Research Article
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Evaluation of Systemic and Hematological Inflammatory Markers in Patients with Vitamin D Deficiency

Year 2024, Volume: 31 Issue: 4, 296 - 303, 26.12.2024
https://doi.org/10.17343/sdutfd.1456455

Abstract

Objective: This study aims to comprehensively examine the effects of vitamin D (VD) on systemic and hematological inflammatory markers.
Material and Method: A total of 2889 patients with albumin, C-reactive protein (CRP), creatinine and leukocyte values within the reference ranges were included in this retrospective study. Patients were divided into three groups based on their 25-hydroxy VD levels: group-1 (VD deficiency, VD<12 ng/mL (30 nmol/L)), group-2 (VD insufficiency, VD=12-20 ng/mL (30-50 nmol/L)) and group-3 (sufficient VD status, VD>20 ng/mL (50 nmol/L)) groups. CRP-albumin ratio (CAR), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and prognostic nutritional index (PNI) were calculated.
Results: The age of the groups did not differ significantly (p=0.094), while the percentage of females was significantly higher in group-1 than in group-2 and group-3 (p<0.05). CRP, CAR, and PLR values were significantly lower in group-2 and group-3 compared to group-1 (p<0.05 for all). Albumin and PNI values were significantly higher in group-2 and group-3 compared to group-1 (p<0.05 for all). In the multinomial multivariate logistic regression analysis, conducted using sex, CAR, PNI, NLR, PLR, and LMR parameters with group-3 as the reference category, significant odds ratios (OR) were observed for female sex, CAR, and PNI in relation to group-1.
Conclusions: These results show that there were increases in CAR and PNI, markers of inflammation and nutritional status, in the VD-deficient population, although routine laboratory parameters were normal.

Ethical Statement

The study was approved by the Bolu Abant Izzet Baysal University Clinical Researches Ethics Committee (No: 2021/295, date: 21/12/2021) and the Declaration of Helsinki for research on humans was followed.

Supporting Institution

None.

Project Number

None

Thanks

None

References

  • 1. Wimalawansa SJ. Vitamin D Deficiency: Effects on oxidative stress, epigenetics, gene regulation, and aging. Biology (Basel) 2019;8(2):30.
  • 2. Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, et al. Global consensus recommendations on prevention and management of nutritional rickets. Hormone Research in Paediatrics 2016;85(2):83-106.
  • 3. Pilz S, Zittermann A, Trummer C, Theiler-Schwetz V, Lerchbaum E, Keppel MH, et al. Vitamin D testing and treatment: a narrative review of current evidence. Endocr Connect 2019;8(2):R27-R43.
  • 4. Cesari M, Incalzi RA, Zamboni V, Pahor M. Vitamin D hormone: a multitude of actions potentially influencing the physical function decline in older persons. Geriatr Gerontol Int 2011;11(2):133-42.
  • 5. E LB, Ismailova A, Dimeloe S, Hewison M, White JH. Vitamin D and immune regulation: Antibacterial, antiviral, anti-inflammatory. JBMR Plus 2021;5(1):e10405.
  • 6. Chen J, Tang Z, Slominski AT, Li W, Zmijewski MA, Liu Y, et al. Vitamin D and its analogs as anticancer and anti-inflammatory agents. European Journal of Medicinal Chemistry 2020;207:112738.
  • 7. Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor? Archives of Biochemistry and Biophysics 2012;523(1):123-33.
  • 8. Shakib H, Rajabi S, Dehghan MH, Mashayekhi FJ, Safari-Alighiarloo N, Hedayati M. Epithelial-to-mesenchymal transition in thyroid cancer: A comprehensive review. Endocrine 2019;66(3):435-55.
  • 9. Hoe E, Nathanielsz J, Toh ZQ, Spry L, Marimla R, Balloch A, et al. Anti-inflammatory effects of vitamin d on human immune cells in the context of bacterial infection. Nutrients 2016;8(12):806.
  • 10. Olliver M, Spelmink L, Hiew J, Meyer-Hoffert U, Henriques-Normark B, Bergman P. Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumoniae. The Journal of Infectious Diseases 2013;208(9):1474-81.
  • 11. Miyazaki T, Saji H, Nakamura H, Nagayasu T, Okumura N, Tsuchida M, et al. The C-reactive protein to albumin ratio is a prognostic factor for stage I non-small cell lung cancer in elderly patients: JACS1303. Surgery Today 2022;52(10):1463-71.
  • 12. Alisik M, Erdogan UG, Ates M, Sert MA, Yis OM, Bugdayci G. Predictive value of immature granulocyte count and other inflammatory parameters for disease severity in COVID‐19 patients. International Journal of Medical Biochemistry 2021;4(3):143-9.
  • 13. Tsai CM, Yu HR, Tang KS, Huang YH, Kuo HC. C-Reactive Protein to albumin ratio for predicting coronary artery lesions and intravenous immunoglobulin resistance in kawasaki disease. Front Pediatr 2020;8:607631.
  • 14. Bayrak M. Predictive value of C-Reactive Protein/Albumin ratio in patients with chronic complicated diabetes mellitus. Pak J Med Sci 2019;35(6):1616-21.
  • 15. Targońska-Stępniak B, Zwolak R, Piotrowski M, Grzechnik K, Majdan M. The relationship between hematological markers of systemic inflammation (Neutrophil-To-Lymphocyte, Platelet-To-Lymphocyte, Lymphocyte-To-Monocyte Ratios) and ultrasound disease activity parameters in patients with rheumatoid arthritis. Journal of Clinical Medicine 2020;9(9):2760.
  • 16. Hu X, Deng H, Wang Y, Chen L, Gu X, Wang X. Predictive value of the prognostic nutritional index for the severity of coronavirus disease 2019. Nutrition 2021;84:111123.
  • 17. Tang M, Jia Z, Zhang J. The prognostic role of prognostic nutritional index in nasopharyngeal carcinoma: A systematic review and meta-analysis. Int J Clin Oncol 2021;26(1):66-77.
  • 18. Okubo K, Arigami T, Matsushita D, Tanaka T, Tsuruda Y, Noda M, et al. Clinical impact of the prognostic nutritional index as a predictor of outcomes in patients with stage ii/iii gastric cancer: A Retrospective cohort study. Oncology-Basel 2021;99(6):380-8.
  • 19. Filgueiras MS, Rocha NP, Novaes JF, Bressan J. Vitamin D status, oxidative stress, and inflammation in children and adolescents: A systematic review. Crit Rev Food Sci Nutr 2020;60(4):660-9.
  • 20. Kruit A, Zanen P. The association between vitamin D and C-reactive protein levels in patients with inflammatory and non-inflammatory diseases. Clin Biochem 2016;49(7-8):534-7.
  • 21. López-Muñoz P, Beltrán B, Sáez-González E, Alba A, Nos P, Iborra M. Influence of vitamin D deficiency on inflammatory markers and clinical disease activity in IBD patients. Nutrients 2019;11(5):1059.
  • 22. Saponaro F, Franzini M, Okoye C, Antognoli R, Campi B, Scalese M, et al. Is there a crucial link between vitamin D status and inflammatory response in patients with cOVID-19? Frontiers in Immunology 2021;12:745713.
  • 23. Zhou A, Hypponen E. Vitamin D deficiency and C-reactive protein: A bidirectional Mendelian randomization study. International Journal of Epidemiology 2023;52(1):260-71.
  • 24. Garg M, Rosella O, Lubel JS, Gibson PR. Association of circulating vitamin D concentrations with intestinal but not systemic inflammation in inflammatory bowel disease. Inflammatory Bowel Diseases 2013;19(12):2634-43.
  • 25. Azizieh F, Alyahya KO, Raghupathy R. Association between levels of vitamin D and inflammatory markers in healthy women. Journal of Inflammation Research 2016;9:51-7.
  • 26. Popovska Jovičić B, Raković I, Gavrilović J, Sekulić Marković S, Petrović S, Marković V, et al. Vitamin D, Albumin, and D-Dimer as significant prognostic markers in early hospitalization in patients with COVID-19. Journal of Clinical Medicine 2023;12(8):2825.
  • 27. Hou J, Feng W, Liu W, Hou J, Die X, Sun J, et al. The use of the ratio of C-reactive protein to albumin for the diagnosis of complicated appendicitis in children. Am J Emerg Med 2022;52:148-54.
  • 28. Yevgi R, Bilge N, Simsek F, Eren A, Cimilli Senocak GN. Vitamin D levels and C-reactive protein/albumin ratio in pregnant women with cerebral venous sinus thrombosis. J Thromb Thrombolysis 2022;53(2):532-9.
  • 29. Kosidlo JW, Wolszczak-Biedrzycka B, Matowicka-Karna J, Dymicka-Piekarska V, Dorf J. Clinical significance and diagnostic utility of NLR, LMR, PLR and SII in the course of COVID-19: A Literature Review. Journal of Inflammation Research 2023;16:539-62.
  • 30. Erkus E, Aktas G, Atak BM, Kocak MZ, Duman TT, Savli H. Haemogram parameters in Vitamin D deficiency. J Coll Physicians Surg Pak 2018;28(10):779-82.
  • 31. Konuksever D, Yucel Karakaya SP, Boluk O, Kocak M, Kilic BO, Sac RU. The association of vitamin D deficiency with hemogram-derived inflammatory biomarkers in children. Nutr Metab Cardiovasc Dis 2022;32(10):2418-23.
  • 32. Akbas EM, Gungor A, Ozcicek A, Akbas N, Askin S, Polat M. Vitamin D and inflammation: Evaluation with neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio. Archives of Medical Science: AMS 2016;12(4):721-7.
  • 33. Santos ATd, Zardo AdLG, Kalva DC, Maciel MAS. Evaluation of vitamin D and inflammatory markers in elderly. Brazilian Journal of Pharmaceutical Sciences 2022;58.
  • 34. Tian LQ, Yu YT, Jin MD, Duan HL, Huang G, Zhang ML. Early 1,25-Dihydroxyvitamin D(3) supplementation effectively lowers the incidence of Type 2 Diabetes Mellitus via ameliorating inflammation in KK-A(y) mice. Journal of Nutritional Science and Vitaminology 2021;67(2):84-90.
  • 35. Gatera VA, Lesmana R, Musfiroh I, Judistiani RTD, Setiabudiawan B, Abdulah R. Vitamin D inhibits lipopolysaccharide (LPS)-induced inflammation in A549 cells by downregulating inflammatory cytokines. Medical Science Monitor Basic Research 2021;27:e931481.
  • 36. Gunasekar P, Swier VJ, Fleegel JP, Boosani CS, Radwan MM, Agrawal DK. Vitamin D and macrophage polarization in epicardial adipose tissue of atherosclerotic swine. PloS One 2018;13(10):e0199411.
  • 37. Mackawy AM, Badawi ME. Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients. Meta Gene 2014;2:540-56.
  • 38. Mirili C, Yilmaz A, Demirkan S, Bilici M, Basol Tekin S. Clinical significance of prognostic nutritional index (PNI) in malignant melanoma. Int J Clin Oncol 2019;24(10):1301-10.
  • 39. Sha S, Gwenzi T, Chen LJ, Brenner H, Schottker B. About the associations of vitamin D deficiency and biomarkers of systemic inflammatory response with all-cause and cause-specific mortality in a general population sample of almost 400,000 UK Biobank participants. Eur J Epidemiol 2023;Online ahead of print.

D vitamini eksikliği olan hastalarda sistemik ve hematolojik inflamatuar belirteçlerin değerlendirilmesi

Year 2024, Volume: 31 Issue: 4, 296 - 303, 26.12.2024
https://doi.org/10.17343/sdutfd.1456455

Abstract

Amaç
D vitamininin (VD) sistemik ve hematolojik inflamatuar belirteçler üzerindeki etkilerini araştırmak amaçlanmıştır.
Gereç ve yöntemler
Bu retrospektif çalışmaya albümin, C-reaktif protein (CRP), kreatinin ve lökosit değerleri referans aralıklarda olan toplam 2889 hasta dahil edilmiştir. Hastalar 25-hidroksi VD düzeylerine göre grup-1 (VD eksikliği, VD<12 ng/mL (30 nmol/L)), grup-2 (VD yetersizliği, VD=12-20 ng/mL (30-50 nmol/L)) ve grup-3 (yeterli VD durumu, VD>20 ng/mL (50 nmol/L)) grupları olmak üzere 3 gruba ayrılmıştır. CRP-albümin oranı (CAR), nötrofil-lenfosit oranı (NLR), trombosit-lenfosit oranı (PLR), lenfosit-monosit oranı (LMR) ve prognostik nutrisyonel indeks (PNI) hesaplanmıştır.
Bulgular
Grupların yaşları arasında anlamlı bir fark bulunmazken (p=0,094), kadın oranı grup-1'de grup-2 ve grup 3'e göre anlamlı derecede yüksekti (p<0,05). CRP, CAR ve PLR değerleri grup 2 ve grup 3'te grup 1'e kıyasla anlamlı derecede düşüktü (hepsi için p<0.05). Albümin ve PNI değerleri Grup 2 ve Grup 3'te grup 1'e kıyasla anlamlı derecede yüksekti (tümü için p<0.05). Cinsiyet, CAR, PNI, NLR, PLR ve LMR parametreleri ile yapılan ve grup-3'ün referans kategori olarak kullanıldığı multinominal çok değişkenli lojistik regresyon analizinde, grup-1 için kadın cinsiyet, CAR ve PNI odd oranları anlamlı bulundu.
Sonuç
Bu sonuçlar, rutin laboratuvar parametreleri normal olsa bile VD eksikliği olan popülasyonda inflamasyon ve beslenme durumu belirteçleri olan CAR’da artış ve PNI’da azalma olduğunu göstermektedir.

Project Number

None

References

  • 1. Wimalawansa SJ. Vitamin D Deficiency: Effects on oxidative stress, epigenetics, gene regulation, and aging. Biology (Basel) 2019;8(2):30.
  • 2. Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, et al. Global consensus recommendations on prevention and management of nutritional rickets. Hormone Research in Paediatrics 2016;85(2):83-106.
  • 3. Pilz S, Zittermann A, Trummer C, Theiler-Schwetz V, Lerchbaum E, Keppel MH, et al. Vitamin D testing and treatment: a narrative review of current evidence. Endocr Connect 2019;8(2):R27-R43.
  • 4. Cesari M, Incalzi RA, Zamboni V, Pahor M. Vitamin D hormone: a multitude of actions potentially influencing the physical function decline in older persons. Geriatr Gerontol Int 2011;11(2):133-42.
  • 5. E LB, Ismailova A, Dimeloe S, Hewison M, White JH. Vitamin D and immune regulation: Antibacterial, antiviral, anti-inflammatory. JBMR Plus 2021;5(1):e10405.
  • 6. Chen J, Tang Z, Slominski AT, Li W, Zmijewski MA, Liu Y, et al. Vitamin D and its analogs as anticancer and anti-inflammatory agents. European Journal of Medicinal Chemistry 2020;207:112738.
  • 7. Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor? Archives of Biochemistry and Biophysics 2012;523(1):123-33.
  • 8. Shakib H, Rajabi S, Dehghan MH, Mashayekhi FJ, Safari-Alighiarloo N, Hedayati M. Epithelial-to-mesenchymal transition in thyroid cancer: A comprehensive review. Endocrine 2019;66(3):435-55.
  • 9. Hoe E, Nathanielsz J, Toh ZQ, Spry L, Marimla R, Balloch A, et al. Anti-inflammatory effects of vitamin d on human immune cells in the context of bacterial infection. Nutrients 2016;8(12):806.
  • 10. Olliver M, Spelmink L, Hiew J, Meyer-Hoffert U, Henriques-Normark B, Bergman P. Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumoniae. The Journal of Infectious Diseases 2013;208(9):1474-81.
  • 11. Miyazaki T, Saji H, Nakamura H, Nagayasu T, Okumura N, Tsuchida M, et al. The C-reactive protein to albumin ratio is a prognostic factor for stage I non-small cell lung cancer in elderly patients: JACS1303. Surgery Today 2022;52(10):1463-71.
  • 12. Alisik M, Erdogan UG, Ates M, Sert MA, Yis OM, Bugdayci G. Predictive value of immature granulocyte count and other inflammatory parameters for disease severity in COVID‐19 patients. International Journal of Medical Biochemistry 2021;4(3):143-9.
  • 13. Tsai CM, Yu HR, Tang KS, Huang YH, Kuo HC. C-Reactive Protein to albumin ratio for predicting coronary artery lesions and intravenous immunoglobulin resistance in kawasaki disease. Front Pediatr 2020;8:607631.
  • 14. Bayrak M. Predictive value of C-Reactive Protein/Albumin ratio in patients with chronic complicated diabetes mellitus. Pak J Med Sci 2019;35(6):1616-21.
  • 15. Targońska-Stępniak B, Zwolak R, Piotrowski M, Grzechnik K, Majdan M. The relationship between hematological markers of systemic inflammation (Neutrophil-To-Lymphocyte, Platelet-To-Lymphocyte, Lymphocyte-To-Monocyte Ratios) and ultrasound disease activity parameters in patients with rheumatoid arthritis. Journal of Clinical Medicine 2020;9(9):2760.
  • 16. Hu X, Deng H, Wang Y, Chen L, Gu X, Wang X. Predictive value of the prognostic nutritional index for the severity of coronavirus disease 2019. Nutrition 2021;84:111123.
  • 17. Tang M, Jia Z, Zhang J. The prognostic role of prognostic nutritional index in nasopharyngeal carcinoma: A systematic review and meta-analysis. Int J Clin Oncol 2021;26(1):66-77.
  • 18. Okubo K, Arigami T, Matsushita D, Tanaka T, Tsuruda Y, Noda M, et al. Clinical impact of the prognostic nutritional index as a predictor of outcomes in patients with stage ii/iii gastric cancer: A Retrospective cohort study. Oncology-Basel 2021;99(6):380-8.
  • 19. Filgueiras MS, Rocha NP, Novaes JF, Bressan J. Vitamin D status, oxidative stress, and inflammation in children and adolescents: A systematic review. Crit Rev Food Sci Nutr 2020;60(4):660-9.
  • 20. Kruit A, Zanen P. The association between vitamin D and C-reactive protein levels in patients with inflammatory and non-inflammatory diseases. Clin Biochem 2016;49(7-8):534-7.
  • 21. López-Muñoz P, Beltrán B, Sáez-González E, Alba A, Nos P, Iborra M. Influence of vitamin D deficiency on inflammatory markers and clinical disease activity in IBD patients. Nutrients 2019;11(5):1059.
  • 22. Saponaro F, Franzini M, Okoye C, Antognoli R, Campi B, Scalese M, et al. Is there a crucial link between vitamin D status and inflammatory response in patients with cOVID-19? Frontiers in Immunology 2021;12:745713.
  • 23. Zhou A, Hypponen E. Vitamin D deficiency and C-reactive protein: A bidirectional Mendelian randomization study. International Journal of Epidemiology 2023;52(1):260-71.
  • 24. Garg M, Rosella O, Lubel JS, Gibson PR. Association of circulating vitamin D concentrations with intestinal but not systemic inflammation in inflammatory bowel disease. Inflammatory Bowel Diseases 2013;19(12):2634-43.
  • 25. Azizieh F, Alyahya KO, Raghupathy R. Association between levels of vitamin D and inflammatory markers in healthy women. Journal of Inflammation Research 2016;9:51-7.
  • 26. Popovska Jovičić B, Raković I, Gavrilović J, Sekulić Marković S, Petrović S, Marković V, et al. Vitamin D, Albumin, and D-Dimer as significant prognostic markers in early hospitalization in patients with COVID-19. Journal of Clinical Medicine 2023;12(8):2825.
  • 27. Hou J, Feng W, Liu W, Hou J, Die X, Sun J, et al. The use of the ratio of C-reactive protein to albumin for the diagnosis of complicated appendicitis in children. Am J Emerg Med 2022;52:148-54.
  • 28. Yevgi R, Bilge N, Simsek F, Eren A, Cimilli Senocak GN. Vitamin D levels and C-reactive protein/albumin ratio in pregnant women with cerebral venous sinus thrombosis. J Thromb Thrombolysis 2022;53(2):532-9.
  • 29. Kosidlo JW, Wolszczak-Biedrzycka B, Matowicka-Karna J, Dymicka-Piekarska V, Dorf J. Clinical significance and diagnostic utility of NLR, LMR, PLR and SII in the course of COVID-19: A Literature Review. Journal of Inflammation Research 2023;16:539-62.
  • 30. Erkus E, Aktas G, Atak BM, Kocak MZ, Duman TT, Savli H. Haemogram parameters in Vitamin D deficiency. J Coll Physicians Surg Pak 2018;28(10):779-82.
  • 31. Konuksever D, Yucel Karakaya SP, Boluk O, Kocak M, Kilic BO, Sac RU. The association of vitamin D deficiency with hemogram-derived inflammatory biomarkers in children. Nutr Metab Cardiovasc Dis 2022;32(10):2418-23.
  • 32. Akbas EM, Gungor A, Ozcicek A, Akbas N, Askin S, Polat M. Vitamin D and inflammation: Evaluation with neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio. Archives of Medical Science: AMS 2016;12(4):721-7.
  • 33. Santos ATd, Zardo AdLG, Kalva DC, Maciel MAS. Evaluation of vitamin D and inflammatory markers in elderly. Brazilian Journal of Pharmaceutical Sciences 2022;58.
  • 34. Tian LQ, Yu YT, Jin MD, Duan HL, Huang G, Zhang ML. Early 1,25-Dihydroxyvitamin D(3) supplementation effectively lowers the incidence of Type 2 Diabetes Mellitus via ameliorating inflammation in KK-A(y) mice. Journal of Nutritional Science and Vitaminology 2021;67(2):84-90.
  • 35. Gatera VA, Lesmana R, Musfiroh I, Judistiani RTD, Setiabudiawan B, Abdulah R. Vitamin D inhibits lipopolysaccharide (LPS)-induced inflammation in A549 cells by downregulating inflammatory cytokines. Medical Science Monitor Basic Research 2021;27:e931481.
  • 36. Gunasekar P, Swier VJ, Fleegel JP, Boosani CS, Radwan MM, Agrawal DK. Vitamin D and macrophage polarization in epicardial adipose tissue of atherosclerotic swine. PloS One 2018;13(10):e0199411.
  • 37. Mackawy AM, Badawi ME. Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients. Meta Gene 2014;2:540-56.
  • 38. Mirili C, Yilmaz A, Demirkan S, Bilici M, Basol Tekin S. Clinical significance of prognostic nutritional index (PNI) in malignant melanoma. Int J Clin Oncol 2019;24(10):1301-10.
  • 39. Sha S, Gwenzi T, Chen LJ, Brenner H, Schottker B. About the associations of vitamin D deficiency and biomarkers of systemic inflammatory response with all-cause and cause-specific mortality in a general population sample of almost 400,000 UK Biobank participants. Eur J Epidemiol 2023;Online ahead of print.
There are 39 citations in total.

Details

Primary Language English
Subjects Clinical Sciences (Other)
Journal Section Research Articles
Authors

Tuğba Alışık 0000-0003-1856-9513

Project Number None
Publication Date December 26, 2024
Submission Date March 21, 2024
Acceptance Date September 20, 2024
Published in Issue Year 2024 Volume: 31 Issue: 4

Cite

Vancouver Alışık T. Evaluation of Systemic and Hematological Inflammatory Markers in Patients with Vitamin D Deficiency. Med J SDU. 2024;31(4):296-303.

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