Dietary Iron and Colorectal Cancer Risk: A Review of Human Population Studies

Iron is an essential micronutrient that is involved in many redox processes and serves as an integral component in various physiological functions. However, excess iron can cause tissue damage through its pro-oxidative effects, potentiating the development of many diseases such as cancer through the generation of reactive oxidative species. The two major forms of iron in the diet are heme and nonheme iron, both of which are found in several different foods. In addition to natural food sources, intake of nonheme iron may also come from fortified foods or in supplement form. This review summarizes the results of human population studies that have examined the role of dietary iron (heme and nonheme), heme iron alone, and iron from supplements in colorectal carcinogenesis.     

HEME IRON RELATIVE TO TOTAL DIETARY INTAKES OF IRON — REVIEW

Iron deficiency is a common nutritional anomaly encountered in surveys in diverse populations throughout the world. Etiological factors, including gastrointestinal disorders such as gastric ulcers or ulcerative colitis have a significant effect on and may cause this nutritional disorder. Research has indicated that dietary iron is found predominantly as either heme (absorbable) iron or as nonheme (less readily absorbable) iron. The absorption of nonheme iron is enhanced by the presence, in the diet, of certain factors, mainly ascorbic acid and meat, fish or poultry. Certain inhibitors and their effects have also been identified. Understanding the mechanism and regulation of intestinal iron absorption and the relationship to absorbable iron versus total iron intakes is of importance. This paper includes a review of the following information: food sources of both types of iron; factors affecting absorption — enhancers and inhibitors; and physiological states affecting iron absorption. Meats serve as a source of heme iron as well as having a promoting effect on absorption of nonheme iron.     

Measurement and Content of Nonheme and Total Iron in Muscle

A method for determining the nonheme iron content of meats was evaluated and used to determine the nonheme and heme iron content of selected muscles from beef, pork, and lamb. The method allows a quantitative determination of nonheme iron in meat and is influenced to only a minor degree by the presence of heme iron. Heating meat in a boiling water bath increased the nonheme iron content of the meat. Possibly, heating accelerates oxidative cleavage of the prophyrin ring thereby allowing release of the iron from the heme complex. Total iron content differed between muscles in pork and beef but not in lamb. Heme iron, expressed as percent of the total iron, in raw pork, lamb, and beef average 49, 57, and 62%, respectively.     

Heating and the Distribution of Total and Heme Iron Between Meat and Broth

The effect of heat on movement of total and heme iron from meat to broth was investigated. Total iron by a wet ash method was nearly identical to the sum of heme iron plus nonheme iron. The total amount of nonheme iron increased with cooking temperature (r = 0.98), as did the amount of nonheme iron in the broth (r = 0.93). Leaching of heme pigments into the broth was greatest at 60°C. Boiling (97°C) rapidly coagulated the meat pigments and minimized the leaching of heme pigments into the broth. More total iron (85.3%) was retained in boiled (97°C) meat than in meat heated 1 hr at 60°C (81.6%), 77°C (78.2%) or autoclaved (77.5%).     

Endogenous Factors Affecting Oxidative Stability of Beef Loin, Pork Loin, and Chicken Breast and Thigh Meats

ABSTRACT:  The susceptibility of meats from different animal species (chicken breast [CB] and thigh [CT], pork [PL], and beef [BL]) to lipid oxidation was studied. The amounts of TBARS in raw PL, CB, and CT did not change during a 7-d storage period. TBARS values of raw BL, however, significantly increased during 7-d storage because of high heme iron content, high lipoxygenase-like activities, and low 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities. Ferric ion reducing capacities (FRC) were detected in all raw meats, but their characteristics were different: storage-unstable in CB and CT and storage-stable in PL and BL. Ferric ion reducing capacities in raw CB and CT was higher than those of PL and BL, and could be related to their high oxidative stability. The TBARS values of cooked meat increased significantly with storage. The rates of TBARS increase in cooked CT and BL were significantly higher than those of cooked CB and PL after a 7-d storage. Nonheme iron content in cooked BL was higher than other meats and increased significantly after 7 d. Cooked BL had a higher amount of heat-stable FRC, which acted as a prooxidant in the presence of high free ionic irons, than other meats. Therefore, high heat-stable FRC and increased nonheme iron content in cooked BL were responsible for its high susceptibility to lipid oxidation. Despite relatively low nonheme iron and heat-stable FRC levels, cooked CT showed similar levels of TBARS to cooked BL after a 7-d storage because of its high PUFA content.     

Iron bioavailability in iron-fortified cereal foods: The contribution of in vitro studies

Iron deficiency anemia is the most common nutritional deficiency in humans. Not all dietary ingested iron, heme or nonheme, will be available to absorption and negative imbalance between iron requirements and absorption leads to iron deficiency and/or anemia. The recommended iron values usually are based on the genetic and on diet iron-bioavailability, which can be considered as the principal factor that change among the cultures and influences the distinct levels of recommendation among countries. Dietary changes present practical limitations due to be difficult to change food habits. The iron food fortification is considered more cost effective and economically more attractive than iron supplementation. There are many iron compounds available to be used in iron fortification. Cereals represent a target food group to iron fortification programs due to high consumption and the in vitro studies can be useful to estimate the relative iron bioavailability in large number of products in short time and with a low cost. Wheat flour baked into bread or not was the main product tested in in vitro bioavailability studies and ferrous sulfate was the principal iron compound used in the fortification studies. However, iron bioavailability from ferrous sulfate is lower than from other compounds, such FeNaEDTA or ferric pyrophosphate. The variables level of fortification, storage, level of extraction, baking and also the association or not with other chemical compound seems to influence the results obtained.     

芹菜叶绿素铁钠与其他补血药物功效的比较研究

目的：探讨芹菜叶绿素铁钠与其他补血剂对大鼠缺铁性贫血的效果。方法：采用低铁饲料建立大鼠缺铁性贫血(IDA)模型,给予叶绿素铁钠、血红素铁、NaFeEDTA和FeSO4,通过测定大鼠血液指标血红蛋白(Hb)含量、红细胞(RBC)数和红细胞压积(HCT),观察补血疗效。结果：在实验30d时,与模型组和FeSO4组相比,叶绿素铁钠组的Hb、RBC、HCT显著增加(P＜0.05);与血红素铁组和NaFeEDTA组相比,差异不显著。结论：芹菜叶绿素铁钠对治疗实验贫血鼠有明显的效果。     

Lipid Stability of Beef Model Systems with Heating and Iron Fractions

Catalytic effects of different temperatures (55, 70, 85, and 100°C) on lipid oxidation were studied in aqueous- and chloroform/methanol-extracted beef model lipid systems containing iron forms inherent in beef (water-extractable, diffusate, nondiffusate, ferritin, myoglobin, hemoglobin), hematin, FeCl₂, or FeCl₃. Heating increased thiobarbituric acid and peroxide values in both systems. All forms of iron catalyzed lipid oxidation in aqueous systems, with greatest oxidation by heme and low molecular weight iron fractions. Oxidation in lipid extracts was not increased by ferritin, FeCl₂, or FeCl₃, but heme iron was the major oxidation catalyst. Lipid stability decreased with addition of any iron forms inherent in beef or with increased heating, which helps understanding of rapid oxidation of meat during refrigerated storage or after cooking.     

Modification of the Schricker Nonheme Iron Method to Minimize Pigment Effects for Red Meats

A calorimetric nonheme iron assay procedure for meat was modified to avoid pigment effects in determining the nonheme iron content of red meats. The modification consisted of mixing the red meat sample with NaNO₂ before incubation with an acid mixture to minimize the breakdown of heme pigments into nonheme iron, and inclusion of a second blank for the brownish color of the incubated liquid phase, in addition to the reagent blank.     

Some Factors Influencing the Nonheme Iron Content of Meat and Its Implications in Oxidation

Three different methods for determining nonheme iron content of meat extracts which differed in final pH and either in heating or not heating of the samples, were compared. The final pH of meat extracts had little effect on the level of nonheme iron but heating gave higher values. Both final temperature and rate of heating influenced release of nonheme iron from meat pigment extracts, with the optimum temperature being 63-70°C. Slow heating resulted in release of more noneheme iron than fast heating. Nitrite was shown to prevent release of heme iron, apparently through stabilizing the porphyrin ring. Sources of nonheme iron and their relationship to oxidation in cooked meat are discussed.     

Iron bioavailability from Amaranthus species: 1—In vitro dialysable iron for estimation of genetic variation

Green leafy vegetables have the potential to contribute significant amounts of iron to the diet, if the bioavailability of iron from these foods is improved. In order to determine the potential for genetic manipulation of this trait, 46 lines from 12 species of Amaranthus were evaluated for total and bioavailable iron in greenhouse and field experiments. Bioavailable iron was estimated using an in vitro assay for dialysable, low-molecular-weight iron compounds. Significant differences (P < 0·01) were detected among lines and species for total and bioavailable iron. Total iron ranged from 358 to 880 ppm (dry weight) in field-grown plants and 55 to 123 ppm (dry weight) in greenhouse-grown plants. Bioavailable iron ranged from 41 to 63 ppm in field-grown plants and from 24 to 51 ppm in greenhouse-grown plants. Amaranthus tricolor and A lividus had the highest total and bioavailable iron; A hypochondriacus had the lowest levels of the species tested. Although field-grown Amaranthus accumulated higher levels of total and bioavailable iron, a greater proportion of the total iron was sequestered in insoluble, unavailable forms. Generally, species with higher total iron had higher levels of bioavailable iron. These analyses indicated potential for genetic improvement of iron nutritional quality from Amaranthus, especially within the species A tricolor. © 1998 Society of Chemical Industry     

Post-translational modifications of the AFET3 gene product: a component of the iron transport system in budding cells and mycelia of the yeast Arxula adeninivorans

The yeast Arxula adeninivorans is characterized by a temperature-dependent dimorphism. A. adeninivorans grows as budding cells at temperatures up to 42 degrees C, but forms mycelia at higher temperatures. A strong correlation exists between morphological status and iron uptake, achieved by two transport systems that differ in iron affinity. In the presence of high Fe(II) concentrations (>2 microm), budding cells accumulate iron concentrations up to seven-fold higher than those observed in mycelia, while at low Fe(II) concentrations (<2 microm), both cell types accumulate similar amounts of iron. The copper-dependent Fe(II) oxidase Afet3p, composed of 615 amino acids, is a component of the high-affinity iron transport system. This protein shares a high degree of homology with other yeast iron transport proteins, namely Fet3p of Saccharomyces cerevisiae, Cafet3p of Candida albicans and Pfet3p of Pichia pastoris. Expression of the AFET3 gene is found to be strongly dependent on iron concentration but independent of the morphological stage; however, cell morphology was found to influence post-translational modifications of the gene product. O-glycosylation was observed in budding cells only, whereas N-glycosylation occurred in both cell types. The N-glycosylated 103 kDa glycoprotein matures into the 108.5 kDa form, further characterized by serine phosphorylation. Both N-glycosylation and phosphorylation occur at low iron concentrations (< or =5 microm). The mature Afet3p of 108.5 kDa is uniformly distributed within the plasma membrane in cells of both morphological stages.     

Bioactive dietary polyphenols inhibit heme iron absorption in a dose-dependent manner in human intestinal Caco-2 cells

Abstract: Although heme iron is an important form of dietary iron, its intestinal absorption mechanism remains elusive. Our previous study revealed that (‐)‐epigallocatechin‐3‐gallate (EGCG) and grape seed extract (GSE) markedly inhibited intestinal heme iron absorption by reducing the basolateral iron export in Caco‐2 cells. The aim of this study was to examine whether small amounts of EGCG, GSE, and green tea extract (GT) could inhibit heme iron absorption, and to test whether the inhibitory action of polyphenols could be offset by ascorbic acid. A heme‐⁵⁵Fe absorption study was conducted by adding various concentrations of EGCG, GSE, and GT to Caco‐2 cells in the absence and presence of ascorbic acid. Polyphenolic compounds significantly inhibited heme‐⁵⁵Fe absorption in a dose‐dependent manner. The addition of ascorbic acid did not modulate the inhibitory effect of dietary polyphenols on heme iron absorption when the cells were treated with polyphenols at a concentration of 46 mg/L. However, ascorbic acid was able to offset or reverse the inhibitory effects of polyphenolic compounds when lower concentrations of polyphenols were added (≤ 4.6 mg/L). Ascorbic acid modulated the heme iron absorption without changing the apical heme uptake, the expression of the proteins involved in heme metabolism and basolateral iron transport, and heme oxygenase activity, indicating that ascorbic acid may enhance heme iron absorption by modulating the intracellular distribution of ⁵⁵Fe. These results imply that the regular consumption of dietary ascorbic acid can easily counteract the inhibitory effects of low concentrations of dietary polyphenols on heme iron absorption but cannot counteract the inhibitory actions of high concentrations of polyphenols. Practical Application: Bioactive dietary polyphenols inhibit heme iron absorption in a dose‐dependent manner. The small amounts of polyphenolic compounds present in foods are capable of reducing heme iron transport across the intestinal enterocyte. However, the inhibitory effects of dietary polyphenolic compounds on heme iron absorption can be offset by ascorbic acid and can possibly be avoided by decreasing the consumption of polyphenols while simultaneously taking ascorbic acid.     

Free iron in pale, dark and alcohol-free commercial lager beers

BACKGROUND: A highly sensitive, selective, rapid, reliable and inexpensive method has been developed for the direct analysis of free iron in 40 samples of bottled lager beer. RESULTS: A differential pulse adsorptive stripping voltammetry technique at a hanging mercury drop electrode without any sample digestion was performed. The iron content in the analysed samples was in the range of 41 to 165 ppb. CONCLUSIONS: The results point out that dark beers keep the highest free iron concentrations, which may be related to the highest amounts of minor ingredients in dark beers. Meanwhile, alcohol‐free beers present the lowest free iron concentrations. Some discussion is presented regarding the basis of the free and complexed iron in beer and its participation as an essential element in the human diet. Copyright © 2011 Society of Chemical Industry     

Three Methods for Determining Nonheme Iron in Turkey Meat

The ferrozine, the Schricker and modified Schricker methods were used to measure the non-heme iron in raw and cooked turkey meat. The ferrozine method gave the lowest non-heme iron values, while results from the Schricker and modified Schricker were not different (p<0.05). When hemoglobin (Hb) was added to breast meat, how-ever, differences (p<0.05) between the Schricker and modified Schricker, and Schricker and ferrozine methods were observed in cooked meat with NaCl. Cooking and addition of NaCl caused increase in measured nonheme iron content and had a synergistic effect on the release of nonheme iron in meat.     

The relationship of red meat with cancer: Effects of thermal processing and related physiological mechanisms

Red meat is consumed globally and plays an important role in the Western diet. Its consumption is however linked with various types of diseases. This review focuses on the relationship of red meat with cancer, its dependency on the thermal processing methodology and the subsequent physiological effects. The epidemiological evidence is discussed, followed by introduction of the species that were hypothesized to contribute to these carcinogenic effects including polycyclic aromatic hydrocarbons (PAHs), heterocyclic amines (HCAs), N-nitroso compounds (NOCs), heme iron, and macromolecular oxidation products. Their carcinogenic mechanisms were then addressed with further emphasis on the involvement of inflammation and oxidative stress. The thermal processing dependency of the carcinogen generation and the partially elucidated carcinogenic mechanism both represent doorways of opportunities available for the scientific manipulation of their impact after human consumption, to minimize the cancer risks associated with red meat.     

Processing and Frozen Storage Effects on the Iron Content of Cod and Mackerel

Processing and subsequent frozen storage affected the iron content of cod (Gadus morhua) and mackerel (Scomber scombrus) muscle tissue. Frame mince was obtained from the bone rack, without the head or viscera remaining, after filleting. Frame mince had significantly higher iron levels than intact fillets with or without skin or fillets that were subsequently minced. Skin-on fillets had more iron than skin-off fillets. Cod frame mince had about 50% heme iron, while mackerel frame mince ranged from 20-64%. Nonheme iron increased during frozen storage due to heme breakdown. Storage above ?14°C was more deleterious to the heme molecule than lower temperatures (?20°C or ?40°C).     

Effect of Cabbage Phospholipase D Treatment on the Oxidative Stability of Beef Homogenate and Egg Yolk Phosphatidylcholine Liposomes

The possibility that enzymatic hydrolysis of phospholipids increases the oxidative stability of muscle food was examined using cabbage phospholipase D (PLD). As judged by the amounts of thiobarbituric acid‐reactive substances and carbonyl content, treatment of meat homogenate with 500 ppm (840 units) PLD increased its oxidative stability during storage at 4°C for 7 d, as compared to the nontreated ones. The thin‐layer chromatographic analysis confirmed the formation of phosphatidic acid (PA) in the 500 ppm (840 units) cabbage PLD‐treated samples. In a nonheme and heme iron‐induced lipid oxidation of egg yolk phosphatidylcholine liposomes, cabbage PLD treatment also improved their oxidative stability. Cabbage PLD treatment is, therefore, likely to improve the oxidative stability of meat homogenate via PA generation.     

生物态补铁剂-血红素铁研究进展

血红素铁是一种生物态铁,可直接被肠粘膜细胞吸收,不产生任何消化道刺激症状,生物利用率高,是理想补铁剂。该文综述血红素铁结构与性质、功能、提取、测定方法和在食品工业中应用情况。     

Total Heme and Non-heme Iron in Raw and Cooked Meats

ABSTRACT: This study provides data on the total heme and non-heme iron contents in poultry (chicken, turkey), beef, veal, lamb, horse, ostrich, rabbit, and pork meat cuts. The effect of cooking on heme iron content was also studied. Total iron and heme iron contents markedly differed between muscles in poultry. Heme iron in red meats ranged from 72 to 87%. Heme iron in rabbit and pork was 56 and 62% of total iron. Heating decreased heme iron, the severity of the losses depended on cooking methods: in poultry, losses ranged from 22 to 43%; less severe impact was detected in pan-cooked meat, where the losses ranged from 1 to 24%.