Skip to main content

Advertisement

Log in

Association Between Blood Calcium, Magnesium, and Non-alcoholic Fatty Liver Disease in Adults: a Cohort-Based Case-Control Study

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Previous studies have shown that calcium (Ca), magnesium (Mg), and Ca/Mg ratio are associated with inflammation and metabolic disorders, but their relationship with non-alcoholic fatty liver disease (NAFLD) is unclear. Thus, we aimed to explore the association between Ca, Mg, Ca/Mg ratio, and NAFLD in Chinese adults. We conducted a case-control study based on the Kailuan Cohort in China, including 1816 cases and 1111 gender- and age-matched controls. Dose-response relationships between blood Ca, Mg, Ca/Mg ratio, and NAFLD were evaluated using restricted cubic splines. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated by logistic regression models. A negative association between blood Ca (overall association P < 0.001 and linear association P < 0.001) and NAFLD as well as Ca/Mg ratio (overall association P = 0.002 and linear association P = 0.024) and NAFLD was observed. Compared with the highest quartile, the adjusted OR (95% CI) for the lowest quartile of Ca and Ca/Mg ratio was 2.116 (1.679–2.667) and 1.358 (1.076–1.713), respectively. A U-shaped relationship was found for blood Mg and NAFLD, with the highest OR of 1.685 in the lowest quartile group when using the second quartile as a reference. Additionally, we observed the interaction between alanine aminotransferase and blood Ca (P = 0.024), total cholesterol (P = 0.017), low-density lipoprotein-cholesterol (P = 0.013), and blood Mg, as well as total cholesterol and Ca/Mg ratio (P = 0.014). Lower blood Ca and Ca/Mg ratio were significantly associated with the risk of NAFLD. Liver function or lipid metabolism parameters may modify their association, suggesting an individualized prevention strategy for NAFLD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

The data of this study are based on the population data of Linxi Hospital in Kailuan queue, which cannot be disclosed due to the limitation of data confidentiality.

Abbreviations

ALT:

Alanine aminotransferase

Ca:

Calcium

CI:

Confidence interval

HDL-C:

High-density lipoprotein-cholesterol

LDL-C:

Low-density lipoprotein-cholesterol

Mg:

Magnesium

NAFLD:

Non-alcoholic fatty liver disease

OR:

Odds ratio

RCS:

Restricted cubic spline

TC:

Total cholesterol

References

  1. Powell EE, Wong VW-S, Rinella M (2021) Non-alcoholic fatty liver disease. The Lancet 397:2212–2224. https://doi.org/10.1016/s0140-6736(20)32511-3

    Article  CAS  Google Scholar 

  2. Younossi Z, Tacke F, Arrese M, Chander Sharma B, Mostafa I, Bugianesi E et al (2019) Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology 69:2672–2682. https://doi.org/10.1002/hep.30251

    Article  PubMed  Google Scholar 

  3. Wong SW, Chan WK (2020) Epidemiology of non-alcoholic fatty liver disease in Asia. Indian J Gastroenterol 39:1–8. https://doi.org/10.1007/s12664-020-01018-x

    Article  PubMed  Google Scholar 

  4. Wang Z, Zhao X, Chen S, Wang Y, Cao L, Liao W et al (2021) Associations between nonalcoholic fatty liver disease and cancers in a large cohort in China. Clin Gastroenterol Hepatol 19:788–796.e784. https://doi.org/10.1016/j.cgh.2020.05.009

    Article  PubMed  Google Scholar 

  5. Simon TG, Roelstraete B, Sharma R, Khalili H, Hagstrom H, Ludvigsson JF (2021) Cancer risk in patients with biopsy-confirmed nonalcoholic fatty liver disease: a population-based cohort study. Hepatology 74:2410–2423. https://doi.org/10.1002/hep.31845

    Article  CAS  PubMed  Google Scholar 

  6. Targher G, Corey KE, Byrne CD, Roden M (2021) The complex link between NAFLD and type 2 diabetes mellitus - mechanisms and treatments. Nat Rev Gastroenterol Hepatol 18:599–612. https://doi.org/10.1038/s41575-021-00448-y

    Article  PubMed  Google Scholar 

  7. Byrne CD, Targher G (2020) NAFLD as a driver of chronic kidney disease. J Hepatol 72:785–801. https://doi.org/10.1016/j.jhep.2020.01.013

    Article  PubMed  Google Scholar 

  8. Leake I (2019) NAFLD and risk of cardiovascular disease. Nat Rev Gastroenterol Hepatol 16:706. https://doi.org/10.1038/s41575-019-0234-7

    Article  PubMed  Google Scholar 

  9. European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O (2016) EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 64:1388–1402. https://doi.org/10.1016/j.jhep.2015.11.004

    Article  Google Scholar 

  10. Semmler G, Datz C, Reiberger T, Trauner M (2021) Diet and exercise in NAFLD/NASH: beyond the obvious. Liver Int 41:2249–2268. https://doi.org/10.1111/liv.15024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Oliva-Vilarnau N, Hankeova S, Vorrink SU, Mkrtchian S, Andersson ER, Lauschke VM (2018) Calcium signaling in liver injury and regeneration. Frontiers in Medicine 5:192. https://doi.org/10.3389/fmed.2018.00192

    Article  PubMed  PubMed Central  Google Scholar 

  12. Mohammadifard N, Gotay C, Humphries KH, Ignaszewski A, Esmaillzadeh A, Sarrafzadegan N (2019) Electrolyte minerals intake and cardiovascular health. Critical reviews in food science and nutrition 59:2375–2385. https://doi.org/10.1080/10408398.2018.1453474

    Article  PubMed  Google Scholar 

  13. Pelczynska M, Moszak M, Bogdanski P (2022) The role of magnesium in the pathogenesis of metabolic disorders. Nutrients 14. https://doi.org/10.3390/nu14091714

  14. Grober U, Schmidt J, Kisters K (2015) Magnesium in prevention and therapy. Nutrients 7:8199–8226. https://doi.org/10.3390/nu7095388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hands JM, Moy LS (2021) Calcium: more than bone? Implications for clinical practice and theory. J Clin Med Res 13:253–257. https://doi.org/10.14740/jocmr4505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hashemi Kani A, Alavian SM, Esmaillzadeh A, Adibi P, Azadbakht L (2013) Dietary quality indices and biochemical parameters among patients with non alcoholic fatty liver disease (NAFLD). Hepatitis monthly 13:e10943. https://doi.org/10.5812/hepatmon.10943

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lu L, Chen C, Li Y, Guo W, Zhang S, Brockman J et al (2022) Magnesium intake is inversely associated with risk of non-alcoholic fatty liver disease among American adults. Eur J Nutr 61:1245–1254. https://doi.org/10.1007/s00394-021-02732-8

    Article  CAS  PubMed  Google Scholar 

  18. Li W, Zhu X, Song Y, Fan L, Wu L, Kabagambe EK et al (2018) Intakes of magnesium, calcium and risk of fatty liver disease and prediabetes. Public Health Nutr 21:2088–2095. https://doi.org/10.1017/S1368980018000642

    Article  PubMed  PubMed Central  Google Scholar 

  19. Shin JY, Kim MJ, Kim ES, Mo EY, Moon SD, Han JH et al (2015) Association between serum calcium and phosphorus concentrations with non-alcoholic fatty liver disease in Korean population. Journal of gastroenterology and hepatology 30:733–741. https://doi.org/10.1111/jgh.12832

    Article  CAS  PubMed  Google Scholar 

  20. Rhee EJ, Kim MK, Park SE, Park CY, Baek KH, Lee WY et al (2013) High serum vitamin D levels reduce the risk for nonalcoholic fatty liver disease in healthy men independent of metabolic syndrome. Endocrine journal 60:743–752. https://doi.org/10.1507/endocrj.ej12-0387

    Article  CAS  PubMed  Google Scholar 

  21. Eshraghian A, Nikeghbalian S, Geramizadeh B, Malek-Hosseini SA (2018) Serum magnesium concentration is independently associated with non-alcoholic fatty liver and non-alcoholic steatohepatitis. United European Gastroenterol J 6:97–103. https://doi.org/10.1177/2050640617707863

    Article  CAS  PubMed  Google Scholar 

  22. Guerrero-Romero F, Mercado M, Rodriguez-Moran M, Ramírez-Renteria C, Martínez-Aguilar G, Marrero-Rodríguez D et al (2022) Magnesium-to-calcium ratio and mortality from COVID-19. Nutrients 14. https://doi.org/10.3390/nu14091686

  23. Dong H, Hu P, Wang J, Zhang Y, Lu N (2021) Associations of serum calcium, magnesium levels, and their ratio with apolipoproteins in chinese adults with coronary artery disease: a cross-sectional study. Biol Trace Elem Res. https://doi.org/10.1007/s12011-021-03015-3

  24. Zhao J, Giri A, Zhu X, Shrubsole MJ, Jiang Y, Guo X et al (2019) Calcium: magnesium intake ratio and colorectal carcinogenesis, results from the prostate, lung, colorectal, and ovarian cancer screening trial. Br J Cancer 121:796–804. https://doi.org/10.1038/s41416-019-0579-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Emamat H, Ghalandari H, Totmaj AS, Tangestani H, Hekmatdoost A (2021) Calcium to magnesium intake ratio and non-alcoholic fatty liver disease development: a case-control study. BMC Endocr Disord 21:51. https://doi.org/10.1186/s12902-021-00721-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang L, Lee Y, Wu Y, Zhang X, Jin C, Huang Z et al (2021) A prospective study of waist circumference trajectories and incident cardiovascular disease in China: the Kailuan Cohort Study. Am J Clin Nutr 113:338–347. https://doi.org/10.1093/ajcn/nqaa331

    Article  PubMed  Google Scholar 

  27. American Gastroenterological Association (2002) Medical position statement: nonalcoholic fatty liver disease. Gastroenterology 123:1702–1704. https://doi.org/10.1053/gast.2002.36569

    Article  Google Scholar 

  28. Yue T, Zhang Q, Cai T, Xu M, Zhu H, Pourkarim MR et al (2022) Trends in the disease burden of HBV and HCV infection in China from 1990-2019. Int J Infect Dis 122:476–485. https://doi.org/10.1016/j.ijid.2022.06.017

    Article  PubMed  Google Scholar 

  29. Lv T, Li M, Zeng N, Zhang J, Li S, Chen S et al (2019) Systematic review and meta-analysis on the incidence and prevalence of autoimmune hepatitis in Asian, European, and American population. J Gastroenterol Hepatol 34:1676–1684. https://doi.org/10.1111/jgh.14746

    Article  PubMed  Google Scholar 

  30. Gao X, Fan JG (2013) Diagnosis and management of non-alcoholic fatty liver disease and related metabolic disorders: consensus statement from the Study Group of Liver and Metabolism, Chinese Society of Endocrinology. J Diabetes 5:406–415. https://doi.org/10.1111/1753-0407.12056

    Article  PubMed  Google Scholar 

  31. Herbers J, Miller R, Walther A, Schindler L, Schmidt K, Gao W et al (2021) How to deal with non-detectable and outlying values in biomarker research: best practices and recommendations for univariate imputation approaches. Compr Psychoneuroendocrinol 7:100052. https://doi.org/10.1016/j.cpnec.2021.100052

    Article  PubMed  PubMed Central  Google Scholar 

  32. Batis C, Sotres-Alvarez D, Gordon-Larsen P, Mendez MA, Adair L, Popkin B (2014) Longitudinal analysis of dietary patterns in Chinese adults from 1991 to 2009. Br J Nutr 111:1441–1451. https://doi.org/10.1017/S0007114513003917

    Article  CAS  PubMed  Google Scholar 

  33. Yang Y, Wang GY, Pan XC (2005) Chinese food composition table 2004. Peking University Medical Press, Beijing. https://scholar.google.com/scholar_lookup?title=Chinese%20Food%20Composition%202004&author=Y.%20Yang&publication_year=2005

  34. Institute of Medicine Committee to Review Dietary Reference Intakes for Vitamin, D. & Calcium (2011) Dietary reference intakes for calcium and vitamin D. National Academies Press, US.

  35. Institute of Medicine Standing Committee on the Scientific Evaluation of Dietary Reference (1997) Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. National Academies Press, US. https://pubmed.ncbi.nlm.nih.gov/23115811/

  36. Costello RB, Rosanoff A, Dai Q, Saldanha LG, Potischman NA (2021) Perspective: characterization of dietary supplements containing calcium and magnesium and their respective ratio-is a rising ratio a cause for concern? Adv Nutr 12:291–297. https://doi.org/10.1093/advances/nmaa160

    Article  PubMed  Google Scholar 

  37. (2004) Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363:157–163. https://doi.org/10.1016/s0140-6736(03)15268-3

  38. Society, C. D (2018) Guideline for prevention and control of type 2 diabetes in China (2017). Chinese Journal of Diabetes Mellitus 10:4–67

    Google Scholar 

  39. Zhao M, Song L, Sun L, Wang M, Wang C, Yao S et al (2021) Associations of type 2 diabetes onset age with cardiovascular disease and mortality: the Kailuan study. Diabetes Care 44:1426–1432. https://doi.org/10.2337/dc20-2375

    Article  PubMed  PubMed Central  Google Scholar 

  40. Pagana KD, Pagana TJ, Pagana TN (2019) Mosby’s Diagnostic and Laboratory Test Reference. St. Louis, MO. https://scholar.googleusercontent.com/scholar.bib?q=info:nsz5nUBdl3wJ:scholar.google.com/&output=citation&scisdr=CgXmLzs2ELLT1CfgWRA:AAGBfm0AAAAAY7PmQRDLxaWY13LkdstcyjhGroqgF47&scisig=AAGBfm0AAAAAY7PmQbBfd5BhGXvpeYBaoUSvk3NOQRGk&scisf=4&ct=citation&cd=-1&hl=zh-CN

  41. Desquilbet L, Mariotti F (2010) Dose-response analyses using restricted cubic spline functions in public health research. Stat Med 29:1037–1057. https://doi.org/10.1002/sim.3841

    Article  PubMed  Google Scholar 

  42. (2007) Chinese guidelines on prevention and treatment of dyslipidemia in adults. Zhonghua Xin Xue Guan Bing Za Zhi 35:390–419

  43. Gawrieh S, Wilson LA, Cummings OW, Clark JM, Loomba R, Hameed B et al (2019) Histologic findings of advanced fibrosis and cirrhosis in patients with nonalcoholic fatty liver disease who have normal aminotransferase levels. Am J Gastroenterol 114:1626–1635. https://doi.org/10.14309/ajg.0000000000000388

    Article  PubMed  PubMed Central  Google Scholar 

  44. Yuan Z, Liu C, Tian Y, Zhang X, Ye H, Jin L et al (2016) Higher levels of magnesium and lower levels of calcium in whole blood are positively correlated with the metabolic syndrome in a Chinese population: a case-control study. Annals of nutrition & metabolism 69:125–134. https://doi.org/10.1159/000450761

    Article  CAS  Google Scholar 

  45. Weaver CM, Peacock M (2019) Calcium. Adv Nutr 10:546–548. https://doi.org/10.1093/advances/nmy086

    Article  PubMed  Google Scholar 

  46. Hajhashemy Z, Rouhani P, Saneei P (2022) Dietary calcium intake in relation to type-2 diabetes and hyperglycemia in adults: a systematic review and dose-response meta-analysis of epidemiologic studies. Sci Rep 12:1050. https://doi.org/10.1038/s41598-022-05144-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Cheng L, Hu D, Jiang W (2019) Dietary calcium intake and the risk of metabolic syndrome: evidence from observational studies. Public Health Nutr 22:2055–2062. https://doi.org/10.1017/S1368980019000247

    Article  PubMed  PubMed Central  Google Scholar 

  48. Liu Z, Zhao L, Man Q, Wang J, Zhao W, Zhang J (2019) Dietary micronutrients intake status among chinese elderly people living at home: data from CNNHS 2010-2012. Nutrients 11. https://doi.org/10.3390/nu11081787

  49. Lorvand Amiri H, Agah S, Tolouei Azar J, Hosseini S, Shidfar F, Mousavi SN (2017) Effect of daily calcitriol supplementation with and without calcium on disease regression in non-alcoholic fatty liver patients following an energy-restricted diet: randomized, controlled, double-blind trial. Clin Nutr 36:1490–1497. https://doi.org/10.1016/j.clnu.2016.09.020

    Article  CAS  PubMed  Google Scholar 

  50. Jiao Y, Li W, Wang L, Jiang H, Wang S, Jia X et al (2022) Relationship between dietary magnesium intake and metabolic syndrome. Nutrients 14. https://doi.org/10.3390/nu14102013

  51. Tan X, Huang Y (2022) Magnesium supplementation for glycemic status in women with gestational diabetes: a systematic review and meta-analysis. Gynecol Endocrinol 38:202–206. https://doi.org/10.1080/09513590.2021.1988558

    Article  CAS  PubMed  Google Scholar 

  52. Asbaghi O, Moradi S, Nezamoleslami S, Moosavian SP, Hojjati Kermani MA, Lazaridi AV et al (2021) The effects of magnesium supplementation on lipid profile among type 2 diabetes patients: a systematic review and meta-analysis of randomized controlled trials. Biol Trace Elem Res 199:861–873. https://doi.org/10.1007/s12011-020-02209-5

    Article  CAS  PubMed  Google Scholar 

  53. Gaman MA, Dobrica EC, Cozma MA, Antonie NI, Stanescu AMA, Gaman AM et al (2021) Crosstalk of magnesium and serum lipids in dyslipidemia and associated disorders: a systematic review. Nutrients 13. https://doi.org/10.3390/nu13051411

  54. Dent A, Selvaratnam R (2022) Measuring magnesium - physiological, clinical and analytical perspectives. Clin Biochem. https://doi.org/10.1016/j.clinbiochem.2022.04.001

  55. Elin RJ (2010) Assessment of magnesium status for diagnosis and therapy. Magnes Res 23:S194–S198. https://doi.org/10.1684/mrh.2010.0213

    Article  CAS  PubMed  Google Scholar 

  56. Dai Q, Cantwell MM, Murray LJ, Zheng W, Anderson LA, Coleman HG et al (2016) Dietary magnesium, calcium:magnesium ratio and risk of reflux oesophagitis, Barrett’s oesophagus and oesophageal adenocarcinoma: a population-based case-control study. Br J Nutr 115:342–350. https://doi.org/10.1017/S0007114515004444

    Article  CAS  PubMed  Google Scholar 

  57. Dasarathy S, Dasarathy J, Khiyami A, Joseph R, Lopez R, McCullough AJ (2009) Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study. J. Hepatol. 51:1061–1067. https://doi.org/10.1016/j.jhep.2009.09.001

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Thanks to all the authors and participants for their contribution to this study.

Funding

This work was supported by the Beijing Municipal Health Commission Capital Health Development Research Project (2022-1-2021) and CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-023).

Author information

Authors and Affiliations

Authors

Contributions

LW designed the study. SLW and SHC collected the data. YHW and YQL processed the data. CLY performed the statistical analysis. CLY, LW, YHW, YQL, WL, and DZ interpreted the data. CLY drafted the manuscript. LW and YYS revised the manuscript critically. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Li Wang.

Ethics declarations

Ethics Approval

This study was carried out according to the tenets of the Declaration of Helsinki. Our research is registered on this website (http://www.chictr.org.cn/), and the ID is ChiCTR-TNRC-11001489. The Ethics Committee of the Kailuan General Hospital and Institute of Basic Medicine Chinese Academy of Medical Sciences approved this study.

Consent to Participate

Written informed consent was obtained from all participants.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 51.4 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, C., Wu, S., Lan, Y. et al. Association Between Blood Calcium, Magnesium, and Non-alcoholic Fatty Liver Disease in Adults: a Cohort-Based Case-Control Study. Biol Trace Elem Res 201, 4625–4636 (2023). https://doi.org/10.1007/s12011-022-03543-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-022-03543-6

Keywords

Navigation