The association between maternal iron, zinc, copper levels in serum and pregnancy outcomes.

AIMS: To investigate the associations of serum trace elements (iron, zinc, and copper) between women with different pregnancy outcomes. METHODS: About 774 pregnant women who came to The Fourth Hospital of Shijiazhuang for prenatal examination were investigated. The concentrations of trace elements in the serum of pregnant women in the third trimester were collected. Multivariate logistic regression was used to analyze the relationship between serum trace element levels and the different pregnancy outcomes. Multiple linear regression was used to analyze the relationship between serum trace elements levels and hypersensitive-C-reactive-protein. RESULTS: Results of the multiple logistic regression showed that zinc, copper and copper/zinc ratio were found to be associated with the risk of gestational diabetes mellitus, and zinc was a protective factor (p = 0.002) while copper and copper/zinc ratio as risk factors (p = 0.030 and p = 0.001, respectively) after adjusting for major confounders. It was found that iron and zinc were negatively associated with the risk of moderate or severe anemia (p = 0.022 and p = 0.001, respectively). In contrast, the copper/zinc ratio was positively related to the risk of moderate or severe anemia (p = 0.021). The adjusted relationships between copper and copper/zinc ratio with premature rupture of membranes were statistically significant (p = 0.007 and p = 0.037). Iron and zinc were negatively associated with the risk of chorioamnionitis, while copper and copper/zinc ratio were positively associated with the risk of chorioamnionitis (all p < 0.05). CONCLUSIONS: Serum iron, zinc and copper levels are closely related to pregnancy outcomes.

Retrospective study on the therapeutic efficacy of zinc acetate hydrate administration to patients with hypozincemia-induced dysgeusia.

BACKGROUND: Dysgeusia is a relatively early symptom of zinc deficiency, and zinc replacement is effective in treating dysgeusia. The administration of zinc acetate hydrate (ZAH) was approved in 2017 for patients with hypozincemia in Japan. This retrospective study was conducted to explore the efficacy and safety of ZAH administration in patients with hypozincemia-induced dysgeusia. METHODS: Patients with hypozincemia-induced dysgeusia who visited our hospital from May 2013 to December 2019 were included in this study. ZAH (zinc content; 50 mg/day) was administered to 42 patients for 24 weeks. The taste test was performed using the filter paper disk method, and the total cognitive thresholds of the left and right chorda tympani regions were used. Changes in taste function, serum zinc and copper levels, and copper/zinc ratio were analyzed. A total of 28 patients who received polaprezinc (PPZ, zinc content; 34 mg/day) for 24 weeks, who were prescribed until ZAH was approved, were registered as controls. RESULTS: Serum zinc levels at 12 and 24 weeks after ZAH or PPZ administration were higher than those before administration. These levels were significantly higher in the ZAH-treated group than in the PPZ-treated group. However, serum copper levels did not significantly change before and after administration. In the taste test, the taste thresholds for the acidity and salty at 12 and 24 weeks after ZAH administration were significantly decreased compared to before administration. In contrast, in the PPZ group, the taste thresholds for the acidity and salty were significantly decreased 24 weeks after administration. CONCLUSIONS: ZAH (50 mg/day) administration was effective in improving the gustatory sensitivity of patients with dysgeusia and hypozincemia 12 weeks after administration without affecting the serum copper level. ZAH was also more effective than PPZ.

Use of serum copper and zinc levels in the diagnostic evaluation of endometrioma and epithelial ovarian carcinoma.

OBJECTIVE: The aim of this study is to evaluate serum copper (Cu) and zinc (Zn) levels in patients with epithelial ovarian cancer and endometrioma. MATERIALS AND METHODS: We included 21 epithelial ovarian cancer patients, 47 endometrioma patients, 31 healthy women of reproductive age, and 10 healthy women in menopause. Cu and Zn levels and Cu/Zn ratios were compared. RESULTS: In the endometrioma group, Cu levels (P = 0.04) and Cu/Zn ratio (P < 0.01) were higher, while Zn levels (P < 0.01) were lower compared to the control group. The threshold value of 1.15 with 62% sensitivity and 61% specificity was calculated for the Cu/Zn ratio using the ROC curve (AUC = 0.688; P = 0.005). In the ovarian cancer group, Cu levels (P ≤ 0.01) and Cu/Zn ratio (P = 0.02) were higher, whereas Zn levels (P ≤ 0.02) were lower compared to the control group. The Cu/Zn ratio threshold value of 1.37 was calculated with 76% sensitivity and 90% specificity (AUC = 0.829; P = 0.004). The Zn level was lower (P = 0.02), and the Cu/Zn ratio was higher (P = 0.01) in the ovarian cancer group compared to the endometrioma group. CONCLUSION: The threshold value of the Cu/Zn ratio for ovarian cancer could be determined with a specificity of 90%, whereas the sensitivity and specificity of the Cu/Zn ratio for endometrioma were low.

Serum concentrations of heavy metals in women with endometrial polyps.

Endometrial polyps are one of the common reasons of abnormal uterine bleeding in women. Industrialisation, urbanisation and increased air pollution cause increased heavy metal exposure. Heavy metals that have oestrogenic effects in human body are named as metalloestrogens. The aim of this study was to investigate the serum metalloestrogen levels such as copper (Cu), zinc (Zn), aluminium (Al), lead (Pb), nickel (Ni) and Cu/Zn ratio and their possible relationship with the occurrence of endometrial polyps. Eighty women with abnormal uterine bleeding were divided into two groups: 40 women diagnosed with endometrial polyp (study group) and 40 women without endometrial polyp (control group). Ages, body mass indices, smoking behaviours, drinking water choices, chronic diseases and intrauterine device histories were noted for all patients. Blood levels of Cu, Zn, Al, Pb, Ni and Cu/Zn ratio were analysed by inductively coupled plasma-mass spectrometry method for both groups. No statistically significant differences were observed in terms of serum median levels of Cu and Pb between the study and the control groups. The serum median levels of Zn, Ni and Al were found to be statistically lower in the study group when compared with the control group. The Cu/Zn ratio was statistically higher in the study group. High Cu/Zn ratio, as a biomarker of oxidative stress, suggests the role of oxidative stress in etiopathogenesis of endometrial polyps.IMPACT STATEMENTWhat is already known on this subject? Studies demonstrate that oestrogen and progesterone play an important role in pathogenesis of endometrial polyps. Inorganic heavy metal ions that bind and activate oestrogen receptors are referred to as 'metalloestrogens'. Apart from toxic effects, metalloestrogens have been linked to the aetiology of oestrogen-dependent diseases such as breast and endometrium cancer and endometriosis. However, serum levels of heavy metals were not investigated in a large group of endometrial polyp patients.What do the results of this study add? This is the first study investigating the serum levels of heavy metals in a large group of endometrial polyp patients. We did not observe any increased serum levels of heavy metals in endometrial polyp patients. Our results might suggest that oestrogenic heavy metal exposure has no role in the appearance of endometrial polyps. However, increased Cu/Zn ratio due to low serum levels zinc suggests oxidative stress might play a role in endometrial polyps.What are the implications of these findings for clinical practice and/or further research? Further research of heavy metals in endometrial polyps with simultaneous blood and tissue samples could show the precise effect of environmental exposure of metalloestrogens in aetiopathogenesis of endometrial polyps.

Serum Levels of Copper and Zinc and Survival in Breast Cancer Patients.

There is emerging interest in the relationship between several serum micronutrients and the prognosis of patients with breast cancer. The relationship between serum zinc and copper levels and breast cancer prognosis is unclear. In our study, we included 583 patients with breast cancer diagnosed between 2008 and 2015 in the region of Szczecin, Poland. In a blood sample obtained before treatment, serum zinc and copper levels were quantified by mass spectroscopy. Each patient was assigned to one of four categories (quartiles) based on the distribution of the elements in the entire cohort. Patients were followed from diagnosis to death over a mean of 10.0 years. The 10-year overall survival was 58.3% for women in the highest and 82.1% for those in the lowest quartile of serum copper/zinc ratio (p < 0.001). The multivariate hazard ratio (HR) for breast cancer death was 2.07 (95% CI 1.17-3.63; p = 0.01) for patients in the highest quartile of serum copper/zinc ratio compared to those in the lowest. There is evidence that the serum zinc level and copper/zinc ratio provide an independent predictive value for overall survival and breast cancer-specific survival after breast cancer diagnosis.

Prediction of cardiovascular disease risk by serum zinc and copper concentrations and anthropometric measurements.

INTRODUCTION: We aimed to investigate the association between cardiovascular disease (CVD) and various anthropometric indices, as well as the serum levels of copper (Cu) and zinc (Zn), copper-zinc ratio (Cu/Zn ratio) and zinc-copper ratio (Zn/Cu ratio), in a large population sample from northeastern Iranian. METHOD: 9704 individuals aged 35 to 65 were enrolled in the first phase of the study. After a 10-year follow-up, 7560 participants were enrolled into the second phase. The variables used in this study included demographic characteristics, such as gender and age; biochemical parameters including: serum Zn, Cu, Cu/Zn ratio, and Zn/Cu ratio; anthropometric parameters including: waist circumference (WC), body mass index (BMI), and waist-to-hip ratio (WHR). The relationship between the aforementioned indices and CVD was examined using decision tree (DT) and logistic regression (LR) models. RESULTS: A total of 837 individuals were diagnosed with CVD among the 7560 participants. LR analysis showed that BMI, age, WH zinc-copper ratio (Zn/Cu ratio), and serum Zn/Cu ratio were significantly associated the development of CVD in men, and WHR, age, BMI, serum Cu, and Cu/Zn ratio in women. DT analysis showed that, age was the most important predictor of CVD in both genders. 71% of women, older than 49 years, with a WHR≥ 0.89, serum Cu< 75 (µg/dl), BMI≥ 22.93 (kg/m2), and serum Cu≥ 14 (µg/dl), had the highest risk of CVD. In men, among those who were ≥ 53 years, with a WHR≥ 0.98, serum Zn/Cu ratio< 1.69, and BMI≥ 22.30, had the highest risk of CVD. CONCLUSION: Among Iranian adult population, BMI, age, and WHR were one of the predictors of CVD for both genders. The Zn/Cu ratio was CVD predictor for men while Cu/Zn ratio was CVD predictor for women.

Serum copper, zinc and copper/zinc ratio in relation to survival after breast cancer diagnosis: A prospective multicenter cohort study.

BACKGROUND: The essential trace elements copper and zinc, and their ratio (copper/zinc), are important for maintaining redox homeostasis. Previous studies suggest that these elements may impact breast cancer survival. However, no epidemiological study has so far been conducted on the potential association between copper and copper/zinc levels and survival after breast cancer diagnosis. In this study, we aimed to examine the relationship between serum copper, zinc and copper/zinc levels and survival following breast cancer diagnosis. PATIENTS AND METHODS: The Sweden Cancerome Analysis Network - Breast Initiative (SCAN-B) is a population-based cohort study including multiple participating hospitals in Sweden. A total of 1998 patients diagnosed with primary invasive breast cancer were followed for approximately nine years. Serum levels of copper and zinc and their ratio at the time of diagnosis was analyzed in relation to breast cancer survival using multivariate Cox regression, yielding hazard ratios (HR) with 95% confidence intervals. RESULTS: A higher copper/zinc ratio was associated with lower overall survival after breast cancer diagnosis. Comparing patients with a copper/zinc ratio in quartile 4 vs 1, the crude HR was 2.29 (1.65-3.19) (Ptrend <0.01) and the fully adjusted HR was 1.58 (1.11-2.25) (Ptrend = 0.01). No overall associations were seen between serum copper or zinc levels on their own and survival after breast cancer diagnosis, although a tendency toward lower breast cancer survival was seen for higher copper levels and lower zinc levels. CONCLUSION: There is evidence that the serum copper/zinc ratio provides an independent predictive value for overall survival following breast cancer diagnosis.

The first trimester plasma copper-zinc ratio is independently related to pregnancy-specific psychological distress symptoms throughout pregnancy.

OBJECTIVES: High plasma copper (Cu) and low zinc (Zn) levels have been associated with depression. However, most studies used low sample sizes and a cross-sectional design, and perinatal data are scarce. We investigated the possible association between pregnancy-specific psychological distress and the plasma CuZn ratio using a prospective design. METHODS: Pregnancy-specific distress symptoms were assessed at each trimester by means of the Tilburg Pregnancy Distress Scale, negative affect subscale, in 2036 pregnant women. Cu and Zn were assessed at 12 wk of gestation in plasma samples by inductively coupled plasma mass spectrometry. Growth mixture modeling determined trajectories of women's pregnancy-specific negative affect (P-NA) symptoms, which were entered in a multiple logistic regression analysis as dependent variable and the CuZn ratio as independent variable. RESULTS: Two P-NA symptom classes were found: 1) persistently low (n = 1820) and 2) persistently high (n = 216). A higher CuZn ratio was independently associated with persistently high P-NA symptom scores (odds ratio = 1.52; 95% confidence interval, 1.13-2.04) after adjustment for confounders. A sensitivity analysis was performed excluding all women with high P-NA scores at 12 wk of gestation (>1 SD above the mean P-NA score). In the 1719 remaining women, a higher CuZn ratio significantly predicted the development of increasing P-NA symptom scores after adjustment for confounders (odds ratio = 1.40; 95% confidence interval, 1.04-1.95). CONCLUSIONS: A higher CuZn plasma ratio is an independent determinant of developing pregnancy-specific distress symptoms throughout pregnancy, suggesting that micronutrients could be used as novel biomarkers for psychological distress research of perinatal mood disorders.

Association between serum copper, zinc and their ratio and handgrip strength among adults: a study from National Health and Nutrition Examination Survey (NHANES) 2011-2014.

Evidence for the association between serum copper and zinc status and handgrip strength is very limited only in several observational studies with study participants of specific population or a narrower age range. The aim of this study was to evaluate the association between serum copper, zinc and their ratio and handgrip strength in the general population. This study included adult participants aged 20-80 years with complete data of serum copper and zinc status and handgrip strength from NHANES 2011-2014. Handgrip strength was calculated as the average of the maximum measure obtained in each hand with a grip strength dynamometer and corrected using BMI. Serum copper and zinc levels were measured using inductively coupled plasma dynamic reaction cell mass spectrometry, and their ratios were calculated. The multivariable linear regression and restricted cubic spline models were used. Serum copper level was inversely associated with BMI-corrected handgrip strength, and the beta coefficients (95% confidence intervals) comparing the second, third, and fourth to the lowest quartiles of serum copper level were - 0.17 kg (- 0.26; - 0.08), - 0.22 kg (- 0.32; - 0.13), and - 0.36 kg (- 0.44; - 0.28), respectively (P for trend < 0.001). Non-linear association was detected between serum copper level and BMI-corrected handgrip strength (P < 0.01). Consistent with serum copper, serum copper/zinc ratio was inversely associated with BMI-corrected handgrip strength. However, no significant associations were observed between serum zinc level and BMI-corrected handgrip strength (all P > 0.05). Higher serum copper level and copper/zinc ratios were significantly associated with lower handgrip strength. Further research is needed to address related issues.

Association between serum copper/zinc ratio and lung cancer: A systematic review with meta-analysis.

BACKGROUND: Numerous studies have investigated the relationship between serum copper/zinc ratio and lung cancer. However, the results are inconsistent. Therefore, we evaluated the association between copper/zinc ratio and lung cancer. MATERIALS AND METHODS: Observational studies reporting serum copper/zinc ratio in lung cancer patients and controls were identified from PubMed, Web of Science, EMBASE, CNKI and Wanfang databases online before December 2021. Summary standard mean difference (SMD) and the corresponding 95 % confidence interval (95 % CI) were applied to compare the serum serum copper/zinc ratio between lung cancer patients and controls using a random-effects model. RESULTS: Thirty-nine articles including 3598 lung cancer patients, 1402 benign lung diseases, and 3314 healthy controls were included in this study. The pooled results showed that the lung cancer patients had significantly higher serum copper/zinc ratio than healthy controls [SMD (95 % CI): 1.62 (1.31, 1.93)] and patients with benign lung diseases [SMD (95 % CI): 0.60 (0.36, 0.84)]. The results were robust according to sensitivity analysis. Meanwhile, consistent results were obtained both in European populations and Asian populations. Moreover, serum copper/zinc ratio was significant higher in patients with advanced stage of lung cancer than that in patients with early stage of lung cancer. CONCLUSION: The results showed that elevated serum copper/zinc ratio might be associated with increased risk of lung cancer.

Study of Serum Zinc and Copper Levels and Tumor Pathology: A Pilot Study in People Affected with Head and Neck Cancers.

This study aimed to determine understanding the role of serum copper, zinc and copper/zinc ratio with tumor staging in people newly diagnosed to be affected with Head and Neck cancer and by comparing with age matched health individuals devoid of any orodental maladies. The study included patients confirmed to be affected with HN cancer with histological diagnosis of Head and Neck cancer (60) and age matched healthy volunteers (N = 23). The demographic details like age, domicile, menopausal status and pathological details (like tumor stage, number of lymph node involvement, tumor size) were collected from the patient's hospital data file. The serum levels of zinc and copper assayed as per standard procedures and the zinc/copper was calculated for the cancer patients and controls. The data were subjected to unpaired "t" test and ANOVA with Bonferroni's multiple comparisons. The association between zinc and copper levels with pathological details between the variables was ascertained using the Pearson correlation coefficient(r). A statistical value of p < 0.05 was considered to be significant in agreeance to the accepted norms. Results: This result of the study indicates that when compared to the healthy individuals, the serum levels of copper, and zinc, and copper/zinc ratio were high in patients with H&N cancer. Also when compared with controls, the levels of zinc decreased, while that of copper and copper/zinc ratio increased in people affected with H&N cancer (p = 0.017 to 0.0001) and with the stage of the tumor (p = 0.03 to 0.001). The results of the study suggest that levels of serum zinc were significantly lower and that of copper higher in H&N cancer patients than that in controls and also that it was dependent on the tumor stage. When analyzed cumulatively the results hint that zinc and copper, due to their role in free radical generation and prevention have an important role in cancer progression and possible prevention by judicious intervention.

Synergistic association of the copper/zinc ratio under inflammatory conditions with diabetic kidney disease in patients with type 2 diabetes: The Asahi Diabetes Complications Study.

AIMS/INTRODUCTION: We aimed to study the relationships among the copper (Cu)/zinc (Zn) ratio, inflammatory biomarkers, and the prevalence of diabetic kidney disease (DKD) in patients with type 2 diabetes. MATERIALS AND METHODS: A cross-sectional study was performed on 651 patients with type 2 diabetes. DKD was defined as a urinary albumin-to-creatinine ratio of ≥30 mg/g creatinine and/or an estimated glomerular filtration rate using cystatin C of < 60 mL/min/1.73 m2 . Areas under the curves (AUCs), cutoff values, and thresholds for detecting DKD were determined for the Cu/Zn ratio, soluble tumor necrosis factor-α receptor 1 (sTNFαR1), and high-sensitivity C-reactive protein (hsCRP). Patients were categorized by each cutoff value of sTNFαR1 and the Cu/Zn ratio. Odds ratios (ORs) and biological interactions for the prevalence of DKD were determined. RESULTS: DKD was identified in 220 patients. AUC/optimal cutoff values were 0.777/1300 pg/mL for sTNFαR1, 0.603/1.1648 for the Cu/Zn ratio, and 0.582/305 ng/mL for hsCRP. The ORs for DKD were higher, but not significantly, in the sTNFαR1 < 1300 and Cu/Zn ≥ 1.1648 group, significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P < 0.0001), and further synergistically elevated in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group (P < 0.0001) compared with the sTNFαR1 < 1300 and Cu/Zn < 1.1648 group after multivariable adjustment. Levels of sTNFαR1 were significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group than in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P = 0.0006). CONCLUSIONS: Under an inflammatory initiation signal of elevated serum sTNFαR1 levels, an increase in the Cu/Zn ratio may further exacerbate inflammation and is synergistically associated with a high prevalence of DKD in patients with type 2 diabetes.

Assessment of Copper and Zinc Levels in Hair and Urine of Children With Attention Deficit Hyperactivity Disorder: A Case-Control Study in Eastern India.

Background Attention deficit hyperactivity disorder (ADHD) is a neuro-developmental ailment diagnosed with inattention and hyperactivity-impulsivity. It is one of the most prevalent neurodevelopmental disorders and has complex aetiology, both genetic and environmental. There is a perceived decrease in skill acquirement, leading to insufficient income and job opportunities as adults, which drives them towards poor physical and mental outcomes compared to their contemporaries without ADHD. The impact of heavy metals on ADHD is a topic of interest but is much less studied. Copper has been implicated as a pro-oxidant and in the metal accelerated production of free radicals that may affect oxidative stress. Zinc also serves as an antioxidant, and changes in its concentrations may impact the homeostasis of oxidative stress. Methods Twenty-four children diagnosed with ADHD were taken as cases and matched with 24 healthy controls. Hair and urine samples were collected from all the study participants. The samples were collected in sterile containers according to established protocols. Acid digestion of hair samples was done using 65% nitric acid and 30% hydrogen peroxide. Urine samples were extracted by a solution of 0.1% Triton-X-100 and 1% ultrapure nitric acid. The levels of zinc and copper were determined in both samples by inductively coupled plasma optical emission spectrometry (ICP-OES). The copper/zinc ratio (Cu/Zn) was calculated from these values. Mann Whitney U Test and receiver operating characteristic (ROC) analysis were done to estimate statistical significance. Results The median age of the study population was eight years. Overall, 34 male and 14 female subjects participated. There was no significant difference in height, weight and BMI between the cases and controls. Hair zinc levels in the ADHD group (198.49 µg g-1 of hair) was significantly lower than the control group (527.05 µg g-1 of hair). However, hair copper levels were increased significantly in the ADHD children (14.01 µg g-1 of hair) compared to the controls (7.43 µg g-1 of hair). Urine zinc levels were significantly lower in cases than controls (525.7 µg g-1 of spot urine creatinine vs 1374.09 µg g-1 of spot urine creatinine). However, copper levels in urine were higher in the ADHD children (17.01 µg g-1 of spot urine creatinine compared to 7.26 µg g-1 of spot urine creatinine in controls). Both hair and urine copper to zinc ratio was significantly higher in the ADHD group. On ROC analysis, the hair Cu/Zn ratio had an area under the curve (AUC) of 0.920 (p-value <0.001), and the urine Cu/Zn ratio had an AUC of 0.967 (p-value <0.001). When used as a diagnostic classifier for ADHD based on the cut-off value determined by ROC, both hair and urine Cu/Zn ratio had high sensitivity and specificity. Conclusion Low zinc levels in the urine and hair of children and higher levels of copper may impact the aetiology of ADHD in these children. At an early stage, the Cu/Zn ratio in both hair and urine samples may be used as a precise biomarker to identify and monitor such children.

Possible Associations of Disturbed Neurometals and Ammonia with Glycaemic Control in Type 1 Diabetic Children with Attention Deficit Hyperactivity Disorder.

The chronicity of type 1 diabetes mellitus (T1DM) is reported to be associated with various psychological disorders. The current study aimed to evaluate the levels of serum ammonia and various neurometals (zinc, copper, and magnesium) in patients with T1DM with and without ADHD and to correlate their levels with glycaemic status. A prospective case-control study was conducted with 60 diabetic children with T1DM (allocated into a group of 20 patients with a diagnosis of ADHD and a group of 40 patients without ADHD) who were comparable to 60 matched controls. Assays of glucose, glycated haemoglobin (HbA1c), ammonia, zinc, copper, and magnesium were performed. Overall, ammonia and copper levels were significantly higher in the diabetic patients especially those with ADHD than in the control group (p Ë‚ 0.05 for all). The calculated copper/zinc ratio was significantly higher in the diabetic patient group than in the control group and higher in diabetic children with ADHD than in diabetic children without ADHD (p Ë‚ 0.05 for all). Diabetic children had significantly lower magnesium levels than the controls (p Ë‚ 0.05), but no significant difference between the diabetic subgroups was detected. A positive correlation between glycaemic control (HbA1c %) and ammonia level was found in the diabetic group and subgroups, and a positive correlation was found between HbA1c % and the Cu/Zn ratio in diabetic children with ADHD (p Ë‚ 0.05 for all). The current study confirms an association of elevated ammonia and copper/zinc ratio with poor glycaemic control and ADHD development among children with T1DM.

Copper and Copper/Zinc Ratio in a Series of Cystic Fibrosis Patients.

Cystic fibrosis (CF) patients require a stable and sufficient supply of micronutrients. Since copper is an essential micronutrient for human development, a cross-sectional study was carried out to investigate the serum copper levels, serum copper/zinc (Cu/Zn) ratios, and their relationship with nutritional indicators in a group of CF patients. Anthropometric, biochemical, and dietary measurements, an abdominal ultrasound, and respiratory and pancreatic tests were conducted. Seventeen CF patients were studied (10 females, 59%), 76.5% of whom were ∆F580. Their mean serum copper (113 ± 23 µg/dL) was normal, and there was only one teenager with hypocupremia (6%) and two children with hypercupremia (18%). A significant association between serum copper and zinc levels was discovered. The Cu/Zn ratio was higher than 1.00 for 94% of patients, which is an indicator of an inflammation status. There was no significant correlation between the serum copper concentrations and respiratory and pancreatic function, respiratory colonization, and the results of the abdominal ultrasound. Linear regression analysis showed that serum copper had a positive association with both the Z-score body mass index (BMI) and mean bone conduction speed (BCS). Therefore, since 94% of CF patients had a Cu/Zn ratio > 1.00, this factor must alert us to consider the risk of zinc deficiency and high inflammatory response. The measurement of serum zinc alone does not show one's zinc status. However, the Cu/Zn ratio may be an indicator of zinc deficiency and the inflammatory status of CF patients.

The Copper/Zinc Ratio Correlates With Markers of Disease Activity in Patients With Inflammatory Bowel Disease.

BACKGROUND: Zinc (Zn) and copper (Cu) are trace elements that serve as cofactors in catalytic processes with impact on immune responses. In patients with inflammatory bowel disease (IBD), decreased levels of serum Zn and Cu have been observed. Here, we investigated the effect of inflammation on serum concentrations of these trace elements in patients with IBD. METHODS: In this cross-sectional study, 98 patients with Crohn disease (CD) and 56 with ulcerative colitis (UC) were prospectively enrolled. Disease activity parameters, such as C-reactive protein (CRP) and fecal calprotectin (FC) were compared to serum Zn, Cu, and Cu/Zn ratio. RESULTS: Zinc insufficiency was observed in 11.2% of patients with CD and 14.3% with UC, Cu insufficiency in 20.4% with CD and 7.1% with UC. Anemia, hypoalbuminemia, increased FC, and elevated CRP were more frequently present in Zn-insufficient patients with IBD. In contrast, lower serum CRP values and a trend to lower FC were observed in Cu-insufficient patients. In multiple linear regression models adjusted for age, gender, and serum albumin, CRP positively correlated with serum Cu (P < 0.001) and the Cu/Zn ratio in both CD and UC (P < 0.001) but not with serum Zn concentrations. FC levels correlated only with the Cu/Zn ratio in patients with UC (P < 0.038). CONCLUSION: Systemic inflammation inversely affected the serum Zn and Cu concentrations and, consequently, resulted in an increased Cu/Zn ratio.

Nutritional status in irritable bowel syndrome: A North American population-based study.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) affects 12% of the population, and the evidence supporting current medical interventions is poor. There is increasing focus on the therapeutic benefit of diet and supplementation. We aim to compare dietary composition and hematologic and biochemical markers in those with and without IBS to determine potential targets for therapeutic supplementation. METHODS: All 17 national surveys between 1959 and 2019 were screened, and only 1, the Second National Health and Nutrition Examination Survey (NHANES II) (1976-1980), provided comprehensive data on IBS. We performed a cross-sectional analysis of hematologic and biochemical markers and dietary composition of 12 295 individuals, aged 18-74, in NHANES II. RESULTS: Individuals with IBS had significantly higher copper-zinc ratios (1.70 vs 1.55, P = 0.048) and were more likely to have ratios above 1.8 (odds ratio 1.79, 95% confidence interval 1.02-3.13), indicative of underlying copper-zinc imbalance. While more likely to report dietary avoidances, they had no other evidence of nutritional deficiencies. In addition, dietary recall showed that those with IBS consumed more calories (P = 0.02), were more likely to take vitamin supplements (P = 0.003), and that their macro and micronutrient intake was not significantly different. CONCLUSIONS: The findings suggest that individuals with IBS should be screened for copper-zinc imbalance. Given zinc's role in the immune system, the "brain-gut" axis, and the gastrointestinal barrier, the identified copper-zinc imbalance may play a role in perpetuating the underlying pathophysiology of IBS. Further studies are needed to investigate this hypothesis and the potential role of therapeutic zinc supplementation.

Serum levels of copper, zinc and disease severity scores in sickle cell disease patients in Benin City, Nigeria.

BACKGROUND: Micronutrient deficiency is recognized in sickle cell anaemia (SCA) but it is not known for certain whether changes in zinc, copper and copper-to-zinc ratio are associated with Sickle cell disease severity scores. OBJECTIVE: To compare serum levels of copper, zinc and copper-to-zinc ratio in SCA subjects with control group and correlate the variables with objective disease severity scores. METHODS: Serum copper and zinc were determined in 100 SCA patients and 50 controls using kits supplied by Centronic, Germany. Unpaired Students't-test was used to compare the variables between SCA patients in steady clinical state, vaso-occlusive crisis and controls, while Spearman correlation coefficient was used to associate the parameters with disease severity scores. RESULTS: Serum copper level was higher (P=0.008) in SCA patients than controls, while serum zinc level was lower (P<0.001) in SCA patients than controls. The copper/zinc ratio was higher (P<0.001) in SCA patients than controls. Significantly higher (P<0.001) copper and lower (P<0.001) zinc levels were observed in patients in vaso-occlusive crisis than in steady clinical state. Zinc correlated inversely (r=-0.2743; P=0.006) while copper-to-zinc ratio correlated positively with disease severity scores. CONCLUSION: Copper-to-zinc ratio may be an indicator of disease severity in SCA patients.

Associations Between Copper and Zinc and Risk of Hypertension in US Adults.

Evidence linking copper and zinc to hypertension are limited and conflicting. Data from the National Health and Nutrition Examination Survey (NHANES) 2007-2014 were used. Zinc and copper intake from diet and supplements was assessed with 24-h dietary recall. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg/diastolic blood pressure (DBP) ≥ 90 mmHg/treatment with hypertensive medications. In a sensitivity analysis, according to the 2017 American College of Cardiology and American Heart Association guideline, hypertension was also defined as SBP ≥ 130 mmHg/DBP ≥ 80 mmHg/treatment with hypertensive medications. A total of 17,811 adults (8430 men and 9381 women) were included. After adjustment for age, gender, body mass index (BMI), race, educational level, smoking status, family income, and total daily energy intake, the OR of hypertension for highest vs. lowest quartile intake of copper, zinc, and copper/zinc ratio was 1.11 (0.90-1.37), 1.11 (0.90-1.35), and 0.95 (0.81-1.11), respectively. In stratified analysis by BMI (< 25 kg/m2, 25-30 kg/m2, > 30 kg/m2), no significant association was found between hypertension and intakes of copper, zinc, and copper/zinc ratio (highest vs. lowest quartile) in multivariate analysis. In multivariate analysis, the OR of hypertension for highest vs. lowest quartile levels of serum copper, zinc, and copper/zinc ratio was 1.11 (0.61-2.04), 1.43 (0.84-2.44), and 0.68 (0.34-1.33), respectively. Similar results were found in the sensitivity analysis. Zinc and copper might be not independently associated with hypertension in US adults.

Trace elements (copper, zinc, selenium and molybdenum) as markers in oral sub mucous fibrosis and oral squamous cell carcinoma.

Oral cancer is a major cause of cancer morbidity and mortality worldwide and is prevalent in most areas where tobacco related practices are observed. Essential elements play a role in many biochemical reactions as a micro-source and there is growing evidence that their concentrations are altered on the onset and progress of malignant disease. In this study the levels of copper (Cu), zinc (Zn), selenium (Se) and molybdenum (Mo) in serum of patients with oral sub mucous fibrosis (OSMF) (n = 30) and oral squamous cell carcinoma (OSCC) (n = 30); were determined and the alterations of these critical parameters were analyzed in comparison with controls (n = 30) to identify predictors amongst these parameters for disease occurrence and progression. The serum Cu and Zn were established using Flame Atomic Absorption Spectrometry. Serum estimation of Se and Mo was done by graphite furnace atomic absorption spectrometry (GFAAS). Data analysis revealed a marked, progressive and significant increase in Cu levels in precancer (OSMF) and cancer (OSCC) groups as compared to the normal group. The level of Zn in serum was slightly elevated in OSMF and OSCC though not statistically significant. Cu/Zn ratio was slightly but not significantly elevated. Serum levels of Se and Mo were significantly decreased in the precancer and cancer groups as compared to the normals.