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The fractional absorption of a stable isotope-labeled folate dose can be estimated from the subsequent short-term temporal changes in the concentration of labeled L-5-methyltetrahydrofolate (L-5-methyl-THF) in plasma using mathematical modeling. However, the model is dependent on the use of an accurate value for the apparent volume of distribution of L-5-methyl-THF. Previous studies that estimated the apparent volume of distribution of L-5-methyl-THF used large (nonphysiological) doses of unlabeled folates that are not found to any great extent in the circulatory system. The current study estimates the apparent volume of distribution at steady state in 16 healthy humans aged 18-65 y after an iv. dose (440 nmoll of a stable isotope-labeled version of the naturally circulating plasma folate, L-5-methyl-THF. Blood was collected from 2 mm to 2 h postinjection and plasma assayed by specific and sensitive liquid chromatography-tandem Ms. The apparent volume of distribution for L-5-methyl-THF was 32.0 ± 11.6 L Imean ± SD; 392 ± 110 mL/kg bodyweightl. There was a positive association with volunteer body weight Ir = 0.64; P = 0.0101, which allowed a simple linear equation to be developed relating apparent volume of distribution to body weight. This has important implications for predicting apparent absorption of labeled folates in future bioavailability studies. [ABSTRACT FROM AUTHOR]

Single (13)C(6)-labeled doses of pteroylmonoglutamic acid (PteGlu: 634 nmol; n = 14), (6S-)5-formyltetrahydrofolic acid (431-569 nmol; n = 16), or [(15)N(1-7)]-intrinsically labeled spinach (mainly 5-methyltetrahydrofolate) (588 nmol; n = 14) were fed to fasting adult volunteers. Plasma-labeled 5-methyltetrahydrofolic acid responses were monitored for 8 h. There was a slower rate of increase in plasma-labeled 5-methyltetrahydrofolic acid and longer time to peak (171 +/- 9 min; mean +/- SEM) following an oral dose of [(13)C(6)]PteGlu than either [(13)C(6)]5-formyltetrahydrofolic acid (54 +/- 10 min) or [(15)N(1-7)]spinach folate (60 +/- 13 min) suggesting saturated metabolic capacity for the biotransformation of PteGlu. Mathematical modeling generated a significantly higher mean "apparent absorption" for 5-formyltetrahydrofolic acid (38%) and spinach folate (44%) than for PteGlu (24%). The high "relative absorption" of reduced folates to PteGlu was unexpected given that PteGlu itself, from (14)C-tracer mass balance experiments, is almost completely absorbed. Although it is ubiquitously accepted that a physiological dose of PteGlu is reduced and methylated in the epithelial cells of the small intestine, and that essentially only 5-methyltetrahydrofolic acid is exported into the hepatic portal vein (HPV), as is the case for absorbed reduced 1-carbon-substituted folates, modeling indicated greater liver sequestration when PteGlu was used as the test dose, suggesting that PteGlu enters the HPV unaltered and that the liver is the primary site of initial metabolism. Because of the observed differential plasma response and the hypothesized difference in the site of initial metabolism, the historical use of PteGlu as a "reference folate" in studies of folate bioavailability is seriously questioned. [ABSTRACT FROM AUTHOR]

Folic acid fortification, mandatory in the United States, is currently being considered by the UK. The hypothesis that the matrix of some cereal-product vehicles may result in low fortificant bioavailability was tested using a dual oral/intravenous (i.v.) isotopic-label approach, which was evaluated concurrently. Fifteen women received 225 microg oral folate (capsules, fortified white bread and fortified branflakes), mainly as folic acid labeled with (13)C on 6 carbons of the benzoyl ring ((13)C(6)-PteGlu), followed by i.v. injection of 100 microg folic acid labeled with (2)H on 4 hydrogens of the glutamic acid group ((2)H(4)-PteGlu). The urinary excretion ratio (UER) in intact folate of the percentage of labeled oral dose excreted divided by the percentage of i.v. dose excreted was used as the primary index of absorption. The geometric mean (95% confidence interval) UER for folic acid capsules was 3.68 (1.90, 7.14) at 24 h and 2.18 (1.24, 3.83) at 48 h. Because these were significantly in excess of 1.0, indicative of 100% absorption of the oral dose, it was concluded that oral and i.v. labeled folic acid are handled differently by the body and that "absolute" absorption cannot be calculated. Compared with the 48-h UER for folic acid capsules, the "relative" 48-h UER for white bread and branflakes was 0.71 and 0.37, respectively, indicating that some cereal-based vehicles may inhibit absorption of fortificant. However, even the validity of this "relative" approach is questioned. [ABSTRACT FROM AUTHOR]

Folate may be associated with reduced risks of vascular disease and cancer. A limiting factor can be the bioavailability from various food sources. We studied the bioaccessibility of folate (5MTHF) and folic acid (PGA) from dairy products, drinks, rye bread, and vegetables fortified or processed under various conditions. The experiments were performed in a validated, computer-controlled gastrointestinal model (TIM), simulating physiological conditions in stomach and small intestine of humans. From nonfortified pasteurized milk with 7 µg folate/ 100 g, 5MTHF was 86% ± 2% bioaccessible. From pasteurized and ultra-high-temperature milk fortified with 40 µg/100 g, PGA was 74-77% ± 2% bioaccessible and 5MTHF was 90% ± 2% bioaccessible. From fortified fermented milk, PGA and 5MTHF were 82-90% bioaccessible. However, folate bioaccessibility was significantly lowered by the addition of folate binding protein (1:1 to folate) in PGA-enriched milk and the addition of 5MTHF and PGA in enriched fermented milk. The bioaccessibility of folates from orange juice (40 µg/100 g, heat or high pressure pasteurized) and beer (11 µg/100 g, with or without alcohol) was 87-89% ± 3% and 83-87% ± 1%, respectively. From peas (canned, 38 µg/100 g; frozen, 65 µg/100 g), spinach (soup, 53 µg/100 g; leaves, 110 µg/100 g), rye bread (78 µg/100 g), and gazpacho (49 µg/100 mL), the availability for absorption was 78% ± 3%, 82% ± 4%, 88% ± 2%, and 94% ± 5%, respectively. Because of high folate bioaccessibility, dairy products are good sources for folate fortification if folate binding protein is not added. Because of the high content and bioaccessibility of folates, processed food products such as spinach, peas, gazpacho, rye bread, and orange juice seem good sources of folates. However, complex matrices and mucosal folate transport could lower bioavailability. Further research should focus on combined food products and intestinal transport. [Supported by EU project "Folate: from food to functionality and optimal health" QLK1-1999-00576. [ABSTRACT FROM AUTHOR]