The Binding of Folic acid and 5-methyltetrahydrofolate to Folate-Binding Proteins during Gastric Passage Differs in a dynamic in vitro gastrointestinal model

M. Verwei, K. Arkbåge, H. Mocking, R. Havenaar, J. Groten

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)

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-H(4)folate), is bound to folate-binding proteins (FBP). In this study, the extent of binding to FBP for folic acid and 5-CH3-H(4)folate was investigated in a dynamic in vitro model simulating human gastric passage. Protein binding of folic acid and 5-CH3-H(4)folate was characterized using gel-exclusion chromatography. Before gastric passage, folic acid and 5-CH3-H(4)folate 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-H(4)folate, 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-H(4)folate 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-H(4)folate in the duodenal lumen. This could result in different bioavailability from folic acid- and 5-CH3-H(4)folate-fortified milk products.
Original languageEnglish
Pages (from-to)31-37
JournalThe Journal of Nutrition
Volume134
Issue number1
DOIs
Publication statusPublished - Jan 2004

Keywords

  • neural-tube defects
  • red-cell folate
  • bovine-milk
  • cows milk
  • plasma homocysteine
  • vascular-disease
  • dairy-products
  • dietary-folate
  • bioavailability
  • prevention

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