Design and characterization of Ca-Fe(III) pyrophosphate salts with tunable pH-dependent solubility for dual-fortification of foods

Food-fortification using poorly water-soluble mineral-containing compounds is a common approach to deliver iron. However, it comes with the challenge of ensuring iron bio-accessibility and limiting iron-phenolic interactions that can change organoleptic properties. Mixed Ca-Fe(III) pyrophosphate salts with the general formula Ca2(1-x)Fe4x(P2O7)(1+2x) were designed as a system for simultaneous delivery of iron and calcium. The salts were synthesized via a co-precipitation method and characterized by TEM-EDX, XRD, and FT-IR. All mixed salts with 0.14 ≤ x ≤ 0.35 yielded homogenous amorphous particles. The iron dissolution from these mixed salts showed a fourfold increase at gastric pH compared to Fe(III) pyrophosphate. In the food-relevant pH range, the salts with x ≤ 0.15 showed up to an eight-fold decrease in iron solubility. Despite this, reactivity of the mixed salts in tea was similar to that of FePP. Our results indicate that these mixed salts are potential dual-fortificants with tunable iron content and solubility

Iron fortification of foods: Multi-mineral pyrophosphate-based salts

Iron deficiency is one of the most prevalent nutritional problems in the world. However, iron is a challenging mineral to add to food products. Iron-containing compounds can react with the (phyto)chemicals present in foods and as a result cause severe changes in the organoleptic properties, for instance off-flavor and off-color. To date, iron fortification of foods has proven to be an efficient and cost-effective approach to overcome iron deficiency. Iron-containing compounds that are applied as iron fortificants are divided into three main categories; water-soluble, poorly watersoluble (but soluble in dilute acid), and water-insoluble (and poorly soluble in dilute acid). Although water-soluble compounds have the advantage of high iron bioavailability, the other categories are more in the center of attention because of their minimum influence on the organoleptic properties of the foods which is a consequence of their limited solubilities. Among the poorly water-soluble or water-insoluble iron compounds, ferric pyrophosphate (Fe(III)PP) has attracted a great deal of attention. Fe(III)PP is a white solid that prevents addition of unwanted colors to foods. It has been shown that Fe(III)PP is very poorly soluble in the food relevant pH (3-7) which is the reason for the limited reactivity of this salt with the fortified food vehicle. Furthermore, Fe(III)PP has low solubility at low pH and enhanced dissolution at high pH which is advantageous for ensuring the sufficient iron bio-accessibility. However, it has previously been shown that addition of iron in the form of Fe(III)PP cannot fully prevent the discoloration of the phenolic-rich foods. Therefore, improving the function of Fe(III)PP as an iron fortificant (i.e., decreasing the iron-mediated reactivity while ensuring the iron bio-accessibility) still remains of interest. In this work, we seek the strategies by which we can design iron-containing compounds with minimum solubility in the food-relevant pH (3-7), and high and/or fast dissolution in gastric and intestinal pH (1-3 and 6-8, respectively). Interestingly, mother nature can help us find the answer. Inspired by naturally-occurring minerals such as anapaite (i.e., a mixed calcium–iron phosphate mineral), we intend to embed iron in the matrix of a second (divalent) metal (or mineral) salt, which is less chemically reactive, aiming for: (i) decreasing the iron-mediated reactivity to preserve the organoleptic properties of the food vehicle, and (ii) increasing iron dissolution from the designed multi-mineral salt in the gastric conditions to ensure bio-accessibility of iron (and the other mineral). Another benefit of using these multi-mineral salts is the possibility of simultaneous delivery of at least two minerals by the fortified food vehicle. In Part I of this thesis, we explore the possibilities of improving the function of Fe(III)PP as an iron-fortificant by mixing Ca along Fe in one salt matrix. Part II of the present thesis is dedicated to iron (II)-containing pyrophosphate salts that are potential iron fortificants. In this part we explore the possibility of applying ferrous pyrophosphate (Fe(II)PP) in food fortification. Finally, in Part III of this thesis, we challenge the notion that cooperative binding only happens in complicated biological systems like hemoglobin

Iron fortification of foods: Multi-mineral pyrophosphate-based salts

Iron deficiency is one of the most prevalent nutritional problems in the world. However, iron is a challenging mineral to add to food products. Iron-containing compounds can react with the (phyto)chemicals present in foods and as a result cause severe changes in the organoleptic properties, for instance off-flavor and off-color. To date, iron fortification of foods has proven to be an efficient and cost-effective approach to overcome iron deficiency. Iron-containing compounds that are applied as iron fortificants are divided into three main categories; water-soluble, poorly watersoluble (but soluble in dilute acid), and water-insoluble (and poorly soluble in dilute acid). Although water-soluble compounds have the advantage of high iron bioavailability, the other categories are more in the center of attention because of their minimum influence on the organoleptic properties of the foods which is a consequence of their limited solubilities. Among the poorly water-soluble or water-insoluble iron compounds, ferric pyrophosphate (Fe(III)PP) has attracted a great deal of attention. Fe(III)PP is a white solid that prevents addition of unwanted colors to foods. It has been shown that Fe(III)PP is very poorly soluble in the food relevant pH (3-7) which is the reason for the limited reactivity of this salt with the fortified food vehicle. Furthermore, Fe(III)PP has low solubility at low pH and enhanced dissolution at high pH which is advantageous for ensuring the sufficient iron bio-accessibility. However, it has previously been shown that addition of iron in the form of Fe(III)PP cannot fully prevent the discoloration of the phenolic-rich foods. Therefore, improving the function of Fe(III)PP as an iron fortificant (i.e., decreasing the iron-mediated reactivity while ensuring the iron bio-accessibility) still remains of interest. In this work, we seek the strategies by which we can design iron-containing compounds with minimum solubility in the food-relevant pH (3-7), and high and/or fast dissolution in gastric and intestinal pH (1-3 and 6-8, respectively). Interestingly, mother nature can help us find the answer. Inspired by naturally-occurring minerals such as anapaite (i.e., a mixed calcium–iron phosphate mineral), we intend to embed iron in the matrix of a second (divalent) metal (or mineral) salt, which is less chemically reactive, aiming for: (i) decreasing the iron-mediated reactivity to preserve the organoleptic properties of the food vehicle, and (ii) increasing iron dissolution from the designed multi-mineral salt in the gastric conditions to ensure bio-accessibility of iron (and the other mineral). Another benefit of using these multi-mineral salts is the possibility of simultaneous delivery of at least two minerals by the fortified food vehicle. In Part I of this thesis, we explore the possibilities of improving the function of Fe(III)PP as an iron-fortificant by mixing Ca along Fe in one salt matrix. Part II of the present thesis is dedicated to iron (II)-containing pyrophosphate salts that are potential iron fortificants. In this part we explore the possibility of applying ferrous pyrophosphate (Fe(II)PP) in food fortification. Finally, in Part III of this thesis, we challenge the notion that cooperative binding only happens in complicated biological systems like hemoglobin

Iron-fortified food product

Disclosed is a food product comprising multimineral iron-containing particles of general formula i MlwM2xM3yM4zLlaL2bL3cL4ct, wherein• Ml is Fe2+, • M2 is Fe3+, • M3 is selected from Na+, K+, NH4+ and combinations thereof, M4 is selected from Ca2+, Mg2+, Mn2+, Zn2+ and combinations thereof, • LI is selected from Off, HCO3-, H2PO4-, H3P2O7- and combinations thereof, L2 is selected from CO32, HPO42, H2PsO72 and combinations thereof, L3 is selected form PO43, HP2O73 and combinations thereof, • L4 is P O7 4-, • 2w + 3x + y + 2z = a+ 2b + 3c + 4d, • each of w, x, y, a, b, c and dare 2: 0, • z > 0, • wx > 0, and• [(w + x) I (w + x + y 2+ z)] < 0.5

Reactivity of Fe(III)-containing pyrophosphate salts with phenolics : complexation, oxidation, and surface interaction

Mixed pyrophosphate salts with the general formula Ca2(1-x)Fe4x(P2O7)(1+2x) potentially possess less iron-phenolic reactivity compared to ferric pyrophosphate (FePP), due to decreased soluble Fe in the food-relevant pH range 3–7. We investigated reactivity (i.e., complexation, oxidation, and surface interaction) of FePP and mixed salts (with x = 0.14, 0.15, 0.18, and 0.35) in presence of structurally diverse phenolics. At pH 5–7, increased soluble iron from all salts was observed in presence of water-soluble phenolics. XPS confirmed that water-soluble phenolics solubilize iron after coordination at the salt surface, resulting in increased discoloration. However, color changes for mixed salts with x ≤ 0.18 remained acceptable for slightly water-soluble and insoluble phenolics. Furthermore, phenolic oxidation in presence of mixed salts was significantly reduced compared to FePP at pH 6. In conclusion, these mixed Ca-Fe(III) pyrophosphate salts with x ≤ 0.18 can potentially be used in designing iron-fortified foods containing slightly water-soluble and/or insoluble phenolics

Design and characterization of Ca-Fe(III) pyrophosphate salts with tunable pH-dependent solubility for dual-fortification of foods

Food-fortification using poorly water-soluble mineral-containing compounds is a common approach to deliver iron. However, it comes with the challenge of ensuring iron bio-accessibility and limiting iron-phenolic interactions that can change organoleptic properties. Mixed Ca-Fe(III) pyrophosphate salts with the general formula Ca2(1-x)Fe4x(P2O7)(1+2x) were designed as a system for simultaneous delivery of iron and calcium. The salts were synthesized via a co-precipitation method and characterized by TEM-EDX, XRD, and FT-IR. All mixed salts with 0.14 ≤ x ≤ 0.35 yielded homogenous amorphous particles. The iron dissolution from these mixed salts showed a fourfold increase at gastric pH compared to Fe(III) pyrophosphate. In the food-relevant pH range, the salts with x ≤ 0.15 showed up to an eight-fold decrease in iron solubility. Despite this, reactivity of the mixed salts in tea was similar to that of FePP. Our results indicate that these mixed salts are potential dual-fortificants with tunable iron content and solubility

Design and characterization of Ca-Fe(III) pyrophosphate salts with tunable pH-dependent solubility for dual-fortification of foods

Food-fortification using poorly water-soluble mineral-containing compounds is a common approach to deliver iron. However, it comes with the challenge of ensuring iron bio-accessibility and limiting iron-phenolic interactions that can change organoleptic properties. Mixed Ca-Fe(III) pyrophosphate salts with the general formula Ca2(1-x)Fe4x(P2O7)(1+2x) were designed as a system for simultaneous delivery of iron and calcium. The salts were synthesized via a co-precipitation method and characterized by TEM-EDX, XRD, and FT-IR. All mixed salts with 0.14 ≤ x ≤ 0.35 yielded homogenous amorphous particles. The iron dissolution from these mixed salts showed a fourfold increase at gastric pH compared to Fe(III) pyrophosphate. In the food-relevant pH range, the salts with x ≤ 0.15 showed up to an eight-fold decrease in iron solubility. Despite this, reactivity of the mixed salts in tea was similar to that of FePP. Our results indicate that these mixed salts are potential dual-fortificants with tunable iron content and solubility