Vitamin a and B-Carotene Can Improve Nonheme Iron Absorption Rice, Wheat and Corn

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    Nutrient Requirements and Interactions

    Vitamin A and b-Carotene Can Improve Nonheme Iron Absorption fromRice, Wheat and Corn by Humans1,2

    Mara Nieves Garca-Casal,* Miguel Layrisse,*3 Liseti Solano, Mara Adela Baron,Franklin Arguello, Daisy Llovera, Jose Ramrez,* Irene Leets* and Eleonora Tropper*

    *Centro de Medicina Experimental, Laboratorio de Fisiopatologa, Instituto Venezolano de InvestigacionesCientficas (IVIC), Caracas 1020A, Venezuela; Unidad de Investigaciones en Nutricion, Universidad deCarabobo, Valencia, Venezuela; and Universidad Central de Venezuela, Caracas, Venezuela

    ABSTRACT After the rapid decrease in the prevalence of iron deficiency and iron-deficiency anemia in theVenezuelan population when a national program for fortification of flours with iron and vitamins was instituted,we studied micronutrient interactions in Venezuelan diets. One hundred human adults were fed three cereal-baseddiets, labelled with either 59Fe or 55Fe in six studies. Each diet contained different concentrations of vitamin A(from 0.37 to 2.78 mmol/100 g cereal) or b-carotene (from 0.58 to 2.06 mmol/100 g cereal). The presence of vitamin

    A increased iron absorption up to twofold for rice, 0.8-fold for wheat and 1.4-fold for corn. b-carotene increased

    absorption more than threefold for rice and1.8-fold for wheat and corn, suggesting that both compounds preventedthe inhibitory effect of phytates on iron absorption. Increasing the doses of vitamin A or b-carotene did not furthersignificantly increase iron absorption. We measured the iron remaining in solution performing in vitro studies inwhich the pH of solutions was adjusted from 2 to 6 in the presence of vitamin A or b-carotene. All of the ironfrom ferrous fumarate was soluble after changing the pH of the solution containing 3.4 mmol of b-carotene to 6.0.

    Vitamin A was less effective. However, 78 { 18% of iron was soluble in the presence of 3.3 mmol of vitamin A,whereas with no vitamin addition, only 26 { 13% of iron was soluble (0.05). Vitamin A and b-carotene mayform a complex with iron, keeping it soluble in the intestinal lumen and preventing the inhibitory effect of phytatesand polyphenols on iron absorption. J. Nutr. 128: 646 650, 1998.

    KEY WORDS: iron vitamin A b-carotene humans phytates

    Vitamin A is a vital nutrient for cellular differentiation, population (Taylor et al. 1995), we continued studies of micro-vision, bone growth, reproduction and integrity of the immune nutrient interactions on iron ab sorption, especially sincesystem (Olson 1984). It is also essential for erythropoiesis. 1993, when the fortification of precooked corn and whiteDeficiency of this vitamin results in anemia in humans and wheat flours with iron and vitamins was started (Layrisse etanimals that is reversed only by vitamin A supplementation al. 1996).(Bloem et al. 1989, Hodges et al. 1978, MejBa 1986, MejBa and The first experiments already were presented in two work-Arroyave 1982, MejBa and Chew 1988, MejBa et al. 1979). shops (GarcBa-Casal and Layrisse 1996, Layrisse and GarcBa-b-carotene is the most abundant provitamin A in foods. Casal 1997); and published (Layrisse et al 1997, Layrisse and

    Approximately 1050% of the total b-carotene consumed is GarcBa 1997). The studies showed that addition of vitamin Aabsorbed in the gastrointestinal tract and within the intestinal (as retinol palmitate) and iron to corn or wheat flours usedwall is partially converted into vitamin A. The efficiency of to prepare a typical Venezuelan breakfast (basal breakfast)b-carotene absorption decreases as intake increases and con- containing corn or wheat bread, cheese, margarine and coffeeversion to vitamin A is regulated by the vitamin A status of or tea, diminished the inhibitory effect of phytates andthe individual. b-carotene accumulation is not toxic, so it is polyphenols on iron absorption.considered a safe source of vitamin A (Roche Laboratories We examined the effects of increasing doses of vitamin1994, Wang 1994). A and b-carotene on nonheme iron absorption. In addition,

    After reporting the results on iron availability from diets solubility changes of various iron compounds at pH 2 and 6

    consumed by different socioeconomic strata of the Venezuelan with and without vitamin A and b-carotene are presented.

    MATERIALS AND METHODS1 Supported in part by CONICIT, Caracas, Venezuela. One hundred and four adult subjects (27 men and 77 women from2 The costs of publication of this article were defrayed in part by the payment

    Valencia City, Venezuela) voluntarily participated in this study. Theof page charges. This article must therefore be hereby marked advertisementCommittee for the Protection of Human Subjects of the Venezuelanin accordance with 18 USC section 1734 solely to indicate this fact.

    3 To whom correspondence should be addressed. Institute for Scientific Research approved the studies. The subjects

    0022-3166/98 $3.00 1997 American Society for Nutritional Sciences.Manuscript received 4 June 1997. Initial revision completed 3 July 1997. Revision accepted 12 November 1997.

    646

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    647NONHEME IRON ABSORPTION IMPROVEMENT

    TABLE 1

    Composition of meals administered to human subjects participating in iron absorption studies

    Meals2

    TestStudy Subjects Food1 1 2 3 4

    n

    1 17 Rice ( 59Fe) 0.55 mmol Vitamin A 1.51 mmol Vitamin A 2.78 mmol Vitamin A(55Fe) ( 59Fe) ( 55Fe)

    2 17 Corn ( 59Fe) 0.37 mmol Vitamin A 0.61 mmol Vitamin A 0.73 mmol Vitamin A(55Fe) ( 59Fe) ( 55Fe)

    3 20 Wheat ( 59Fe) 1.10 mmol Vitamin A 0.66 mmol Vitamin A 1.51 mmol Vitamin A(55Fe) ( 59Fe) ( 55Fe)

    4 11 Rice ( 59Fe) 1.51 mmol Vitamin A 0.58 mmol b-carotene 0.95 mmol b-carotene(55Fe) / coffee (59Fe) ( 55Fe)

    5 20 Corn ( 59Fe) 0.61 mmol Vitamin A 0.67 mmol b-carotene 1.53 mmol b-carotene(55Fe) ( 59Fe) / coffee (55Fe)

    6 19 Wheat ( 59Fe) 0.66 mmol Vitamin A 0.85 mmol b-carotene 2.06 mmol b-carotene(55Fe) ( 59Fe) / coffee (55Fe)

    1 Rice test: 100 g polished rice / 10 g margarine; corn test: 100 g precooked corn flour / 50 g cheese / 10 g margarine; wheat test: 100 gwhite wheat flour / 50 g cheese / 10 g margarine.

    2 Parentheses enclose supplemented isotope.

    were selected from a low socioeconomic stratum in a section of a estimated blood volume based on sex, weight and height (Nadler etal. 1962).Venezuelan city. They were in apparent good health, but some of

    the women had moderate iron-deficiency anemia (hemoglobin 120 The protocol for the administration of radioactive food in themorning after an overnight fast and the afternoon of the same dayg/L). Blood (30 ml) was taken from each subject in a tube with

    ethylenediamine tetraacetic acid (EDTA) and kept refrigerated at was based on experiments previously published (Taylor et al. 1995).Four-hour intervals between meals are sufficient for iron absorption4C until used to measure hemoglobin concentration (Crosby et al.

    1954), serum iron (International Committee for Standardization in studies.Chemical analysis. The total iron concentration of foods wasHematology 1978), unsaturated iron bin ding capacity (International

    Committee for Standardization in Hematology 1978), serum ferritin determined by the digestion method (Bothwell et al. 1979), phytatesby the method of Haug and Lantzsch (1983), tannate by the methodconcentration (Flowers et al. 1986) and radioactivity measurements

    (see next section). of Price and Butler (1977), vitamin A by the method of Stroheckerand Heming (1965) modified by Covenin (1989) and b-carotene byThree cereals were tested: corn, wheat and rice. The corn test

    contained bread from 100 g nonfortified precooked corn flour and 5 the method of Strohecker and Heming (1967).Phytate concentrations in precooked corn flour, wheat flour andmg iron as ferrous fumarate; the flour was given with 10 g margarine

    and 50 g cheese. The wheat test contained a bread prepared from rice were 257, 161 and 170 mg/100 g, respectively. The mean tannin

    concentration in coffee was 2500 mg/100 g. In studies in which coffee100 g of commercial white wheat flour enriched with 0.15 mg thia-mine, 0.2 mg riboflavin, 2 mg niacin and 2 mg iron as ferrous fumarate. was included, each subject consumed coffee prepared by the infusion

    of 8 g of ground coffee beans.It also contained 10 g margarine and 50 g cheese. The rice testcontained 100 g polished rice and was administered with 10 g marga- The mean iron concentration was 6 mg/100 g in the fortified

    precooked corn flour, 3 mg/100 g in white wheat flour, and 4 mg/100rine.Corn, wheat and rice tests were given alone or with different g in boiled rice. The molar ratio of iron to phytate was 0.29 in

    precooked corn flour, 0.23 in the wheat flour and 0.30 in boiled rice.amounts of vitamin A or b-carotene. The vitamin A used was water-soluble retinol palmitate, and b-carotene was a 10% water-solublepowder. Both products kindly were supplied by Roche Laboratoriesof Venezuela (Caracas).

    TABLE 2Absorption studies. Six studies were performed. Each included

    20 randomly selected subjects. The studies were designed to deter- Changes in added Vitamin A andb-carotene centrationmine iron absorption from each test given alone in meal 1, and with

    during preparation and cooking of meals1different amounts of vitamin A, b-carotene or coffee in meals 24(Table 1).

    After cooking proceduresEach subject was included in only one study. Four meals were given

    to each individual. Radiolabeled iron was added to the water to prepare Initially added Rice test Corn test Wheat testthe cereal. Each meal contained either 59Fe or 55Fe (Table 1).The first meal in each study was the corn, wheat or rice test given

    mmol mmol per 100 g cerealalone and administered after an overnight fast. The second meal wasgiven in the afternoon of the same day. Blood was drawn 15 d later

    Vitamin A 1.1 (1000) 0.55 (496) 0.37 (338) 1.1 (1000)2to determine the hematological profile of the subjects and measure2.2 (2000) 1.51 (1376) 0.61 (554) 0.66 (600)the radioactivity of blood samples. The subjects were fed again in4.4 (4000) 2.78 (2526) 0.73 (661) 1.51 (1372)the morning and in the afternoon of d 15 with meals 3 and 4, and

    blood was drawn again on d 30 to measure the radioactivity in blood b-carotene 1.7 (1000) 0.58 (342) 0.67 (395) 0.85 (500)and serum ferritin. 3.4 (2000) 0.95 (558) 1.53 (902) 2.06 (1211)

    Duplicate 10 ml blood samples and triplicate samples of the radio-active foods were prepared for scintillation counting using the tech- 1 Values are means, n 3; numbers in parentheses are in IU.nique of Dern and Hart (1961a and 1961b). Iron absorption from 2 Vitamin A was not added to the dough. It was dissolved in water

    and administered, freshly prepared, as a beverage.food was calculated from the radioactivity in the subjects blood using

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    648 GARCIA-CASAL ET AL.

    TABLE 3

    Effect of increasing doses of vitamin A on iron absorption in humans from rice, corn and wheat tests1

    Iron absorption

    Subjects and Serum transferringender2 Hemoglobin saturation Serum ferritin Meal 13 Meal 2 Meal 3 Meal 4

    g/L % mg/L Vitamin A administered, mmol

    Rice, study 1 0.55 1.51 2.78

    6 M, 11 F 126 { 4 23 { 2 29 { 1 3.9a { 1.1 8.4b,c { 1.1 7.5b { 1.2 11.7c { 1.2

    Corn, study 2 0.37 0.61 0.73

    6 M, 11 F 135 { 5 27 { 2 28 { 1 5.8a { 1.2 9.8b { 1.2 13.9c { 1.1 11.8b,c { 1.1

    Wheat, study 3 1.10 0.66 1.51

    3 M, 17 F 130 { 2 29 { 2 31 { 1 4.2a { 1.2 7.4b { 1.1 7.1b { 1.1 7.5b { 1.1

    1 Values are means { SEM. Means in a row with dissimilar letters are significantly different, P 0.05. Vitamin A was administered as a beveragewhile eating the bread in the wheat study, meal 2.

    2 M, male; F, female.3 No Vitamin A was added to any meal 1.

    The mean tannin content in 8 g of coffee powder was 200 mg. bion Laboratories, Clearfield, UT) were tested due to their stabilityat alkaline pH.The molar ratio of iron to tannin content in the corn test was 1.0,0.50 in the wheat test, and 0.66 in the rice test. Iron solutions from each of the compounds mentioned, containing

    5 mg of iron, were prepared in 0.1 mol/L HCl containing 0, 0.55,Because of the long distance between the laboratory and the placewere the experiments were performed, the meals were administered 1.1, 1.65, 2.2 and 3.3 mmol (0, 500, 1000, 1500, 2000 and 3000 IU)

    of vitamin A or 0, 0,85, 1.70, 2.55, 3,40 and 5.10 mmol (0, 500,to the subjects 1 d after the meals were prepared. Variations in addedvitamin A and b-carotene content due to cooking procedures are 1000, 1500, 2000 and 3000 IU) ofb-carotene. A 2-ml aliquot was

    taken to measure soluble iron at pH 2, and to the remaining solution,shown in Table 2. In the case of the administration of 1.1 mmol(1000 IU) of vitamin A, the wheat bread was prepared separately, the pH was adjusted to 6 with careful addition of NaOH.

    After standing 10 min at room temperature, duplicate 1-ml aliquotsand this amount of vitamin A was dissolved in 20 ml water anddrunk while eating the baked bread. In a previous experiment, we from the top of the solution were taken, and iron was measured for all iron

    compounds with different concentrations of vitamin A andb-carotene atdemonstrated that80% of the vitamin A is lost during preparationof the dough and baking procedures due to the effect of yeast and pH 2 and 6 by the digestion method (Bothwell et al. 1979).

    Statistical analysis. Paired t test was performed for iron absorp-the prolonged heat (Layrisse et al. 1997).tion studies comparing all meals within each study. It also was usedSolubility of iron compounds at pH 2 and pH 6. The effect ofto compare iron solubility at pH 2 and 6 in presence of vitamin Avitamin A and b-carotene on iron solubility at pH 2 and 6 was

    or b-carotene.measured. Four iron compounds were tested: ferrous sulfate, ferrousfumarate, an iron-amino acid chelate (Ferrochel) and Ferric-sodiumRESULTSEDTA. Ferrous sulfate was studied because it is a reference compound

    Iron absorption studies. The effect of increasing doses offor iron studies. Fumarate is the salt used in Venezuela for enrichmentof corn and wheat flours. Ferric-sodiumEDTA and Ferrochel (Al- vitamin A on nonheme iron absorption from meals containing

    TABLE 4

    Iron absorption from meals containing rice, corn or wheat given alone or administered with Vitamin A or b-carotene1

    Iron absorption

    Subjects and Serum transferringender2 Hemoglobin saturation Serum ferritin Meal 1 Meal 2 Meal 3 Meal 4

    Vitamin A b-Caroteneg/L % mg/L

    mmolRice, study 4 1.51 0.58 0.95

    3 M, 8 F 129 { 11 28 { 2 21 { 1 2.1a { 1.1 4.6b { 1.1 6.4b,c { 1.1 8.8c { 1.1

    Corn, study 5 0.61 0.67 1.53

    6 M, 14 F 130 { 11 30 { 2 24 { 1 3.0a { 1.1 6.6b { 1.2 8.5b { 1.1 6.3b { 1.2

    Wheat, study 6 0.66 0.85 2.06

    3 M, 16 F 132 { 11 25 { 2 18 { 1 3.0a { 1.1 5.5b { 1.1 8.3c { 1.1 8.4c { 1.1

    1 Values are means { SEM. Means in a row with dissimilar letters are significantly different, P 0.05. Coffee infusion was administered withmeal 3 for the rice meal and with meal 4 for the other two studies.

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    649NONHEME IRON ABSORPTION IMPROVEMENT

    TABLE 5

    Effects of vitamin A content and pH on in vitro iron solubility

    Ferrous fumarate Ferrous sulfate

    pH Vitamin A 2 Fe Soluble iron Fe Soluble iron

    mmol mg % mg %

    2 3.87 { 0.1b 100 { 2.6 6.18 { 0.4b 100 { 6.56 0.99 { 0.2a 25.6 { 5.2 2.24 { 0.2a 36.2 { 3.26 0.55 (500) 1.32 { 0.3a 34.1 { 7.8 3.33 { 0.1a 53.9 { 1.66 1.10 (1000) 1.75 { 0.2a 45.2 { 5.2 3.85 { 0.4a 62.3 { 6.56 1.65 (1500) 1.90 { 0.2a 49.1 { 5.2 3.88 { 0.2a 62.8 { 3.26 2.20 (2000) 2.01 { 0.1a 51.9 { 2.6 4.18 { 0.1a 67.6 { 1.66 3.30 (3000) 3.0 { 0.5b 77.5 { 12.9 5.47 { 0.3b 88.5 { 4.9

    1 Values are means { SEM, n 5. Means in a column with dissimilar letters are significantly different, P 0.05. Initial iron content: 5 mg.2 Values in parentheses are in IU.

    rice, corn and wheat is shown in Table 3. Iron absorption creased as a function of vitamin concentration. Iron solubilityincreased in 20% with 1.1 mmol (100 IU) of vitamin A, andfrom the meal given alone was significantly lower than when

    vitamin A was included. There were no significant differences when 3.3 mmol (3000 IU) was added, solubility was 80%.Ferrous sulfate showed a similar pattern. Iron solubility de-in iron absorption from rice meals containing from 0.55 to

    2.78 mmol (4962526 IU) vitamin A. The same patterns of creased in 64% when pH was raised to 6. When vitamin Awas added iron solubility increased, and at 3.3 mmol (3000iron absorption were observed from the tests containing pre

    cooked corn flour and white wheat flour. IU), iron solubility was near 90%.When b-carotene was added to ferrous fumarate solutionsIn study 4, iron absorption from the rice meal containing

    vitamin A (meal 2, Table 4), was more than double the absorp- at pH 2 and then raised to pH 6, virtually all of iron remainedin solution when 3.4 mmol (2000 IU) or 5.1 mmol (3000 IU)tion from the meal given alone. In the absorption test in which

    the meal contained 0.58 and 0.95 mmol (342 and 558 IU) b- ofb-carotene was added (Table 6). For ferrous sulfate, 92%of iron remained in solution at pH 6 when 5.1 mmol (3000carotene, iron absorption was more than two and three times

    greater than the meal given alone. The same pattern of iron IU) of b-carotene was added, whereas only 36% was solubleat pH 6 without any provitamin addition.absorption was observed for corn and wheat tests. The addition

    of 8 g of coffee powder as a beverage to meal 3 for rice test Differences in percentage of soluble iron are not statisticallysignificant between ferrous fumarate and ferrous sulfate for the(0.58 mmol b-carotene) and meal 4 for corn and wheat tests

    (1.53 and 2.06 mmol b-carotene, respectively) (Table 4), pro- same content of vitamin A or b-carotene, except for 0.55mmol vitamin A or 0.85 mmol b-carotene (P 0.05).duced no difference in iron absorption compared with meals

    with lower or higher content ofb-carotene and without coffee, It was not possible to observe an effect of vitamin A or b-carotene on iron solubility for EDTA and Ferrochel becausebut the values were still significantly higher than those ob-tained when the meal alone was consumed. iron is 100% soluble at pH 6 without any vitamin addition.

    Iron solubility with pH changes. Changes in iron solubil-ity when pH is raised from 2 to 6 in presence of vitamin A DISCUSSIONare shown in Table 5. For ferrous fumarate, pH increase pro-duced a 75% decrease in iron solubility. However, when vita- Vitamin A content is reduced to less than half during cook-

    ing procedures, but this amount of vitamin A significantlymin A was added and the pH raised to 6, iron solubility in-

    TABLE 6

    Effects ofb-carotene content and pH on in vitro iron solubility

    Ferrous fumarate Ferrous sulfate

    pH b-Carotene2 Fe Soluble iron Fe Soluble iron

    mmol mg % mg %

    2 3.78 { 0.1d 100 { 2.6 6.25 { 0.1e 100 { 1.66 0.99 { 0.1a 26.2 { 2.6 2.24 { 0.3a 35.8 { 4.86 0.85 (500) 1.00 { 0.2a 26.5 { 5.3 2.57 { 0.1a 41.1 { 1.66 1.70 (1000) 1.96 { 0.1b 51.9 { 2.6 3.17 { 0.2b 50.7 { 3.26 2.55 (1500) 3.18 { 0.1c 84.1 { 2.6 3.57 { 0.2c 57.1 { 3.26 3.40 (2000) 3.54 { 0.1d 93.7 { 2.6 4.96 { 0.1d 79.4 { 1.66 5.10 (3000) 3.81 { 0.1d 100 { 2.6 5.74 { 0.1e 91.8 { 1.6

    1 Values are means { SEM, n 5. Values in a column with dissimilar letters are significantly different, P 0.05. Initial iron content: 5 mg.2 Values in parentheses are in IU.

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    Covenin, N. V. de A. (1989) Determinacion de vitamina A. Caracas, Verezuela.increased iron absorption from rice, corn and wheat mealsDern, J. R. & Hart, W. L. (1961a) Studies with doubly labeled iron. I. Simultane-compared with these meals given alone. It also shows that the

    ous liquid scintillation counting isotopes of 55Fe and 59Fe as ferrous perchlo-increase in doses from 0.37 to 2.78 mmol (338 to 2526 IU) did rate. J. Lab. Clin. Med. 57: 322330.

    Dern, J. R. & Hart, W. L. (1961b) Studies with doubly labeled iron. II.Separationnot produce any further significant increase.of iron from blood samples and preparation of ferrous perchlorate for liquidb-carotene has the same effect on iron absorption thanscintillation counting. J. Lab. Clin. Med. 57: 460467.

    vitamin A. In the case of rice meal, it was shown that 0.95 Flowers, C. A., Kuizon, M., Beard, S. L., Skikne, B. S., Covell, A. & Cook, J. D.(1986) A serum ferritin assay for prevalence studies of iron deficiency. Am.mmol (558 IU) ofb-carotene increases iron absorption moreJ. Hematol. 23: 141151.than threefold compared with the meal given alone. Absorp-

    GarcBa-Casal, M. & Layrisse M. (1996) Fortificacion del hierro de los alimentostion from the other two cereals showed similar behavior. It

    y su impacto sobre la deficiencia de hierro. In: Anemia por deficiencia dehierro en la region Andina. Definicion y estrategias de intervencion (Berger,seems that b-carotene also prevents the inhibitory effect ofJ., San Miguel, J., Arze, R., Fernandez, E., and Aguanyo, V., eds) pp 193polyphenols on iron absorption. When coffee was administered200. Orstom, La Paz, Bolivia.

    with the test meals containing b-carotene, iron absorption did Haug, W. & Lantzsch, H. J. (1983) Sensitive method for the rapid deter mina-tion of phytate in cereals and cereal products. J. Sci. Food. Agric. 34: 1423not show a significant decrease as expected. On the contrary,1426.it increased from one- to twofold compared with the meal

    Hodges, R., Sauberlich, H., Ganham, J., Wallace, D., Rucker, R., MejBa, L. &without b-carotene or coffee. Mohanram, M. (1978) Hematopoietic studies in vitamin A deficiency. Am.

    Solubility tests demonstrated that vitamin A and b-caro- J. Clin. Nutr. 31: 876885.International Committeefor Standardizationin Hematology (1978) Recommen-tene are capable of solubilizing iron at pH 6. It seems that b-

    dation for measurement of serum iron in human blood. Br. J. Haematol. 38:carotene is more efficient that vitamin A at least for ferrous291294.

    fumarate. This is may be due to a greater stability ofb-carotene International Committee for Standardization in Hematology (1978) The mea-surement of total and saturated iron-binding capacity in serum. Br. J. Haema-to storage, handling and pH changes.tol. 38: 281290.Results from solubility experiments as well as human ab-

    Layrisse, M., Chaves, J. F., Mendez-Castellano, H., Bosch, V., Tropper, E., Bas-sorption studies show an important role for vitamin A and b- tardo, B. & Gonzalez E. (1996) Early response to the impact of iron fortifi-

    cation in the Venezuelan population. Am. J. Clin Nutr. 64: 903907.carotene in improving iron absorption especially from foodsLayrisse, M. & GarcBa-Casal, M. (1997) Strategies for the prevention of iron

    with a high content of inhibitors, which are the staple foods deficiency through foods in the household. Taller: desnutricion oculta en Lat-of many countries worldwide. inoamerica. Deficiencia de Hierro. CESNI, Nutr. Rev. 55: 233239.Layrisse, M. & GarcBa, M. N. La respuesta a la fortificacion con hierro en la pobla-The unexpected behavior of vitamin A and b-carotene of

    cion venezolana. Revista de Salud Publica de Mexico (in press).improving iron absorption requires further studies to discoverLayrisse, M., GarcBa-Casal. M., Solano, L., Baron, M., Arguello, F., Llovera, D.,

    the mechanism for this peculiar reaction. A previous publica- RamBrez, J., Leets, I. & Tropper, E. (1997) The role of vitamin A on theinhibitors of nonheme iron absorption: preliminary results, J. Nutr. Biochem.tion (Layrisse et al. 1997) showed that spectrophotometric8: 6167.results, elution patterns from high-performance liquid chroma-

    MejBa, L. A. (1986) Ladeficiencia de lavitaminaA como factord anemianutrici-tography (HPLC) and solubility of iron with vitamin A at pH 6 onal. In: Vitaminas, agentes nutritivos y terapeuticos. (C. Rozo and M Ma-suggest that vitamin A binds iron liberated during the digestive mome., eds.), pp. 6574. Ediciones Doyoma S.A. Barcelona, Spain.

    MejBa, L. and Arroyave, G. (1982) The effect of vitamin A fortification of sugarprocess and forms a complex that acts as chelating agent pre-on iron metabolism in preschool children in Guatemala. Am. J. Clin. Nutr. 36:venting the inhibitory effect of phytates and polyphenols on8793.

    nonheme iron absorption. This hypothesis agrees with the MejBa, L. A. & Chew, V. (1988) Hematological effect of supplementing iron withvitamin A alone and in combination with iron. Am. J. Clin. Nutr. 48: 595600.results of Mejia (1986), who demonstrated interactions be-

    Mejia, L. A., Hodges, E. & Rucker R. B. (1979) Role of Vitamin A in the absorp-tween vitamin A and iron metabolisms. It also supported thetion, retention and distribution of iron in the rat. J. Nutr. 109: 129137.

    dramatic reduction of the prevalence of iron deficiency after Nadler, S. B., Hidalgo, J. U. & Bloch, T. (1962) The Tulane table of blood vol-ume in normal men. Surgery (St Louis) 51: 224232.1 y of an iron-fortification program in Venezuelan population,

    Olson, J. (1984) Vitamin A. In: Handbook of Vitamins. Nutritional, Biochemicalin which one food vehicle, precooked corn flour, was fortifiedand Clinical Aspects (Machlin, L. J., ed.), vol. 28, pp. 145. Marcel Dekker,

    with vitamin A (Layrisse et al. 1996). New York, NY.Price, M. L. & Butler, L. (1977) Rapid visualestimation and spectrophotometricBecause iron and vitamin A deficiencies are the two main

    determination of tannin content of sorghum grain. J. Agric. Food. Chem. 25:deficiencies in many developing populations (Bloem et al.12681273.

    1989, MejBa and Arroyave 1982), it is recommended that both Roche Laboratories (1994). b-Carotene. In: Vitamins. Basics. Basel, Switzerland.F. Hoffmann-La Roche, pp. 58.micronutrient should be used in fortification programs.

    Strohecker, R. & Heming, H. (1965) Vitamins assay test method. Verlag Chem.CMBV, Weinheim.

    Strohecker, R. & Heming, H. (1967) Analisis de vitaminas (Paz, ed.). pp. 73LITERATURE CITED79. Montalvo, Madrid, Spain.

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