Altered dietary iron intake is a strong modulator of renal DMT1 expression

Divalent metal transporter1 (DMT1; also known as DCT1 or NRAMP2) is an important component of the cellular machinery responsible for dietary iron absorption in the duodenum. DMT1 is also highly expressed in the kidney where it has been suggested to play a role in urinary iron handling. In this study, we determined the effect on renal DMT1 expression of feeding an iron-restricted diet (50 mg/kg) or an iron-enriched diet (5 g/kg) for 4 wk and measured urinary and fecal iron excretion rates. Feeding the low-iron diet caused a reduction in serum iron concentration and fecal iron output rate with an increase in renal DMT1 expression. Feeding an iron-enriched diet had the converse effect. Therefore, DMT1 expression in the kidney is sensitive to dietary iron intake, and the level of expression is inversely related to the dietary iron content. Changes in DMT1 expression occurred intracellularly in the proximal tubule and in the apical membrane and subapical region of the distal convoluted tubule. Increased DMT1 expression was accompanied by a decrease in urinary iron excretion rate and vice versa when DMT1 expression was reduced. Together, these findings suggest that modulation of renal DMT1 expression may influence renal iron excretion rate.

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Erythropoiesis and red cell survival in the hypothyroid dog

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1963.204.3.415 ◽

1963 ◽

Vol 204 (3) ◽

pp. 415-418 ◽

Cited By ~ 26

Author(s):

Martin J. Cline ◽

Nathaniel I. Berlin

Keyword(s):

Cell Survival ◽

Iron Concentration ◽

Vitamin B ◽

Dietary Iron ◽

Red Cell ◽

Iron Intake ◽

Turnover Rates ◽

Erythrocyte Survival ◽

Red Cell Survival ◽

Cell Synthesis

Determinations of blood volume, total red cell volume, plasma and red cell iron turnover rates, and red cell survival were performed in seven dogs prior to and subsequent to radioiodine destruction of the thyroid gland. Anemia developed slowly in all animals as a result of a diminished rate of red cell synthesis. Erythrocyte survival was unaffected by thyroid ablation. Serum iron concentration decreased in five animals despite the apparent adequacy of dietary iron intake and the absence of detectable external loss. In two animals, parenteral administration of iron failed to correct the anemia. Vitamin B12 was ineffective in correcting the anemia or in producing a reticulocyte response in two other animals.

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Deferasirox (Exjade®, ICL670) Demonstrates Dose-Related Effects on Body Iron Levels Related to Transfusional Iron Intake in Transfusion-Dependent Anemia.

Blood ◽

10.1182/blood.v106.11.2694.2694 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2694-2694 ◽

Cited By ~ 4

Author(s):

P. Greenberg ◽

G. Dine ◽

A. Ganser ◽

G. Verhoef ◽

L. DeBusscher ◽

...

Keyword(s):

Serum Ferritin ◽

Chelation Therapy ◽

Iron Concentration ◽

Intake Rate ◽

Iron Intake ◽

Absolute Change ◽

Body Iron ◽

Transfusion Requirements ◽

Iron Excretion ◽

Intake Ratio

Abstract Iron overload, a potentially serious consequence of multiple blood transfusions, can be effectively managed with chelation therapy. Deferasirox, an investigational once-daily oral chelator, has been evaluated in a 1 year study of iron-overloaded adult and pediatric patients (n=184) with transfusion-dependent anemia including β-thalassemia, myelodysplastic syndromes (MDS) and Diamond-Blackfan anemia (DBA). Patients were stratified into four daily dose groups (5, 10, 20 and 30 mg/kg) according to baseline liver iron concentration (LIC; 2–3, >3–7, >7–14 and >14 mg Fe/g dw, respectively). Iron balance was determined for all patients, based on transfusional iron intake and chelator-induced iron excretion, derived from the change in LIC during the study (Table 1). Patient characteristics, LIC, serum ferritin and iron excretion/intake ratio during deferasirox treatment β-thalassemia (n=85) DBA (n=30) MDS (n=47) Other anemias (n=22) *Mean ± SD Age*, years 24.7 ± 10.0 16.1 ± 10.3 65.1 ± 12.5 35.8 ± 22.9 Body weight, kg 51.1 ± 14.1 39.1 ± 18.7 70.4 ± 12.5 56.1 ± 18.5 Deferasirox dose*, mg/kg 23.8 ± 7.2 23.6 ± 7.4 20.0 ± 8.3 21.9 ± 6.5 Iron intake*, mg/kg/day 0.35 ± 0.12 0.40 ± 0.11 0.28 ± 0.14 0.31 ± 0.19 <0.3, n (%) 28 (33) 6 (20) 25 (53) 10 (45) 0.3–0.5, n (%) 49 (58) 19 (63) 20 (43) 7 (32) >0.5, n (%) 8 (9) 5 (17) 2 (4) 5 (23) Serum ferritin*, ng/mL Baseline 4321 ± 2881 3245 ± 2439 3343 ± 1978 3144 ± 1850 Absolute change −386 ± 1626 −118 ± 1373 −268 ± 2053 −750 ± 1517 LIC*, mg Fe/g dw (n=76) (n=26) (n=28) (n=17) Baseline 19.3 ± 10.9 18.8 ± 10.7 15.6 ± 11.9 15.1 ± 6.2 Absolute change −4.7 ± 8.6 −1.6 ± 6.5 −5.7 ± 6.3 −3.7 ± 6.3 Iron excretion/intake ratio 1.5 ± 0.90 1.1 ± 0.46 1.7 ± 0.93 1.6 ± 1.48 Transfusion requirements and iron intake during the study varied widely between diseases. However, LIC and serum ferritin decreases were consistently achieved in all patient groups. More than one-third (38%) of patients, most of whom had MDS or other anemias, had an iron intake rate <0.3 mg/kg/day (average: 0.2 mg/kg/day; corresponding to 5.6 ml RBC/kg/month). In these patients, deferasirox at 10 and 20 mg/kg reduced LIC. Overall, an iron intake- and dose-related response pattern was observed for both LIC and serum ferritin (Figure 1). Effect of deferasirox dose and iron intake on changes in serum ferritin and LIC over 1 year Effect of deferasirox dose and iron intake on changes in serum ferritin and LIC over 1 year According to these results, deferasirox demonstrates the ability to stabilize and effectively decrease body iron levels at doses of 10, 20 and 30 mg/kg/day, depending on the degree of iron intake. In conclusion, dosing of chelation therapy should be guided by a patient’s transfusion requirements and the treatment goal, which is either to maintain or reduce body iron.

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Iron Chelation Efficiency of Deferasirox (Exjade®, ICL670) in Patients with Transfusional Hemosiderosis.

Blood ◽

10.1182/blood.v106.11.2690.2690 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2690-2690 ◽

Cited By ~ 9

Author(s):

J. Porter ◽

C. Borgna-Pignatti ◽

M. Baccarani ◽

A. Saviano ◽

S. Abish ◽

...

Keyword(s):

Binding Capacity ◽

Iron Concentration ◽

Iron Chelation ◽

Iron Chelator ◽

Tridentate Ligand ◽

Average Dose ◽

Iron Intake ◽

Liver Iron ◽

Molecular Weights ◽

Iron Excretion

Abstract Iron excretion can be calculated according to Angelucci et al (NEJM 2000). As applied to the novel oral iron chelator deferasirox (DSX), chelation efficiency can then be determined as the % iron excretion vs theoretical iron binding capacity of chelator dose: % efficiency = [iron excretion (mg/kg/day)/chelator dose (mg/kg/day)] x [374/56] x 2 x 100 (374 and 56 represent the molecular weights of DSX and iron; factor 2 accounts for the tridentate ligand). In a total of 325 patients with β-thalassemia (n=285) or rare anemias, such as MDS (n=13), DBA (n=14) or other anemias (n=13), included in the DSX Phase II and III Studies 0108 and 0107, liver iron concentration (LIC) was evaluated by liver biopsy at baseline and study end. All patients were treated with once-daily oral DSX 5, 10, 20 or 30 mg/kg according to baseline LIC (2–3, >3–7, >7–14 and >14 mg Fe/g dw, respectively). In these patients, the average dose during study was 22.8 ± 7.6 mg/kg. The average iron intake was 0.37 mg/kg/day and was similar between dose cohorts. Efficiency of daily DSX treatment (mean ± SD) Baseline LIC 2–3 >3–7 >7–14 >14 DSX, mg/kg 5 (n=9) 10 (n=49) 20 (n=81) 30 (n=186) Iron excretion (mg/kg/day) 0.14 ± 0.1 0.21 ± 0.1 0.39 ± 0.1 0.57 ± 0.2 Iron intake (mg/kg/day) 0.39 ± 0.1 0.37 ± 0.1 0.38 ± 0.1 0.36 ± 0.1 Ratio iron excretion/intake 0.33 ± 0.2 0.53 ± 0.4 1.09 ± 0.5 1.66 ± 0.8 Efficiency (%) 31.6 ± 26.4 27.5 ± 18.4 27.1 ± 10.3 27.3 ± 12.4 There were no differences in the chelation efficiency of DSX between the overall initial dose groups, and thus between different LIC categories at baseline, or between age and disease groups. Using the estimated efficiency of 27%, and the formula above, the approximate dose (mg) needed to achieve iron balance corresponds to an iron intake in mg Fe/kg/day divided by 0.02. For a patient receiving 0.2, 0.4 or 0.6 mg/kg Fe/day the doses of 10, 20 or 30 mg/kg, respectively, are estimated to achieve iron balance (eg for a 44 kg person receiving 4 units of blood/month a dose of 30 mg/kg would be required to achieve iron balance). Further analysis reveals that chelation efficiency does appear to increase somewhat with iron intake: in patients with <0.3 mg/kg/day Fe (average 0.23) the estimated efficiency is 22%, but becomes 34% in those with >0.5 mg/kg/day Fe (average 0.55). Applying different chelation efficiency estimates for low and high iron intake, 14 and 22 mg/kg/day DSX, respectively, would be required to chelate the transfused iron. In Study 0107, 230 patients were treated with deferoxamine (DFO) at an average daily dose of 45 mg/kg (5 days/week). Using the molecular weight of DFO (656) and a factor of 1 for a hexadentate ligand in the calculation, the overall chelation efficiency for DFO is 13% (10–17% in the lowest and highest iron intake categories, respectively). These calculations, based on the formula of Angelucci et al, correspond well to the overall observation in the DSX clinical studies, that iron balance or net negative iron balance is achieved by daily doses of 20–30 mg/kg in regularly transfused patients. The results also confirm that the estimated chelation efficiency of DSX is around twice that of DFO.

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A Dose Escalation Study of the Pharmacokinetics, Safety & Efficacy of Deferitrin, an Oral Iron Chelator in Beta Thalassaemia Patients.

Blood ◽

10.1182/blood.v110.11.2669.2669 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2669-2669 ◽

Cited By ~ 1

Author(s):

R. Galanello ◽

G. Forni ◽

A. Jones ◽

A. Kelly ◽

A. Willemsen ◽

...

Keyword(s):

Quantum Interference ◽

Renal Toxicity ◽

Iron Concentration ◽

Iron Chelator ◽

Iron Accumulation ◽

Iron Intake ◽

Post Dose ◽

Once Daily ◽

Beta Thalassaemia ◽

Iron Excretion

Abstract Iron accumulation and overload in beta thalassaemia patients are associated with significant morbidity and mortality. Iron chelators are used to manage iron accumulation but side effects and compliance issues restrict the use of available chelators. Deferitrin (Genzyme Corporation) is an orally available iron chelator intended for iron overload. Method: Patients were dosed in 4 cohorts, receiving 5, 10, 15 and 25 mg/kg/day of deferitrin. Deferitrin dosing in cohorts 1–3 was once daily for 12 weeks. Cohort 4 received deferitrin twice daily (BD) for 48 weeks (12.5mg/kg BD, 25 mg/kg/day). Pharmacokinetics (PK) were assessed in a subset of up to 5 patients in each cohort, pre-dose and 1, 2, 4 and 8 hours post dose. All patients had trough levels assessed at weeks 1, 6 and 12 (all Cohorts) and additionally at weeks 24, 36 and 48 for Cohort 4. PK parameters were determined by model independent (non-compartmental) analyses. Safety was assessed by collection of adverse events and laboratory assessments with renal parameters measured weekly due to observations of renal toxicity in preclinical testing. Efficacy (change in liver iron concentration (LIC)) was assessed by SQUID (superconducting quantum interference device) in Turin, Italy, between screening and end of study. Iron excretion and intake were estimated by calculation:Iron excretion due to deferitrin = Iron Intake (mg/kg/day) - TBI (mg/kg/day)Iron Intake (mg/kg/day) = [total mL pRBC (exclude last BT×) × 1.08] / [Weight (kg) × Days (Between 1st & last BT×)]TBI (mg/kg/day) = Change in LIC (mg Fe/g dry weight) × [10.6 (Angelucci Factor) / D (Days on deferitrin)] Key: pRBC = packed red blood cells, BT× = blood transfusion, TBI=Total Body Iron. Results: PK: PK for deferitrin dosed once daily was linear and dose proportional. The serum half-life was 1.3–1.8 hrs, clearance was 226–340 mL/min and mean residence time was 2.8–3.4 hrs for once daily dosing. PK data from BD dosing is not yet available. Safety: Deferitrin dosed once daily was generally well tolerated (Cohorts 1–3). Slight rises in transaminases were seen at 10 and 15 mg/kg/day. A large proportion of enrolled patients were hepatitis C positive (73%). When dosed BD (12.5 mg/kg BD in Cohort 4), 3 patients developed renal toxicity after 4–5 weeks of treatment. Two patients experienced increased proteinuria (max 3.73 g/L & 3.29 g/L) and one patient suffered acute renal failure (peak serum creatinine 4.1 mg/dL, lowest GFR 27 mmol/L). All patients recovered normal renal function after stopping treatment. No patients were re-challenged with deferitrin. Dosing was terminated in all patients because of safety concerns. Efficacy: Mean iron excretion in mg/kg/day (S.D) for Cohort 1 was 0.22 (0.22), Cohort 2 was 0.45 (0.14) and Cohort 3 was 0.33 (0.12). The reasons for the lack of dose proportionality in iron excretion are unclear. Efficacy could not be assessed in Cohort 4 due to early termination of the study. Conclusions: Deferitrin dosed once daily was generally well tolerated and associated with a mean iron excretion of 0.34 mg/kg/day. Deferitrin dosed BD (12.5mg/kg BD) was associated with unacceptable renal toxicity and led to study termination. Deferitrin does not appear to have an acceptable therapeutic margin to allow sufficient iron excretion for long-term administration.

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Impact on Iron Removal of Dose Reduction for Non-Progressive Serum Creatinine Increases during Treatment with the Once-Daily, Oral Iron Chelator Deferasirox (Exjade®, ICL670).

Blood ◽

10.1182/blood.v108.11.3824.3824 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3824-3824 ◽

Cited By ~ 5

Author(s):

N. Gattermann ◽

N. Zoumbos ◽

E. Angelucci ◽

G. Drelichman ◽

J. Siegel ◽

...

Keyword(s):

Serum Creatinine ◽

Dose Reduction ◽

Iron Concentration ◽

Development Program ◽

Iron Removal ◽

Iron Intake ◽

Liver Iron ◽

Elevated Creatinine ◽

The Impact ◽

Iron Excretion

Abstract Introduction: During the deferasirox clinical development program, mild, non-progressive increases in serum creatinine >33% above baseline were observed in around one-third of patients receiving the chelator. Most increases resolved spontaneously, while the rest were managed by dose reduction. This post-hoc analysis evaluates the impact on efficacy of reducing deferasirox dose following increases in serum creatinine during 1-year core trials. Methods: Patients with a range of transfusion-dependent anemias, including β-thalassemia, sickle cell disease, myelodysplastic syndromes and other anemias, were enrolled into four trials. Creatinine and creatinine clearance levels were assessed monthly, and liver iron concentration (LIC) was measured at baseline and study end. Results: In total, 652 patients received treatment with deferasirox. Non-progressive creatinine increases >33% above baseline were noted in 237 (36.3%) patients, although these increases rarely exceeded the upper limit of normal (4.4%). These non-progressive increases generally occurred early, were dose- and iron intake-dependent, and were consistent across all ages and underlying anemias. Creatinine levels spontaneously reduced in 169 patients (71.3%); the remainder (n=68, 28.7%) underwent dose reduction by 5–10 mg/kg/day. Patients receiving high versus low doses and with low (<7 mL RBC/kg/month) versus high (>14 mL RBC/kg/month) transfusion rates tended to have the greatest and most rapid reductions in LIC. This greater velocity of iron removal tended to result in elevated creatinine levels. Patients with elevated creatinine who required dose reduction actually had more pronounced reductions in LIC than patients with no creatinine increase or with a creatinine increase that did not require dose reduction (Table). Change from baseline in LIC (mg Fe/g dw) by creatinine levels Initial dose, mg/kg/day No creatinine increase (n=415) Creatinine increase (n=237) No dose reduction (n=169) Dose reduction (n=68) All Iron intake, mg/kg/day 0.35 ± 0.15 0.34 ± 0.13 0.30 ± 0.11 All Median 0.4 −3.2 −6.9 Range (−24.9–15.0) (−42.2–10.8) (−21.6–5.0) 5 Median 4.9 2.1 0.8 Range (−1.0–11.4) (2.1) (0.8) 10 Median 1.3 0.2 −1.0 Range (−11.8–15.0) (−7.3–10.8) (−2.1–3.6) 20 Median 0.0 −1.9 −3.9 Range (−9.4–10.3) (−10.3–6.5) (−10.6–1.1) 30 Median −5.7 −9.9 −9.3 Range (−24.9–13.3) (−42.2–8.6) (−21.6–5.0) Non-progressive increases in creatinine were more commonly observed in patients with an iron excretion/intake ratio >1.5 (14%) than in those with a ratio 1−1.5 (11%) or <1 (9%). Conclusions: An early-onset, non-progressive, dose- and iron intake-dependent increase in creatinine has been observed in around one-third of patients receiving deferasirox. Most of these increases resolved spontaneously, while the rest were manageable with dose reduction. As decreases in LIC were generally greatest in patients with increased creatinine levels, supported by the iron excretion/intake ratios, it is hypothesized that excessively rapid iron removal may modify renal hemodynamics. A reduction in deferasirox dose maintained efficacy, but allowed the dose to be tailored so that iron was removed at a rate appropriate for an individual patient.

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Whole-body arginine dimethylation is associated with all-cause mortality in adult renal transplant recipients

Amino Acids ◽

10.1007/s00726-021-02965-1 ◽

2021 ◽

Author(s):

Adrian Post ◽

Alexander Bollenbach ◽

Stephan J. L. Bakker ◽

Dimitrios Tsikas

Keyword(s):

Renal Transplant ◽

Excretion Rate ◽

Whole Body ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Kidney Donors ◽

Body Protein ◽

All Cause Mortality ◽

Arginine Residues ◽

Excretion Rates

AbstractArginine residues in proteins can be singly or doubly methylated post-translationally. Proteolysis of arginine-methylated proteins provides monomethyl arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). ADMA and SDMA are considered cardiovascular risk factors, with the underlying mechanisms being not yet fully understood. SDMA lacks appreciable metabolism and is almost completely eliminated by the kidney, whereas ADMA is extensively metabolized to dimethylamine (DMA), with a minor ADMA fraction of about 10% being excreted unchanged in the urine. Urinary DMA and ADMA are useful measures of whole-body asymmetric arginine-dimethylation, while urinary SDMA serves as a whole-body measure of symmetric arginine-dimethylation. In renal transplant recipients (RTR), we previously found that higher plasma ADMA concentrations and lower urinary ADMA and SDMA concentrations were associated with a higher risk of all-cause mortality. Yet, in this RTR collective, no data were available for urinary DMA. For the present study, we additionally measured the excretion rate of DMA in 24-h collected urine samples of the RTR and of healthy kidney donors in the cohort, with the aim to quantitate whole-body asymmetric (ADMA, DMA) and symmetric (SDMA) arginine-dimethylation. We found that lower DMA excretion rates were associated with higher all-cause mortality, yet not with cardiovascular mortality. In the healthy donors, kidney donation was associated with considerable decreases in ADMA (by − 39%, P < 0.0001) and SDMA (by − 21%, P < 0.0001) excretion rates, yet there was no significant change in DMA (by − 9%, P = 0.226) excretion rate. Our results suggest that protein-arginine dimethylation is altered in RTR compared to healthy kidney donors and that it is pronouncedly shifted from symmetric to asymmetric arginine-dimethylation, with whole-body protein-arginine dimethylation being almost unaffected.

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Iron status and dietary iron intake of female blood donors

Transfusion ◽

10.1111/trf.12347 ◽

2013 ◽

Vol 54 (3pt2) ◽

pp. 770-774 ◽

Cited By ~ 8

Author(s):

Alison O. Booth ◽

Karen Lim ◽

Hugh Capper ◽

David Irving ◽

Jenny Fisher ◽

...

Keyword(s):

Blood Donors ◽

Iron Status ◽

Dietary Iron ◽

Iron Intake

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Effect of transfusional iron intake on response to chelation therapy in β-thalassemia major

Blood ◽

10.1182/blood-2007-08-109306 ◽

2008 ◽

Vol 111 (2) ◽

pp. 583-587 ◽

Cited By ~ 103

Author(s):

Alan R. Cohen ◽

Ekkehard Glimm ◽

John B. Porter

Keyword(s):

Chelation Therapy ◽

Iron Concentration ◽

Chelating Agent ◽

Thalassemia Major ◽

Phase Iii ◽

Iron Loading ◽

Iron Intake ◽

Liver Iron ◽

Iron Stores ◽

Using Data

The success of chelation therapy in controlling iron overload in patients with thalassemia major is highly variable and may partly depend on the rate of transfusional iron loading. Using data from the 1-year phase III study of deferasirox, including volumes of transfused red blood cells and changes in liver iron concentration (LIC) in 541 patients, the effect of iron loading on achieving neutral or negative iron balance was assessed in patients receiving different doses of deferasirox and the comparator deferoxamine. After dose adjustment, reductions in LIC after 1 year of deferasirox or deferoxamine therapy correlated with transfusional iron intake. At a deferasirox dose of 20 mg/kg per day, neutral or negative iron balance was achieved in 46% and 75% of patients with the highest and lowest transfusional iron intake, respectively; 30 mg/kg per day produced successful control of iron stores in 96% of patients with a low rate of transfusional iron intake. Splenectomized patients had lower transfusional iron intake and greater reductions in iron stores than patients with intact spleens. Transfusional iron intake should be monitored on an ongoing basis in thalassemia major patients, and the rate of transfusional iron loading should be considered when choosing the appropriate dose of an iron-chelating agent. This study is registered at http://clinicaltrials.gov as NCT00061750.

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IRON-FORTIFIED FORMULAS

PEDIATRICS ◽

10.1542/peds.47.4.786 ◽

1971 ◽

Vol 47 (4) ◽

pp. 786-786

Author(s):

L. J. Filer ◽

Lewis A. Barness ◽

Richard B. Goldbloom ◽

Malcolm A. Holliday ◽

Robert W. Miller ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Deficiency Anemia ◽

Dietary Iron ◽

Iron Intake ◽

Feeding Problems ◽

Whole Milk ◽

Dietary Component ◽

Recent Statement ◽

Marketing Information

In its recent statement on iron,1 the Committee on Nutrition emphasized the value of iron-fortified, proprietary milk formulas for the prevention of iron-deficiency anemia of infancy. Despite this recommendation, the most recent marketing information available to the Committee shows that more than 70% of the proprietary formulas currently prescribed by physicians do not contain added iron. The reasons for continuing routine use of formulas not fortified with iron are not entirely clear. One reason may be that some physicians still believe iron additives increase the incidence of feeding problems or gastrointestinal disturbances. There is no documented evidence that this is a significant problem. The Committee strongly recommends when proprietary formulas are prescribed that iron-supplemented formulas be used routinely as the standard–that is, that this be the rule rather than the exception. There seems to be little justification for continued general use of proprietary formulas not fortified with iron. The Committee is fully aware that only a small percentage of American infants are fed proprietary formulas after 6 months of age. Fluid whole milk (available in bottle or carton ) or evaporated milk, both of which contain only trace amounts of iron, are substituted at the time of greatest iron need and highest prevalence of iron-deficiency anemia. The infant's diet is usually deficient in iron, unless other foods are carefully selected to insure adequate iron intake. Since the major dietary component during infancy is milk, two courses of action should be taken: (1) Pediatricians and other health professionals should engage in a program of public education to convince American mothers to provide their infants with a source of dietary iron.

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Total and Nonheme Dietary Iron Intake Is Associated with Metabolic Syndrome and Its Components in Chinese Men and Women

Nutrients ◽

10.3390/nu10111663 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1663 ◽

Cited By ~ 15

Author(s):

Zhenni Zhu ◽

Fan Wu ◽

Ye Lu ◽

Chunfeng Wu ◽

Zhengyuan Wang ◽

...

Keyword(s):

Metabolic Syndrome ◽

Serum Ferritin ◽

Smoking Status ◽

Heme Iron ◽

Nonheme Iron ◽

Total Iron ◽

Positive Trend ◽

Dietary Iron ◽

Iron Intake ◽

Men And Women

The causal relationship between serum ferritin and metabolic syndrome (MetS) remains inconclusive. Dietary iron intake increases serum ferritin. The objective of this study was to evaluate associations of total, heme, and nonheme dietary iron intake with MetS and its components in men and women in metropolitan China. Data from 3099 participants in the Shanghai Diet and Health Survey (SDHS) obtained during 2012–2013 were included in this analysis. Dietary intake was assessed by 24-h diet records from 3 consecutive days. Multivariate generalized linear mixed models were used to evaluate the associations of dietary iron intake with MetS and its components. After adjustment for potential confounders as age, sex, income, physical exercise, smoking status, alcohol use, and energy intake, a positive trend was observed across quartiles of total iron intake and risk of MetS (p for trend = 0.022). Compared with the lowest quartile of total iron intake (<12.72 mg/day), the highest quartile (≥21.88 mg/day) had an odds ratio (95% confidence interval), OR (95% CI), of 1.59 (1.15,2.20). In addition, the highest quartile of nonheme iron intake (≥20.10 mg/day) had a 1.44-fold higher risk of MetS compared with the lowest quartile (<11.62 mg/day), and higher risks of MetS components were associated with the third quartiles of total and nonheme iron intake. There was no association between heme iron intake and risk of MetS (p for trend = 0.895). Associations for total and nonheme iron intake with MetS risk were found in men but not in women. Total and nonheme dietary iron intake was found to be positively associated with MetS and its components in the adult population in metropolitan China. This research also revealed a gender difference in the association between dietary iron intake and MetS.

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