A complete diet-based algorithm for predicting nonheme iron absorption in adults.

Many algorithms have been developed in the past few decades to estimate nonheme iron absorption from the diet based on single meal absorption studies. Yet single meal studies exaggerate the effect of diet and other factors on absorption. Here, we propose a new algorithm based on complete diets for estimating nonheme iron absorption. We used data from 4 complete diet studies each with 12-14 participants for a total of 53 individuals (19 men and 34 women) aged 19-38 y. In each study, each participant was observed during three 1-wk periods during which they consumed different diets. The diets were typical, high, or low in meat, tea, calcium, or vitamin C. The total sample size was 159 (53 × 3) observations. We used multiple linear regression to quantify the effect of different factors on iron absorption. Serum ferritin was the most important factor in explaining differences in nonheme iron absorption, whereas the effect of dietary factors was small. When our algorithm was validated with single meal and complete diet data, the respective R(2) values were 0.57 (P < 0.001) and 0.84 (P < 0.0001). The results also suggest that between-person variations explain a large proportion of the differences in nonheme iron absorption. The algorithm based on complete diets we propose is useful for predicting nonheme iron absorption from the diets of different populations.

Iron deficiency and overload.

In the past seven years numerous genes that influence iron homeostasis have been discovered. Dr. Beutler provides a brief overview of these genes, genes that encode HFE, DMT-1, ferroportin, transferrin receptor 2, hephaestin, and hepcidin to lay the groundwork for a discussion of the various clinical forms of iron storage disease and how they differ from one another. In Section I, Dr. Beutler also discusses the types of hemochromatosis that exist as acquired and as hereditary forms. Acquired hemochromatosis occurs in patients with marrow failure, particularly when there is active ineffective erythropoiesis. Hereditary hemochromatosis is most commonly due to mutations in the HLA-linked HFE gene, and hemochromatosis clinically indistinguishable from HFE hemochromatosis is the consequence of mutations in three transferrin receptor-2 gene. A more severe, juvenile form of iron storage disease results from mutations of the gene encoding hepcidin or of a not-yet-identified gene on chromosome 1q. Autosomal dominant iron storage disease is a consequence of ferroportin mutations, and a polymorphism in the ferroportin gene appears to be involved in the African iron overload syndrome. Evidence regarding the biochemical and clinical penetrance of hemochromatosis due to mutations of the HFE gene is rapidly accumulating. These studies, emanating from several centers in Europe and the United States, all agree that the penetrance of hemochromatosis is much lower than had previously been thought. Probably only 1% of homozygotes develop clinical findings. The implications of these new findings for the management of hemochromatosis will be discussed. In Section II, Dr. Victor Hoffbrand discusses the management of iron storage disease by chelation therapy, treatment that is usually reserved for patients with secondary hemochromatosis such as occurs in the thalassemias and in patients with transfusion requirements due to myelodysplasia and other marrow failure states. Tissue iron can be estimated by determining serum ferritin levels, measuring liver iron, and by measuring cardiac iron using the MRI-T2* technique. The standard form of chelation therapy is the slow intravenous or subcutaneous infusion of desferoxamine. An orally active bidentate iron chelator, deferiprone, is now licensed in 25 countries for treatment of patients with thalassemia major. Possibly because of the ability of this compound to cross membranes, it appears to have superior cardioprotective properties. Agranulocytosis is the most serious complication of deferiprone therapy and occurs in about 1% of treated patients. Deferiprone and desferoxamine can be given together or on alternating schedules. A new orally active chelating agent ICL 670 seems promising in early clinical studies. In Section III, Dr. James Cook discusses the most common disorder of iron homeostasis, iron deficiency. He will compare some of the standard methods for identifying iron deficiency, the hemoglobin level, transferrin saturation, and mean corpuscular hemoglobin and compare these with some of the newer methods that have been introduced, specifically the percentage of hypochromic erythrocytes and reticulocyte hemoglobin content. The measurement of storage iron is achieved by measuring serum ferritin levels. The soluble transferrin receptor is a truncated form of the cellular transferrin receptor and the possible value of this measurement in the diagnosis of iron deficiency will be discussed. Until recently iron dextran was the only parental iron preparation available in the US. Sodium ferric gluconate, which has been used extensively in Europe for many years, is now available in the United States. It seems to have a distinct advantage over iron dextran in that anaphylactic reactions are much less common with the latter preparation.

Regular consumption of NaFeEDTA-fortified fish sauce improves iron status and reduces the prevalence of anemia in anemic Vietnamese women.

BACKGROUND: Fish sauce is consumed daily by a large proportion of the Vietnamese population and could therefore be a potentially useful food vehicle for iron-fortification programs. OBJECTIVE: We evaluated the efficacy of iron-fortified fish sauce in improving the iron status of anemic women. DESIGN: In a randomized, double-masked study of 152 anemic (hemoglobin concentration of 81-119 g/L) women, a meal based on noodles or rice was served 6 d/wk with 10 mL fish sauce containing either 10 mg Fe as NaFeEDTA (iron-fortified group) or no added iron (control group). Concentrations of hemoglobin, serum ferritin (SF), and serum transferrin receptor (TfR) were measured at baseline and after 3 and 6 mo. RESULTS: After 6 mo, hemoglobin and SF concentrations were higher and TfR concentrations were lower in the iron-fortified group than in the control group [hemoglobin: 116.3 +/- 8.7 ( +/- SD) compared with 107.6 +/- 11.0 g/L (P < 0.0001); SF: 30.9 (95% CI: 23.4, 40.6) compared with 14.6 (11.3, 19.0) micro g/L (P = 0.0002); TfR: 7.2 (6.4, 7.9) compared with 9.0 (8.1, 9.9) mg/L (P = 0.002)]. The prevalence of iron deficiency (SF < 12 micro g/L or TfR > 8.5 mg/L) and iron deficiency anemia (iron deficiency with hemoglobin < 120 g/L) was lower in the iron-fortified group than in the control group [32.8% compared with 62.5% (P = 0.0005) and 20.3% compared with 58.3% (P < 0.0001), respectively]. CONCLUSIONS: Regular consumption of iron-fortified fish sauce significantly reduced the prevalence of iron deficiency anemia in Vietnamese women during the 6-mo intervention. Fortifying fish sauce with iron by using a water-soluble, highly bioavailable compound (NaFeEDTA) is a promising strategy for combating iron deficiency anemia in Vietnam.

Degradation of phytic acid in cereal porridges improves iron absorption by human subjects.

BACKGROUND: Phytic acid in cereal-based and legume-based complementary foods inhibits iron absorption. Low iron absorption from cereal porridges contributes to the high prevalence of iron deficiency in infants from developing countries. OBJECTIVE: The objective was to measure the influence of phytic acid degradation on iron absorption from cereal porridges. DESIGN: An exogenous phytase was used to fully degrade phytic acid during the manufacture of 9 roller-dried complementary foods based on rice, wheat, maize, oat, sorghum, and a wheat-soy blend. Iron absorption from the phytate-free and native phytate porridges prepared with water or milk (wheat only) was measured in adult humans with an extrinsic-label radioiron technique. Ascorbic acid was added to some porridges. RESULTS: When the foods were reconstituted with water, dephytinization increased iron absorption from rice porridge from 1.73% to 5.34% (P < 0.001), from oat from 0.33% to 2.79% (P < 0.0001), from maize from 1.80% to 8.92% (P < 0.0001), from wheat from 0.99% to 11.54% (P < 0.0001), from the wheat-soy blend without ascorbic acid from 1.15% to 3.75% (P < 0.005), and from the wheat-soy blend with ascorbic acid from 2.40% to 8.46% (P < 0.005). Reconstituting wheat porridge with milk instead of water markedly decreased or completely removed the enhancing effect of dephytinization on iron absorption in the presence and absence of ascorbic acid. Dephytinization did not increase iron absorption from high-tannin sorghum porridge reconstituted with water but increased iron absorption from low-tannin sorghum porridge by approximately 2-fold (P < 0.01). CONCLUSIONS: Phytate degradation improves iron absorption from cereal porridges prepared with water but not with milk, except from high-tannin sorghum.

The quantitative assessment of body iron.

Current initiatives to reduce the high prevalence of nutritional iron deficiency have highlighted the need for reliable epidemiologic methods to assess iron status. The present report describes a method for estimating body iron based on the ratio of the serum transferrin receptor to serum ferritin. Analysis showed a single normal distribution of body iron stores in US men aged 20 to 65 years (mean +/- 1 SD, 9.82 +/- 2.82 mg/kg). A single normal distribution was also observed in pregnant Jamaican women (mean +/- 1 SD, 0.09 +/- 4.48 mg/kg). Distribution analysis in US women aged 20 to 45 years indicated 2 populations; 93% of women had body iron stores averaging 5.5 +/- 3.35 mg/kg (mean +/- 1 SD), whereas the remaining 7% of women had a mean tissue iron deficit of 3.87 +/- 3.23 mg/kg. Calculations of body iron in trials of iron supplementation in Jamaica and iron fortification in Vietnam demonstrated that the method can be used to calculate absorption of the added iron. Quantitative estimates of body iron greatly enhance the evaluation of iron status and the sensitivity of iron intervention trials in populations in which inflammation is uncommon or has been excluded by laboratory screening. The method is useful clinically for monitoring iron status in those who are highly susceptible to iron deficiency.

The usefulness of elemental iron for cereal flour fortification: a SUSTAIN Task Force report. Sharing United States Technology to Aid in the Improvement of Nutrition.

Fortification of cereal flours may be a useful public health strategy to combat iron deficiency. Cereal flours that are used shortly after production (e.g., baking flour) can be fortified with soluble iron compounds, such as ferrous sulfate, whereas the majority of flours stored for longer periods is usually fortified with elemental iron powders to avoid unacceptable sensory changes. Elemental iron powders are less well absorbed than soluble iron compounds and they vary widely in their absorption depending on manufacturing method and physicochemical characteristics. Costs vary with powder type, but elemental iron powders are generally less expensive than ferrous sulfate. This review evaluates the usefulness of the different elemental iron powders based on results from in vitro studies, rat assays, human bioavailability studies, and efficacy studies monitoring iron status in human subjects. It concludes that, at the present time, only electrolytic iron powder can be recommended as an iron fortificant. Because it is only approximately half as well absorbed as ferrous sulfate, it should be added to provide double the amount of iron.