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Although the iron-heart disease hypothesis is prevalent, the epidemiological findings are incongruent. The relationship of serum ferritin with early cardiovascular disease (CVD), particularly atherosclerosis, has not been evaluated extensively, particularly with accounting for inflammation. We examined this association in a case-control study of 124 age- and sex-matched pairs embedded in the population-based random sample (MONICA survey) in Southwest France, taking into account inflammation status. Cases had >or=2 carotid atherosclerotic plaques and controls had none. Inflammation was assessed using several markers, including serum alpha-1 acid glycoprotein (AGP) and high sensitivity C-reactive protein. There was an interaction of inflammation with group (case/control) for serum ferritin. In adults without elevated AGP, serum ferritin was significantly greater in atherosclerotic cases than in adults in the control group. In models adjusted for CVD risk factors, the odds of atherosclerosis increased with the increase in serum ferritin in individuals without elevated AGP; for every 10-microg/L increase in serum ferritin, the risk for atherosclerosis increased by 3% (odds ratio [95% CI]: 1.03 [1.01-1.06]). In conclusion, carotid atherosclerosis was positively associated with serum ferritin in individuals free from subclinical inflammation based on AGP. Further prospective and/or experimental studies are needed to corroborate the observed association of iron status with atherosclerosis.

Background: Spot ferritin assay on dried serum spot (DSS) samples provides reliable and accurate assessment. Standard DSS preparations, however, involve precise serum aliquots and require some skill and training of field personnel., Objective: We evaluated the validity of the spot ferritin assay on DSS samples prepared by simplified approaches and standard technique in Guatemala City., Design: Venous blood (5 mL) was obtained from 104 subjects aged 24 +/- 15 y (x +/- SD) and transferred into nonheparin-containing (2 plain and 2 self-sealing) capillary blood collection tubes. Three DSS samples were prepared: A (standard, 20 microL serum), B (blot, approximately 30-35 mm serum column), and C (dispenser, 20 microL serum pushed directly from self-sealing capillary tubes with a dispenser). Spots were air-dried and placed in hermetic plastic bags with a desiccant. Two weeks later, entire spots for DSS A and C samples and a circle in the center for DSS B samples were analyzed., Results: DSS ferritin A, B, and C correlated strongly with traditional ferritin (r = 0.71-0.88, P < 0.001). The geometric mean (-1 SD and +1 SD) values for the DSS A, B, and C and traditional ferritin methods were 27.5 (12.6, 60.2), 32.4 (13.5, 77.6), 27.5 (11.7, 64.6), and 30.2 (13.8, 66.1) microg/L, respectively, and did not differ significantly. The difference in ferritin values by various DSS approaches compared with the traditional approach was small (<4 microg/L; P > 0.05)., Conclusions: Simplified and standard DSS methods provide accurate iron-status assessment in population studies. The simplified DSS approaches for serum ferritin measurement need to be evaluated further in populations in whom iron deficiency is prevalent.

Despite advances in scientific knowledge regarding multiple etiology, treatment, and potential strategies for combating iron deficiency and deficiencies of other micronutrients, iron deficiency anemia, vitamin A deficiency, and iodine deficiency remain significant public health challenges for growing children and adolescents. The short-term efficient supplementation approach, although technically feasible, has not been successful due to problems with delivery and compliance. Evidence is building that preventive supplementation coupled with nutrition education may be a more effective strategy associated with better compliance and improvement in iron status. Long-term, effective approaches include fortification, dietary modification, public health and disease control measures, and income generation programs. Food fortification can be a cost-effective intervention strategy if technologically feasible, nutritionally sound, culturally acceptable and economically viable food vehicle(s) and fortificant(s) can be identifed. Foods such as wheat, rice, and salt are commonly consumed in India; research is underway to evaluate various fortificants for these foods. Doubly fortified salt with iodine and iron may be particularly promising in the Indian situation as it is affordable, culturally acceptable, and may enhance iron absorption from Indian dietaries containing inhibitors of iron absorption. Feasibility studies are underway to evalute the stability and storage issues as well as bioavailability of fortificant iron. Dietary modification involves increased iron intake, by increasing total food intake and consumption of locally available iron-rich foods, and dietary practices favoring iron absorption. Blood loss associated with worm infestation can be controlled by periodic deworming and reducing reinfestation. Coordinating these major intervention approaches by building partnerships between the community, existing nutrition and health programs, government, industry, and academic institutions is critical for success of these programs. Nutrition education must be integral to all of these strategies discusssed. Primary health care system and school infrastructure and staff, along with school children and community members, can be powerful resources for addressing malnutrition in children and adolescents.

In the context of a larger study examining the interaction of vitamin A (VA) status and age on immune function, we examined age-related changes in hematologic and iron status variables in male Lewis rats. Animals were fed a nutritionally adequate purified diet containing either 0.35 (marginal), 4.0 (control) or 50 (supplemented) mg retinol equivalents (as retinyl palmitate) per kg of diet from the time of weaning until killing at 8-10 (middle-aged) or 20-22 (old) mo of age. Neither VA nor VA and age interaction effects were significant for most iron variables examined. After controlling for body weight, old rats had significantly lower hemoglobin, hematocrit and plasma iron than middle-aged rats. This decrease in hematologic and transport iron variables was not accompanied by a shift of iron into other storage compartments. Old rats also had significantly lower total iron content and iron concentration in liver, spleen and bone marrow. Hemosiderin iron in marrow smears correlated significantly (r = 0.43-0.76, P: < 0.05) with chemical estimates of iron in storage, transport and functional pools. Old rats also tended to have less stained iron in femur marrow smears. Thus, body iron in functional, transport and storage compartments, namely the liver, spleen and bone marrow, were significantly lower in old than in middle-aged rats. Although iron stores and status are usually considered to increase with advancing age, our data show a consistent pattern of lower hematologic and storage iron variables in old than in middle-aged Lewis rats. Future research is indicated to understand the biology and functional consequences of the observed age-associated decline in body iron.

The effect of erythropoietin administration on the absorption of dietary and therapeutic iron was examined in patients with anemia of chronic renal failure on maintenance hemodialysis. Absorption from test meals tagged extrinsically with iron 55, iron 59, or both was determined 2 weeks later by using incorporated red blood cell radioactivity and whole body counting. In an initial study of food iron absorption, the effect of initiating erythropoietin therapy was determined by measuring the absorption of heme and nonheme iron before and 2 weeks after the administration of 64 U/kg body weight erythropoietin (range, 46-85 U/kg body weight) three times weekly. Absorption of heme iron increased 1.6-fold from 18.6% to 30.1% (P < .05), and nonheme iron increased 3.7-fold from 1.3% to 4.9% (P < .01) after erythropoietin therapy. In a second study therapeutic iron absorption was evaluated at baseline and after erythropoietin administration (63 U/kg body weight (range, 48-74 U/kg body weight) three times weekly). The absorption of 50 mg of iron as ferrous sulfate increased 2.4-fold from 3.8% to 9.4% (P < .05) when given without food and 4.2-fold from 1.4% to 5.9% (P < .05) when given with food after erythropoietin administration. After adjusting for changes in iron stores with serum ferritin after erythropoietin therapy, the enhanced erythropoiesis associated with erythropoietin therapy increased absorption about 2-fold, which was similar to the response observed previously in normal subjects. In a final study we examined the absorption of therapeutic iron during the steadystate phase of erythropoietin therapy after an erythroid response to erythropoietin had occurred. The absorption of 50 mg of iron was lower than that occurring with the initiation of erythropoietin therapy at 2.2% when given alone and 1.3% when taken with food. We conclude that iron absorption with or without erythropoietin stimulation is unimpaired in patients with chronic renal failure.

A spot method was developed for analyzing ferritin from 20-microL serum samples (n = 71) that were spotted and dried on filter paper and stored frozen (2 d). Spot samples were thawed, incubated in a buffer containing cellulase, and centrifuged and the supernate assayed for ferritin by a commercial radioimmunoassay. The geometric means (+/- 1 SD) for ferritin analyzed with the spot and traditional methods were 49.4 (range: 14.9-164.0) and 47.5 (range: 14.4-156.0) micrograms/L, respectively. The two methods correlated strongly (r = 0.98, P = 0.0001). Storage of spot samples (n = 31) under various conditions (at room temperature, refrigerated, or frozen for 2 wk, or at room temperature for 4 wk) in airtight bags before analysis yielded ferritin values that were not significantly different from those obtained by the traditional method. Ferritin values from spotted samples stored at room temperature for 4 wk before being analyzed were only 2.2 micrograms/L higher than those from samples analyzed by the traditional method. With iron depletion defined as a serum ferritin concentration < 15 micrograms/L, this method corresponded absolutely with the traditional method in classifying individuals as iron sufficient or deficient. Thus, the spot ferritin method (with samples stored at room temperature for 4 wk) offers a reliable, accurate, and practical tool for iron status assessment in field studies. Capillary blood can be sampled to avoid the costs and concerns associated with venipuncture and spotted serum samples can be stored at room temperature for > or = 4 wk, eliminating the need for freezing during storage and transportation.

Objective: To determine the day-to-day variation in biochemical measures of iron status in a group of elderly women with rheumatoid arthritis compared with a group of healthy elderly women., Design: Venous blood samples were collected from each subject on 3 nonconsecutive days during a 2-week study period; subjects had fasted overnight. Variability in hemoglobin level, hematocrit value, serum iron concentration, total iron-binding capacity, transferrin saturation, serum ferritin concentration, and plasma transferrin receptor level was determined., Subjects: Two groups of women, one with rheumatoid arthritis (n=10) and another that was apparently healthy (n=10)., Statistical Analyses: Variance component analysis was used to estimate the biological variation (sigma square day) and analytic variation (sigma square rep) for each iron index. The coefficient of variation (CV) for each variance component was calculated: coefficient of biological variation = CV day, coefficient of analytic variation = CV rep, and coefficient of a single future determination = CV fd., Results: The CV rep for all iron indexes was smaller than the CV day in both groups. The CV day was considerably higher for serum iron concentration and for transferrin saturation than for the other indexes in both groups (16.6% and 16.6% in healthy subjects and 33.6% and 28.2%, respectively, in subjects with rheumatoid arthritis). The higher CV day for serum iron concentration and transferrin saturation translated into a higher CV fd for these indexes. Because of the higher variance for these two indexes, more sampling days were required for reliable estimates. CV day and CV fd for plasma transferrin receptor level were relatively low., Conclusions: These findings corroborate our previous finding that variation of serum ferritin concentration in the elderly is lower than that demonstrated in younger populations. This aging effect persists in the presence of rheumatoid arthritis. Fasting appeared to improve reliability in the determinations for serum iron concentration and transferrin saturation. Variability estimates for the indexes other than serum iron concentration and transferrin saturation were not altered by the inflammation of rheumatoid arthritis. Plasma transferrin receptor level is a reliable index for assessing iron status in populations with rheumatoid arthritis.

To differentiate iron-deficiency anemia and anemia associated with chronic inflammatory diseases in elderly women, subsets of laboratory, dietary, and functional assessment variables were obtained by using discriminant analysis. Fifty-one subjects (70-79 y of age) were classified into one of four groups on the basis of the presence of iron deficiency and chronic inflammatory disease. Iron deficiency was defined on the basis of a significant response in hemoglobin concentration after iron supplementation. The discriminating subset of laboratory tests consisted of measures for serum ferritin, plasma transferrin receptors, and erythrocyte sedimentation rate. The discriminant function classified subjects into iron-deficient, anemia of chronic disease, or a category in which the two coexist, with an error rate of 18.6%. The addition of other variables (dietary iron and functional assessment information) did not appreciably improve the classification. The results of these three key laboratory tests may help to identify functional iron deficiency in the presence of chronic inflammation.

The present investigation was undertaken to assess the efficacy of oral iron supplementation during pregnancy by using a gastric delivery system (GDS). Three hundred seventy-six pregnant women between 16 and 35 y of age and 14 and 22 wk gestation were selected if mild anemia was present (hemoglobin concentration 80-110 g/L). The participants were randomly assigned to one of three study groups given no iron, two FeSO4 tablets (100 mg Fe) daily, or one GDS capsule (50 mg Fe) daily. Blood was obtained initially and after 6 and 12 wk for measurement of red blood cell and iron indexes, including serum transferrin receptor. There was a significant and comparable improvement in hematologic and iron-status measurements in the two groups of women given iron whereas iron deficiency evolved in women given no iron supplement. We conclude that by eliminating gastrointestinal side effects and reducing the administration frequency of an iron supplement to once daily, a GDS offers significant advantages for iron supplementation of pregnant women.

Day-to-day variability in biochemical indicators of iron status in well-hydrated and healthy women 70-79 y old (n = 10) was determined. Venous blood was collected on 4 nonconsecutive days during a 2-wk period. Analytical (sigma 2 rep) and biological (sigma 2 fd) variance components were computed based on a previously established scheme in younger adults. These two variance components were summed to obtain the total day-to-day variability (sigma 2 fd). Our results indicate that biological variation contributed most to the intraindividual variation. We calculated that sampling once for most iron indexes and twice for plasma transferrin receptors in elderly individuals is adequate to accurately determine these indexes whereas serum iron and transferrin saturation, indexes with high CVfd, require seven and eight measurements, respectively. These data, compared with previously published data in younger adults, demonstrate that aging is associated with a decreased variation in some indexes of iron status such as serum ferritin.