Oral Iron Intake Research Articles

Pseudomelanosis duodeni: Associated with multiple clinical conditions and unpredictable iron stainability - a case series

Pseudomelanosis duodeni is seen endoscopically as dark spots in the duodenal mucosa and is generally considered to be local deposition of iron from oral iron intake. However, pseudomelanosis duodeni may be identified histologically even before it becomes endoscopically evident; iron stainability within the mucosa is uneven and unpredictable, and multiple clinical conditions other than oral iron intake may be associated. We reviewed 17 adult patients with histologically detected pseudomelanosis duodeni, their endoscopic appearances, iron stainability, and clinical findings including oral iron and drug intake. Only 6/17 (35 %) had endoscopically apparent dark spots. Perl's iron stain was entirely positive in 18 %, partially positive in 64 %, and negative in 18 % of cases. History of oral iron was present in 76 % of patients, but other clinical conditions consistently associated were hypertension in 88 %, end stage renal disease in 59 %, and diabetes mellitus in 35 % of patients.

Prevalence of Anemia among Healthy Women in 2 Metropolitan Areas of Japan

Anemia is common among young women, and iron deficiency is one of the leading causes. In Europe and the US, the iron fortification of flour increased oral iron intake and decreased anemia prevalence from 30% to 10%. The National Nutrition Survey in Japan revealed that anemia prevalence among young Japanese women is increasing; however, no nationwide preventive policy has been aimed at iron deficiency anemia. The endpoint of this study was the estimation of anemia prevalence among healthy Japanese woman, based on a large sample size. We collected data from the consecutive check-up examination records of apparently healthy women (n = 13,147). We defined hemoglobin lower than 12 g/dL as anemia, hemoglobin lower than 10 g/dL as severe anemia, and a mean corpuscular volume lower than 80 fl as microcytic anemia. Of the 13,147 persons, anemia was identified in 2331 (17.3 %), and severe and microcytic anemia in 438 (3.3 %) and 700 (5.2 %), respectively. Among women younger than 50 years, anemia was identified in 22.3 %, and 25.2 % of them had severe anemia. In conclusion, the prevalence of anemia and severe anemia among young women is high in Japan. Some action needs to be considered to improve women's quality of life.

Iron‐induced mucosal injury to the upper gastrointestinal tract

To define the causes and associations of mucosal iron deposition in upper gastrointestinal biopsy specimens and to describe the morphological features of iron-related injury. The histological pattern, intensity and distribution of iron in biopsies obtained from 1991 to 2005 were recorded and correlated with endoscopic and clinical findings. Twenty-five biopsies (16 gastric, four duodenal, five oesophageal) were accrued. Iron deposition was seen in two groups: 10 cases showed erosive injury, with brown-black crystalline material overlying eroded epithelium. These patients were taking oral iron tablets. The remaining 15 cases showed variable iron deposition in the surface epithelium, lamina propria and glands. In nine patients, there was a history of oral iron intake and at least eight had had blood transfusions. The most intense iron deposition was noted in patients with end-stage liver disease. The mean age of patients with erosive injury was 43% higher than in the iron overload group (76 versus 53 years). Iron stains were also performed on 15 normal gastric biopsies and five biopsies with chronic, non-specific gastritis; all were negative for haemosiderin deposition. Iron-related erosive injury is related to oral iron pill ingestion and occurs in older patients. Mucosal iron deposition is also associated with iron overload disorders.

The Prevalence of Anemia among Healthy Women in Japan.

IntroductionAnemia is common among young women. National Health and Nutrition Examination Survey (NHENES) revealed that the insufficient iron intake is one of the leading causes of anemia in the US. In Europe and the US, iron fortification of flour increased oral iron intake and decreased anemia prevalence from 30% to 10%. The National Nutrition Survey in Japan by the Ministry of Health, Labour and Welfare in 2002 revealed the estimated anemia prevalence of 19 %. Currently, no nationwide preventive policy aims at iron deficiency anemia. However, the prevalence of 19% was estimated based on 3,156 persons in the Survey.ObjectiveThe endpoint of this study was to estimate anemia prevalence among healthy Japanese woman based on a larger sample size.MethodWe collected data from consecutive check-up examination records of apparently healthy women in different age groups in Toranomon Hopital (between January 2002 and March 2005, n = 8,264) and Yuai Memorial Hospital (between February 1998 and February 2005, n = 5,153). We defined hemoglobin lower than 12 g/dL as anemia, hemoglobin lower than 10 g/dL as severe anemia, and mean corpuscular volume lower than 80 fl as microcytic anemia.ResultsThe median age was 47 years (range, 11–87 years). Of the 13,147 persons, anemia was identified in 2,331 (17.3 %), and severe and microcytic anemia in 438 (3.3 %) and 700 (5.2 %), respectively. The prevalence of anemia and median hemoglobin values by age groups are shown in Figure. The median hemoglobin values tended to be lower in women of the age groups with high anemia prevalence.ConclusionThe prevalence of anemia among women of child-bearing age and of working age is high in Japan. As the Japanese population is rapidly decreasing and aging, some action needs to be considered to improve quality of life during pregnancy and working efficiency. [Display omitted]

Monitoring of hematological, inflammatory and oxidative reactions to acute oral iron exposure in human volunteers: Preliminary screening for selection of potentially-responsive biomarkers

Background: Iron is an essential micronutrient but also a major catalyst of oxidative and inflammatory reactions. Objective: To evaluate the potential utility of selected biomarkers in blood or urine to indicate in vivo oxidative or inflammatory response to oral iron intake at pharmacological doses. Methods: Three healthy volunteers provided morning, fasting samples of blood and urine on up to 13 study days—3 before, 7 during and 3 following a 7-consecutive-day period of receiving 120 mg of iron per day as ferrous sulfate in commercially available syrup. A series of 23 biomarkers were measured on each collection of biological fluids to monitor iron-responsive changes in biomarkers related to hematological or iron status, inflammation and in vivo oxidation. Results: Among the inflammatory biomarkers measured, white blood cells, serum CRP and urinary neopterin showed no response to iron dosing. Only circulating interleukin-4 (IL-4) and TNF-α had abnormal responses with a time association to the oral iron intake. Among the oxidative biomarkers, expression of blood superoxide dismutase (SOD), hemoxygenase-1, catalase as well as circulating thiobarbituric acid reactive substances (TBARS), total oxidative capacity and carbonyl proteins were stable in response to iron exposure. Only urinary TBARS, 8-hydroxy-2-desoxyguanosine and isoprostanes evidenced consistent or suggestive responses to ingestion of the iron challenge. Serum hepcidin concentration increased dramatically in all three subjects after only the first 120 mg dose of iron, and remained elevated even 9 days after cessation of the iron intervention. Conclusions: Most of the candidate biomarkers show very limited promise as response-indicators to oral iron dosing at the 120 mg dosages or lower, but circulating IL-4, TNF-α as well as urinary TBARS, 8-hydroxy-2-desoxyguanosine and isoprostanes showed potential utility as reliable indicators of oxidative and inflammatory response to oral ferrous sulfate.

Does nitric oxide contribute to iron-dependent brain injury after experimental cerebral ischaemia?

Experimental and clinical data suggest that iron has a key role in cerebral ischaemia. We measure infarct volume and analyse the nitric oxide responses to brain injury in rat stroke model after increased oral iron intake. Permanent middle cerebral artery occlusion (MCAO) was performed in a group of 20 male Wistar rats, 10 of which were fed with a control diet and 10 of which were fed with iron-enriched diet containing 2.5% carbonyl iron for 9 weeks. L-arginine and nitric oxide metabolites were determined in blood samples before and at 2, 6, 8 and 48 h after MCAO. Infarct volume, thiobarbituric acid reaction substances (TBARS) and tissue iron were measured at 48 h. Infarct volume was 66% greater in the iron-fed rats than in the control group. Iron-fed animals showed significantly higher levels of TBARS. Liver iron stores (3500 +/- 199 vs 352 +/- 28 microg Fe/g, p<0.0001) but not brain iron stores (131 +/- 11 vs 139 +/- 8 microg Fe/g, p=0.617), were significantly higher in the iron-fed group. L-arginine levels were slightly lower in iron-fed rats and decreased significantly in both groups at 6 and 8 hours after MCAO. The levels of the stable end products of NOS (NOx = nitrite + nitrate) were significantly higher in iron-fed rats before MCAO (16.2 +/- 2.2 vs. 9.6 +/- 0.8 micromol x L(-1), p<0.05), with a further increase during the six first hours after MCAO in both groups. These results suggest that the iron overload that increases both superoxide and nitric oxide production leads to peroxynitrite formation, thus enhancing brain damage.

Iron intake increases infarct volume after permanent middle cerebral artery occlusion in rats

Experimental and clinical data suggest an important role of iron in cerebral ischaemia. We measured infarct volume and analysed the oxidative stress, and also the excitatory and inflammatory responses to brain injury in a rat stroke model after an increased oral iron intake. Permanent middle cerebral artery occlusion (MCAO) was performed in ten male Wistar rats fed with a diet containing 2.5% carbonyl iron for 9 weeks, and in ten control animals. Glutamate, interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were determined in blood samples before and at 2, 4, 6, 8, 24 and 48 h after MCAO, and thiobarbituric acid reaction substances (TBARS) were analysed at 48 h. Infarct volume was measured at 48 h by image analysis on brain slices stained with 1% TTC. Tissue iron was measured by atomic absorption spectrophotometry. Infarct volume was 66% greater in the iron fed rats than in the control group (178±49 mm 3 versus 107±53 mm 3, P<0.01). Significant higher levels of glutamate, IL-6 and TNF-α were observed in the group with iron intake (peak values were obtained at 6, 8 and 4 h, respectively). Iron-fed animals also showed significantly higher levels of TBARS than those receiving a normal diet (6.52±0.59 vs. 5.62±0.86 μmol/l, P=0.033) Liver iron stores (3500±199 vs. 352±28 μg Fe/g, P<0.0001), but not brain iron stores (131 vs. 139 μg Fe/g, P=0.617), were significantly higher in the iron fed rats group. These results suggest that iron intake is associated with larger infarct volumes after MCAO in the rat. This effect seems to be associated with higher oxidative stress, excitotoxicity and inflammatory responses.

Bioavailability of Petit-Suisse cheese as food vehicle for iron fortification estimated by the prophylactic method.

Microencapsulated ferrous sulfate (SFE-171) and ferric orthophosphate in Petit-Suisse cheese were examined for iron bioavailability by the prophylactic method. The iron sources were industrially added to different samples of Petit-Suisse cheese, which were mixed with other food components in our laboratory before use. A reference standard diet inclusive of nonmicroencapsulated ferrous sulfate and a control diet low in iron content were prepared in the laboratory. The final iron content in the fortified diets was approximately 15 mg Fe/kg diet. These diets were administered to weaning rats for 23 days. The iron bioavailability was evaluated as the ratio of iron incorporated into hemoglobin to oral iron intake, thereby being estimated as 62.6 +/- 8.8% for ferrous sulfate and 59.2 +/- 10.6% for SFE-171, which were significantly effective at p < 0.01 compared to 43.4 +/- 10.5% for ferric orthophosphate. It thus turned out that SFE-171 was stable through industrial processing with Petit-Suisse cheese as the food vehicle and served as an iron fortifier equal to ferrous sulfate in bioavailability.

The Clinical Expression of Hemochromatosis in Oslo, Norway: Excessive Oral Iron Intake May Lead to Secondary Hemochromatosis Even in HFE C282Y Mutation Negative Subjects

Background: The prevalence of hereditary hemochromatosis in Norway is one of the highest reported in the world. However, the clinical presentation in patients with hemochromatosis in Norway seems to be different compared with recent studies elsewhere. The aim of this study was to investigate patients with hemochromatosis in one community hospital in Norway and to study the prevalence of the C282Y mutation. Methods: One hundred and twenty patients were consecutively admitted to one medical department in Oslo. Serum transferrin and ferritin concentrations were measured in all patients, and a percutaneous liver biopsy was obtained in 108 of 120 (90%) patients. Stainable iron (Perls stain) in hepatocytes was graded from 0 to 4+ and fibrosis from 1 to 4. Genotyping for the C282Y and H63D mutation in the HFE gene was performed by PCR-RFLP. Results: Forty-eight (40%) of the patients suffered from tiredness and astenia and 29 (24%) had typical arthropathy. Only 5 of 105 (4.5%) had biopsy confirmed cirrhosis and 5 had diabetes mellitus. Patients referred from a blood bank had significantly less symptoms and signs compared with other patients. Twenty-one of 120 (17.5%) patients were C282Y mutation negative. Seventeen (81%) of these patients (16 women and 1 man) had a history of extensive oral iron intake lasting from 5 to 50 years. When excluding those with extensive oral iron intake (n = 17), 92 of 103 (89%) were homozygous for the C282Y mutation, 7 (7%) were heterozygous including 3 compound heterozygous and 4 (4%) were mutation negative. Conclusions: Only a minority of our patients with hemochromatosis had a far advanced disease at the time of diagnosis (less than 5% had cirrhosis) and hemochromatosis in a majority of the C282Y mutation negative patients was associated with excessive oral iron intake for several years.

Oral iron intake for several years may induce hemochromatosis in patients without the HFE-gene C282Y mutation

Oral iron intake for several years may induce hemochromatosis in patients without the HFE-gene C282Y mutation

Oral intake of cadmium, cobalt, copper, iron, lead, nickel, manganese and zinc in the University student's diet

A duplicate diet meal study was carried out with a group of university students living in a hostel, in order to estimate the intake of Zn, Cd, Co, Cu, Fe, Mn, Ni and Pb. Zn, Cu, Fe, Mn and Ni were determined by flame atomic absorption spectrophotometry and Cd, Co and Pb by graphite furnace atomic absorption spectrophotometry after a nitric acid wet digestion procedure. The estimated intake values from the contents of breakfast, lunch, dinner and drinks were compared with the values of the Provisional Tolerable Daily Intake (PTDI) in the case of Cd and Pb, Recommended Dietary Allowances (RDA) of Co, Fe and Zn and Estimated Safe and Adequate Dietetic Daily Intake (ESADDI) of Cu and Mn. Neither excessive intake of Pb and Cd nor deficiencies in Zn, Co, Fe, Mn or Ni were observed, but Cu intake was lower than the ESADDI.

ESTIMATED IRON BALANCE AND PLASMA FERRITIN LEVELS IN VLBW INFANTS

25 VLBW infants (BW 1.3 kg) had plasma ferritin levels (PF), Hgb, Hct, and MCV measured when they reached about 2 kg in weight. 10 of them had bronchopulmonary dysplasia (BPD). None of these infants were supplemented with medicinal iron or received iron-fortified formula. Estimated iron balance (EIB) was determined by calculating iron intake from milk ingested, whole blood and packed red cells, and losses from blood drawing. Plasma ferritin was measured by RIA. Their gestational age was 29 ±2.4 wks. Results are expressed in the table as × ± SD. Plasma ferritin levels ranged from 34 to 430 ug/l. There was no significant correlation between oral intake of iron and plasma ferritin levels. However, there was correlation between iron balance and plasma ferritin levels (y=43+1.43×, r:0.58, SEE:18.3, p 0.01). Infants with BPD had higher plasma ferritin levels than those without BPD, which may reflect the more frequent transfusions. These data suggest that in VLBW infants, iron supplementation is not indicated prior to their reaching 2 kg in weight.

EXCESSIVE ORAL IRON THERAPY CAUSING HAEMOCHROMATOSIS.

There are many similarities between primary haemochromatosis and the iron-overload state induced in some patients by multiple blood transfusions (Aufderheide, Horns, and Goldish, 1953) or excessive iron intake (Wallerstein and Robbins, 1953 ; Goldish and Aufderheide, 1953). However, it is uncertain whether the end state in the two disorders is the same. Only a few patients given excess iron develop pathological changes, while the majority merely show increased iron deposition without cell damage. There is doubt, therefore, whether the tissue changes result from the presence of the iron alone or from some other factor, possibly related to the illness for which the transfusion or iron has been given (Bothwell and Finch, 1962). The occurrence of a patient with features of haemochromatosis apparently induced by excessive oral intake of iron and who is otherwise normal is therefore of interest. The following case is believed to be only the second one to be described (Castleman and Towne, 1958).