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WO1999005920A1 - Cooked cereal ingredient-containing products fortified with edta/iron compositions and methods for use - Google Patents

Cooked cereal ingredient-containing products fortified with edta/iron compositions and methods for use Download PDF

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Publication number
WO1999005920A1
WO1999005920A1 PCT/US1998/016036 US9816036W WO9905920A1 WO 1999005920 A1 WO1999005920 A1 WO 1999005920A1 US 9816036 W US9816036 W US 9816036W WO 9905920 A1 WO9905920 A1 WO 9905920A1
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WO
WIPO (PCT)
Prior art keywords
iron
edta
product
subject
ferrous
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1998/016036
Other languages
French (fr)
Inventor
Sungsoo S. Cho
Luis Mejia
Louis Morel
Priscilla Samuel-Fernando
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kellanova
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Kellogg Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kellogg Co filed Critical Kellogg Co
Priority to CA002267559A priority Critical patent/CA2267559A1/en
Priority to EP98939154A priority patent/EP0966209A1/en
Priority to JP51130599A priority patent/JP2001507579A/en
Priority to AU87641/98A priority patent/AU8764198A/en
Priority to BR9806080A priority patent/BR9806080A/en
Publication of WO1999005920A1 publication Critical patent/WO1999005920A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L7/00Cereal-derived products; Malt products; Preparation or treatment thereof
    • A23L7/10Cereal-derived products
    • A23L7/101Addition of antibiotics, vitamins, amino-acids, or minerals
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16Inorganic salts, minerals or trace elements
    • A23L33/165Complexes or chelates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06Antianaemics

Definitions

  • This invention is related to a cooked cereal ingredient-containing, storage stable product ("storage stable cereal product") fortified with iron.
  • storage stable cereal product fortified with iron.
  • a combination of an EDTA source and an iron source is used to fortify the storage stable cereal product.
  • a storage stable cereal product fortified with an EDTA source in combination an iron source combination has surprising and unexpected advantages. The combination provides a storage stable cereal product with improved iron bioavailability and is significantly less expensive than a like product fortified with ferric EDTA alone.
  • Heme iron which is derived primarily from hemoglobin and myoglobin in meat, is transferred as intact porphyrin complex to intestinal cells, where the heme oxygenase enzyme rapidly releases the iron. It blends with other iron taken up by the cell before the regulated transfer to the blood stream occurs. This form of iron is readily absorbed and is generally not affected by the contents of the meal with which the heme containing food is consumed.
  • the non-heme iron has a heterogenous origin, being derived from vegetable foods and inorganic forms of iron, and can be used to fortify foods by increasing the level of iron present.
  • Non-heme iron which is derived from plant foods and fortified foods is not as well absorbed as heme (meat) iron.
  • beverages such as coffee and tea consumed at meal time and other factors can cont ⁇ bute to poor absorption of non-heme iron.
  • ascorbic acid or vitamin C can enhance iron absorption in the diet, generally without affecting consumer acceptability.
  • ascorbic acid fortification is expensive and when exposed to oxygen and moisture can be unstable du ⁇ ng storage.
  • ascorbic acid is unstable and is partially lost.
  • the most efficient and cost-effective way of preventing and treating iron deficiency is to fortify food products with a form of iron that provides for adequate absorption. While cost is not necessarily a controlling factor in whether an affluent consumer would purchase an iron fortified product, among the poor and in less-well developed countnes cost often becomes the controlling factor Currently used iron fortificants, such as ferrous sulfate, are bioavailable, however they adversely affect the organoleptic properties of the cooked cereal mgredient- containing storage stable products, (hereinafter referred to as storage stable cereal products).
  • U.S. patent no. 5,534,274 discloses that feme EDTA is suitable for fortifying storage stable cereal products and that it may be combined with other fortificants, e.g , reduced iron.
  • the patent suggests multiple iron sources, such as feme EDTA with an additional iron fortificant such as ferrous fumarate, ferrous sulfate, reduced iron, ferric citrate, ferrous citrate, ferrous lactate, ferrous succinate, feme phosphate, ferrous gluconate, ferrous pyrophosphate, ferrous glutamate, ferric tartrate, ferrous carbonate, feme chloride, ferric ammonium citrate, ferrous ascorbate, ferrous glycinate, ferrous malate, and ferrous cholinisocitrate and other similar feme or ferrous compounds which would be readily determinable by those skilled in the art may be combined to fortify the products.
  • ferric EDTA is a pale yellow water-soluble powder that can be added to many food vehicles.
  • ferric EDTA is consumed with foods containing large quantities of absorption inhibitors, iron is protected from agents which inhibit its absorption.
  • Iron from ferric EDTA has been reported to be two to three times more bioavailable than iron presented as a FeSO 4 complex in some diets. Furthermore, ferric EDTA is more stable under adverse storage conditions and is unaffected by cooking.
  • Ferric EDTA is used in a variety food ingredients or condiments, i.e., fish sauce in Thailand (Garby et al., 1974, Ann. Tro. Med. Parasitol. 68:467-76), curry powder in South Africa (Macphail et al. , Experimental Fortificants, in: Clydesdale FM et al. eds. Iron Fortification of Foods, 1985), Egyptian flat bread (Guindi et al., Brit. J. Nutr. 59:205-213, 1988), sugar in Guatemala (MacPhail et al, Br. J. Nutr. 45;215-227, 1981). Absorption of iron in dietary foods such as flat breads has also been studied in Guindi et al., 1988, cite monograph table.
  • Sodium EDTAs are safe for use in food products. (Iron EDTA for Food Fortification: A Report of the International Nutritional ANEMIA Consultative Group. The Nutrition Foundation, Inc., Bates et al. Eds (1993)). Disodium EDTA, a white, water soluble chelating agent, is deemed to be safe for use in aqueous multi-vitamins, a variety of canned foods including peas, beans, pie fillings, salad dressings, frozen potatoes, mayonnaise, and dried bananas used in ready-to-eat breakfast cereals. Disodium EDTA is used to promote color retention and as a preservative. It is also used as a cure accelerator in cooked sausages.
  • calcium disodium EDTA is used to promote color, flavor, and texture retention in pickled cucumbers and cabbage, in canned foods, such as carbonated soft drinks, white potatoes, clams, mushrooms, beans, and in dry processed foods, such as pinto beans and lima beans. It is also used as a preservative in foods, such as salad dressings, oleomargarine, and potato salad.
  • calcium disodium EDTA is used to retard struvite formation in sea foods, such as canned crabmeat and shrimp, and to promote stability of color, flavor and/or clarity of distilled alcoholic beverages.
  • food products were not fortified with combinations of disodium EDTA or other EDTA salts with an iron source such as reduced iron to enhance iron bioavailability
  • composition composing an EDTA source such as ferric EDTA, calcium disodium EDTA, or disodium EDTA
  • an iron source other than ferric EDTA
  • the storage stable cereal product is prepared with the iron and EDTA combination by either incorporating it into the cereal dough mix p ⁇ or to cooking or by spraying an iron/EDTA solution onto the finished storage stable cereal product
  • the combination of the iron source and the EDTA source results in unexpectedly enhanced iron bioavailability over a like product fortified with reduced iron alone It does not adversely affect taste and maintains excellent b ⁇ ghtness characte ⁇ stics and oxidative stability, as well as having a significant reduction m cost over a like product fortified with ferric EDTA alone
  • a storage stable cereal product which is fortified with an EDTA source, such as feme EDTA, calcium disodium EDTA, tetrasodmm EDTA, t ⁇ sodium EDTA, or disodium EDTA, m combination with an iron source, such as reduced iron or iron orthophosphate
  • an EDTA source such as feme EDTA, calcium disodium EDTA, tetrasodmm EDTA, t ⁇ sodium EDTA, or disodium EDTA
  • an iron source such as reduced iron or iron orthophosphate
  • This invention also relates to fortifying storage stable cereal products with combinations of EDTA salts and other minerals, such as calcium, magnesium, zinc, selenium and copper and to methods for supplementing diets that are inadequate m these minerals SUMMARY OF THE INVENTION
  • This invention provides for a storage stable cereal product, which is fortified with an EDTA source, such as ferric EDTA, calcium disodium EDTA, tetrasodium EDTA, trisodium EDTA, and disodium EDTA, and an iron source, such as reduced iron or iron orthophosphate.
  • an EDTA source such as ferric EDTA, calcium disodium EDTA, tetrasodium EDTA, trisodium EDTA, and disodium EDTA
  • an iron source such as reduced iron or iron orthophosphate.
  • the bioavailability of the iron is unexpectedly enhanced by the EDTA source.
  • the total iron content in the storage stable cereal product ranges from 1.5-18 mg per ounce of cereal product, or preferably 2.5-8.5 mg/ounce of cereal product.
  • the preferred ratio on a molar basis of EDTA to iron ranges from 1 : 1 to 1 :4 more preferably 1 : 1 to 1 :2.
  • the invention also provides for a method of preventing or treating iron-deficiency anemia by administration of the fortified storage stable cereal product of this invention to those in need of such treatment.
  • This invention also relates to enhancing the bioavailability of other minerals, such as calcium, zinc, copper, selenium and magnesium by fortifying a storage stable cereal product with a combination of an EDTA source and a mineral source, such as calcium, zinc, magnesium, selenium, or copper.
  • Figure 1 demonstrates the hemoglobin iron change for rats fed diets comprising EDTA:Iron at various concentrations of iron per kg diet.
  • Figure 2 demonstrates the hemoglobin iron change over two weeks for rats fed diets comprising reduced iron and FeOP on an equal cereal basis.
  • Figure 3 demonstrates the hemoglobin iron change over two weeks for rats fed diets comprising FeSO 4 , reduced iron, or FeOP and mixtures thereof at various concentrations of iron per kg diet.
  • Figure 4 demonstrates the hemoglobin iron change over two weeks for rats fed diets comprising various mixtures/combinations of iron sources and EDTA sources at various concentrations of iron per kg diet.
  • an iron source such as reduced iron or iron orthophosphate
  • an EDTA source such as feme EDTA or a disodium EDTA
  • a molar ratio of about 1 4 (EDTA iron) to about 1 1 (EDTA iron) to fortify a storage stable cereal product has not been reported p ⁇ or to this invention
  • the Examples infra demonstrate that the combination of an EDTA source with an iron source enhances iron bioavailability
  • a storage stable cereal product is unusual in that du ⁇ ng its preparation the iron fortificant may be added to a cereal dough product, which is cooked/heated and formed into cereal pieces, or alternatively the iron fortificant may be sprayed onto the formed cereal pieces The cereal pieces are then d ⁇ ed and stored for a potentially long pe ⁇ od of time
  • the storage stable cereal product is not generally subjected to any further cooking means prior to consumption, it may be subjected to conditions that destabilize the storage stable cereal product containing the iron fortificant Oxidation of the iron fortificant may adversely affect the overall characte ⁇ stics of the product Therefore, the stability of any iron fortificant added to a storage stable cereal product is extremely important to the palatabihty and physical acceptability of the product to the consumer
  • a storage stable cereal product includes not only ready-to-eat breakfast cereals, such as
  • Corn Flakes and Rice Knspies'' but also includes other food products, such as snackbars, such as NurtnGrain 11 bars and Rice Knspies TreatsTM Squares, toaster pastries, such as PopTarts ® , and pastry products, which are produced using cooked cereal ingredients
  • snackbars such as NurtnGrain 11 bars and Rice Knspies TreatsTM Squares
  • toaster pastries such as PopTarts ®
  • pastry products which are produced using cooked cereal ingredients
  • the storage stable cereal products of this invention may be prepared from cereal ingredients selected from the group consisting of wheat, rice, oat, corn, barley, rye, millet, sorghum, amaranth seed and mixtures thereof
  • other ingredients including but not limited to, sugars, salts, spices, flavo ⁇ ngs, fruits, nuts, vitamins and minerals, which may add to the flavor or nut ⁇ tional aspects of the final product, may be added to the storage stable cereal product without departing from the spi ⁇ t and scope of the invention
  • high fiber sources such as psyllmm as disclosed in U S patent no 5,227,248 and PCT US94/10290 incorporated herein by reference in their entirety, may also be included in the storage stable cereal products
  • the iron fortified storage stable cereal products of this invention may also be administered to individuals or population groups to prevent or treat iron-deficiency anemia, i.e., a low hemoglobin value, a low hematoc ⁇ t value or a low red blood cell count
  • the storage stable cereal products of this invention may also be used to supplement a diet that is inadequate in minerals, such as calcium, magnesium, zinc, copper, and selenium
  • Example 1 The relative iron bioavailability of various iron containing compositions in a ready-to-eat cereal product was assayed using a widely accepted method, commonly referred to as the rat hemoglobin repletion method, (modified AOAC method for assessment of relative iron bioavailability), see Williams, S ed Official methods of analysis of the Association of Official Analytical Chemists, 14th ed Arlington, VA AOAC, 1984, Fritz, J C et al , Collaborative Study of rat hemoglobin repletion test for bioavailability of iron, AOAC 1974, 57 513-517
  • rat hemoglobin repletion method modified AOAC method for assessment of relative iron bioavailability
  • Sprague Dawley rats individually housed in temperature and light controlled units, were fed an iron deficient diet obtained from Harland Tekland Laboratories for 24 days After this iron depletion phase, the rats were weighed and blood was drawn to test for baseline hemoglobin concentrations These anemic animals, with hemoglobin levels between 2 9 to 4 1 g/1, were then randomly assigned to the control and test groups Ferrous sulfate, reduced iron and the feme EDTA compounds were added to the test diets to achieve concentrations of 6 and 18 and 24 mg iron/kg diet These diets were then fed to groups of ten animals, ad libitum, for 14 days Iron levels in the diets, were ve ⁇ fied by atomic absorption spectrometry (Bhn et al , J Assoc Off Anal. Chem. 1977, 60: 1 170-1 174). After the 14-day test period, hemoglobin concentrations were determined for all animals.
  • the slope of the line generated from ferric EDTA is similar to that from the ferrous sulfate standard.
  • the slope value for the reduced iron diet was markedly less than the value for ferric EDTA.
  • Treatment bO se bl se Ratio means Ratio of
  • Ratio of treatment slopes to the slope of FeSO 4 .
  • Ratio of the treatment means at 50 mg/kg diet of added iron to the mean hemoglobin change of FeSO 4
  • the hemoglobin change for rats fed a 1 :2 test diet is not significantly different from rats fed the 1.1 and the FeSO diets
  • the hemoglobin change for rats fed a 1 :3 diet is significantly different from those fed the 1 : 1 and FeSO 4 diets, the change is still significantly higher than the values in rats fed diets fortified with just reduced iron
  • Table 2 and Figure 1 indicate that combining disodium EDTA with reduced iron enhances the bioavailability of the iron as measured by the average hemoglobin change (g/dL) relative to the amount of added iron (mg/kg diet). The ratio percent are calculated based on the hemoglobin change for the standard, ferrous sulfate. The bioavailability of reduced iron alone is 51.9% while the rat ⁇ o% of the iron bioavailability in a test diet comp ⁇ sing EDTA:iron at 1 :4 is 63%. This is a significant difference (P ⁇ .10). As the ratio of EDTA to iron in the test diet increases so does the bioavailability of the iron until, at an EDTA: ⁇ ron ratio of 1 :2 or 1 :1, and
  • Example 3 Rats were fed a pu ⁇ fied rat diet/Corn Flakes ® fortified with feme orthophosphate either alone or in combination with reduced iron or disodium EDTA or mixtures of both
  • the iron bioavailability in the feme orthophosphate fortified diets were compared to the iron bioavailability m diets fortified with reduced iron or ferrous sulfate As desc ⁇ bed above the bioavailability was determined by assaying the relative change m hemoglobin m rats fed with the various fortified diets

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Abstract

The invention provides for a cooked cereal ingredient-containing product fortified with a composition comprising an EDTA source and an iron source that is other than ferric EDTA. The cooked cereal ingredient-containing product comprises about 1.5 to about 18 mg of total iron from the combination of the iron source and the EDTA source per ounce of said cooked cereal ingredient-containing product, and preferably comprises 2.5 to 8.5 mg of total iron per ounce. The invention also provides for a method to prevent or treat iron-deficiency anemia by administering an iron/EDTA fortified cooked cereal ingredient-containing product. The molar ratio of EDTA:iron is in the range of 1:1 to 1:4.

Description

COOKED CEREAL INGREDIENT-CONTAINING PRODUCTS
FORTIFIED WITH EDTA/IRON COMPOSITIONS
AND METHODS FOR USE
FIELD OF THE INVENTION
This invention is related to a cooked cereal ingredient-containing, storage stable product ("storage stable cereal product") fortified with iron. A combination of an EDTA source and an iron source is used to fortify the storage stable cereal product. A storage stable cereal product fortified with an EDTA source in combination an iron source combination has surprising and unexpected advantages. The combination provides a storage stable cereal product with improved iron bioavailability and is significantly less expensive than a like product fortified with ferric EDTA alone.
BACKGROUND OF THE INVENTION Approximately one-fifth of the world's population suffer from some level of nutritional iron deficiency. Young children and women of childbearing age are the most adversely affected by anemia and other iron deficiency related conditions. Anemia during pregnancy can lead to risk of premature labor, (Lieberman et al., Am.J.Obstet.Gyn. 159: 107-1 14) and an increased perinatal morbidity and mortality, (Bothwell et al. In Iron Metabolism in Man, 1979). Children's development may also be impaired, subsequently having an effect on their performance in school. Iron deficiency can also adversely affect productivity as seen among laborers (Edgerton et al, Brit. Med. J. 2: 1546-9, 1979).
Heme iron, which is derived primarily from hemoglobin and myoglobin in meat, is transferred as intact porphyrin complex to intestinal cells, where the heme oxygenase enzyme rapidly releases the iron. It blends with other iron taken up by the cell before the regulated transfer to the blood stream occurs. This form of iron is readily absorbed and is generally not affected by the contents of the meal with which the heme containing food is consumed. The non-heme iron has a heterogenous origin, being derived from vegetable foods and inorganic forms of iron, and can be used to fortify foods by increasing the level of iron present. Non-heme iron, which is derived from plant foods and fortified foods is not as well absorbed as heme (meat) iron. Furthermore, beverages such as coffee and tea consumed at meal time and other factors can contπbute to poor absorption of non-heme iron.
The addition of ascorbic acid or vitamin C to shelf stable cereal based products can enhance iron absorption in the diet, generally without affecting consumer acceptability.
However, ascorbic acid fortification is expensive and when exposed to oxygen and moisture can be unstable duπng storage. In cases where food preparation involves baking, prolonged boiling or reheating, ascorbic acid is unstable and is partially lost.
The most efficient and cost-effective way of preventing and treating iron deficiency is to fortify food products with a form of iron that provides for adequate absorption. While cost is not necessarily a controlling factor in whether an affluent consumer would purchase an iron fortified product, among the poor and in less-well developed countnes cost often becomes the controlling factor Currently used iron fortificants, such as ferrous sulfate, are bioavailable, however they adversely affect the organoleptic properties of the cooked cereal mgredient- containing storage stable products, (hereinafter referred to as storage stable cereal products).
Therefore, other readily available and inexpensive sources of iron, which do not adversely affect the organoleptic properties of the storage stable cereal products are desirable Other inexpensive sources of iron, such as reduced iron and iron orthophosphate have the disadvantage that the iron is not as bioavailable as is the iron in ferrous sulfate and ferric EDTA Applicants have discovered that the bioavailability of total iron can be enhanced by combining sources such as reduced iron or iron orthophosphate with an EDTA source such as ferric EDTA or another sodium EDTA. such as disodium EDTA and calcium disodium EDTA Surprisingly, the ratio of EDTA to iron source may also influence the bioavailability of the iron.
U.S. patent no. 5,534,274 (incorporated by reference) discloses that feme EDTA is suitable for fortifying storage stable cereal products and that it may be combined with other fortificants, e.g , reduced iron. The patent suggests multiple iron sources, such as feme EDTA with an additional iron fortificant such as ferrous fumarate, ferrous sulfate, reduced iron, ferric citrate, ferrous citrate, ferrous lactate, ferrous succinate, feme phosphate, ferrous gluconate, ferrous pyrophosphate, ferrous glutamate, ferric tartrate, ferrous carbonate, feme chloride, ferric ammonium citrate, ferrous ascorbate, ferrous glycinate, ferrous malate, and ferrous cholinisocitrate and other similar feme or ferrous compounds which would be readily determinable by those skilled in the art may be combined to fortify the products. That patent does not suggest using ferric EDTA to enhance the bioavailability of the iron sources. Furthermore, the patent does not suggest that other EDTA sources could also be used in combination with an iron source in shelf stable cereal products to enhance iron bioavailability. Ferric EDTA is a pale yellow water-soluble powder that can be added to many food vehicles. In addition, when ferric EDTA is consumed with foods containing large quantities of absorption inhibitors, iron is protected from agents which inhibit its absorption. Iron from ferric EDTA has been reported to be two to three times more bioavailable than iron presented as a FeSO4 complex in some diets. Furthermore, ferric EDTA is more stable under adverse storage conditions and is unaffected by cooking.
Ferric EDTA is used in a variety food ingredients or condiments, i.e., fish sauce in Thailand (Garby et al., 1974, Ann. Tro. Med. Parasitol. 68:467-76), curry powder in South Africa (Macphail et al. , Experimental Fortificants, in: Clydesdale FM et al. eds. Iron Fortification of Foods, 1985), Egyptian flat bread (Guindi et al., Brit. J. Nutr. 59:205-213, 1988), sugar in Guatemala (MacPhail et al, Br. J. Nutr. 45;215-227, 1981). Absorption of iron in dietary foods such as flat breads has also been studied in Guindi et al., 1988, cite monograph table.
Sodium EDTAs are safe for use in food products. (Iron EDTA for Food Fortification: A Report of the International Nutritional ANEMIA Consultative Group. The Nutrition Foundation, Inc., Bates et al. Eds (1993)). Disodium EDTA, a white, water soluble chelating agent, is deemed to be safe for use in aqueous multi-vitamins, a variety of canned foods including peas, beans, pie fillings, salad dressings, frozen potatoes, mayonnaise, and dried bananas used in ready-to-eat breakfast cereals. Disodium EDTA is used to promote color retention and as a preservative. It is also used as a cure accelerator in cooked sausages. Additionally, calcium disodium EDTA is used to promote color, flavor, and texture retention in pickled cucumbers and cabbage, in canned foods, such as carbonated soft drinks, white potatoes, clams, mushrooms, beans, and in dry processed foods, such as pinto beans and lima beans. It is also used as a preservative in foods, such as salad dressings, oleomargarine, and potato salad. In addition, calcium disodium EDTA is used to retard struvite formation in sea foods, such as canned crabmeat and shrimp, and to promote stability of color, flavor and/or clarity of distilled alcoholic beverages. However, prior to this invention, food products were not fortified with combinations of disodium EDTA or other EDTA salts with an iron source such as reduced iron to enhance iron bioavailability
This is the first known use of a composition composing an EDTA source, such as ferric EDTA, calcium disodium EDTA, or disodium EDTA, and an iron source, other than ferric EDTA, to fortify a storage stable cereal product by enhancing the bioavailability of iron from the iron source.
The storage stable cereal product is prepared with the iron and EDTA combination by either incorporating it into the cereal dough mix pπor to cooking or by spraying an iron/EDTA solution onto the finished storage stable cereal product The combination of the iron source and the EDTA source results in unexpectedly enhanced iron bioavailability over a like product fortified with reduced iron alone It does not adversely affect taste and maintains excellent bπghtness characteπstics and oxidative stability, as well as having a significant reduction m cost over a like product fortified with ferric EDTA alone These unexpected properties for the iron/EDTA fortified storage stable cereal product descπbed above have not been established pπor to this application
Thus, it is a principal object of this invention to provide for a storage stable cereal product, which is fortified with an EDTA source, such as feme EDTA, calcium disodium EDTA, tetrasodmm EDTA, tπsodium EDTA, or disodium EDTA, m combination with an iron source, such as reduced iron or iron orthophosphate The use of iron/EDTA combination as an iron fortificant in a storage stable cereal product produces a product which is organoleptically acceptable to consumers The color, odor, and taste of the product are not adversely affected by the addition of the combined iron source and EDTA source and the bioavailability of the iron in the storage stable cereal product appeared not be adversely affected by the other constituents of cereals, which might inhibit the absorption of iron It is a further object of the invention to provide a method to prevent or to treat iron- deficiency anemia by admmisteπng the storage stable cereal products to individuals or population groups in need of such treatment
This invention also relates to fortifying storage stable cereal products with combinations of EDTA salts and other minerals, such as calcium, magnesium, zinc, selenium and copper and to methods for supplementing diets that are inadequate m these minerals SUMMARY OF THE INVENTION
This invention provides for a storage stable cereal product, which is fortified with an EDTA source, such as ferric EDTA, calcium disodium EDTA, tetrasodium EDTA, trisodium EDTA, and disodium EDTA, and an iron source, such as reduced iron or iron orthophosphate. Fortifying a storage stable cereal product with the EDTA, such as ferric EDTA or calcium disodium EDTA in combination with an iron source yields surprising results in a novel storage stable cereal product. The storage stable cereal products' organoleptic qualities, i.e., its color, odor, stability, and taste, are unaffected by the combination of the iron source and EDTA source. Further, the bioavailability of the iron is unexpectedly enhanced by the EDTA source. The total iron content in the storage stable cereal product ranges from 1.5-18 mg per ounce of cereal product, or preferably 2.5-8.5 mg/ounce of cereal product. The preferred ratio on a molar basis of EDTA to iron ranges from 1 : 1 to 1 :4 more preferably 1 : 1 to 1 :2.
The invention also provides for a method of preventing or treating iron-deficiency anemia by administration of the fortified storage stable cereal product of this invention to those in need of such treatment.
This invention also relates to enhancing the bioavailability of other minerals, such as calcium, zinc, copper, selenium and magnesium by fortifying a storage stable cereal product with a combination of an EDTA source and a mineral source, such as calcium, zinc, magnesium, selenium, or copper.
DETAILED DESCRIPTION OF THE INVENTION
Figure 1 demonstrates the hemoglobin iron change for rats fed diets comprising EDTA:Iron at various concentrations of iron per kg diet.
Figure 2 demonstrates the hemoglobin iron change over two weeks for rats fed diets comprising reduced iron and FeOP on an equal cereal basis.
Figure 3 demonstrates the hemoglobin iron change over two weeks for rats fed diets comprising FeSO4, reduced iron, or FeOP and mixtures thereof at various concentrations of iron per kg diet.
Figure 4 demonstrates the hemoglobin iron change over two weeks for rats fed diets comprising various mixtures/combinations of iron sources and EDTA sources at various concentrations of iron per kg diet. Adding an iron source, such as reduced iron or iron orthophosphate, and an EDTA source, such as feme EDTA or a disodium EDTA, at a molar ratio of about 1 4 (EDTA iron) to about 1 1 (EDTA iron) to fortify a storage stable cereal product has not been reported pπor to this invention The Examples infra demonstrate that the combination of an EDTA source with an iron source enhances iron bioavailability
A storage stable cereal product is unusual in that duπng its preparation the iron fortificant may be added to a cereal dough product, which is cooked/heated and formed into cereal pieces, or alternatively the iron fortificant may be sprayed onto the formed cereal pieces The cereal pieces are then dπed and stored for a potentially long peπod of time Although the storage stable cereal product is not generally subjected to any further cooking means prior to consumption, it may be subjected to conditions that destabilize the storage stable cereal product containing the iron fortificant Oxidation of the iron fortificant may adversely affect the overall characteπstics of the product Therefore, the stability of any iron fortificant added to a storage stable cereal product is extremely important to the palatabihty and physical acceptability of the product to the consumer
The advantages of using a combination of an iron source and an EDTA source to fortify a storage stable cereal product include enhancing iron bioavailability, and doing so in a cost- effective manner, and producing a cereal product that has high intensity on the bπghtness scale, a pleasing taste and oxidative stability A storage stable cereal product includes not only ready-to-eat breakfast cereals, such as
Corn Flakes and Rice Knspies'' . but also includes other food products, such as snackbars, such as NurtnGrain11 bars and Rice Knspies Treats™ Squares, toaster pastries, such as PopTarts®, and pastry products, which are produced using cooked cereal ingredients These storage stable cereal products can be fortified in the same manner with the combination of an iron source and an EDTA source as descπbed herein
The storage stable cereal products of this invention may be prepared from cereal ingredients selected from the group consisting of wheat, rice, oat, corn, barley, rye, millet, sorghum, amaranth seed and mixtures thereof Furthermore, other ingredients, including but not limited to, sugars, salts, spices, flavoπngs, fruits, nuts, vitamins and minerals, which may add to the flavor or nutπtional aspects of the final product, may be added to the storage stable cereal product without departing from the spiπt and scope of the invention In addition, high fiber sources, such as psyllmm as disclosed in U S patent no 5,227,248 and PCT US94/10290 incorporated herein by reference in their entirety, may also be included in the storage stable cereal products
The iron fortified storage stable cereal products of this invention may also be administered to individuals or population groups to prevent or treat iron-deficiency anemia, i.e., a low hemoglobin value, a low hematocπt value or a low red blood cell count The storage stable cereal products of this invention, may also be used to supplement a diet that is inadequate in minerals, such as calcium, magnesium, zinc, copper, and selenium
This invention will be better understood by reference to the following examples, which establish a greater relative iron bioavailability by fortifying storage stable cereal products with an iron source that is not ferric EDTA with an EDTA source These examples are included here for purposes of exemplification and are not to be construed as limitations
Example 1 The relative iron bioavailability of various iron containing compositions in a ready-to-eat cereal product was assayed using a widely accepted method, commonly referred to as the rat hemoglobin repletion method, (modified AOAC method for assessment of relative iron bioavailability), see Williams, S ed Official methods of analysis of the Association of Official Analytical Chemists, 14th ed Arlington, VA AOAC, 1984, Fritz, J C et al , Collaborative Study of rat hemoglobin repletion test for bioavailability of iron, AOAC 1974, 57 513-517
Relative bioav ailability of the vanous iron EDTA composition was carried out m a seπes of separate expenments In each of these expeπments, ferrous sulfate was used as the standard or control compound
Sprague Dawley rats, individually housed in temperature and light controlled units, were fed an iron deficient diet obtained from Harland Tekland Laboratories for 24 days After this iron depletion phase, the rats were weighed and blood was drawn to test for baseline hemoglobin concentrations These anemic animals, with hemoglobin levels between 2 9 to 4 1 g/1, were then randomly assigned to the control and test groups Ferrous sulfate, reduced iron and the feme EDTA compounds were added to the test diets to achieve concentrations of 6 and 18 and 24 mg iron/kg diet These diets were then fed to groups of ten animals, ad libitum, for 14 days Iron levels in the diets, were veπfied by atomic absorption spectrometry (Bhn et al , J Assoc Off Anal. Chem. 1977, 60: 1 170-1 174). After the 14-day test period, hemoglobin concentrations were determined for all animals.
The iron bioavailability of each iron source, assayed relative to ferrous sulfate, was calculated using the slope ratio procedure by comparing the gain in hemoglobin concentration with the iron concentration in the diet (Finney, D.J., Statistical methods in biological assay. 2nd ed. 1964; Amine et L., Biological assessment of available iron in food products, J. Agric. Food Chem. 1974, 22:470-476). Intercept and slope estimates were obtained for the rats fed diets that were not fortified (negative controls) and rats fed each test diet using the ordinary least square's method. All test diet intercepts were compared to the negative control diets to validate the fitting of a common intercept. Comparison of the slopes of the test diets with the standard (ferrous sulfate) diet was performed after fitting the data through a common intercept. Bioavailability was defined as the ratio of the slope of each diet to the slope of ferrous sulfate diet. The statistical program SAS V.608 was used. The slope values and ratios are set forth in Table 1.
Table 1
Iron Source Slope Value Ratio
Ferrous Sulfate 0.33+0.02* 1.00 Ferric EDTA 0.31 +0.03* 0.94
Reduced Iron 0.16+0.03* 0.48 * = 95% confidence interval
The slope of the line generated from ferric EDTA is similar to that from the ferrous sulfate standard. The slope value for the reduced iron diet was markedly less than the value for ferric EDTA. These data indicate that the iron from ferric EDTA is absorbed at a rate not significantly different from ferrous sulphate and significantly better than reduced iron. Example 2
To compare the bioavailability of iron from varying ratios of EDTA:Iron (1:1, 1:2, 1:3 and 1 :4) with the bioavailability of iron from 100% reduced iron and from 100% ferrous sulfate, Sprague Dawley rats were fed the above diet at various levels, 0, 10, 16, 29 and 50 mg, iron per kg of total diet1. The relative iron bioavailability was accessed by the rat hemoglobin repletion test AOAC method as described in Example 1 supra. The slopes value and the intercepts values are set forth in Table 2.
Table 2: Intercept and Slope Comparisons Among Treatments (Study 6706-102)
1 2 3 4 5 6 7
Treatment bO se bl se Ratio means Ratio of
EDTA/IRON (%) (level=50) means
None -2.01 NA NA NA NA NA NA
FeSO4 -2.55 0.35 0.27a 0.02 - 7.22ab -
1 : 1 -2.88 0.25 0.23b 0.01 85.2 7.29a 100.0
1 :2 -2.33 0.28 0.21c 0.01 77.8 7.10ab 98.3
1 :3 -2.92 0.26 0.19cd 0.01 70.3 6.21bc 86.0
1 :4 -2.59 0.21 0.17d 0.01 63.0 6.05c 83.8
100% reduced -2.76 0.15 0.14e 0.01 51.9 4.31d 59.7 iron
-AOAC Standard requires; 0, 6, 12, 24. Although the study was designed to be 0, 6, 12, 24, and 28, the real numbers (0, 10, 16, 29 and 50) are due to the variation in preparation of the diets. 1. Expected hemoglobin change when there is no added iron (intercept).2
2. Estimates of standard error of intercepts.
3. Estimates of hemoglobin change for every unit increase in added iron (slope; obtained after fitting a common intercept) 2
4. Estimates of standard errors of slopes.
5. Ratio of treatment slopes to the slope of FeSO4.
6. Average hemoglobin change at 50 mg/kg diet of added iron.
7. Ratio of the treatment means at 50 mg/kg diet of added iron to the mean hemoglobin change of FeSO4
Linear regression suggests that the total change in hemoglobin (g/dL) in rats fed diets fortified with L I and 1.2 EDTA iron were significantly higher than the hemoglobin change observed when the rats were fed a diet fortified with only reduced iron as the iron source (diets fortified with 100% FeSO served as the standard). At 50 mg Fe/kg diet, the change in hemoglobin among rats fed the L I test diet is not significantly different from the hemoglobin change in rats fed the reference FeSO4 diet. Additionally, the hemoglobin change for rats fed a 1 :2 test diet is not significantly different from rats fed the 1.1 and the FeSO diets Although the hemoglobin change for rats fed a 1 :3 diet is significantly different from those fed the 1 : 1 and FeSO4 diets, the change is still significantly higher than the values in rats fed diets fortified with just reduced iron
Table 2 and Figure 1 indicate that combining disodium EDTA with reduced iron enhances the bioavailability of the iron as measured by the average hemoglobin change (g/dL) relative to the amount of added iron (mg/kg diet). The ratio percent are calculated based on the hemoglobin change for the standard, ferrous sulfate. The bioavailability of reduced iron alone is 51.9% while the ratιo% of the iron bioavailability in a test diet compπsing EDTA:iron at 1 :4 is 63%. This is a significant difference (P< .10). As the ratio of EDTA to iron in the test diet increases so does the bioavailability of the iron until, at an EDTA:ιron ratio of 1 :2 or 1 :1, and
-' Slopes of means associated with different letters are significantly different from each other (P<.10). a total of 50 mg Fe/kg diet, the bioavailability of iron provided by the EDTA iron is not significantly different from the bioavailability of iron provided by ferrous sulfate
Example 3 Rats were fed a puπfied rat diet/Corn Flakes® fortified with feme orthophosphate either alone or in combination with reduced iron or disodium EDTA or mixtures of both The iron bioavailability in the feme orthophosphate fortified diets were compared to the iron bioavailability m diets fortified with reduced iron or ferrous sulfate As descπbed above the bioavailability was determined by assaying the relative change m hemoglobin m rats fed with the various fortified diets
Six test diets were evaluated
A) 45% RDA reduced iron
B) 20% RDA reduced iron/25% RDA FeOP C) 20% RDA reduced iron/50% RDA FeOP
D) 45% RDA FeOP
E) 45% RDA FeOP - EDTA (1 1 Fe EDTA)
F) 20% RDA reduced iron/25% RDA FeOP - EDTA (1 1 Fe EDTA)
All products, except the product with additional FeOP (C), were fed at levels equivalent to 6, 12, 24 and 48 mg Fe/kg diet The product with additional FeOP (C) was fed at an equal cereal level to the other test diets resulting in 9 4, 18 7, 37 4, and 74 9 mg Fe/kg diet
The results depicted in Tables 3 and Figures 2, 3, and 4 indicate that (1) there was no statistically significant difference in the iron absorption (l e slope/relative bioavailability) of FeOP and reduced iron (see Table 3), and (2) the addition of disodium EDTA greatly improved bioavailability, approximately doubling bioavailability, and approached the bioavailability obtained with the reference FeSO4 Table 3: Intercept and Slope Comparisons Among Various Iron Sources in Corn
Flakes®
Iron Source Intercept Intercept Slope Slope Differences* Differences*
None -1.40 a NA NA
A) Reduced Iron -1.73 a 0.1 1 a (45% RDA)
B) Red. Iron/FeOP -1.73 a 0.10 a (20% / 25% RDA)
D) FeOP -1.82 a 0.10 a
(45% RDA)
E) FeOP - EDTA -2.16 a 0.22 b
(45% RDA 1 : 1 Fe:EDTA)
F) Red. Iron FeOP - EDTA -2.03 a 0.24 b
(20%) / 25% RDA 1 :1 Fe:EDTA)
FeSO4 -2.10 a 0.30 c
C) Red. Iron/FeOP -2.07 NA 0.10 NA
(20% / 50% RDA)
'Estimates with the same letter do not differ (PO.10).
At an iron concentration of 48 mg Fe/kg diet, the absorbed iron began to plateau for the products having high bioavailability (FeSO4 and the two products containing EDTA (E) and (F)). This is demonstrated in Figure 3.
The animals fed Corn Flakes* fortified with reduced iron generally had slightly greater increases in absorbed iron than the animals fed equal amounts of FeOP fortified Corn Flakes® or the Corn Flakes® fortified with reduced iron and FeOP. As shown in Table 3, the slope of the iron absorption line for reduced iron was approximately 10% greater than reduced iron and FeOP (0.11 vs. 0.10). However, the addition of Na2 EDTA to Corn Flakes® fortified with FeOP alone or reduced iron in combination with FeOP (1:1, EDTA:Iron) greatly improved the bioavailability of iron. The relative bioavailability was roughly twice that of similar products without Na2 EDTA. EDTA improves the bioavailability of other iron sources in cereal as seen in Figure 4. It is not intended that the present invention be limited to only the described embodiments. Rather, the invention should be circumscribed by the scope of the appended claims.

Claims

We claim:
1. A cooked cereal ingredient-containing product comprising: a) a cereal ingredient; b) an EDTA source, and; c) an iron source other than ferric EDTA.
2. The cooked cereal ingredient-containing product of claim 1 , wherein said EDTA source is a sodium EDTA.
3. The cooked cereal ingredient-containing product of claim 1, wherein the ratio of EDTA to iron is 1 :1 to 1 :4.
4. The cooked cereal ingredient-containing product of claim 2, wherein said EDTA source is selected from the group consisting of a NaFeEDTA, Na2EDTA, trisodium EDTA, tetrasodium EDTA, and calcium sodium EDTA.
5. The cooked cereal-ingredient-containing product of claim 1, comprising about 1.5 to about 18 mg of total iron from the combination of the iron source and the EDTA source per ounce of said cereal product.
6. The cooked cereal ingredient-containing product of claim 1 , comprising about 2.5 to about 8.5 mg of total iron from the combination of the iron source and the EDTA source per ounce of said cereal product.
7. The cooked cereal ingredient-containing product of claim 1, wherein said cereal ingredient is selected from the group consisting of wheat, rice, oat, corn, barley, rye, millet, and amaranth seed. The cooked cereal-mgredient-containmg product of claim 1 , further compπsmg at least one iron fortificant selected from the group consisting of ferrous fumarate, ferrous sulfate, reduced iron, feme citrate, ferrous citrate, ferrous lactate, ferrous succmate, feme phosphate, ferrous gluconate, ferrous pyrophosphate, ferrous glutamate, feme tartrate, ferrous carbonate, feme chloπde, feme ammonium citrate, ferrous ascorbate, ferrous glycmate, ferrous malate, and ferrous cholmisocitratem, encapsulated iron and feme orthophosphate
The cooked cereal ingredient-contaimng product of claim 1 , wherein the product is a R- T-E breakfast cereal
The cooked cereal ingredient-contaimng product of claim 1 , wherein the product is a toaster pastry
The cooked cereal ingredient-contaimng product of claim 1 , wherein the product is a snack bar
A method for preventing iron-deficiency anemia in a subject compπsing administering to said subject an amount of the cooked cereal ingredient-contaimng product of claim 1 , sufficient to prevent said anemia in said subject
A method for preventing iron-deficiency anemia in a subject compπsing administering to said subject an amount of the cooked cereal ingredient-contaimng product of claim 7, sufficient to prevent said anemia in said subject
A method for treating iron-deficiency anemia in a subject comprising admimsteπng to said subject an amount of the cooked cereal ingredient-contaimng product of claim 1, sufficient to treat said anemia m said subject A method for treating iron-deficiency anemia in a subject compπsing administeπng to said subject an amount of the cooked cereal ingredient-contaimng product of claim 5, sufficient to treat said anemia m said subject
A gram based cereal product organoleptically acceptable for human consumption compπsing a) a cooked gram product, b) an EDTA source, and. c) a mineral source
The grain based cereal products of claim 15, wherein the mineral is selected from the group consisting of calcium, potassium, magnesium, copper, selenium, and zmc
A method for treating iron-deficiency anemia in a subject compnsing administeπng to said subject an amount of the cooked-cereal ingredient containing product of claim 8, sufficient to treat said anemia in said subject
A method for preventing iron-deficiency anemia in a subject compπsing administeπng to said subject an amount of the cooked cereal ingredient-contaimng product of claim 8, sufficient to prevent said anemia in said patient
PCT/US1998/016036 1997-08-01 1998-07-31 Cooked cereal ingredient-containing products fortified with edta/iron compositions and methods for use Ceased WO1999005920A1 (en)

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JP51130599A JP2001507579A (en) 1997-08-01 1998-07-31 Products containing cooked cereal ingredients enhanced by EDTA source / iron composition and methods of use
AU87641/98A AU8764198A (en) 1997-08-01 1998-07-31 Cooked cereal ingredient-containing products fortified with EDTA/iron compositi ons and methods for use
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6461651B1 (en) 2000-09-26 2002-10-08 General Mills, Inc. Sodium-free iron complex for food fortification
US6720728B2 (en) 1997-10-30 2004-04-13 Canon Kabushiki Kaisha Devices containing a carbon nanotube
GB2487304A (en) * 2011-01-14 2012-07-18 Chiasma Inc Oral ferric iron composition with bioavailability enhancer

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JP2005325080A (en) * 2004-05-17 2005-11-24 Daiichi Fine Chemical Co Ltd Composition containing calcium pantothenate and vitamins

Citations (1)

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Publication number Priority date Publication date Assignee Title
US5534275A (en) * 1994-02-28 1996-07-09 Kellogg Company Foodstuffs containing a cereal ingredient and ferric EDTA

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5534275A (en) * 1994-02-28 1996-07-09 Kellogg Company Foodstuffs containing a cereal ingredient and ferric EDTA
US5667825A (en) * 1994-02-28 1997-09-16 Kellogg Company Ready-to-eat cereal product fortified with ferric EDTA and process of making

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6720728B2 (en) 1997-10-30 2004-04-13 Canon Kabushiki Kaisha Devices containing a carbon nanotube
US6461651B1 (en) 2000-09-26 2002-10-08 General Mills, Inc. Sodium-free iron complex for food fortification
GB2487304A (en) * 2011-01-14 2012-07-18 Chiasma Inc Oral ferric iron composition with bioavailability enhancer

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