Journal of Nutrition OpenSOurce Diets- www.ResearchDiets.com

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mehansho, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mehansho, H.
© 2006 American Society for Nutrition J. Nutr. 136:1059-1063, April 2006

Symposium: Food Fortification in Developing Countries

Iron Fortification Technology Development: New Approaches1

Haile Mehansho2

Nutrition Science Institute, Snacks and Beverages Technology Development Division, The Procter and Gamble Co., Cincinnati, OH 45239

2 To whom correspondence should be addressed. E-mail: mehansho.h{at}pg.com.


   ABSTRACT
TOP
 ABSTRACT
LITERATURE CITED
 
The objective of our fortification technology development has been to deliver meaningful levels of bioavailable iron via commonly consumed foods and beverages without compromising taste, appearance, and stability. However, fortification of foods is accompanied with unsolved problems such as unacceptable taste, color, stability, and bioavailability. To solve these problems, we developed a fortification technology that prevents the iron-mediated undesirable taste and appearance of the final product while preserving stability and bioavailability. Iron was stabilized by applying principles of colloid chemistry (encapsulation), chelation, and electrochemical chemistry (redox modulation). Results from color and sensory evaluations showed that formulation of products using the new fortification technology known as "GrowthPlus" eliminated detrimental effects on taste, appearance, and product stability. Bioavailability evaluation using animal models and human subjects showed the GrowthPlus technology does not interfere with the bioavailability of iron from either ferrous bis-glycinate or ferrous fumarate. Multiple intervention trials showed that repeated consumption of the redox stabilized iron in the form of a powdered fruit beverage increased iron status indicators (hemoglobin and ferritin) and reduced iron deficiency anemia significantly in school children, adolescent girls, and pregnant women.

KEY WORDS: • iron • fortification • encapsulation • redox modulation

Iron deficiency is one of the most widespread nutritional deficiencies. Globally >2 billion people are suffering from iron-deficiency anemia (1). If not prevented or corrected, iron-deficiency anemia may cause stunted growth, impaired mental development, poor school performance, reduced productivity, increased morbidity and mortality, and lower self-esteem (2). Food fortification with iron has been recommended as one of the preferred approaches for preventing and eradicating iron deficiency. However, fortification with bioavailable iron sources often presents multiple challenges in product acceptance, product shelf life, and effectiveness in improving iron status (3,4). The success of iron fortification is dependent on delivering a meaningful level of bioavailable iron without affecting the taste and appearance of the finally consumed product. Iron fortification may cause 1) metallic aftertaste, 2) unacceptable flavor as a result of the oxidation-mediated rancidity of fats, 3) undesirable color changes resulting from interactions with anthocyanins, flavonoids, and tannins, and 4) degradation of vitamins (e.g., vitamin C and vitamin A, which are important for iron absorption and utilization) and minerals (i.e., iodine from the oxidation of iodide/iodate to free iodine that escapes as a gas). In addition, the bioavailability of iron is dependent not only on the iron source but also the type of food and/or beverage consumed with it (3–8). Many staple foods and commonly consumed beverages (e.g., rice, beans, coffee, tea, and milk) contain components that interfere with iron absorption (3–8).

Currently, there are a number of iron sources available as food fortificants (3,4). Based on bioavailability, these iron fortificants are classified into 2 groups. The highly bioavailable iron sources (e.g., ferrous sulfate and ferrous fumarate), which are soluble in neutral and/or acidic aqueous environments but may cause organoleptic changes such as poor product acceptability and shortened product shelf life (3,4), and those with poor bioavailability (e.g., iron pyrophosphate and reduced iron), which are less soluble in water but are more compatible with the foods used as vehicles (3,4). Developing a fortification technology that makes either the bioavailable iron sources more compatible with the food vehicle or the compatible ones more bioavailable remains a challenge for food scientists and the food industry.

    Iron fortification technology development. The success of iron fortification in addressing the prevalence of iron deficiency anemia, particularly in developing countries, has been limited by the lack of a robust, simple, and easy-to-transfer fortification technology (4,5). The challenges are chemistry based. Both the vehicle (food or beverage) and the fortificants (nutrient sources) have reactive functional groups. Most commonly used vehicles contain moisture and oxidizing agents. Such an environment is conducive to a reaction process that causes undesirable taste (e.g., metallic aftertaste, rancidity), off color, degradation of vitamins, and reduced bioavailability (3–8). In developing an effective iron fortification technology, it is critical that the chemical property of iron that contributes to the development of undesirable organoleptic properties is taken into consideration (5,7,8). Two iron forms that are commonly used in food fortification are ferrous (Fe2+) and ferric (Fe3+). Because both of these species contain unfilled d orbitals, they readily form complexes with electron-rich components yielding species that influence taste and bioavailability. Also, iron has the ability to undergo oxidation-reduction (redox) reactions that cause many of the unwanted outcomes related to taste, appearance, and bioavailability (5,7,8). The species of iron in a given environment are shown in the Eh–pH diagram (Fig. 1). It is defined by the Nernst equation (Eh = Eo + 0.059/n log [Fe3+]/[Fe2+]) (9). Eh, Eo, and n are system redox potential, standard redox potential, and number of electrons, respectively. The oxidation state of iron is dependent on both pH and redox potential (9). At low pH, iron prefers to stay as [Fe2+]. However, as pH increases, it rapidly oxidizes to [Fe3+] to form Fe(OH)3, which with time precipitates as rust. Likewise, the oxidative state of iron is dependent on the redox potential (Eh) of the environment. At a higher Eh, iron prefers to remain as ferric. The electrochemical property of iron shown in Fig. 1 was used in developing our iron fortification technology. It is based on a model called "Lock-Unlock" (7). During the "Lock Stage," the technology is designed to keep the iron unreactive. Two different strategies, 1) chelation-redox modulation (for products with a pH <5) and 2) encapsulation (for products with a pH >5), were used.


Figure 1
View larger version (15K):
[in this window]
[in a new window]
  		FIGURE 1  Redox potential (Eh)–pH diagram for iron in an aqueous system (9).

 
In the chelation-redox modulation–based iron fortification strategy, the iron-mediated metallic aftertaste was prevented through chelation. Ferrous bis-glycinate (Albion Laboratories), an amino acid–chelated iron source, was used. A mole of ferrous iron is chelated by 2 moles of glycine. Similar to the other water-soluble iron compounds, ferrous bis-glycinate is easily oxidized to [Fe3+], which then causes off-color development and fat oxidation (5,10,11). Redox modulation was applied to prevent the oxidation of ferrous to ferric. The environment was made reducing rather than oxidizing by lowering the pH and reducing Eh (adding organic acids and reducing agents, respectively). The effect of redox modulation on the rate of ferrous iron oxidation is shown in Table 1. [Fe2+] was measured using a modified Ferrozine method, which is specific to ferrous iron (5,12). Lowering pH with citric acid and Eh with ascorbic acid prevented the oxidation of ferrous iron to ferric. In contrast, when the ferrous bis-glycinate was added to water without the redox modulation technology, it rapidly oxidized to the ferric form. However, as indicated by the absorbance at 560 nm and the percentage of ferrous iron recovered, the redox modulation technology is effective in preventing the oxidation of [Fe2+] to [Fe3+]. It is important to note that this phenomenon of iron oxidation is not unique to ferrous bis-glycinate. Ferrous compounds in general are known to be oxidized to the ferric form when added to foods and beverages (5,8,9,13).


View this table:
[in this window]
[in a new window]
  		TABLE 1 Oxidative status of ferrous iron from ferrous bis-glycinate

 
Stabilizing ferrous iron by redox modulation has its own limitation in an environment above pH 5. Higher pH favors the formation of [Fe3+] over [Fe2+] (Fig. 1). Also, according to Hsieh and Hsieh (13), the reduction rate of ferric iron by reducing agents such as ascorbic acid decreases markedly as the pH increases. Thus, encapsulation-based technology was used to solve the iron-mediated problems in products above pH 5. The iron was made unreactive during formulation and storage by isolating it from the vehicle components (e.g., tannins, fat, and vitamins) and oxidizing agents (e.g., dissolved oxygen and chlorine) using vesicle- or liposome-forming emulsifiers (e.g., lecithin). The technology works only for ferrous fumarate and ferrous succinate. The likely reason is that these are less polar than the other water-soluble iron sources such as ferrous citrate, ferrous tartrate, and ferrous sulfate. Ferrous fumarate is mixed with lecithin, which is a vesicle-forming emulsifier. When the iron–lecithin mixture is exposed to water, the lecithin molecules rapidly form a bilayer. After mixing, they are transformed into vesicles. Results obtained by adding known bilayer stabilizers (e.g., cholesterol and phytosterols) showed that stabilization of ferrous fumarate and ferrous succinate is dependent on the bilayer formation by lecithin (data not shown).

    Technology evaluation and product acceptance. For an iron-fortified product to be consumed by target groups, the iron added should not cause the development of undesirable color or flavor changes. Therefore, iron fortification should not change the appearance of the product. The effectiveness of the "GrowthPlus" technology to keep the iron sources (ferrous bis-glycinate and ferrous fumarate) nonreactive has been tested using different vehicles (e.g., water, chocolate milk, and baby cereal). The prevention of the iron-mediated off-color development by redox modulation technology is shown in Figure 2. Relative to the control samples (no iron), addition of ferrous iron (ferrous bis-glycinate) caused the water, chocolate milk, and baby cereal to become brown, grayish brown, and dark-green, respectively. However, this was prevented when the stabilized ferrous bis-glycinate was used.


Figure 2
View larger version (59K):
[in this window]
[in a new window]
  		FIGURE 2  Effect of iron on off-color development. Ferrous bis-glycinate was added to water, a chocolate-containing beverage, and a baby cereal (prepared as a slurry) with warm deionized water. Photos were taken after 1 h.

 
The prevention of the ferrous fumarate–mediated off-color development in chocolate milk by lecithin-based encapsulation is shown in Table 2. Hunter colorimetry was used to measure color change (14). A decrease in Hunter "a" value is an indication of off-color development. Fortification with ferrous fumarate caused a decrease of the "a" value from 6.8 (control with no iron) to 3.2. In contrast, the ferrous fumarate–mediated change in "a" value was prevented by encapsulation with lecithin.


View this table:
[in this window]
[in a new window]
  		TABLE 2 Effect of encapsulated ferrous fumarate on chocolate milk's color

 
In addition to off-color development, iron fortification is also known to cause metallic aftertaste and lipid oxidation. The effect of the redox modulation–stabilized iron (ferrous bis-glycinate) was evaluated by carrying out a home-use test among households in the Philippines (7) and anthropologic study in pregnant women in Tanzania (15). The evaluation was done in the form of an iron-containing, multiple-micronutrient-fortified powdered fruit beverage. In addition to the iron, the beverage contained 8 vitamins (vitamin A, vitamin C, vitamin E, niacin, B-6, B-2, B-12, and folate) and 2 minerals (zinc and iodine). The composition of the beverage and the levels of micronutrients are explained in detail elsewhere (7). In the home-use test, each family received either an unfortified (placebo) or fortified powder beverage adequate for 5 d consumption. At the end of the 5 d, they were asked to rate the products for an overall acceptance, color, flavor, and metallic aftertaste. The powdered fruit beverage fortified with the chelation-redox modulation–stabilized ferrous bis-glycinate had no significant effect on the multiple sensory parameters when compared with the same powder beverage but without the iron-containing multiple micronutrients (7). The anthropologic study was based on home visits and interviews to understand what the pregnant women who were participating in the micronutrient fortified field trial in Tanzania (16) thought about the powdered beverage. Overall, the women liked the beverage. In addition, they preferred the beverage over pills as a micronutrients delivery vehicle and as beneficial to health (15).

    Technology evaluation: iron bioavailability. For an iron fortification program to be effective in improving the iron status of the target groups, the iron from the fortified product has to be absorbed. During the "Unlock" stage of the "Lock-Unlock" model, the iron fortification technology is designed to make the unreactive iron become available for absorption after ingestion. The bioavailability of iron from the lecithin-encapsulated ferrous fumarate was evaluated using the hemoglobin depletion–repletion assay in young rats (17). Comparison was made against the standard ferrous sulfate and ferrous fumarate. The hemoglobin gains and relative bioavailability values after a 2-week repletion period are presented in Table 3. The encapsulated ferrous fumarate has the same bioavailability as that of the nonencapsulated ferrous fumarate. Consistent with the published data, the relative bioavailability value of ferrous fumarate was comparable to that of ferrous sulfate (3,4).


View this table:
[in this window]
[in a new window]
  		TABLE 3 Bioavailability of iron from encapsulated ferrous fumarate

 
The bioavailability of iron from the chelation-redox modulation–stabilized ferrous bis-glycinate, which was delivered in the form of fortified powdered fruit beverage, was determined in nonpregnant women using a double isotope labeling technique (18). The treatments included an iron-fortified powdered beverage alone and with rice. The absorption values were normalized to the 40% absorption of the reference iron compound, ferrous ascorbate. The bioavailability of iron from the fortified powdered fruit drink when consumed alone was 23.4%. However, when the beverage is taken with rice, the bioavailability of iron decreased from 23.4% to 10.7% (7). Even though the bioavailability of redox-stabilized ferrous bis-glycinate in a fruit beverage was quite good when consumed alone, simultaneous consumption with rice reduced absorption by about 50%. Foods of plant origin do contain components (e.g., phytates, tannins, dietary fibers, and calcium) that interfere with iron absorption (3,4,19) Repeated bioavailability studies have shown that both intrinsic and extrinsic iron are poorly absorbed from foods of plant origin (19). The percentage of iron absorbed from rice in human subjects was extremely low (about 1%) compared with that from the other plant foods (19). Thus, even in the presence of a full serving of rice, the 10.7% absorption from the chelation-redox–stabilized iron (in powdered fruit beverage) is comparable to that from fish (19) and milk fortified with ferrous sulfate and vitamin C (20).

    Product efficacy evaluation. The effectiveness of the redox-stabilized ferrous bis-glycinate added to a multiple-micronutrient–fortified powdered fruit beverage has been evaluated with randomized, double-blind, placebo-controlled clinical trials in school children (21), adolescent girls (22), and pregnant women (23). The school children, adolescent girls, and pregnant women received 5.4 mg, 7 mg, and 10.8 mg of iron daily, respectively. The duration of the intervention phases were 6 mo for the school children, 6 and 12 mo for the adolescent girls, and 8 weeks for the pregnant women. The changes in hemoglobin concentration among the subjects who were anemic at the baseline are shown (Fig. 3). In all 3 studies, there was a significant increase in hemoglobin among the groups that received the powdered beverage fortified with the redox-stabilized iron as compared with the groups that received the placebo. A similarly significant increase in ferritin was observed in the group that received the iron-fortified product but not in the placebo group (16,21,22). The results from these efficacy trials do show that the iron stabilized through amino acid chelation and redox modulation is effective in improving iron status.


Figure 3
View larger version (16K):
[in this window]
[in a new window]
  		FIGURE 3  Effect of consuming an iron-fortified beverage on hemoglobin level in school children, pregnant women, and adolescent girls (16,21,22).

 
    Conclusion and remarks. Although successful iron fortification programs have been implemented in many countries, fortifying foods with meaningful levels of bioavailable iron without the development of undesirable taste and appearance remains a challenge. Iron sources stabilized with either the chelation-redox modulation or vesicle-based encapsulation approaches have the potential to contribute to the eradication of iron-deficiency anemia. The iron fortification technology based on chelation-redox modulation has been demonstrated to 1) solve the problem of the iron-mediated off-color and off-flavor development, and 2) deliver clinically proven bioavailable iron. In addition, stability data in both the powdered and beverage form showed that it has no effect on the stability of the multiple vitamins and iodine that were codelivered with the iron (7). The technology has been shown to be robust during manufacturing, storage, distribution, and consumption of a fortified powdered fruit beverage (7). Note that there is a limitation in the use of the redox-stabilized iron. Because it is pH dependent, it works only in products with pH <5.

The lecithin-based encapsulation of ferrous fumarate has been shown to be effective in preventing the development of off-color, off-flavor, and metallic aftertaste without compromising bioavailability. Also, because it is compatible with products with pH above 5, it has potential for broad food fortification applications. However, the technology's robustness is yet to be demonstrated during scaling up, storage, distribution, and consumption. Currently, there are a number of encapsulated iron sources (e.g., ferrous sulfate, ferrous fumarate, and micronized ferric pyrophosphate) available in the market (23). Hydrogenated oils are used to encapsulate the iron sources. However, the technology has limitations in products that are likely to be exposed to higher temperatures during processing, storage, or preparation. Products fortified with the encapsulated iron have been shown to cause off-color development when the preparation is carried above the melting point of the hydrogenated oils (45–65°C) (7,23). Also, salts fortified with hydrogenated oil–encapsulated iron sources (ferrous sulfate, ferrous fumarate) were observed to develop undesirable appearance when stored in a relatively humid environment (23).


   FOOTNOTES
 
1 Presented as part of the symposium "Food Fortification in Developing Countries" given at the 2005 Experimental Biology meeting, April 5, 2005, in San Diego, CA. The symposium was sponsored by the American Society for Nutrition and the Society for International Nutrition Research and was supported in part by an educational grant from Akzo Nobel, Inc. The proceedings are published as a supplement to The Journal of Nutrition. This supplement is the responsibility of the editors to whom the Editor of The Journal of Nutrition has delegated supervision of both technical conformity to the published regulations of The Journal of Nutrition and general oversight of the scientific merit of each article. The opinions expressed in this publication are those of the authors and are not attributable to the sponsors or the publisher, editor, or editorial board of The Journal of Nutrition. Guest editors for the symposium are Jere D. Haas and Dennis D. Miller, Cornell University, Ithaca, NY. Guest Editor Disclosure: Jere Haas and Dennis Miller have no relationships to disclose. Back


   LITERATURE CITED
TOP
 ABSTRACT
 LITERATURE CITED
 

1. ACC/SCNThird report on the world nutrition situation. Geneva: World Health Organization; 1997.

2. Yip R. Iron deficiency: Contemporary scientific issues and international programmatic approaches. J Nutr. 1994;124:S1479–90.[Abstract/Free Full Text]

3. Hurrell RF. Preventing iron deficiency through food fortification. Nutr Rev. 1997;55:210–22.[Medline]

4. Hurrell RF, Cook JD. Strategies for iron fortification of foods. Trends Food Sci Technol. 1990;1:56–61.

5. Mellican RI, Li J, Mehansho H, Nielsen SS. The role of iron and the factors affecting off-color development of polyphenols. J Agric Food Chem. 2003;51:2304–16.[Medline]

6. Mehansho H. Eradication of iron deficiency anemia through food fortification: the role of the private sector. J Nutr. 2002;132:S831–33.[Abstract/Free Full Text]

7. Mehansho H, Mellican RI, Hughes DL, Compton DB, Walter T. Multiple micronutrient fortification technology development and evaluation: From lab to market. Food Nutr Bull. 2003;24:S111–19.[Medline]

8. Clydesdale FM. Mineral additives. In: Bauernfeind JC, Lachance PA, editors. Nutrient additions to food. Westport, CT: Food and Nutrition Press Inc.; 1991. pp. 87–107.

9. Snoeyink V, Jenkins D. Water chemistry. New York: John Wiley & Sons, Inc.; 1980.

10. Hurrell RF. Fortification: Overcoming technical and practical barriers. J Nutr. 2002;132:S806–12.[Abstract/Free Full Text]

11. Bovell-Benjamin AC, Viteri FE, Allen LH. Iron absorption from ferrous bis-glycinate and ferrous tris-glycinate in whole maize is regulated by iron stores. Am J Clin Nutr. 2000;71:1563–69.[Abstract/Free Full Text]

12. Dorey C, Dickson DP, St. Pierre T, Pollard RK, Gibson JF, Simpson RJ, Peters TJ. Iron species in iron ascorbate solutions at physiological pH. Biochem Soc Trans. 1997;15:688.

13. Hsieh YHP, Hsieh YP. Valence state of iron in the presence of ascorbic acid and ethylenediaminetetraacetic acid. J Agric Food Chem. 1997;45:1126–29.

14. Hunter RS. Photoelectric color difference meter. J Opt Soc Am. 1958;48:985–95.

15. Benjamin M, Ash DM. Drinking to their health: Social analysis of a micronutrient-fortified beverage field trial. Food Nutr Bull. 2003;24:S141–45.[Medline]

16. Makola D, Ash DM, Tatalla SR, Latham ML, Ndossi G, Mehansho H. A Micronutrient fortified beverage prevents iron deficiency, reduces anemia and improves the hemoglobin concentration of pregnant Tanzanian women. J Nutr. 2003;133:1339–46.[Abstract/Free Full Text]

17. Mahoney AW, Hendricks DG. Efficiency of hemoglobin regeneration as a method of assessing iron bioavailability in food products. In: Keis C, editor. Nutritional bioavailability of iron. Washington, D.C.: American Chemical Society; 1982. pp. 1–11.

18. Olivares M, Pizarro F, Pineda O, Name JJ, Hertrampf E, Walter T. Milk inhibits and ascorbic acid favors ferrous bis-glycine chelate bioavailability in humans. J Nutr. 1997;127:1407–11.[Abstract/Free Full Text]

19. Clydesdale FM. Physicochemical properties of food. In: Kies C, editor. Nutritional bioavailability of iron. Washington, DC: American Chemical Society. 1982. pp. 55–84.

20. Stekel A, Amar M, Calvo E, Chadud P, Hertrampf E, Llaguno S, Olivares M, Pizarro F. Nutritional significance of interactions between iron and food components. Arch Latinoam Nutr. 1983;33:33–41.[Medline]

21. Ash DM, Tatala SR, Frongillo EA, Ndossi GD, Latham MC. Randomized efficacy trial of a micronutrient-fortified beverage in primary school children in Tanzania. Am J Clin Nutr. 2003;77:891–8.[Abstract/Free Full Text]

22. Hyder SMZ, Chowdhury J, Haseen F, Khan MA, Mehansho H, Schaetzel T, Lonnerdal B. A multiple micronutrient beverage treats anemia and iron deficiency and prevents further fall in hemoglobin and serum ferritin concentration among adolescent girls in Bangladesh. FASEB J. 2004;18:A482.

23. Zimmermann MB. The potential of encapsulated iron compounds in food fortification: A review. Int J Vitam Nutr Res. 2004;74:453–61.[Medline]





This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mehansho, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mehansho, H.

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]