Ferrazone® in Beverages
Beverage is an ideal food vehicle because it is an integral part of our diet and is a convenient avenue for some functional nutrients. Fortified beverages, also known as functional beverages, can be consumed anytime, anywhere. They are different from dietary supplements, which are often looked upon as medicine.
An ideal iron-fortified beverage should be free from unacceptable off-tastes or off-flavors, even at relatively high iron levels. In addition, it should possess enhanced iron bioavailability and excellent storage stability.
Yet, fortifying beverages with iron compound is technically problematic. Beverages have high water activity (aw) and moisture content which facilitate the movement and reactivity of water-soluble iron compounds. Water-insoluble and/or inert iron compounds are generally low in reactivity. They limit the development of off-flavors and off-colors commonly associated with iron fortification. Unfortunately, the water-insoluble and/or inert iron compounds have limited bioavailability and are not readily utilized by the body. Further, due to its limited solubility, sediments are likely to form when used in beverage products.
Prior attempts of fortifying foods and beverages directly with soluble iron forms—such as ferrous sulfate—has proven complicated, often causing unpleasant odor and metallic off-tastes, which render the food and beverages unpalatable. To mask the metallic off-tastes, L-ascorbic acid is often used, such as the study of iron fortification of drinking water in Brazil. L-ascorbic acid also enhances iron absorption in the body. However, reactive iron compounds break down L-ascorbic acid to dehydro-ascorbic acid. To protect the integrity of L-ascorbic acid in aqueous beverages, the use of disodium ethylenediaminetetraacetic acid (Ferrazone®) was suggested.
Ferrazone® in Powdered Beverage
Ferric sodium EDTA does not interact with other cations often present in a beverage formulation with added vitamin/mineral mixes. The iron in ferric sodium EDTA is tightly bound to the EDTA molecule and as a consequence, no significant free iron is generated in the solution to be available to react and form off-flavors or colors, as is often the case with other water-soluble iron forms.
In one study, sensory evaluation of iron-fortified beverage was conducted over a period of 16 weeks of accelerated storage (90oF and 85% relative humidity). The beverage samples were presented to the panelists at room temperature in randomly coded beakers. The sensory evaluation results are summarized below. Beverages fortified with ferric sodium EDTA were stable and comparable to the control (no iron) through the duration of the 16-week test. Beverage fortified with ferric sodium EDTA (Ferrazone®) rated nearly the same in organoleptic attributes as the “no iron” control without requiring any additional preservatives or flavor-masking agent.
Ferrazone® in Ready-to-eat Breakfast Cereals
In one study of iron fortified ready-to-eat cereal, it was found that ferric sodium EDTA (Ferrazone®) provides for the best combined result for iron fortification, in terms of improved bioavailability, excellent brightness value, little, if any, metallic off-tastes and excellent oxidative stability. For comparison, the same study also employed other types of iron compounds such as reduced iron, ferrous fumarate, and ferrous sulfate.
Ready-to-eat cereals fortified with ferric sodium EDTA yielded the lowest level of hexanal value, rancid and off-odor value as compared to reduced iron, ferrous fumarate and ferrous sulfate. Metallic flavor was organoleptically measured in a 0 to 10 scale; from no metallic taste to high metallic flavor. Cereals fortified with ferric sodium EDTA demonstrated a statistically significant lower level of metallic off-taste as compared to ferrous fumarate and ferrous sulfate.
The brightness of vibrancy of the color of the cereals was measured using a scale from 0 to 10 points; from no brightness to extremely bright. Cereals fortified with ferric sodium EDTA displayed a statistically significant higher level of brightness as compared to ferrous fumarate and ferrous sulfate.
Table 1: Organoleptic effects evoked by iron compounds in ready-to-eat cereal
| Iron source |
Fe content (ppm) |
Metallic flavor* |
Hexanal value** |
Rancid odor value |
Off odor value |
| Reduced iron |
400 |
1.3A |
0.76±8.52 |
1.22±0.70 |
1.17±0.50 |
| FeNa-EDTA |
400 |
2.3A |
0.40±0.22 |
0.56±0.43 |
0.78±0.44 |
| Ferrous fumarate |
400 |
4.1B |
2.37±1.00 |
2.89±0.62 |
2.67±0.41 |
| Ferrous sulfate |
200 |
4.7B |
2.13±2.02 |
1.22±0.57 |
2.33±0.48 |
*values having the same letter designation are not statistically significant
**95% confidence interval
Ferrazone® in Coffee
An ideal iron compound for fortification of coffee should have the following requirements:
Solubility. It should quickly soluble in water, otherwise (part of) the iron compound will stay behind on the filter and the fortification level might become too unpredictable.
Organoleptic effects. Naturally the iron compound should not evoke unpleasant flavors, smell or color in the coffee powder or beverage.
Bio-availability. In order to be effective in the battle against iron deficiency anemia the human body should be able to absorb the iron compound in the presence of coffee, which is known to be an inhibitor of Fe absorption.
The sensorial effects of Ferrazone®-fortified coffee have been evaluated by several companies. At a brewing strength of 80 g/l and fortification levels of 5 mg Fe as Ferrazone®, there is no sensory difference between Ferrazone®-fortified coffe and control (no iron).
Coffee is a well known inhibitor of human iron absorption as was clearly demonstrated by Morck et al. They fed volunteers with a healthy iron status a hamburger meal with either water, tea of coffee. Mean iron absorption decreased by 39% when consumed with freshly brewed coffee and by 60% when consumed with tea. Instant coffee had a similar inhibitory effect as freshly brewed coffee, which was maintained, even if the coffee was consumed one hour after the meal. Consuming the coffee one hour before the meal however caused no decrease in iron absorption, indicating that the coffee must mix with other meal ingredients including of course the food iron in order to exert its inhibitory effect.
Similar results were obtained by Hallberg et al., who found a reduction in iron absorption of 35% when coffee was consumed with a hamburger, string beans and mashed potatoes that were fortified with ferrous sulfate.
In another study the inhibitory effect of coffee on the iron uptake by healthy man from a meal consisting of bread rolls fortified with ferrous sulfate was 61%. Galloyl groups and chlorogenic acid are thought to be the substances in coffee, which are mainly responsible for the inhibitory effect. These compounds are assumed to complex with iron in the intestinal lumen making it unavailable for absorption.
Hurell et al found that the inhibitory effect of these polyphenol structures is dose dependent. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced iron absorption from a bread meal fortified with FeCl3 by 50-70%, whereas beverages containing 100-400 mg total polyphenol per serving reduced the iron absorption by 60-90%. Adding milk to coffee or tea has little or no effect on their inhibitory nature.
Morck et al also studied the effect of coffee on iron absorption from FeNaEDTA in comparison with FeCl3 in the absence of food on healthy volunteers with a normal iron status. Compared to water a 70% decrease in iron absorption was observed for coffee, independent of the iron compound.
Identical iron absorption was also found for ferrous sulfate and FeNaEDTA when consumed with a breakfast consisting of black bean gruel (120 g), 4 corn tortillas (120 g), a roll of bread (40 g) and a cup of coffee by healthy men in Central America. However, when the same meal was consumed by iron depleted men iron absorption from FeNa-EDTA was 2.7 times higher than from ferrous sulfate. Therefore it was concluded that the intestinal regulatory mechanism operates for FeNaEDTA as well as it does for dietary iron.
In conclusion, it is clear that coffee reduces the iron absorption by 40-60%. It is also a fact that people will always drink coffee simply because they like it. Therefore it makes sense to fortify the coffee with iron to enhance the absolute amount of iron uptake.
Field trial, such as the one in Guatemala, proved that the iron status of the population can increase to a healthy level when the sugar is fortified with Ferrazone®, despite the consumption of coffee.
Ferrazone® in Curry Powder
The acceptability of curry powder fortified with ferric sodium EDTA was assessed in a double blind randomized fortification trial. The fortified premix curry powder was acceptable in terms of color, palatability and stability. There was no tendency for the ferric sodium EDTA to sediment out of the curry powder and the powder remained stable over storage periods of several months.
Ballott et al. used FeNaEDTA in a double blind controlled iron fortification trial with human subject from an iron-deficient Indian population in Chatsworth, Durban, South Africa. The curry powder was fortified with FeNaEDTA (± 7.7 mg Fe/person/day) and was administered for two years. The study was conducted in a single community, with the 263 families randomly assigned to control (129 families) and test group (134 families), which were matched for iron status. The total subjects in the study were 672 individuals. Individuals with Hb lower than 90 g/L were excluded.
Care was taken to ensure that crossover between groups did not occur and the curry powder, fortified or unfortified, was distributed directly to each family. In addition to evaluating the usual monitors of improved iron status (increasing hematocrit or hemoglobin and ferritin), an attempt was made to estimate the total body iron in each individual by using a composite of percent transferrin saturation, Hb concentration and serum ferritin concentration. This comprehensive index of iron nutrition made it possible to compare subjects with wide variations in iron status and thus to assess both the beneficial and potentially adverse effects of additional iron, i.e. development of iron overload.
The study showed that FeNaEDTA was effective in improving Hb-, ferritin- and body-iron status, as well as counteracting iron deficiency anemia. A significant improvement in body iron as assessed by the index was detectable in the group of women receiving fortified curry powder after 1 year of the program. This improvement continued during the second year, when the rise in Hb concentration became significantly greater than that in the control group. The prevalence of iron deficiency dramatically dropped in the women receiving fortified masala, from 22% at the start of the study to 4.9% at the completion of the study.
The most significant improvement in iron status was noted in women who entered the trial with iron deficiency and especially in those with anemia. Those with anemia showed an increase in calculated body iron of 505 mg, which is equivalent to the absorption of an additional 0.7 mg Fe/day. The latter figure is close to the predicted improvement in iron balance of 0.8 mg/day based on radioisotope absorption studies using FeNaEDTA-fortified curry powder.19
In iron-replete males the rise in calculated body iron was modest and reached statistical significance only in alcohol abusers receiving fortified masala. This suggests that iron-replete males are unlikely to accumulate excessive amounts of iron under these fortification conditions.
Ferrazone® in Drinking Water
Water is an essential component of daily food intake and is one of the most ideal food carrier for mineral elements, such as iron. Over the years, the public health authorities have shown greater interests in the treatment and distribution of iron fortified drinking water. Ferreira et al. (1994) have shown that iron fortification of drinking water is simple, inexpensive, practical and offers advantages over other food carriers such as wheat flour, sugar and salt. They argued that iron fortification of wheat flour is constrained by the bioavailability of the iron compound. In sugar and salt, the issue is the discoloration and darkening of the food products.
Dutra de Oliveira et al. (1996) evaluated the feasibility of iron fortification of household drinking water to prevent iron deficiency anemia in Brazil. They reported that iron-fortified drinking water was well received and effective in improving the iron status of the children and adults in Ribeirão Preto, an agricultural town in Southern Brazil. After a period of four months, the hemoglobin and serum ferritin levels improved dramatically.
Nevertheless, iron fortification of drinking water has several challenges. First, the pool of suitable iron compounds is limited to the water soluble ones. Second, although the water soluble compounds have high bioavailability, they commonly exhibit metallic taste thus rendering the drinking water unacceptable. Finally, in neutral pH environment, the iron metal from these water soluble compounds will precipitate into Fe(OH)3 over time. The formation of Fe(OH)3 does not make iron fortification of drinking water commercially feasible.
One way to mask the metallic taste and to overcome the formation of Fe(OH)3 is by adding a sufficient quantity of ascorbic acid. Dutra de Oliveira et al. (1996) added 100 mg of ascorbic acid per liter of water, ten times the amount of iron added. Ascorbic acid lowers the pH and keeps the iron in the solution. Unfortunately, the addition of ascorbic acid gives a distinct taste to the drinking water.
Furthermore, the economic feasibility of adding ascorbic acid into iron fortified drinking water is not fully explored. Due to the relatively huge amount of drinking water consumed per person per day, the addition of significant quantity of ascorbic acid will increase the costs of iron-fortified drinking water and make it economically not feasible.
Scientific literatures recognize sodium iron (III) ethylenediaminetetraacetate (NaFeEDTA) as one of the most promising iron compounds that can overcome the dilemma of effectiveness vs. organoleptic acceptance. Akzo Nobel produces and markets this molecule under the brand name Ferrazone®.
Ferrazone® is a water soluble iron compound and has a remarkably enhanced absorption efficiency. It is about two to ten times more effective as compared to other iron sources.
Loong and Goh (2004) studied the physical and sensory characteristics of iron fortified water. They evaluated four water soluble iron compounds: ferrous sulfate, ferrous gluconate, ferric ammonium citrate and ferric sodium EDTA. The level of fortification is 1.9 mg Fe (10% RDA) per 250 ml of water.
After two months of storage at ambient temperature, they found that all iron compounds showed yellowish and brownish tinge, except ferric sodium EDTA (Fig. 1). All iron compounds, except ferric sodium EDTA, showed some degree of Fe(OH)3 precipitation after 6 months (Fig 2.).
They continued with an analysis of iron content in the water solution. They found that the iron content from the ferrous sulfate-fortified water was significantly lower than the initial concentration of 7.6 ppm (p<0.05). Except for Ferrazone®, the other iron compounds does not statistically exhibit a drop in iron content, however the appearance of these iron fortified water is no longer acceptable.
After six months of storage, sensory evaluation is based on the flavor characteristics, appearance and overall acceptability. The flavor characteristics of control and iron fortified water is not statistically significant. Water with ferric sodium EDTA was found to have sensory characteristics closest to the control.
Ferrazone® in Fish Sauce
Fish sauce is largely consumed in Thailand, Vietnam and other countries in South East Asia. The earliest study on the efficacy of FeNaEDTA in fish sauce was conducted by Garby and Areekul in 1974. The study involved 614 individuals (284 test subjects, 330 control) in the Nakorn Nayok Province. In this study, the subjects consumed meals containing 10-15 mL/person/day of fish sauce fortified with FeNaEDTA (10-15 mg Fe/person/day). Period of study is 12 months. Rexolin AB of Sweden (now part of Akzo Nobel Chemicals) donated FeNaEDTA in this trial.
Packed cell volume (PCV) values showed a significant increase as compared with a control village supplied with unfortified fish sauce. The largest mean change of +4.67 was seen in a sub-group of women who were anemic at the start of the study (initial PCV < 33). The PCV increase of +4.67 units represented an increase of about 187 mg in total body iron or an increase in daily absorption of about 0.5 mg over the trial. Iron stores were not measured in the trial and the calculation does not take into account iron laid down in stores. The calculated value is therefore an underestimation of the iron actually absorbed. Nevertheless, it illustrates that fortification with FeNaEDTA is a highly effective method for improving iron status.
Thuy et al. (2003) continued the fish sauce study in Vietnam. In a randomized, double-masked study of 152 anemic (hemoglobin concentration of 81–119 g/L) women working in garment factories, a meal based on noodles or rice was served 6 d/wk with 10 mL fish sauce containing either 10 mg Fe as NaFeEDTA (iron-fortified group) or no added iron (control group). Concentrations of hemoglobin, serum ferritin (SF), and serum transferrin receptor (TfR) were measured at baseline and after 3 and 6 months.
After 6 months, hemoglobin and SF concentrations were higher and TfR concentrations were lower in the iron-fortified group than in the control group. The hemoglobin level in the treated group is 116.3 ± 8.7 compared with 107.6 ± 11.0 g/L (P < 0.0001). The serum ferritin is 30.9 (95% CI) compared with 14.6 mg/L (P = 0.0002). Meanwhile the TfR value is 7.2 compared with 9.0 mg/L (P = 0.002).
The prevalence of iron deficiency (SF < 12 _g/L or TfR > 8.5 mg/L) and iron deficiency anemia (iron deficiency with hemoglobin < 120 g/L) was lower in the iron-fortified group than in the control group [32.8% compared with 62.5% (P = 0.0005) and 20.3% compared with 58.3% (P < 0.0001), respectively.
The results of this study clearly show that fish sauce fortified with NaFeEDTA is efficacious in improving iron status and reducing the prevalence of IDA in anemic Vietnamese women. These results add to the body of evidence that food fortification with iron compounds having high bioavailability is a useful approach to combat ID and IDA.
Thuy et al. followed up their 2003 study with a large scale effectiveness study to show that fish sauce fortified with FeNaEDTA is effective in improving iron status of the Vietnaese people under real-life conditions. Such an evaluation is currently being undertaken in 2 districts in the Red River delta of northern Vietnam, with fish sauce fortified with NaFeEDTA at 0.5 mg Fe/mL, ie, at a fortification level 50% lower than that used in the present study. Effectiveness will be monitored by changes in iron status over 18 mo in representative segments of the population.
Ferrazone® in Soy Sauce
Soy sauce is a traditional condiment consumed commonly in all parts of China and used in all types of cooking and cuisines. The average consumption of soy sauce in China was around 12.6 g per capita in the early 1990s and it is less varied in the different regions of China than other potential food carriers such as flour, rice, sugar and vinegar. Because of its high salt content, the amount of soy sauce used in food preparation is self limited. Therefore, the chance of excess iron intake from iron-fortified soy sauce is negligible. Soy sauce fortified with NaFeEDTA retained the same features of regular soy sauce in terms of its flavour, colour and precipitant when compared with non-fortified soy sauce. This is a critical advantage of using NaFeEDTA over other commonly used iron compounds (such as FeSO4) as a nutrient fortificant in soy sauce.
In 2002, Huo et al. reported that nutrition intervention for anemic students using FeNaEDTA-fortified soy sauce could play a positive role in the improvement of iron status and control of anemia.
The study involved 304 iron deficient anemic school children (11-17 years) which were randomly assigned to three treatment groups: control group, low-fortified group (5 mg Fe/person/day) and high-fortified group (20 mg Fe/person/day). Soy sauce was selected as the food vehicle. The study was conducted in the Wancheng District, Nanyang City, Henan Province.
Blood haemoglobin (Hb) levels were determined before and after 1 month, 2 months and 3 months of intervention. In addition, serum iron (SI), serum ferritin (SF), free erythrocytic porphyrin (FEP), total iron binding capability (TIBC) and transferritin (TF) were measured before and after consumption of soy sauce for 3 months. The results obtained herein show that the parameters measured were not changed remarkably within the 3-month intervention in the control group (P < 0.05). However, increased Hb, SI, SF and TF levels and decreased TIBC and FEP levels were observed in both the high-NaFeEDTA group (P < 0.01) and the low-FeNaEDTA group (P < 0.05). The effectiveness of iron intervention in the low-NaFeEDTA group and high-FeNaEDTA group had no statistical significance after 3 months.
After 6 months, there was a highly significant increase in Hb levels and a reduction in anemia prevalence rate of ± 50% for all age groups in the intervention group receiving the iron fortified sauce. In contrast, there were no significant changes in the control group.
Following Huo (2002) study, Chen et al. (2005) conducted a large scale, real-life study to assess the effectiveness of FeNaEDTA in improving iron status of the people consuming FeNaEDTA-fortified soy sauce. This study was an 18-month, randomized, placebo-controlled intervention trial in 14,000 residents aged three years or older in Bijie City, Guizhou Province, China. Half of the resident received placebo and half received FeNaEDTA-fortified soy sauce (29.6 mg Fe/100 ml).
At the end of the trial, Chen et al. concluded that all age and sex subgroups receiving NaFeEDTA had significantly higher hemoglobin levels, a lower prevalence of anemia, and higher plasma ferritin levels than the controls. The effects became statistically significant after six months of intervention and were maintained throughout the study period. We conclude that NaFeEDTA-fortified soy sauce was highly effective in controlling iron deficiency and reducing the prevalence of iron-deficiency anemia in men, women, and children. NaFeEDTA-fortified soy sauce is affordable and was well accepted by the study population.
Ferrazone® in Sugar
Viteri et al. (1995) studied 1,022 individuals of various age groups in four Guatemalan communities. One community (234 subjects) served as control. Period of study is 32 months. Sugar was chosen as the food vehicle and was fortified with FeNaEDTA (4.29 mg Fe/person/day). Hampshire Chemical Co. of USA (now part of Akzo Nobel Chemicals) donated FeNaEDTA in this study. The sugar was tested in a number of typical Guatemalan diets, like cookies, cakes, bread, deserts, sugar added juices, coffee (with or without milk) and tea. The appearance of the coffee did not change with the addition of milk. All pregnant women and subjects with severe anemia received iron therapy or supplements and they were excluded from the analysis.
Fortification of sugar with FeNaEDTA resulted in absorption of iron at 0.95-3.1 mg/day. In addition, children in two of the communities showed a significant improvement in Hb concentrations when compared with children in the control community.
Ferrazone® in Wheat Flour
Ferric sodium EDTA, unlike ferrous sulfate, does not provoke the fat oxidation reactions that lead to rancid, oxidized products. Fat oxidation was quantified by measuring the accumulation of pentane. Unfortified wheat flour and wheat flour fortified with ferric sodium EDTA underwent little or no fat oxidation during 6 months storage at 37oC. In contrast, when the flour was fortified with FeSO4.7H2O or FeSO4.7H2O plus Na2EDTA, lipids in the wheat flour were progressively oxidized during the storage periods and progressively more pentane accumulated in the headspace.
