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The apical divalent metal transporter 1 (DMT1) and the iron exporter ferroportin 1 (FPN1) are responsible for the absorption of iron and other divalent metals (manganese, lead, and cadmium). Thus, an iron-deficient diet can lead to excess absorption of manganese, lead, and cadmium, and high blood concentrations of these metals. Relative to males, females of childbearing age have higher blood concentrations of manganese because of their lower blood concentrations of ferritin. Moreover, relative to premenopausal women, menopausal women have lower blood manganese levels because their higher concentrations of ferritin. There is also a significant increase in the whole blood manganese level throughout pregnancy due to the upregulation of iron absorption at this time. Several previous studies reported a temporal relationship between iron deficiency and increased blood lead concentrations in children. However, this association does not occur in postmenarcheal or postmenopausal women because estrogen promotes bone mineralization and redistributes blood lead into the bone, overshadowing the effect of ferritin on blood lead level. Although blood cadmium concentrations are higher in females of childbearing age because of their lower ferritin concentrations, there is no association of blood cadmium and iron levels in infants and postmenopausal women.
Departments of Occupational and Environmental Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
*Address all correspondence to: yanghokm@ulsan.ac.kr
1. Introduction
Iron deficiency affects approximately one-third of the world’s population, and is the most common nutritional deficiency [1]. Iron deficiency is most common in rapidly growing children (aged 6 months to 3 years) who have inadequate intake of dietary iron [2]. Iron deficiency is the only micronutrient deficiency that also has a high prevalence in virtually all developed countries [3].
Toxic metals, such as manganese, lead, and cadmium, have become ubiquitous in the developed world, and general populations are increasingly exposed to these metals. Inhalation of toxic metals is the most common route of exposure in environmental and occupational settings [4]; food intake is the major source of exposure in general populations and in children, who are more vulnerable to toxic metals absorbed through the intestine [5]. The mechanisms of iron absorption are similar to those of other divalent metals [6, 7, 8, 9, 10, 11], and an iron-deficient diet can lead to excess absorption of manganese [12, 13, 14], lead [15, 16, 17], and cadmium [18, 19, 20].
The gastrointestinal absorption of these divalent metals appears to be mediated by intestinal iron transporters, such as apical divalent metal transporter 1 (DMT1), which also mediates the uptake of other divalent metals [21]. There is up-regulation of DMT1 in the presence of low iron stores [22], and this explains the increased uptake of divalent metals [13, 14] and the higher blood concentrations of these metals in iron-deficient individuals. New evidence indicates that the iron exporter ferroportin 1 (FPN1) also transports these divalent metal ions [8, 9, 10, 11]. Thus, the major transporters responsible for the absorption of nonheme iron, apical DMT1 and the FPN1, also function in the absorption of divalent toxic metal ions.
Elevated levels of manganese, lead, and cadmium may adversely affect neurodevelopment, cognitive and motor development, and behavioral development in children [23]. Iron deficiency in children may lead to cognitive impairment, caused by the deficiency of iron itself or by the increased levels of these toxic metals (Figure 1). Therefore, decreased levels of iron, combined with increased levels of cadmium, manganese, or lead, have major effects on the neurodevelopment of children [24].
Figure 1.
The direct and indirect effect of iron deficiency on neurodevelopment in children.
2. Effect of iron deficiency on blood concentrations of manganese, lead, and cadmium
2.1. Manganese
Manganese is a naturally occurring element that is abundant in the environment. It is also an essential dietary nutrient, and the body requires specific concentrations for proper function. More specifically, at the physiological level, manganese functions in bone formation, protein and energy metabolism, and metabolic regulation; at the molecular level, it functions as a cofactor for a number of enzymes [25]. Because manganese is an essential element, homeostatic mechanisms regulate its absorption, disposition, and biliary excretion [25]. These homeostatic processes also play important roles in manganese toxicokinetics, which differ from those of nonessential toxic metals, such as lead and cadmium. Inhalation is the most common route of adult manganese exposure in environmental and occupational settings [25], whereas food is the major source of absorbed manganese in children, who are more vulnerable than adults to manganese due to higher intestinal absorption rate. Another source is the presence of a portal systemic shunt due to liver cirrhosis, which impairs the clearance of manganese through biliary excretion [25]. Blood manganese concentration appears to be related to manganese body burden on a group basis [25]. Chronic occupational exposure to manganese can cause a neurologic impairment known as “manganism,” a motor disorder with some similarities to idiopathic Parkinson’s disease in adults [25]. Recently, manganese excess have been reported to be associated with neurodevelopmental deficits, reduced IQ, and increased risk of behavioral problems, and attention deficit hyperactivity disorder in children [26].
Animal and human studies have demonstrated that iron deficiency markedly enhances intestinal absorption of manganese [12, 13]. DMT1 and FPN1 are responsible for the absorption of iron and other essential divalent metals, particularly manganese. Thus, an iron-deficient diet can lead to excess absorption of manganese; therefore, iron deficiency can be a risk factor for the accumulation of toxic levels of manganese in the central nervous system [27].
Previous studies have shown that iron deficiency leads to increased blood manganese concentrations in adults and children [14, 28, 29]. We recently showed that blood manganese levels are also elevated in iron-deficient infants [30]. After iron therapy, the blood manganese levels of iron-deficient infants declined significantly relative to their pretherapy levels (2.045 vs. 2.971 μg/dL), and their hemoglobin and ferritin levels increased significantly. Females of childbearing age have reduced concentrations of ferritin, and therefore increased levels of blood manganese relative to males [14, 31, 32, 33] and relative to menopausal women (who have higher levels of ferritin) [33] (Figure 2). Previous research reported significant increases in the whole blood manganese levels throughout pregnancy [34, 35, 36, 37, 38] (Table 1). This may be related to the enhanced absorption of manganese due to upregulation of iron absorption, particularly during the late periods of pregnancy [39], because the mechanisms of iron and manganese absorption are similar.
Figure 2.
Changes in blood manganese levels according to sex, age, and menstrual status.
Variables
No. (n)
Study subjects and findings
Sex
(n = 2005)
Korean general population 20 y or more; KNHANES 2008/GM of blood Mn in female vs. male: 1.403 vs. 1.192 μg/dL* [14]
(n = 297)
Canadian general population/GM of blood Mn in female vs. male: 0.750 vs. 0.675 μg/dL* [31]
(n = 7720)
USA general population (NHANES 2010–2011)/GM of blood Mn in female vs. male: 0.99 vs. 0.87 μg/dL* [32]
Menopause
(n = 1826)
Korean general population KNHANES 2008–2009/GM of blood Mn in premenopause vs. postmenopause: 1.443 vs. 1.296 μg/dL* [33]
(n = 66)
Sweden general population/Maternal blood median Mn during pregnancy at 3rd, vs. 2nd, vs. 1st trimester 1.26 vs. 1.04 vs. 0.85 μg/dL [34]
Pregnancy
(n = 34)
Australian general population/Maternal blood Mn during pregnancy from 10 to 20 weeks vs. 25 vs. 34 weeks; 0.82 vs. 0.94 vs. 1.26 μg/dL [35]
(n = 290)
Canadian general population/Maternal blood GM Mn during pregnancy at 3rd, vs. 2nd, vs. 1st trimester vs. nonpregnant 1.56 vs. 0.95 vs. 0.85 and 0.746 μg/dL [36]
(n = 470)
Canadian general population/Maternal blood AM Mn during pregnancy at delivery vs. nonpregnant; 2.4 vs. (0.8–1.2) μg/dL [37]
(n = 1085)
USA general population/blood GM Mn in pregnancy vs. nonpregnant; 1.19 vs. 1.02 μg/dL [32]
(n = 265)
Korean general population/blood GM Mn in pregnancy; 2.25 μg/dL [38]
Table 1.
Behavior of blood manganese (Mn) concentrations according to gender-related variables.
Statistically significant.
AM, arithmetic mean; GM, geometric mean; KNHANES, Korea National Health and Nutrition Examination Survey; NHANES, National Health and Nutrition Examination Survey [22].
2.2. Lead
Lead is a widespread environmental pollutant that can damage the central nervous, peripheral nervous, renal, cardiovascular, reproductive, and hematological systems in adults [40]. Exposure to lead induces a wide range of adverse health effects in children [40], because children are more sensitive to toxic effects. Very low blood lead levels (<10 μg/dL) have been associated with reduced IQ, deficits in executive function, and attention deficit hyperactivity disorder in children [26]. The environmental exposure to lead are mainly from leaded gasoline, lead paint such as lead paint-contaminated dust and soil, water from lead pipes, and emissions due to industrial activities [40]. Thus, main route of environmental exposure to lead is inhalation or ingestion [40]. Bone lead reflects total body burden of lead. However, blood lead concentration accounts for a part of the total body burden, and it reflects a recent exposure [40].
Many cross-sectional studies have found that iron-deficiency anemia in children is associated with poor cognitive development, poor motor development, and behavioral problems due to the increased uptake of lead [23, 24]. There is also evidence that decreased cognitive development of children with iron deficiency persists after iron treatment and correction of anemia [23, 24]. Approximately 90% of the lead in the body is stored in the skeleton [40], and lead in bones has a half-life ranging from years (trabecular bone) to decades (cortical bone).
Several previous studies have assessed the temporal relationship between iron deficiency and increased blood lead concentration [15, 16, 41]. A longitudinal study showed an association between iron deficiency and high blood lead level in young children who had blood lead levels ranging from less than 5 to 40 μg/dL [42]. Another study of children aged 10–15 years reported the mean blood lead concentration was 6.9 μg/dL in iron-deficient children and 4.3 μg/dL in those with normal iron levels, and that iron supplementation significantly decreased blood lead concentrations in the former group [16]. A clinical trial assessing the impact of iron supplementation on blood lead concentrations in infants with iron deficiency found that blood lead concentration decreased as iron status improved [15, 41]. In contrast to these studies, other studies have found no association between iron deficiency and increased blood lead concentration [42, 43, 44, 45, 46].
This discrepancy may be partly due to the different ages of the study subjects and the extent of their exposures to lead. For example, studies of older female children or adolescents reported no association of blood iron and lead levels [42, 44, 47]. Postmenarcheal women have lower blood lead concentrations than men, because estrogen promotes bone mineralization and redistributes blood lead into bone, and this estrogen effect overshadows the increasing effect of ferritin on blood lead level [48]. Hence, there is no association between high blood lead level and iron deficiency in postmenarcheal adolescents [48]. Some studies of children with lower blood lead concentrations (11.0 and 11.4 μg/dL) reported no association of blood lead and iron levels [43, 45]. However, longitudinal studies of children with blood lead levels in a similar age range reported an association between iron status and blood lead concentration following iron supplementation [16, 41]. Furthermore, we recently showed that blood lead levels are elevated among iron-deficient infants with very low blood lead concentrations (1.416–1.846 μg/dL) [15]; moreover, iron therapy significantly decreased the blood lead levels of iron deficient infants [12]. Even minor increases in blood lead concentration due to iron deficiency may have clinical implications in children, considering the lack of evidence that any level of lead in the blood can be considered safe [26].
2.3. Cadmium
Cadmium is a ubiquitous environmental pollutant, and the main environmental sources are air, soil, and water contamination due to industrial activities, use of phosphate fertilizers, combustion of motor fuels, and particles released by tire wear. Smoking is the most important source, because tobacco plants, like other plants, take up cadmium from soil. In nonsmokers, diet is the major source of cadmium exposure [49]. Cadmium increases the risk of overall mortality and cardiovascular including hypertension, neurologic, renal, and developmental diseases in adults [49]. A recent paper showed that prenatal low-level exposure to cadmium had adverse effects on neurodevelopment in children [50]. Cadmium levels in the body increase with age, because only small amounts (0.01–0.02%) are excreted each day [49]. Blood cadmium is a biomarker of recent exposure, and urinary cadmium is a biomarker of lifetime exposure [49].
The body absorbs iron and cadmium by similar mechanisms [6, 22], and animal experiments have shown there may be metabolic interactions between cadmium and iron [6, 22]. In particular, animals with low iron stores have increased cadmium uptake [18, 20, 51]. Moreover, high cadmium concentrations are present in premenopausal women with low iron stores [33, 42, 52, 53, 54, 55]. Females of childbearing age have higher blood cadmium concentrations than males because of their lower ferritin levels [53, 56, 57, 58, 59, 60, 61]. There is also a significant increase in the whole blood cadmium level during late pregnancy in particular [53, 62, 63, 64] (Table 2). This increase may be caused by an enhanced cadmium absorption due to upregulated iron absorption during late pregnancy [53], because the mechanisms of iron absorption are similar to those of other divalent metals, particularly manganese and cadmium [6, 7]. However, there is no association between iron deficiency and elevated cadmium levels in postmenopausal women [60, 65, 66]. This may be because of the higher cadmium absorption rate in older-aged females than males, and the interaction of iron and cadmium uptake. Our recent study showed no association between iron deficiency and cadmium concentration in infants [67], but assessment of the same study subjects showed that iron deficiency was associated with increased blood lead and manganese concentrations [15, 30]. It is possible that the lower likelihood of exposure to cadmium in infants explains the lack of an association of blood cadmium level with iron deficiency in these individuals. The placenta may partially prevent fetal exposure to cadmium [68] and only 5–10% of maternal blood cadmium is transferred to human milk, because metallothionein binds to cadmium in blood cells [69]. Moreover, blood cadmium concentrations tend to increase with age [49, 70, 71, 72].
Variables
No. (n)
Study subjects and findings
Gender
(n = 7920)
US general population NHANES 2011–2012/ GM blood cadmium in men vs. women: 0.255 vs. 0.304 μg/L* [57]
(n = 5924)
Korean general population aged 20 years or more; KNHANES 2008–2010/GM blood cadmium in men vs. women: 0.780 vs. 1.194 μg/L* [56]
(n = 2257)
US general population aged 6 years and older; NHANES 2003–2004 / GM urinary cadmium in men aged 12 years or older lower than women; but no difference in children aged 6–11 [58]
(n = 1055)
Bangladesh general population aged 8 years and older/Median urinary cadmium in men aged 30–50, 51–88 years vs. women; 0.66 vs. 0.81, 0.88 vs. 1.1 μg/L [59]
Menopause
(n = 3700)
Korean general population/ blood GM cadmium in premenopause vs. postmenopause: 0.995 vs. 1.165 μg/L* [60]
(n = 149)
Bangladesh general population aged more than 51 years/median urinary cadmium in women vs. men; 1.1 vs. 0.88 μg/L [59]
(n = 1670)
German general population aged 25 or older/between-gender differences in blood GM cadmium greater in subjects >50 than <50 years of age [61]
Pregnancy
(n = 120)
Spain general population/No significant changes in urinary GM cadmium during pregnancy and postpartum; 0.44 vs. 0.64 μg/L [62]
(n = 2882)
Chinese general population/Significant changes in the blood median cadmium between during late pregnancy and nonpregnancy; 0.75 vs. 0.5 μg/L [63]
(n = 281)
Bangladesh general population/Median blood cadmium increased 15% from early pregnancy (0.5 μg/L) to 6 months postpartum [64]
(n = 216)
Swedish general population/Median blood cadmium increased 13% from early pregnancy (0.16 μg/L) to 3 months postpartum [53]
Table 2.
Behavior of blood/urine cadmium concentrations according gender-related variables.
Statistically significant.
GM, geometric mean; KNHANES, Korea National Health and Nutrition Examination Survey; NHANES, National Health and Nutrition Examination Survey [22].
The effect of iron deficiency on blood concentrations of other divalent metals has several clinical and toxicological implications. First, the present paper emphasizes the importance of assessing the iron level and hematologic status of individuals for studies of environmental exposure to divalent metals (manganese, lead, and cadmium) in general populations. In particular, given the high prevalence of iron deficiency in children, iron deficiency status must be considered as an important factor affecting their susceptibility to heavy metal toxicity, especially for environmental health risk assessments of low exposure to these toxic metals. Second, our results also emphasize that exposure to neurotoxic metals may aggravate iron-related developmental and behavioral problems in children and lead to subclinical neuropsychological problems in adults.
The apical divalent metal transporter 1 (DMT1) and the iron exporter ferroportin 1 (FPN1) are responsible for the absorption of iron and other divalent metals (manganese, lead, and cadmium). Thus, an iron-deficient diet can lead to excess absorption of manganese, lead, and cadmium, and high blood concentrations of these metals. Relative to males and postmenopausal women, females of childbearing age have higher blood concentrations of manganese because of their lower blood concentrations of ferritin. Several previous studies reported a temporal relationship between iron deficiency and increased blood lead concentrations in children. Blood cadmium concentrations are higher in females of childbearing age because of their lower ferritin concentrations than in men.
1.de Benoist B, McLean E, Egli I, Cogswell M. Worldwide Prevalence of Anaemia 1993-2005: WHO Global Database of Anaemia. Technical Report. Geneva: World Health Organization; 2008
2.Centers for Disease Control and Prevention. Recommendations to prevent and control iron deficiency in the United States. Centers for Disease Control and Prevention. MMWR - Recommendations and Reports. 1998;47(RR-3):1-29
3.World Health Organization. Iron Deficency Anaemia: Assessment, Prevention and Control: A Guide for Programme Managers. Geneva: World Health Organization; 2001
4.Lucchini RG, Kim Y. Health effects of manganese. In: Vojtisek M, Prakash R, et al., editors. Metals and Neurotoxicity. India: Society for Science and Environment; 2009. pp. 119-147
5.Lonnerdal B. Manganese nutrition of infants. In: Klimis-Tavantzis DJ, editor. Manganese in Health and Disease. Boca Raton: CRC Press; 1994. pp. 175-191
6.Hurley LS, Keen CL. Manganese. In: Underwood E, Mertz W, editors. Trace Elements in Human Health and Animal Nutrition. New York: Academic Press; 1987. pp. 185-223
7.Mackenzie B, Garrick MD. Iron imports. II. Iron uptake at the apical membrane in the intestine. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2005;289:G981-G986
8.Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, Andrews NC. The iron exporter ferroportin/Sc40a1 is essential for iron homeostasis. Cell Metabolism. 2005;1:191-200
9.Madejczyk MS, Ballatori N. The iron transporter ferroportin can also function as a manganese exporter. Biochimica et Biophysica Acta. 2012;1818:651-657
10.Canonne-Hergaux F, Gruenheid S, Ponka P, Gros P. Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. Blood. 1999;93:4406-4417
11.Zoller H, Koch RO, Theurl I, et al. Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload. Gas-troenterology. 2001;120:1412-1419
12.Davis CD, Wolf TL, Greger JL. Varying levels of manganese and iron affect absorption and gut endogenous losses of manganese by rats. The Journal of Nutrition. 1992;122:1300-1308
13.Kim Y, Park JK, Choi Y, Yoo CI, Lee CR, Lee H, et al. Blood manganese concentration is elevated in iron deficiency anemia patients, whereas globus pallidus signal intensity is minimally affected. Neurotoxicology. 2005;26:107-111
14.Kim Y, Lee BK. Iron deficiency increases blood manganese level in the Korean general population according to KNHANES 2008. Neurotoxicology. 2011;32:247-254
15.Park S, Sim CS, Lee H, Kim Y. Effects of iron therapy on blood lead concentrations in infants. Journal of Trace Elements in Medicine and Biology. 2014;28:56-59
16.Choi JW, Kim SK. Association between blood lead concentrations and body iron status in children. Archives of Disease in Childhood. 2003;88:791-792
17.Watson WS, Hume R, Moore MR. Iron and lead absorption in humans. The American Journal of Clinical Nutrition. 1982;36:823-829
18.Piasek M, Blanusa M, Kostial K, Laskey JW. Low iron diet and parenteral cadmium exposure in pregnant rats: The effects on trace elements and fetal viability. Biometals. 2004;17:1-14
19.Tallkvist J, Bowlus CL, Lonnerdal B. DMT1 gene expression and cadmium absorption in human absorptive enterocytes. Toxicology Letters. 2001;122:171-177
20.Ryu DY, Lee SJ, Park DW, Choi BS, Klaassen CD, Park JD. Dietary iron regulates intestinal cadmium absorption through iron transporters in rats. Toxicology Letters. 2004;152:19-25
21.Garrick MD, Dolan KG. An expression system for a transporter of iron and other metals. Methods in Molecular Biology. 2002;196:147-154
22.Lee B-K, Kim Y. Sex-specific profiles of blood metal levels associated with metal–iron interactions. Safety and Health at Work. 2014;5:113-117
23.Kim Y, Park S. Iron deficiency increases blood concentrations of neurotoxic metals in children. Korean Journal of Pediatrics. 2014;57:345-350
24.Jeong KS, Park H, Ha E, Hong YC, Ha M, Park H, Kim BN, Lee SJ, Lee KY, Kim JH, Kim Y. Evidence that cognitive deficit in children is associated not only with iron deficiency, but also with blood lead concentration: A preliminary study. Journal of Trace Elements in Medicine and Biology. 2015;29:336-341
25.ATSDR. Toxicological Profile for Manganese. Atlanta, GA: Agency for Toxic Substances and Disease Registry; 2012
26.Bellinger DC. Prenatal exposures to environmental chemicals and children's neurodevelopment: An update. Safety and Health at Work. 2013;4:1-11
27.Erikson KM, Shihabi ZK, Aschner JL, Aschner M. Manganese accumulates in iron-deficient rat brain regions in a heterogeneous fashion and is associated with neurochemical alterations. Biological Trace Element Research. 2002;87:143-156
28.Boojar MM, Goodarzi F, Basedaghat MA. Long-term follow-up of workplace and well water manganese effects on iron status indexes in manganese miners. Archives of Environmental Health. 2002;57:519-528
29.Brna P, Gordon K, Dooley JM, Price V. Manganese toxicity in a child with iron deficiency and polycythemia. Journal of Child Neurology. 2011;26:891-894
30.Park S, Sim CS, Lee H, Kim Y. Blood manganese concentration is elevated in infants with iron deficiency. Biological Trace Element Research. 2013;155:184-189
31.Baldwin M, Mergler D, Larribe F, Bélanger S, Tardif R, Bilodeau L, Hudnell K. Bioindicator and exposure data for a population based study of manganese. Neurotoxicology. 1999;20:343-353
32.Oulhote Y, Mergler D, Bouchard MF. Sex- and age-differences in blood manganese levels in the U.S. general population: National Health and Nutrition Examination Survey 2011-2012. Environmental Health. 2014;13:87
33.Lee BK, Kim Y. Effects of menopause on blood manganese levels in women: Analysis of 2008-2009 Korean National Health and Nutrition Examination Survey Data. Neurotoxicology. 2012;33:401-405
34.Tholin K, Sandström B, Palm R, Hallmans G. Changes in blood manganese levels during pregnancy in iron supplemented and non supplemented women. Journal of Trace Elements in Medicine and Biology. 1995;9:13-17
35.Spencer A. Whole blood manganese levels in pregnancy and the neonate. Nutrition. 1999;15:731-734
36.Takser L, Lafond J, Bouchard M, St-Amour G, Mergler D. Manganese levels during pregnancy and at birth: Relation to environmental factors and smoking in a Southwest Quebec population. Environmental Research. 2004;95:119-125
37.Zota AR, Ettinger AS, Bouchard M, Amarasiriwardena CJ, Schwartz J, Hu H, Wright RO. Maternal blood manganese levels and infant birth weight. Epidemiology. 2009;20:367-373
38.Chung SE, Cheong H-K, Ha E-H, Kim B-N, Ha M, Kim Y, Hong Y-C, Park H, Oh S-Y. Maternal blood manganese and early neurodevelopment: The Mothers and Children’s Environmental Health (MOCEH) Study. Environmental Health Perspectives. 2015;123:717-722
39.Kirchgessner M, Sherif YS, Schwarz FJ. Changes in absorption of manganese during gravidity and lactation. Annals of Nutrition & Metabolism. 1982;26:83-89. [in German]
40.ATSDR. Toxicological profile for lead. Atlanta, GA: Agency for Toxic Substances and Disease Registry; 2007
41.Wright RO, Tsaih SW, Schwartz J, Wright RJ, Hu H. Association between iron deficiency and blood lead level in a longitudinal analysis of children followed in an urban primary care clinic. The Journal of Pediatrics. 2003;142:9-14
42.Barany E, Bergdahl IA, Bratteby LE, Lundh T, Samuelson G, Skerfving S, et al. Iron status influences trace element levels in human blood and serum. Environmental Research. 2005;98:215-223
43.Hammad TA, Sexton M, Langenberg P. Relationship between blood lead and dietary iron intake in preschool children. A cross-sectional study. Annals of Epidemiology. 1996;6:30-33
44.Hershko C, Konijn AM, Moreb J, Link G, Grauer F, Weissenberg E. Iron depletion and blood lead levels in a population with endemic lead poisoning. Israel Journal of Medical Sciences. 1984;20:1039-1043
45.Wolf AW, Jimenez E, Lozoff B. No evidence of developmental III effects of low-level lead exposure in a developing country. Journal of Developmental and Behavioral Pediatrics. 1994;15:224-231
46.Clark M, Royal J, Seeler R. Interaction of iron deficiency and lead and the hematologic findings in children with severe lead poisoning. Pediatrics. 1988;81:247-254
47.Yip R, Dallman PR. Developmental changes in erythrocyte protoporphyrin: Roles of iron deficiency and lead toxicity. The Journal of Pediatrics. 1984;104:710-713
48.Sim CS, Kim Y, Lee H, Park CY, Ham JO, Lee BK. Iron deficiency increases blood lead levels in boys and pre-menarche girls surveyed in KNHANES 2010-2011. Environmental Research. 2014;130:1-6
49.ATSDR. Toxicological Profile for Cadmium. Atlanta, GA: Agency for Toxic Substances and Disease Registry; 2008
50.Jeong KS, Park H, Ha E, Hong YC, Ha M, Park H, Kim BN, Lee BE, Lee SJ, Lee KY, Kim JH, Kim Y. Performance IQ in children is associated with blood cadmium concentration in early pregnancy. Journal of Trace Elements in Medicine and Biology. 2015;30:107-111
51.Flanagan PR, McLellan JS, Haist J, Cherian G, Chamberlain MJ, Valberg LS. Increased dietary cadmium absorption in mice and human subjects with iron deficiency. Gastroenterology. 1978;74:841-846
52.Vahter M, Berglund M, Akesson A, Liden C. Metals and women's health. Environmental Research. 2002;88:145-155
53.Åkesson A, Berglund M, Schütz A, Bjellerup P, Bremme K, Vahter M. Cadmium exposure in pregnancy and lactation in relation to iron status. American Journal of Public Health. 2002;92:284-287
54.Berglund M, Akesson A, Nermell B, Vahter M. Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake. Environmental Health Perspectives. 1994;102:1058-1066
55.Gallagher CM, Chen JJ, Kovach JS. The relationship between body iron stores and blood and urine cadmium concentrations in US never-smoking, non-pregnant women aged 20-49 years. Environmental Research. 2011;111:702-707
56.Kim Y, Lee BK. Associations of blood lead, cadmium, and mercury with estimated glomerular filtration rate in the Korean general population: Analysis of 2008-2010 Korean National Health and Nutrition Examination Survey Data. Environmental Research. 2012;118:124-129
57.Centers for Disease Control and Prevention. Fourth National Report on Human Exposure to Environmental Chemicals; 2018. p. 285 [Accessed: May 12, 2018]
59.Berglund M, Lindberg AL, Rahman M, Yunus M, Grandér M, Lönnerdal B, Vahter M. Gender and age differences in mixed metal exposure and urinary excretion. Environmental Research. 2011;111:1271-1279
60.Kim SH, Kim Y, Kim NS, Lee BK. Gender difference in blood cadmium concentration in the general population: Can it be explained by iron deficiency? Journal of Trace Elements in Medicine and Biology. 2014;28:322-327
61.Hoffmann K, Krause C, Seifert B. The German Environmental Survey 1990/92 (GerES II): Primary predictors of blood cadmium levels in adults. Archives of Environmental Health. 2001;56:374-379
62.Hernandez M, Schuhmacher M, Fernandez JD, Domingo JL, Llobet JM. Urinary cadmium levels during pregnancy and postpartum. A longitudinal study. Biological Trace Element Research. 1996;53:205-212
63.Zhang Z, Yuan E, Liu J, Lou X, Jia L, Li X, Zhang L. Gestational age-specific reference intervals for blood copper, zinc, calcium, magnesium, iron, lead, and cadmium during normal pregnancy. Clinical Biochemistry. 2013;46:777-780
64.Kippler M, Goessler W, Nermell B, Ekström EC, Lönnerdal B, El Arifeen S, Vahter M. Factors influencing intestinal cadmium uptake in pregnant Bangladeshi women—A prospective cohort study. Environmental Research. 2009;109:914-921
65.Horiguchi H, Oguma E, Sasaki S, Miyamoto K, Ikeda Y, Machida M, et al. Comprehensive study of the effects of age, iron deficiency, diabetes mellitus, and cadmium burden on dietary cadmium absorption in cadmium-exposed female Japanese farmers. Toxicology and Applied Pharmacology. 2004;196:114-123
66.Tsukahara T, Ezaki T, Moriguchi J, Furuki K, Fukui Y, Ukai H, et al. No significant effect of iron deficiency on cadmium body burden or kidney dysfunction among women in the general population in Japan. International Archives of Occupational and Environmental Health. 2003;76:275-281
67.Park JH, Park S, Kim Y. Iron deficiency is not associated with increased blood cadmium in infants. Annals of Occupational and Environmental Medicine. 2014;26:3
68.Truska P, Rosival L, Balazova G, Hinst J, Rippel A, Palusova O, et al. Blood and placental concentrations of cadmium, lead, and mercury in mothers and their newborns. Journal of Hygiene, Epidemiology, Microbiology, and Immunology. 1989;33:141-147
69.Radisch B, Luck W, Nau H. Cadmium concentrations in milk and blood of smoking mothers. Toxicology Letters. 1987;36:147-152
70.Olsson IM, Bensryd I, Lundh T, Ottosson H, Skerfving S, Oskarsson A. Cadmium in blood and urine: Impact of sex, age, dietary intake, iron status, and former smoking: Association of renal effects. Environmental Health Perspectives. 2002;110:1185-1190
71.Lee BK, Kim Y. Iron deficiency is associated with increased levels of blood cadmium in the Korean general population: Analysis of 2008-2009 Korean National Health and Nutrition Examination Survey Data. Environmental Research. 2012;112:155-163
72.Centers for Disease Control and Prevention. NHANES, Key Statistics From NHANES (Data are for 2003-2006) [Internet]. Atlanta, GA: US Centers for Disease Control and Prevention. [Cited 2012 Dec 1]. Available from: http://wwwn.cdc.gov/nchs/nhanes/bibliography/key_statistics.asp
Written By
Yangho Kim
Submitted: 22 March 2018Reviewed: 21 May 2018Published: 05 November 2018
Open access peer-reviewed chapter
