Reduction Of Body Iron Stores Research Articles

Biology of Anemia: A Public Health Perspective

Our goal is to present recent progress in understanding the biological mechanisms underlying anemia from a public health perspective. We describe important advances in understanding common causes of anemia and their interactions, including iron deficiency (ID), lack of other micronutrients, infection, inflammation, and genetic conditions. ID develops if the iron circulating in the blood cannot provide the amounts required for red blood cell production and tissue needs. ID anemia develops as iron-limited red blood cell production fails to maintain the hemoglobin concentration above the threshold used to define anemia. Globally, absolute ID (absent or reduced body iron stores that do not meet the need for iron of an individual but may respond to iron supplementation) contributes to only a limited proportion of anemia. Functional ID (adequate or increased iron stores that cannot meet the need for iron because of the effects of infection or inflammation and does not respond to iron supplementation) is frequently responsible for anemia in low- and middle-income countries. Absolute and functional ID may coexist. We highlight continued improvement in understanding the roles of infections and inflammation in causing a large proportion of anemia. Deficiencies of nutrients other than iron are less common but important in some settings. The importance of genetic conditions as causes of anemia depends upon the specific inherited red blood cell abnormalities and their prevalence in the settings examined. From a public health perspective, each setting has a distinctive composition of components underlying the common causes of anemia. We emphasize the coincidence between regions with a high prevalence of anemia attributed to ID (both absolute and functional), those with endemic infections, and those with widespread genetic conditions affecting red blood cells, especially in sub-Saharan Africa and regions in Asia and Oceania.

Necessity of Implementing Ferritin Testing for Regular Blood Donors – A Cross-sectional Analysis of Serum Ferritin Levels in Individuals Donating Blood at Various Frequencies in a Year at a Regional Blood Transfusion Center

Background and Objectives: The virtuous act of blood donations should be encouraged and promoted by all means while safeguarding the well-being of the donor. If regular blood donations lead to iron store depletion in any individual, it may be identified and preventive measures should be taken. The current practice of hemoglobin (Hb) testing alone before donation may not detect the depletion of iron stores. Yet, a policy to introduce tests for iron stores and iron supplementation in regular donors requires extensive research in this area because of the cost and feasibility concerns. The objectives were to study the prevalence of subclinical anemia among voluntary blood donors using serum ferritin levels attending the blood transfusion center and to compare the average Hb and serum ferritin levels of donors across different age groups, gender, and donation frequencies. Methods: A cross-sectional study was done on 300 consecutively enrolled voluntary whole-blood donors (December 2018–November 2019) who fulfilled eligibility criteria. Donors were further divided into four groups, depending on their number of donations. Their samples were tested for Hb and serum ferritin to check for reduced body iron stores. The data obtained were analyzed using SPSS version 23. Results: A total of 300 regular voluntary donors were included in the study. 57.7% of donors were in the age group of 20–29 years, of which 83.33% were males. The total prevalence of subclinical anemia was 16%, in whom 54.2% were males and 45.8% were females. Out of the total female donors in our study (50), 44% suffered from subclinical anemia. Out of the total male donors in the study (250), 10.4% suffered from subclinical anemia. There was a significant association between frequency of donation and subclinical anemia (odds ratio [OR] =6.36, P < 0.001). There was a significant association between subclinical anemia across gender (high for females; OR = 6.76, P < 0.001). There was a significant correlation between the frequency of donation and serum ferritin (Spearman correlation coefficient: −0.299), but there was no correlation observed between the frequency of donation and Hb levels. Conclusion: The study demonstrates the depletion of iron store with increasing donation frequency. This calls for continual supervision of body iron stores rather than Hb alone to ensure the continuous supply of healthy blood donors.

Effect of HFE Gene Mutation on Changes in Iron Metabolism Induced by Nordic Walking in Elderly Women.

BackgroundExcess iron accumulation in human tissue is associated with the diet, lack of exercise, or genetic factors. Iron accumulation increases the risk of acute myocardial infarction, diabetes, and cancer. On the other hand, exercise reduces the risk of several morbidities and influences iron metabolism. Here, we evaluated changes in iron metabolism induced by exercise in elderly women bearing the H63A HFE mutation.PurposeTo identify a factor that modulates the effect of exercise on iron metabolism. We investigated whether regular exercise induces similar changes in iron metabolism, mainly manifested by lowered body iron stores, in individuals bearing the wild-type (WT) and mutated HFE gene.Subjects and MethodsSeventy-six women (average age 69.2±5.6 years old) were enrolled in the study. Thirty-nine women participated in 12 weeks of Nordic walking (NW) training; the remaining participants were assigned to the control group. Based on the H63A HFE mutation status, the NW group was divided into women bearing the mutation (HET, n=12) and women with the WT gene (WT, n=27).ResultsThe training resulted in a statistically significant reduction in the serum iron (p=0.03) and ferritin levels (p=0.001); hepcidin levels remained unchanged. No differences in these parameters were noted between the HET and WT groups.ConclusionThese observations suggest that a reduction in body iron stores might constitute an important aspect of the health-promoting effect of exercise, regardless of the genetic background.

Hematological, biochemical and antioxidant indices variations in regular blood donors among Mediterranean regions

Background & objectivesOne of the most important problems in Mediterranean regions is finding blood donors to overcome the high need of its population. Understanding the health benefits of blood donation frequency will activate more volunteers to donate. The aim of this study variations of hematological and biochemical indices in regular male and female donors from Greece and Italy MethodsA cross-sectional study consisted of 350 voluntary blood donors (VDs)was conducted in two mediterranean Blood Banks, Greece and Italy. The first one from the General Hospital of Naousa, Greece on samples of 90 regular and 60 first-time blood donors. The second one from AOU Sassari, Sardinia, Italy on convenient samples of 100 first-time samples and 100 regular blood donors. Donors' particulars were obtained from blood bank records. The hematological and biochemical parameters were determined for all donors and Total Antioxidant Status (TAS) only for greek VDs. ResultsHigh frequency blood donation of Greek VDs could be associated with evidence of reduction of body iron stores, reduced oxidative stress and improvement of liver function biomarkers in regular groups. Interestingly, Sardinian regular male VDs presented increased iron stores in compare with the first time VDs. In both Mediterranean populations (Greeks and Italians) the lipid profile of the female regular blood donors has been improved in compare with the first timers. ConclusionRegular blood donation increases antioxidant capacity and affects positively the hematological parameters and biochemical biomarkers in donors. Gender plays an important role in relation to all hematological and biochemical parameters. Further studies in larger population should evaluate the beneficial-effect of blood donation and promote people to donate more frequent.

Impact of Regular Whole-Blood Donation on Body Iron Stores

Background and Objectives: Regular and repeat blood donations may cause reduced body iron stores (BIS), which may lead to a shrinking donor pool. Furthermore, hemoglobin (Hb) itself is quite an inadequate measure to detect iron deficiency. Hence, our primary aim was to understand the effect of repeated blood donations on BIS in regular blood donors. Study Design and Setting: We conducted a prospective study on voluntary whole-blood donors (September 2015 through August 2017). Donor demographics were noted. Donors were further divided into four groups, depending on their number of donations. Their samples were tested for Hb, red cell indices, and serum ferritin to check for reduced BIS. The data obtained were analyzed using SPSS version 20 (IBM, USA). Results: A total of 374 regular voluntary blood donors were included in the study. The mean serum ferritin levels in males and females were 75.4 and 36.2µg/L, respectively. There was a 45% decrement in the mean serum ferritin values in Group I (101.57 µg/L) in contrast to Group III (56.69 µg/L) (p < 0.0032). In the study, 9.8, 11.2, and 4.8% of the donors were in Stage 1, Stage 2, and Stage 3 of reduced BIS, respectively. Of the donors, 11.2% were in Stage 2 of reduced BIS. Further donations in such cases can compromise donor safety. Conclusion: The present study demonstrates iron depletion in regular voluntary blood donors. In 11.2% of the donors, iron deficiency erythropoiesis was noted. A ferritin screening after the first donation followed up at the tenth donation might help detect iron-deficient individuals. Iron supplementation for all regular blood donors and female donors in particular will help prevent the shrinking donor pool due to iron deficiency.

Assessment of ultrasound flow-mediated dilation of brachial artery in regular blood donors in a Nigerian Tertiary Hospital

Background: Iron is a pro-oxidant cofactor that may be linked to cardiovascular disease (CVD) progression and reduction of body iron stores have been hypothesized to reduce the risk of CV disease. Aim: The aim of this study is to assess reduction in CVD risk susceptibility among regular blood donors compared with nondonors using ultrasound brachial artery flow-mediated dilation (BAFMD). Settings and Design: A prospective comparative study designed to establish the difference between mean flow-mediated dilatation (FMD) in the patients who are regular blood donors compared with nondonors recruited from a Teaching Hospital donor clinic. Materials and Methods: Data were collected over 7 months from December 2014 to June 2015. 100 eligible regular male blood donors, aged 21–50 years, were selected from a Teaching Hospital blood donor records and their BAFMD assessed. 50 nondonors/ first time donors, of equivalent age group, consecutively were assessed for comparison. Serum markers of iron stores, markers of oxidative stress and other related cardiac risk factors were also assessed in all patients. Results: BAFMD was significantly greater in regular blood donors when compared with nondonors (13.95% ± 7.02% vs. 8.20% ± 4.19%, P = 0.000). Serum ferritin was significantly decreased in regular blood donors when compared with nondonors (mean value 41.92 ng/ml ± 23.12 ng/ml vs. 61.97 ± 30.19 ng/ml, P = 0.000), but Hb did not differ between the groups. High FMD was significantly associated with high C-high-density lipoprotein and low C-LDL (r = −0.215*, P = 0.032, r = 0.188, P = 0.031, r = 0.193, P = 0.027, r = 0.0279, P = 0.002, r = 0.139, P = 0.084). LDL was decreased in regular blood donors compared with nondonors. Conclusion: The study provides prognostic information for assessing ultrasound BAFMD as a cardiac risk marker. Regular blood donors have enhanced cardiovascular function with increased flow-mediated dilation, decreased body iron stores, and decreased oxidative stress compared with nondonors.

Nordic walking training attenuation of oxidative stress in association with a drop in body iron stores in elderly women

Excess body iron accumulation and oxidative stress has been associated with ageing. Regular exercise has been shown to reduce oxidative stress and induce some changes in iron metabolism. However, the effects of exercise on both of these parameters have been poorly investigated. In our study, 35 elderly women participated in 12 weeks of Nordic walking (NW) training (three times a week). We demonstrated that the training caused a significant reduction in malondialdehyde advanced oxidation protein products—markers of oxidative stress but had no effects on paraoxonase 1 activity. These changes were associated with the decrease of blood ferritin (99.4 ± 62.7 vs. 81.4 ± 61.7 ng/ml p < 0.05). Measurement of physical fitness revealed that the training caused a significant improvement in performance and a negative correlation between the blood ferritin and endurance test was recorded (r = −0.34, p = 0.03). In addition, a significant correlation between blood ferritin and fasting glucose level was noted. The training induced a rise of HDL cholesterol from 70.8 ± 19.3–75.3 ± 21.1, p < 0.05, whereas other lipid parameters remained unchanged. In conclusion, NW training reduced body iron stores and it was associated with lower oxidative stress and better endurance.

Donor vigilance: a global update

BackgroundWithout blood donations and the availability of blood transfusion, many important therapeutic advances could not have been achieved. Donor haemovigilance is the systematic monitoring of adverse reactions and incidents in the whole chain of blood donor care, with a view to improving quality and safety for blood donors.MethodThis ‘global update’ draws on work by the International Haemovigilance Network and International Society for Blood Transfusion haemovigilance working party, experience in the Netherlands, as well as a PubMed search using terms blood donor and adverse reaction. Results are discussed for vasovagal reactions, needle‐related complications, long‐term morbidity, donor iron status and frequent apheresis.Results and DiscussionThe occurrence of vasovagal reactions is associated with young, female donors, smaller estimated blood volume, first‐time donor status. A reduction in vasovagal reactions has been documented with use of a water drink before donation, muscle tensing, social distraction and lower collection volume for donors with small estimated blood volume. Needle injury is relatively frequent as a cause in cases of long‐term morbidity; needle injury is associated with traumatic phlebotomy, and in some cases, nerve damage is documented. Repeated whole blood donations lead to reduction in body iron stores and in some cases anaemia. Some blood services adjust donation intervals to avoid or reduce this, while others have or are considering a policy of iron replacement therapy. Fewer studies on acute complications in plasma and other types of apheresis have been published. Preliminary studies of bone density and protein levels in non‐commercial frequent plasma donors have not substantiated any specific hazard despite theoretical concerns of calcium or protein depletion. International collaboration in strengthening donor vigilance definitions and data analysis may in future increase potential for study of risk factors and measures to improve donor care worldwide.ConclusionDonor vigilance is gaining international interest and has increased knowledge of risk factors for vasovagal reactions associated with blood donation. There remains a need of research and of developing preventive measures, including prevention and treatment of needle injury as well as possible long‐term effects of frequent donation.

Vascular beneficial effects of polyphenol-rich olive oil and reduced body iron stores

Vascular beneficial effects of polyphenol-rich olive oil and reduced body iron stores

Might the beneficial effects of statin drugs be related to their action on iron metabolism?

Although the cholesterol-heart hypothesis is often regarded as a dogmatic belief, controversy continues to surround the aetiology and pathogenesis of atherosclerosis. In fact, lowering cholesterol with statin drugs has been shown to reduce cardiovascular risk. However, statins have pleiotropic effects independent of their capacity to lower cholesterol. We highlight that statin drugs exert an important action on iron metabolism, which in turn may prevent progression and destabilization of atherosclerotic plaque. If it is found that the effect of statins on iron metabolism is a mechanism of their beneficial action, this consequence of statin use can be clinically replicated by other methods, such as controlled reduction of body iron stores. This might allow the use of lower doses or even obviate the use of statins in primary cardiovascular prevention, and therefore avoid the side effects and expense of these drugs.

Blood Donation and Colorectal Cancer Incidence and Mortality in Men

BackgroundAlthough blood donations may reduce body iron stores, to date, prospective data on frequent blood donation and colorectal cancer risk are limited.Methodology/Principal FindingsWe tested whether frequent blood donation is associated with a lower risk of colorectal cancer in the Health Professionals Follow-up Study. We prospectively followed 35,121men who provide the information on lifetime number of blood donations in 1992 through 2008. Serum ferritin levels were measured in a random sample of 305 men. Cox proportional hazard regression models were used to calculate the multivariable relative risks (RRs, 95%CIs) after adjusting for age and other established colorectal cancer risk factors. We documented 684 incident colorectal cancer cases and 224 deaths from colorectal cancer. The mean serum ferritin levels varied from 178 µg/L for men who did not donate blood to 98 µg/L for men who had at least 30 donations. Age-adjusted results for both incidence and mortality were essentially the same as the multivariable-adjusted results. Comparing with non-donors, the multivariable RRs (95%CIs) for colorectal cancer incidence were 0.92 (0.77, 1.11) for 1–5 donation, 0.85 (0.64, 1.11) for 6–9 donations, 0.96 (0.73, 1.26) for 10–19 donations, 0.91 (0.63, 1.32) for 20–29 donations, and 0.97 (0.68, 1.38) for at least 30 donations (P trend = 0.92). The multivariable RRs for colorectal cancer mortality were 0.99 (0.72, 1.36) for 1–5 donation, 0.93 (0.57, 1.51) for 6–9 donations, 0.85 (0.50, 1.42) for 10–19 donations, and 1.14 (0.72, 1.83) for at least 20 donations (P trend = 0.82). The results did not vary by cancer sub-sites, intake levels of total iron, heme iron, or family history of colorectal cancer.Conclusions/SignificanceFrequent blood donations were not associated with colorectal cancer incidence and mortality in men. Our results do not support an important role of body iron stores in colorectal carcinogenesis.

Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome: results from a randomized clinical trial

BackgroundMetabolic syndrome (METS) is an increasingly prevalent but poorly understood clinical condition characterized by insulin resistance, glucose intolerance, dyslipidemia, hypertension, and obesity. Increased oxidative stress catalyzed by accumulation of iron in excess of physiologic requirements has been implicated in the pathogenesis of METS, but the relationships between cause and effect remain uncertain. We tested the hypothesis that phlebotomy-induced reduction of body iron stores would alter the clinical presentation of METS, using a randomized trial.MethodsIn a randomized, controlled, single-blind clinical trial, 64 patients with METS were randomly assigned to iron reduction by phlebotomy (n = 33) or to a control group (n = 31), which was offered phlebotomy at the end of the study (waiting-list design). The iron-reduction patients had 300 ml of blood removed at entry and between 250 and 500 ml removed after 4 weeks, depending on ferritin levels at study entry. Primary outcomes were change in systolic blood pressure (SBP) and insulin sensitivity as measured by Homeostatic Model Assessment (HOMA) index after 6 weeks. Secondary outcomes included HbA1c, plasma glucose, blood lipids, and heart rate (HR).ResultsSBP decreased from 148.5 ± 12.3 mmHg to 130.5 ± 11.8 mmHg in the phlebotomy group, and from 144.7 ± 14.4 mmHg to 143.8 ± 11.9 mmHg in the control group (difference -16.6 mmHg; 95% CI -20.7 to -12.5; P < 0.001). No significant effect on HOMA index was seen. With regard to secondary outcomes, blood glucose, HbA1c, low-density lipoprotein/high-density lipoprotein ratio, and HR were significantly decreased by phlebotomy. Changes in BP and HOMA index correlated with ferritin reduction.ConclusionsIn patients with METS, phlebotomy, with consecutive reduction of body iron stores, lowered BP and resulted in improvements in markers of cardiovascular risk and glycemic control. Blood donation may have beneficial effects for blood donors with METS.Trial registrationClinicalTrials.gov: NCT01328210Please see related article: http://www.biomedcentral.com/1741-7015/10/53

Effect of controlled reduction of body iron stores on clinical outcomes in peripheral arterial disease

Published results from a controlled clinical trial in patients with peripheral arterial disease found improved outcomes with iron (ferritin) reduction among middle-aged subjects but not the entire cohort. The mechanism of the age-specific effect was explored. Randomization to iron reduction (phlebotomy, n = 636) or control (n = 641) stratified by prognostic variables permitted analysis of effects of age and ferritin on primary (all-cause mortality) and secondary (death, nonfatal myocardial infarction, and stroke) outcomes. Iron reduction improved outcomes in youngest age quartile patients (primary outcome hazard ratio [HR] 0.44, 95% CI 0.21-0.92, P = .028; secondary outcome HR 0.34, 95% CI 0.19-0.61, P < .001). Mean follow-up ferritin levels (MFFL) declined with increasing entry age in controls. Older age (P = .035) and higher ferritin (P < .001) at entry predicted poorer compliance with phlebotomy and rising MFFL in iron-reduction patients. Intervention produced greater ferritin reduction in younger patients. Improved outcomes with lower MFFL were found in iron-reduction patients (primary outcome HR 1.11, 95% CI 1.01-1.23, P = .028; secondary outcome HR 1.10, 95% CI 1.0-1.20, P = .044) and the entire cohort (primary outcome HR 1.11, 95% CI 1.01-1.23, P = .037). Improved outcomes occurred with MFFL below versus above the median of the entire cohort means (primary outcome HR 1.48, 95% CI 1.14-1.92, P = .003; secondary outcome HR 1.22, 95% CI 0.99-1.50, P = .067). Lower iron burden predicted improved outcomes overall and was enhanced by phlebotomy. Controlling iron burden may improve survival and prevent or delay nonfatal myocardial infarction and stroke.

Reduced body iron stores and atherosclerosis in patients with cyanotic congenital heart disease

Cyanotic patients with congenital heart disease have been shown to be protected against atherosclerosis [1,2]. The mechanisms underlying this association are not fully elucidated. We suggest that the erythropoietic adaptations with consequent changes in iron metabolism that occur when cyanotic patients are exposed to hypoxia may have an important role in reducing the development of atherosclerosis.

Reduction of body iron stores to normal range levels in thalassaemia by using a deferiprone/deferoxamine combination and their maintenance thereafter by deferiprone monotherapy

Iron overload and toxicity is the major cause of morbidity and mortality in thalassaemia patients. New chelating drug protocols are necessary to treat completely transfusional iron overload and eliminate associated toxicity. Appropriate deferiprone/deferoxamine combinations could achieve this goal. A single-centre, single-armed, proof-of-concept study of the combination of deferiprone (75-100 mg/kg/d) and deferoxamine (40-60 mg/kg, at least 3 d per week) was carried out in eight patients with thalassaemia major (four men and four women) for 21-68 months. The patients were previously treated with deferoxamine and had variable serum ferritin [geometric (G) mean ± SD = 1446 ± 1035 μg/L] and magnetic resonance imaging relaxation times T2* cardiac (Gmean ± SD = 10.32 ± 6.72 ms) and liver (G mean ± SD = 3.77 ± 4.69 ms). The use of deferiprone (80-100 mg/kg/d) continued for 7-26 months in seven of the eight patients following the combination therapy. Organ function, blood and other biochemical parameters were monitored for toxicity. The deferiprone/deferoxamine combination caused an absolute value increase in cardiac (G mean ± SD = 29.6 ± 6.6 ms, P < 0.00076) and liver (G mean ± SD = 25.9 ± 8.07 ms, P < 0.00075) T2* and reduction in serum ferritin (G mean ± SD = 114.7 ± 139.8 μg/L, P < 0.0052) to within the normal body iron store range levels. In two cases, normalisation was achieved within a year. Deferiprone monotherapy was sufficient thereafter in maintaining normal range cardiac (G mean ± SD = 31.4 ± 5.25 ms, P < 0.79) and liver (G mean ± SD = 26.2 ± 12.4 ms, P < 0.58) T2* and normal serum ferritin (G mean ± SD = 150.7 ± 159.1, μg/L, P < 0.17) in five of the seven patients. No serious toxicity was observed. Transfusional iron overload in patients with thalassaemia could be reduced to normal body iron range levels using effective deferiprone/deferoxamine combinations. These levels could be maintained using deferiprone monotherapy.

Hemochromatosis and pregnancy: iron stores in the Hfe−/− mouse are not reduced by multiple pregnancies

Hereditary hemochromatosis (HH), a widespread hereditary iron metabolism disorder, is characterized by an excessive absorption of dietary iron, resulting in increased body iron stores. Some studies indicate a sex difference in disease expression, with women showing a slower disease progression and a less severe clinical profile. This is usually attributed to iron loss during menstruation and pregnancy. However, this link has not been clearly demonstrated. The Hfe-/- mouse model recapitulates key aspects of HH, including an iron overload phenotype similar to that observed in human patients. In this study, we use it to test the impact of multiple pregnancies in the iron stores. One-year-old nulliparous and pluriparous (averaging 29 weaned pups per female) C57BL/6 (B6) and Hfe-/- mice were euthanized, and blood and tissues were collected. Several serological and erythroid parameters were evaluated, as well as tissue nonheme iron content and serum ferritin. Hepcidin 1, hepcidin 2, and bone morphogenetic protein 6 (BMP6) expressions in the liver were determined by real-time PCR. No significant differences were observed for many serological and erythroid parameters although differences occurred in transferrin saturation and mean corpuscular volume in Hfe-/- mice and total iron-binding capacity in B6 mice. Hepatic iron concentration was similar for nulliparous and pluriparous mice of both genotypes, but total iron per organ (liver, spleen, heart, and pancreas) was higher overall in pluriparous females than nulliparous. Hepcidin 1 and 2 and BMP6 expressions were significantly decreased in pluriparous females, when compared with nulliparous, in both genotypes. In conclusion, multiple pregnancies do not reduce body iron stores in Hfe-/- mice.

Incidence of Anemia and Iron Deficiency in Strenuously Trained Adolescents: Results of a Longitudinal Follow-Up Study

Purpose Combat soldiers have a higher prevalence of anemia than age- and gender-matched civilians. This may be caused by hemodilution, which is typical among athletes, or by reduced body iron stores. The aim of this study was to investigate the incidence of iron-deficiency anemia in recruits to the Israel Defense Force after 6 months of training. Methods Blood was collected from recruits before training. After 6 months of follow-up, 153 paired blood samples were collected from the initial cohort. Total blood count and serum iron, transferrin, and ferritin were measured at both time points. Soluble transferrin receptor (sTfR) was measured in 119 of the paired samples and the sTfR/log ferritin ratio was calculated. Results At recruitment, mean hemoglobin concentration was 14.7 ± .9 g/dl. Iron-transferrin saturation was 34.1% ± 13.6%, and mean ferritin concentration was 53.6 ± 33.2 ng/ml. Anemia prevalence (Hb <14 g/dl) was 17.6%, and 14.9% of participants were iron-deficient (ferritin <22 mg/dl). At 6 months, 50.3% of the cohort was anemic, and 27.3% demonstrated iron-store depletion. Paired analysis showed an average reduction of .83 g/dl in hemoglobin ( p < .001), and of 9.8 mg/dl in ferritin ( p < .001). sTfR increased from 1.9 to 2.1 mg/dl ( p < .003) among recruits who became anemic. Half of the recruits experienced mild anemia after 6 months of training. Iron store depletion was observed among 24.5% of the cohort after training, as opposed to 15% at recruitment. Overall, these changes were not accompanied by a significant increase in sTfR, but among the subset of anemic subjects, there was a slight increase in index value. Conclusions In half of the cases, new-onset anemia was attributable to iron deficiency, and in the remainder, to hemodilution.

Silybin Treatment is Associated With Reduction in Serum Ferritin in Patients With Chronic Hepatitis C

The goal of this study was to examine the effect of a standardized silybin and soy phosphatidylcholine complex (IdB 1016) on serum markers of iron status. Milk thistle and its components are widely used as an alternative therapy for liver disease because of purported antioxidant, anti-inflammatory, and iron chelating properties. Thirty-seven patients with chronic hepatitis C and Batts-Ludwig fibrosis stage II, III, or IV were randomized to 1 of 3 doses of IdB 1016 for 12 weeks. Serum ferritin, serum iron, total iron binding capacity, and transferrin-iron saturation were measured at baseline, during treatment, and 4 weeks thereafter. Wilcoxon signed rank tests were used to compare baseline and posttreatment values. There was a significant decrease in serum ferritin from baseline to end of treatment (mean, 244 vs. 215 mug/L; median, 178 vs. 148 mug/L; P=0.0005); 78% of subjects had a decrease in serum ferritin level. There was no significant change in serum iron or transferrin-iron saturation. Multivariate logistic regression analysis in a model that included dose, age, sex, HFE genotype, history of alcohol use, and elevated baseline ferritin levels demonstrated that stage III or IV fibrosis was independently associated with decreased posttreatment serum ferritin level. Treatment with IdB 1016 is associated with reduced body iron stores, especially among patients with advanced fibrosis stage.

Helicobacter pylori Infection and Iron Stores: A Systematic Review and Meta‐analysis

We carried out a systematic literature review and meta-analysis to evaluate the existing evidence on the association between Helicobacter pylori infection and iron stores. Twelve case reports and case series, 19 observational epidemiologic studies and six intervention trials were included in the review. Although only few studies controlled for multiple potential confounders, most studies reported a positive association, linking between H. pylori and decreased body iron stores in symptomatic and asymptomatic H. pylori-infected subjects. H. pylori infection may be regarded as a risk factor for reduction in body iron stores and also for iron deficiency or iron deficiency anemia, especially in high-risk groups. The results of the meta-analysis of thoroughly designed and analyzed studies revealed an increased risk for iron deficiency anemia; pooled odds ratio (OR) 2.8 (95% confidence interval (CI) 1.9, 4.2) and also for iron deficiency; pooled OR 1.38 (95%CI 1.16-1.65) among H. pylori-infected subjects. The biologic mechanism by which H. pylori induces the alteration in the iron stores is not fully understood, but it seems to involve several pathways, including gastrointestinal blood loss, decrease in the absorption of dietary iron, and enhanced uptake of the iron by the bacterium. H. pylori is associated with reduced iron stores. Future research is needed to determine whether this relationship is a causal association and to better understand its biologic mechanism. The impact of anti-H. pylori therapy on improvement of iron stores needs to be further evaluated in large and well-controlled trials.

Does metformin improve polycystic ovary syndrome symptoms through reduction in body iron stores?

To The Editor – Tan et al. (1) found that metformin improved polycystic ovary syndrome (PCOS) symptoms irrespective of pretreatment insulin resistance or obesity. However, the mechanisms underlying this association are not clearly understood. We suggest that some of the involved mechanisms might be related to the reduction in body iron stores induced by metformin. Indeed, it has recently been found that metformin, increasing insulin sensitivity, may decrease intestinal iron absorption in patients with PCOS (2). Mounting evidence indicates that higher body iron stores are associated with an increased risk of other insulin-resistant disorders such as type 2 diabetes (3). In fact, it has been demonstrated that increased iron stores may contribute to insulin resistance by reducing hepatic insulin extraction and metabolism (4), and by decreasing glucose uptake in muscle (5). On the other hand, induction of near-iron deficiency in carbohydrate-intolerant subjects has been shown to improve insulin sensitivity (6). Furthermore, a small intervention study in patients with type 2 diabetes and elevated ferritin levels showed that bloodletting, which resulted in a 50% reduction in serum ferritin concentrations, improved glycemia and insulin sensitivity (7).