Iron status in Danish men 1984-94: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload

BACKGROUND AND OBJECTIVES: From 1954 to 1987, flour in Denmark was fortified with 30 mg carbonyl iron per kg. This mandatory fortification was abolished in 1987. The aim of this study was to compare iron status in Danish men before and after abolition of iron fortification. METHODS: Iron status (serum ferritin, haemoglobin), was assessed in population surveys in Copenhagen County during 1983-84 comprising 1324 Caucasian men (1024 non-blood-donors, 300 blood donors) and in 1993-94 comprising 1288 Caucasian men (1103 non-blood-donors, 185 donors), equally distributed in age cohorts of 40, 50, 60 and 70 yr. RESULTS: In the 1984 survey median serum ferritin values in the four age cohorts in non-blood-donors were 136, 141, 133 and 111 microg/L, and in the 1994 survey 177, 173, 186 and 148 microg L(-1), respectively. The difference was significant in all age groups (P<0.001). There was no significant difference between the two surveys concerning the prevalence of small iron stores (ferritin 16-32 micro g L(-1)), depleted iron stores (ferritin <16 microg L(-1)) or iron-deficiency anaemia (ferritin <13 microg L(-1) and Hb <5th percentile for iron-replete men). However, from 1984 to 1994, the prevalence of iron overload (ferritin >300 microg L(-1)) increased from 11.3% to 18.9% (P<0.0001). During the study period there was an increase in body mass index (P<0.0001), alcohol consumption (P<0.03) and use of non-steroid anti-inflammatory drugs (NSAID) (P<0.0001), and a decrease in the use of vitamin-mineral supplements (P<0.04) and in the prevalence of tobacco smoking (P<0.0001). In contrast, median ferritin in blood donors showed a significant fall from 1984 to 1994 (103 vs. 74 micro g L(-1), P<0.02). CONCLUSION: Abolition of iron fortification reduced the iron content of the Danish diet by an average of 0.24 mg MJ(-1), and the median dietary iron intake in men from 17 to 12 mg d(-1). From 1984 to 1994, body iron stores and the prevalence of iron overload in Danish men increased significantly, despite the abolition of food iron fortification. The reason appears to be changes in dietary habits, with a lower consumption of dairy products and eggs, which inhibit iron absorption, and a higher consumption of alcohol, meat, and poultry, containing haem iron and enhancing iron absorption. The high prevalence of iron overload in men may constitute a health risk.     

Iron status in Danes 1994

 Iron status, i.e. serum ferritin and haemoglobin (Hb) levels, was assessed in a population survey in 1994 (Dan-Monica 10) comprising 1319 Caucasian Danish women in age cohorts of 40, 50, 60 and 70 years. In the entire series, ferritin levels increased significantly from 40 years to 60 years of age. The prevalence of small iron stores (ferritin 16–32 μg/l), depleted iron stores (ferritin <16 μg/l) and of iron deficiency anaemia (ferritin <13 μg/l and Hb <121 g/l) decreased steadily with age. Blood donors (n=109) had lower ferritin levels than non-donors (P<0.0001). Ferritin levels in donors were inversely correlated with the cumulated number of lifetime phlebotomies (r _s =–0.25, P<0.01). Ferritin levels in non-donors (n=1208) were low in 40-year-old women (median 40 μg/l) and increased to a median of 95 μg/l in 60- and 70-year-old women (P<0.0001). In non-donors 40 years of age, the prevalence of small iron stores was 40.4%, the prevalence of depleted iron stores 10.8% and the prevalence of iron deficiency anaemia 2.16%. The prevalence of iron overload (ferritin >300 μg/l) was 1.54%. Ferritin levels in 60- and 70-year-old non-donors were correlated with the body mass index (r _s =0.11, P=0.01). Ferritin levels in 50- to 60-year-old non-donors were correlated with alcohol intake (r _s =0.23, P<0.0001). In the entire series, 37.5% of non-donors took supplemental ferrous iron (median 14 mg iron per day). Iron supplements had a significant positive influence on iron status in 40-year-old premenopausal non-donors but no effect in postmenopausal women or in donors. Non-donors (n=170) treated with acetylsalicylic acid had lower ferritin levels (median 55 μg/l) than non-treated (n=1038; median 75 μg/l) (P<0.0001). Compared with the Dan-Monica 1 iron status survey in 1984, the prevalence of iron deficiency and iron deficiency anaemia was unchanged, whereas the prevalence of iron overload displayed a slight increase. The 1987 abolition of the mandatory iron fortification of flour apparently had no negative effect on iron status. Received: 8 November 1999 / Accepted: 17 April 2000     

Haemoglobin concentrations appear to be lower in indigenous Greenlanders than in Danes: assessment of haemoglobin in 234 Greenlanders and in 2804 Danes

OBJECTIVE: To compare haemoglobin concentrations in Greenlanders and Danes. METHODS: Haemoglobin was measured in a population survey in 1993-1994 comprising 234 indigenous Greenlandic individuals (115 men) aged 19-82 yr. and in Copenhagen County 1983-1984 comprising 2804 Caucasian Danes (1444 men) aged 30-60 yr. The Greenlandic participants were residents in the capital Nuuk (n=70), the town Ilulissat (n=74), and four settlements in the Uummannaq district (n=90). The significance of differences was assessed by Student's t-test, and the xi2-test. Correlations were assessed by Spearman's correlation coefficient (rs). RESULTS: Greenlanders: Haemoglobin levels were not correlated with age or consumption of traditional foods, and were not significantly different in the three residential areas. Mean haemoglobin was higher in men, 146+/-9.6 (SD) g/L, than in women, 132+/-9.6 g/L (p<0.0001). Mean haemoglobin in iron-replete men with serum ferritin >32 microg/L (n=104) was 146+/-9.3 g/L, and in iron-replete women (n=68) 133+/-10.4 g/L (p<0.0001). The 5th percentile for haemoglobin in iron-replete men was 133 g/L (8.3 mmol/L) and in women 118 g/L (7.3 mmol/L). The prevalence of iron deficiency anaemia (i.e. ferritin <13 microg/L and Hb <5th percentile for iron-replete men and women) was 0% in men, 2.78% in women < or =50 yr of age and 0% in women >50 yr of age. Danes: Mean haemoglobin in men was 154+/-10.0 g/L and in women 138+/-10.4 g/L (p<0.0001). Haemoglobin in iron-replete men (n=1379) (i.e. serum ferritin >32 microg/L) was 154+/-10.7 g/L, and in iron-replete women (n=1003) 140+/-9.6 g/L (p<0.0001). Mean haemoglobin was lower in premenopausal than in postmenopausal women (p<0.0001). The 5th percentile for haemoglobin in iron-replete men was 137 g/L (8.5 mmol/L) and in women 124 g/L (7.7 mmol/L). The prevalence of iron deficiency anaemia (i.e. ferritin <13 microg/L and Hb <5th percentile for iron replete men and women) was 0% in men, 1.92% in women < or =50 yr of age and 0% in women >50 yr of age. CONCLUSION: Haemoglobin concentrations in Greenlanders were significantly lower than in Danes both in men (p<0.0001) and in women (p<0.0001). Delta(mean haemoglobin) in men was 8.0 g/L (0.5 mmol/L) and in women 6.2 g/L (0.4 mmol/L). Variations in haemoglobin levels may be due to genetic differences.     

Iron status markers in 224 indigenous Greenlanders: influence of age, residence and traditional foods

OBJECTIVE: To evaluate iron status in indigenous Greenlanders and its relationship to gender, age and intake of traditional Greenlandic foods. Methods: Serum ferritin, serum transferrin saturation and haemoglobin were evaluated in a population survey in 1993-1994 comprising 224 Greenlandic individuals (109 men) aged 19-82 yr. The participants were residents in the capital Nuuk (n=73) with a predominantly Western style of living, the town Ilulissat (n=60) with a mixture of Western and Greenlandic style of living, and the small town Uummannaq (n=91) with a predominantly Greenlandic style of living. Consumption of traditional foods was assessed by questionnaire. RESULTS: Intake of traditional foods was more prevalent among elderly than among young individuals and more frequent in Uummannaq than in Ilulissat and Nuuk. Ferritin levels were higher in men than in women (p<0.0001). Median ferritin levels were lowest in Nuuk (men, 92 microg/L; women, 40 microg/L), higher in Ilulissat (men, 104 microg/L; women, 69 microg/L) and in Uummannaq (men, 118 microg/L; women, 46 microg/L) (p<0.001). The prevalence of iron load (ferritin >200 microg/L) was lowest in Nuuk (men: 13.8%, women: 2.3%) intermediate in Ilulissat (men, 11.1%; women, 9.1%) and highest in Uummannaq (men, 32.1%; women, 21.1%). The prevalence of iron depletion (ferritin <16 microg/L) was high in Nuuk (men, 0%; women, 20.5%), and lower in Ilulissat (men, 3.7%; women, 6.1%) and in Uummannaq (men, 0%; women, 10.5%). The prevalence of iron deficiency anaemia (ferritin <13 microg/L and Hb <5th percentile for iron-replete men and women) was 0.92% in men and 0.87% in women. Correlations between age and ferritin were lowest in Nuuk (men, r(s)=0.26, p=0.2; women, r(s)=0.50, p=0.001) intermediary in Ilulissat (men, r(s)=0.37, p=0.06; women, r(s)=0.73, p<0.0001) and highest in Uummannaq (men, r(s)=0.59, p<0.0001; women, rs=0.74, p<0.0001). Intake of traditional foods was correlated with ferritin in men (r(s)=0.29, p=0.01) and women (r(s)=0.40, p<0.0001). CONCLUSION: The observed differences in estimated body iron stores in Greenlanders from the three residential areas can be explained by differences in the dietary intake of haem iron.     

Serum ferritin concentrations and body iron stores in a multicenter, multiethnic primary-care population

How often elevated serum ferritin in primary-care patients reflects increased iron stores (normally 0.8 g in men, 0.4 g in women) is not known. The Hereditary Hemochromatosis and Iron Overload Screening (HEIRS) study screened 101,168 primary-care participants (44% Caucasians, 27% African-Americans, 14% Asians/Pacific Islanders, 13% Hispanics, 2% others). Follow-up clinical evaluation was performed in 302 of 333 HFE C282Y homozygotes regardless of iron measures and 1,375 of 1,920 nonhomozygotes with serum ferritin >300 microg/L (men), >200 microg/L (women) and transferrin saturation >50% (men), >45% (women). Quantitative phlebotomy was conducted in 122 of 175 C282Y homozygotes and 122 of 1,102 nonhomozygotes with non-transfusional serum ferritin elevation at evaluation. The estimated prevalence in the Caucasian population of C282Y homozygotes with serum ferritin >900 microg/L at evaluation was 20 per 10,000 men and 4 per 10,000 women; this constellation was predictive of iron stores >4 g in men and >2 g in women. The estimated prevalence per 10,000 of non-C282Y homozygotes with serum ferritin >900 microg/L at evaluation was 7 among Caucasians, 13 among Hispanics, 20 among African Americans, and 38 among Asians and Pacific Islanders, and this constellation was predictive of iron stores >2 g but <4 g. In conclusion, serum ferritin >900 microg/L after initial elevations of both serum ferritin and transferrin saturation is predictive of mildly increased iron stores in multiple ethnic populations regardless of HFE genotype. Serum ferritin >900 microg/L in male C282Y homozygotes is predictive of moderately increased iron stores.     

HFE genotypes and dietary heme iron: no evidence of strong gene-nutrient interaction on serum ferritin concentrations in middle-aged women

BACKGROUND AND AIM: Hereditary hemochromatosis (HH) is a disorder characterized by inappropriately high intestinal iron absorption. In populations of Northern European descent, HH is most commonly caused by mutations (C282Y/H63D) in the HFE gene. METHODS AND RESULTS: We investigated the effects of dietary heme iron intake and HFE mutations on serum ferritin concentrations in a population-based random sample of 1611 women aged >50 years using analysis of covariance (ANCOVA). Higher heme iron intake was associated with significantly higher serum ferritin concentrations (P(trend) < 0.001). Also, women with the compound or C282Y homozygous genotype had significantly higher serum ferritin concentrations (geometric mean 115.2 microg/L (95% CI 81.4-162.9 microg/L) than women carrying normal alleles (geometric mean 76.6 microg/L (95% CI 72.5-80.9 microg/L). We observed the highest serum ferritin concentrations among postmenopausal women who are compound heterozygous or C282Y homozygous, and who consume relatively high amounts of heme iron (geometric mean 183.9 microg/L (95% CI 97.2-347.8 microg/L). CONCLUSIONS: Even when there are currently no clinical signs, women with the compound or C282Y homozygous genotype may still be at risk for developing iron overload sometime after menopause.     

Response in serum ferritin and haemoglobin to iron therapy in blood donors

Seven hundred seventeen healthy male blood donors regularly donating four or more units a year were surveyed for haemoglobin and serum ferritin levels. One hundred fifty-one (21%) had a haemoglobin less than 13.5 g/dl and were therefore disqualified from further blood donation, having a mean serum ferritin of 28 micrograms/liter. Of the remaining 566 donors with haemoglobin levels equal to or greater than 13.5 g/dl, the mean serum ferritin was 33 micrograms/liter, although in 299 (53%) the value was less than 28 micrograms/liter. To document response to iron therapy 46 donors with haemoglobin levels equal to or greater than 13.5 g/dl were stratified into those with the lowest iron stores (group 1; n = 23), defined as a serum ferritin less than 20 micrograms/liter, and controls (group 2; n = 23), with serum ferritin between 50 and 150 micrograms/liter. Within each stratum donors randomly received ferric polymaltose at a dose of 100 mg elemental iron twice daily for 56 days (groups 1a and 2a) or an identical iron-free placebo tablet administered on the same schedule (groups 1b and 2b). Iron therapy in the iron-deficient group (group 1a:n = 11) resulted in a significant rise in haemoglobin (p = .03) and iron stores reflected in serum ferritin (p = .002) compared to those receiving placebo (group 1b). In the control group iron therapy or placebo was without significant effect. Thus, ferric polymaltose preparation is bioavailable and is notable for the virtual absence of gastrointestinal tract side effects.     

Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major

Clinical complications of transfusional iron overload are still common in patients with thalassaemia major (TM) and it is not clear how best to monitor body iron stores during long-term follow-up to anticipate tissue damage. In this study, we have reviewed a group of 32 patients who underwent liver biopsy between 1984 and 1986. We developed a method of assessing the trend in serum ferritin (TSF) during long-term monitoring and compared this with mean serum ferritin (MSF) and initial liver iron (LI) concentration to determine whether, individually or in combination, they were accurate in predicting clinical outcome. LI levels were low (< 7 mg/g), medium (7-15 mg/g) and high (> 15 mg/g dry weight) in 15, 7 and 10 patients respectively. MSF was low (< 1500 microg/l), medium (1500-2500 microg/l) and high (> 2500 microg/l) in 10, 14 and 8 patients. TSF was low, medium and high risk in 9, 9 and 11 out of 29 evaluable patients. During a median follow-up of 13.6 years (range 2.3-14.8 years) after biopsy, nine patients died and an additional three patients developed heart failure. Hypothyroidism developed in five, hypoparathyroidism in four, and diabetes mellitus in seven patients. Cirrhosis developed in four of 10 evaluable patients. The clinical end-point of death or cardiac failure was significantly associated with increasing iron load using all three means of assessment. Although numbers were insufficient for statistical analysis, MSF or TSF were more closely associated with complications of iron overload than LI. There was no clear additional value in combining LI with MSF or TSF. The data show that quantitation of liver iron from a single liver biopsy has little value in long-term monitoring of iron stores. Most complications can be avoided if ferritin levels can be brought down to <1500 microg/l.     

The impact of weekly iron supplementation on the iron status and growth of adolescent girls in Tanzania

We evaluated the effect of weekly doses of 400 mg of ferrous sulphate for 4 months on the iron status of adolescent girls in a controlled trial in Tanga, Tanzania. Supplementation led to a significantly greater increase in serum ferritin compared with the control group (+ 15.6 microg/l vs. 8.6 microg/l) (P = 0.002) but there was no significant difference in change in haemoglobin. Children given iron showed a significantly greater weight gain than controls (+ 2.4 kg vs. + 1.4 kg) (P = 0.03). Weekly iron supplementation may be an effective means of increasing iron stores and growth in children vulnerable to iron deficiency.     

The relationship between iron deficiency anemia and lipid metabolism in premenopausal women

BACKGROUND/AIM: Iron deficiency and lipid metabolism disorders are common health problems. We investigated the relationship between iron deficiency anemia and lipid metabolism in premenopausal women, in whom iron deficiency anemia is not uncommon. METHODS: This prospective cohort study was carried out in 64 premenopausal women (median age of 40 years, ranging from 15 to 52) with iron deficiency anemia and 21 non-anemic control women (median age of 38 years, ranging from 28 to 50). Serum ferritin values less than 11 ng/mL and transferrin saturation below 15% were accepted as indicators of iron deficiency. All anemic patients were treated with oral iron replacement. RESULTS: The mean levels of total and low density lipoprotein cholesterol of anemic women were lower than those of non-anemic control patients (173.6 +/- 39.3 vs 205.7 +/- 36.0, P = 0.001, 105.3 +/- 32.7 vs 135.6 +/- 31.3 mg/dL, P < 0.001, respectively). Despite increasing significantly after treatment of anemia (from 173.6 +/- 39.3 to 181.6 +/- 35.2, P = 0.018, from 105.3 +/- 32.7 to 111.3 +/- 29.4 mg/dL, P = 0.029, respectively), their levels were still lower than in the control subjects (181.6 +/- 35.2 vs 205.7 +/- 36.0 mg/dL, P = 0.008, 111.3 +/- 29.4 vs 135.6 +/- 31.3 mg/dL, P = 0.002, respectively). In anemic patients, statistically significant positive correlations were found between the pre-treatment total cholesterol levels and hemoglobin (r = 0.336, P = 0.007), hematocrit (r = 0.326, P = 0.009), serum iron (r = 0.404, P = 0.001), serum ferritin (r = 280, P = 0.026), and transferrin saturation (r = 0.314, P = 0.012). The only significant factor affecting pre-treatment total cholesterol levels was serum iron. CONCLUSIONS: We hypothesize that low iron states in premenopausal women may exert an additional protective effect against atherosclerotic heart disease via lipid metabolism.     

Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration

This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration. In a randomized, double-blinded, placebo-controlled study, 90 premenopausal women presenting with fatigue, serum ferritin ≤ 50 ng/mL, and hemoglobin ≥ 120 g/L were randomized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo. Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks. Median fatigue at baseline was 4.5 (on a 0-10 scale). Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group (P = .07). Efficacy of iron was bound to depleted iron stores: In patients with baseline serum ferritin ≤ 15 ng/mL, fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group (P = .005), and 82% of iron-treated compared with 47% of placebo-treated patients reported improved fatigue (P = .03). Drug-associated adverse events were observed in 21% of iron-treated patients and in 7% of placebo-treated patients (P = .05); none of these events was serious. Intravenous administration of iron improved fatigue in iron-deficient, nonanemic women with a good safety and tolerability profile. The efficacy of intravenous iron was bound to a serum ferritin concentration ≤ 15 ng/mL. This study was registered at the International Standard Randomized Controlled Trial Number Register (www.isrctn.org) as ISRCTN78430425.     

Predictive risk factors and prevalence of malignancy in patients with iron deficiency anemia in Taiwan

Gastrointestinal (GI) tract malignancy is one of the important causes of chronic iron deficiency anemia (IDA). The present study was designed to find out the prevalence and the predictive risk factors of malignancy in the IDA patients. We performed a prospective study in 148 patients with chronic IDA. A series of examinations to explore the GI tract were performed either by radiology and/or endoscopy. A Tc-RBC GI bleeding study was also performed, and prevalence and risk factors of malignancy were calculated. Totally 148 patients were enrolled, with mean age 66.2 years; 88 were male. Eighteen patients (12.2%) were found to have malignant tumors. Ten (6.8%) had benign tumors, and 96 (64.9%) had other benign conditions. No lesions could be detected in 24 patients (16.2%). Clinical symptoms and presence of fecal occult blood could not predict malignancy or any GI lesions. Multivariate logistic regression analysis showed serum ferritin < or =10 microg/L, LDH >250 U/L, and aging as the risk factors of malignancy in the IDA patients (P = 0.003, 0.002, and 0.027; and OR = 7.614, 8.955, and 1.062, respectively). An IDA patient with both serum ferritin < or =10 microg/L and LDH >250 U/L ran a 74.33-times higher risk of malignancy than the patient without (95% CI: 7.115-776.479). Malignancy was an important cause of IDA. High LDH, low serum ferritin, and aging were the risk factors of malignancy in the IDA patients.     

Iron status markers,serum ferritin and hemoglobin in 1359 Danish women in relation to menstruation,hormonal contraception,parity, and postmenopausal hormone treatment

Summary Iron status was assessed by measuring serum (S-) ferritin and hemoglobin (Hb) in a population survey comprising 1359 nonpregnant Danish women, in age cohorts of 30,40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal. Median age for menarche was 14 years, for menopause (artificial and natural) 48 years. Premenopausal women had lower S-ferritin (median 37g/l) than postmenopausal women (median 71g/l;p<0.0001). Of the premenopausal women, 17.7% had S-ferritin < 15g/l (i.e., depleted iron stores), and 23.1% S-ferritin of 15–30g/l (i.e., small iron stores). Corresponding figures in postmenopausal women were 3.3% and 10.3%. Hb values in premenopausal women were mean 137±10 (SD) g/l (8.5±0.6 mmol/l) vs. 140±10 g/l (8.7±0.6 mmol/l) in postmenopausal women (p<0.0001); 4.1% of pre- and 3.3% of postmenopausal women had values < 121 g/l (7.5 mmol/l). Iron deficiency anemia (i.e., S-ferritin < 15g/l and Hb < 121 g/l) was found in 2.6% of pre- and 0.36% of postmenopausal women. Premenopausal multipara had lower S-ferritin than nulli- and unipara (p<0.04). The use of oral contraceptives had a marked influence on iron stores; premenopausal women taking the pill had higher S-ferritin and a lower frequency of depleted iron reserves than nonusers (p<0.01). Postmenopausal estrogen treatment had no influence on S-ferritin or Hb.     

Relation between bone marrow hemosiderin iron,serum iron status markers,and chemical and histochemical liver iron content in 82 patients with alcoholic and nonalcoholic hepatic disease

Summary Bone marrow hemosiderin iron was assessed in 48 patients with alcoholic, and in 34 patients with nonalcoholic liver disease (53 men, 29 women, median age 55 years, range 18–84) and correlated to serum (S)-iron status markers (iron, transferrin, ferritin), as well as to histochemical hepatocyte iron and chemical liver iron content. In a control group of 53 healthy subjects (23 men, 30 women, median age 28 years, range 18–90) marrow hemosiderin iron and iron status markers were evaluated as well. Among liver patients, the marrow iron grade was higher in men than in women (p=0.03). Correlations were found between marrow iron and histochemical liver iron (rho=0.38,p=0.0001) as well as chemical liver iron (rho=0.33,p=0.01). Marrow iron was correlated to S-ferritin (rho=0.53,p=0.0001), mean red cell volume (rho=0.34,p=0.003), and S-transferrin (rho=–0.24,p=0.02). Alcoholics had a higher marrow iron grade than nonalcoholics (p=0.001) and controls (p=0.0001). Among controls, the marrow iron grade was likewise higher in men than in women (p=0.01). Correlations were found between marrow iron and ferritin (rho=0.64,p=0.0001), transferrin saturation (rho=0.56,p= 0.001), transferrin (rho=–0.53,p=0.001), S-iron (rho= 0.37,p=0.01), and hemoglobin in women (rho= 0.38,p=0.05). The results indicate that alcoholics either have increased marrow hemosiderin iron stores, or display a redistribution of iron in reticuloendothelial cells from soluble ferritin-bound iron to insoluble hemosiderin iron. Among patients with absent marrow hemosiderin iron, 81% had absent hepatocyte hemosiderin iron as well. Among patients with absent hepatocyte hemosiderin iron, 23% had absent and 77% normal or increased marrow hemosiderin iron. Therefore, in patients with iron depletion, assessment of marrow hemosiderin iron yields more relevant information of iron status than assessment of hepatocyte hemosiderin iron.     

Hepatic iron, liver steatosis and viral genotypes in patients with chronic hepatitis C

Hepatic iron has been described in hepatitis C virus (HCV) infection as an important cofactor of disease outcome. The mechanisms leading to hepatic iron deposits (HIDs) in HCV patients are partially understood. We investigated HIDs in the liver biopsies of a consecutive series of 242 HCV-infected patients with well-compensated liver disease. Serum ferritin was elevated in 20.7% and transferrin saturation in 19.0%, while 38.8% had stainable HIDs indicating that serum markers of systemic iron overload have low sensitivity in predicting HIDs in hepatitis C. A cut-off value of serum ferritin (350 microg/L in females and 450 microg/L in males) had good negative predictive value in excluding presence of mild-moderate HIDs (grade II-III). Hepatic iron deposits correlated by multivariate analysis with serum ferritin [odds ratio (OR) 1.008, 95% confidence interval (CI) 1.005-1.011] and albumin (OR 1.15, 95% CI 1.02-1.297). Hepatic iron deposits were more frequent in HCV-3-infected cases than in other genotypes (P = 0.027) while raised serum iron indices were more frequent in non-HCV-3 genotypes (P = 0.02). Furthermore, advanced fibrosis (F3-F4 by METAVIR) was more frequent in non-HCV-3 genotypes (P = 0.04). In HCV-3 cases there was a close association between HIDs and severe (grade II-III) steatosis (P < 0.00001). These results indicate that in well-compensated chronic hepatitis C HIDs are strongly associated with HCV-3 and viral-induced hepatic steatosis, while in the presence of other genotypes they might merely reflect a more advanced stage of liver disease and/or a systemic iron overload. Serum ferritin could identify a subgroup of patients in which the need of venesection could be excluded without liver biopsy.     

Red cell ferritin and iron stores in patients with chronic disease

Serum and red cell ferritin were determined in a heterogeneous group of 59 patients with chronic disease undergoing a bone marrow biopsy. There was very little correlation between serum and red cell ferritin (r = 0.53). Although serum ferritin increased in relation to increased bone marrow iron stores, only 1 out of 8 patients with absent marrow iron stores and none of 8 patients with reduced marrow iron stores had a decreased serum ferritin. In contrast, 6 of 8 patients with absent iron stores had a reduced red cell ferritin concentration. There was no significant difference between the mean red cell ferritin of the patients with reduced, normal and mild-moderately increased marrow iron stores (30, 26 and 34 ag/cell). Red cell ferritin was decreased in 78% of a group of 32 patients with a low mean cell volume. In the patients studied, red cell ferritin was a better indicator of absent iron stores than serum ferritin. However, red cell ferritin did not detect a reduction in the iron status until the marrow iron stores were completely depleted. Apparently, during normal erythropoiesis the primitive erythroblasts continue to take up iron irrespective of the amount of iron available in the stores.     

Anemia, iron deficiency, meat consumption, and hookworm infection in women of reproductive age in northwest Vietnam

Iron deficiency anemia poses an important public health problem for women of reproductive age living in developing countries. We assessed the prevalence of iron deficiency and anemia and associated risk factors in a community-based sample of women living in a rural province of northwest Vietnam. A cross-sectional survey, comprised of written questionnaires and laboratory analysis of hemoglobin (Hb), ferritin, transferrin receptor, and stool hookworm egg count, was undertaken, and the soluble transferrin receptor/log ferritin index was calculated. Of 349 non-pregnant women, 37.53% were anemic (Hb < 12 g/dL), and 23.10% were iron deficient (ferritin < 15 ng/L). Hookworm infection was present in 78.15% of women, although heavy infection was uncommon (6.29%). Iron deficiency was more prevalent in anemic than non-anemic women (38.21% versus 14.08%, P < 0.001). Consumption of meat at least three times a week was more common in non-anemic women (51.15% versus 66.67%, P = 0.042). Mean ferritin was lower in anemic women (18.99 versus 35.66 ng/mL, P < 0.001). There was no evidence of a difference in prevalence (15.20% versus 17.23%, P = 0.629) or intensity (171.07 versus 129.93 eggs/g, P = 0.412) of hookworm infection between anemic and non-anemic women. Although intensity of hookworm infection and meat consumption were associated with indices of iron deficiency in a multiple regression model, their relationship with hemoglobin was not significant. Anemia, iron deficiency, and hookworm infection were prevalent in this population. Intake of meat was more clearly associated with hemoglobin and iron indices than hookworm. An approach to addressing iron deficiency in this population should emphasize both iron supplementation and deworming.     

Inflammation and iron deficiency in the hypoferremia of obesity

CONTEXT: Obesity is associated with hypoferremia, but it is unclear if this condition is caused by insufficient iron stores or diminished iron availability related to inflammation-induced iron sequestration. OBJECTIVE: To examine the relationships between obesity, serum iron, measures of iron intake, iron stores and inflammation. We hypothesized that both inflammation-induced sequestration of iron and true iron deficiency were involved in the hypoferremia of obesity. DESIGN: Cross-sectional analysis of factors anticipated to affect serum iron. SETTING: Outpatient clinic visits. PATIENTS: Convenience sample of 234 obese and 172 non-obese adults. MAIN OUTCOME MEASURES: Relationships between serum iron, adiposity, and serum transferrin receptor, C-reactive protein, ferritin, and iron intake analyzed by analysis of covariance and multiple linear regression. RESULTS: Serum iron was lower (75.8+/-35.2 vs 86.5+/-34.2 g/dl, P=0.002), whereas transferrin receptor (22.6+/-7.1 vs 21.0+/-7.2 nmol/l, P=0.026), C-reactive protein (0.75+/-0.67 vs 0.34+/-0.67 mg/dl, P<0.0001) and ferritin (81.1+/-88.8 vs 57.6+/-88.7 microg/l, P=0.009) were higher in obese than non-obese subjects. Obese subjects had a higher prevalence of iron deficiency defined by serum iron (24.3%, confidence intervals (CI) 19.3-30.2 vs 15.7%, CI 11.0-21.9%, P=0.03) and transferrin receptor (26.9%, CI 21.6-33.0 vs 15.7%, CI 11.0-21.9%, P=0.0078) but not by ferritin (9.8%, CI 6.6-14.4 vs 9.3%, CI 5.7-14.7%, P=0.99). Transferrin receptor, ferritin and C-reactive protein contributed independently as predictors of serum iron. CONCLUSIONS: The hypoferremia of obesity appears to be explained both by true iron deficiency and by inflammatory-mediated functional iron deficiency.     

HFE mutations, iron deficiency and overload in 10,500 blood donors

People with genetic haemochromatosis (GH) accumulate iron from excessive dietary absorption. In populations of northern European origin, over 90% of patients are homozygous for the C282Y mutation of the HFE gene. While about 1 in 200 people in the general population have this genotype the proportion who develop clinical haemochromatosis is not known. The influence of HFE genotype on iron status was investigated in 10 556 blood donors. The allele frequencies of the C282Y and H63D mutations were 8.23% and 15.3% respectively. Heterozygosity for C282Y occurred in 1 in 7.9 donors, for H63D in 1 in 4.2 donors, and 1 in 42 were compound heterozygotes. Homozygosity for H63D occurred in 1 in 42 donors and 1 in 147 (72) were homozygous for C282Y. Mean values increased for transferrin saturation (TS) and serum ferritin (sFn), and decreased for unsaturated iron binding capacity (UIBC) in the order: donors lacking the mutations, H63D heterozygotes, C282Y heterozygotes, H63D homozygotes, compound heterozygotes and C282Y homozygotes, but serum ferritin (sFn) concentrations were no higher in H63D heterozygotes and C282Y heterozygous women than in donors lacking mutations. The percentage of donors failing the screening test for anaemia or of those with sFn < 15 microg/l did not differ among the genotype groups. C282Y and H63D heterozygotes and donors homozygous for H63D were at no greater risk of iron accumulation than donors lacking mutations, of whom 1 in 1200 had both a raised TS and sFn. The risk was higher for compound heterozygotes (1 in 80, P = 0.003) and for C282Y homozygotes (1 in 5, P < 0.0001). There was no correlation between sFn and either age or donation frequency in C282Y homozygotes. None of the 63 C282Y homozygous donors interviewed showed physical signs of overload or were aware of relatives with haemochromatosis. The Welsh Blood Service collects blood from about 140 000 people each year including an estimated 950 who are homozygous for HFE C282Y. They are probably healthy and unaware of any family history of iron overload.     

The influence of blood donation on iron stores assessed by serum ferritin and hemoglobin in a population survey of 1359 Danish women

Summary The general impact of blood donation on iron status was studied in a population survey comprising 1359 nonpregnant Danish women in age cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal; 180 (13%) were blood donors. Iron stores were assessed by serum (S-)ferritin and hemoglobin (Hb). Hb levels were not significantly different in donors: mean 137±10 (SD) g/l (8.5±0.6 mmol/l) compared with nondonors, 139±11 g/l (8.6±0.7 mmol/l). Values < 121 g/l (7.5 mmol/l) were observed in 3.3% of donors vs 3.8% of nondonors. Correlations between S-ferritin and Hb were without practical relevance:r _s=0.29,p<0.0001 in donors vsr _s=0.22, p<0.0001 in nondonors. Blood donation had a profound influence on iron status, especially in the premenopausal women population. Donors had lower S-ferritin than nondonors in all age-groups and in pre- and postmenopausal groups (p<0.001 in all groups). Premenopausal donors had a median S-ferritin of 31g/l vs 39g/l in nondonors, postmenopausal donors of 47g/l vs 72g/l in nondonors. S-ferritin values < 15g/l (i.e., depleted iron stores) were observed in 31.7% of premenopausal donors vs 15.2% of nondonors, and in 7.0% of postmenopausal donors vs 2.9% of nondonors. Iron deficiency anemia (i.e., S-ferritin < 15g/l and Hb < 121 g/l) was seen in 2.8% of donors vs 1.5% of nondonors. Donors using oral contraceptives had higher S-ferritin, median 33g/l compared with nonusers, 22g/l, and a lower frequency of depleted iron stores, 29% vs 39%. Ideally, the frequency of phlebotomy should be adjusted according to S-ferritin as well as Hb levels. If Hb is used as single criterion for donation, only donors with predonation values 124–125 g/l should be allowed to undergo phlebotomy.This study was supported by grants from the Health Insurance Foundation (H 11-23-89); the Danish Hospital Foundation for Medical Research, Region of Copenhagen, the Faroe Islands, and Greenland (no. 46-83); the Research Foundation of Danish Voluntary Blood Donors; the Danish National Board of Health; and Hässle A/S, DK-2620 Albertslund