A study on the correlation between serum levels of 7 mineral nutrients and the risk of non-alcoholic fatty liver disease in patients with metabolic syndrome

Abstract

Abstract: Objective To investigate the correlation between seven serum minerals (calcium, iron, phosphorus, potassium, sodium, selenium, manganese) and the risk of non-alcoholic fatty liver disease (NAFLD) in patients with metabolic syndrome (MS). Methods By analyzing the laboratory data of the NHANES database from 2017 to 2018, the variables such as age, gender, race/nationality, marital status, body mass index, smoking status, drinking status, education level, intensity of physical activity, diabetes history and cardiovascular history were included in the model. The Spearman correlation analysis was used to evaluate the cross correlation between biomarkers, and Bayesian kernel machine regression (BKMR) model was used to fit the association between serum minerals and the risk of NAFLD. Results Among the 1661 MS patients included, NAFLD patients were found to have the higher serum selenium and manganese concentrations and the lower serum phosphorus concentrations. The results of the BKMR model showed a positive linear relationship between mineral mixed serum concentration and the risk of NAFLD prevalence. The increase in selenium concentration of a single mineral in the mixture is significantly positively correlated with the risk of NAFLD. When the concentration of other mineral concentrations is fixed, the IQR of serum selenium concentration increases from 2.25 μmol/L to 2.64 μmol/L, and the correlation with the proportion of increased risk of NAFLD is 19.3% (95% CI: 10%~27.5%), 19.1% (95% CI: 11.2%~25.8%), and 17.8% (95% CI: 8.9%~26.3%), respectively. In addition, the research suggests that there may be interactions among selenium, potassium, and phosphorus. Conclusion There is a positive linear relationship between the mixed serum concentration of minerals and the risk of NAFLD, with an increase in serum selenium concentration being significantly positively correlated with the risk of NAFLD.

Key words: Metabolic syndrome, Non-alcoholic fatty liver, Serum, Mineral, BKMR model

CHEN Xiao-yan, SUN Pei-qi, YUAN Yi-fu, CAO Qin, JIANG Yuan-ye. A study on the correlation between serum levels of 7 mineral nutrients and the risk of non-alcoholic fatty liver disease in patients with metabolic syndrome[J]. Chinese Hepatolgy, 2025, 30(5): 659-665.

References

[1] Alberti K G, Zimmet P, Shaw J,et al.The metabolic syndrome--a new worldwide definition[J].Lancet,2005,366(9491):1059-1062.
[2] Sun H,Saeedi P,Karuranga S,et al. IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045[J].Diabetes Res Clin Pract, 2022,183:109119.
[3] Saklayen M.G.The global epidemic of the metabolic syndrome[J]. Curr Hypertens Rep, 2018,20(2):12.
[4] Singh S, Allen A M, Wang Z, et al.Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies[J]. Clin Gastroenterol Hepatol,2015,13(4):643-e40.
[5] Vanni E, Marengo A, Mezzabotta L,et al.Systemic complications of nonalcoholic fatty liver disease: when the liver is not an innocent bystander[J].Semin Liver Dis,2015,35(3):236-249.
[6] Adams L A, Waters O R, Knuiman M W,et al. NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven-year follow-up study[J].Am J Gastroenterol,2009,104(4):861-867.
[7] Zelber-Sagi S, Nitzan-Kaluski D, Halpern Z,et al.Prevalence of primary non-alcoholic fatty liver disease in a population-based study and its association with biochemical and anthropometric measures[J].Liver Int,2006,26(7):856-863.
[8] Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R,et al.Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study[J]. Hepatology,2008,48(6):1791-1798.
[9] Eshraghian A, Nikeghbalian S, Geramizadeh B,et al.Serum magnesium concentration is independently associated with non-alcoholic fatty liver and non-alcoholic steatohepatitis.[J]. United European Gastroenterol J,2018,6(1):97-103.
[10] Contempré B, Duale N L, Dumont J E,et al.Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population.[J]. Clin Endocrinol (Oxf),1992,36(6):579-583.
[11] Chen L, Fan Z, Sun X,et al.Diet-derived antioxidants and nonalcoholic fatty liver disease: a Mendelian randomization study[J].Hepatol Int,2023,17(2):326-338.
[12] Yuan D, Zhan X A, Wang Y X. Effect of selenium sources on the expression of cellular glutathione peroxidase and cytoplasmic thioredoxin reductase in the liver and kidney of broiler breeders and their offspring.[J]. Poult Sci,2012,91(4):936-942.
[13] Ju W, Ji M, Li X,et al.Relationship between higher serum selenium level and adverse blood lipid profile[J].Clin Nutr,2018,37(5):1512-1517.
[14] Wang X, Seo Y A, Park S K.Serum selenium and non-alcoholic fatty liver disease (NAFLD) in U.S. adults: national health and nutrition examination survey (NHANES) 2011-2016[J].Environ Res,2021,197:111190.
[15] Wu J, Zeng C, Yang Z,et al.Association between dietary selenium intake and the prevalence of nonalcoholic fatty liver disease: a cross-sectional study.[J]. J Am Coll Nutr,2020,39(2):103-111.
[16] Kozeniecki M, Ludke R, Kerner J, et al.Micronutrients in liver disease: roles, risk factors for deficiency, and recommendations for supplementation[J].Nutr Clin Pract,2020,35(1):50-62.
[17] Steinbrenner H, L H Duntas, and M P Rayman.The role of selenium in type-2 diabetes mellitus and its metabolic comorbidities[J].Redox Biol,2022,50:102236.
[18] Urbano T, Filippini T, Lasagni D, et al.Association of urinary and dietary selenium and of serum selenium species with serum alanine aminotransferase in a healthy italian population[J].Antioxidants (Basel),2021,10(10):1516.
[19] Rayman M P. The importance of selenium to human health[J].Lancet,2000,356(9225):233-241.
[20] Baj J, Flieger W, Teresiński G,et al.Magnesium, calcium, potassium, sodium, phosphorus, selenium, zinc, and chromium levels in alcohol use disorder: a review[J]. J Clin Med,2020,9(6):1901.
[21] Whanger P.Selenium and its relationship to cancer: an update[J].Br J Nutr,2004,91(1):11-28.
[22] Thompson J N, Scott M L. Role of selenium in the nutrition of the chick[J]. J Nutr,1969,97(3):335-342.
[23] Xing G, Huang Y, Liu X. Association between dietary pattern, nutritional status, metabolic factors, and nonalcoholic fatty liver disease[J]. Contrast Media Mol Imaging,2022,2022:4157403.
[24] Sun K, Lu J, Jiang Y,et al.Low serum potassium level is associated with nonalcoholic fatty liver disease and its related metabolic disorders[J]. Clin Endocrinol (Oxf),2014,80(3):348-355.
[25] Calvo M S, Uribarri J. Contributions to total phosphorus intake: all sources considered[J]. Semin Dial,2013,26(1):54-61.
[26] Molony D A and B W Stephens.Derangements in phosphate metabolism in chronic kidney diseases/endstage renal disease: therapeutic considerations[J]. Adv Chronic Kidney Dis,2011,18(2):120-131.
[27] Farese R V, M P Sajan, and M L Standaert.Insulin-sensitive protein kinases (atypical protein kinase C and protein kinase B/Akt): actions and defects in obesity and type II diabetes[J]. Exp Biol Med (Maywood),2005,230(9):593-605.
[28] Zhang Y, Dong T, Hu W,et al. Association between exposure to a mixture of phenols, pesticides, and phthalates and obesity: Comparison of three statistical models.[J]. Environ Int,2019,123:325-336.