The Binding of Folic acid and 5-methyltetrahydrofolate to Folate-Binding Proteins during Gastric Passage Differs in a dynamic in vitro gastrointestinal model
Verwei, M. ; Arkbåge, K. ; Mocking, H. ; Havenaar, R. ; Groten, J. - \ 2004
The Journal of Nutrition 134 (2004)1. - ISSN 0022-3166 - p. 31 - 37.
neural-tube defects - red-cell folate - bovine-milk - cows milk - plasma homocysteine - vascular-disease - dairy-products - dietary-folate - bioavailability - prevention
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.
Folic acid and 5-methyltetrahydrofolate in fortified milk are bioaccessible as determined in a dynamic in vitro gastrointestinal model
Verwei, M. ; Arkbåge, K. ; Havenaar, R. ; Berg, H. van den; Witthöft, C. ; Schaafsma, G. - \ 2003
The Journal of Nutrition 133 (2003)7. - ISSN 0022-3166 - p. 2377 - 2383.
folate-binding-protein - neural-tube defects - red-cell folate - cows milk - plasma homocysteine - small-intestine - dietary-folate - bovine-milk - bioavailability - prevention
Dairy products are a potential matrix for folate fortification to enhance folate consumption in the Western world. Milk folate-binding proteins (FBP) are especially interesting because they seem to be involved in folate bioavailability. In this study, folate bioaccessibility was investigated using a dynamic computer-controlled gastrointestinal model [TNO gastrointestinal model (TIM)]. We used both ultrahigh temperature (UHT)-processed milk and pasteurized milk, differing in endogenous FBP concentrations and fortified with folic acid or 5-methyltetrahydrofolate (5-CH3-H(4)folate). To study FBP stability during gastrointestinal passage and the effect of additional FBP on folate bioaccessibility, FBP-fortified UHT and pasteurized milk products were also tested. Folate bioaccessibility and FBP stability were measured by taking samples along the compartments of the gastrointestinal model and measuring their folate and FBP concentrations. Folate bioaccessibility from folic acid-fortified milk products without additional FBP was 58-61%. This was lower (P <0.05) than that of the 5-CH3-H(4)folate-fortified milk products (71%). Addition of FBP reduced (P <0.05) folate bioaccessibility from folic acid-fortified milk (44-51%) but not from 5-CH3-H(4)folate-fortified milk products (72%). The residual FBP levels in the folic acid- and 5-CH3-H(4)folate-fortified milk products after gastrointestinal passage were 13-16% and 0-1%, respectively, of the starting amounts subjected to TIM. In conclusion, milk seems to be a suitable carrier for folate, because both folic acid and 5-CH3-H(4)folate are easily released from the matrix and available for absorption. However, our results suggest that folic acid remains partly bound to FBP during passage through the small intestine, which reduces the bioaccessibility of folic acid from milk in this model.