-
1.
Serum Ferritin and the Risk of Metabolic Syndrome: A Systematic Review and Dose-Response Meta-Analysis of Cross-sectional Studies.
Zhang, WCB, Xing, Y, Shao, B
Biomedical and environmental sciences : BES. 2021;(8):623-631
Abstract
OBJECTIVE This study aims to assess the dose-response relationship between serum ferritin (SF) and metabolic syndrome (MetS) in the two sexes. METHODS We searched for articles on PubMed, the Cochrane Library, EMBASE, and the Web of Science databases that were published from 1950 to 2020. The summary odds ratio ( OR) and 95% confidence interval ( CI) of the association between SF and MetS were estimated using a random-effects model through a meta-analysis. Based on the methods described by Greenland and Longnecker, we explored the dose-response relationship between the two sexes. RESULTS This study included 14 studies and 74,710 samples. The results of the classical meta-analysis showed that SF was positively associated with MetS ( OR = 1.77, 95% CI: 1.59-1.98). Regarding the components of MetS (8 studies included), the results showed that SF was positively associated with abdominal obesity ( OR = 1.42, 95% CI: 1.24-1.62), elevated fasting plasma glucose ( OR = 1.84, 95% CI: 1.50-2.25), elevated blood pressure ( OR = 1.17, 95% CI: 1.08-1.26), elevated triglycerides ( OR= 2.09, 95% CI: 1.72-2.54), and reduced high-density lipoprotein cholesterol ( OR = 1.33, 95% CI: 1.19-1.49). In the linear dose-response meta-analysis, the ORs of males, females, and postmenopausal females were 1.14 (95% CI: 1.13-1.16), 1.32 (95% CI: 1.26-1.39), and 1.34 (95% CI: 1.22-1.47), respectively. CONCLUSIONS Our study shows that SF is significantly and positively associated with MetS, and the risk in the male population is higher than that in the female population. This finding also supports the recommendation of using SF as an early warning marker of MetS.
-
2.
Serum or plasma ferritin concentration as an index of iron deficiency and overload.
Garcia-Casal, MN, Pasricha, SR, Martinez, RX, Lopez-Perez, L, Peña-Rosas, JP
The Cochrane database of systematic reviews. 2021;(5):CD011817
-
-
Free full text
-
Abstract
BACKGROUND Reference standard indices of iron deficiency and iron overload are generally invasive, expensive, and can be unpleasant or occasionally risky. Ferritin is an iron storage protein and its concentration in the plasma or serum reflects iron stores; low ferritin indicates iron deficiency, while elevated ferritin reflects risk of iron overload. However, ferritin is also an acute-phase protein and its levels are elevated in inflammation and infection. The use of ferritin as a diagnostic test of iron deficiency and overload is a common clinical practice. OBJECTIVES To determine the diagnostic accuracy of ferritin concentrations (serum or plasma) for detecting iron deficiency and risk of iron overload in primary and secondary iron-loading syndromes. SEARCH METHODS We searched the following databases (10 June 2020): DARE (Cochrane Library) Issue 2 of 4 2015, HTA (Cochrane Library) Issue 4 of 4 2016, CENTRAL (Cochrane Library) Issue 6 of 12 2020, MEDLINE (OVID) 1946 to 9 June 2020, Embase (OVID) 1947 to week 23 2020, CINAHL (Ebsco) 1982 to June 2020, Web of Science (ISI) SCI, SSCI, CPCI-exp & CPCI-SSH to June 2020, POPLINE 16/8/18, Open Grey (10/6/20), TRoPHI (10/6/20), Bibliomap (10/6/20), IBECS (10/6/20), SCIELO (10/6/20), Global Index Medicus (10/6/20) AIM, IMSEAR, WPRIM, IMEMR, LILACS (10/6/20), PAHO (10/6/20), WHOLIS 10/6/20, IndMED (16/8/18) and Native Health Research Database (10/6/20). We also searched two trials registers and contacted relevant organisations for unpublished studies. SELECTION CRITERIA We included all study designs seeking to evaluate serum or plasma ferritin concentrations measured by any current or previously available quantitative assay as an index of iron status in individuals of any age, sex, clinical and physiological status from any country. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methods. We designed the data extraction form to record results for ferritin concentration as the index test, and bone marrow iron content for iron deficiency and liver iron content for iron overload as the reference standards. Two other authors further extracted and validated the number of true positive, true negative, false positive, false negative cases, and extracted or derived the sensitivity, specificity, positive and negative predictive values for each threshold presented for iron deficiency and iron overload in included studies. We assessed risk of bias and applicability using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. We used GRADE assessment to enable the quality of evidence and hence strength of evidence for our conclusions. MAIN RESULTS Our search was conducted initially in 2014 and updated in 2017, 2018 and 2020 (10 June). We identified 21,217 records and screened 14,244 records after duplicates were removed. We assessed 316 records in full text. We excluded 190 studies (193 records) with reasons and included 108 studies (111 records) in the qualitative and quantitative analysis. There were 11 studies (12 records) that we screened from the last search update and appeared eligible for a future analysis. We decided to enter these as awaiting classification. We stratified the analysis first by participant clinical status: apparently healthy and non-healthy populations. We then stratified by age and pregnancy status as: infants and children, adolescents, pregnant women, and adults. Iron deficiency We included 72 studies (75 records) involving 6059 participants. Apparently healthy populations Five studies screened for iron deficiency in people without apparent illness. In the general adult population, three studies reported sensitivities of 63% to 100% at the optimum cutoff for ferritin, with corresponding specificities of 92% to 98%, but the ferritin cutoffs varied between studies. One study in healthy children reported a sensitivity of 74% and a specificity of 77%. One study in pregnant women reported a sensitivity of 88% and a specificity of 100%. Overall confidence in these estimates was very low because of potential bias, indirectness, and sparse and heterogenous evidence. No studies screened for iron overload in apparently healthy people. People presenting for medical care There were 63 studies among adults presenting for medical care (5042 participants). For a sample of 1000 subjects with a 35% prevalence of iron deficiency (of the included studies in this category) and supposing a 85% specificity, there would be 315 iron-deficient subjects correctly classified as having iron deficiency and 35 iron-deficient subjects incorrectly classified as not having iron deficiency, leading to a 90% sensitivity. Thresholds proposed by the authors of the included studies ranged between 12 to 200 µg/L. The estimated diagnostic odds ratio was 50. Among non-healthy adults using a fixed threshold of 30 μg/L (nine studies, 512 participants, low-certainty evidence), the pooled estimate for sensitivity was 79% with a 95% confidence interval of (58%, 91%) and specificity of 98%, with a 95% confidence interval of (91%, 100%). The estimated diagnostic odds ratio was 140, a relatively highly informative test. Iron overload We included 36 studies (36 records) involving 1927 participants. All studies concerned non-healthy populations. There were no studies targeting either infants, children, or pregnant women. Among all populations (one threshold for males and females; 36 studies, 1927 participants, very low-certainty evidence): for a sample of 1000 subjects with a 42% prevalence of iron overload (of the included studies in this category) and supposing a 65% specificity, there would be 332 iron-overloaded subjects correctly classified as having iron overload and 85 iron-overloaded subjects incorrectly classified as not having iron overload, leading to a 80% sensitivity. The estimated diagnostic odds ratio was 8. AUTHORS' CONCLUSIONS At a threshold of 30 micrograms/L, there is low-certainty evidence that blood ferritin concentration is reasonably sensitive and a very specific test for iron deficiency in people presenting for medical care. There is very low certainty that high concentrations of ferritin provide a sensitive test for iron overload in people where this condition is suspected. There is insufficient evidence to know whether ferritin concentration performs similarly when screening asymptomatic people for iron deficiency or overload.
-
3.
A case-control study in Taiwanese cohort and meta-analysis of serum ferritin in pancreatic cancer.
Park, JM, Mau, CZ, Chen, YC, Su, YH, Chen, HA, Huang, SY, Chang, JS, Chiu, CF
Scientific reports. 2021;(1):21242
Abstract
Pancreatic cancer is one of the most lethal diseases which lack an early diagnostic marker. We investigated whether serum ferritin (SF) reflects risk for pancreatic cancer and potential genes that may contribute ferritin and pancreatic cancer risks. We performed a meta-analysis of relevant studies on SF and pancreatic cancer risk by searching articles in PUBMED and EMBASE published up to 1 March 2020. We also collected serum samples from Taipei Medical University Joint Biobank and compared SF levels in 34 healthy controls and 34 pancreatic cancer patients. An Oncomine database was applied as a platform to explore a series of genes that exhibited strong associations between ferritin and pancreatic cancer. Herein, we show that high levels of SF can indicate risk of pancreatic cancer, suggesting SF as the new tumor marker that may be used to help pancreatic cancer diagnosis. We also found that expressions of iron homeostasis genes (MYC, FXN) and ferroptosis genes (ALOX15, CBS, FDFT1, LPCAT3, RPL8, TP53, TTC35) are significantly altered with pancreatic tumor grades, which may contribute to differential expression of ferritin related to pancreatic cancer prognosis.
-
4.
Iron metabolism and type 2 diabetes mellitus: A meta-analysis and systematic review.
Liu, J, Li, Q, Yang, Y, Ma, L
Journal of diabetes investigation. 2020;(4):946-955
Abstract
AIMS/INTRODUCTION Iron metabolism can directly or indirectly affect the occurrence and development of type 2 diabetes. This meta-analysis and systematic review aimed to analyze the association between serum iron metabolism indicators and type 2 diabetes. MATERIALS AND METHODS The databases PubMed and Embase were searched for studies on the correlations between serum iron metabolism indicators (iron, ferritin, transferrin, hepcidin and soluble transferrin receptor) and type 2 diabetes since January 2006. Relevant data were extracted from the included studies, and meta-analysis was carried out. RESULTS A total of 12 case-control and cohort studies were analyzed. Of the 12 studies, 11 described the correlation between serum ferritin levels and type 2 diabetes. The median and high serum ferritin concentrations were significantly associated with the risks of type 2 diabetes (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.08-1.33 and OR 1.43, 95% CI 1.29-1.59, respectively). However, the low concentration was not correlated with the risk of type 2 diabetes (OR 0.99, 95% CI 0.89-1.11). No significant association was observed between serum soluble transferrin receptor and type 2 diabetes, whereas the soluble transferrin receptor-to-ferritin ratio was significantly inversely related to the risk of type 2 diabetes in the median and high ratio subgroups (OR 0.71, 95% CI 0.51, 0.99 and OR 0.65, 95% CI 0.45-0.95). CONCLUSIONS The elevated serum ferritin was one of the risk factors for type 2 diabetes, and soluble transferrin receptor-to-ferritin ratio was inversely related to the risk of type 2 diabetes. A systematic review showed that serum transferrin and hepcidin might be directly or indirectly related to the development of diabetes.
-
5.
The impact of iron chelation therapy on patients with lower/intermediate IPSS MDS and the prognostic role of elevated serum ferritin in patients with MDS and AML: A meta-analysis.
Yang, Y, Tang, Z, An, T, Zhao, L
Medicine. 2019;(40):e17406
-
-
Free full text
-
Abstract
Serum ferritin (SF) has been identified as a potential prognostic factor for patients undergoing stem cell transplantation, but the prognostic value of SF in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients and the impact of iron chelation therapy (ICT) on MDS patients are controversial. The present meta-analysis aimed to better elucidate these relationships.Three electronic databases were searched systematically to identify reports on the prognostic role of SF in MDS and AML patients, and those investigating the impact of ICT on prognosis of MDS patients. The hazard ratios (HRs) and its 95% confidence interval (95%CI) were extracted from the identified studies using Cox proportional hazard regression model for overall survival (OS) and progression of MDS to AML.Twenty reports including 1066 AML patients and 4054 MDS patients were included in present study. The overall pooled HRs for OS of AML and MDS patients with elevated SF prior to transplantation was 1.73 (1.40-2.14), subgroup analyses stratified by the cut-off value of SF ≥1400/1000 ng/mL showed that the pooled HRs were 1.45 (0.98-2.15) and 1.65 (1.30-2.10), respectively. The pooled HRs for ICT in MDS patients was 0.30 (0.23-0.40). For ICT, the pooled HRs for the progression of MDS to AML was 0.84 (0.61-1.61).SF has a negative impact on the OS of AML and MDS patients when it is higher than 1000 ng/mL. ICT can improve the OS of MDS patients with iron overload but it is not associated with the progression of MDS to AML.
-
6.
Decreased serum ferritin may be associated with increased restless legs syndrome in Parkinson's disease (PD): a meta-analysis for the diagnosis of RLS in PD patients.
Li, K, Liu, B, Wang, F, Bao, J, Wu, C, Huang, X, Hu, F, Xu, Z, Ren, H, Yang, X
The International journal of neuroscience. 2019;(10):995-1003
Abstract
Objective: Restless legs syndrome (RLS) is one of the most common non-motor symptoms of Parkinson's disease (PD), but its pathogenesis in a PD background is unclear. Abnormal iron metabolism may be involved, in which case it may be a marker of RLS risk. Here, the literature was systematically searched and meta-analyzed to compare iron metabolism markers between PD patients with or without RLS. Method: The databases PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, Web of Science, and SinoMed were searched for case-control and observational studies examining RLS-related changes in iron metabolism in PD, in terms of serum iron, serum ferritin and hemoglobin. Eligible studies were meta-analyzed using Stata 12.0. Results: Meta-analysis of 11 case-control studies showed that serum ferritin concentration was lower in PD patients with RLS than in those without RLS. (95%CI -0.32 to -0.03, p = 0.018). In contrast, levels of serum iron or hemoglobin did not differ significantly between PD patients with or without RLS. Conclusion: This meta-analysis may provide the first reliable pooled estimate of the correlation between abnormal iron metabolism and RLS in PD. The available evidence indicates that levels of ferritin, but not of serum iron or hemoglobin, correlate significantly with RLS in PD, with lower ferritin levels correlating to greater prevalence of RLS.
-
7.
Sex-Specific Association of Circulating Ferritin Level and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Studies.
Jiang, L, Wang, K, Lo, K, Zhong, Y, Yang, A, Fang, X, Akezhuoli, H, Song, Z, Chen, L, An, P, et al
The Journal of clinical endocrinology and metabolism. 2019;(10):4539-4551
Abstract
CONTEXT Although the role of iron in the development of type 2 diabetes (T2D) has long been a concern, prospective studies directly linking body iron stores to T2D risk in a sex-dependent context have been inconsistent. OBJECTIVE A systematic meta-analysis was conducted to explore the sex-specific association of circulating ferritin with T2D risk. DATA SOURCES We searched PubMed, Web of Science, and EMBASE databases to identify available prospective studies through 1 August 2018. RESULTS Fifteen prospective studies comprising 77,352 participants and 18,404 patients with T2D, aged 20 to 80 years, and with ∼3 to 17 years of follow-up were identified. For each 100-μg/L increment in ferritin levels of overall participants, T2D risk increased by 22% (RR, 1.22; 95% CI, 1.14 to 1.31). Of note, major heterogeneities by sex were identified, with increased ferritin level having an apparently greater effect on T2D risk in women (RR, 1.53; 95% CI, 1.29 to 1.82) than in men (RR, 1.21; 95% CI, 1.15 to 1.27) after exclusion of a study with high heterogeneity (41,512 men and 6974 women for sex-specific analyses; P = 0.020 for sex difference). Further nonlinear analysis between circulating ferritin and T2D risk also showed sex-dimorphic association in that the T2D risk of women was twice as strong in magnitude as that of men at the same ferritin level. CONCLUSIONS Greater circulating ferritin levels were independently associated with increased T2D risk, which appeared stronger among women than men. Our findings provide prospective evidence for further testing of the utility of ferritin levels in predicting T2D risk in a sex-specific manner.
-
8.
Ferritin, metabolic syndrome and its components: A systematic review and meta-analysis.
Suárez-Ortegón, MF, Ensaldo-Carrasco, E, Shi, T, McLachlan, S, Fernández-Real, JM, Wild, SH
Atherosclerosis. 2018;:97-106
-
-
Free full text
-
Abstract
BACKGROUND AND AIMS Mechanisms for the association between iron stores and risk factors for diabetes and cardiovascular disease, such as metabolic syndrome (MetS) and its components, are still not clear. We evaluated the associations between ferritin levels, MetS and its individual components, and potential role of confounding, in a meta-analysis. METHODS We searched articles in MEDLINE and EMBASE until February 14th, 2018. There were two approaches: meta-analysis of 1) cross-sectional and longitudinal studies and 2) only cross-sectional studies. Meta-regressions were conducted to identify sources of heterogeneity in the associations of ferritin with MetS and its individual components. RESULTS Information from 26 studies (5 prospective) was systematically reviewed and 21 studies were meta-analysed. The pooled OR for MetS by increased ferritin was 1.78 (95%CI: 1.60-1.97) in the meta-analysis 1, and 1.70 (95%CI: 1.49-1.95) in the meta-analysis 2. The pooled association was weaker in studies adjusted for hepatic injury markers (meta-regression coefficient (95% CI): -0.34 (-0.60,-0.09) p = 0.008) and body mass index (BMI) (meta-regression coefficient (95% CI): -0.27 (-0.53,-0.01) p = 0.039). Among MetS components, the pooled association with increased ferritin was strongest with high triglycerides [OR (95%CI): 1.96 (1.65-2.32)] and high glucose levels [OR 95%CI: 1.60 (1.40-1.82)]. Higher cut-off points used to define high ferritin concentrations were more strongly associated with high triglycerides [meta-regression coefficient (95% CI): 0.22 (0.03, 0.041), p = 0.023]. CONCLUSIONS High triglycerides and glucose are the components more strongly associated with ferritin. Hepatic injury and BMI appear to influence the ferritin-MetS association, and a threshold effect of high ferritin concentration on the ferritin-high triglycerides association was observed.
-
9.
The effect of vegetarian diets on iron status in adults: A systematic review and meta-analysis.
Haider, LM, Schwingshackl, L, Hoffmann, G, Ekmekcioglu, C
Critical reviews in food science and nutrition. 2018;(8):1359-1374
Abstract
BACKGROUND Vegetarian diets exclude meat, seafood, and products containing these foods. Although the vegetarian lifestyle could lead to a better health status in adults, it may also bear risks for certain nutritional deficiencies. Cross-sectional studies and narrative reviews have shown that the iron status of vegetarians is compromised by the absence of highly bioavailable haem-iron in meatless diets and the inhibiting effect of certain components present in plant foods on non-haem iron bioavailability. METHODS The databases Pubmed, Scopus, Embase, and Cochrane CentralRegister of Controlled Trials were searched for studies comparing serum ferritin, as the major laboratory parameter for iron status of adult vegetarians with non-vegetarian control groups. A qualitative review was conducted as well as an inverse-variance random-effects meta-analysis to pool available data. In addition the effect of vegetarian diets according to gender was investigated with a subgroup analysis. The results were validated using a sensitivity analysis. RESULTS A total of 27 cross-sectional studies and three interventional studies were selected for the systematic review. The meta-analysis which combined data of 24 cross-sectional studies showed that adult vegetarians have significantly lower serum ferritin levels than their non-vegetarian controls (-29.71 µg/L, 95% CI [-39.69, -19.73], p < 0.01). Inclusion of semi-vegetarian diets did not change the results considerably (-23.27 µg/L, 95% CI [-29.77, -16.76], p < 0.01). The effects were more pronounced in men (-61.88 µg/L, 95% CI [-85.59, -38.17], p < 0.01) than in both premenopausal women (-17.70 μg/L, 95% CI [-29.80, -5.60], p < 0.01) and all women (-13.50 μg/L, 95% CI [-22.96, -4.04], p < 0.01), respectively. CONCLUSIONS In conclusion our results showed that vegetarians are more likely to have lower iron stores compared with non-vegetarians. However, since high iron stores are also a risk factor for certain non-communicable diseases, such as type 2 diabetes, it is recommended that not only vegetarians but also non-vegetarians should regularly control their iron status and improve their diet regarding the content and bioavailability of iron by consuming more plants and less meat.
-
10.
Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.
Namaste, SM, Rohner, F, Huang, J, Bhushan, NL, Flores-Ayala, R, Kupka, R, Mei, Z, Rawat, R, Williams, AM, Raiten, DJ, et al
The American journal of clinical nutrition. 2017;(Suppl 1):359S-371S
-
-
Free full text
-
Abstract
Background: The accurate estimation of iron deficiency is important in planning and implementing interventions. Ferritin is recommended as the primary measure of iron status, but interpretability is challenging in settings with infection and inflammation.Objective: We assessed the relation between ferritin concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and investigated adjustment algorithms to account for these effects.Design: Cross-sectional data from 15 surveys for PSC (n = 27,865) and 8 surveys for WRA (24,844), from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to estimate depleted iron stores (ferritin concentration <12 μg/L in PSC and <15 μg/L in WRA) in inflammation and malaria settings as follows: 1) increase ferritin-concentration cutoff to <30 μg/L; 2) exclude individuals with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L; 3) apply arithmetic correction factors; and 4) use a regression correction approach.Results: Depleted iron-store estimates incrementally increased as CRP and AGP deciles decreased (4% compared with 30%, and 6% compared with 29% from highest compared with lowest CRP deciles for pooled PSC and WRA, respectively, with similar results for AGP). Depending on the approach used to adjust for inflammation (CRP plus AGP), the estimated prevalence of depleted iron stores increased by 7-25 and 2-8 absolute median percentage points for PSC and WRA, respectively, compared with unadjusted values. Adjustment for malaria in addition to CRP and AGP did not substantially change the estimated prevalence of depleted iron stores.Conclusions: Our results lend support for the use of internal regression correction to estimate the prevalence of depleted iron stores in regions with inflammation. This approach appears to mathematically reflect the linear relation of ferritin concentrations with acute-phase proteins. More research is warranted to validate the proposed approaches, but this study contributes to the evidence base to guide decisions about how and when to adjust ferritin for inflammation.