title: The binding of folic acid and 5-methyltetrahydrofolate to folate-binding proteins during gastric passage differs in a dynamic in vitro gastrointestinal model.
abstract: Despite its low natural folate concentration, milk is responsible for 10-15% of the daily folate intake in countries with a high dairy consumption. Milk products can be considered as a potential matrix for folate fortification, e.g., with synthetic folic acid, to enhance the daily intake of folate. In untreated milk, the natural folate, 5-methyltetrahydrofolate (5-CH3-H4folate), is bound to folate-binding proteins (FBP). In this study, the extent of binding to FBP for folic acid and 5-CH3-H4folate was investigated in a dynamic in vitro model simulating human gastric passage. Protein binding of folic acid and 5-CH3-H4folate was characterized using gel-exclusion chromatography. Before gastric passage, folic acid and 5-CH3-H4folate were bound mainly to FBP (76-79%), whereas 7% was free. Folic acid remained bound to FBP to a similar extent after gastric passage. For 5-CH3-H4folate, the FBP-bound fraction gradually decreased from 79 to 5% and the free fraction increased from 7 to 93%. Although folic acid enters the proximal part of the intestine bound to FBP, 5-CH3-H4folate appears to be present mainly as free folate in the duodenal lumen. The stability of FBP was similar in both folate/FBP mixtures, i.e., 70% of the initial FBP content was retained after gastric passage. This study indicated that FBP are partly stable during gastric passage but have different binding characteristics for folic acid and 5-CH3-H4folate in the duodenal lumen. This could result in different bioavailability from folic acid- and 5-CH3-H4folate-fortified milk products.
authors.affiliation: Department of Nutritional Physiology, TNO Nutrition and Food Research, 3700 AJ Zeist, The Netherlands. Verwei@voeding.tno.nl
authors.forename: Miriam
authors.initials: M
authors.lastname: Verwei
authors.forename: Karin
authors.initials: K
authors.lastname: Arkbåge
authors.forename: Hans
authors.initials: H
authors.lastname: Mocking
authors.forename: Robert
authors.initials: R
authors.lastname: Havenaar
authors.forename: John
authors.initials: J
authors.lastname: Groten
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D002850:Chromatography, Gel; D004386:Duodenum / Q000378:metabolism; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D005527:Food, Fortified; D005772:Gastrointestinal Transit; D006801:Humans; D066298:In Vitro Techniques; D008892:Milk / Q000737:chemistry; D008894:Milk Proteins / Q000737:chemistry; D008954:Models, Biological; D011485:Protein Binding; D011956:Receptors, Cell Surface; D013763:Tetrahydrofolates / Q000378:metabolism*; D000067816:Whey Proteins
chemical_list: D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D008894:Milk Proteins; D011956:Receptors, Cell Surface; D013763:Tetrahydrofolates; D000067816:Whey Proteins; D005492:Folic Acid; C005984:5-methyltetrahydrofolate