Cu9.0

Copper Research

82 peer-reviewed studies · Evidence score: 9/10

1

Misoprostol for intrauterine device placement

Zapata LB et al. • The Cochrane database of systematic reviews (2025)

Evidence from RCTs of women seeking routine IUD placement suggests that receiving misoprostol compared to placebo or no treatment makes little to no difference to pain during tenaculum placement or after IUD placement; and may make little to no difference to pain during IUD placement.

Misoprostol may result in little to no difference in pain during IUD placement (MD -0.47, 95% CI -1.23 to 0.29; 7 RCTs, 766 women; low-certainty evidence).
Providers' ease of placement: misoprostol may result in little to no difference in a clinically meaningful effect on ease of IUD placement for providers (MD -0.89, 95% CI -1.55 to -0.22; 8 RCTs, 848 women; low-certainty evidence).
Need for cervical dilation: misoprostol may result in little to no difference in need for cervical dilation for women without a recent failed placement attempt (RR 0.84, 95% CI 0.38 to 1.85; 6 RCTs, 562 women; low-certainty evidence).

Meta-Analysisn=1,972

2

Micronutrient deficiencies in patients with celiac disease: A systematic review and meta-analysis

Lamjadli S et al. • International journal of immunopathology and pharmacology (2025)

This study highlighted significantly higher micronutrient deficiencies in patients diagnosed with CeD than in controls, underscoring the importance of systematic nutritional assessment and multidisciplinary management to address micronutrient deficiencies and minimize negative health impact(s).

Meta-analysis revealed a significant difference in hemoglobin levels between patients with CeD and controls (standardized mean difference (SMD) -0.59 (95% confidence interval (CI) -0.8459 to -0.3382); P = 0.0003).
No significant differences were found in MCV, or copper or vitamin B12 levels between patients with CeD and controls.
This study highlighted significantly higher micronutrient deficiencies in patients diagnosed with CeD than in controls, underscoring the importance of systematic nutritional assessment and multidisciplinary management to address micronutrient deficiencies and minimize negative health impact(s).

Meta-Analysisn=4,140

3

Trace Elements and Risk of Immune-Mediated Skin Disease: A Systematic Review and Meta-analysis

Shao X et al. • Nutrition reviews (2025)

Serum trace element levels showed more significant changes in patients with IMSDs than in healthy controls.

Serum trace element levels showed more significant changes in patients with IMSDs than in healthy controls.
These findings suggest that alterations in trace element levels may be associated with the occurrence, development, and prognosis of IMSDs.
Further research warranted to confirm findings

Meta-Analysisn=7,014

4

Healthy lifestyle choices: new insights into vitiligo management

Liang X et al. • Frontiers in immunology (2024)

Patients with vitiligo should reduce smoking and alcohol consumption and take appropriate vitamin E, B12, copper, and zinc supplements.

Vitamin C [mean difference (MD), -0.342; 95% confidence interval (CI), -1.090-0.407; p >0.05), folic acid (MD, -1.463; 95% CI, -7.133-4.208; p >0.05), and selenium (MD, 0.350; 95% CI, -0.687-1.387; p >0.05) levels did not differ between the groups.
The serum iron level of the vitiligo group was significantly higher than that of the control group (MD, 1.181; 95% CI, 0.390-1.972; p <0.005).
Patients with vitiligo should reduce smoking and alcohol consumption and take appropriate vitamin E, B12, copper, and zinc supplements.

Meta-Analysisn=8,542

5

Metal Exposure and Risk of Parkinson Disease: A Systematic Review and Meta-Analysis

Zhao Y et al. • American journal of epidemiology (2023)

We did not find associations between other metals and PD.

We did not find associations between other metals and PD.
The current level of evidence for associations between metals and PD risk is limited, as biases from methodological limitations cannot be ruled out.
High-quality studies assessing metal levels before disease onset are needed to improve our understanding of the role of metals in the etiology of PD.© The Author(s) 2023.

Meta-Analysisn=2,021

6

Orthodontic treatment for crowded teeth in children

Turner S et al. • The Cochrane database of systematic reviews (2021)

Most interventions were assessed by single, small studies.

Fixed appliances and auxiliaries One study found that use of a lip bumper may reduce crowding in the early permanent dentition (MD -4.39 mm, 95% CI -5.07 to -3.71; 34 participants).
One study concluded that coaxial nickel-titanium (NiTi) archwires may cause more tooth movement in the lower arch than single-stranded NiTi archwires (MD 6.77 mm, 95% CI 5.55 to 7.99; 24 participants).
Another study, comparing copper NiTi versus NiTi archwires, found NiTi to be more effective for reducing crowding (MD 0.49 mm, 95% CI 0.35 to 0.63, 66 participants).

Meta-Analysisn=1,512

7

A systematic review and meta-analysis of the hyperuricemia risk from certain metals

Gu T et al. • Clinical rheumatology (2022)

The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).

Data were pooled by random-effects models and expressed as pooled odds ratios (OR) and 95% confidence intervals (CIs).
Exposure to molybdenum (pooled OR = 0.804, 0.724, 0.975, 3, 0%) was linked to a decreased risk of HUA, however.
Molybdenum exposure was associated with a decreased prevalence of HUA; however, aluminum, cobalt, copper, iron, magnesium, manganese, mercury, selenium, thallium and zinc are not associated with HUA risk.

Meta-Analysisn=63,283

8

A systematic review on clinical effectiveness, side-effect profile and meta-analysis on continuation rate of etonogestrel contraceptive implant

Moray KV et al. • Reproductive health (2021)

ESI is clinically effective and safe contraceptive method to use, yet 1-year continuation rates are lower as compared to LNG-IUS and copper-IUD, mostly attributed to the disturbances in the menstruation.

Eight of the 15 studies reporting clinical effectiveness reported 100% effectiveness and overall pearl index ranged from 0 to 1.4.
One-year continuation rates ranged from 57-97%; 44-95% at the end of second year and 25-78% by 3 years of use.
ESI is clinically effective and safe contraceptive method to use, yet 1-year continuation rates are lower as compared to LNG-IUS and copper-IUD, mostly attributed to the disturbances in the menstruation.

Meta-Analysisn=2,019

9

Interventions for emergency contraception

Shen J et al. • The Cochrane database of systematic reviews (2019)

Levonorgestrel and mid-dose mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen.

Levonorgestrel users were less likely to have any side effects than Yuzpe users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high-quality evidence).
UPA users were more likely than levonorgestrel users to have resumption of menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n = 3593, I2 = 0%, high-quality evidence).
Levonorgestrel and mid-dose mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen.

Meta-Analysisn=4,750

10

Biomarkers for diagnosis of Wilson's disease

Ryan A et al. • The Cochrane database of systematic reviews (2019)

The cut-offs used for caeruloplasmin, 24-hour urinary copper and hepatic copper for diagnosing Wilson's disease are method-dependent and require validation in the population in which such index tests are going to be used.

The cut-offs used for caeruloplasmin, 24-hour urinary copper and hepatic copper for diagnosing Wilson's disease are method-dependent and require validation in the population in which such index tests are going to be used.
Binary cut-offs and use of single-test strategies to rule Wilson's disease in or out is not supported by the evidence in this review.
There is insufficient evidence to inform testing in specific subgroups, defined by age, ethnicity or clinical subgroups.

Meta-Analysisn=5,699

11

Interventions for pain with intrauterine device insertion

Lopez LM et al. • The Cochrane database of systematic reviews (2015)

Nearly all trials used modern IUC.

Here we synthesize results from trials with sufficient outcome data and moderate- or high-quality evidence.For lidocaine, meta-analysis showed topical 2% gel had no effect on pain at tenaculum placement (two trials) or on pain during IUC insertion (three trials).
Mean score for IUC-insertion pain was lower with lidocaine and prilocaine cream (MD -1.96, 95% CI -3.00 to -0.92).
Among nulliparous women, topical 4% formulation showed lower scores for IUC-insertion pain assessed within 10 minutes (MD -15.90, 95% CI -22.77 to -9.03) and at 30 minutes later (MD -11.10, 95% CI -19.05 to -3.15).

Meta-Analysisn=5,710

12

Copper in depressive disorder: A systematic review and meta-analysis of observational studies

Ni M et al. • Psychiatry research (2018)

Weighted mean difference (WMD) with a 95% confidence interval (95%CI) was calculated using STATA 12.0.

Weighted mean difference (WMD) with a 95% confidence interval (95%CI) was calculated using STATA 12.0.
Subgroup analysis suggested that age had influence on the relationship between copper and depression.
No evidence of publication bias was observed.

Meta-Analysisn=1,487

13

Effects of Copper Supplementation on Blood Lipid Level: a Systematic Review and a Meta-Analysis

Asbaghi O et al. • Biological Trace Element Research (2021)

Copper supplementation may have favorable effects on lipid metabolism.

Meta-analysis of RCTs
Evaluated effects on lipid profile
Potential cardiovascular benefits

Meta-Analysisn=892

14

Trace elements and Alzheimer dementia in population-based studies: A bibliometric and meta-analysis

Li K et al. • Environmental pollution (Barking, Essex : 1987) (2023)

In a further meta-analysis, standardized mean differences (SMDs) of 13 elements were calculated to evaluate their altered in AD patients, including copper, iron, zinc, selenium, manganese, lead, al...

In a further meta-analysis, standardized mean differences (SMDs) of 13 elements were calculated to evaluate their altered in AD patients, including copper, iron, zinc, selenium, manganese, lead, aluminum, cadmium, chromium, arsenic, mercury, cobalt, and manganese.
We identified four trace elements-copper (serum), iron (plasma), zinc (hair), and selenium (plasma)-altered in AD patients, with SMDs of 0.37 (95% confidence interval [CI]: 0.10, 0.65), -0.68 (95% CI: -1.34, -0.02), -0.35 (95% CI: -0.62, -0.08), and -0.61 (95% CI: -0.97, -0.25), respectively.
Finally, we formed a database of various trace element levels in AD patients and healthy controls.

Meta-Analysisn=73

15

Sleep disorders in Wilson disease: a systematic review and meta-analysis

Xu J et al. • Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine (2020)

Our study indicates that sleep disorders are frequent in patients with WD.

We found that 54.1% of patients with WD experience sleep disorders and up to 7.65-fold higher odds compared to control patients.
Furthermore, objective sleep disruptions based on polysomnographic studies included prolonged sleep onset latency and REM sleep onset latency, reduced total sleep time and sleep efficiency, higher percentage of stage N1 sleep and lower percentage of stage N2 sleep were observed in patients with WD.
Our study indicates that sleep disorders are frequent in patients with WD.

Meta-Analysisn=501

16

Dietary Copper Intake and Bone Health: A Systematic Review and Meta-Analysis of Observational Studies

Gutiérrez-Guerra MA et al. • Calcified tissue international (2025)

This meta-analysis examined the effects of Copper.

Data were pooled via a generic inverse-variance random-effects model, with heterogeneity assessed by the Q test and I2 statistic.
Higher dietary copper intake is modestly associated with increased lumbar spine BMD, while evidence for hip BMD remains inconclusive, underscoring copper's potential role in osteoporosis prevention.
Further research warranted to confirm findings

Meta-Analysis

17

Zinc, copper, and selenium levels in vitiligo: a systematic review and meta-analysis

Anam K et al. • Scientific reports (2024)

This meta-analysis examined the effects of Copper.

Publication bias was not found for the studies analysed.
This study analyses the association of serum micronutrient levels and vitiligo among patients and controls from published research along with sub-group analysis specific to Asian populations using a meta-analysis.
Low serum levels of Zinc and copper and high selenium levels are associated with Vitiligo.

Meta-Analysisn=41

18

ATP7A-related copper transport disorders: A systematic review and definition of the clinical subtypes

De Feyter S et al. • Journal of inherited metabolic disease (2023)

Truncating mutations are frequently associated with CMD, in contrast with splice site and intronic mutations which are more prevalent in OHS.

Bony exostoses, radial head dislocations, herniations and dental abnormalities are specific for occipital horn syndrome (OHS) that may further present with developmental delay and connective tissue manifestations.
Intracranial tortuosity and bladder diverticula, both with high risk of complications, are common among all subtypes.
Low ceruloplasmin is a more sensitive and discriminating biomarker for ATP7A-related disorders than serum copper.

Systematic Reviewn=162

19

Surface water quality, public health, and ecological risks in Bangladesh-a systematic review and meta-analysis over the last two decades

Bilal H et al. • Environmental science and pollution research international (2023)

The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Mercury poses the greatest hazard with 90.91% of the samples falling into the highest risk category.
Mercury is followed by zinc 57.53% and copper 29.16% in terms of the dangers they pose to public health and the ecosystem.
Results show that a considerable percentage of the population is at risk, being exposed to contaminated water.

Meta-Analysis

20

Environmental toxic metal contaminants and risk of cardiovascular disease: systematic review and meta-analysis

Chowdhury R et al. • BMJ (Clinical research ed.) (2018)

Exposure to arsenic, lead, cadmium, and copper is associated with an increased risk of cardiovascular disease and coronary heart disease.

Exposure to arsenic, lead, cadmium, and copper is associated with an increased risk of cardiovascular disease and coronary heart disease.
Mercury is not associated with cardiovascular risk.
These findings reinforce the importance of environmental toxic metals in cardiovascular risk, beyond the roles of conventional behavioural risk factors.

Meta-Analysisn=348

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