Copper level
Most serum copper is carried by ceruloplasmin. A US report cites a normal adult range of about 64 to 159 µg/dL, and a European guideline acts below 51. Inflammation, oral contraceptives and pregnancy raise the result without more copper in the body. Higher levels were linked to more strokes and cardiovascular deaths in pooled cohorts.
- Status
- A blood test ordered by a clinician. FDA classifies copper test systems, which measure copper in plasma, serum and urine, as class I devices [1]. The related ceruloplasmin immunological test system is a class II device [2].
- Measures
- The total concentration of copper in serum or plasma, most of which is carried by the protein ceruloplasmin [3][4].
- Also called
- serum copper, plasma copper, copper serum, copper plasma, copper blood test, total copper, Cu, cupremia
- Tested for
- copper deficiency, anemia workup, low white blood cell count, nerve symptoms after weight loss surgery, monitoring long-term zinc use, Wilson disease workup, copper excess
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Linked in research3
- ModerateLinked to more strokes and cardiovascular deaths at higher serum copper in two meta-analyses of cohorts, while a genetic study pointed the other way for heart disease.
- ModerateLinked to more deaths from any cause at higher serum copper, about 22% more per 20 µg/dL across pooled cohort studies.
- LimitedCase reports: people with very low serum copper had anemia, low neutrophil counts and nerve damage, most often after stomach or weight loss surgery.
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in µg/dL. Also reported in µmol/L. Where sources differ, each is shown.
Institute of Medicine Dietary Reference Intakes report, 2001
Adults, as the normal range the report cites for serum copper · [3], [4]
| Range | What the source calls it |
|---|---|
| below 63.7 µg/dL | No name given |
| 63.7 to 159.2 µg/dL | "normal range" |
| above 159.2 µg/dL | No name given |
Printed as 10 to 25 µmol/L and converted here to µg/dL by dividing by 0.157. That factor is the one a European nutrition guideline prints for copper, 1 µg/dL to 0.157 µmol/L [4]. The report takes the range from a 1984 reference table and gives one range for both sexes. Beside it the report prints a ceruloplasmin range of 180 to 400 mg/L, which is a different test and is not placed against a result typed here. The report calls serum copper a reliable indicator of copper deficiency that falls to very low concentrations in deficient people, and states that it does not reflect dietary intake except when intake is low. It adds that serum copper and ceruloplasmin increase during pregnancy and with a number of diseases, which can mask a deficiency [3].
ESPEN micronutrient guideline, 2022, whatever the C-reactive protein
Adults under medical nutrition care, with or without a raised C-reactive protein · [4]
| Range | What the source calls it |
|---|---|
| below 51 µg/dL | No name given |
| 51 or above µg/dL | No name given |
Printed as below 8 µmol/L and converted here to µg/dL by dividing by 0.157, the guideline's own factor. At that level the guideline calls for copper repletion whether or not C-reactive protein is elevated. It gives the band no name, and it gives no cut point for a high result, so this block does not classify high results. The guideline was written for people receiving enteral or parenteral nutrition or followed after surgery such as bariatric procedures, and it asks for C-reactive protein to be measured with every plasma copper [4].
ESPEN micronutrient guideline, 2022, C-reactive protein above 20 mg/L
Adults under medical nutrition care whose C-reactive protein is above 20 mg/L · [4]
| Range | What the source calls it |
|---|---|
| below 51 µg/dL | No name given |
| 51 to 76.3 µg/dL | "deficiency is likely" |
| 76.4 or above µg/dL | No name given |
Printed as below 8 µmol/L and below 12 µmol/L and converted here to µg/dL by dividing by 0.157. The middle band applies only when C-reactive protein is above 20 mg/L. The guideline's reasoning is that plasma copper rises with inflammation because ceruloplasmin is a positive acute phase reactant, so a copper result that looks normal beside an elevated C-reactive protein would suggest depletion. It adds that a low ceruloplasmin confirms deficiency where the picture is uncertain. It gives no cut point for a high result [4].
Lin and colleagues, US pediatric reference intervals, 2012, children under 10.3 years
Children aged 6 months to under 10.3 years · [5]
| Range | What the source calls it |
|---|---|
| below 75 µg/dL | No name given |
| 75 to 153 µg/dL | "reference interval" |
| above 153 µg/dL | No name given |
The central 95% of results in 2,115 clinically healthy US children aged 6 months to 18 years, 85.4% of them Caucasian, measured by inductively coupled plasma mass spectrometry. The study found copper intervals differed by age and found no significant effect of sex or fasting [5]. An interval of this kind describes where most children in the study fell. It is not a threshold for deficiency or excess.
Lin and colleagues, US pediatric reference intervals, 2012, children 10.3 to 12.5 years
Children aged 10.3 to 12.5 years · [5]
| Range | What the source calls it |
|---|---|
| below 64 µg/dL | No name given |
| 64 to 132 µg/dL | "reference interval" |
| above 132 µg/dL | No name given |
From the same study of 2,115 US children, with the same method [5].
Lin and colleagues, US pediatric reference intervals, 2012, children over 12.5 years
Children and adolescents older than 12.5 years, up to 18 · [5]
| Range | What the source calls it |
|---|---|
| below 57 µg/dL | No name given |
| 57 to 129 µg/dL | "reference interval" |
| above 129 µg/dL | No name given |
From the same study of 2,115 US children, with the same method. The lower limit for this age group sits below the 63.7 µg/dL that a US report cites as the lower end of the normal range [5][3].
Liu and colleagues, Chinese national survey, 2017, pregnancy
Pregnant women at any stage of pregnancy · [6]
| Range | What the source calls it |
|---|---|
| below 107 µg/dL | No name given |
| 107 to 362.4 µg/dL | "reference values" |
| above 362.4 µg/dL | No name given |
The 2.5th to 97.5th percentiles in 1,400 pregnant women, mean age 27, in the China Nutrition and Health Survey of 2010 to 2012, measured by high-resolution inductively coupled plasma mass spectrometry. The median was 195.5 µg/dL. By trimester the medians were 157.5, 198.6 and 208.2 µg/dL, and the intervals were 89.7 to 366.0, 122.6 to 343.5 and 121.0 to 375.0 µg/dL. Its upper limit is more than twice the upper end of the adult range cited on this page, and a US report states that serum copper and ceruloplasmin increase during pregnancy [3]. The values come from one country and describe where most women in the survey fell [6].
How it compares with the reference method
Mixed results2
Week to week variation in one person
One study found serum copper varied 7.8% from week to week within the same person over 10 weeks.
The numbers and sources
- Compared with
- The same person's results on 10 weekly draws
- Effect
- Within-person variation was 7.8% (95% CI 7.3 to 8.3), similar in men and women. Mean copper differed between men and women by 2.0 µmol/L (14.1%). The authors describe marked individuality for copper and conclude that population reference limits are of limited use for following one person over time [14].
- Population
- 68 adults in Turkey whom the study classed as healthy, 36 women and 32 men, sampled weekly for 10 weeks and measured by inductively coupled plasma mass spectrometry [14].
- Sources
- [14]
- Caveats
- One laboratory and 68 people. The study states no threshold for agreement, so the result is given as numbers only [14].
Ceruloplasmin as a test for Wilson disease
One study found a ceruloplasmin below 20 mg/dL was a true Wilson disease result 48% of the time, against 100% below 14 mg/dL.
The numbers and sources
- Compared with
- ATP7B genotype by DNA sequencing
- Effect
- Ceruloplasmin is a separate blood test, reported in mg/dL or g/L, and its results are not placed against the copper ranges on this page. In a study that confirmed every diagnosis by sequencing the Wilson disease gene, ceruloplasmin below 0.20 g/L (20 mg/dL) had a positive predictive value of 48.3% and a negative predictive value of 98.7%. Below 0.14 g/L (14 mg/dL) the values were 100% and 97.1%, and below 0.10 g/L (10 mg/dL) they were 100% and 91.9%. Forty of 690 people without the disease had ceruloplasmin below 0.20 g/L, and none had a value below 0.14 g/L [15]. A US report cites a normal ceruloplasmin range of 180 to 400 mg/L, which is 18 to 40 mg/dL [3].
- Population
- 57 people with Wilson disease, 71 family members, 25 people with suspected disease and 690 people without it, in Hong Kong [15].
- Sources
- [15], [3]
- Caveats
- One center and one nephelometric assay. The authors suggest that laboratories set their own decision thresholds from local populations [15]. Serum copper itself was not the test evaluated.
Did not match the reference method3
Inflammation and infection
Limited evidence: serum copper rises with inflammation because ceruloplasmin is an acute phase protein, so a result inside the range can hide low body copper.
The numbers and sources
- Compared with
- Copper status in the same person without inflammation
- Effect
- A US report states that ceruloplasmin is an acute phase protein that increases markedly with liver disease, malignancy, inflammatory diseases, myocardial infarction and a variety of infectious diseases, and that with any of these conditions copper deficiency might not be diagnosed from serum copper or ceruloplasmin [3]. A European guideline states that, unlike most micronutrients, plasma copper increases with an inflammatory response, and sets a higher cut point for likely deficiency when C-reactive protein is above 20 mg/L [4]. In 2,217 blood samples from a hospital laboratory, plasma copper and vitamin E were the only measured micronutrients that did not fall as C-reactive protein rose [12].
- Population
- 2,217 samples from 1,303 patients screened for micronutrients in one UK laboratory between 2001 and 2011 [12].
- Sources
- [3], [4], [12]
- Caveats
- The laboratory study's abstract does not report by how much copper rose. The two official sources state the direction of the effect and do not give a correction factor [3][4].
Oral contraceptives and estrogen
One German survey found serum copper 34% to 55% higher in women using oral contraceptives, depending on the progestin in the pill.
The numbers and sources
- Compared with
- Serum copper in women in the same survey not using oral contraceptives
- Effect
- Among women aged 18 to 44 in a national survey, use of oral contraceptives was associated with higher serum copper for every type of pill. The increase was 55% (95% CI 37 to 76) with antiandrogen progestins, 46% (36 to 56) with desogestrel, 42% (29 to 57) with norethisterone or lynestrenol and 34% (24 to 45) with levonorgestrel. Copper varied more by progestin than by estrogen content [13]. A US report states that ceruloplasmin increases with oral contraceptive use [3].
- Population
- 610 nonpregnant, nonlactating women aged 18 to 44 in West Germany, surveyed in 1987 to 1988 [13].
- Sources
- [13], [3]
- Caveats
- Cross-sectional, with pills in use in the 1980s. The published adult range cited on this page was not set separately for women using hormonal contraception [3].
Pregnancy
One Chinese survey found median serum copper rose from 157.5 µg/dL in the first trimester to 208.2 in the third, above the adult range a US report cites.
The numbers and sources
- Compared with
- Results in the first trimester of the same survey, and the adult range of 10 to 25 µmol/L cited by a US report
- Effect
- In pregnant women in a national survey, median serum copper was 157.5 µg/dL in the first trimester, 198.6 in the second and 208.2 in the third, and the central 95% of all results ran from 107.0 to 362.4 µg/dL [6]. The adult range a US report cites tops out at 25 µmol/L, about 159 µg/dL, and the same report states that serum copper and ceruloplasmin increase during pregnancy, so that a deficiency could be masked [3].
- Population
- 1,400 pregnant women in the China Nutrition and Health Survey of 2010 to 2012 [6].
- Sources
- [6], [3]
- Caveats
- A cross-sectional survey, so different women were sampled in each trimester. The survey did not measure ceruloplasmin [6].
What studies tie it to
Linked in research3
Stroke, heart attack and cardiovascular death at higher levels
Linked to more strokes and cardiovascular deaths at higher serum copper in two meta-analyses of cohorts, while a genetic study pointed the other way for heart disease.
The numbers and sources
- Effect
- In a meta-analysis of 17 cohort studies, higher circulating copper went with more stroke (OR 1.52, 95% CI 1.30 to 1.78), coronary artery disease death (RR 2.77, 1.82 to 4.19) and cardiovascular death (RR 1.79, 1.52 to 2.11), and not with acute myocardial infarction (RR 2.01, 0.63 to 6.47). Per 20 µg/dL higher copper, the odds ratio for stroke was 1.23 (1.14 to 1.33) and the hazard ratio for cardiovascular death was 1.28 (1.07 to 1.53) [7]. A second meta-analysis, comparing the highest with the lowest category, found pooled odds ratios of 1.49 (1.22 to 1.82) for stroke, 1.31 (1.17 to 1.46) for myocardial infarction and 1.60 (1.39 to 1.86) for cardiovascular death [8]. A Mendelian randomization study found the reverse direction: genetically predicted copper was associated with less ischemic heart disease (OR 0.94, 95% CI 0.90 to 0.98) [9].
- Population
- 47,813 people in 17 cohort studies [7]. 41,322 participants in 16 observational studies [8]. Up to 76,014 cases of ischemic heart disease and 264,785 controls [9].
- Sources
- [7], [8], [9]
- Caveats
- Observational, and the two meta-analyses share studies and disagree on myocardial infarction. Serum copper rises with inflammation because ceruloplasmin is an acute phase protein [3][4], so a higher level may mark inflammation already present. The genetic study used variants tied to copper in red blood cells, not serum copper, and its authors call for further investigation [9]. No trial that lowered serum copper and counted cardiovascular events was located.
Death from any cause at higher levels
Linked to more deaths from any cause at higher serum copper, about 22% more per 20 µg/dL across pooled cohort studies.
The numbers and sources
- Effect
- In a meta-analysis of cohort studies, elevated circulating copper went with more deaths from any cause (RR 1.56, 95% CI 1.35 to 1.79), and each 20 µg/dL higher copper had a hazard ratio of 1.22 (1.04 to 1.44). The authors rated the certainty of this evidence as moderate [7]. In US adults from the 2011 to 2016 national survey, those in the top third of serum copper (19.84 µmol/L or above, about 126 µg/dL) had more deaths from any cause than those in the bottom third (below 16.31 µmol/L, about 104 µg/dL), with a hazard ratio of 2.84 (1.66 to 4.87) [10].
- Population
- 47,813 people in 17 cohort studies [7]. 5,412 US adults followed for a mean of 5.85 years, with 356 deaths [10].
- Sources
- [7], [10]
- Caveats
- Observational. The US cohort had 356 deaths and wide intervals, and its authors state that causal relationships require further investigation [10]. The abstract prints the cut points for the thirds as mol/L, read here as µmol/L, and the µg/dL figures are converted with the factor on this page. Inflammation and illness raise serum copper [3], which may account for part of the link.
Anemia, low white cell counts and nerve damage at very low levels
Case reports: people with very low serum copper had anemia, low neutrophil counts and nerve damage, most often after stomach or weight loss surgery.
The numbers and sources
- Effect
- A review of records from 1970 to 2005 at one US center identified 40 patients with copper deficiency and blood abnormalities. Ten (25%) had undergone bariatric surgery and 14 (35%) other surgery on the gastrointestinal tract, most often gastric resection. In 12 no cause was identified. Anemia and neutropenia were the most common blood findings, and the majority also had neurologic findings, most commonly myeloneuropathy [11]. A US report describes six patients fed a low-copper enteral diet for 12 to 66 months whose serum copper ranged from 0.9 to 7.2 µmol/L, about 6 to 46 µg/dL. Two had neutropenia, one had anemia and some had reduced bone density, and neutrophil counts normalized after copper was given [3].
- Population
- 40 patients at one US center [11]. Six patients aged 4 to 24 on long-term enteral feeding [3].
- Sources
- [11], [3]
- Caveats
- Case series with no comparison group, drawn from people already found to be deficient. The authors of the review note that copper deficiency is frequently misdiagnosed and may resemble a myelodysplastic syndrome [11]. The µg/dL figures are converted here with the factor on this page.
Sources
- US Food and Drug Administration. 21 CFR 862.1190, Copper test system. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-862.1190
- US Food and Drug Administration. 21 CFR 866.5210, Ceruloplasmin immunological test system. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-866.5210
- Institute of Medicine, Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academies Press. 2001. https://doi.org/10.17226/10026
- Berger MM, Shenkin A, Schweinlin A, et al. ESPEN micronutrient guideline. Clinical Nutrition. 2022. https://doi.org/10.1016/j.clnu.2022.02.015
- Lin CN, Wilson A, Church BB, et al. Pediatric reference intervals for serum copper and zinc. Clinica Chimica Acta. 2012. https://doi.org/10.1016/j.cca.2011.12.005
- Liu X, Zhang Y, Piao J, et al. Reference Values of 14 Serum Trace Elements for Pregnant Chinese Women: A Cross-Sectional Study in the China Nutrition and Health Survey 2010-2012. Nutrients. 2017. https://doi.org/10.3390/nu9030309
- Zhao H, Mei K, Hu Q, et al. Circulating copper levels and the risk of cardio-cerebrovascular diseases and cardiovascular and all-cause mortality: A systematic review and meta-analysis of longitudinal studies. Environmental Pollution. 2024. https://doi.org/10.1016/j.envpol.2023.122711
- Muñoz-Bravo C, Soler-Iborte E, Lozano-Lorca M, et al. Serum copper levels and risk of major adverse cardiovascular events: a systematic review and meta-analysis. Frontiers in Cardiovascular Medicine. 2023. https://doi.org/10.3389/fcvm.2023.1217748
- Kodali HP, Pavilonis BT, Schooling CM. Effects of copper and zinc on ischemic heart disease and myocardial infarction: a Mendelian randomization study. The American Journal of Clinical Nutrition. 2018. https://doi.org/10.1093/ajcn/nqy129
- Li X, Ling J, Hu Q, et al. Association of serum copper (Cu) with cardiovascular mortality and all-cause mortality in a general population: a prospective cohort study. BMC Public Health. 2023. https://doi.org/10.1186/s12889-023-17018-3
- Halfdanarson TR, Kumar N, Li CY, et al. Hematological manifestations of copper deficiency: a retrospective review. European Journal of Haematology. 2008. https://doi.org/10.1111/j.1600-0609.2008.01050.x
- Duncan A, Talwar D, McMillan DC, et al. Quantitative data on the magnitude of the systemic inflammatory response and its effect on micronutrient status based on plasma measurements. The American Journal of Clinical Nutrition. 2012. https://doi.org/10.3945/ajcn.111.023812
- Berg G, Kohlmeier L, Brenner H. Effect of oral contraceptive progestins on serum copper concentration. European Journal of Clinical Nutrition. 1998. https://doi.org/10.1038/sj.ejcn.1600631
- Coşkun A, Carobene A, Aarsand AK, et al. Within- and between-subject biological variation data for serum zinc, copper and selenium obtained from 68 apparently healthy Turkish subjects. Clinical Chemistry and Laboratory Medicine. 2022. https://doi.org/10.1515/cclm-2021-0886
- Mak CM, Lam CW, Tam S. Diagnostic Accuracy of Serum Ceruloplasmin in Wilson Disease: Determination of Sensitivity and Specificity by ROC Curve Analysis among ATP7B-Genotyped Subjects. Clinical Chemistry. 2008. https://doi.org/10.1373/clinchem.2008.103432