Pellagra associated with iron deficiency

Dietary iron and heme, likely through their effect on gut commensal bacteria and colonic barrier function, have been shown to modulate colonic inflammation in animal models of colitis. Nonetheless, the link between dietary total and heme iron and risk of Crohn's disease (CD) and ulcerative colitis (UC) has not been previously explored. We conducted a prospective cohort study of 165,331 U.S. women enrolled in the Nurses' Health Study and Nurses' Health Study II. Dietary information was collected using a validated food frequency questionnaire at baseline (1984) and updated every 2 to 4 years. Self-reported CD and UC diagnoses were confirmed through medical records review. We used Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals while adjusting for potential confounders. In a case-control study nested within these cohorts, we evaluated the interaction between single-nucleotide polymorphisms associated with genome-wide susceptibility to CD and UC and dietary total and heme iron intake on risk of CD and UC using logistic regression modeling. Through 2011, over 3,038,049 person-years of follow-up, we documented 261 incident cases of CD and 321 incident cases of UC. Dietary heme iron was nonsignificantly associated with increased risk of UC (Ptrend = 0.12). This association seemed to be modified by the UC susceptibility locus, rs1801274, a coding variant in the FcγRIIA gene (Pinteraction = 7.00E-05). In contrast, there was no association between dietary heme iron and risk of CD (Ptrend = 0.67). We also did not observe an association between total dietary intake of iron and risk of CD or UC (All Ptrend > 0.35). In 2 large prospective cohort studies, dietary total and heme iron were not associated with risk of CD or UC. Our suggestive finding that the association between dietary heme iron intake and risk of UC may be modified by a coding variant in FcγRIIA gene warrants additional investigation.

Bone Marrow Iron in CKD: Correlation With Functional Iron Deficiency

Background:Developing neurons have high thyroid hormone and iron requirements to support their metabolism and growth. Early-life iron and thyroid hormone deficiencies are prevalent, often coexist, and increase the risk of permanently impaired neurobehavioral function in children. Early-life dietary iron deficiency reduces thyroid hormone levels and impairs thyroid hormone-responsive gene expression in the neonatal rat brain.Objective:This study determined whether neuronal-specific iron deficiency alters thyroid hormone-regulated gene expression in developing neurons.Methods:Iron deficiency was induced in primary mouse embryonic hippocampal neuron cultures with the iron chelator deferoxamine (DFO) beginning at 3 days in vitro (DIV). At 11DIV and 18DIV, mRNA levels for thyroid hormone-regulated genes indexing thyroid hormone homeostasis (Hr, Crym, Dio2, Slco1c1, Slc16a2) and neurodevelopment (Nrgn, Pvalb, Klf9) were quantified. To assess the effect of iron repletion, DFO was removed at 14DIV from a subset of DFO-treated cultures and gene expression and ATP levels were quantified at 21DIV.Results:At 11DIV and 18DIV, neuronal iron deficiency decreased Nrgn, Pvalb, and Crym, and by 18DIV, Slc16a2, Slco1c1, Dio2, and Hr were increased; collectively suggesting cellular sensing of a functionally abnormal thyroid hormone state. Dimensionality reduction with Principal Component Analysis (PCA) reveals that thyroid hormone homeostatic genes strongly correlate with and predict iron status (Tfr1 mRNA). Iron repletion from 14–21DIV restored neurodevelopmental genes, but not all thyroid hormone homeostatic genes, and ATP concentrations remained significantly altered. PCA clustering suggests that cultures replete with iron maintain a gene expression signature indicative of previous iron deficiency.Conclusions:These novel findings suggest there is an intracellular mechanism coordinating cellular iron/thyroid hormone activities. We speculate this is a part of homeostatic response to match neuronal energy production and growth signaling for these important metabolic regulators. However, iron deficiency may cause permanent deficits in thyroid hormone-dependent neurodevelopmental processes even after recovery from iron deficiency.

Abstract: BACKGROUND: Anaemia may aggravate symptoms and even masquerade as coronary heart disease (CHD). Correction of anaemia leads to improvement in the quality of life. Cardiologists should be aware of the problem of anaemia, its pathogenesis and the systematic workup of anaemia in CHD and heart failure (HF) populations. AIMS AND OBJECTIVES: To study the prevalence, severity, and causes of anaemia in ambulatory coronary heart disease and heart failure populations. MATERIALS AND METHODS: In this single centre, retrospective observational study, we reviewed 26,600 consecutive electronic prescriptions generated in an adult cardiology outpatient service between September 2017 and August 2024. The prescriptions were assessed for the primary diagnosis, presence and severity of anaemia, and iron and vitamin B12 deficiency. RESULTS: Anaemia was recorded in 1,600/26,600 (6.01%) prescriptions in unselected population, 1,100/14,600 (7.53%) prescriptions in CHD population, 20/488 (4.09%) in dilated cardiomyopathy (DCMP) and 104/272 (38.2%) in heart failure population. Majority of CHD and HF patients had mild anaemia 49.9% and 47.1% respectively. Severe anaemia was found in 2.0% and 1.92% in of CHD and HF patients respectively. Iron Deficiency was found in 921/1600 (57.5%), 877/1100 (79.7%) and 32/104 (30.7%) in unselected, CHD and HF patients respectively. Vitamin B12 deficiency was found in 236/1600 (14.7%), 458/1100 (41.6%) and 23/104 (22.1%) in unselected CHD and HF patients respectively. Several patients had concomitant iron and B12 deficiency. CONCLUSION: Anaemia in CHD and HF population is multifactorial. Routine screening for anaemia and workup for iron and B12 deficiency should be done in suitable cases. Iron deficiency may have varied consequences, anaemia being one of them.

HFEC282Y homozygotes have an increased risk for developing increased iron stores and related disorders. It is controversial whether dietary iron restrictions should be recommended to such individuals. To determine whether dietary iron content influences iron stores in HFEC282Y homozygotes as assessed by serum ferritin concentration. Serum ferritin concentration was measured and a dietary iron questionnaire was completed as part of the evaluation of 213 HFEC282Y homozygotes who were identified through screening of >100,000 primary care patients at five HEmochromatosis and IRon Overload Screening (HEIRS) Study Field Centers in the United States and Canada. No significant relationships between serum ferritin concentration and dietary heme iron content, dietary nonheme iron content or reports of supplemental iron use were found. These results do not support recommending dietary heme or nonheme iron restrictions for HFEC282Y homozygotes diagnosed through screening in North America.

Both dietary iron and copper were inversely related to lead absorption as indicated by erythrocyte and kidney lead levels, dietary iron having the greatest effect. Kidney copper values were depressed when dietary iron was low, a condition which was worsened by lead. Lead tended to lower heart cytochrome c oxidase especially when dietary copper was low, but also when dietary copper and zinc were high. Lead interfered with hematopoiesis when dietary copper and/or iron were low, the effect being expecially severe when both essential nutrients were low. These results show the importance of copper and iron nutriture and metabolism as factors which reduce lead toxicity, and emphasize the necessity of considering nutritional status in evaluating lead toxicity.

The spatial expression and regulation of transcription factors IDEF1 and IDEF2

BackgroundDeveloping countries have high prevalence of diseases, but facilities to diagnose and treat them are limited. We must use available resources in ways not needed where there are sophisticated equipment and trained staff. Anaemia is common; iron deficiency affects health and productivity; folate deficiency in pregnant women causes foetal abnormalities. Few developing countries can measure serum folate or ferritin, but standard automated blood analyses are widely available and can help predict folate and iron deficiency. The RDW-CV% (coefficient of variation of the red cell width) measures the variability in the size of red blood cells (RBC) in routine automated analysis of blood cells, but is seldom reported. Levels of RDW-CV% and haemoglobin (Hb) can predict iron deficiency anaemia.Method and resultsI have written a computer model based on the standard mechanism for blood formation and destruction. This shows that before anaemia develops and during recovery, there are both normal and abnormal RBC (small in iron deficiency and large in folate deficiency) in the circulation. The model calculates the abnormality in the RDW-CV% in standard automated blood analyses. In early iron deficiency and during recovery the full blood count shows the Hb near the lower limit of normal, a low MCV and a high RDW-CV%. A similar pattern, but with a higher MCV, develops in folate deficiency. Folate deficiency is often brief and may not cause anaemia. The high RDW-CV% may persist for three months.ConclusionThis long footprint could be medically useful for detecting folate deficiency and so limiting foetal damage in individuals and communities. Few clinicians or public health workers know about RDW-CV%. Standard blood reports for clinical use should include the RDW-CV% and note the possible significance of abnormal values.

This paper examines the development of iron (Fe) deficiency and its possible interactions with trace elements such as zinc (Zn) and copper (Cu) by investigating iron-deficient and control rats. The effects of iron deficiency were studied at day 0, 10, 20, 30 and 40 in rats fed on an iron-free diet (diet ID). It was found that the critical period in the development of nutritional iron deficiency occurs after 30 to 40 days without iron supplementation. At this time the organism is unable to maintain haemoglobin levels without endangering the iron-dependent enzymatic groups which are essential for life. It was also demonstrated that in a situation of iron deficiency, there occurs a greater absorption of copper, while that of zinc remains unchanged. As iron deficiency progresses, the levels of copper in the spleen and the sternum increase. It is apparent that iron deficiency provokes more marked alterations in the metabolism of copper than of zinc.

Hematologic values, including concentrations of iron and folate in blood were studied in pregnant women and in a group of patients in the puerperium period, and compared with those in a group of non-pregnant women. Except for red cell folate, which was low in all groups, and total iron binding capacity, which was high in the pregnant and puerperium groups, the mean values for all other parameters studied were within normal limits. Thirty-six percent of the pregnant and 38% of the puerperium patients, were found to be anemic, while no anemia was recorded in the non-pregnant group. In the anemic group, combined iron and folate deficiency was the most common finding (30% and 36%), followed by isolated iron deficiency in pregnant patients (17%), and serum folate deficiency alone in puerperium group (27%). In the iron anemic group, low folate values were most frequent in the pregnant and puerperium patients. In the latter there was a frequency of 22% and 44% of serum and red cell folate deficiency respectively, while in the non-pregnant patients frequency of iron deficiency was higher (13%). No correlation was found between hemoglobin and folate concentration. A good correlation was encountered between hemoglobin and the transferrin saturation index. A significant correlation between neutrophil hypersegmentation and folate was found only in iron-deficient patients, although low folate generally corresponded to increased neutrophil lobe average.

Iron deficiency (ID) is the most common nutritional deficiency, and iron metabolism becomes further deteriorated in the presence of certain conditions, such as heart failure (HF). Atrial fibrillation (AF) has many similarities to HF, including a chronic inflammatory pathophysiology; however, the prevalence of ID and other hematinic deficiencies in AF patients have not been determined. In this study, the prevalence of iron (serum ferritin <100 µg/L or ferritin 100-299 µg/L with transferrin saturation <20%), vitamin B12 (<200 pg/mL), and folate deficiency (<4.0 ng/mL) was evaluated in 101 patients with non-valvular AF with preserved left ventricular ejection fraction and no signs of HF, and the results were compared with 35 age- and gender-matched controls. Anemia was detected in 26% of the patients. A total of 48 (47.6%) patients had ID, 10 (9.9%) had a vitamin B12 deficiency, and 13 (12.9%) had a folate deficiency. The prevalence of ID was similar in the controls and the paroxysmal AF patients, but increased gradually in persistent and permanent AF. Univariate logistic regression analysis demonstrated that permanent vs. paroxysmal AF [Odds ratio (OR): 2.17; 95% confidence interval (CI): 0.82-5.69; p=0.011], high sensitive C-reactive protein (OR: 1.47; 95% CI: 0.93-2.36; p=0.019), N-terminal pro b-type natriuretic peptide (OR: 1.24; 95% CI: 0.96-1.71; p=0.034), and white blood cell count (OR: 1.21; 95% CI: 0.95-1.58; p=0.041) were associated with ID. In multivariable analysis, permanent AF remained as an independent clinical associate of ID (OR: 4.30; 95% CI: 0.83-12.07; p=0.039). ID is common in permanent AF, as in HF. Inflammation and neurohormonal activation seem to contribute to its development.

The Impact of Intravenous Iron on Renal Injury and Function Markers in Patients With Chronic Kidney Disease and Iron Deficiency Without Anemia

Silicon (Si) mitigates the negative effects of iron deficiency in common bean (Phaseolus vulgaris L.) by improving photosystem activities and nutritional status

Most frequent red cell (RBC) donors and many first-time donors are iron deficient, but meet haemoglobin standards. However, the effects of donation-induced iron deficiency on RBC storage quality are unknown. Thus, we used a mouse model to determine if donor iron deficiency reduced post-transfusion RBC recovery. Weanling mice received a control diet or an iron-deficient diet. A third group receiving the iron-deficient diet was also phlebotomised weekly. This provided 3 groups of mice with different iron status: (1) iron replete, (2) mild iron deficiency with iron-deficient erythropoiesis, and (3) iron-deficiency anaemia. At ten weeks of age, blood was collected, leucoreduced, and stored at 4 ºC. After 12 days of storage, 24-hour (h) post-transfusion RBC recovery was quantified in recipients by flow cytometry. Before blood collection, mean haemoglobin concentrations in the iron-replete, iron-deficient, and iron-deficiency anaemia donor mice were 16.5±0.4, 11.5±0.4, and 7.0±1.4 [g/dL± 1 standard deviation (SD)], respectively (p<0.01 for all comparisons between groups). The 24-h post-transfusion RBC recoveries in recipients receiving transfusions from these three cohorts were 77.1±13.2, 66.5±10.9, and 46.7±15.9 (% ±1 SD), respectively (p<0.05 for all comparisons between groups). In summary, donor iron deficiency significantly reduced 24-h post-transfusion RBC recovery in recipient mice. RBCs from mice with mild iron deficiency and iron-deficient erythropoiesis, with haemoglobin levels similar to those used for human autologous blood donation, had intermediate post-transfusion RBC recovery, as compared to iron-replete donors and those with iron-deficiency anaemia. This suggests that, in addition to the effects of iron deficiency on donor health, frequent blood donation, leading to iron-deficient erythropoiesis, may also have adverse effects for transfusion recipients.

Prevalence of iron and zinc deficiencies among preschool children ages 3 to 5 y in Vhembe district, Limpopo province, South Africa