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The Relationship Between Serum Copper and Overweight/Obesity: a Meta-analysis


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.

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  1. 1.

    Pereira-Santos M, Costa PR, Assis AM, Santos CA, Santos DB (2015) Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obesity reviews : an official journal of the. Int Assoc Study Obes 16:341–349. https://doi.org/10.1111/obr.12239

  2. 2.

    WHO (2018) Obesity and overweight. http://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed 11 September 2018

  3. 3.

    WHO Obesity. http://www.who.int/topics/obesity/en/. Accessed 11 September 2018

  4. 4.

    Withrow D, Alter DA (2011) The economic burden of obesity worldwide: a systematic review of the direct costs of obesity. Obes Rev 12:131–141. https://doi.org/10.1111/j.1467-789X.2009.00712.x

  5. 5.

    Tang L, Ye H, Hong Q, Chen F, Wang Q, Xu L, Bu S, Liu Q, Ye M, Wang DW, Mai Y, Duan S (2014) Meta-analyses between 18 candidate genetic markers and overweight/obesity. Diagn Pathol 9:56. https://doi.org/10.1186/1746-1596-9-56

  6. 6.

    Chin SH, Kahathuduwa CN, Binks M (2016) Physical activity and obesity: what we know and what we need to know. Obes Rev 17:1226–1244. https://doi.org/10.1111/obr.12460

  7. 7.

    Grundy SM (1998) Multifactorial causation of obesity: implications for prevention. Am J Clin Nutr 67:563s–572s. https://doi.org/10.1093/ajcn/67.3.563S

  8. 8.

    Mytton OT, Nnoaham K, Eyles H, Scarborough P, Ni Mhurchu C (2014) Systematic review and meta-analysis of the effect of increased vegetable and fruit consumption on body weight and energy intake. BMC Public Health 14:886. https://doi.org/10.1186/1471-2458-14-886

  9. 9.

    Cayir Y, Cayir A, Turan MI, Kurt N, Kara M, Laloglu E, Ciftel M, Yildirim A (2014) Antioxidant status in blood of obese children: the relation between trace elements, paraoxonase, and arylesterase values. Biol Trace Elem Res 160:155–160. https://doi.org/10.1007/s12011-014-0038-0

  10. 10.

    Azab SFA, Saleh SH, Elsaeed WF, Elshafie MA, Sherief LM, Esh AMH (2014) Serum trace elements in obese Egyptian children: a case-control study. Ital J Pediatr 40. https://doi.org/10.1186/1824-7288-40-20

  11. 11.

    Habib SA, Saad EA, Elsharkawy AA, Attia ZR (2015) Pro-inflammatory adipocytokines, oxidative stress, insulin, Zn and Cu: interrelations with obesity in Egyptian non-diabetic obese children and adolescents. Adv Med Sci 60:179–185. https://doi.org/10.1016/j.advms.2015.02.002

  12. 12.

    Dambal SS (2011) Relationship Of obesity with micronutrient status

  13. 13.

    Pereira TC, Campos MM, Bogo MR (2016) Copper toxicology, oxidative stress and inflammation using zebrafish as experimental model. J Appl Toxicol 36:876–885. https://doi.org/10.1002/jat.3303

  14. 14.

    Formigari A, Gregianin E, Irato P (2013) The effect of zinc and the role of p53 in copper-induced cellular stress responses. J Appl Toxicol 33:527–536. https://doi.org/10.1002/jat.2854

  15. 15.

    Yakinci C, Pac A, Kucukbay FZ, Tayfun M, Gul A (1997) Serum zinc, copper, and magnesium levels in obese children. Acta Paediatr Jpn 39:339–341

  16. 16.

    Cayir A, Doneray H, Kurt N, Orbak Z, Kaya A, Turan MI, Yildirim A (2014) Thyroid functions and trace elements in pediatric patients with exogenous obesity. Biol Trace Elem Res 157:95–100. https://doi.org/10.1007/s12011-013-9880-8

  17. 17.

    Lima SC, Arrais RF, Sales CH, Almeida MG, de Sena KC, Oliveira VT, de Andrade AS, Pedrosa LF (2006) Assessment of copper and lipid profile in obese children and adolescents. Biol Trace Elem Res 114:19–29. https://doi.org/10.1385/bter:114:1:19

  18. 18.

    Chen Z, Tian X, Ying X, Pan L, Li C (2015) Results of serum minerals detection in obese children. Zhejiang Prev Med:1247–1250

  19. 19.

    Gao R, Chen J, Zhou X (2011) The effect of serum calcium, iron, zinc and copper on lipid metabolism in simple obesity high school students. Chin J Public Health:494–495

  20. 20.

    Zhang H, Li Z, Huang J (2011) Relationship between simple obesity in children and trace elements in serum. Lab Med Clin:716–717. https://doi.org/10.3969/j.issn.1672-9455.2011.06.039

  21. 21.

    Yerlikaya FH, Toker A, Aribas A (2013) Serum trace elements in obese women with or without diabetes. Indian J Med Res 137:339–345

  22. 22.

    Suliburska J, Cofta S, Gajewska E, Kalmus G, Sobieska M, Samborski W, Krejpcio Z, Drzymala-Czyz S, Bogdanski P (2013) The evaluation of selected serum mineral concentrations and their association with insulin resistance in obese adolescents. Eur Rev Med Pharmacol Sci 17:2396–2400

  23. 23.

    Perrone L, Gialanella G, Moro R, Feng SL, Boccia E, Palombo G, Carbone MT, Di Toro R (1998) Zinc, copper and iron in obese children and adolescents. Nutr Res 18:183–189. https://doi.org/10.1016/s0271-5317(98)00011-6

  24. 24.

    Tascilar ME, Ozgen IT, Abaci A, Serdar M, Aykut O (2011) Trace elements in obese Turkish children. Biol Trace Elem Res 143:188–195. https://doi.org/10.1007/s12011-010-8878-8

  25. 25.

    Qi K, Qian Y, Wu K, Zheng D (1997) Study on the correlation of plasma lipid, apolipoproteins and serum Zn, Cu, Fe in simple obese children. Chin J Child Health Care:74–77

  26. 26.

    Peng R, Liao J, Rao S (2015) Study on blood trace element levels in infants and young children under different nutritional status. Med Recapitulate:164–166. https://doi.org/10.3969/j.issn.1006-2084.2015.01.068

  27. 27.

    Lin S (2001) Changes and significance of serum zinc, copper, iron and calcium in children with simple obesity, Guangdong Trace Elements Science, pp 40–42. https://doi.org/10.3969/j.issn.1006-446X.2001.08.011

  28. 28.

    Alasfar F, Ben-Nakhi M, Khoursheed M, Kehinde EO, Alsaleh M (2011) Selenium is significantly depleted among morbidly obese female patients seeking bariatric surgery. Obes Surg 21:1710–1713. https://doi.org/10.1007/s11695-011-0458-2

  29. 29.

    Ghayour-Mobarhan M, Taylor A, New SA, Lamb DJ, Ferns GA (2005) Determinants of serum copper, zinc and selenium in healthy subjects. Ann Clin Biochem 42:364–375. https://doi.org/10.1258/0004563054889990

  30. 30.

    Choi MK, Lee SH, Kim SK (2014) Relationship between adiposity-related biomarkers and calcium, magnesium, iron, copper, and zinc in young adult men with different degrees of obesity. Trace Elem Electrolytes 31:148–155. https://doi.org/10.5414/tex01341

  31. 31.

    Gu Y, Chen W, Qi Z, Chen Y (2016) Investigating relationship between plasma zinc and copper level and elderly obesity. World Latest Med Inf 16:4–6

  32. 32.

    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269, w264

  33. 33.

    Wells GA SB OCD, J Peterson, V Welch, M Losos, et al. (2011) The Newcastle-Ottawa Scale (NOS) for assessing the quality ofnonrandomised studies in meta-analyses. doi:wwwohrica/programs/ clinical_epidemiology/oxfordasp

  34. 34.

    Rostom A DC, Cranney A, et al. (2004) Celiac disease. https://www.ncbi.nlm.nih.gov/books/NBK35156/. Accessed 20 March 2019

  35. 35.

    Patsopoulos NA, Evangelou E, Ioannidis JP (2008) Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol 37:1148–1157. https://doi.org/10.1093/ije/dyn065

  36. 36.

    Tobias. A (1999) Assessing the influence of a single study in the meta-anyalysis estimate. Stata Tech Bull 8:7526–7529

  37. 37.

    Marseglia L, Manti S, D’Angelo G, Nicotera A, Parisi E, Di Rosa G, Gitto E, Arrigo T (2014) Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci 16:378–400. https://doi.org/10.3390/ijms16010378

  38. 38.

    Sfar S, Boussoffara R, Sfar MT, Kerkeni A (2013) Antioxidant enzymes activities in obese Tunisian children. Nutr J 12:18. https://doi.org/10.1186/1475-2891-12-18

  39. 39.

    Roussel AM (2008) Oxidative stress and antioxidant trace elements in obesity. In: Collery P, Maymard I, Theophanides T, Khassanova L, Collery T (eds) Metal ions in biology and medicine, vol 10, vol 10. Metal ions in biology and medicine, pp 758–763

  40. 40.

    Mangge H, Summers K, Almer G, Prassl R, Weghuber D, Schnedl W, Fuchs D (2013) Antioxidant food supplements and obesity-related inflammation. Curr Med Chem 20:2330–2337

  41. 41.

    Song X, Li B, Li Z, Wang J, Zhang D (2017) High serum copper level is associated with an increased risk of preeclampsia in Asians: a meta-analysis. Nutr Res 39:14–24. https://doi.org/10.1016/j.nutres.2017.01.004

  42. 42.

    Karkonen A, Kuchitsu K (2015) Reactive oxygen species in cell wall metabolism and development in plants. Phytochemistry 112:22–32. https://doi.org/10.1016/j.phytochem.2014.09.016

  43. 43.

    Kim OY, Shin MJ, Moon J, Chung JH (2011) Plasma ceruloplasmin as a biomarker for obesity: a proteomic approach. Clin Biochem 44:351–356. https://doi.org/10.1016/j.clinbiochem.2011.01.014

  44. 44.

    Fox PL, Mukhopadhyay C, Ehrenwald E (1995) Structure, oxidant activity, and cardiovascular mechanisms of human ceruloplasmin. Life Sci 56:1749–1758

  45. 45.

    Arner E, Forrest AR, Ehrlund A, Mejhert N, Itoh M, Kawaji H, Lassmann T, Laurencikiene J, Ryden M, Arner P (2014) Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells. PLoS One 9:e80274. https://doi.org/10.1371/journal.pone.0080274

  46. 46.

    Ranjkesh F, Jaliseh HK, Abutorabi S (2011) Monitoring the copper content of serum and urine in pregnancies complicated by preeclampsia. Biol Trace Elem Res 144:58–62. https://doi.org/10.1007/s12011-011-9026-9

  47. 47.

    Guzik TJ, Korbut R, Adamek-Guzik T (2003) Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol 54:469–487

  48. 48.

    Oestreicher P, Cousins RJ (1985) Copper and zinc absorption in the rat: mechanism of mutual antagonism. J Nutr 115:159–166. https://doi.org/10.1093/jn/115.2.159

  49. 49.

    Gu K, Xiang W, Zhang Y, Sun K, Jiang X (2018) The association between serum zinc level and overweight/obesity: a meta-analysis. Eur J Nutr. https://doi.org/10.1007/s00394-018-1876-x

  50. 50.

    Olusi S, Al-Awadhi A, Abiaka C, Abraham M, George S (2003) Serum copper levels and not zinc are positively associated with serum leptin concentrations in the healthy adult population. Biol Trace Elem Res 91:137–144. https://doi.org/10.1385/bter:91:2:137

  51. 51.

    Licinio J, Caglayan S, Ozata M, Yildiz BO, de Miranda PB, O’Kirwan F, Whitby R, Liang L, Cohen P, Bhasin S, Krauss RM, Veldhuis JD, Wagner AJ, DePaoli AM, McCann SM, Wong ML (2004) Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci U S A 101:4531–4536. https://doi.org/10.1073/pnas.0308767101

  52. 52.

    Sainz N, Barrenetxe J, Moreno-Aliaga MJ, Martinez JA (2015) Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metab Clin Exp 64:35–46. https://doi.org/10.1016/j.metabol.2014.10.015

  53. 53.

    Ramirez S, Claret M (2015) Hypothalamic ER stress: a bridge between leptin resistance and obesity. FEBS Lett 589:1678–1687. https://doi.org/10.1016/j.febslet.2015.04.025

  54. 54.

    Myers MG Jr, Leibel RL, Seeley RJ, Schwartz MW (2010) Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol Metab 21:643–651. https://doi.org/10.1016/j.tem.2010.08.002

  55. 55.

    Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, Hayashi T, Inoue G, Hosoda K, Kojima M, Kangawa K, Nakao K (2001) Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 50:227–232

  56. 56.

    Wang X, Zhang P, Ning Y, Yang L, Yu F, Guo X (2018) Serum and hair zinc levels in patients with endemic osteochondropathy in China: a meta-analysis. Biol Trace Elem Res 181:227–233. https://doi.org/10.1007/s12011-017-1054-7

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This work was funded by the Natural Science Foundation of Shandong Province (grant number ZR2015HM029) and Qingdao Science and Technology Bureau (grant number 186179nsh).

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Correspondence to Xiubo Jiang.

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Influence analysis of an individual study on the pooled estimate for studies on the association between Cu level and obesity risk in children (PNG 76 kb)


Influence analysis of an individual study on the pooled estimate for studies on the association between Cu level and obesity risk in adults (PNG 39 kb)


Funnel plot for the analysis of Cu level and obese children (PNG 84 kb)


Funnel plot for the analysis of Cu level and obese adults (PNG 86 kb)


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Gu, K., Li, X., Xiang, W. et al. The Relationship Between Serum Copper and Overweight/Obesity: a Meta-analysis. Biol Trace Elem Res 194, 336–347 (2020). https://doi.org/10.1007/s12011-019-01803-6

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  • Copper
  • Cu
  • Overweight
  • Obesity
  • Meta-analysis