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Sodium pyrophosphate enhances iron bioavailability from bouillon cubes fortified with ferric pyrophosphate

  • Colin I. Cercamondi (a1), Guus S. M. J. E. Duchateau (a2), Rajwinder K. Harika (a2), Robin van den Berg (a2), Peter Murray (a2), Wieneke P. Koppenol (a2), Christophe Zeder (a1), Michael B. Zimmermann (a1) and Diego Moretti (a1)...


Fe fortification of centrally manufactured and frequently consumed condiments such as bouillon cubes could help prevent Fe deficiency in developing countries. However, Fe compounds that do not cause sensory changes in the fortified product, such as ferric pyrophosphate (FePP), exhibit low absorption in humans. Tetra sodium pyrophosphate (NaPP) can form soluble complexes with Fe, which could increase Fe bioavailability. Therefore, the aim of this study was to investigate Fe bioavailability from bouillon cubes fortified with either FePP only, FePP+NaPP, ferrous sulphate (FeSO4) only, or FeSO4+NaPP. We first conducted in vitro studies using a protocol of simulated digestion to assess the dialysable and ionic Fe, and the cellular ferritin response in a Caco-2 cell model. Second, Fe absorption from bouillon prepared from intrinsically labelled cubes (2·5 mg stable Fe isotopes/cube) was assessed in twenty-four Fe-deficient women, by measuring Fe incorporation into erythrocytes 2 weeks after consumption. Fe bioavailability in humans increased by 46 % (P<0·005) when comparing bouillons fortified with FePP only (4·4 %) and bouillons fortified with FePP+NaPP (6·4 %). Fe absorption from bouillons fortified with FeSO4 only and with FeSO4+NaPP was 33·8 and 27·8 %, respectively (NS). The outcome from the human study is in agreement with the dialysable Fe from the in vitro experiments. Our findings suggest that the addition of NaPP could be a promising strategy to increase Fe absorption from FePP-fortified bouillon cubes, and if confirmed by further research, for other fortified foods with complex food matrices as well.

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Corresponding author

* Corresponding author: C. Cercamondi, fax +41 44 632 14 70, email


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1. Kassebaum, NJ, Jasrasaria, R, Naghavi, M, et al. (2014) A systematic analysis of global anemia burden from 1990 to 2010. Blood 123, 615624.
2. Hurrell, R, Ranum, P, de Pee, S, et al. (2010) Revised recommendations for iron fortification of wheat flour and an evaluation of the expected impact of current national wheat flour fortification programs. Food Nutr Bull 31, S7S21.
3. Zimmermann, MB, Wegmueller, R, Zeder, C, et al. (2004) Triple fortification of salt with microcapsules of iodine, iron, and vitamin A. Am J Clin Nutr 80, 12831290.
4. Ballot, DE, Macphail, AP, Bothwell, TH, et al. (1989) Fortification of curry powder with NaFe(III)EDTA in an iron-deficient population – report of a controlled iron-fortification trial. Am J Clin Nutr 49, 162169.
5. Chen, J, Zhao, X, Zhang, X, et al. (2005) Studies on the effectiveness of NaFeEDTA-fortified soy sauce in controlling iron deficiency: a population-based intervention trial. Food Nutr Bull 26, 177186.
6. Zimmermann, MB, Wegmueller, R, Zeder, C, et al. (2004) Dual fortification of salt with iodine and micronized ferric pyrophosphate: a randomized, double-blind, controlled trial. Am J Clin Nutr 80, 952959.
7. Andersson, M, Thankachan, P, Muthayya, S, et al. (2008) Dual fortification of salt with iodine and iron: a randomized, double-blind, controlled trial of micronized ferric pyrophosphate and encapsulated ferrous fumarate in southern India. Am J Clin Nutr 88, 13781387.
8. Engle-Stone, R, Ndjebayi, AO, Nankap, M, et al. (2012) Consumption of potentially fortifiable foods by women and young children varies by ecological zone and socio-economic status in Cameroon. J Nutr 142, 555565.
9. Hess, SY, Brown, KH, Sablah, M, et al. (2013) Results of Fortification Rapid Assessment Tool (FRAT) surveys in sub-Saharan Africa and suggestions for future modifications of the survey instrument. Food Nutr Bull 34, 2138.
10. Staubli-Asobayire, F (2000) Development of a food fortification strategy to combat iron deficiency in the Ivory Coast. PhD Thesis, ETH Zurich.
11. Bovell-Benjamin, AC, Viteri, FE & Allen, LH (1999) Sensory quality and lipid oxidaton of maize porridge as affected by iron amino acid chelate and EDTA. J Food Sci 64, 371.
12. Hurrell, R (2007) Linking the bioavailability of iron compounds to the efficacy of iron-fortified foods. Int J Vitam Nutr Res 77, 166173.
13. Moretti, D, Lee, TC, Zimmermann, MB, et al. (2005) Development and evaluation of iron-fortified extruded rice grains. J Food Sci 70, S330S336.
14. Hurrell, RF, Furniss, DE, Burri, J, et al. (1989) Iron fortification of infant cereals: a proposal for the use of ferrous fumarate or ferrous succinate. Am J Clin Nutr 49, 12741282.
15. Hurrell, RF, Reddy, MB, Dassenko, SA, et al. (1991) Ferrous fumarate fortification of a chocolate drink powder. Br J Nutr 65, 271283.
16. Moretti, D, Zimmermann, MB, Muthayya, S, et al. (2006) Extruded rice fortified with micronized ground ferric pyrophosphate reduces iron deficiency in Indian schoolchildren: a double-blind randomized controlled trial. Am J Clin Nutr 84, 822829.
17. Blanco-Rojo, R, Perez-Granados, AM, Toxqui, L, et al. (2011) Efficacy of a microencapsulated iron pyrophosphate-fortified fruit juice: a randomised, double-blind, placebo-controlled study in Spanish iron-deficient women. Br J Nutr 105, 16521659.
18. Wegmuller, R, Camara, F, Zimmermann, MB, et al. (2006) Salt dual-fortified with iodine and micronized ground ferric pyrophosphate affects iron status but not hemoglobin in children in Cote d’Ivoire. J Nutr 136, 18141820.
19. Fidler, MC, Davidsson, L, Zeder, C, et al. (2004) Effect of ascorbic acid and particle size on iron absorption from ferric pyrophosphate in adult women. Int J Vitam Nutr Res 74, 294300.
20. Hurrell, RF, Lynch, S, Bothwell, T, et al. (2004) Enhancing the absorption of fortification iron. A SUSTAIN Task Force report. Int J Vitam Nutr Res 74, 387401.
21. Belitz, HD, Grosch, W, Schieberle, P, et al. (2009) Food Chemistry, 4th ed. Berlin: Springer.
22. Tian, T, Blanco, E, Smoukov, SK, et al. (2016) Dissolution behaviour of ferric pyrophosphate and its mixtures with soluble pyrophosphates: potential strategy for increasing iron bioavailability. Food Chem 208, 97102.
23. Walczyk, T, Davidsson, L, Zavaleta, N, et al. (1997) Stable isotope labels as a tool to determine the iron absorption by Peruvian school children from a breakfast meal. Fresen J Anal Chem 359, 445449.
24. World Health Organization, United Nations International Children Emergency Fund & United Nations University (2001) Iron Deficiency Anemia: Assessment, Prevention and Control. Geneva: WHO.
25. Erhardt, JG, Estes, JE, Pfeiffer, CM, et al. (2004) Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique. J Nutr 134, 31273132.
26. Dati, F, Schumann, G, Thomas, L, et al. (1996) Consensus of a group of professional societies and diagnostic companies on guidelines for interim reference ranges for 14 proteins in serum based on the standardization against the IFCC/BCR/CAP reference material (CRM 470). Eur J Clin Chem Clin Biochem 34, 517520.
27. Hotz, K, Krayenbuehl, PA & Walczyk, T (2012) Mobilization of storage iron is reflected in the iron isotopic composition of blood in humans. J Biol Inorg Chem 17, 301309.
28. Petry, N, Rohner, F, Gahutu, JB, et al. (2016) In Rwandese women with low iron status, iron absorption from low-phytic acid beans and biofortified beans is comparable, but low-phytic acid beans cause adverse gastrointestinal symptoms. J Nutr 146, 970975.
29. Brown, E, Hopper, J Jr, Hodges, JL Jr, et al. (1962) Red cell, plasma, and blood volume in the healthy women measured by radiochromium cell-labeling and hematocrit. J Clin Invest 41, 21822190.
30. Kastenmayer, P, Davidsson, L, Galan, P, et al. (1994) A double stable isotope technique for measuring iron absorption in infants. Br J Nutr 71, 411424.
31. Hosain, F, Marsaglia, G, Noyes, W, et al. (1962) The nature of internal iron exchange in man. Trans Assoc Am Physicians 75, 5963.
32. Miller, DD, Schricker, BR, Rasmussen, RR, et al. (1981) An in vitro method for estimation of iron availability from meals. Am J Clin Nutr 34, 22482256.
33. Luten, J, Crews, H, Flynn, A, et al. (1996) Interlaboratory trial on the determination of the in vitro iron dialysability from food. J Sci Food Agric 72, 415424.
34. Viollier, E, Inglett, PW, Hunter, K, et al. (2000) The ferrozine method revisited: Fe(II)/Fe(III) determination in natural waters. Appl Geochem 15, 785790.
35. Glahn, RP, Lee, OA, Yeung, A, et al. (1998) Caco-2 cell ferritin formation predicts nonradiolabeled food iron availability in an in vitro digestion/Caco-2 cell culture model. J Nutr 128, 15551561.
36. Moretti, D, Zimmermann, MB, Wegmuller, R, et al. (2006) Iron status and food matrix strongly affect the relative bioavailability of ferric pyrophosphate in humans. Am J Clin Nutr 83, 632638.
37. Hurrell, RF (2004) Phytic acid degradation as a means of improving iron absorption. Int J Vitam Nutr Res 74, 445452.
38. Cercamondi, CI, Egli, IM, Zeder, C, et al. (2013) Sodium iron EDTA and ascorbic acid, but not polyphenol oxidase treatment, counteract the strong inhibitory effect of polyphenols from brown sorghum on the absorption of fortification iron in young women. Br J Nutr 111, 19.
39. Armah, SM, Carriquiry, A, Sullivan, D, et al. (2013) A complete diet-based algorithm for predicting nonheme iron absorption in adults. J Nutr 143, 11361140.
40. Davidsson, L, Kastenmayer, P, Szajewska, H, et al. (2000) Iron bioavailability in infants from an infant cereal fortified with ferric pyrophosphate or ferrous fumarate. Am J Clin Nutr 71, 15971602.
41. Walczyk, T, Kastenmayer, P, Storcksdieck Genannt Bonsmann, S, et al. (2013) Ferrous ammonium phosphate (FeNH(4)PO(4)) as a new food fortificant: iron bioavailability compared to ferrous sulfate and ferric pyrophosphate from an instant milk drink. Eur J Nutr 52, 13611368.
42. Fidler, MC, Walczyk, T, Davidsson, L, et al. (2004) A micronised, dispersible ferric pyrophosphate with high relative bioavailability in man. Br J Nutr 91, 107112.
43. Zimmermann, MB, Biebinger, R, Egli, I, et al. (2011) Iron deficiency up-regulates iron absorption from ferrous sulphate but not ferric pyrophosphate and consequently food fortification with ferrous sulphate has relatively greater efficacy in iron-deficient individuals. Br J Nutr 105, 12451250.
44. Food and Agriculture Organization, World Health Organization & UNU (2004) Vitamin and Mineral Requirements in Human Nutrition. Report of A Joint FAO/WHO Expert Consultation, 2nd ed. Bangkok: FAO/WHO.
45. Cercamondi, CI, Icard-Verniere, C, Egli, IM, et al. (2014) A higher proportion of iron-rich leafy vegetables in a typical Burkinabe maize meal does not increase the amount of iron absorbed in young women. J Nutr 144, 13941400.
46. World Health Organization (2012) Guideline: Sodium Intake for Adults and Children. Geneva: WHO.
47. Sandberg, AS (2005) Methods and options for in vitro dialyzability: benefits and limitations. Int J Vitam Nutr Res 75, 395404.
48. Fairweather-Tait, S, Phillips, I, Wortley, G, et al. (2007) The use of solubility, dialyzability, and Caco-2 cell methods to predict iron bioavailability. Int J Vitam Nutr Res 77, 158165.
49. Fairweather-Tait, S, Lynch, S, Hotz, C, et al. (2005) The usefulness of in vitro models to predict the bioavailability of iron and zinc: a consensus statement from the HarvestPlus expert consultation. Int J Vitam Nutr Res 75, 371374.


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