Low iron stores are related to higher blood concentrations of manganese, cobalt and cadmium in non-smoking, Norwegian women in the HUNT 2 study.

Low iron (Fe) stores may influence absorption or transport of divalent metals in blood. To obtain more knowledge about such associations, the divalent metal ions cadmium (Cd), manganese (Mn), cobalt (Co), copper (Cu), zinc (Zn) and lead (Pb) and parameters of Fe metabolism (serum ferritin, haemoglobin (Hb) and transferrin) were investigated in 448 healthy, menstruating non-smoking women, age 20-55 years (mean 38 years), participating in the Norwegian HUNT 2 study. The study population was stratified for serum ferritin: 257 were iron-depleted (serum ferritin < 12 microg/L) and 84 had iron deficiency anaemia (serum ferritin < 12 microg/L and Hb < 120 g/L). The low ferritin group had increased blood concentrations of Mn, Co and Cd but normal concentrations of Cu, Zn and Pb. In multiple regression models, ferritin emerged as the main determinant of Mn, Co and Cd (p < 0.001), while no significant associations with Cu, Zn and Pb were found. Adjusted r(2) for the models were 0.28, 0.48 and 0.34, respectively. Strong positive associations between blood concentrations of Mn, Co and Cd were observed, also when controlled for their common association with ferritin. Apart from these associations, the models showed no significant interactions between the six divalent metals studied. Very mild anaemia (110 < or = Hb < 120 g/L) did not seem to have any effect independent of low ferritin. Approximately 26% of the women with iron deficiency anaemia had high concentrations of all of Mn, Co and Cd as opposed to 2.3% of iron-replete subjects. The results confirm that low serum ferritin may have an impact on body kinetics of certain divalent metal ions, but not all. Only a fraction of women with low iron status exhibited an increased blood concentration of divalent metals, providing indication of complexities in the body's handling of these metals.

[1]  P. Bucciarelli,et al.  Blood levels of homocysteine, folate, vitamin B6 and B12 in women using oral contraceptives compared to non-users. , 2003, Thrombosis research.

[2]  P. H. Petersen,et al.  Appropriate sera for calibration and control of specific protein assays. , 1993, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[3]  S. Sensi,et al.  Oxidative stress and brain aging: is zinc the link? , 2006, Biogerontology.

[4]  G C Cotzias,et al.  Chronic manganese poisoning , 1969, Neurology.

[5]  Staffan Skerfving,et al.  Trace elements in blood and serum of Swedish adolescents: relation to gender, age, residential area, and socioeconomic status. , 2002, Environmental research.

[6]  M. Ikeda,et al.  No significant effect of iron deficiency on cadmium body burden or kidney dysfunction among women in the general population in Japan , 2003, International archives of occupational and environmental health.

[7]  R. Ulvik,et al.  Iron status in manganese alloy production workers , 2003, Journal of applied toxicology : JAT.

[8]  Gunnar F. Nordberg,et al.  Handbook on the Toxicology of Metals , 1979 .

[9]  W. Goessler,et al.  Factors influencing intestinal cadmium uptake in pregnant Bangladeshi women--a prospective cohort study. , 2009, Environmental research.

[10]  B. Fowler,et al.  MECHANISMS OF NEPHROTOXICITY FROM METAL COMBINATIONS: A REVIEW , 2000, Drug and chemical toxicology.

[11]  W. Crosby,et al.  Interrelationship of Iron and Manganese Metabolism∗ , 1968, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[12]  D. Birchall,et al.  T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation , 2008, Neurology.

[13]  J. Finley,et al.  Manganese absorption and retention by young women is associated with serum ferritin concentration. , 1999, The American journal of clinical nutrition.

[14]  G. Hallmans,et al.  Changes in blood manganese levels during pregnancy in iron supplemented and non supplemented women. , 1995, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[15]  S. Skerfving,et al.  Cadmium in blood and urine--impact of sex, age, dietary intake, iron status, and former smoking--association of renal effects. , 2002, Environmental health perspectives.

[16]  M. Garrick,et al.  Iron Imports. II. Iron uptake at the apical membrane in the intestine. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[17]  David S. Barber,et al.  Effects of micronutrients on metal toxicity. , 1998 .

[18]  M. Sütterlin,et al.  Serum folate and Vitamin B12 levels in women using modern oral contraceptives (OC) containing 20 microg ethinyl estradiol. , 2003, European journal of obstetrics, gynecology, and reproductive biology.

[19]  Mikael Fogelholm,et al.  [Nordic nutrition recommendations]. , 2006, Ugeskrift for laeger.

[20]  B. Fowler,et al.  Biological Monitoring and Biomarkers , 2007 .

[21]  J. Olynyk,et al.  The Regulation of Cellular Iron Metabolism , 2007, Critical reviews in clinical laboratory sciences.

[22]  W. Goessler,et al.  Influence of iron and zinc status on cadmium accumulation in Bangladeshi women. , 2007, Toxicology and applied pharmacology.

[23]  J. Staessen,et al.  Transfer of cadmium from a sandy acidic soil to man: a population study. , 1992, Environmental research.

[24]  J. Bogden,et al.  Dietary calcium intakes of urban children at risk of lead poisoning. , 1999, Environmental Health Perspectives.

[25]  J. Cook,et al.  Iron Deficiency and the Measurement of Iron Status , 1992, Nutrition Research Reviews.

[26]  R. Goyer Nutrition and metal toxicity. , 1995, The American journal of clinical nutrition.

[27]  G. Turgut,et al.  Interaction between anemia and blood levels of iron, zinc, copper, cadmium and lead in children , 2007, Indian journal of pediatrics.

[28]  C. Enns,et al.  Iron Homeostasis: Recently Identified Proteins Provide Insight into Novel Control Mechanisms* , 2009, Journal of Biological Chemistry.

[29]  N. Milman,et al.  Calibration of Abbott AxSYM Ferritin kit using the WHO Human Liver Ferritin International Standard 80/602. , 1997, European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies.

[30]  M. Ahamed,et al.  Interaction of lead with some essential trace metals in the blood of anemic children from Lucknow, India. , 2007, Clinica chimica acta; international journal of clinical chemistry.

[31]  G Samuelson,et al.  Iron status influences trace element levels in human blood and serum. , 2005, Environmental research.

[32]  M. Berglund,et al.  Cadmium exposure in pregnancy and lactation in relation to iron status. , 2002, American journal of public health.

[33]  L. Teppo,et al.  Health effects of cadmium exposure - a review of the literature and a risk estimate , 1998 .

[34]  Daniela Berg,et al.  Role of Iron in Neurodegenerative Disorders , 2006, Topics in magnetic resonance imaging : TMRI.

[35]  L. Defebvre,et al.  Neurodegeneration with brain iron accumulation : clinical , radiographic and genetic heterogeneity and corresponding therapeutic options , 2022 .

[36]  J. V. Dijk,et al.  The biology of transferrin. , 1990 .

[37]  T. Ganz Iron homeostasis: fitting the puzzle pieces together. , 2008, Cell metabolism.

[38]  Prasad N. Paradkar,et al.  Comparison of mammalian cell lines expressing distinct isoforms of divalent metal transporter 1 in a tetracycline-regulated fashion. , 2006, The Biochemical journal.

[39]  Y. Akçay,et al.  Effects of iron(II) salts and iron(III) complexes on trace element status in children with iron-deficiency anemia , 2003, Biological Trace Element Research.

[40]  D. Milne,et al.  Manganese content of the cellular components of blood. , 1990, Clinical chemistry.

[41]  A. Åsberg,et al.  Iron status among 3005 women aged 20–55 years in Central Norway: The Nord‐Trøndelag Health Study (the HUNT Study) , 2005, Scandinavian journal of clinical and laboratory investigation.

[42]  Stephan Nussberger,et al.  Cloning and characterization of a mammalian proton-coupled metal-ion transporter , 1997, Nature.

[43]  M. Vahter,et al.  Interactions between essential and toxic elements in lead exposed children in Katowice, Poland. , 1998, Clinical biochemistry.

[44]  M. Aschner,et al.  Globus pallidus: a target brain region for divalent metal accumulation associated with dietary iron deficiency. , 2004, The Journal of nutritional biochemistry.

[45]  J. Cook,et al.  Serum ferritin as a measure of iron stores in normal subjects. , 1974, The American journal of clinical nutrition.

[46]  M. Berglund,et al.  Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake. , 1994, Environmental health perspectives.

[47]  Jian Wang,et al.  Regulation of cellular iron metabolism , 2011, The Biochemical journal.