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Nutrition Reviews Jul 2023Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and... (Meta-Analysis)
Meta-Analysis
The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials.
CONTEXT
Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and treat iron deficiency, despite poor bioavailability and frequently reported adverse side effects. Ferrous bisglycinate is a novel amino acid iron chelate that is thought to be more bioavailable and associated with fewer gastrointestinal (GI) adverse events as compared with iron salts.
OBJECTIVE
A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of ferrous bisglycinate supplementation compared with other iron supplements on hemoglobin and ferritin concentrations and GI adverse events.
DATA SOURCES
A systematic search of electronic databases and grey literature was performed up to July 17, 2020, yielding 17 RCTs that reported hemoglobin or ferritin concentrations following at least 4 weeks' supplementation of ferrous bisglycinate compared with other iron supplements in any dose or frequency.
DATA EXTRACTION
Random-effects meta-analyses were conducted among trials of pregnant women (n = 9) and children (n = 4); pooled estimates were expressed as standardized mean differences (SMDs). Incidence rate ratios (IRRs) were estimated for GI adverse events, using Poisson generalized linear mixed-effects models. The remaining trials in other populations (n = 4; men and nonpregnant women) were qualitatively evaluated.
DATA ANALYSIS
Compared with other iron supplements, supplementation with ferrous bisglycinate for 4-20 weeks resulted in higher hemoglobin concentrations in pregnant women (SMD, 0.54 g/dL; 95% confidence interval [CI], 0.15-0.94; P < 0.01) and fewer reported GI adverse events (IRR, 0.36; 95%CI, 0.17-0.76; P < 0.01). We observed a non-significant trend for higher ferritin concentrations in pregnant women supplemented with ferrous bisglycinate. No significant differences in hemoglobin or ferritin concentrations were detected among children.
CONCLUSION
Ferrous bisglycinate shows some benefit over other iron supplements in increasing hemoglobin concentration and reducing GI adverse events among pregnant women. More trials are needed to assess the efficacy of ferrous bisglycinate against other iron supplements in other populations.
PROSPERO REGISTRATION NO
CRD42020196984.
Topics: Adult; Child; Female; Humans; Male; Pregnancy; Anemia, Iron-Deficiency; Dietary Supplements; Ferritins; Hemoglobins; Iron; Iron Deficiencies; Randomized Controlled Trials as Topic; Salts; Ferrous Compounds
PubMed: 36728680
DOI: 10.1093/nutrit/nuac106 -
Molecular Metabolism Jun 2022With long-term metabolic malfunction, diabetes can cause serious damage to whole-body tissue and organs, resulting in a variety of complications. Therefore, it is... (Review)
Review
BACKGROUND
With long-term metabolic malfunction, diabetes can cause serious damage to whole-body tissue and organs, resulting in a variety of complications. Therefore, it is particularly important to further explore the pathogenesis of diabetes complications and develop drugs for prevention and treatment. In recent years, different from apoptosis and necrosis, ferroptosis has been recognized as a new regulatory mode of cell death and involves the regulation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Evidence shows that ferroptosis and ferritinophagy play a significant role in the occurrence and development of diabetes complications.
SCOPE OF REVIEW
we systematically review the current understanding of ferroptosis and ferritinophagy, focusing on their potential mechanisms, connection, and regulation, discuss their involvement in diabetes complications, and consider emerging therapeutic opportunities and the associated challenges with future prospects.
MAJOR CONCLUSIONS
In summary, ferroptosis and ferritinophagy are worthy targets for the treatment of diabetes complications, but their complete molecular mechanism and pathophysiological process still require further study.
Topics: Apoptosis; Autophagy; Diabetes Complications; Diabetes Mellitus; Ferritins; Ferroptosis; Humans
PubMed: 35304332
DOI: 10.1016/j.molmet.2022.101470 -
Critical Reviews in Food Science and... May 2018Vegetarian diets exclude meat, seafood, and products containing these foods. Although the vegetarian lifestyle could lead to a better health status in adults, it may... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Adult; Diet, Vegetarian; Ferritins; Humans; Iron; Risk Factors
PubMed: 27880062
DOI: 10.1080/10408398.2016.1259210 -
The American Journal of Clinical... Dec 2015Guidelines on the diagnosis and treatment of iron deficiency (ID) vary widely across indications. (Review)
Review
BACKGROUND
Guidelines on the diagnosis and treatment of iron deficiency (ID) vary widely across indications.
OBJECTIVE
We reviewed all available guidelines on the management of ID worldwide.
DESIGN
A literature search was conducted in PubMed, Cochrane, and EMBASE and in main professional association websites, limited to documents published between 1 January 2004 and 30 June 2014.
RESULTS
Of 127 guidelines identified, 29 were selected, involving 29 professional associations and issued from the United States (n = 8), Europe (n = 6), Britain (n = 4), Canada (n = 3), international organizations (n = 2), France (n = 2), Poland (n = 1), Australia (n = 1), Mexico (n = 1), and Japan (n = 1). A total of 22 and 27 guidelines provided recommendations on diagnosis and treatment of ID, respectively. To define ID, all guidelines recommended a concentration for serum ferritin. One-half of them (10 of 22) proposed transferrin saturation (TSAT) as an alternative or complementary diagnostic test. To treat ID, most of the guidelines (18 of 27) recommended preferentially the oral route if possible, particularly in children and in women in the pre- or postpregnancy period. Iron supplementation should be administered intravenously according to 13 of 27 guidelines, particularly in patients with chronic kidney disease (CKD) (n = 7) and chemotherapy-induced anemia (n = 5). Treatment targets for ID included an increase in hemoglobin concentrations to 10-12 g/dL or normalization (n = 8) and serum ferritin >100 μg/L (n = 7) or 200 μg/L (n = 4). For the latter, in some situations, such as CKD, ferritin concentrations should not exceed 500 μg/L (n = 5) or 800 μg/L (n = 5). Only 9 guidelines recommended TSAT as a target, proposing various thresholds ranging from 20% to 50%.
CONCLUSIONS
It appears that for the diagnosis of ID, a cutoff of 100 μg/L for serum ferritin concentration should be considered in most conditions and 20% for TSAT, except in particular situations, including young healthy women with heavy menstrual flow. New indications of intravenous iron supplementation are emerging.
Topics: Administration, Intravenous; Algorithms; Anemia, Iron-Deficiency; Biomarkers; Dietary Supplements; Down-Regulation; Ferric Compounds; Ferritins; Global Health; Hematinics; Humans; Iron Overload; Iron, Dietary; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Societies, Medical
PubMed: 26561626
DOI: 10.3945/ajcn.114.103366 -
The American Journal of Gastroenterology Jun 2015Persistent disease activity is associated with a poor prognosis in inflammatory bowel disease (IBD). Therefore, monitoring of patients with intent to suppress... (Meta-Analysis)
Meta-Analysis Review
C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis.
OBJECTIVES
Persistent disease activity is associated with a poor prognosis in inflammatory bowel disease (IBD). Therefore, monitoring of patients with intent to suppress subclinical inflammation has emerged as a treatment concept. As endoscopic monitoring is invasive and resource intensive, identification of valid markers of disease activity is a priority. The objective was to evaluate the diagnostic accuracy of C-reactive protein (CRP), fecal calprotectin (FC), and stool lactoferrin (SL) for assessment of endoscopically defined disease activity in IBD.
METHODS
Databases were searched from inception to November 6, 2014 for relevant cohort and case-control studies that evaluated the diagnostic accuracy of CRP, FC, or SL and used endoscopy as a gold standard in patients with symptoms consistent with active IBD. Sensitivities and specificities were pooled to generate operating property estimates for each test using a bivariate diagnostic meta-analysis.
RESULTS
Nineteen studies (n=2499 patients) were eligible. The pooled sensitivity and specificity estimates for CRP, FC, and SL were 0.49 (95% confidence interval (CI) 0.34-0.64) and 0.92 (95% CI 0.72-0.96), 0.88 (95% CI 0.84-0.90) and 0.73 (95% CI 0.66-0.79), and 0.82 (95% CI 0.73-0.88) and 0.79 (95% CI 0.62-0.89), respectively. FC was more sensitive than CRP in both diseases and was more sensitive in ulcerative colitis than Crohn's disease.
CONCLUSIONS
Although CRP, FC, and SL are useful biomarkers, their value in managing individual patients must be considered in specific clinical contexts.
Topics: Biomarkers; C-Reactive Protein; Colitis, Ulcerative; Crohn Disease; Endoscopy, Gastrointestinal; Feces; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Sensitivity and Specificity
PubMed: 25964225
DOI: 10.1038/ajg.2015.120 -
PloS One 2022A wealth of human and experimental studies document a causal and aggravating role of iron deficiency in neurodevelopmental disorders. While pre-, peri-, and early...
BACKGROUND
A wealth of human and experimental studies document a causal and aggravating role of iron deficiency in neurodevelopmental disorders. While pre-, peri-, and early postnatal iron deficiency sets the stage for the risk of developing neurodevelopmental disorders, iron deficiency acquired at later ages aggravates pre-existing neurodevelopmental disorders. Yet, the association of iron deficiency and neurodevelopmental disorders in childhood and adolescence has not yet been explored comprehensively. In this scoping review, we investigate 1) the association of iron deficiency in children and adolescents with the most frequent neurodevelopmental disorders, ADHD, ASD, and FASD, and 2) whether iron supplementation improves outcomes in these disorders.
METHOD
Scoping review of studies published between 1994 and 2021 using "iron deficiency / iron deficiency anemia" AND "ADHD" OR "autism" OR "FASD" in four biomedical databases. The main inclusion criterion was that articles needed to have quantitative determination of iron status at any postnatal age with primary iron markers such as serum ferritin being reported in association with ADHD, ASD, or FASD.
RESULTS
For ADHD, 22/30 studies and 4/4 systematic reviews showed an association of ADHD occurrence or severity with iron deficiency; 6/6 treatment studies including 2 randomized controlled trials demonstrated positive effects of iron supplementation. For ASD, 3/6 studies showed an association with iron deficiency, while 3/6 and 1/1 systematic literature review did not; 4 studies showed a variety of prevalence rates of iron deficiency in ASD populations; 1 randomized controlled trial found no positive effect of iron supplementation on behavioural symptoms of ASD. For FASD, 2/2 studies showed an association of iron deficiency with growth retardation in infants and children with prenatal alcohol exposure.
CONCLUSION
Evidence in favor of screening for iron deficiency and using iron supplementation for pediatric neurodevelopmental disorders comes primarily from ADHD studies and needs to be further investigated for ASD and FASD. Further analysis of study methodologies employed and populations investigated is needed to compare studies against each other and further substantiate the evidence created.
Topics: Adolescent; Anemia, Iron-Deficiency; Child; Female; Ferritins; Humans; Infant; Iron; Iron Deficiencies; Neurodevelopmental Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Randomized Controlled Trials as Topic
PubMed: 36173945
DOI: 10.1371/journal.pone.0273819 -
The Lancet. Haematology Jul 2021Numerous iron preparations are available for the treatment of iron deficiency anaemia in pregnancy. We aimed to provide a summary of the effectiveness and safety of iron... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous iron preparations are available for the treatment of iron deficiency anaemia in pregnancy. We aimed to provide a summary of the effectiveness and safety of iron preparations used in this setting.
METHODS
We did a systematic review and network meta-analysis of randomised trials. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature for trials published in any language from Jan 1, 2011, to Feb 28, 2021. We included trials including pregnant women with iron deficiency anaemia and evaluating iron preparations, irrespective of administration route, with at least 60 mg of elemental iron, in comparison with another iron or non-iron preparation. Three authors independently selected studies, extracted data, and did a risk of bias assessment using the Cochrane tool (version 1.0). The primary outcome was the effectiveness of iron preparations, evaluated by changes in haemoglobin concentration at 4 weeks from baseline. The secondary outcomes were change in serum ferritin concentration at 4 weeks from baseline and treatment-related severe and non-severe adverse events. We did random-effects pairwise and network meta-analyses. Side-effects were reported descriptively for each trial. This study is registered with PROSPERO, CRD42018100822.
FINDINGS
Among 3037 records screened, 128 full-text articles were further assessed for eligibility. Of the 53 eligible trials (reporting on 9145 women), 30 (15 interventions; 3243 women) contributed data to the network meta-analysis for haemoglobin and 15 (nine interventions; 1396 women) for serum ferritin. The risk of bias varied across the trials contributing to network meta-analysis, with 22 of 30 trials in the network meta-analysis for haemoglobin judged to have a high or medium global risk of bias. Compared with oral ferrous sulfate, intravenous iron sucrose improved both haemoglobin (mean difference 7·17 g/L, 95% CI 2·62-11·73; seven trials) and serum ferritin (mean difference 49·66 μg/L, 13·63-85·69; four trials), and intravenous ferric carboxymaltose improved haemoglobin (mean difference 8·52 g/L, 0·51-16·53; one trial). The evidence for other interventions compared with ferrous sulfate was insufficient. The most common side-effects with oral iron preparations were gastrointestinal effects (nausea, vomiting, and altered bowel movements). Side-effects were less common with parenteral iron preparations, although these included local pain, skin irratation, and, on rare occasions, allergic reactions.
INTERPRETATION
Iron preparations for treatment of iron deficiency anaemia in pregnancy vary in effectiveness, with good evidence of benefit for intravenous iron sucrose and some evidence for intravenous ferric carboxymaltose. Clinicians and policy makers should consider the effectiveness of individual preparations before administration, to ensure effective treatment.
FUNDING
None.
Topics: Anemia, Iron-Deficiency; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Ferrous Compounds; Hemoglobins; Humans; Maltose; Nausea; Pregnancy
PubMed: 34171281
DOI: 10.1016/S2352-3026(21)00137-X -
BMJ Open Apr 2018Iron supplementation in iron-deficiency anaemia is standard practice, but the benefits of iron supplementation in iron-deficient non-anaemic (IDNA) individuals remains...
OBJECTIVE
Iron supplementation in iron-deficiency anaemia is standard practice, but the benefits of iron supplementation in iron-deficient non-anaemic (IDNA) individuals remains controversial. Our objective is to identify the effects of iron therapy on fatigue and physical capacity in IDNA adults.
DESIGN
Systematic review and meta-analysis of randomised controlled trials (RCTs).
SETTING
Primary care.
PARTICIPANTS
Adults (≥18 years) who were iron deficient but non-anaemic.
INTERVENTIONS
Oral, intramuscular or intravenous iron supplementation; all therapy doses, frequencies and durations were included.
COMPARATORS
Placebo or active therapy.
RESULTS
We identified RCTs in Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health, SportDiscus and CAB Abstracts from inception to 31 October 2016. We searched the WHO's International Clinical Trials Registry Platform for relevant ongoing trials and performed forward searches of included trials and relevant reviews in Web of Science. We assessed internal validity of included trials using the Cochrane Risk of Bias tool and the external validity using the Grading of Recommendations Assessment, Development and Evaluation methodology. From 11 580 citations, we included 18 unique trials and 2 companion papers enrolling 1170 patients. Using a Mantel-Haenszel random-effects model, iron supplementation was associated with reduced self-reported fatigue (standardised mean difference (SMD) -0.38; 95% CI -0.52 to -0.23; I 0%; 4 trials; 714 participants) but was not associated with differences in objective measures of physical capacity, including maximal oxygen consumption (SMD 0.11; 95% CI -0.15 to 0.37; I 0%; 9 trials; 235 participants) and timed methods of exercise testing. Iron supplementation significantly increased serum haemoglobin concentration (MD 4.01 g/L; 95% CI 1.22 to 6.81; I 48%; 12 trials; 298 participants) and serum ferritin (MD 9.23 µmol/L; 95% CI 6.48 to 11.97; I 58%; 14 trials; 616 participants).
CONCLUSION
In IDNA adults, iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity. Given the global prevalence of both iron deficiency and fatigue, patients and practitioners could consider consumption of iron-rich foods or iron supplementation to improve symptoms of fatigue in the absence of documented anaemia.
PROSPERO REGISTRATION NUMBER
CRD42014007085.
Topics: Adult; Fatigue; Female; Ferritins; Humans; Iron; Iron Deficiencies; Male; Randomized Controlled Trials as Topic
PubMed: 29626044
DOI: 10.1136/bmjopen-2017-019240 -
American Journal of Hematology Jul 2020COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding,...
COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL-6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID-19 patients. Elevated D-Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life-threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID-19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.
Topics: Anticoagulants; Betacoronavirus; Biomarkers; Blood Coagulation Tests; Blood Donors; C-Reactive Protein; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Cytokine Release Syndrome; Cytokines; Disseminated Intravascular Coagulation; Early Diagnosis; Ferritins; Fibrin Fibrinogen Degradation Products; Humans; Lymphopenia; Meta-Analysis as Topic; Pandemics; Pneumonia, Viral; Risk; SARS-CoV-2; Thrombophilia; Venous Thromboembolism
PubMed: 32282949
DOI: 10.1002/ajh.25829 -
Sports Health 2018Supplementing iron-deficient nonanemic (IDNA) athletes with iron to improve performance is a trend in endurance sports. (Review)
Review
CONTEXT
Supplementing iron-deficient nonanemic (IDNA) athletes with iron to improve performance is a trend in endurance sports.
OBJECTIVES
To investigate the benefits of iron on performance, identify a ferritin level cutoff in IDNA athletes, and determine which iron supplementation regimens are most effective.
DATA SOURCES
A search of the PubMed, CINAHL, Embase, ERIC, and Cochrane databases was performed in 2014 including all articles. Citations of pertinent review articles were also searched. In 2017, the search was repeated.
STUDY SELECTION
Inclusion criteria comprised studies of level 1 to 3 evidence, written in the English language, that researched iron supplementation in nonanemic athletes and reported performance outcomes.
STUDY DESIGN
Systematic review.
LEVEL OF EVIDENCE
Level 3.
DATA EXTRACTION
The search terms used included athletic performance, resistance training, athletes, physical endurance, iron, iron deficiency, supplement, non-anemic, low ferritin, ferritin, ferritin blood level, athletes, and sports.
RESULTS
A total of 1884 studies were identified through the initial database search, and 13 were identified through searching references of relevant review articles. A subsequent database search identified 46 studies. Following exclusions, 12 studies with a total of 283 participants were included. Supplementing IDNA athletes with iron improved performance in 6 studies (146 participants) and did not improve performance in the other 6 studies (137 participants). In the 6 studies that showed improved performance with iron supplementation, all used a ferritin level cutoff of ≤20 μg/L for treatment. Additionally, all studies that showed improved performance used oral iron as a supplement.
CONCLUSION
The evidence is equivocal as to whether iron supplementation in IDNA athletes improves athletic performance. Supplementing athletes with ferritin levels <20 μg/L may be more beneficial than supplementing athletes with higher baseline ferritin levels.
Topics: Athletic Performance; Dietary Supplements; Ferritins; Humans; Iron; Iron Deficiencies
PubMed: 29792778
DOI: 10.1177/1941738118777488