A human model to determine folate bioavailability from food: a pilot study for evaluation

Abstract

Background: Knowledge about folate bioavailability from food is essential for the estimation of dietary requirements. Yet, there is a lack of data obtained from validated human studies performed with physiological folate doses. Objective: In this pilot study, a new model for the determination of folate absorption is developed and validated. Design: Under strictly standardized procedures, two healthy ileostomy volunteers consumed single portions of test foods or an oral dose of a pharmaceutical folate preparation of the natural folate diastereomer (6S)-5-methyltetrahydrofolate. Relative folate absorption from oral doses versus an intramuscular injection of the same pharmaceutical preparation was determined using postdose plasma folate concentration curves. Nonabsorbed folate was estimated by postdose folate excretion into stomal effluent. Results: Estimated by plasma areas under the curve, relative folate absorption ranged from 47 to 67% for oral doses from the test foods strawberries and broccoli and the pharmaceutical (6S)-5-methyltetrahydrofolate preparation. During 10 h postdose, 19 Á/44% of the dietary folate was excreted with the stomal effluent. Varying gut passage times were observed for different food matrices by determining ileostomal folate excretion in 2 h intervals. Around 90% of the folate from the oral doses was recovered in the collected body fluids, plasma and stomal effluent, by 10 h postdose, independent of the size of the administered folate doses of 200 or 400 mg (0.4 or 0.9 mmol). Conclusion: The results imply that this model provides a suitable tool to estimate folate bioavailability from foods.

Human Folate Bioavailability

“…Renal excretion of intact folate is as low as ~5% after physiological doses [34,40,41,42], but it increases at higher folate intake [37]. In human feces, about 400 nmol/day folate can be found, originating mainly from bacterial production, lysed enterocytes, and gastrointestinal secretions (e.g., bile) [34,43].…”

Analytical Methods to Assess the Bioavailability of Water‐Soluble Vitamins in Food–Exemplified by Folate

“…Therefore, data derived from studies simply comparing absorption by folate C max or by (extrapolated) AUCs derived from post -dose collection periods shorter than 6 h must be interpreted with care, especially when different modes of dose application (orally in the form of food versus bolus versus intravenous) were used. Using ileostomy volunteers, who lack a colon and its microfl ora affecting fecal folate excretion, the AUC approach can be extended by accounting for nonabsorbed folate using post -dose ileostomal effl uent samples [53,67,68] (Figure 2.4 ). Non -absorbed folate from oral doses can be estimated by quantifying postdose folate excretion in ileostomal effl uent samples collected in regular intervals up to 24 h post -dose.…”

“…Non -absorbed folate from oral doses can be estimated by quantifying postdose folate excretion in ileostomal effl uent samples collected in regular intervals up to 24 h post -dose. Effl uent samples either can be pooled [67,68] for estimation of total folate excretion, or can be analyzed individually, providing information on the intestinal passage time of different food matrices and folate excretion over time [53] . By the AUC or AUC -ileostomy approach, equivalent relative folate absorption from pharmaceutical preparations of (6 S ) -5 -methyltetrahydrofolate and folic acid was determined [67,69] .…”

“…By the AUC or AUC -ileostomy approach, equivalent relative folate absorption from pharmaceutical preparations of (6 S ) -5 -methyltetrahydrofolate and folic acid was determined [67,69] . Short -term absorption from endogenous food folates from cereal products [70] , vegetables and fruit [53,68,71,72] , and fortifi ed dairy and cereal products [67] was also assessed. McKillop et al [73] reported that folate absorption was not affected by the extent of conjugation (monoglutamyl versus polyglutamyl folates).…”

“…The human AUC -ileostomy model for the assessment of folate bioavailability[53,67] . AUC, area under the plasma (concentration) curve.…”