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The Correlation Between Serum Copper and Non-alcoholic Fatty Liver Disease in American Adults: an Analysis Based on NHANES 2011 to 2016

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Abstract

Copper functions as an essential micronutrient influencing diverse metabolic processes in mammals, encompassing oxidative stress responses, lipid metabolism, and participation in enzymatic reactions. However, the impact of serum copper on non-alcoholic fatty liver disease (NAFLD) remains controversial. Our aim was to explore the precise correlation between serum copper and NAFLD in a large-scale population-based study. A total of 1377 participants from the National Health and Nutrition Examination Survey (NHANES) 2011–2016 were included in our study. The diagnosis of NAFLD and its progress to advanced liver fibrosis were based on serological indexes. One-way ANOVA, Kruskal–Wallis H test, and Chi-square test were used to access variations between quartiles groups of serum copper. We conducted multivariate-adjusted logistic regression models and subgroup analyses to investigate the association between serum copper and NAFLD, along with several metabolic diseases. Among the 1377 participants, 661 were diagnosed with NAFLD, and 141 of whom were classified into advanced liver fibrosis. Higher serum copper levels (≥ 21.00 μmol/L) were associated with an increased incidence of NAFLD (odds ratio (OR) = 2.07 (1.38–3.10), p < 0.001), as well as advanced liver fibrosis (OR = 2.40 (1.17–5.19), p = 0.025). Moreover, serum copper exhibited a positive correlation with hypertension, overweight, and abdominal obesity, all of which have been identified as risk factors of NAFLD. Additionally, female participants, under the age of 60, and with a higher body mass index (BMI) (> 24.9 kg/m2) emerged as the most vulnerable subgroup concerning the relationship between serum copper and NAFLD. In the U.S. population, a notable association has been identified, linking elevated serum copper to an increased susceptibility for both the onset and progression of NAFLD, along with several metabolic disorders associated with NAFLD. The adverse effects of excess copper warrant attention in the context of public health considerations.

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Data Availability

The data that supports the study’s conclusions is available upon request from the authors. The data used in this study are from a public database at https://www.cdc.gov/nchs/nhanes/index.htm,which can be accessed by everyone through the links provided in the paper.

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Acknowledgements

We appreciate the NHAENS 2011-2016 staff and participants’ donation, data collection, and data sharing efforts.

Funding

The National Natural Science Foundation of China (No. 82172983) provided research funding for this study.

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  1. Lurao Li and Yun Yi contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Zhong Nan Hospital of Wuhan University, Wuhan, China

    Lurao Li, Yun Yi, **awen Shu, Jianghui Li, Hui Kang & Ying Chang

  2. Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China

    Lurao Li, Yun Yi, **awen Shu, Jianghui Li, Hui Kang & Ying Chang

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  1. Lurao Li
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Contributions

LRL and YY: article conception and design. LRL, HK, XWS and JHL: data collection, data management, and formal statistical analysis. LRL and YY: manuscript writing. YC: manuscript revising. All authors involved in writing and approved the final manuscript.

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Correspondence to Ying Chang.

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The NCHS Ethics Review Broad investigated and authorized the human subject’s research. Subjects provided written informed consent to participate in this investigation.

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Statement of Significance

1. High serum copper levels are associated with NAFLD and its progression to advanced liver fibrosis in the US population, as detected by serological non-invasive tests.

2. Overweight, abdominal obesity, and hypertension are linked with NAFLD, and all of these parameters are strongly correlated with serum copper levels.

3. We found that some individuals are more susceptible to the adverse effects of elevated serum copper concentrations.

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Li, L., Yi, Y., Shu, X. et al. The Correlation Between Serum Copper and Non-alcoholic Fatty Liver Disease in American Adults: an Analysis Based on NHANES 2011 to 2016. Biol Trace Elem Res (2024). https://doi.org/10.1007/s12011-023-04029-9

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