A New Inflammatory Marker: Vitamin B12

Year 2019, Volume: 4 Issue: 1, 1 - 12, 31.03.2019

Dilek Oztas Serpil Erdogan , Ali Benzil Osman Nadar Ozcan Erel

Abstract

Introduction: For years, decreased vitamin B12 level and its clinical
importance have been investigated. İncreased vitamin B12 was not fully investigated.
However, it has been proposed that increased vitamin B12 is associated with several
diseases such as cancer, alcoholism, liver disease. Secretion of ferritin, an
acute phase reactant, is controlled via cytokines and it has been established increasing
with inflammatory diseases. It has been proved that C-reactive protein (CRP) is
a useful marker in several diseases including cancer, cardiovascular diseases
and diabetes mellitus. Aim of this study is to investigate whether or not
increased vitamin B12 levels are associated with serum ferritin and CRP levels.

Materials and Methods: Vitamin B12, ferritin and CRP levels were screened
via hospital information system. According to vitamin B12 levels patients were divided
into three groups: Low level (Group A), normal level (Group B), high level (Group
C). For thousand seven hundred and seven patients were included in study I
investigated association between vitamin B12 and ferritin, while 1071 patients
were included in study II investigated association between vitamin B12 and CRP.

Results: In study I, it has been demonstrated that there is an important difference
Group A and C; and Group B and C. In study II, it has been demonstrated that
there is an important difference Group A and C; and Group B and C.

Conclusions: It has been demonstrated that vitamin B12 level is
associated with ferritin and CRP. It has been thought that vitamin B12 levels
might be an inflammatory marker. 

Keywords

Vitamin B12, inflammation, ferritin, crp

Yeni Bir İnflamatuar Belirteç: Vitamin B12

Abstract

Amaç: Yıllardır serum vitamin B12 düzeyinin düşüklüğü
ve bu durumun klinik önemi araştırılmaktadır. Yüksek vitamin B12 düzeyleri ise
gereğince araştırılamamıştır. Oysa ki yüksek vitamin B12 düzeylerinin kanser,
alkolizm, karaciğer hastalığı gibi bazı önemli hastalıklarla ilişkili olduğu
ileri sürülmüştür. Bir akut faz reaktanı olan ferritinin salınımı sitokinlerle
kontrol edilir ve inflamatuar olaylarda arttığı gösterilmiştir. C reaktif
proteinin (CRP) kanser, kardiyovasküler hastalıklar ve diabetes mellitus dahil
pek çok hastalıkta faydalı bir belirteç olduğu kanıtlanmıştır. Bu çalışmanın
amacı yüksek vitamin B12 düzeylerinin serum ferritin ve CRP düzeyleri ile
ilişkili olup olmadığının araştırılmasıdır.

Gereç ve Yöntem: Hastane bilgi yönetim sistemi üzerinden vitamin
B12, ferritin ve CRP sonuçları tarandı. Hastalar vitamin B12 testine göre üç
gruba ayrıldı: Vitamin B12 düzeyi düşük (Grup A), normal (Grup B) ve yüksek
(Grup C) olanlar. Vitamin B12 ile ferritin arasındaki ilişkinin araştırıldığı
Çalışma I’e 4707, Vitamin B12 ile CRP arasındaki ilişkinin araştırıldığı
Çalışma II’ye 1071 hasta dahil edildi.

Bulgular: Çalışma I’de serum ferritin konsantrasyonu açısından
Grup A ve C ile Grup B ve C arasında istatistiksel açıdan anlamlı bir farklılık
olduğu bulundu. Çalışma II’de serum CRP konstantrasyonu açısından Grup B ve C
arasında istatistiksel açıdan anlamlı bir farklılık olduğu görüldü.

Sonuç: Sonuç olarak bu çalışmada vitamin B12 düzeyinin
inflamatuar belirteçlerden ferritin ve CRP ile ilişkili olduğu gösterilmiştir.
Bu verilere dayanılarak vitamin B12 düzeyinin de inflamasyon ile ilişkili bir
belirteç olabileceği düşünülmektedir.

Keywords

Vitamin B12, inflamasyon, ferritin, CRP

References

• 1. Kunimura S, Tokuoka Y, Aono U. Trace determination of cyanocobalamin (vitamin B12) by analyzing cobalt using a portable total reflection X-ray fluorescence spectrometer. Analytical sciences : the international journal of the Japan Society for Analytical Chemistry. 2018.
• 2. Elliott TR, Guildford AL. An In Vitro Model of Gastric Inflammation and Treatment with Cobalamin. International journal of inflammation. 2017;2017:5968618.
• 3. Kamath A, Pemminati S. Methylcobalamin in Vitamin B12 Deficiency: To Give or not to Give? Journal of pharmacology & pharmacotherapeutics. 2017;8(1):33-4.
• 4. Ermens AA, Vlasveld LT, Lindemans J. Significance of elevated cobalamin (vitamin B12) levels in blood. Clinical biochemistry. 2003;36(8):585-90.
• 5. Greibe E, Nymark O, Fedosov SN, Heegaard CW, Nexo E. Dietary Intake of Vitamin B12 is Better for Restoring a Low B12 Status Than a Daily High-Dose Vitamin Pill: An Experimental Study in Rats. Nutrients. 2018;10(8).
• 6. Watson J, Lee M, Garcia-Casal MN. Consequences of Inadequate Intakes of Vitamin A, Vitamin B12, Vitamin D, Calcium, Iron, and Folate in Older Persons. Current geriatrics reports. 2018;7(2):103-13.
• 7. Beyazit F, Pek E. Effects of vitamin B12, folate, uric acid, and serum biomarkers of inflammation on bone mineral density in postmenopausal women. Przeglad menopauzalny = Menopause review. 2018;17(2):69-76.
• 8. Carmel R, Vasireddy H, Aurangzeb I, George K. High serum cobalamin levels in the clinical setting--clinical associations and holo-transcobalamin changes. Clinical and laboratory haematology. 2001;23(6):365-71.
• 9. Zulfiqar AA, Sebaux A, Drame M, Pennaforte JL, Novella JL, Andres E. Hypervitaminemia B12 in elderly patients: Frequency and nature of the associated or linked conditions. Preliminary results of a study in 190 patients. European journal of internal medicine. 2015;26(10):e63-4.
• 10. Andres E, Serraj K, Zhu J, Vermorken AJ. The pathophysiology of elevated vitamin B12 in clinical practice. QJM : monthly journal of the Association of Physicians. 2013;106(6):505-15.
• 11. Arendt JF, Nexo E. Cobalamin related parameters and disease patterns in patients with increased serum cobalamin levels. PloS one. 2012;7(9):e45979.
• 12. Shipton MJ, Thachil J. Vitamin B12 deficiency - A 21st century perspective. Clinical medicine. 2015;15(2):145-50.
• 13. Ahmed MS, Jadhav AB, Hassan A, Meng QH. Acute phase reactants as novel predictors of cardiovascular disease. ISRN inflammation. 2012;2012:953461.
• 14. Kiechl S, Willeit J, Egger G, Poewe W, Oberhollenzer F. Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation. 1997;96(10):3300-7.
• 15. Sung KC, Kang JH, Shin HS. Relationship of cardiovascular risk factors and serum ferritin with C-reactive protein. Archives of medical research. 2007;38(1):121-5.
• 16. Shrotriya S, Walsh D, Nowacki AS, Lorton C, Aktas A, Hullihen B, et al. Serum C-reactive protein is an important and powerful prognostic biomarker in most adult solid tumors. PloS one. 2018;13(8):e0202555.
• 17. Pastorino U, Morelli D, Leuzzi G, Gisabella M, Suatoni P, Taverna F, et al. Baseline and postoperative C-reactive protein levels predict mortality in operable lung cancer. European journal of cancer. 2017;79:90-7.
• 18. Rasic I, Rebic V, Rasic A, Aksamija G, Radovic S. The Association of Simultaneous Increase in Interleukin-6, C Reactive Protein, and Matrix Metalloproteinase-9 Serum Levels with Increasing Stages of Colorectal Cancer. Journal of oncology. 2018;2018:2830503.
• 19. Shinohara S, Sugaya M, Onitsuka T, Machida K, Matsuo M, Tanaka F. Prognostic Impact of Postoperative C-reactive Protein for Non-small Cell Lung Cancer Following Lobectomy. Anticancer research. 2018;38(5):3193-8.
• 20. Barber MD, Ross JA, Fearon KC. Changes in nutritional, functional, and inflammatory markers in advanced pancreatic cancer. Nutrition and cancer. 1999;35(2):106-10.
• 21. Emerging Risk Factors C, Kaptoge S, Di Angelantonio E, Pennells L, Wood AM, White IR, et al. C-reactive protein, fibrinogen, and cardiovascular disease prediction. The New England journal of medicine. 2012;367(14):1310-20.
• 22. Lamblin N, Mouquet F, Hennache B, Dagorn J, Susen S, Bauters C, et al. High-sensitivity C-reactive protein: potential adjunct for risk stratification in patients with stable congestive heart failure. European heart journal. 2005;26(21):2245-50.
• 23. Ragy MM, Kamal NN. Linking senile dementia to type 2 diabetes: role of oxidative stress markers, C-reactive protein and tumor necrosis factor-alpha. Neurological research. 2017;39(7):587-95.
• 24. Di Napoli M, Godoy DA, Campi V, del Valle M, Pinero G, Mirofsky M, et al. C-reactive protein level measurement improves mortality prediction when added to the spontaneous intracerebral hemorrhage score. Stroke. 2011;42(5):1230-6.
• 25. Bulzacka E, Boyer L, Schurhoff F, Godin O, Berna F, Brunel L, et al. Chronic Peripheral Inflammation is Associated With Cognitive Impairment in Schizophrenia: Results From the Multicentric FACE-SZ Dataset. Schizophrenia bulletin. 2016;42(5):1290-302.
• 26. Seddon JM, Gensler G, Milton RC, Klein ML, Rifai N. Association between C-reactive protein and age-related macular degeneration. Jama. 2004;291(6):704-10.
• 27. Moll R, Davis B. Iron, vitamin B12 and folate. Medicine. 2017;45(4):198-203.
• 28. Pant V, Tumbapo A, Yadav BK. Vitamin B12 immunoassay interference in a patient with multiple myeloma - troubleshooting in a two step reagent kit based on enhanced chemiluminescence testing. Ejifcc. 2018;29(2):152-5.
• 29. Argan O, Ural D, Karauzum K, Bozyel S, Aktas M, Karauzum IY, et al. Elevated levels of vitamin B12 in chronic stable heart failure: a marker for subclinical liver damage and impaired prognosis. Therapeutics and clinical risk management. 2018;14:1067-73.
• 30. Abdelkader NA, Zaky DZ, Afifi H, Saad WE, Shalaby SI, Mansour MA. Neuropathies in hepatitis C-related liver cirrhosis. Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology. 2014;33(6):554-9.
• 31. Brah S, Chiche L, Mancini J, Meunier B, Arlet JB. Characteristics of patients admitted to internal medicine departments with high serum cobalamin levels: results from a prospective cohort study. European journal of internal medicine. 2014;25(5):e57-8.
• 32. Norredam K, Chainuvati T, Gimsing P, Hippe E, Viranuvatti V. Plasma cobalamin and transcobalamin in patients with primary carcinoma of the liver. A study from Thailand. Scandinavian journal of gastroenterology. 1983;18(2):229-32.
• 33. Arendt JF, Pedersen L, Nexo E, Sorensen HT. Elevated plasma vitamin B12 levels as a marker for cancer: a population-based cohort study. Journal of the National Cancer Institute. 2013;105(23):1799-805.
• 34. Oh HK, Lee JY, Eo WK, Yoon SW, Han SN. Elevated Serum Vitamin B12 Levels as a Prognostic Factor for Survival Time in Metastatic Cancer Patients: A Retrospective Study. Nutrition and cancer. 2018;70(1):37-44.
• 35. Lin CY, Kuo CS, Lu CL, Wu MY, Huang RF. Elevated serum vitamin B(12) levels in association with tumor markers as the prognostic factors predictive for poor survival in patients with hepatocellular carcinoma. Nutrition and cancer. 2010;62(2):190-7.
• 36. Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. International immunology. 2017;29(9):401-9.
• 37. Dignass A, Farrag K, Stein J. Limitations of Serum Ferritin in Diagnosing Iron Deficiency in Inflammatory Conditions. International journal of chronic diseases. 2018;2018:9394060.
• 38. Song A, Eo W, Kim S, Shim B, Lee S. Significance of serum ferritin as a prognostic factor in advanced hepatobiliary cancer patients treated with Korean medicine: a retrospective cohort study. BMC complementary and alternative medicine. 2018;18(1):176.
• 39. Ma H, Lin H, Hu Y, Li X, He W, Jin X, et al. Serum ferritin levels are associated with insulin resistance in Chinese men and post-menopausal women: the Shanghai Changfeng study. The British journal of nutrition. 2018;120(8):863-71.
• 40. Choi B, Yeum KJ, Park SJ, Kim KN, Joo NS. Elevated serum ferritin and mercury concentrations are associated with hypertension; analysis of the fourth and fifth Korea national health and nutrition examination survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). Environmental toxicology. 2015;30(1):101-8.
• 41. Jung JY, Shim JJ, Park SK, Ryoo JH, Choi JM, Oh IH, et al. Serum ferritin level is associated with liver steatosis and fibrosis in Korean general population. Hepatology international. 2018.
• 42. Su XW, Clardy SL, Stephens HE, Simmons Z, Connor JR. Serum ferritin is elevated in amyotrophic lateral sclerosis patients. Amyotrophic lateral sclerosis & frontotemporal degeneration. 2015;16(1-2):102-7.
• 43. Unal AU, Kostek O, Takir M, Caklili O, Uzunlulu M, Oguz A. Prognosis of patients in a medical intensive care unit. Northern clinics of Istanbul. 2015;2(3):189-95.