism

Cited by 16 publications

References 105 publications

Does obesity modify the association of supplemental folic acid with folate status among nonpregnant women of childbearing age in the United States?

Does obesity modify the association of supplemental folic acid with folate status among nonpregnant women of childbearing age in the United States?

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

Scientific Opinion on Dietary Reference Values for folate

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