Ferric EDTA Research Articles

Differential Effects of Iron Chelates vs. Iron Salts on Induction of Pro-Oncogenic Amphiregulin and Pro-Inflammatory COX-2 in Human Intestinal Adenocarcinoma Cell Lines

We previously showed that two iron compounds that are orally ingested by humans, namely ferric EDTA and ferric citrate, can induce an oncogenic growth factor (amphiregulin) in human intestinal epithelial adenocarcinoma cell lines. Here, we further screened these iron compounds, plus four other iron chelates and six iron salts (i.e., 12 oral iron compounds in total), for their effects on biomarkers of cancer and inflammation. Ferric pyrophosphate and ferric EDTA were the main inducers of amphiregulin and its receptor monomer, IGFr1. Moreover, at the maximum iron concentrations investigated (500 µM), the highest levels of amphiregulin were induced by the six iron chelates, while four of these also increased IGfr1. In addition, we observed that ferric pyrophosphate promoted signaling via the JAK/STAT pathway by up-regulating the cytokine receptor subunit IFN-γr1 and IL-6. For pro-inflammatory cyclooxygenase-2 (COX-2), ferric pyrophosphate but not ferric EDTA elevated intracellular levels. This, however, did not drive the other biomarkers based on COX-2 inhibition studies and was probably downstream of IL-6. We conclude that of all oral iron compounds, iron chelates may particularly elevate intracellular amphiregulin. Ferric pyrophosphate additionally induced COX-2, probably because of the high IL-6 induction that was observed with this compound.

Evaluation of Oral Therapy Based on Ferric Sodium EDTA, in Combination With Vitamin C, Folic Acid, Copper Gluconate, Zinc Gluconate and Selenomethionine, in Iron-Deficiency Anemia: A Real-Life Study

Iron deficiency (ID) and iron-deficiency anemia (IDA) are still frequent conditions in several patients’ settings. Oral iron supplementation is one of available treatments of IDA, representing a convenient strategy since is cost-saving, effective and does not require intravenous (IV) access. However, often traditional oral iron therapies, mainly based on ferrous sulphate, are poorly tolerated, and with low iron absorption, causing gastrointestinal adverse events and limiting adherence to treatment and efficacy. The aim of this study is to evaluate the efficacy and safety of a new oral iron supplementation based on Ferric Sodium EDTA, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) for IDA treatment in real-life clinical practice. Patients (N=103) were allocated to treatment with this new formulation at dosage of 1 tab/day, containing 30 mg of iron for 72 days. Patients were evaluated at basal conditions (T0), after 24 and 72 days of therapy (T1 and T2, respectively), collecting blood parameters of hemoglobin (Hb) and sideremia, evaluated as primary objective. The secondary outcomes were symptoms improvement (evaluated through a 4-points score) and safety profile of oral therapy. Treatment with Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) showed improvements statistically significant (P < 0.001) of Hb and sideremia levels both at time T1 and T2. Symptoms evaluation showed an almost total resolution of symptomatology after only 72 days of therapy, and treatment was safe and well tolerated. In conclusion, this study confirmed the efficacy and the safety of the new oral iron formulation evaluated, for IDA patients in real-life clinical practice.

Quintuply-fortified salt for the improvement of micronutrient status among women of reproductive age and preschool-aged children in Punjab, India: protocol for a randomized, controlled, community-based trial

BackgroundMultiple micronutrient (MN) deficiencies remain highly prevalent among women of reproductive age (WRA) and preschool-aged children (PSC) in many areas within India. Salt is an attractive vehicle for MN fortification in this context, as it is universally consumed in fairly consistent amounts and coverage of iodized salt (IS) is 94%. The overall objective of this trial is to evaluate the nutritional impact of quintuply-fortified salt with iron in the form of encapsulated ferrous fumarate, zinc, vitamin B12, folic acid, and iodine (eFF-Q5S) vs. quintuply-fortified salt with iron in the form of ferric pyrophosphate plus EDTA, zinc, vitamin B12, folic acid, and iodine (FePP-Q5S) vs. IS for the improvement of MN status among non-pregnant WRA and PSC.MethodsThe study is a community-based, randomized, controlled trial that will be conducted in Punjab, India. 780 non-pregnant WRA 18–49 years old and 468 PSC 12–59 months old will be enrolled and assigned to one of three intervention groups. Salt will be provided to participants monthly for 12 months. Primary outcomes include changes in mean concentration of biomarkers of iron, zinc, vitamin B12, folate and iodine. Secondary outcomes include changes in the composition of the gut microbiome, and discretionary salt intake of PSC.DiscussionIf proven efficacious, multiply-fortified salt (MFS) has the potential to drastically reduce the burden of MN deficiencies in India, and around the world. Although effectiveness research will be needed to examine the impact of MFS under programmatic conditions, salt fortification will piggy-back on existing platforms to produce IS and doubly-fortified salt (DFS), making it possible to scale-up the intervention quickly.Trial registrationClinicaltrials.gov: NCT05166980; date of registration: December 22, 2021. Clinical Trials Registry-India: CTRI/2022/040332 and CTRI/2022/02/040333; date of registration: February 15, 2022.

Delivery of Ferric Sodium EDTA by Water-in-Oil-in-Water (W1/O/W2) Double Emulsions: Influence of Carrier Oil on its in Vitro Bioaccessibility

Delivery of Ferric Sodium EDTA by Water-in-Oil-in-Water (W1/O/W2) Double Emulsions: Influence of Carrier Oil on its in Vitro Bioaccessibility

Preparation of iron-loaded water-in-oil-in-water (W1/O/W2) double emulsions: optimization using response surface methodology

Iron deficiency anemia is a major public health problem caused by low iron intake or bioavailability. To overcome the problem of anemia, iron fortification of a variety of food products is being tested worldwide. Ferric sodium EDTA is a desirable iron source for food fortification due to its high bioavailability and ability to prevent binding of iron to phytates during absorption. This study investigated the application of double emulsions for encapsulation and controlled delivery of ferric sodium EDTA stabilized by the lipophilic Span®80 and hydrophilic complex of sodium alginate and sodium caseinate emulsifiers. The influence of factors such as the ratio of internal water to the oil phase, concentrations of alginate or Span®80 and the ratio of water-in-oil emulsion to the external water on internal (din ) and external emulsion droplet sizes (dout ) was studied by response surface methodology. The feasible range for selection of factors for achieving target values of din and dout was proposed by the response optimizer confirmed by the results of experiments. The results indicate that double emulsion systems may be useful for iron fortification of food products.

Tea Consumption Reduces Iron Bioavailability from NaFeEDTA in Nonanemic Women and Women with Iron Deficiency Anemia: Stable Iron Isotope Studies in Morocco

BackgroundAvailable data suggest that polyphenols from tea can inhibit iron absorption from ferric sodium EDTA (NaFeEDTA), but previous studies were done in small groups of mostly nonanemic adults. Morocco recently introduced national wheat flour fortification with NaFeEDTA, but tea is the national beverage and is consumed with most meals. ObjectivesOur objective was to quantify bioavailability of iron from NaFeEDTA when added to a wheat flour–based meal in both nonanemic women and women with iron deficiency anemia (IDA), when consumed with and without traditional Moroccan green tea. MethodsWe recruited 2 groups of healthy Moroccan women (n = 46): women with IDA (n = 25; hemoglobin <12 g/dL, serum ferritin <15 μg/L) and nonanemic women (n = 21). Each group received in random order 2 standardized test meals containing 6 mg Fe as isotopically labeled NaFeEDTA and either 300 mL of tea or water. Fractional iron absorption (FIA) was measured by the erythrocyte incorporation of stable iron isotopes after 14 d. We performed linear mixed-model analysis and post hoc sample t tests to assess the effects of group and tea on FIA. ResultsThe polyphenol content of the tea serving was 492 mg. Tea consumption reduced iron absorption from NaFeEDTA by >85% in both IDA and nonanemic women. There were group (P < 0.001) and tea (P < 0.001) effects on FIA, but no group by tea interaction (P = 0.312). Median (IQR) FIA (%) in women with IDA from test meals consumed without and with tea was 36.7 (24.2–39.8) and 4.1 (2.8–6.1), respectively (P < 0.001). Median (IQR) FIA (%) in nonanemic women from test meals consumed without and with tea was 16.7 (9.2–24.2) and 1.4 (0.8–2.9), respectively (P < 0.001). ConclusionsFIA from wheat flour–based meals without and with tea was ∼2-fold higher in women with IDA than in nonanemic women. Providing fortificant iron as NaFeEDTA cannot overcome the inhibition of tea polyphenols on iron absorption, even in IDA, where iron absorption is strongly upregulated. This trial was registered at www.clinicaltrials.gov as NCT02175888.

Effect of L-calcium lactate, zinc lactate, and ferric sodium EDTA on the physicochemical and functional properties of liquid whole egg.

The study aimed to evaluate the physicochemical and functional properties of liquid whole egg (LWE) with L-calcium lactate (L-Ca), zinc lactate (L-Zn), and sodium ferric EDTA (NaFeEDTA), and to compare with NaCl addition to determine the application potential of these mineral supplements. Results showed that salts addition significantly influenced the foaming, emulsifying, and gelling properties of LWE, which was possible through affecting the pH, particle size, surface hydrophobicity, apparent viscosity, and solubility. The addition of all the four salts reduced pH but increased the d4,3 diameter of LWE. Additionally, the addition of 200mM L-Ca and 6mM L-Zn significantly improved the emulsifying capacity by 41.73% and 13.6%, the foaming capacity by 26.57% and 10%, and the protein solubility by 13.89% and 12.70%, respectively. In the meantime, mineral supplements tend to produce lower hardness gel, especially with 25mML-Ca and 8mM L-Zn, and the hardness was decreased from 2401.13 to 1138.29 and 1175.59g, respectively. A relative decrease in hardness was desirable in gelled egg products. Moreover, the addition of NaCl and L-Ca showed a higher redness and yellowness, but the addition of NaFeEDTA showed an undesirable color in dark brown, which may be not accepted by the public. In summary, L-Ca and L-Zn had great potential for application in LWE, which was more appropriate than adding NaCl. This study provides a basis for improving the functional properties of LWE products in the future. PRACTICAL APPLICATION: The addition of L-Ca and L-Zn to liquid whole egg (LWE) could improve the foaming and emulsifying capacity of LWE as well as produce a lower hardness gel, which may be more conducive to the production of cake, custards, and meat products. Meantime, it is more in line with people's pursuit of a healthy diet.

Benefit of Iron Supplementation with Ferric Sodium EDTA (NaFe &amp;lt;sup&amp;gt;3+&amp;lt;/sup&amp;gt;-EDTA) in the Treatment of Anemia during Pregnancy in Democratic Republic of Congo (FERARI Study)

Background: Oral iron supplements, usually in the form of ferrous salts, are associated with gastric side effects, poor compliance and failure of anemia treatment. To make iron more bioavailable, reduce the gastric side effects and increase the patient compliance, newer iron form, Ferric Sodium EDTA, has become available on the market. Objective: To assess the change in hemoglobin level after iron supplementation with Ferric Sodium EDTA during pregnancy. Materials and Methods: This is a longitudinal study concerning 337 women attending antenatal care in maternity hospitals in the Democratic Republic of Congo from May to December 2020. The study included sociodemographic and anthropometric variables along with type of feed, hemoglobin level at recruitment and after three weeks of taking iron supplement with Ferric Sodium EDTA (Hemoforce Plus Zinc® syrup). For statistical analysis, we used t-test or ANOVA and chi-square test, the significance being stated at p Results: The frequency of pregnancy anemia was 51.4%. The mean hemoglobin value of the overall study group was 8.7 ± 0.5 g/dL. The mean maternal age and weight were 28.9 ± 6.2 years and 65.3 ± 11.7 kg, respectively. Most pregnant women (83.1%) had a diet consisting of food of plant and animal origin in equal proportions. Mean of Body Mass Index (BMI) was 24.6 ± 4.6 Kg/m2 and 44.3% were overweight and obese. The co-morbidities associated were malaria and intestinal parasitosis found in 45% and 5.9% of cases, respectively. After iron treatment with Ferric Sodium EDTA, the average hemoglobin level increased to 11.2 g/dL with mean gain of 2.5 g/dL (p Conclusion: Ferric Sodium EDTA as a novel iron formulation (Hemoforce Plus Zinc®) has shown a rapid increase in hemoglobin levels in pregnant women suffering from anemia. The speedy rise in hemoglobin is related to the property of Ferric Sodium EDTA to enhance the iron absorption by inhibiting the dietary iron inhibitors. Thus, Ferric Sodium EDTA should be used as an effective and promising iron supplement in pregnant women with iron deficiency anemia.

The best therapeutic option for oral treatment of secondary anaemia in chronic kidney disease: role of Ferric Sodium EDTA, in association with Vitamin C, Folic acid, Copper gluconate, Zinc Gluconate and Selenomethionine

The best therapeutic option for oral treatment of secondary anaemia in chronic kidney disease: role of Ferric Sodium EDTA, in association with Vitamin C, Folic acid, Copper gluconate, Zinc Gluconate and Selenomethionine

Short study on the use of oral Ferric Sodium EDTA in association with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine, in patients with advanced chronic kidney disease

Short study on the use of oral Ferric Sodium EDTA in association with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine, in patients with advanced chronic kidney disease

Rapid and Reliable Method for Qualitative and Quantitative Assessment of Iron Fortificants Used for Flour Fortification

Food fortification with iron has potential to reduce anemia if the manufacturers comply with fortification standards using highly bioavailable and required quantities of iron. Our objective was to develop a quick and simple method to identify and quantify iron compounds commonly used for flour fortification to help agencies monitor fortification programs. Wheat and corn flours were fortified with 40-60 mg Fe/kg using ferric pyrophosphate, ferrous sulfate, ferrous citrate, ferrous fumarate, sodium ferric EDTA, and electrolytic iron. Using potassium thiocyanate with hydrochloric acid and hydrogen peroxide, we identified EFe, ferric, and ferrous fortificants. Ferric and ferrous salts were differentiated based on their solubility in water using ferrozine with and without added ascorbic acid. Semi-quantification by visual analysis was not significantly different from two standard quantitative methods. This study provides practical options to identify and quantify Fe fortificants based on the resources available at the facilities in various countries. Correct identification of unknown iron samples by independent personnel and accuracy of visual quantification suggested the reliability, ease, and accuracy of these methods in identifying and quantifying iron fortificants.

A pilot study on secondary anemia in "frailty" patients treated with Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine: safety of treatment explored by HRV non-linear analysis as predictive factor of cardiovascular tolerability.

Iron deficiency anemia (IDA) in patients with heart disease is correlated with decreased exercise capacity and poor health-related quality of life, and predicts worse cardiovascular outcomes, especially for elderly patients. IDA can worsen cardiac function that can be monitored with Heart Rate Variability (HRV) analysis, providing important information about cardiac health. In a recent study we explored the effect and the tolerability of the administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) in "frailty" patients with secondary anemia and low kidney failure, by analysing the HRV frequency domain. The aim of the present study is the further confirmation of the safety of the already evaluated intervention, by analysing non-linear domain of HRV. In this pilot study we enrolled 52 "frailty" elderly patients, with a recent diagnosis of secondary anemia due to iron deficiency, with Class II New York Heart Association (NYHA) hypertensive heart disease, low kidney failure, and atherosclerosis. The patients were divided in 2 groups: Group A (N=23 patients) received oral administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) 2 tabs/day, containing 60 mg of Fe3+, for 24 days; Group B (N=29 patients) received intravenous administration of ferrous gluconate 63 mg/day added to saline solution, while they were hospitalized (15±5 days). We evaluated laboratory values of hemoglobin (Hb) and sideremia levels. Furthermore, we measured ECG signals before and after treatment, using non-linear analysis techniques. Both intravenous and oral treatments evaluated in this study, were effective and safe about the cardiovascular risk in "frailty" elderly patients, as resulted from non-linear HRV analysis. Efficacy results showed that hemoglobin and sideremia levels after treatments are significantly increased. The HRV non-linear analysis showed that all parameters evaluated, except for the SD1 values in the Group A, were not affected by treatments, confirming the absence of cardiovascular risk of the therapy. Non-linear HRV evaluation confirmed that oral administration of Ferric Sodium EDTA, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) did not impact the cardiovascular risk, without causing adverse events typically reported with other iron supplementation therapies, both oral and intravenous.

Technical report on the technical assistance for the evaluation of additional information on ferric sodium EDTA as a novel food

Technical report on the technical assistance for the evaluation of additional information on ferric sodium EDTA as a novel food

Iron Supplements and Oncogenic Effects in Human Intestinal Cells (P05-011-19)

ObjectivesWe have previously shown that different iron supplements affect mechanisms for cell growth and viability in different ways and specifically we observed that two common iron supplements/fortificants, ferric citrate and ferric EDTA, promoted induction of the oncogenic growth factor Amphiregulin whilst ferrous sulfate did not. This difference is important and raises the question if some iron compounds should not be used as dietary supplements or for iron fortification of foods. MethodsTherefore, we have been screening iron compounds on the safe list of the European Food Safety Authority (EFSA) using human intestinal cell lines (Hutu-80 and Caco-2) and a proteomic immunoassay for 92 known markers related to cancer. ResultsPreliminary data show that a few more iron compounds, than the previously observed, have oncogenic properties and that amphiregulin protein levels are up-regulated. ConclusionsThese properties need further investigation and translation into the in vivo situation to evaluate if these iron compounds should be avoided as dietary supplements. Funding SourcesFORMAS.

Preparation and effect of complexing agents on ternary FeZnS2 thin films by chemical bath deposition method for photo catalytic degradation of dye molecules

In the present paper the studies on iron zinc sulphide thin films that have been deposited at room temperature on to the glass slides by chemical bath deposition technique using a solution mixture of ferrous sulphate, zinc sulphate, sodium sulphide, EDTA and Leishman stain is reported. Both EDTA and Leishman stain act as complexing agents and are expected to play a main role in the growth of FeZnS2 thin films. The structure of FeZnS2 thin films analysed by X-ray diffraction (XRD) study reveal that the thin films have a multi crystalline feature together with a solid three dimensional appearances at room temperature. The microstructure and the surface texture of the deposited filmsare characterised using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The SEM images show that the deposited films have a fine texture due to the presence of complexing agents. AFM studies revealed that the grain size of the deposited films to be around 80–100 nm with the thickness being approximately uniform. FTIR spectral studies of the thin films were recorded between 400 and 7000 cm−1. FeZnS2 thin films illustrated excellent optical properties with great absorbance in the visible region. The band gap value found to be 2.37–2.77 eV. The Hall Effect measurements show that the FeZnS2 thin films to have a n-type behaviour which exhibits p-type behaviour after the addition of complexing agents which is an ideal condition for solar cell applications. Towards this direction, the photo catalytic activities of FeZnS2 thin films were also assessed by the degradation of crystal violet, malachite green and methylene blue in aqueous solution under sun light irradiation.

Effect of Ferric Sodium EDTA administration, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine, on cardiovascular risk evaluation: exploration of the HRV frequency domain

Background: Anaemia is a frequent co-morbidity in old patients affected by chronic heart failure and/or respiratory diseases. Using the Heart Rate Variability (HRV) analysis is possible to provide an evaluation of the safety and the effectiveness of intervention. Objective: To evaluate the efficacy and safety of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) 2 tabs/day for 24 days in elderly patients with secondary anaemia, by exploring the HRV frequency domain. Methods: In 45 elderly patients with secondary anaemia and/or low-moderate kidney failure, laboratory values after administration of Ferric Sodium EDTA, 2 tabs a day, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) for 24 days (N=16 patients) or ferrous gluconate 63 mg/day added to saline solution administered using intravenous access during the hospitalization period of 15+5 days (N=29 patients) were evaluated. Also, ECG signals and bioelectrical impedance (BIA) were measured. Results: Oral iron supplementation with Ferric Sodium EDTA, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) confirmed to be effective and safe about the cardiovascular risk in old patients. This study showed the real superiority of the oral administration about the cardiovascular risk in elderly patients in comparison with intravenous administration of ferrous gluconate. Conclusion: This study confirms that Ferric Sodium EDTA combination (Ferachel forte®) can be a valid alternative to ferrous gluconate intravenous therapy (gold standard) in the treatment of secondary anaemia in elderly patients. In fact, during the treatment, efficacy results have been maintained without statistically significant variations about cardiovascular risk, evaluated by exploring the HRV frequency domain.

Role of Ferric Sodium EDTA Associated with Vitamin C, Folic acid, Copper gluconate, Zinc Gluconate and Selenomethionine Administration in Patients with Secondary Anaemia: Effects on Hemoglobin Value and Cardiovascular Risk

Iron-Deficiency anaemia (IDA) has a high impact on the quality of life in old patients when affected by chronic heart failure and/or respiratory diseases. The aim of this study is to investigate the efficacy and safety of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) 2 tabs/day for 24 days, in elderly patients with secondary anaemia, analysing cardiovascular risk and quality of life by means of ECG and bioelectrical impedance (BIA) analyses. Materials

Ferric citrate and ferric EDTA but not ferrous sulfate drive amphiregulin-mediated activation of the MAP kinase ERK in gut epithelial cancer cells.

Ferric chelates may be used as oral iron supplements or phosphate binders but both ferric citrate and ferric EDTA have been shown to promote tumor burden in murine models of colon cancer. Here we studied their effects on cancer cell growth, at typical supplemental iron levels encountered in the gastrointestinal tract (0.01-0.2 mM). Caco-2 and/or Hutu-80 cells were exposed to these forms of chelated iron or to ferrous sulfate and outcomes were assessed using cell proliferation assays, proteome profiler arrays, western blot, and ELISA. Ferric EDTA and ferric citrate increased cellular levels of the onco-protein amphiregulin and its receptor (EGFr) which in turn stimulated the activation of the MAP kinase ERK. Simultaneously, the expression of the negative Wnt regulator, DKK-1, increased suggesting that cell proliferation through the Wnt pathway may be less pronounced in the presence of ferric EDTA and ferric citrate, unlike for ferrous sulfate. Moreover, ferrous sulfate did not increase levels of cellular amphiregulin or EGFr. We conclude that specific iron compounds affect cell signaling differently and some may increase the risk of colon cancer advancement in an amphiregulin-dependent fashion. Further scrutiny of safe oral iron use is merited.

Development of Spectrophotometric Quantification Method of Iron-Polyphenol Complex in Iron-Fortified Black Tea at Relevant pH Levels

The formation of iron complexes with phenolic compounds in foods causes discoloration and reduces iron bioavailability. Black tea is a beverage of particular interest because of its high polyphenol content and widespread consumption. A simple spectrophotometric method for the quantification of iron-polyphenol complexes was developed and used to compare complex formation of iron with black tea polyphenols and gallic acid, a monomeric polyphenol. The amount of iron-polyphenol complex formation was quantified with a variety of iron sources (ferrous sulphate, ferrous fumarate, and ferric sodium EDTA) at pH levels relevant to brewed tea and iron absorption into the body. The results confirm the potential usefulness of ferric sodium EDTA in the fortification of high polyphenol content foods, particularly in black tea. This method has the potential to assist in the development of an optimal formulation of iron-fortified black tea and may also be easily adapted for use with other polyphenol containing foods.

EDTA compounds, used for food stabilizing agents, aggravate inflammation and drive tumorigenesis in a mouse model of colitis-associated carcinogenesis

Western lifestyle is associated with increasing prevalence of IBD, processed food being a likely cause. We have shown that ferric EDTA, used for iron fortification, but not other iron agents aggravate gut inflammation and colitis-associated cancer (CAC) in mice. We extend our observations to other EDTA compounds, which are used in the food industry as stabilizing agents.