The Binding of Folic Acid and 5-Methyltetrahydrofolate to Folate-Binding Proteins during Gastric Passage Differs in a Dynamic In Vitro Gastrointestinal Model

• Published in: The Journal of nutrition Vol. 134; no. 1; pp. 31 - 37
• Main Authors: Verwei, Miriam, Arkbåge, Karin, Mocking, Hans, Havenaar, Robert, Groten, John
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.01.2004; American Society for Nutritional Sciences
• Subjects: 5-methyltetrahydrofolate; analysis; Animals; binding capacity; bioavailability; Biological and medical sciences; bovine-milk; Carrier Proteins; Carrier Proteins - analysis; Carrier Proteins - metabolism; chemistry; Chromatography, Gel; cows milk; dairy products; dietary nutrient sources; dietary-folate; Duodenum; Duodenum - metabolism; Feeding. Feeding behavior; Folate Receptors, GPI-Anchored; folate-binding protein; folate-binding proteins; folic acid; Folic Acid - metabolism; Food, Fortified; Fundamental and applied biological sciences. Psychology; gastric passage; Gastrointestinal Transit; Humans; in vitro digestion; In Vitro Techniques; intestinal absorption; metabolism; Milk; Milk - chemistry; milk products; Milk Proteins; Milk Proteins - chemistry; Models, Biological; neural-tube defects; nutrient availability; plasma homocysteine; prevention; Protein Binding; Receptors, Cell Surface; red-cell folate; Tetrahydrofolates; Tetrahydrofolates - metabolism; vascular-disease; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Whey Proteins; folate-binding protein; 5-methyltetrahydrofolate; milk products; folic acid; gastric passage; Stomach; Digestive system; Gastrointestinal; In vitro; Folic acid; Folate; Micronutrient; Binding protein; Models; Milk
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/134.1.31

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.