A Comprehensive Evaluation of Serum Iron Status Indicators in Patients with Age-Related Macular Degeneration.

Objectives: Iron is recognized as a significant contributor to oxidative damage, and its levels tend to rise with age, potentially worsening age-related diseases. The aim of this study was to investigate the role of serum iron metabolism markers in the pathogenesis of age-related macular degeneration (AMD). Methods: The files of all AMD patients in Kocaeli University School of Medicine between January 2017 and March 2020 were reviewed retrospectively. By examining the files of AMD patients who applied to the eye outpatient clinic on the same dates, those dry AMD (dAMD) and neovascular AMD (nAMD) were recorded. As a control group, the records of patients without any AMD findings were obtained from the files of all patients who visited the clinic during the same time period. All records were recorded for analysis, including a comprehensive ophthalmological examination, laboratory data of fasting blood tests, and an internal medicine outpatient examination. Results: Of the 164 participants, 50 were dAMD patients, 51 were nAMD patients, and 63 were patients non-AMD (control group). There was a significant difference between the groups' mean corpuscular volume (MCV), serum ferritin, and total iron-binding capacity (TIBC) (p<0.050). It was observed that the ferritin of those with AMD was significantly higher than the control group, whereas MCV and TIBC were found to be significantly lower (p<0.050). There was no significant difference in serum iron marker levels between nAMD and dAMD patients (p>0.05). Conclusion: Assessing serum iron status indicators during the routine monitoring of AMD may provide insights into the associated risk profile of the condition.

Acute and Chronic Effects of Interval Aerobic Exercise on Hepcidin, Ferritin, and Liver Enzymes in Adolescents With Beta-Thalassemia Major.

PURPOSE: This study aimed to determine the acute and chronic effects of interval aerobic exercise on hepcidin, ferritin, and liver enzymes in adolescents with beta-thalassemia major. METHODS: Twenty-six beta-thalassemia major adolescents referred to the Thalassemia Clinic and Research Center were selected as study participants and randomly divided into control (n = 13) and training (n = 13) groups. Participants performed 3 sessions per week for 45 minutes in each session for 8 weeks of aerobic interval exercise with an intensity of 50% to 65% of the heart rate reserve. Blood samples were taken before, immediately after the exercise session, and 48 hours after the last training session, and liver enzymes aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase (ALP), ferritin, and hepcidin were evaluated. RESULTS: The results showed a decrease in aspartate aminotransferase, ALT, ALP, ferritin, and hepcidin levels due to 8 weeks of aerobic interval training (P = .14, P = .97, P = .03, P < .001, P < .001; respectively). Intergroup changes in all variables except ALT and hepcidin were significant (P < .05). Besides, acute aerobic exercise increased levels of aspartate aminotransferase, ALT, ferritin, and hepcidin (P = .04, P = .52, P < .001, P < .001; respectively), whereas ALP levels decreased (P < .001). In addition, changes in ALP and hepcidin levels were significant between the 2 groups (P = .05, P < .001; respectively). CONCLUSION: Based on the study's results, it can be concluded that 8 weeks of aerobic interval training can decrease ferritin and hepcidin levels, but acute aerobic exercise increases them.

Association between iron status, preeclampsia and gestational hypertension: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Several recent observational studies have reported that iron overload during pregnancy is associated with preeclampsia (PE) and gestational hypertension (GH). However, the causal association between iron status, PE, and GH is still not clear. METHODS: We performed a two-sample Mendelian randomization (MR) study using the genome-wide association study (GWAS) summary statistics of iron status, included serum iron, ferritin, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) from the largest available GWAS meta-analysis, and the summary statistics of PE and GH were obtained from the FinnGen consortium. Fixed-effect inverse variance weighted (IVW), random-effect IVW, maximum likelihood (ML), MR-Egger regression, weighted median, and MR-PRESSO methods were used. RESULTS: A total of 21, 58, 28, and 22 SNPs were used as IVs for serum iron, ferritin, TIBC, and TSAT, respectively. The F-statistics of IVs ranged from 95.23 to 421.36. The results of the fixed effects IVW method suggested that for per SD unit increase in serum iron, the risk of PE increases by 24 % (OR = 1.24, 95 % CI: 1.03-1.50, P = 0.02). No significant heterogeneity or horizontal pleiotropy was found. The association between ferritin, TIBC, TSAT and PE were statistically insignificant (P>0.05). Furthermore, the results of each MR methods do not support a causal association between iron status and GH, nor a reverse causal association between PE and GH and iron status. CONCLUSION: This two-sample MR study provides evidence supporting a causal association between serum iron level and PE.

Association between overweight/obesity and iron deficiency anaemia among women of reproductive age: a systematic review.

OBJECTIVE: Numerous studies have examined the relationship between overweight/obesity and iron deficiency anaemia (IDA) across diverse population groups, but a definitive link has not been clearly determined. This systematic review examined the association between overweight/obesity and IDA in women of reproductive age (WRA). DESIGN: The initial search was performed in the CINAHL, Embase, MEDLINE, SCOPUS and Web of Science databases. The studies included should report at least one Fe status with/without an inflammatory marker, using the BMI to define overweight/obesity. Only baseline data were extracted for longitudinal studies. SETTING: Global. PARTICIPANT: Pregnant or non-pregnant women aged 18-50 years. RESULTS: In total, twenty-seven papers were included (twelve addressing pregnant women and fifteen addressing non-pregnant women). Overall, most of the studies reported no association between overweight/obesity and Hb concentration. However, a positive association was reported more frequently in pregnant women. The association between overweight/obesity and serum ferritin concentrations was mixed. Most of the studies on non-pregnant women reported a positive association. Only a few studies measured hepcidin and inflammatory markers, and the majority revealed an increased level among overweight/obese WRA. Among pregnant women, overweight/obesity was positively associated with anaemia and IDA but negatively associated with iron deficiency (ID). Meanwhile, overweight/obese non-pregnant women were positively associated with anaemia, ID and IDA. CONCLUSIONS: Overweight/obesity was associated with a decreased prevalence of anaemia and IDA but an increased prevalence of ID, while its association with several Fe markers was inconclusive. Further studies integrating the assessment of various Fe markers, inflammatory markers and hepcidin are needed.

Association between serum iron status and the risk of five bone and joint-related diseases: a Mendelian randomization analysis.

Background: According to reports, iron status has been associated with the risk of bone and joint-related diseases. However, the exact role of iron status in the development of these conditions remains uncertain. Method: We obtained genetic data on iron status, specifically serum iron, ferritin, transferrin saturation (TSAT), and transferrin, as well as data on five common bone and joint-related diseases (osteoarthritis, osteoporosis, rheumatoid arthritis [RA], ankylosing spondylitis [AS], and gout) from independent genome-wide association studies involving individuals of European ancestry. Our primary approach for causal estimation utilized the inverse variance weighted (IVW) method. To ensure the reliability of our findings, we applied complementary sensitivity analysis and conducted reverse causal analysis. Result: Using the IVW method, we revealed a positive causal relationship between ferritin levels and the risk of osteoarthritis (OR [95% CI], 1.0114 [1.0021-1.0207]). Besides, we identified a protective causal relationship between serum iron levels and TSAT levels in the risk of RA (OR [95% CI] values of serum iron and TSAT were 0.9987 [0.9973-0.9999] and 0.9977 [0.9966-0.9987], respectively). Furthermore, we found a positive causal relationship between serum iron levels and the risk of AS (OR [95% CI], 1.0015 [1.0005-1.0026]). Regarding gout, both serum iron and TSAT showed a positive causal relationship (OR [95% CI] values of 1.3357 [1.0915-1.6345] and 1.2316 [1.0666-1.4221] for serum iron and TSAT, respectively), while transferrin exhibited a protective causal relationship (OR [95% CI], 0.8563 [0.7802-0.9399]). Additionally, our reverse causal analysis revealed a negative correlation between RA and ferritin and TSAT levels (OR [95% CI] values of serum iron and TSAT were 0.0407 [0.0034-0.4814] and 0.0049 [0.0002-0.1454], respectively), along with a positive correlation with transferrin (OR [95% CI], 853.7592 [20.7108-35194.4325]). To ensure the validity of our findings, we replicated the results through sensitivity analysis during the validation process. Conclusion: Our study demonstrated a significant correlation between iron status and bone and joint-related diseases.

Micronutrient Status During Military Training and Associations With Musculoskeletal Health, Injury, and Readiness Outcomes.

OBJECTIVE: Micronutrient status, specifically vitamin D and iron, represent modifiable factors for optimizing military readiness. The primary purpose of this investigation was to determine associations between micronutrient deficiency (i.e., iron status and 25-hydroxy-vitamin D [25(OH)D]) and operationally relevant outcomes (i.e., skeletal health, musculoskeletal injury) at baseline and post-10 weeks of arduous military training. METHODS: A total of 227 (177 men, 50 women) Marine Officer Candidates School (OCS) candidates who completed OCS training with complete data sets were included in this analysis. Vitamin D and iron status indicators were collected at two timepoints, pre (baseline) and post OCS. Musculoskeletal outcomes at the mid- and proximal tibial diaphysis were assessed via peripheral quantitative computed tomography. RESULTS: Micronutrient status declined following OCS training in men and women and was associated with musculoskeletal outcomes including greater bone strength (strength strain index) at the mid-diaphysis site in those with optimal status (M = 38.26 mm3, SE = 15.59) versus those without (M = -8.03 mm3, SE = 17.27). In women (p = .037), endosteal circumference was greater in the deficient group (M = 53.26 mm, SE = 1.19) compared with the optimal group (M = 49.47 mm, SE = 1.31) at the proximal diaphysis. In men, greater baseline hepcidin concentrations were associated with an increased likelihood of suffering musculoskeletal injury during training. CONCLUSIONS: Vitamin D and iron status declined over the course of training, suggesting impaired micronutrient status. Differences in musculoskeletal outcomes by micronutrient group suggests optimal vitamin D and ferritin concentrations may exert beneficial effects on bone fatigability and fracture reduction during military training.

Associations of genetically predicted iron status with 24 gastrointestinal diseases and gut microbiota: a Mendelian randomization study.

Background: Iron status has been implicated in gastrointestinal diseases and gut microbiota, however, confounding factors may influence these associations. Objective: We performed Mendelian randomization (MR) to investigate the associations of iron status, including blood iron content, visceral iron content, and iron deficiency anemia with the incidence of 24 gastrointestinal diseases and alterations in gut microbiota. Methods: Independent genetic instruments linked with iron status were selected using a genome-wide threshold of p = 5 × 10-6 from corresponding genome-wide association studies. Genetic associations related to gastrointestinal diseases and gut microbiota were derived from the UK Biobank, the FinnGen study, and other consortia. Results: Genetically predicted higher levels of iron and ferritin were associated with a higher risk of liver cancer. Higher levels of transferrin saturation were linked to a decreased risk of celiac disease, but a higher risk of non-alcoholic fatty liver disease (NAFLD) and liver cancer. Higher spleen iron content was linked to a lower risk of pancreatic cancer. Additionally, higher levels of liver iron content were linked to a higher risk of NAFLD and liver cancer. However, certain associations lost their statistical significance upon accounting for the genetically predicted usage of cigarettes and alcohol. Then, higher levels of iron and ferritin were associated with 11 gut microbiota abundance, respectively. In a secondary analysis, higher iron levels were associated with lower diverticular disease risk and higher ferritin levels with increased liver cancer risk. Higher levels of transferrin saturation were proven to increase the risk of NAFLD, alcoholic liver disease, and liver cancer, but decrease the risk of esophageal cancer. MR analysis showed no mediating relationship among iron status, gut microbiota, and gastrointestinal diseases. Conclusion: This study provides evidence suggesting potential causal associations of iron status with gastrointestinal diseases and gut microbiota, especially liver disease.

Source and level of dietary iron influence semen quality by affecting inflammation, oxidative stress and iron utilization levels in boars.

BACKGROUND: Boars fed a mixed form of inorganic and organic iron in excess of the NRC recommended levels still develop anemia, which suggested that the current level and form of iron supplementation in boar diets may be inappropriate. Therefore, 56 healthy Topeka E line boars aged 15-21 months were randomly divided into 5 groups: basal diet supplemented with 96 mg/kg ferrous sulfate (FeSO4) and 54 mg/kg glycine chelated iron (Gly-Fe, control); 80 mg/kg or 115 mg/kg Gly-Fe; 80 mg/kg or 115 mg/kg methionine hydroxyl analogue chelated iron (MHA-Fe, from Calimet-Fe) for 16 weeks. The effects of dietary iron supplementation with different sources and levels on semen quality in boars were investigated. RESULTS: 1) Serum Fe and hemoglobin concentrations were not affected by reduced dietary iron levels in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups compared with the control group (P > 0.05). 2) Serum interleukin-6 (IL-6) and sperm malondialdehyde (MDA) levels in the 80 mg/kg or 115 mg/kg MHA-Fe groups were lower than those in the control group (P < 0.05), and higher serum superoxide dismutase levels and lower MDA levels in the 115 mg/kg MHA-Fe group (P < 0.05). 3) Boars in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups had lower serum hepcidin (P < 0.01), ferritin (P < 0.05), and transferrin receptor (P < 0.01) concentrations, and boars in the 115 mg/kg MHA-Fe group had higher seminal plasma Fe concentrations compared with the control group. 4) Boars in the 80 mg/kg and 115 mg/kg MHA-Fe groups had lower abnormal sperm rate and in situ oscillating sperm ratio compared to the control group at weeks 12 and/or 16 of the trial. However, the effect of Gly-Fe on improving semen quality in boars was not evident. 5) Serum IL-6 level was positively correlated with hepcidin concentration (P < 0.05), which in turn was significantly positively correlated with abnormal sperm rate (P < 0.05). Furthermore, significant correlations were also found between indicators of iron status and oxidative stress and semen quality parameters. CONCLUSIONS: Dietary supplementation with 80 mg/kg or 115 mg/kg MHA-Fe did not induce iron deficiency, but rather reduced serum inflammatory levels and hepcidin concentration, alleviated oxidative stress, increased body iron utilization, and improved semen quality in adult boars.

Examining the impact of polyfluoroalkyl substance exposure on erythrocyte profiles and its related nutrients: Insights from a prospective study on young Taiwanese.

Per- and polyfluoroalkyl substances (PFAS) constitute a group of synthetic chemicals extensively utilized across various commonplace products. PFAS are known to have various toxic effects on human health. The relationship between PFAS exposure and erythrocytes has been a subject of interest in epidemiological research, but so far, only limited cross-sectional studies have investigated. Additionally, the role of erythrocyte related nutrition indicators on PFAS-induced changes in erythrograms has not been explored. To fill these knowledge gaps, we launched a longitudinal study over a decade, tracking 502 adolescents and young adults aged 12 to 30 from the YOung TAiwanese Cohort (YOTA). Our analysis encompassed 11 types of plasma PFAS, as well as erythrograms and serum levels of ferritin, transferrin saturation, vitamin B12, and folate. Our examination unveiled positive associations between specific average levels of PFAS compounds, including linear perfluorooctanoic acid (PFOA), branched perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), and transferrin saturation. Furthermore, linear PFOA and both linear and branched PFOS were negatively correlated with vitamin B12 levels. Specifically, we observed that the average linear PFOA demonstrated positive correlations with mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), while average PFNA also exhibited positive associations with hemoglobin (Hb) and hematocrit (Hct) in a multiple linear regression model. Subsequent analysis revealed noteworthy interactions between vitamin B12 and PFNA, as well as folate and PFNA, in the context of their impact on Hb, Hct, and PFNA relationships. Additionally, an interaction with transferrin saturation was identified in the correlation between Hct and PFNA. These findings suggest a plausible link between PFAS exposure and erythrograms among young populations, underscoring the potential involvement of iron status, vitamin B12, and folate in this association. Further studies are imperative to elucidate the precise effects of PFAS on erythrocyte in human subjects.

Exploring genetic association of systemic iron status and risk with incidence of diabetic neuropathy.

BACKGROUND: Diabetic neuropathy (DN), a frequent complication in individuals with diabetes mellitus (DM), is hypothesized to have a correlation with systemic iron status, though the nature of this relationship remains unclear. This study employs two-sample Mendelian randomization (MR) analysis to explore this potential genetic association. METHODS: We used genetic instruments significant associated with iron status including serum iron, ferritin, transferrin, and transferrin saturation, derived from an extensive Genome-Wide Association Study (GWAS) undertaken by the Genetics of Iron Status Consortium, involving a cohort of 48,972 European ancestry individuals. Summary statistics for DN were collected from a public GWAS, including 1,415 patients and 162,201 controls of European descent. Our MR analysis used the inverse-variance-weighted (IVW) method, supplemented by MR-Egger, weighted-median (WM) methods, Cochran's Q test, MR-Egger intercept analysis, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method, and leave-one-out analysis to ensure robustness and consistency of the findings. RESULTS: No genetic causal relationship was found between iron status markers and DN (all IVW p value > 0.05). Interestingly, a causative effect of DN on ferritin (IVW: OR = 0.943, 95% CI = 0.892-0.996, p = 0.035) and transferrin saturation (IVW: OR = 0.941, 95% CI = 0.888-0.998, p = 0.044) emerged. Sensitivity analyses confirmed the absence of significant heterogeneity and horizontal pleiotropy. CONCLUSION: While systemic iron status was not found to be causally related to DN, our findings suggest that DN may increase the risk of iron deficiency. These results provide further evidence supporting iron supplementation in patients with DN.

Acute inflammatory response following lower-and upper-body Wingate anaerobic test in elite gymnasts in relation to iron status.

Introduction: Artistic gymnastics is one of the most demanding sports disciplines, with the athletes demonstrating extremely high levels of explosive power and strength. Currently, knowledge of the effect of gymnastic training adaptation on exercise-induced inflammatory response is limited. The study aimed to evaluate inflammatory response following lower- and upper-body high-intensity exercise in relation to the iron status in gymnasts and non-athletes. Methods: Fourteen elite male artistic gymnasts (EAG, 20.6 ± 3.3 years old) and 14 physically active men (PAM, 19.9 ± 1.0 years old) participated in the study. Venous blood samples were taken before and 5 min and 60 min after two variants of Wingate anaerobic test (WAnT), upper-body and lower-body WAnT. Basal iron metabolism (serum iron and ferritin) and acute responses of selected inflammatory response markers [interleukin (IL) 6, IL-10, and tumour necrosis factor α] were analysed. Results: EAG performed significantly better during upper-body WAnT than PAM regarding relative mean and peak power. The increase in IL-6 levels after upper-body WAnT was higher in EAG than in PAM; the opposite was observed after lower-body WAnT. IL-10 levels were higher in EAG than in PAM, and tumour necrosis factor α levels were higher in PAM than those in EAG only after lower-body WAnT. The changes in IL-10 correlated with baseline serum iron and ferritin in PAM. Discussion: Overall, gymnastic training is associated with the attenuation of iron-dependent post-exercise anti-inflammatory cytokine secretion.

Relationships between Iron Status and Selected Physical Fitness Components of South African Adolescents: The PAHL-Study.

Poor iron status is detrimental to physical and cognitive performance in adolescents. Due to the limited studies investigating the association between iron status and physical fitness components in adolescents from low- and middle-income countries, we aimed to determine the association of iron status with selected physical fitness components in South African adolescents. A cross-sectional study design, including 178 adolescents (102 girls and 76 boys) from the Physical Activity and Health Longitudinal Study (PAHLS), was followed. Height and weight were measured to calculate the body mass index (BMI). Subsequently, WHO BMI-for-age-specific categorised body fatness. Cardiorespiratory fitness was determined with a 20-m shuttle run test (V˙O2max), and lower-body explosive power by the standing broad jump (SBJ). Fasting haemoglobin (Hb) and ferritin were analysed from blood samples. Correlation analyses determine the association between iron status, explosive power and cardiorespiratory fitness. Of the 178 participants, 18.5% (n = 33) had low Hb, and 14% (n = 25) iron deficiency without anaemia. Significant positive correlations were found between the selected physical fitness components, ferritin, and Hb. In boys, a positive association was found between Hb and SBJ (r = 0.30, p = 0.006), whilst in girls, positive associations were found between ferritin (r = 0.25, p = 0.04) and SBJ, and Hb with both SBJ (r = 0.21, p = 0.03) and V˙O2max (r = 0.32, p = 0.001). Hb concentration remained associated with V˙O2max and SBJ in girls after adjustment for age, whilst in boys, Hb concentration was associated with SBJ. Higher iron status in South African adolescents is associated with higher lower-limb explosive power and cardiorespiratory fitness. We suggest monitoring of haematological parameters, and interventions to improve the iron status of South African adolescents.

Baby Food Pouches, Baby-Led Weaning, and Iron Status in New Zealand Infants: An Observational Study.

Iron deficiency in infants can impact development, and there are concerns that the use of baby food pouches and baby-led weaning may impair iron status. First Foods New Zealand (FFNZ) was an observational study of 625 New Zealand infants aged 6.9 to 10.1 months. Feeding methods were defined based on parental reports of infant feeding at "around 6 months of age": "frequent" baby food pouch use (five+ times per week) and "full baby-led weaning" (the infant primarily self-feeds). Iron status was assessed using a venepuncture blood sample. The estimated prevalence of suboptimal iron status was 23%, but neither feeding method significantly predicted body iron concentrations nor the odds of iron sufficiency after controlling for potential confounding factors including infant formula intake. Adjusted ORs for iron sufficiency were 1.50 (95% CI: 0.67-3.39) for frequent pouch users compared to non-pouch users and 0.91 (95% CI: 0.45-1.87) for baby-led weaning compared to traditional spoon-feeding. Contrary to concerns, there was no evidence that baby food pouch use or baby-led weaning, as currently practiced in New Zealand, were associated with poorer iron status in this age group. However, notable levels of suboptimal iron status, regardless of the feeding method, emphasise the ongoing need for paying attention to infant iron nutrition.

Urinary Ferritin as a Noninvasive Means of Assessing Iron Status in Young Children.

BACKGROUND: Iron deficiency (ID) is the most common nutritional deficiency affecting young children. Serum ferritin concentration is the preferred biomarker for measuring iron status because it reflects iron stores; however, blood collection can be distressing for young children and can be logistically difficult. A noninvasive means to measure iron status would be attractive to either diagnose or screen for ID in young children. OBJECTIVES: This study aimed to determine the correlation between urinary and serum ferritin concentrations in young children; to determine whether correcting urinary ferritin for creatinine and specific gravity improves the correlation; and to determine a urine ferritin cut point to predict ID. METHODS: Validation study was conducted using paired serum and urine collected from 3-y-old children (n = 142) participating in a longitudinal birth cohort study: the ORIGINS project in Perth, Western Australia. We calculated the sensitivity, specificity, positive, and negative predictive values of urinary ferritin amount in identifying those with ID at the clinical cut point used by the World Health Organization (serum ferritin concentration of <12 ng/mL). RESULTS: Urine ferritin, corrected for creatinine, correlated moderately with serum ferritin [r = 0.53 (0.40-0.64)] and performed well in predicting those with ID (area under the curve: 0.85; 95% confidence interval: 0.75, 0.94). Urine ferritin <2.28 ng/mg creatinine was sensitive (86%) and specific (77%) in predicting ID and had a high negative predictive value of 97%; however, the positive predictive value was low (40%) owing to the low prevalence of ID in the sample (16%). CONCLUSIONS: Urine ferritin shows good diagnostic performance for ID. This noninvasive biomarker maybe a useful screening tool to exclude ID in healthy young children; however, further research is needed in other populations.

Iron parameters analysis in dogs with myxomatous mitral valve disease.

BACKGROUND: Myxomatous mitral valve disease (MMVD) is the most common acquired cardiovascular disease in small breed dogs. In contrast to human patients with heart failure (HF), iron deficiency (ID) prevalence in dogs with MMVD is weakly known. The study aimed to assess the usability of ID markers in serum and reticulocyte parameters from whole blood of dogs with MMVD to evaluate early ID symptoms. RESULTS: Sixty-eight dogs (43 male and 25 female) were included in the study. MMVD dogs were assigned according to the 2019 ACVIM guidelines for groups B1 (n = 9), B2 (n = 10), C (n = 27) and D (n = 10). Groups were also combined into B1 and B2 as non-symptomatic HF and C with D as symptomatic HF. Healthy controls were 12 dogs. Serum iron concentration below the reference range in dogs with MMVD was 12.5%. Other ID indices, such as %SAT, UIBC, and TIBC were similar in the MMVD groups and healthy controls (p > 0.05 for all parameters). Statistical comparison between control group and 4 groups of different stages of MMVD showed that significant differences occur only in serum transferrin. The assessment of ferritin and soluble transferrin receptors using Western Blotting did not show differences between control (n = 7) and MMVD (n = 33) dogs. Study has shown positive correlation between ID parameters and echocardiographic indices such as LA/Ao and LVIDdN, and some biochemical parameters. A significant increase in reticulocytes percentage, assessed manually, was observed in the HF group of animals (p = 0.027) compared to the control group. CONCLUSIONS: Studies have shown that ID parameters in serum are not significantly different in dogs with MMVD compared to healthy dogs. However, there is a clear correlation between atrial size and normalised left ventricular size to body size and some biochemical parameters, including ID parameters and therefore the severity of MMVD.

Seasonal Variation in Vitamin D Status Does Not Interfere with Improvements in Aerobic and Muscular Endurance in Conscripts during Basic Military Training.

Considering a lack of respective data, the primary objective of this study was to assess whether seasonal variation in vitamin D status (D-status) affects the extent of improvement in physical performance (PP) in conscripts during basic military training (BMT). D-status, PP and several blood parameters were measured repeatedly in conscripts whose 10-week BMT started in July (cohort S-C; n = 96) or in October (cohort A-C; n = 107). D-status during BMT was higher in S-C compared to A-C (overall serum 25(OH)D 61.4 ± 16.1 and 48.5 ± 20.7 nmol/L, respectively; p < 0.0001). Significant (p < 0.05) improvements in both aerobic and muscular endurance occurred in both cohorts during BMT. Pooled data of the two cohorts revealed a highly reliable (p = 0.000) but weak (R2 = 0.038-0.162) positive association between D-status and PP measures both at the beginning and end of BMT. However, further analysis showed that such a relationship occurred only in conscripts with insufficient or deficient D-status, but not in their vitamin D-sufficient companions. Significant (p < 0.05) increases in serum testosterone-to-cortisol ratio and decreases in ferritin levels occurred during BMT. In conclusion, a positive association exists between D-status and PP measures, but seasonal variation in D-status does not influence the extent of improvement in PP in conscripts during BMT.

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation.

CONTEXT: Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation. OBJECTIVE AND METHODS: Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73 m2; CKDG3a/b; n = 35) or normal renal function (eGFR >90 ml/min/1.73 m2; CKDG1; n = 35) received 12,000, 24,000 or 48,000 IU D3/month for 1 year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression. RESULTS: Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNFα were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNFα significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR. CONCLUSION: Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.

No genetic causal association between iron status and pulmonary artery hypertension: Insights from a two-sample Mendelian randomization.

To explore the genetic causal association between pulmonary artery hypertension (PAH) and iron status through Mendelian randomization (MR), we conducted MR analysis using publicly available genome-wide association study (GWAS) summary data. Five indicators related to iron status (serum iron, ferritin, total iron binding capacity (TIBC), soluble transferrin receptor (sTfR), and transferrin saturation) served as exposures, while PAH was the outcome. The genetic causal association between these iron status indicators and PAH was assessed using the inverse variance weighted (IVW) method. Cochran's Q statistic was employed to evaluate heterogeneity. We assessed pleiotropy using MR-Egger regression and MR-Presso test. Additionally, we validated our results using the Weighted median, Simple mode, and Weighted mode methods. Based on the IVW method, we found no causal association between iron status (serum iron, ferritin, TIBC, sTfR, and transferrin saturation) and PAH (p ß > 0.05). The Weighted median, Simple mode, and Weighted mode methods showed no potential genetic causal association (p ß > 0.05 in the three analyses). Additionally, no heterogeneity or horizontal pleiotropy was detected in any of the analyses. Our results show that there are no genetic causal association between iron status and PAH.

Association among attention-deficit hyperactivity disorder, restless legs syndrome, and peripheral iron status: a two-sample Mendelian randomization study.

Background: Epidemiological evidence indicates a high correlation and comorbidity between Attention Deficit Hyperactivity Disorder (ADHD) and Restless Legs Syndrome (RLS). Objective: We aimed to investigate the causal relationship and shared genetic architecture between ADHD and RLS, as well as explore potential causal associations between both disorders and peripheral iron status. Methods: We performed two-sample Mendelian randomization (MR) analyses using summary statistics from genome-wide meta-analyses of ADHD, RLS, and peripheral iron status (serum iron, ferritin, transferrin saturation, and total iron binding capacity). Additionally, we employed linkage disequilibrium score regression (LDSC) to assess genetic correlations between ADHD and RLS using genetic data. Results: Our MR results supports a causal effect from ADHD (as exposure) to RLS (as outcome) (inverse variance weighted OR = 1.20, 95% CI: 1.08-1.34, p = 0.001). Conversely, we found no a causal association from RLS to ADHD (inverse variance weighted OR = 1.04, 95% CI: 0.99-1.09, p = 0.11). LDSC analysis did not detect a significant genetic correlation between RLS and ADHD (Rg = 0.3, SE = 0.16, p = 0.068). Furthermore, no evidence supported a causal relationship between peripheral iron deficiency and the RLS or ADHD onset. However, RLS may have been associated with a genetic predisposition to reduced serum ferritin levels (OR = 1.20, 95% CI: 1.00-1.04, p = 0.047). Conclusion: This study suggests that ADHD is an independent risk factor for RLS, while RLS may confer a genetic predisposition to reduced serum ferritin levels. Limitations: The GWAS summary data utilized originated from populations of European ancestry, limiting the generalizability of conclusions to other populations. Clinical implications: The potential co-occurrence of RLS in individuals with ADHD should be considered during diagnosis and treatment. Moreover, iron supplementation may be beneficial for alleviating RLS symptoms.