Serum Concentrations of Trace Elements Zinc, Copper, Selenium, and Manganese in Critically Ill Patients.
Lee Yeon Hee,Bang Eun-Sook,Lee Ji-Hyun,Lee Jung-Dong,Kang Dae Ryong,Hong Jeong,Lee Jae-Myeong
Biological trace element research
We measured serum concentrations of trace elements and evaluated their clinical significance in relation to treatment outcomes of critically ill patients. A total of 167 participants (105 men and 62 women; average age, 61.4 years; age range, 18-90 years) were enrolled. Arterial blood concentrations of the trace elements zinc, copper, selenium, and manganese were measured every 14 days. At the time of intensive care unit (ICU) admission, serum concentrations of zinc, selenium, copper, and manganese were lower than the normal values in 75.1, 1.8, 37.8, and 2.1% of patients, respectively. Serum trace element concentrations measured on day 14 of ICU stay were higher than those measured at the time of ICU admission for zinc (53.3 → 80.7 μg/L) and copper (87.1 → 102.3 μg/L). Increased serum zinc and copper concentrations during ICU care were associated with a significantly lower mortality compared to decreased concentrations of zinc (15.6 vs. 83.3%, p = 0.003) and copper (5.6 vs. 50.0%, p = 0.013). At the time of ICU admission, low serum levels of zinc and copper were observed. Patients with increased serum concentrations of zinc and copper had significantly lower mortality.
Associations of Serum Zinc, Copper, and Zinc/Copper Ratio with Sleep Duration in Adults.
Biological trace element research
The existing evidence on the relationships of serum zinc, copper, and zinc/copper ratio with sleep duration is limited and conflicting. The present cross-sectional study aimed to investigate these associations in general adults by utilizing data from the 2011-2016 National Health and Nutrition Examination Survey. The concentrations of zinc and copper were measured in serum samples. Sleep duration (self-reported usual sleep duration) was categorized as < 7 h/night (short sleep duration), 7-8 h/night (optimal sleep duration), and > 8 h/night (long sleep duration). Multinomial logistic regression models and restricted cubic splines were constructed to examine the associations of serum zinc, copper, and zinc/copper ratio with sleep duration. A total of 5067 adults were included. After multivariate adjustment, compared with the optimal sleep duration group, the odds ratios (ORs) (95% confidence intervals, CIs) in the long sleep duration group for the highest versus lowest quartile of serum zinc concentration and zinc/copper ratio were 0.61 (0.39-0.96) and 0.58 (0.38-0.89), respectively. Furthermore, among males, the OR (95% CI) of long sleep duration for the highest versus lowest quartile of serum copper concentration was 2.23 (1.15-4.32). Finally, the dose-response trends suggested that participants with optimal sleep duration had the highest serum zinc concentration and zinc/copper ratio and a slightly lower serum copper concentration. No significant association was found between serum zinc, copper concentrations and the zinc/copper ratio and short sleep duration. In conclusion, serum zinc and zinc/copper ratio were inversely related to long sleep duration in adults, while serum copper was positively associated with long sleep duration in males.
Serum Copper and Zinc Concentrations and Cognitive Impairment in Older Adults Aged 60 Years and Older.
Gong Zonglin,Song Wenlei,Gu Minjun
Biological trace element research
Epidemiological evidence on serum zinc and copper and cognitive impairment in older adults are not consistent. Results on serum zinc and copper and cognitive impairment in older adults from the National Health and Nutrition Examination Survey (NHANES) have not been reported. Data on serum zinc and copper and cognitive impairment from individuals ≥ 60 years of age were obtained from the 2011-2014 NHANES. Serum zinc and copper concentrations were determined with inductively coupled plasma dynamic reaction cell mass spectrometry. Cognitive impairment was assessed with four cognitive tests: the Digit Symbol Substitution Test (DSST), the Animal Fluency (AF), the Consortium to Establish a Registry for Alzheimer's Disease Delayed Recall (CERAD-DR), and the Word Learning (CERAD-WL) tests. Compared with the lowest tertile of serum copper, the multivariate-adjusted odds ratios of scoring low on the AF were 0.86 (0.44-1.68) in tertile 2 and 0.46 (0.25-0.82) in tertile 3, and the inverse association was also found in women. No association was found between serum copper and the DSST, CERAD-DR, and CRAD-WL, respectively. Compared with the lowest tertile of serum zinc, the multivariate-adjusted odds ratios of scoring low on the DSST were 0.83 (0.37-1.90) in tertile 2 and 0.42 (0.22-0.80) in tertile 3, and the inverse association was also found in men. No association was found between serum zinc and the AF, CERAD-DR, and CRAD-WL, respectively. In conclusion, serum copper and zinc were associated with certain cognitive performance tests among older adults, and the causality deserves to be confirmed further.
Association between copper levels and myocardial infarction: a meta-analysis.
Chen An,Li Gonghui,Liu Yingfeng
BACKGROUND AND AIMS:There are conflicting reports as to the correlation between copper (Cu) levels and myocardial infarction (MI). The purpose of the present study is to clarify the association between Cu levels and MI. METHODS:We searched articles in Pubmed and the Chinese Journal Full-text Database published as of October 2014. A meta-analysis was used to pool estimates of the standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS:Pooled analysis indicated that subjects with MI had higher serum Cu levels than healthy controls (SMD = 1.629, 95%CI = [1.027, 2.232], Z = 5.30, p < 0.001). Further subgroup analysis stratified by ethnicity indicated that subjects with MI had higher serum Cu levels than healthy controls among members of the Asian race (SMD = 2.191, 95%CI = [1.401, 2.981], Z = 5.43, p < 0.001), but not among members of the Caucasian race (SMD = 0.411, 95%CI = [-0.030, 0.851], Z = 1.83, p = 0.068). The results obtained from hairs showed no association between MI and hair Cu levels (SMD = 0.338, 95% CI = [-0.171, 0.848], Z = 1.30, p = 0.193). But the subgroup analysis stratified by geological location indicated that subjects with MI had higher hair Cu levels than healthy controls in Pakistan (SMD = 0.785, 95% CI = [0.587, 0.983], Z = 10.29, p < 0.001), but not in India (SMD = -9.028, 95% CI = [-10.747, -7.309], Z = 7.77, p < 0.001). CONCLUSION:This meta-analysis indicates a significant association between high serum Cu levels and MI. However, the subgroup analysis found that there was significant effect modification of Cu levels by ethnicity. Thus, we suggest that a trans-regional multicenter study is needed to obtain better understanding of causal relationships between Cu and MI in different human races.
Serum Iron, Zinc, and Copper Levels in Patients with Alzheimer's Disease: A Replication Study and Meta-Analyses.
Wang Zi-Xuan,Tan Lan,Wang Hui-Fu,Ma Jing,Liu Jinyuan,Tan Meng-Shan,Sun Jia-Hao,Zhu Xi-Chen,Jiang Teng,Yu Jin-Tai
Journal of Alzheimer's disease : JAD
To evaluate whether iron, zinc, and copper levels in serum are disarranged in Alzheimer's disease (AD), we performed meta-analyses of all studies on the topic published from 1984 to 2014 and contextually carried out a replication study in serum as well. Our meta-analysis results showed that serum zinc was significantly lower in AD patients. Our replication and meta-analysis results showed that serum copper was significantly higher in AD patients than in healthy controls, so our findings were consistent with the conclusions of four previously published copper meta-analyses. Even if a possible role of iron in the pathophysiology of the disease could not be ruled out, the results of our meta-analysis showed no change of serum iron levels in AD patients, but this conclusion was not robust and requires further investigation. The meta-regression analyses revealed that in some studies, differences in serum iron levels could be due to the different mean ages, while differences in zinc levels appeared to be due to the different sex ratios. However, the effect of sex ratio on serum zinc levels in our meta-analysis is subtle and needs further confirmation. Also, diverse demographic terms and methodological approaches appeared not to explain the high heterogeneity of our copper meta-analysis. Therefore, when investigating trace elements, covariants such as age and sex have to be taken into account in the analyses. In the light of these findings, we suggest that the possible alteration of serum zinc and copper levels are involved in the pathogenesis of AD.
Can iron, zinc, copper and selenium status be a prognostic determinant in COVID-19 patients?
Environmental toxicology and pharmacology
In severe COVID-19, the levels of iron (Fe), copper (Cu), zinc (Zn) and selenium (Se), do not only regulate host immune responses, but modify the viral genome, as well. While low serum Fe concentration is an independent risk factor for the increased death rate, Zn controls oxidative stress, synthesis of inflammatory cytokines and viral replication. Therefore, Zn deficiency associates with a worse prognosis. Although Cu exposure inactivates the viral genome and exhibits spike protein dispersal, increase in Cu/Zn due to high serum Cu levels, are correlated with enhanced risk of infections. Se levels are significantly higher in surviving COVID-19 patients. Meanwhile, both Zn and Se suppress the replication of SARS-CoV-2. Since the balance between the deficiency and oversupply of these metals due to a reciprocal relationship, has decisive effect on the prognosis of the SARS-CoV-2 infection, monitoring their concentrations may facilitate improved outcomes for patients suffering from COVID-19.
Copper in Alzheimer's disease: a meta-analysis of serum, plasma, and cerebrospinal fluid studies.
Ventriglia Mariacarla,Bucossi Serena,Panetta Valentina,Squitti Rosanna
Journal of Alzheimer's disease : JAD
This contribution reviews and corrects data from our previous meta-analysis, which appeared in the Journal of Alzheimer's Disease in 2011 concerning the role of copper in Alzheimer's disease. We repeated the meta-analysis after excluding four of the five studies from our laboratory to avoid possible bias in the result. In addition, we included two studies on serum copper levels in Alzheimer's disease not previously considered. The results indicate higher levels of copper in Alzheimer's disease patients than in controls, confirming our previous conclusion.
Trace Element and Mineral Levels in Serum, Hair, and Urine of Obese Women in Relation to Body Composition, Blood Pressure, Lipid Profile, and Insulin Resistance.
Tinkov Alexey A,Bogdański Paweł,Skrypnik Damian,Skrypnik Katarzyna,Skalny Anatoly V,Aaseth Jan,Skalnaya Margarita G,Suliburska Joanna
The objective of this study was to evaluate serum, hair, and urinary trace element and mineral content in normal-weight and obese women in relation to metabolic risk factors. A total of 80 women aged 30-70 y.o. were enrolled in the obese group (n = 40) and normal-weight group (n = 40). Serum, hair, and urinary trace element and mineral levels were assessed using inductively coupled plasma spectrometry. Body fat percentage was evaluated using bioimpedance. Obese subjects were characterized by significantly higher body fat percentage, blood pressure, serum triglyceride concentration, and insulin resistance. Serum Ca, Fe, Mg, Se, V, Zn levels, hair Fe, Mg, V content, and urinary Se and V concentrations were found to be lower in obese subjects as compared to lean controls. In turn, serum Cu and urinary Fe levels in obese women were characterized by a significant increase. In multiple regression models serum Cu, Se, and Zn levels were significantly associated with BMI even after adjustment for blood biochemistry, body composition, and blood pressure. Serum trace element and mineral levels also significantly contributed to group discrimination. These findings allow to propose that obesity-associated disturbances in trace element and mineral status may at least partially contribute to metabolic risk in obese subjects.
Association between serum copper levels and lung cancer risk: A meta-analysis.
Zhang Xiaping,Yang Qun
The Journal of international medical research
OBJECTIVE:To evaluate the association between serum copper levels and lung cancer risk. METHODS:We searched the electronic PubMed, WanFang, CNKI, and SinoMed databases to identify studies including information on serum copper levels and lung cancer. Standard mean differences and corresponding 95% confidence intervals were calculated using Stata 12.0 software. We performed a meta-analysis on the identified studies overall and according to geographic location. We also evaluated heterogeneity among the studies and the occurrence of publication bias. RESULTS:Thirty-three articles including 3026 cases and 9439 controls were included in our study. The combined results showed that serum copper levels were higher in patients with lung cancer compared with controls without lung cancer, though the results showed high heterogeneity. In a subgroup analysis according to geographic location, significant associations between copper levels and lung cancer were found for both Asian and European populations. No publication bias was detected in this meta-analysis. CONCLUSIONS:High serum copper levels could increase the risk of lung cancer, suggesting that environmental copper exposure may be a risk factor for the development of lung cancer.
Association between serum copper and heart failure: a meta-analysis.
Huang Lei,Shen Ronghuan,Huang Longfei,Yu Jing,Rong Hao
Asia Pacific journal of clinical nutrition
BACKGROUND AND OBJECTIVES:Copper dyshomeostasis can lead to many diseases, including cardiovascular disease. However, there are conflicting reports on the relationship between serum copper and heart failure (HF). To explore the relationship between serum copper levels and HF by performing a meta-analysis. METHODS AND STUDY DESIGN:The PubMed and ScienceDirect databases until June 2019 were searched for reports on the association between serum copper levels and HF. RESULTS:A total of thirteen studies including 1504 subjects were chosen for the meta-analysis. The pooled analysis indicated that patients with HF had higher serum copper than the control subjects [standardized mean difference (SMD), 0.982; 95% confidence interval (CI), (0.679, 1.285)]. Subgroup analysis stratified by different geographic locations found that HF patients had higher copper than the control subjects in Asia and Europe [Asia: SMD, 0.948 and 95% CI, (0.569, 1.327); Europe: SMD, 1.275 and 95% CI, (0.633, 1.917)], but not in America [America: SMD, 0.637 and 95% CI, (-0.109, 1.383)]. Additionally, subgroup analysis revealed that patients with ischemic cardiomyopathy (ICM) [SMD, 1.171; 95% CI, (0.717, 1.624)], idiopathic dilated cardiomyopathy (IDCM) [SMD, 0.569; 95% CI, (0.097, 1.042)] and other types of HF [SMD, 1.152; 95% CI, (0.594, 1.710)] all had higher copper levels than controls. Further subgroup analysis stratified by Newcastle-Ottawa Scale (NOS) scores also found higher serum copper in patients with HF than controls within each subgroup. CONCLUSIONS:Our meta-analysis identified a significant association between high serum copper and HF.
Low serum levels of zinc, copper, and iron as risk factors for osteoporosis: a meta-analysis.
Zheng Jianmao,Mao Xueli,Ling Junqi,He Qun,Quan Jingjing
Biological trace element research
Zinc (Zn), copper (Cu), and iron (Fe) are essential trace elements for the growth, development, and maintenance of healthy bones. However, there are conflicting reports as to the relationship between serum level of Zn, Cu, or Fe and osteoporosis (OP). The purpose of the present study is to clarify the relationship between serum Zn, Cu, or Fe and OP using a meta-analysis approach. We searched all articles indexed in PubMed published up to May 2014 concerning the association between serum level of Zn, Cu, or Fe and OP. Eight eligible articles involving 2,188 subjects were identified. Overall, pooled analysis indicated that patients with OP had a lower serum level of Zn, Cu, or Fe than the healthy controls (Zn standardized mean difference (SMD) = -1.396, 95% confidence interval (CI) = [-2.129, -0.663]; Cu SMD = -0.386, 95% CI = [-0.538, -0.234]; Fe SMD = -0.22, 95% CI = [-0.30, -0.13]). Further subgroup analysis found that geographical location and gender had an influence on the serum level of Zn in OP and healthy controls, but not on the serum level of Cu or Fe. No evidence of publication bias was observed. In conclusion, this meta-analysis suggests that low serum levels of Zn, Cu, and Fe seem to be important risk factors for OP and well-designed studies with adequate control for confounding factors are required in future investigations.
The association of serum zinc and copper with hypertension: A meta-analysis.
Li Zhaoying,Wang Weijing,Liu Hui,Li Suyun,Zhang Dongfeng
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
OBJECTIVE:The association of serum zinc (Zn), copper (Cu) with the risk of hypertension (HT) remains controversial. Therefore, we conducted a meta-analysis to explore the relationships. METHODS:We searched relevant literatures on PubMed and Web of Science up to September 2018. Pooled standard mean difference (SMD) with corresponding 95% confidence interval (CI) was calculated by random effects model.I was used to evaluate heterogeneity among studies. RESULTS:25 articles of serum Zn and 22 articles of serum Cu were included in meta-analysis. HT patients had lower serum Zn [SMD (95%CI): -0.612(-0.951, -0.274), z = 3.54, P <0.001; I = 97.0%, P <0.001], whereas no significant difference of serum Cu was shown between HT patients and controls [SMD (95%CI): 0.153(-0.101, 0.407)]. Also, male HT patients had lower serum Zn [SMD (95%CI): -1.443(-2.868, -0.017), z = 1.98, P = 0.047; I = 98.8%, P <0.001]. In subgroup analysis, a lower serum Zn was observed in HT patients in studies conducted in Europe [-1.066(-1.759, -0.374)], in case-control studies [-0.718(-1.294, -0.142)], in matched case-control studies [-0.939(-1.646, -0.233)] and studies involving treated patients [-1.416(-2.195, -0.638)]. Meanwhile, a higher serum Cu was found in HT patients in studies conducted in Africa [1.96(1.402, 2.518)], and in matched case-control studies [0.655(0.204, 1.107)]. CONCLUSION:The present meta-analysis indicates that serum Zn level in HT patients was significantly lower than that in controls, while no significantly different serum Cu level was found between HT patients and controls. Future studies are needed to confirm these results in future research.
Selenium and Other Trace Elements in the Etiology of Parkinson's Disease: A Systematic Review and Meta-Analysis of Case-Control Studies.
Adani Giorgia,Filippini Tommaso,Michalke Bernhard,Vinceti Marco
BACKGROUND:Parkinson's disease (PD) is the most common neurodegenerative disease after Alzheimer's dementia. Whereas the exact etiology of PD remains unknown, risk of developing PD seems to be related to a combination of genetic and environmental factors. This also includes abnormal exposure to trace elements of nutritional and toxicological interest. OBJECTIVES:In this systematic review and meta-analysis, we summarized the results of case-control studies comparing levels of selenium, copper, iron, and zinc in PD patients and controls in either blood (whole blood, serum/plasma) or cerebrospinal fluid (CSF). METHODS:We performed a systematic PubMed search selecting studies reporting trace element levels in different specimens of patients and controls. We performed a meta-analysis using a random-effect model to compute the weighted mean differences (WMD) and corresponding 95% CI of selenium, copper, iron, and zinc levels in the blood or CSF of patients and their matched controls. RESULTS:We retrieved 56 papers reporting data for selenium (cases/controls: 588/721), copper (2,190/2,522), iron (2,956/3,469), and zinc (1,798/1,913) contents in CSF and blood. Cases showed considerably higher levels of selenium in CSF compared with controls (+51.6%; WMD 5.49; 95% CI 2.82 to 8.15), while levels in serum were similar (-0.2%; WMD -0.22; 95% CI -8.05 to 7.62). For copper, cases showed slightly higher levels in CSF and slightly lower concentrations in serum (+4.5%; WMD 1.87; 95% CI -3.59 to 7.33, and -4.5%; WMD -42.79; 95% CI -134.35 to 48.76, respectively). A slight increase was also found for CSF iron -levels (+9.5%; WMD 9.92; 1.23 to 18.61), while levels were -decreased in serum/plasma (-5.7%; WMD -58.19; 95% CI -106.49 to -9.89) and whole blood (-10.8%; WMD -95.69; 95% CI -157.73 to -33.65). Conversely, for zinc cases exhibited lower levels both in CSF (-10.8%; WMD -7.34; 95% CI -14.82 to 0.14) and serum/plasma (-7.5%; WMD -79.93; 95% CI -143.80 to -16.06). A longer duration of the disease tends to be associated with overall lower trace element levels in either CSF or blood. CONCLUSIONS:Due to the study findings and the greater relevance of the CSF compartment compared with the circulating peripheral ones, this meta-analysis suggests that overexposure in the central nervous system to selenium, and possibly to copper and iron, may be a risk factor of the disease, while zinc might have a protective -effect.
Association Between the Change of Serum Copper and Ischemic Stroke: a Systematic Review and Meta-Analysis.
Zhang Mijuan,Li Wei,Wang Yan,Wang Tao,Ma Minjiang,Tian Chune
Journal of molecular neuroscience : MN
Ischemic stroke is the most common stroke subtypes with all strokes. More and more studies found that serum copper was related to the ischemic stroke. However, the correlation between serum copper and ischemic stroke was inconsistent. We performed the meta-analysis to assess the association between the change of serum copper and ischemic stroke. Electronic databases were identified to search for relevant studies about serum copper and ischemic stroke from inception to February 28, 2019. Eight studies with a total of 777 participants were included into this meta-analysis. Because of high heterogeneity (I = 71%), we chose a random effect model. Our results showed the serum copper levels were significantly higher in ischemic stroke group compared with controls group (pooled mean difference, 1.25; 95% confidence intervals (CIs), 0.07-2.43; P = 0.04), in particular studies after the year of 2009 (I = 0%; pooled mean difference, 2.16; 95% CI, 1.37-2.95; P < 0.00001). Serum copper was associated with ischemic stroke, and it may be one of the risk factors of ischemic stroke.
The Association Between Serum Levels of Selenium, Copper, and Magnesium with Thyroid Cancer: a Meta-analysis.
Shen Fei,Cai Wen-Song,Li Jiang-Lin,Feng Zhe,Cao Jie,Xu Bo
Biological trace element research
There are conflicting reports on the correlation between serum levels of selenium (Se), copper (Cu), and magnesium (Mg) with thyroid cancer. The purpose of the present study is to clarify the association between Se, Cu, and Mg levels with thyroid cancer using a meta-analysis approach. We searched articles indexed in PubMed published as of January 2015 that met our predefined criteria. Eight eligible articles involving 1291 subjects were identified. Overall, pooled analysis indicated that subjects with thyroid cancer had lower serum levels of Se and Mg, but higher levels of Cu than the healthy controls [Se: standardized mean difference (SMD) = -0.485, 95% confidence interval (95%CI) = (-0.878, -0.092), p = 0.016; Cu: SMD = 2.372, 95%CI = (0.945, 3.799), p = 0.001; Mg: SMD = -0.795, 95%CI = (-1.092, -0.498), p < 0.001]. Further subgroup analysis found lower serum levels of Se in thyroid cancer in Norway [SMD = -0.410, 95%CI = (-0.758, -0.062), p = 0.021] and Austria [SMD = -0.549, 95%CI = (-0.743, -0.355), p < 0.001], but not in Poland (SMD = -0.417, 95%CI = (-1.724, 0.891), p = 0.532]. Further subgroup analysis also found that patients with thyroid cancer had higher serum levels of Cu in China [SMD = 1.571, 95%CI = (1.121, 2.020), p < 0.001] and Turkey [SMD = 0.977, 95%CI = (0.521, 1.432), p < 0.001], but not in Poland [SMD = 3.471, 95%CI = (-0.056, 6.997], p = 0.054]. In conclusion, this meta-analysis supports a significant association between serum levels of Se, Cu, and Mg with thyroid cancer. However, the subgroup analysis found that there was significant effect modification of Se, Cu levels by ethnic, like China and Poland. Thus, this finding needs further confirmation by a trans-regional multicenter study to obtain better understanding of causal relationship between Se, Cu, and Mg with thyroid cancer of different human races or regions.
Serum Trace Elements in Patients With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.
Yin Jiechen,Hong Xiang,Ma Jun,Bu Yuanqing,Liu Ran
Frontiers in endocrinology
Polycystic ovary syndrome (PCOS) is reported to be associated with certain trace elements. However, previous data are inconsistent and potentially biased due to small sample sizes. The potential utility of trace element levels for screening of PCOS remains to be established. The aim of this meta-analysis was to investigate the potential relationships between PCOS and serum levels of zinc (Zn), copper (Cu), magnesium (Mg), iron (Fe) and ferritin. We carried out a literature search of PubMed, EMBASE, and Web of Science for relevant cross-sectional/case-control studies published prior to October 2019. Random-effect models were used to estimate the overall standard mean differences (SMDs) between PCOS and healthy control subjects. The screening value of potential microelement biomarkers for PCOS was assessed using the receiver operating characteristic (ROC) curve. Twenty-one studies featuring 2,173 women with PCOS and 1,897 healthy women were selected for analysis. Our results showed that Cu and ferritin levels were significantly higher in women with PCOS than healthy controls, with SMDs of 0.52 [95% confidence interval (CI): 0.38-0.67, = 47.6%] and 1.05 (95% CI: 0.25-1.86, = 97.0%), respectively. The serum ferritin concentration was distinguished as a potential biomarker for PCOS based on the high area under ROC curve value of 0.71 (95% CI: 0.57-0.86). Although we did not identify a statistical association between serum Zn concentration and PCOS overall, the concentration of Zn in PCOS women with insulin resistance (IR) was lower than that in healthy women (SMD = -0.89, 95% CI: -1.73 to -0.06). Furthermore, the concentrations of Mg (SMD = 0.31, 95% CI: -0.32-0.94, = 95.4%) and Fe (SMD = -0.59, 95% CI: -1.29-0.12, = 97.2%) were not statistically significant between the PCOS and control groups. We generated hypothetical pathways for associations among serum Cu, ferritin and PCOS. The serum concentrations of both Cu and ferritin were significantly higher in women with PCOS, and ferritin was identified as a potential early indicator for PCOS screening. Further studies are essential to determine the specific underlying mechanisms.
Serum Levels of Copper and Zinc in Patients with Rheumatoid Arthritis: a Meta-analysis.
Xin Lihong,Yang Xiao,Cai Guoqi,Fan Dazhi,Xia Qing,Liu Li,Hu Yanting,Ding Ning,Xu Shengqian,Wang Li,Li Xiaona,Zou Yanfeng,Pan Faming
Biological trace element research
Many publications with conflicting results have evaluated serum levels of copper (Cu) and zinc (Zn) in patients with rheumatoid arthritis (RA). To derive a more precise estimation of the relationship, a meta-analysis was conducted. Relevant published data were retrieved through PubMed, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) before September 20, 2014. Weighted mean difference (WMD) with a 95 % confidence interval (95 % CI) was calculated using STATA 11.0. A total of 26 studies, including 1444 RA cases and 1241 healthy controls, were collected in this meta-analysis. Pooled analysis found that patients with RA had a higher serum level of Cu and a lower serum Zn level than the healthy controls (Cu (μg/dl), WMD = 31.824, 95 % CI = 20.334, 43.314; Zn (μg/dl), WMD = -12.683, 95 % CI = -19.783, -5.584). Subgroup analysis showed that ethnicity had influence on the serum level of Cu (μg/dl) (Caucasian, WMD = 43.907, 95 % CI = 35.090, 52.723, P < 0.001; Asian, WMD = 14.545, 95 % CI = -12.365, 41.455, P = 0.289) and Zn (μg/dl) (Caucasian, WMD = -11.038, 95 % CI = -23.420, 1.344, P = 0.081; Asian, WMD = -14.179, 95 % CI = -18.963, -9.394, P < 0.001) in RA and healthy controls. No evidence of publication bias was observed. This meta-analysis suggests that increased serum level of Cu and decreased serum level of Zn are generally present in RA patients.
Copper concentration in multiple sclerosis: a systematic review and meta-analysis.
Sarmadi Mohammad,Bidel Zeinab,Najafi Fereshteh,Ramakrishnan Rema,Teymoori Farshad,Zarmehri Hassan Azhdari,Nazarzadeh Milad
Multiple sclerosis and related disorders
BACKGROUND:A wide range of risk factors, from genetic to environmental, have been identified to play role in the etiology of multiple sclerosis. However, the role of trace element remains mostly unknown. We sought to combine all available evidence to assess the association between copper concentration and multiple sclerosis. METHODS:This systematic review and meta-analysis was conducted based on PRISMA guidelines. PubMed, Scopus, Embase, and Web of Science were searched since inception till July 2020. Observational studies that assessed copper as exposure in serum, plasma, whole blood, and cerebrospinal fluid were included. Standardized mean differences (SMD), comparing the mean of copper concentration in multiple sclerosis patients versus healthy controls, were considered as the measure of association. The fixed-effect model with inverse variance weighting was used to combine the findings. RESULTS:Twenty studies inclusive of 797 multiple sclerosis cases and 875 healthy controls were included in the meta-analysis (all case-control studies). The combined SMDs were 1.25 (95% confidence interval [CI] 0.95 to 1.55, number of included studies [n]=4) in plasma, 0.45 (CI 0.22 to 0.68, n=4) in whole blood, 0.19 (CI 0.06 to 0.33, n=12) in blood serum and 1.23 (CI 0.83 to 1.64, n=4) in cerebrospinal fluid. CONCLUSIONS:We found a higher concentration of copper in multiple sclerosis patients than healthy controls. The possible causal nature of the observed associations warrants further investigation with prospective data.
Serum copper and zinc levels in breast cancer: A meta-analysis.
Feng Yue,Zeng Jia-Wei,Ma Qin,Zhang Shuang,Tang Jie,Feng Jia-Fu
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
BACKGROUND:More and more studies have investigated the relationship between serum copper (Cu) and/or zinc (Zn) levels and breast cancer (BC). However, the results are inconsistent. It is unclear whether the serum Cu to Zn ratio (Cu/Zn) is associated with BC risk. Therefore, we evaluated serum Cu and Zn concentrations, and Cu/Zn in BC through meta-analysis. MATERIALS AND METHODS:Studies reporting serum Cu and/or Zn concentrations in BC patients and controls from 1991 to 2020 were identified from PubMed, CNKI, and Wanfang databases online. Based on a random effects model, summary standard mean differences (SMDs) and the corresponding 95 % confidence intervals (95 % CIs) were applied to compare the serum levels of Cu, Zn and Cu/Zn between BC patients and controls. RESULTS:Thirty-six eligible studies involving 5747 female subjects were included. The present study illustrated that the BC patients had significantly higher serum Cu levels than healthy controls (HC) (SMD (95 % CI): 1.99(1.48, 2.49)) and patients with benign breast diseases (BD) (SMD (95 % CI): 0.99(0.38, 1.61)). However, Zn concentrations were statistically decreased in BC patients than HC (SMD (95 % CI): -1.20(-1.74, -0.66)) and BD (SMD (95 % CI): -1.13 (-1.73, -0.54)). Cu/Zn concentrations were remarkably increased in BC patients than HC (SMD (95 % CI): 2.75(1.79, 3.60)) and BD (SMD (95 % CI): 2.98(1.91, 4.05)) in some studies. CONCLUSION:The results show that elevated serum levels of Cu and Cu/Zn, as well as decreased Zn might be associated with increased risk of breast cancer. These three parameters have the potential to distinguish breast cancer from benign breast diseases.
Beyond the Mind-Serum Trace Element Levels in Schizophrenic Patients: A Systematic Review.
Baj Jacek,Forma Alicja,Sitarz Elżbieta,Karakuła Kaja,Flieger Wojciech,Sitarz Monika,Grochowski Cezary,Maciejewski Ryszard,Karakula-Juchnowicz Hanna
International journal of molecular sciences
The alterations in serum trace element levels are common phenomena observed in patients with different psychiatric conditions such as schizophrenia, autism spectrum disorder, or major depressive disorder. The fluctuations in the trace element concentrations might act as potential diagnostic and prognostic biomarkers of many psychiatric and neurological disorders. This paper aimed to assess the alterations in serum trace element concentrations in patients with a diagnosed schizophrenia. The authors made a systematic review, extracting papers from the PubMed, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Among 5009 articles identified through database searching, 59 of them were assessed for eligibility. Ultimately, 33 articles were included in the qualitative synthesis. This review includes the analysis of serum levels of the following trace elements: iron, nickel, molybdenum, phosphorus, lead, chromium, antimony, uranium, magnesium, aluminum, zinc, copper, selenium, calcium, and manganese. Currently, there is no consistency regarding serum trace element levels in schizophrenic patients. Thus, it cannot be considered as a reliable prognostic or diagnostic marker of schizophrenia. However, it can be assumed that altered concentrations of those elements are crucial regarding the onset and exaggeration of either psychotic or negative symptoms or cognitive dysfunctions.
Serum Copper Level and Polycystic Ovarian Syndrome: A Meta-Analysis.
Jiang Qingtao,Zhang Feng,Han Lei,Zhu Baoli,Liu Xin
Gynecologic and obstetric investigation
INTRODUCTION:The association of serum copper with polycystic ovarian syndrome (PCOS) has been studied for years, but no definite conclusion is drawn. Therefore, we conducted a meta-analysis to investigate serum copper concentrations in PCOS subjects compared with healthy controls. METHODS:Electronic search was performed in PubMed, Google Scholar, and Scopus up to June 30, 2020, without any restriction. Standardized mean differences (SMDs) with corresponding 95% CIs in serum copper levels were employed with random-effects model. I2 was applied to evaluate heterogeneity among studies. RESULTS:Nine studies, measuring plasma copper levels in 1,168 PCOS patients and 1,106 controls, were included. Pooled effect size suggested serum copper level was significantly higher in women with PCOS (SMD = 0.51 μg/mL, 95% CI = [0.30, 0.72], p < 0.0001). The overall heterogeneity was not connected with subgroups of the country, but derived from the opposite result of 1 study. CONCLUSION:Our research generally indicated circulating copper level in PCOS sufferers was significantly higher than normal controls. Large-scale studies are still needed to elucidate the clear relation between copper status and etiology of PCOS.
Copper in Diabetes Mellitus: a Meta-Analysis and Systematic Review of Plasma and Serum Studies.
Qiu Qihong,Zhang Fuping,Zhu Wenjun,Wu Juan,Liang Min
Biological trace element research
Copper (Cu) is an important trace element involved in oxidative stress, which is associated with the onset and progression of diabetes mellitus (DM). However, clinical studies comparing plasma or serum Cu levels in patients with DM and in healthy individuals report conflicting findings. Therefore, in this meta-analysis, we analyzed the circulating levels of Cu associated with DM (including type 1 diabetes mellitus [T1DM] and type 2 diabetes mellitus [T2DM]). We searched the articles indexed in PubMed, OVID, and Cochrane databases, published through January 2016 and meeting our predefined criteria. Requisite data were extracted, and a random-effect model or a fixed-effect model was used to conduct the meta-analysis. Fifteen eligible studies involving a total of 1079 DM patients and 561 healthy controls were identified. Overall, the DM patients showed higher Cu levels than the healthy controls (plasma Cu mean difference [MD] = 1.69 μmol/L, p < 0.0001; serum Cu MD = 4.06 μmol/L, p = 0.005; plasma and serum Cu MD = 2.67 μmol/L, p = 0.006). Stratification based on the type of diabetes also indicated higher levels of Cu in the plasma and serum of DM patients than in healthy controls, respectively. Stratification of DM patients associated with and without complications also revealed similar results. This meta-analysis suggests that DM patients carried higher levels of Cu than healthy individuals. However, international cohort studies are needed to corroborate our findings.
The Relationship Between Serum Copper and Overweight/Obesity: a Meta-analysis.
Gu Kunfang,Li Xuekui,Xiang Wenzhi,Jiang Xiubo
Biological trace element research
The relationship between serum copper (Cu) level and overweight/obesity remains controversial. The purpose of this meta-analysis is to evaluate the relationship. A comprehensive literature search was performed in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases for relevant articles until March 20, 2019. The random-effect model (REM) was adopted to compute the combined standardized mean difference (SMD) with 95% confidence interval (CI). Publication bias was estimated using the visualization of funnel plots and Egger's test. In the end, twenty-one articles were included in the meta-analysis. Compared with controls, serum Cu level was higher in obese children (SMD (95% CI) 0.74 (0.16, 1.32)) and in obese adults (SMD (95% CI) 0.39 (0.02, 0.76)). There was no significant difference in serum Cu between overweight and control groups in children (SMD (95% CI) 1.52 (- 0.07, 3.12)) and in adults (SMD (95% CI) 0.16 (- 0.06, 0.38)). Moreover, subgroup analysis revealed a higher serum Cu level in obese children (SMD (95% CI) 0.90 (0.36, 1.45)) and obese adults (SMD (95% CI) 0.47 (0.05, 0.88)) compared with healthy weight controls. The SMD differs significantly between obese children diagnosed by weight-for-height and controls (SMD (95% CI) 1.56 (0.57, 2.55)), and there was a significant difference of serum Cu level between obese adults diagnosed by BMI (WHO) and controls (SMD (95% CI) 0.54 (0.08, 1.01)). This meta-analysis indicates that a higher serum Cu level might be associated with the risk of obesity in children and adults, and these findings need to be further confirmed.
Relation of Serum Copper Status to Survival in COVID-19.
Hackler Julian,Heller Raban Arved,Sun Qian,Schwarzer Marco,Diegmann Joachim,Bachmann Manuel,Moghaddam Arash,Schomburg Lutz
The trace element copper (Cu) is part of our nutrition and essentially needed for several cuproenzymes that control redox status and support the immune system. In blood, the ferroxidase ceruloplasmin (CP) accounts for the majority of circulating Cu and serves as transport protein. Both Cu and CP behave as positive, whereas serum selenium (Se) and its transporter selenoprotein P (SELENOP) behave as negative acute phase reactants. In view that coronavirus disease (COVID-19) causes systemic inflammation, we hypothesized that biomarkers of Cu and Se status are regulated inversely, in relation to disease severity and mortality risk. Serum samples from COVID-19 patients were analysed for Cu by total reflection X-ray fluorescence and CP was quantified by a validated sandwich ELISA. The two Cu biomarkers correlated positively in serum from patients with COVID-19 (R = 0.42, < 0.001). Surviving patients showed higher mean serum Cu and CP concentrations in comparison to non-survivors ([mean+/-SEM], Cu; 1475.9+/-22.7 vs. 1317.9+/-43.9 µg/L; < 0.001, CP; 547.2.5 +/- 19.5 vs. 438.8+/-32.9 mg/L, = 0.086). In contrast to expectations, total serum Cu and Se concentrations displayed a positive linear correlation in the patient samples analysed (R = 0.23, = 0.003). Serum CP and SELENOP levels were not interrelated. Applying receiver operating characteristics (ROC) curve analysis, the combination of Cu and SELENOP with age outperformed other combinations of parameters for predicting risk of death, yielding an AUC of 95.0%. We conclude that the alterations in serum biomarkers of Cu and Se status in COVID-19 are not compatible with a simple acute phase response, and that serum Cu and SELENOP levels contribute to a good prediction of survival. Adjuvant supplementation in patients with diagnostically proven deficits in Cu or Se may positively influence disease course, as both increase in survivors and are of crucial importance for the immune response and antioxidative defence systems.
Dietary Copper/Zinc Ratio and Type 2 Diabetes Risk in Women: The E3N Cohort Study.
Laouali Nasser,MacDonald Conor-James,Shah Sanam,El Fatouhi Douae,Mancini Francesca Romana,Fagherazzi Guy,Boutron-Ruault Marie-Christine
The serum copper (Cu) to zinc (Zn) ratio could be an important determinant of Type 2 diabetes (T2D) risk, but prospective epidemiological data are scarce. We aimed to investigate the association between T2D incidence and the dietary Cu/Zn ratio. A total of 70,991 women from the E3N cohort study were followed for 20 years. The intakes of copper and zinc were estimated at baseline using a validated food frequency questionnaire. We identified and validated 3292 incident T2D cases. Spline analysis showed that a Cu/Zn ratio < 0.55 was associated with a lower risk of T2D. Subgroup analyses comparing women in the highest versus the lowest quintile of Cu/Zn ratio showed the same pattern of association for obese women and those with zinc intake ≥8 mg/day. However, for women with zinc intake <8 mg/day, higher Cu/Zn ratio appeared to be associated with higher T2D risk. Our findings suggest that a lower dietary Cu/Zn ratio is associated with a lower T2D risk, especially among obese women and women with zinc intake >8 mg/day. Further studies are warranted to validate our results.
Micronutrients and Renal Outcomes: A Prospective Cohort Study.
BACKGROUND:Micronutrients are essential in maintaining normal human physiology. Data regarding the association between micronutrients and renal outcomes in chronic kidney disease (CKD) are lacking. METHODS:This prospective observational cohort study enrolled 261 patients with CKD stages 1-5 and 30 subjects with normal renal function. Baseline serum zinc (Zn), selenium (Se), chromium, manganese, and copper, and laboratory tests were performed at enrolment. The primary endpoint was the presence of end-stage renal disease (ESRD) requiring long-term renal replacement therapy. RESULTS:The median follow-up periods of renal and non-renal survivals were 67.78 and 29.03 months, respectively. Multiple linear regression showed that Zn and Se (β ± SE: 24.298 ± 8.616, = 0.005; 60.316 ± 21.875, = 0.006, respectively) levels were positively correlated with renal function. Time to ESRD was significantly longer for those with Zn levels ≥1287.24 ng/g and Se levels ≥189.28 ng/g (both < 0.001). Cox regression analysis identified a higher Zn level as an independently negative predictor of ESRD after adjusting for renal function (hazard ratio, 0.450, = 0.019). CONCLUSION:Serum Se and Zn concentrations are positively associated with renal function and better renal outcomes. A higher Zn concentration could independently predict better renal survival.