Abstract
Titanium dioxide (TiO2) is widely used to mask the color of iron fortificants in double fortified salt (DFS) and in other foods such as candies and mints, but its regulatory status has prompted the search for alternatives. In 2021, the European Food Safety Authority banned TiO2 due to genotoxicity concerns. This study evaluated TiO2 alternatives, CaCO3, MgCO3, ZnO, CaSO4, Opadry, and Nutrafinish blends (commercial coatings of CaCO3 and HPMC), for masking the color of extruded ferric pyrophosphate (FePP) premixes, including formulations with iron absorption enhancing adjuncts (Na2EDTA, citric acid (CA), trisodium citrate (TSC)) and without adjuncts. Coated extrudates were assessed for color uniformity (ΔE), core coverage, iodine retention after nine months of storage at elevated temperature and humidity, and in vitro iron bioaccessibility.
Effective color masking was achieved with 25% ZnO, 45% CaCO3, 55% MgCO3, 65% CaSO4, 25% Opadry, and 25% Nutrafinish 002, all with 15% soy stearin. FePP premixes containing CA/TSC premixes showed improved color uniformity compared with Na2EDTA formulations. Iodine retention exceeded 50% in most formulations, indicating acceptable shelf life. Iodine loss at elevated temperatures was primarily attributed to increased diffusion through coating defects and subsequent reaction between exposed iron and iodate, rather than complete liquefaction of the fat overcoat. Iron release followed pseudo-first-order kinetics, with CaCO3 > ZnO > CaSO4 in solubility and bioaccessibility. These findings demonstrate that TiO2-free coatings can provide effective color masking, maintain iodine stability, and support iron release in FePP-based DFS, offering viable pathways for regulatory-compliant, consumer-acceptable formulations.
Highlights
- TiO2 alternatives tested for color masking in FePP and FeFum salt premixes.
- Effective color masking was achieved with 25% ZnO, 45% CaCO3, 55% MgCO3, 65% CaSO4, 25% Opadry, 25% Nutrafinish 002, each with 15% soy stearin.
- Iodine retention exceeded 50% after 9 months at elevated temperature and humidity.
- Iron bioaccessibility followed pseudo-first-order kinetics.
- Higher FePP dosing is required to match absorption levels of FeFum.
Introduction
Iron deficiency anemia (IDA) affects approximately 2 billion people worldwide and is most prevalent in low-middle-income countries (LMICs), where access to a diverse diet is not feasible (Gardner et al., 2023). Complications in pregnancy resulting from anemia include preterm labour, postpartum haemorrhage, still birth, neurological impairments. Food fortification is a successful strategy to address IDA, as key nutrients are added to staple foods, thus not requiring consumer lifestyle changes. Ferric pyrophosphate (FePP) has been proposed as a fortificant in foods to combat iron deficiency, due to its sensorial acceptability. Though it has been used in extruded rice (Hackl et al., 2016), and bouillon cubes (Eilander et al., 2019), its limited bioavailability makes fortification a challenge. Ferric iron is insoluble above pH 3.5, such as in the neutral pH of the small intestine, requiring a strategy to increase iron absorption for FePP formulations (Heimbach et al., 1999).
The bioavailability of ferric pyrophosphate is improved by iron absorption enhancing adjuncts, also known as solubilizers such as citric acid, trisodium citrate and disodium ethylenediaminetetraacetic acid (Na2EDTA). When FePP and CA/TSC was incorporated into extruded rice grains, the bioavailability of iron doubled compared to FePP without adjuncts (Hackl et al., 2016). The adjuncts act as chelating agents, which bind to the iron atoms in ferric pyrophosphate, forming a complex. This complex is more soluble and stable in solution, making the iron more bioavailable for absorption in the body. The addition of citric acid (CA) and trisodium citrate (TSC) results in formation of many oligonuclear complexes in which two or more metal ions are linked together by bridging ligands which connect the metal ions, creating a network within the complex (Hider et al., 2024). Citrate is a tricarboxylic acid anion that comes from citric acid and has multiple carboxyl groups that bind to metals (in this case ferric iron) to form stable chelates.
Similarly to citric acid, Na2EDTA increases the bioavailability of ferric pyrophosphate in extruded rice (Scheuchzer et al., 2023). EDTA behaves as a complexing agent to reduce side reactions of ferric iron with absorption inhibitors. It forms a ferric EDTA complex which increases the concentration of soluble iron. The oxygen atoms from the carboxyl (-COO−) groups and nitrogen atoms from the amine (−NH2) groups in EDTA donate electron pairs to Fe3+, forming coordinate bonds. The key difference between EDTA and citrate as chelators is that EDTA is a hexadentate ligand (binds through six donor atoms), whereas citrate is a tridentate ligand (binds through three donor atoms), which makes EDTA more stable (Heimbach et al., 1999).
Chelation by EDTA and citric acid prevents precipitation of ferric iron and increase the solubility of iron, preparing it for uptake (Knutson, 2019). Ferric iron stays complexed under acidic conditions and then the strength of the complex declines as the pH increases, as it moves through the small intestine, enabling release for absorption (Heimbach et al., 1999). Ferric iron is reduced to ferrous iron by the enzyme duodenal cytochrome b (DCYTB) at the apical membrane of the intestine (top surface of intestinal epithelial cells). Ferrous iron is transported across cell membranes from the gut lumen, into the cells by DMT1 (divalent metal transporter 1), (Knutson, 2019) (Gracheva et al., 2024).
Ferric pyrophosphate with iron enhancing adjuncts shows promise as iron source in fortified salts. In a study by Teichman et al., FePP with adjuncts Na2EDTA, CA/TSC, and sodium pyrophosphate as stable extruded formulations with a coating system to prevent iodine loss were developed (Teichman, Chan, et al., 2025). Each adjunct resulted in unacceptable coloration of the FePP, due to the soluble ferric-ligand complexes formed, so, the premix needed a color masking layer. Using extrusion, color-masking with titanium dioxide (TiO2) for sensory acceptability and soy stearin for microencapsulation, premixes were produced and then mixed into iodized salt to produce double fortified salts (DFS). Formulations including FePP with adjuncts, zinc and vitamins B9, B12 were also developed to produce multiple fortified salts (MFS). The fortified salts were stable after 9 months storage studies in accelerated temperature chambers.
TiO2 has been successful for masking the dark brown hue of ferrous fumarate in double (Diosady et al., 2019) and multiple fortified salt, using cold-forming extrusion-based microencapsulation (Modupe, 2020). As of 2019, DFS with ferrous fumarate and potassium iodate has reached 60 million consumers in India to treat iron deficiency anemia (Diosady et al., 2019) (Siddiqui et al., 2022). Although, TiO2 is effective for ensuring organoleptic acceptance of DFS, apprehension regarding possible genotoxic effects has caused debate regarding its safety in the scientific community (Weir et al., 2012), (Winkler et al., 2018), (Ghebretatios et al., 2021). The European Food Safety Authority banned the use of titanium dioxide (E171) in 2021 in food (Von der Leyen, 2021), due to risk of suspected nanoparticles in food and possible cancer implications (Shammas et al., 2015). This was followed by a ban, reversed shortly afterwards, by California. The United States Federal Drug Administration permits titanium dioxide as long as the quantity does not exceed 1% by weight of the food (American Chemistry Council, 2023; United States Federal Drug Administration, 2023). Health Canada, Food Standards Australia New Zealand, U.K. Food Standards Agency also permit titanium dioxide in foods at the currently allowed levels (American Chemistry Council, 2023; Health Canada, 2023).
While the amount of titanium dioxide in DFS is a small fraction of the permitted levels, due to potential safety concerns of TiO2, it is sensible to look for alternate color masking agents for use in fortified salts. Inorganic alternatives CaCO3, CaSO4, MgCO3, ZnO, were investigated as potential replacements for TiO2 in ferrous fumarate double fortified salts, since these were GRAS (generally regarded as safe for consumption) alternatives, commonly used in candies, mints, as food colorants, and in dietary supplements for calcium, zinc and magnesium deficiencies (Teichman, Siddiqui, et al., 2025). Their established safety profile, widespread use in food applications, and inherent whiteness made them attractive candidates for maintaining visual appeal while complying with potential future regulatory restrictions on TiO2. The CaSO4, CaCO3, and ZnO premixes demonstrated favorable appearance and maintained fortificant stability throughout a 9-month storage period, while MgCO3 formulations had poor adhesion (Teichman, Siddiqui, et al., 2025). This prompted further studies to improve coatings of MgCO3 utilizing a gum Arabic-based suspension or soy stearin-based suspension (Vatandoust et al., 2024).
Alternatively, rice starch and rice flour offered organic, cost-effective alternative to titanium dioxide for color masking. However, due to rice starch’s amorphous granules and low electrostatic forces, it adhered poorly to extruded materials, necessitating the development of specialized adhesives to improve its binding performance. Rice starch and rice flour, when crosslinked with citric acid to form ester-based adhesives, was also a promising alternative to TiO2 (Teichman et al., 2024).
Ensuring the bioaccessibility of the iron premix remains essential when selecting alternatives to TiO2 . Bioaccessibility is the quantity of a nutrient that is released from its food matrix, which is then available for absorption (Huey et al., 2024). Subsequently, bioavailability is the quantity of the substance that is absorbed into the bloodstream and reaches the target site. For the substance to be bioavailable, first it needs to be bioaccessible, therefore it is important to determine the bioaccessibility of the premixes for salt fortification.
The purpose of this study was to develop and evaluate TiO2-free coating systems for ferric pyrophosphate (FePP) premixes intended for double-fortified salt. Specifically, the study aimed to: (1) assess FePP, with and without solubility-enhancing adjuncts (citric acid, trisodium citrate, Na2EDTA), as a potential alternative to ferrous fumarate (FeFum), (2) identify and optimize color-masking agents capable of replacing TiO2 in FePP-based premixes; (3) evaluate the appearance and coating performance of these formulations using colorimetry and microscopy; (4) determine their ability to maintain iodine stability during storage; and (5) compare the in vitro iron bioaccessibility of FePP-based formulations with FeFum to assess their potential nutritional efficacy.
Extruded ferric pyrophosphate (FePP), when complexed with solubility-enhancing adjuncts such as citric acid, trisodium citrate, and Na2EDTA, and color-masked with optimized alternatives to TiO2, can effectively replace ferrous fumarate (FeFum) in fortified salt formulations by maintaining comparable bioaccessibility and iodine stability while improving visual appearance. Furthermore, suitable replacements for titanium dioxide can be identified and optimized to achieve effective color masking without compromising the sensory or nutritional quality of the FePP premix.
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Diana L. Teichman, Ariel Chan, Michael B. Zimmermann, Levente L. Diosady, TiO2 alternative coatings for ferric pyrophosphate premixes: Stability and bioaccessibility relative to ferrous fumarate, Innovative Food Science & Emerging Technologies, 2026, 104527, ISSN 1466-8564, https://doi.org/10.1016/j.ifset.2026.104527.
