The impact of iron status and smoking on blood divalent metal concentrations in Norwegian women in the HUNT2 Study.

Low iron (Fe) stores may result in increased absorption of divalent metals, in particular cadmium (Cd). We have previously shown that in non-smoking women participating in the Norwegian HUNT2 cohort study this also included other divalent metals, e.g. manganese (Mn) and cobalt (Co). The diet is the main source of metals in non-smoking individuals, whereas in smoking individuals tobacco smoke contributes significant amounts of Cd and lead (Pb). The aim of the present study was to investigate the impact of smoking on the relationship between low iron status and divalent metals. Blood concentrations of the divalent metals Cd, Mn, Co, Pb, copper (Cu) and zinc (Zn), determined using an Element 2 sector field mass spectrometer (ICP-MS), were investigated in smoking women of fertile age (range 21-55 years) (n=267) from the HUNT2 cohort. Among these, 82 were iron-deplete (serum ferritin<12µg/L) and 28 had iron deficiency anaemia (serum ferritin<12µg/L & Hb<120g/L). 150 (56%) women smoked 10 or more cigarettes daily, 101 (38%) had smoked for more than 20 years, and 107 (40%) had smoked for 11-20 years. Results from the smoking population were compared with results from our previous study in non-smoking women (n=448) of which 132 were previous smokers, all from the same cohort. Increasing concentrations of Cd in blood were observed for previous smokers, low-to-moderate smokers and high intensity smokers in all subgroups compared to never smokers, and according to age groups, education level, BMI and serum ferritin. Smokers had higher Pb concentrations than non-smokers in all subgroups, but less pronounced than for Cd. Smoking was not associated with Mn and Co concentrations in blood. In multiple regression models, low ferritin was associated with increased blood concentrations of Cd, Pb, Mn and Co. Ferritin was strongly associated with Cd at low smoking intensity, but was not a significant factor in heavy smokers, where intensity and duration of smoking emerged as main determinants. Ferritin associations with Co and Pb varied with tertiles of blood Cd. Ferritin emerged as the main determinant of blood Co and Mn, while for blood Pb, age and smoking intensity had higher impact. Cu and Zn remained within reference values and no significant associations with ferritin were found. Strong positive associations between blood concentrations of Pb, Mn, Cd and Co were observed, also when controlled for their common association with ferritin. Apart from these associations, the models showed no significant interactions between the divalent metals studied. Mild anaemia (110

Iron distribution in the liver and duodenum during seasonal iron overload in Svalbard reindeer.

Seasonal iron overload in Svalbard reindeer was studied by light and electron microscopy and by X-ray microanalysis. The hepatic iron overload was of two types. The first type was characterized by massive siderosis of both parenchymal and non-parenchymal cells caused by a diet very rich in iron but low in energy and protein. Hepatocytes contained a moderate amount of free ferritin particles in the cytosol together with numerous siderosomes. This pattern is similar to that seen in primary haemochromatosis and thalassaemia. Kupffer cells contained large quantities of cytosolic ferritin, siderosomes and lysosomes with disintegrating red blood cells as seen in thalassaemia. The second type was characterized by massive non-parenchymal siderosis caused by an energy- and protein-poor diet with normal iron concentration. Hepatocytes contained little cytosolic ferritin and few siderosomes, but there were abundant electron-dense bodies without iron (i.e., autophagosomes). Kupffer cells were as described above. Ferritin was also present within the duodenal mucosa of these animals, located within enterocytes and lamina propria macrophages, as well as in the extracellular space and capillary and lacteal lumina. Ferritin was also present in the acinar cells of submucosal Brunner's glands. Changes consistent with exchange of ferritin particles between different cell types were observed. The role of ferritin as a possible iron transporter in this condition is discussed.

Iron status among 3005 women aged 20-55 years in Central Norway: the Nord-Trøndelag Health Study (the HUNT study).

OBJECTIVE: To describe the iron status of Norwegian women of fertile age, to show the prevalence of iron-deficiency anemia and iron overload, and to demonstrate possible factors connected to and/or influencing iron status. MATERIAL AND METHODS: The diagnostic criteria were: (a) anemia: hemoglobin (Hb) < 120, < 117, or < 115 g/l; (b) depleted iron stores: serum ferritin (SF) < 10 or 12 microg/l; iron-deficiency anemia: (a)+(b). Iron overload: SF > or = 110 microg/l. The study was conducted in Central Norway where a total of 3005 women aged 20 to 55 years were enrolled in a health survey program (the HUNT Study). None of the women were pregnant and none had been blood donors in the two previous years. RESULTS: Median SF was 31.0 microg/l. Depleted iron stores were present in 10.9 and 15.1%, respectively. The Hb 2.5%tile among the iron-replete women was 117 g/l. With this cut-off value, anemia was present in 4.7% and iron-deficiency anemia in about 3%. Iron overload was present among 5.2%, and homozygous primary hemochromatosis among 0.4%. CONCLUSIONS: The prevalence of iron-deficiency anemia was relatively low and similar to that found earlier in small groups of Norwegian women. The prevalence is comparable with results from other developed countries.

Headache prevalence related to haemoglobin and ferritin. The HUNT Study.

As clinic-based studies show an association between headache and both high and low levels of haemoglobin, we analysed this relationship in a population-based cross-sectional study (the HUNT Study). A total of 2385 women aged 20-55 years responded to a headache questionnaire and gave blood samples for measuring haemoglobin and ferritin. In the multivariate analyses, adjusting for age and education, there was a linear trend of decreasing prevalence of headache (P = 0.02) and migraine (P = 0.01) with decreasing haemoglobin. In particular, migraine was less likely among women with low haemoglobin (values < 11.5 g/dl) (odds ratio 0.4, confidence interval 0.2, 0.9). There was no correlation between headache prevalence and ferritin. The present findings may be relevant for the headache reported in polycythaemia and chronic altitude sickness.

Iron status in a group of Norwegian children aged 6-24 months.

UNLABELLED: An adequate iron status is of vital importance for health and development in infancy and early childhood. Iron status was evaluated in a group of full-term Norwegian children followed longitudinally, at the ages of 6 mo (n = 278), 12 mo (n = 249) and 24 mo (n = 231) by measuring haemoglobin (Hb), mean cell volume (MCV) and serum ferritin. At 6, 12 and 24 mo of age, 3, 10 and 12%, respectively, had iron deficiency anaemia (IDA) defined as Hb <110 g/l in combination with ferritin <15 microg/l. With more restrictive criteria for defining IDA (Hb <110 g/l or <105 g/l in combination with ferritin <12 microg/l), the prevalence decreased to 1-2% at 6 mo and 2-5% at 12 and 24 mo of age. If children with a history of fever in the previous month were excluded, the proportion of children with depleted iron stores (ferritin <10 microg/l) increased from 2 to 3% at 6 mo, from 5 to 7% at 12 mo and from 9 to 13% at 24 mo. CONCLUSION: Mild iron deficiency anaemia exists among otherwise healthy Norwegian infants and toddlers. The prevention and early treatment of iron deficiency should be a priority for the child health services.

[Should iron preparations be available only by prescription?]. / Bør jernpreparater reseptbelegges?

Many persons associate fatigue and lassitude with iron deficiency and take extra iron "to be on the safe side". This is an unfortunate practice, as the early symptoms of iron deficiency anaemia and of hereditary iron overload (homozygous primary haemochromatosis) are similar. Primary haemochromatosis is considerably more prevalent than earlier believed. As many as 5 per 1,000 of the Norwegian population may have two mutated genes for haemochromatosis, while up to 15% may be carriers of a single mutated gene, and for these an extra intake of iron may be hazardous. The condition is highly underdiagnosed. In Norway at present, iron preparations of 60-100 mg are sold over the counter in pharmacies without prescription and often by self-service. However, no one should use iron tablets until iron deficiency and its cause has been ascertained. To avoid uncritical use of iron, iron preparations should be available only by doctor's prescription. Prolonged abuse of iron tablets may result in secondary haemochromatosis.

[Primary hemochromatosis and dietary iron]. / Primaer hemokromatose og jern i kosten.

Primary haemochromatosis is characterized by an unusually high degree of iron absorption resulting in the accumulation of excessive amounts of tissue iron. Excess stores of iron are removed by repeated phlebotomy. Health personnel and a number of patients with primary haemochromatosis have expressed their desire for advice on special diets to try and reduce the number of phlebotomies per year. This article gives advice on how patients with primary haemochromatosis can decrease their dietary iron intake and how they can put together meals to obtain low bioavailability, and therefore a lower iron absorption. The diet should be varied and be rich in bread and cereals, and fruit and vegetables. The amount of meat, Norwegian brown whey cheese (iron supplemented) and alcohol should be limited. Tea or coffee with meals will reduce iron absorption. Food rich in ascorbic acid (fruit and fruit juice) should be avoided with meals. Ascorbic acid supplements are not recommended.

Influence of season and diet on liver and kidney content of essential elements and heavy metals in Svalbard reindeer.

Samples of liver (n = 78) and kidney (n = 60) from Svalbard reindeer (Rangifer tarandus platyrhynchus Vrolik) collected at four different seasons in Svalbard were analysed for their content of Cd, Pb, Cu, Zn, Mn, and Se. The study shows that when animals are exposed to large seasonal variations in both the quality and quantity of food, it is crucial to relate element concentrations to the physiological condition of the animal, e.g., to look at seasonal fluctuations in the total element content of the different organs.

Associations between serum ferritin and cardiovascular risk factors in healthy young men. A cross sectional study.

OBJECTIVE: This study examines the association between serum ferritin levels and cardiovascular risk factors. DESIGN: The data were obtained from a cross-sectional survey designed to assess the nutrition situation, with special reference to cardiovascular risk factors. SUBJECTS AND SETTING: The study population was 337 healthy men, median age 38 years (range 21-59), working at oil platforms in the North Sea. RESULTS: The associations between serum ferritin, risk factor levels and anthropometric measurements were analysed by age-adjusted partial correlations, step-wise multiple regression, and one-way ANOVA analysis. Body mass index and waist-to-thigh ratio were the strongest predictors for serum ferritin when controlling for age (P < 0.001). In multiple regression analysis, when anthropometric measurements were excluded, fibrinogen, high density lipoprotein (HDL)-cholesterol and diastolic blood pressure were significant predictors for serum ferritin levels when controlling for age (P < 0.001). There was a significant difference in triglyceride concentration between those with low stores of iron and those with high stores (P = 0.006). There were consistently higher levels of total cholesterol, triglycerides, fibrinogen, diastolic and systolic blood pressure, except for HDL where it was reversed, in the highest quartile of serum ferritin levels compared to the lowest. For all the variables the differences between the quartiles of serum ferritin were significant. CONCLUSION: These findings support the hypothesis that the associations between cardiovascular arteriosclerotic disease and serum ferritin are at least partially caused by confounding. SPONSORSHIP: The project was supported by the Norwegian State Oil Company (STATOIL), Amoco Norway Oil Company and Ross Offshore AS.

Determination of iron status: brief review of physiological effects on iron measures.

In the last 25 years the repertoire for clinical determination of iron status has been extended with important methods. From blood samples it is now possible to obtain information on the size of the body iron stores and on possible tissue iron deficiency by the levels of serum ferritin and serum transferrin receptor, respectively. These iron measures can be used together to distinguish between iron deficiency anaemia and anaemia from other causes.

[Iron status and weaning practices among healthy 1-year old infants]. / Jernstatus og kostholdsutvikling hos friske ettåringer.

Iron status and weaning practices were studied in healthy one-year-old Norwegian and immigrant children (from developing countries) attending Fjell Health centre, Drammen. None of the Norwegian children (n = 33) had empty iron stores (serum ferritin < 10 micrograms/l) or iron deficiency anaemia (serum ferritin < 15 micrograms/l and haemoglobin < 11 g/100 ml). Among the immigrant children (n = 37) the prevalences were 14 and 11% respectively. The immigrant children were given infant formula earlier than the Norwegian and drank cow's milk for a longer period of the first year. There were no differences between the groups as regards introduction of infant cereals or other types of foods (vegetables, meat, fish).

The effect of daily low-dose iron supplements in female blood donors with depleted iron stores: comparison with female non-donors.

Female blood donors with serum ferritin < or = 20 micrograms l-1 and haemoglobin > 120 g l-1 participated in an iron supplement study with two different low-dose supplements in a period without donations. Comparable non-donors served as controls. Serum ferritin, haemoglobin and transferrin were determined. Increases in serum ferritin and in haemoglobin, and decrease in transferrin were highly significant (p < 0.01) in both donor groups. In one of the non-donor groups the increase in serum ferritin and decrease in transferrin were highly significant (p < 0.01), while in the other only transferrin changed significantly (p < 0.03). The increases in serum ferritin and haemoglobin over a 5-month period were significantly higher among donors (p < 0.001) than among non-donors. We interpret the results to mean that the donors have a more efficient iron absorption.

[Do we need new guidelines on iron supplementation during pregnancy?]. / Trenger vi nye retningslinjer for bruk av jerntilskudd i svangerskapet?

Studies have shown that the present official Norwegian recommendations on iron supplementation during pregnancy are not followed. A meeting was arranged in February 1993 to discuss the need to change the recommendations. The article describes the conclusions of the panel. It was proposed that the iron status of the pregnant woman, determined as serum ferritin concentration, should be measured early (before the 15th week of gestation) and iron supplement should be given as selective prophylaxis based on the serum ferritin level. The Directorate of Public Health has been asked to issue new recommendations.