title: Predicted serum folate concentrations based on in vitro studies and kinetic modeling are consistent with measured folate concentrations in humans.
abstract: The nutritional quality of new functional or fortified food products depends on the bioavailability of the nutrient(s) in the human body. Bioavailability is often determined in human intervention studies by measurements of plasma or serum profiles over a certain time period. These studies are time and cost consuming and often appear to lack an optimal study design, leading to follow-up intervention trials. Therefore, an alternative approach is needed that will optimize the development of new products. This study describes an approach to predict human serum concentrations after the consumption of (fortified) food products. The concept is based on the integration of in vitro results with kinetic modeling. As a case study, human serum folate concentrations were predicted after the consumption of folate-fortified milk products for 4 wk. Oral bioavailability was investigated using a step-wise approach in which luminal bioaccessibility and intestinal absorption were independently evaluated. Subsequently, these in vitro data were integrated in a kinetic mathematical (in silico) model to predict serum folate concentrations after the intake of a single dose and during long-term consumption. This approach was evaluated in comparison to a human intervention study in which folic acid-fortified milk products were tested for their effect on serum folate concentrations. A high predictive quality of this alternative in vitro/in silico approach was demonstrated. Finally, this methodology was applied to predict serum folate concentrations after intake of different fortified milk products for 4 wk, showing its benefits for the development of new nutritional products.
authors.affiliation: Business Unit Biosciences, TNO Quality of Life, 3700 AJ Zeist, The Netherlands. miriam.verwei@tno.nl
authors.forename: Miriam
authors.initials: M
authors.lastname: Verwei
authors.forename: Andreas P
authors.initials: AP
authors.lastname: Freidig
authors.forename: Robert
authors.initials: R
authors.lastname: Havenaar
authors.forename: John P
authors.initials: JP
authors.lastname: Groten
mesh_terms: D003611:Dairy Products / Q000032:analysis; D005492:Folic Acid / Q000097:blood*; D006801:Humans; D007082:Ileum / Q000502:physiology; D007408:Intestinal Absorption; D007583:Jejunum / Q000502:physiology; D007700:Kinetics; D008954:Models, Biological; D015203:Reproducibility of Results
chemical_list: D005492:Folic Acid