Investigation of serum magnesium, ferritin, and vitamin B12 levels in restless legs syndrome

Abstract

Purpose: To study magnesium, ferritin, and vitamin B12 levels in patients with restless legs syndrome and assess the relationship between the disease progression and age.
Materials and methods: The retrospective data of 40 restless legs syndrome patients from 2024–2025 were analyzed. Those with chronic diseases (diabetes mellitus, chronic kidney failure, and oncological diseases) were excluded from the study. Before that, serum magnesium, ferritin and vitamin B12 levels were measured. Age was calculated, and Pearson correlation analysis was performed. Patients were followed up for 3 months.
Results: Serum magnesium levels were 2.09±0.24 mg/dL (median: 2.05 mg/dL), ferritin levels were 59.01±43.76 ng/mL (median: 49.88 ng/mL), and vitamin B12 levels were 384.88±108.72 pg/mL (median: 375.50 pg/mL). None of these biochemical parameters showed a statistically significant correlation with age (all p>0.05).
Conclusion: It was evaluated that biochemical imbalances in the restless legs syndrome symptomatology may be independent of the age factor, and that especially changes in the levels of ferritin and magnesium could be due to the pathophysiological process of the disease.

Keywords

• Restless legs syndrome
• age
• magnesium
• ferritin
• vitamin B12

Huzursuz bacak sendromunda serum magnezyum, ferritin ve vitamin B12 düzeylerinin araştırılması

Abstract

Amaç: Huzursuz bacak sendromu hastalarında magnezyum, ferritin ve B12 vitamini düzeylerini incelemek ve hastalığın ilerlemesi ile yaş arasındaki ilişkiyi değerlendirmektir.
Gereç ve yöntem: 2024-2025 yılları arasında 40 huzursuz bacak sendromu hastasının retrospektif verileri analiz edildi. Kronik hastalığı olanlar (diyabetes mellitus, kronik böbrek yetmezliği ve onkolojik hastalıklar) çalışmadan dışlandı. Çalışma öncesinde serum magnezyum, ferritin ve B12 vitamini düzeyleri ölçüldü. Yaş hesaplandı ve Pearson korelasyon analizi yapıldı. Hastalar 3 ay boyunca takip edildi.
Bulgular: Hastaların ortalama yaşı 47,9±12,4 yıl olup, serum magnezyum düzeyi 2,09±0,24 mg/dL (medyan: 2,05 mg/dL), ferritin düzeyi 59,01±43,76 ng/mL (medyan: 49,88 ng/mL) ve B12 vitamini düzeyi 384,88±108,72 pg/mL (medyan: 375,50 pg/mL) olarak bulundu. Serum magnezyum, ferritin ve B12 vitamini düzeyleri ile yaş arasında istatistiksel olarak anlamlı bir korelasyon saptanmadı (p>0,05).
Sonuç: Huzursuz bacak sendromu semptomatolojisindeki biyokimyasal dengesizliklerin yaş faktöründen bağımsız olabileceği, özellikle ferritin ve magnezyum düzeylerindeki değişikliklerin hastalığın patofizyolojik sürecinden kaynaklanabileceği değerlendirildi.

Keywords

• Huzursuz bacak sendromu
• yaş
• magnezyum
• ferritin
• B12 vitamini

References

1. Vlasie, A., Trifu, S. C., Lupuleac, C., Kohn, B., & Cristea, M. B. (2022). Restless legs syndrome: An overview of pathophysiology, comorbidities and therapeutic approaches (Review). Experimental and therapeutic medicine, 23(2), 185. https://doi.org/10.3892/etm.2021.11108
2. Antelmi, E., Rocchi, L., Latorre, A., Belvisi, D., Magrinelli, F., Bhatia, K. P., & Tinazzi, M. (2022). Restless Legs Syndrome: Known Knowns and Known Unknowns. Brain sciences, 12(1), 118. https://doi.org/10.3390/brainsci12010118
3. Wang, T., Xu, J., Xu, Q., Zhao, R., Pan, L., Zhu, D., Pan, Y., Chen, L., Lou, G., Xu, X., Wang, J., & Zhang, L. (2022). Peripheral Iron Metabolism is Associated with Leg Movements on Polysomnography but Not with the Severity of Restless Legs Syndrome or Its Impact on Patients. Nature and science of sleep, 14, 1829–1842. https://doi.org/10.2147/NSS.S378970
4. Cameli, N., Beatrice, A., Colacino Cinnante, E. M., Gullace, C., Lentini, G., Occhipinti, S., Ferri, R., & Bruni, O. (2023). Restless Sleep Disorder and the Role of Iron in Other Sleep-Related Movement Disorders and ADHD. Clinical and Translational Neuroscience, 7(3), 18. https://doi.org/10.3390/ctn7030018
5. McWilliams, S., Hill, O., Ipsiroglu, O. S., Clemens, S., Weber, A. M., Chen, M., Connor, J., Felt, B. T., Manconi, M., Mattman, A., Silvestri, R., Simakajornboon, N., Smith, S. M., & Stockler, S. (2024). Iron Deficiency and Sleep/Wake Behaviors: A Scoping Review of Clinical Practice Guidelines-How to Overcome the Current Conundrum?. Nutrients, 16(15), 2559. https://doi.org/10.3390/nu16152559
6. Allen R. (2004). Dopamine and iron in the pathophysiology of restless legs syndrome (RLS). Sleep medicine, 5(4), 385–391. https://doi.org/10.1016/j.sleep.2004.01.012
7. Zeng, P., Wang, T., Zhang, L., & Guo, F. (2023). Exploring the causes of augmentation in restless legs syndrome. Frontiers in neurology, 14, 1160112. https://doi.org/10.3389/fneur.2023.1160112
8. González-Parejo, P., Martín-Núñez, J., Cabrera-Martos, I., & Valenza, M. C. (2024). Effects of Dietary Supplementation in Patients with Restless Legs Syndrome: A Systematic Review. Nutrients, 16(14), 2315. https://doi.org/10.3390/nu16142315

9. Souza, A. C. R., Vasconcelos, A. R., Dias, D. D., Komoni, G., & Name, J. J. (2023). The Integral Role of Magnesium in Muscle Integrity and Aging: A Comprehensive Review. Nutrients, 15(24), 5127. https://doi.org/10.3390/nu15245127
10. Kothari, M., Wanjari, A., Shaikh, S. M., Tantia, P., Waghmare, B. V., Parepalli, A., Hamdulay, K. F., & Nelakuditi, M. (2024). A Comprehensive Review on Understanding Magnesium Disorders: Pathophysiology, Clinical Manifestations, and Management Strategies. Cureus, 16(9), e68385. https://doi.org/10.7759/cureus.68385
11. Kouri, I., Junna, M. R., & Lipford, M. C. (2023). Restless Legs Syndrome and Periodic Limb Movements of Sleep: From Neurophysiology to Clinical Practice. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society, 40(3), 215–223. https://doi.org/10.1097/WNP.0000000000000934
12. Hornyak, M., Voderholzer, U., Hohagen, F., Berger, M., & Riemann, D. (1998). Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study. Sleep, 21(5), 501–505. https://doi.org/10.1093/sleep/21.5.501
13. Xu, X. M., Ruan, J. H., Tao, T., Xiang, S. L., Meng, R. L., & Chen, X. (2025). Role of vitamins in the pathogenesis and treatment of restless leg syndrome: A systematic review and meta-analysis. PloS one, 20(3), e0313571. https://doi.org/10.1371/journal.pone.0313571
14. Ramadan, E. F., Grisdale, M., & Morais, M. (2022). Maternal Vitamin B12 Levels During Pregnancy and Their Effects on Maternal Neurocognitive Symptoms: A Systematic Review. Journal of obstetrics and gynaecology Canada : JOGC, 44(4), 390–394.e3. https://doi.org/10.1016/j.jogc.2021.11.017
15. Geng, C., Yang, Z., Xu, P., & Zhang, H. (2022). Possible association between vitamin B12 deficiency and restless legs syndrome. Clinical neurology and neurosurgery, 223, 107477. https://doi.org/10.1016/j.clineuro.2022.107477
16. Earley, C. J., Connor, J., Garcia-Borreguero, D., Jenner, P., Winkelman, J., Zee, P. C., & Allen, R. (2014). Altered brain iron homeostasis and dopaminergic function in Restless Legs Syndrome (Willis-Ekbom Disease). Sleep medicine, 15(11), 1288–1301. https://doi.org/10.1016/j.sleep.2014.05.009
17. Kim, T. J., Jun, J. S., Kim, K. T., Yang, T. W., Park, B. S., Lim, J. A., Byun, J. I., Sunwoo, J. S., Shin, J. W., & Jung, K. Y. (2018). Clinical characteristics and efficacy of iron treatment for Restless legs syndrome patients with very low ferritin levels. Sleep Medicine Research, 9(2), 118-123. https://doi.org/10.17241/smr.2018.00171
18. Ondo W. G. (2010). Intravenous iron dextran for severe refractory restless legs syndrome. Sleep medicine, 11(5), 494–496. https://doi.org/10.1016/j.sleep.2009.12.002
19. Ferré, S., Sarasola, L. I., Quiroz, C., & Ciruela, F. (2023). Presynaptic adenosine receptor heteromers as key modulators of glutamatergic and dopaminergic neurotransmission in the striatum. Neuropharmacology, 223, 109329. https://doi.org/10.1016/j.neuropharm.2022.109329
20. Lv, Q., Wang, X., Asakawa, T., & Wang, X. P. (2021). Pharmacologic Treatment of Restless Legs Syndrome. Current neuropharmacology, 19(3), 372–382. https://doi.org/10.2174/1570159X19666201230150127
21. Tang, M., Sun, Q., Zhang, Y., Li, H., Wang, D., Wang, Y., & Wang, Z. (2023). Circadian rhythm in restless legs syndrome. Frontiers in neurology, 14, 1105463. https://doi.org/10.3389/fneur.2023.1105463
22. Ferré, S., García-Borreguero, D., Allen, R. P., & Earley, C. J. (2019). New Insights into the Neurobiology of Restless Legs Syndrome. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry, 25(2), 113–125. https://doi.org/10.1177/1073858418791763
23. Ferré S, Quiroz C, Rea W, Guitart X, García-Borreguero D. (2019). Adenosine mechanisms and hypersensitive corticostriatal terminals in restless legs syndrome. Rationale for the use of inhibitors of adenosine transport. Advances in pharmacology (San Diego, Calif.), 84, 3–19. https://doi.org/10.1016/bs.apha.2018.12.005
24. Xu, Y., Guan, Y., & Lang, B. (2025). Unraveling Restless Legs Syndrome: A Comprehensive Review of Current Research and Future Directions. International journal of general medicine, 18, 4041–4055. https://doi.org/10.2147/IJGM.S544680
25. Allen, R. P., Barker, P. B., Horská, A., & Earley, C. J. (2013). Thalamic glutamate/glutamine in restless legs syndrome: increased and related to disturbed sleep. Neurology, 80(22), 2028–2034. https://doi.org/10.1212/WNL.0b013e318294b3f6
26. Froese, D. S., Fowler, B., & Baumgartner, M. R. (2019). Vitamin B12 , folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation. Journal of inherited metabolic disease, 42(4), 673–685. https://doi.org/10.1002/jimd.12009
27. O’Leary, F., & Samman, S. (2010). Vitamin B12 in health and disease. Nutrients, 2(3), 299–316. https://doi.org/10.3390/nu2030299