Serum Magnesium and Uric Acid Levels in Patients with Rheumatoid Arthritis: A Case-Control Study
Abstract
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterized by joint pain, stiffness, and deformity. Both environmental determinants and genetic factors play a role in RA development and progression. Oxidative stress due to reactive oxygen species (ROS) can aggravate these symptoms. Studies on trace elements such as magnesium (Mg) and uric acid (UA) suggest that these can be potential treatment targets. Therefore, we designed this study to compare Mg and UA levels in patients with RA and healthy individuals.
Methods: This was a case-control study with 43 patients with RA and 43 healthy controls. Patients with RA were diagnosed based on ACR/EULAR criteria and were categorized by Disease Activity Score 28 (DAS28). Blood samples were collected for laboratory tests, including UA, Mg, C-reactive protein (CRP), and anti-cyclic citrullinated peptide (anti-CCP) antibody levels.
Results: The study found no significant difference in serum UA levels between patients with RA and healthy controls. However, Mg levels were significantly lower in patients with RA. Mg levels were not significantly different according to DAS. A significant inverse correlation was found between Mg levels and CRP serum levels. A receiver operating characteristic (ROC) curve analysis revealed that anti-CCP had high sensitivity for RA diagnosis, with an optimal cut-off point of 32.5 U/ml.
Conclusion: Low Mg levels should be expected in patients with RA. Supplementing Mg may be a helpful treatment approach in this group. In contrast, UA does not appear to be influenced by RA, but its antioxidant properties cannot be entirely disregarded. Moreover, anti-CCP shows high sensitivity as a diagnostic tool for RA.
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10. Ma Y, Zhang X, Fan D, Xia Q, Wang M, Pan F. Common trace metals in rheumatoid arthritis: A systematic review and meta-analysis. J Trace Elem Med Biol. 2019;56:81-9. doi: 10.1016/j.jtemb.2019.07.007. [PubMed: 31442958].
11. Fiorentini D, Cappadone C, Farruggia G, Prata C. Magnesium: Biochemistry, nutrition, detection, and social impact of diseases linked to its deficiency. Nutrients. 2021;13(4). doi: 10.3390/nu13041136. [PubMed: 33808247]. [PubMed Central: PMC8065437].
12. Mills BJ, Lindeman RD, Lang CA. Magnesium deficiency inhibits biosynthesis of blood glutathione and tumor growth in the rat. Proc Soc Exp Biol Med. 1986;181(3):326-32. doi: 10.3181/00379727-181-42260. [PubMed: 3945642].
13. Shahi A, Aslani S, Ataollahi M, Mahmoudi M. The role of magnesium in different inflammatory diseases. Inflammopharmacology. 2019;27(4):649-61. doi: 10.1007/s10787- 019-00603-7. [PubMed: 31172335].
14. Tuncer S, Kamanli A, Akcil E, Kavas GO, Seckin B, Atay MB. Trace element and magnesium levels and superoxide dismutase activity in rheumatoid arthritis. Biol Trace Elem Res. 1999;68(2):137-42. doi: 10.1007/BF02784402. [PubMed: 10327024].
15. Chavan VU, Ramavataram D, Patel PA, Rupani MP. Evaluation of serum magnesium, lipid profile and various biochemical parameters as risk factors of cardiovascular diseases in patients with rheumatoid arthritis. J Clin Diagn Res. 2015;9(4):BC01-BC05. doi: 10.7860/JCDR/2015/12206.5740. [PubMed: 26023546]. [PubMed Central: PMC4437057].
16. Hu C, Zhu F, Liu L, Zhang M, Chen G. Relationship between dietary magnesium intake and rheumatoid arthritis in US women: a cross-sectional study. BMJ Open. 2020;10(11):e039640. doi: 10.1136/bmjopen-2020-039640. [PubMed: 33168559]. [PubMed Central: PMC7654130].
17. Nielsen FH, Johnson LK, Zeng H. Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep. Magnes Res. 2010;23(4):158-68. doi: 10.1684/mrh.2010.0220. [PubMed: 21199787].
18. Ayati Firoozabadi M, Nezhad Tabrizi B, Seyed Tabaei SMM, Moharrami A, Mortazavi SJ. Intra-articular injections for pain relief following knee arthroscopy: A literature review. J Orthop Spine Trauma. 2023;9(2):46-52. doi: 10.18502/jost.v9i2.12620.
19. Kuang X, Chiou J, Lo K, Wen C. Magnesium in joint health and osteoarthritis. Nutr Res. 2021;90:24-35. doi: 10.1016/j.nutres.2021.03.002. [PubMed: 34023805].
20. Norouzi M, Rezvankhah B, Haeri MR, Heydari H, Tafaroji J, Shafigh N, et al. Magnesium supplementation and insulin resistance in patients with rheumatoid arthritis. Eur J Transl Myol. 2022;32(3). doi: 10.4081/ejtm.2022.10622. [PubMed: 35791617]. [PubMed Central: PMC9580541].
21. Zinellu A, Mangoni AA. A Systematic Review and Meta-Analysis of the Association between Uric Acid and Allantoin and Rheumatoid Arthritis. Antioxidants (Basel). 2023;12(8). doi: 10.3390/antiox12081569. [PubMed: 37627564]. [PubMed Central: PMC10451740].
22. Mikami T, Yoshino Y, Ito A. Does a relationship exist between the urate pool in the body and lipid peroxidation during exercise? Free Radic Res. 2000;32(1):31-9. doi: 10.1080/10715760000300041. [PubMed: 10625215].
23. Spiga R, Marini MA, Mancuso E, Di FC, Fuoco A, Perticone F, et al. Uric Acid Is Associated With Inflammatory Biomarkers and Induces Inflammation Via Activating the NF-kappaB Signaling Pathway in HepG2 Cells. Arterioscler Thromb Vasc Biol. 2017;37(6):1241-9. doi: 10.1161/ATVBAHA.117.309128. [PubMed: 28408375].
24. Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, et al. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension. 2001;38(5):1101-6. doi: 10.1161/hy1101.092839. [PubMed: 11711505].
25. Rahali FZ, Tarmidi M, Hazime R, Admou B. Clinical significance of anti-cyclic citrullinated peptide (anti-CCP) antibodies in rheumatoid arthritis: Literature review. SN Compr Clin Med. 2023;5(1): 272. doi: 10.1007/s42399-023-01613-x.
26. Salinas M, Blasco A, Flores E, Minguez M, Leiva-Salinas C. Double positivity for rheumatoid factor and anti-CCP autoantibodies: improving referral from primary care of patients suspected of having rheumatoid arthritis. Prim Health Care Res Dev. 2024;25:e6. doi: 10.1017/S1463423623000695. [PubMed: 38229558]. [PubMed Central: PMC10894719].
27. Cho J, Pyo JY, Fadriquela A, Uh Y, Lee JH. Comparison of the analytical and clinical performances of four anti-cyclic citrullinated peptide antibody assays for diagnosing rheumatoid arthritis. Clin Rheumatol. 2021;40(2):565-73. doi: 10.1007/s10067-020-05412-w. [PubMed: 32964298].
28. Pineda-Sic RA, Vega-Morales D, Santoyo-Fexas L, Garza-Elizondo MA, Mendiola-Jimenez A, Gonzalez Marquez KI, et al. Are the cut-offs of the rheumatoid factor and anti-cyclic citrullinated peptide antibody different to distinguish rheumatoid arthritis from their primary differential diagnoses? Int J Immunogenet. 2024;51(1):1-9. doi: 10.1111/iji.12643. [PubMed: 37933209].
2. Rustamovich TD, Alisherovna KM, Nizamitdinovich KS, Djamshedovna KD. Gastrointestinal conditions in rheumatoid arthritis patients. Texas Journal of Medical Science. 2022;15:68-72.
3. Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 2002;4 Suppl 3(Suppl 3): S265-72. doi: 10.1186/ar578. [PubMed: 12110146]. [PubMed Central: PMC3240153].
4. Martinec R, Pinjatela R, Balen D. Quality of life in patients with rheumatoid arthritis - a preliminary study. Acta Clin Croat. 2019;58(1):157-66. doi: 10.20471/acc.2019.58.01.20. [PubMed: 31363338]. [PubMed Central: PMC6629210].
5. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-19. doi: 10.1056/NEJMra1004965. [PubMed: 22150039].
6. Zamudio-Cuevas Y, Martinez-Flores K, Martinez-Nava GA, Clavijo-Cornejo D, Fernandez-Torres J, Sanchez-Sanchez R. Rheumatoid arthritis and oxidative stress. Cell Mol Biol (Noisy -le -grand). 2022;68(6):174-84. doi: 10.14715/cmb/2022.68.6.28. [PubMed: 36227658].
7. Smallwood MJ, Nissim A, Knight AR, Whiteman M, Haigh R, Winyard PG. Oxidative stress in autoimmune rheumatic diseases. Free Radic Biol Med. 2018;125:3-14. doi: 10.1016/j.freeradbiomed.2018.05.086. [PubMed: 29859343].
8. Kunsch C, Sikorski JA, Sundell CL. Oxidative stress and the use of antioxidants for the treatment of rheumatoid arthritis. Current Medicinal Chemistry-Immunology, Endocrine and Metabolic Agents. 2005;5(3):249-58. doi: 10.2174/1568013054022490.
9. Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA. Uricacid and oxidative stress. Curr Pharm Des. 2005;11(32):4145-51. doi: 10.2174/138161205774913255. [PubMed: 16375736].
10. Ma Y, Zhang X, Fan D, Xia Q, Wang M, Pan F. Common trace metals in rheumatoid arthritis: A systematic review and meta-analysis. J Trace Elem Med Biol. 2019;56:81-9. doi: 10.1016/j.jtemb.2019.07.007. [PubMed: 31442958].
11. Fiorentini D, Cappadone C, Farruggia G, Prata C. Magnesium: Biochemistry, nutrition, detection, and social impact of diseases linked to its deficiency. Nutrients. 2021;13(4). doi: 10.3390/nu13041136. [PubMed: 33808247]. [PubMed Central: PMC8065437].
12. Mills BJ, Lindeman RD, Lang CA. Magnesium deficiency inhibits biosynthesis of blood glutathione and tumor growth in the rat. Proc Soc Exp Biol Med. 1986;181(3):326-32. doi: 10.3181/00379727-181-42260. [PubMed: 3945642].
13. Shahi A, Aslani S, Ataollahi M, Mahmoudi M. The role of magnesium in different inflammatory diseases. Inflammopharmacology. 2019;27(4):649-61. doi: 10.1007/s10787- 019-00603-7. [PubMed: 31172335].
14. Tuncer S, Kamanli A, Akcil E, Kavas GO, Seckin B, Atay MB. Trace element and magnesium levels and superoxide dismutase activity in rheumatoid arthritis. Biol Trace Elem Res. 1999;68(2):137-42. doi: 10.1007/BF02784402. [PubMed: 10327024].
15. Chavan VU, Ramavataram D, Patel PA, Rupani MP. Evaluation of serum magnesium, lipid profile and various biochemical parameters as risk factors of cardiovascular diseases in patients with rheumatoid arthritis. J Clin Diagn Res. 2015;9(4):BC01-BC05. doi: 10.7860/JCDR/2015/12206.5740. [PubMed: 26023546]. [PubMed Central: PMC4437057].
16. Hu C, Zhu F, Liu L, Zhang M, Chen G. Relationship between dietary magnesium intake and rheumatoid arthritis in US women: a cross-sectional study. BMJ Open. 2020;10(11):e039640. doi: 10.1136/bmjopen-2020-039640. [PubMed: 33168559]. [PubMed Central: PMC7654130].
17. Nielsen FH, Johnson LK, Zeng H. Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep. Magnes Res. 2010;23(4):158-68. doi: 10.1684/mrh.2010.0220. [PubMed: 21199787].
18. Ayati Firoozabadi M, Nezhad Tabrizi B, Seyed Tabaei SMM, Moharrami A, Mortazavi SJ. Intra-articular injections for pain relief following knee arthroscopy: A literature review. J Orthop Spine Trauma. 2023;9(2):46-52. doi: 10.18502/jost.v9i2.12620.
19. Kuang X, Chiou J, Lo K, Wen C. Magnesium in joint health and osteoarthritis. Nutr Res. 2021;90:24-35. doi: 10.1016/j.nutres.2021.03.002. [PubMed: 34023805].
20. Norouzi M, Rezvankhah B, Haeri MR, Heydari H, Tafaroji J, Shafigh N, et al. Magnesium supplementation and insulin resistance in patients with rheumatoid arthritis. Eur J Transl Myol. 2022;32(3). doi: 10.4081/ejtm.2022.10622. [PubMed: 35791617]. [PubMed Central: PMC9580541].
21. Zinellu A, Mangoni AA. A Systematic Review and Meta-Analysis of the Association between Uric Acid and Allantoin and Rheumatoid Arthritis. Antioxidants (Basel). 2023;12(8). doi: 10.3390/antiox12081569. [PubMed: 37627564]. [PubMed Central: PMC10451740].
22. Mikami T, Yoshino Y, Ito A. Does a relationship exist between the urate pool in the body and lipid peroxidation during exercise? Free Radic Res. 2000;32(1):31-9. doi: 10.1080/10715760000300041. [PubMed: 10625215].
23. Spiga R, Marini MA, Mancuso E, Di FC, Fuoco A, Perticone F, et al. Uric Acid Is Associated With Inflammatory Biomarkers and Induces Inflammation Via Activating the NF-kappaB Signaling Pathway in HepG2 Cells. Arterioscler Thromb Vasc Biol. 2017;37(6):1241-9. doi: 10.1161/ATVBAHA.117.309128. [PubMed: 28408375].
24. Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, et al. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension. 2001;38(5):1101-6. doi: 10.1161/hy1101.092839. [PubMed: 11711505].
25. Rahali FZ, Tarmidi M, Hazime R, Admou B. Clinical significance of anti-cyclic citrullinated peptide (anti-CCP) antibodies in rheumatoid arthritis: Literature review. SN Compr Clin Med. 2023;5(1): 272. doi: 10.1007/s42399-023-01613-x.
26. Salinas M, Blasco A, Flores E, Minguez M, Leiva-Salinas C. Double positivity for rheumatoid factor and anti-CCP autoantibodies: improving referral from primary care of patients suspected of having rheumatoid arthritis. Prim Health Care Res Dev. 2024;25:e6. doi: 10.1017/S1463423623000695. [PubMed: 38229558]. [PubMed Central: PMC10894719].
27. Cho J, Pyo JY, Fadriquela A, Uh Y, Lee JH. Comparison of the analytical and clinical performances of four anti-cyclic citrullinated peptide antibody assays for diagnosing rheumatoid arthritis. Clin Rheumatol. 2021;40(2):565-73. doi: 10.1007/s10067-020-05412-w. [PubMed: 32964298].
28. Pineda-Sic RA, Vega-Morales D, Santoyo-Fexas L, Garza-Elizondo MA, Mendiola-Jimenez A, Gonzalez Marquez KI, et al. Are the cut-offs of the rheumatoid factor and anti-cyclic citrullinated peptide antibody different to distinguish rheumatoid arthritis from their primary differential diagnoses? Int J Immunogenet. 2024;51(1):1-9. doi: 10.1111/iji.12643. [PubMed: 37933209].
| Files | ||
| Issue | Vol 11 No 1 (2025) | |
| Section | Research Articles | |
| DOI | https://doi.org/10.18502/jost.v11i1.18006 | |
| Keywords | ||
| Rheumatoid Arthritis Magnesium Uric Acid Anti-Citrullinated Protein Antibodies Oxidative Stress | ||
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How to Cite
1.
Firoozabadi M, Moghanloo E, Tabrizi B, Teymouri A. Serum Magnesium and Uric Acid Levels in Patients with Rheumatoid Arthritis: A Case-Control Study. J Orthop Spine Trauma. 2025;11(1):11-14.
