Folate bioavailability from foods rich in folates assessed in a short term human study using stable isotope dilution assays

Abstract

Different sources of folate may have different bioavailability and hence may impact the standard definition of folate equivalents. In order to examine this, a short term human study was undertaken to evaluate the relative native folate bioavailabilities from spinach, Camembert cheese and wheat germs compared to pteroylmonoglutamic acid as the reference dose. The study had a single-centre, randomised, four-treatment, four-period, four-sequence, cross-over design, i.e. the four (food) items to be tested (referred to as treatments) were administered in sequences according to the Latin square, so that each experimental treatment occurred only once within each sequence and once within each study period. Each of the 24 subjects received the four experimental items separated by a 14-day equilibrium phase and received a pteroylmonoglutamic acid supplement for 14 days before the first testing and between the testings for saturation of body pools. Folates in test foods, plasma and urine samples were determined by stable isotope dilution assays, and in urine and plasma, the concentrations of 5-methyltetrahydrofolate were evaluated. Standard non-compartmental methods were applied to determine the biokinetic parameters C(max), t(max) and AUC from baseline corrected 5-methyltetrahydrofolate concentrations within the interval from 0 to 12 hours. The variability of AUC and C(max) was moderate for spinach and oral solution of pteroylmonoglutamic acid but high for Camembert cheese and very high for wheat germs. The median t(max) was lowest for spinach, though t(max) showed a high variability among all treatments. When comparing the ratio estimates of AUC and C(max) for the different test foods, highest bioavailability was found for spinach followed by that for wheat germs and Camembert cheese. The results underline the dependence of folate bioavailability on the type of food ingested. Therefore, the general assumption of 50% bioavailability as the rationale behind the definition of folate equivalents has to be questioned and requires further investigation.

Pilot Study on Folate Bioavailability from a Camembert Cheese Reveals Contradictory Findings to Recent Results from a Human Short-term Study

“…For determining the exact folate dose, we analyzed the Camembert cheese for individual folate vitamers and found considerably lower total folate content and a rather different folate profile compared to the Camembert cheese (different brand) assessed in our previous study ( 12 ). Whereas the latter contained as much as 647 nmol/100 g total folate and its major folate vitamer was tetrahydrofolate, the total folate content of the Camembert cheese in the present study was only 224 nmol/100 g, and its major vitamer was 5-formyltetrahydrofolate (Table 1 ).…”

“…All subjects gave written informed consent in accordance with the Declaration of Helsinki. To improve the uniformity among the two subjects and subsequently the precision of bioavailability estimates, a pteroylmonoglutamic acid supplement (800 μg/day = 1.8 μmol/day) was given for 14 days before the first testing and between the testings and was discontinued 2 days prior to the start of the study ( 12 ). The study had a randomized cross-over design, and each subject had the following experimental treatments separated by a 14-day equilibrium phase: 448-nmol total folates via Camembert cheese (200 g) and 453-nmol pteroylmonoglutamic acid via orally administered pteroylmonoglutamic acid solution (100 mL) serving as reference treatment.…”

“…This prompted us to conduct a recently published human study on folate bioavailability by using stable isotope dilution assays for analysis of plasma folate and an area under the curve (AUC) approach ( 11 ). A surprisingly high inter-individual variation in folate bioavailability and also highly different bioavailabilities of the test foods ranging from 8.8% for Camembert cheese to 73% for spinach relative to pteroylmonoglutamic acid could be observed ( 12 ). However, we did not investigate the potential variation in folate bioavailability within the same test food, e.g., Camembert cheese.…”

“…However, we did not investigate the potential variation in folate bioavailability within the same test food, e.g., Camembert cheese. Therefore, the aim of the present pilot study was to compare the oral bioavailability and biokinetic data between pure compound of pteroylmonoglutamic acid as the reference and native folate from a low-fat type Camembert cheese of a brand different to that used in the aforementioned human study ( 12 ). The bioavailability data of the cheese, which is a popular and significant dietary source of folate in Germany ( 13 ), were obtained from analyses of 5-CH 3 -H 4 folate in plasma following oral administration.…”

Role of folic acid in nitric oxide bioavailability and vascular endothelial function

“…The bioavailability of folates in natural foods, however, is approximately 50% of that of the synthetic form of folic acid and varies greatly, depending on the food consumed. 12 Consequently, supplementation with synthetic folic acid, such as that found in dietary supplements and used in food fortification, may be required to obtain the benefits of improved endothelial function observed in clinical randomized controlled trials of folic acid. 8,13,14…”