Food Science and Biotechnology

, Volume 28, Issue 6, pp 1837–1844 | Cite as

In vitro bioaccessibility of added folic acid in commercially available baby foods formulated with milk and milk products

  • Mustafa YamanEmail author
  • Ömer Faruk Mızrak
  • Jale Çatak
  • Hafsa Sena Sargın


Milk contains a certain amount of folate binding proteins. The binding capacity varies in acidic conditions and affects the bioavailability of folic acid. Folic acid is commonly added into baby foods to ensure adequate intake of infants. The aim of this study was to determine the bioaccessibility of added folic acid in baby foods formulated with milk and milk products under different gastric pH values by an in vitro digestive system. The bioaccessibility of folic acid ranged between 56–71 and 35–49% in infant formula samples, between 59–78 and 31–67% in cereal-based baby foods, and between 42–67 and 38–57% in follow-on baby milk at gastric pH 1.5 and pH 4, respectively. Our results demonstrate that the bioaccesibility of folic acid that is added to baby food is affected by gastric pH. Therefore, it was observed that the bioaccesibility of folic acid was lower in the higher gastric pH.


Folic acid Bioaccessibility Folate binding protein Milk Baby foods 



We thank the İstanbul Sabahattin Zaim University for their support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Arkbåge K, Verwei M, Havenaar R, Witthoft C. Bioaccessibility of folic acid and (6S)-5-methyltetrahydrofolate decreases after the addition of folate-binding protein to yogurt as studied in a dynamic in vitro gastrointestinal model. J. Nutr. 133: 3678–3683 (2003)CrossRefGoogle Scholar
  2. Ball GFM. Folate. Vitamins: Their Role in the Human. 1; Blackwell Publishing Ltd, Oxford, UK. pp. 348–349 (2004)Google Scholar
  3. Bourlieu C, Menard O, Bouzerzour K, Mandalari G, Macierzanka A, Mackie AR, Dupont D. Specificity of infant digestive conditions: some clues for developing relevant in vitro models. Crit. Rev. Food Sci. Nut. 54: 1427–1457 (2014)CrossRefGoogle Scholar
  4. Brandon EFA, Bakker M, Kramer E, Bouwmeester H, Zuidema T, Alewijn M. Bioaccessibility of vitamin A, vitamin C and folic acid from dietary supplements, fortified food and infant formula. Int. J. Food. Sci. Nut. 65: 426–435 (2014)CrossRefGoogle Scholar
  5. Campos-Giménez E, Benet S, Oguey Y, Martin F, Redeuil K. The contribution of minor folates to the total vitamin B9 content of Infant formula and clinical nutrition products. Food Chem. 249: 91–97 (2018)CrossRefGoogle Scholar
  6. Colman N, Hettiarachchy N, Herbert V. Detection of a milk factor that facilitates folate uptake by intestinal cells. Science 211: 1427–1429 (1981)CrossRefGoogle Scholar
  7. DiPalma J, Kirk CL, Hamosh M, Colon AR, Benjamin SB, Hamosh P. Lipase and pepsin activity in the gastric mucosa of infants, children, and adults. Gastroenterology 101: 116–121 (1991)CrossRefGoogle Scholar
  8. European Commission. Commission Directive 2006/141/EC of December 22, 2006 on infant formulae and follow-on formulae and amending Directive 1999/21/EC. Available at:, Accessed Nov. 15 (2018)
  9. Eichholzer M, Luthy J, Gutzwiller F, Stahelin HB. The role of folate, antioxidant vitamins and other constituents in fruits and vegetables in the prevention of cardiovascular disease: the epidemiological evidence. Int. J. Vitam. Nutr. Res. 71: 5–17 (2001)CrossRefGoogle Scholar
  10. Eichholzer M, Tonz O, Zimmermann R. Folic acid: a public-health challenge. Lancet 367: 1352–1361 (2006)CrossRefGoogle Scholar
  11. Elliot CM. Folic and health: an overview. Vitamin B: New Research, 1; Nova Biomedical Books, Nova Science Publishers Inc, New York, USA. pp. 39–57 (2008)Google Scholar
  12. Ford JE. Some observations on the possible nutritional significance of vitamin B12- and folate binding proteins in milk. Br. J. Nutr. 31: 243–257 (1974)CrossRefGoogle Scholar
  13. Gregory JF, Sartain DB, Day BPF. Fluorometric determination of folacin in biological materials using high performance liquid chromatography. J. Nutr. 114: 341–353 (1984)CrossRefGoogle Scholar
  14. He H, Shui B. Folate intake and risk of bladder cancer: a meta-analysis of epidemiological studies. Int. J. Food Sci. Nutr. 65: 286–292 (2014)CrossRefGoogle Scholar
  15. Jong DRJ, Verwei M, West CE, Van Vliet T, Siebelink E, Berg VD, Castenmiller JJ. Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans. Eur. J. Clin. Nutr. 59: 906–913 (2005)CrossRefGoogle Scholar
  16. Konings EJM, Roomans HHS, Doran E, Goldbohm RA, Saris WHM, Van Den Brandt, PA. Folate intake of the Dutch population according to newly established liquid chromatography data for foods. Am. J. Clin. Nutr. 73: 765–776 (2001)CrossRefGoogle Scholar
  17. Lee SJ, Lee SY, Chung MS, Hur SJ. Development of novel in vitro human digestion systems for screening the bioavailability and digestibility of foods. J. Funct. Foods. 22: 113–121 (2016)CrossRefGoogle Scholar
  18. Menard O, Cattenoz T, Guillemin H, Souchon I, Deglaire A, Dupont D. Validation of a new in vitro dynamic system to simulate infant digestion. Food Chem. 145:1039–1045 (2014)CrossRefGoogle Scholar
  19. Minekus M, Alminger M, Alvito P, Balance S, Bohn T, Bourlieu C, Carriere F, Boutrou R, Corredig M, Dupont D, Dufour C, Egger L, Golding M, Karakaya S, Kirkhus B, Feunteun SL, Lesmes U, Macierzanka A, Mackie A, Marze S, McClements DJ, Menard O, Recio I, Santos CN, Singh RP, Vegarud GE, Wickham MSJ, Weitschies W, Brodkorb A. A standardised static in vitro digestion method suitable for food—an international consensus. Food Funct. 5: 1113–1124 (2014)CrossRefGoogle Scholar
  20. Nguyen TP, Bhesh B, Julie C, Sangeeta P. A comprehensive review on in vitro digestion of infant formula. Food Res. Int. 76: 373–386 (2015)CrossRefGoogle Scholar
  21. Nygren-Babol L, Sternesjo A, Jagerstad M. Bjorck L (2005) Affinity and rate constants for interactions of bovine folate-binding protein and folate derivatives determined by optical biosensor technology. Effect of stereoselectivity. J. Agric. Food Chem. 53: 473–478CrossRefGoogle Scholar
  22. Papandreou D, Malindretos P, Arvanitidou M, Rousso I. Homocysteine lowering with folic acid supplements in children: Effects on blood pressure. Int. J. Food Sci. Nutr. 61: 11–17 (2010)CrossRefGoogle Scholar
  23. Rychlika M, Englerta K, Kapfera S, Kirchhoff E. Folate contents of legumes determined by optimized enzyme treatment and stable isotope dilution assays. J. Food Comp. Anal. 20: 411–419 (2007)CrossRefGoogle Scholar
  24. Salter D, Blakeborough P. Influence of goat’s-milk folate-binding protein on transport of 5-methyltetrahydrofolate in neonatal-goat small intestinal brush-border-membrane vesicles. Br. J. Nutr. 59: 409–507 (1988)CrossRefGoogle Scholar
  25. Salter DN, Scott K, Slade H, Andrews P. The preparation and properties of folate binding protein from cow’s milk. Biochem. J. 193: 469–476 (1981)CrossRefGoogle Scholar
  26. Sopade PA, Gidley MJ. 2009. A rapid in vitro digestibility assay based on glucometry for investigating kinetics of starch digestion. Starch 61: 245–255.CrossRefGoogle Scholar
  27. Svendsen IB, Martin B, Pedersen TG, Hansen SI, Holm J, Lyngbye J. Isolation and characterization of the folate-binding protein from cow’s milk. Carlsberg Res. Commun. 44: 89–99 (1979)CrossRefGoogle Scholar
  28. Swiatlo N, O’Conner DL, Andrews J, Picciano MF. Relative folate bioavailability from diets containing human, bovine and goat milk. J. Nutr. 120: 172–177 (1990)CrossRefGoogle Scholar
  29. Tani M, Fushiki T, Iwai K. Influence of folate binding protein from bovine milk on the absorption of folate in gastrointestinal tract of rat. Biochim. Biophys. Acta 757: 274–281 (1983)CrossRefGoogle Scholar
  30. Tani M, Iwai K. Some nutritional effects of folate binding protein in bovine milk on the bioavailability of folate to rats. J. Nutr. 114: 778–785 (1984)CrossRefGoogle Scholar
  31. USDA. United States Department of Agriculture. USDA Food Composition Databases. Available at: Accessed Nov. 15, 2018
  32. Verwei M. 2004. Bioavaibility of folate from fortified milk products. PhD thesis, Wageningen University, Wageningen, The Netherlands (2004)Google Scholar
  33. Verwei M, Arkbåge K, Havenaar R, Berg VDH, Witthöft C, Schaafsma G. Folic acid and 5-methyltetrahydrofolate in fortified milk are bioaccessible as determined in a dynamic in vitro gastrointestinal model. J. Nutr. 133: 2377–2383 (2003)CrossRefGoogle Scholar
  34. Verwei M, Arkbåge K, Mocking H, Havenaar R, Groten J. The binding of folic acid and 5-methyltetrahydrofolate to folate-binding proteins during gastric passage differs in a dynamic in vitro gastrointestinal model. J. Nutr. 134: 31–37 (2004)CrossRefGoogle Scholar
  35. Verwei M, Arkbåge K, Groten JP, Witthöft C, Havenaar, R. The effect of folate-binding proteins on bioavailability of folate from milk products. Trends Food Sci. Tech. 16: 307–310 (2005)CrossRefGoogle Scholar
  36. Wigertz K, Svensson UK, Jagerstad M. Folate and folate-binding protein content in dairy products. J. Dairy Res. 64: 239–252 (1997)CrossRefGoogle Scholar

Copyright information

© The Korean Society of Food Science and Technology 2019

Authors and Affiliations

  1. 1.Department of Nutrition and Dietetics, Faculty of Health Sciencesİstanbul Sabahattin Zaim UniversityKüçükçekmeceTurkey

Personalised recommendations