The categorical data were presented as absolute values and as percentages and were compared using Chi-squared test. doi: 10.7759/cureus.31936. The https:// ensures that you are connecting to the Urbanski, G. et al. Symptoms may develop over time and include: 5. The difference was linked to a more frequent occurrence of incident solid cancer in the EE group (p<0.001 compared with EN and NN groups), as the EN and NN groups did not differ (p=0.28). Prevalence of high B12 was evaluated during a 10-month period. . The remainder of vitamin B12 is bound to TC (holo-TC). 26. Is high vitamin B12 status a cause of lung cancer? This site needs JavaScript to work properly. Can Rheumatoid arthritis cause elevated B12? ---Significance of elevated cobalamin (vitamin B12) levels in blood--- Abstract "Elevated levels of serum cobalamin may be a sign of a serious, even life-threatening, disease. This still can be the cause of high B-12 without supplementation but there could be other, more serious, reasons for this as well. However, to our knowledge, no study has evaluated this association according to the persistence of this B12 elevation. hbspt.cta._relativeUrls=true;hbspt.cta.load(119382, 'ab73c5a4-6cc2-47ae-89ec-692921a42cf5', {"useNewLoader":"true","region":"na1"}); Southwest Integrative Medicine 4045 East Bell Road Phoenix, AZ 85032 480.451.5407. 4, 5 All conditions may show elevated concentrations of B12 transport proteins. 2. Moreover, Arendt et al. Clipboard, Search History, and several other advanced features are temporarily unavailable. Pregnant and breastfeeding women may also need to be especially mindful of B12 levels. MeSH Vitamin B12 also plays an important role in hematopoiesis and maintaining the integrity of the nervous system. The following vitamin B12 supplements all feature highly-absorbable forms of the vital vitamin. To date, the mechanism of the elevated vitamin B12 concentrations in ALPS patients has not been determined and we sought to explore the source of elevated vitamin B12. 2022 Aug 9;17(1):310. doi: 10.1186/s13023-022-02453-z. What level of B12 is dangerously high? The prognostic nature of elevated B12 in solid cancers suggested the question of a possible link with the tumor mass or the capacity for proliferation20. Milman, N., Byg, K.-E., Bergholt, T., Eriksen, L. & Hvas, A.-M. Cobalamin status during normal pregnancy and postpartum: A longitudinal study comprising 406 Danish women. 28, 814821 (2019). I have also been on metformin 12 years and know that can lead to b12 deficiency. The occurrence of solid cancers in 20.8% of patients in the EE group could justify careful clinical surveillance and raises the question of carrying out complementary investigations. Some examples include: 664.219; 5131; 700 (high) and 1500 (very high)11; and 601 (high) and 1000 (very high)10. The Content on this Site is presented in a summary fashion, and is intended to be used for educational and entertainment purposes only. Unable to load your collection due to an error, Unable to load your delegates due to an error. 40, 158165 (2016). Remacha AF, Sard MP, Canals C, Queralt JM, Zapico E, Remacha J, Carrascosa C. Ann Hematol. Am. Left untreated, pernicious anemia can cause serious medical issues, including irreversible damage to your nervous system. Therefore the B-12 just, Role of Inflammation in High B12 Without Supplementation, What To Do With High B12 Without Supplementation. We evaluated the incidence of solid cancers following B12 measurement in patients with persistent elevated B12, compared to patients without elevated B12 and to patients with non-persistent elevated B12. Events only referred to solid cancers and not to blood malignancies. Hepatitis and Hepatocellular Carcinoma can also lead to increase release of B-12 from the cells being damaged. Article High blood B12 levels can occur in liver conditions such as cirrhosis and hepatitis. Patients were required to have undergone two B12 measurements at 2 different times (T1 and T2) at 1 to 48months intervals. Let's look at that next. If the kidneys cells have damaged receptors they can no longer take in the B-12 and there is more in in bloodstream. The basis of this article is to discuss some of the more serious or problematic things that could be causing your high vitamin B-12. 11, 715 (2013). All conditions may show elevated concentrations of B12 transport proteins. official website and that any information you provide is encrypted with the methylmalonic acid in particular being of importance. Inflammation is very nonspecific but various cases of autoimmune disease, like lupus etc have been described as causing elevated B-12 levels. One of them is called methylmalonic acid and the other one is called homocysteine. Br. Patients with persistent high levels of serum vitamin B12 were often referred to Hematology departments. Vitamin B12 or folate deficiency anaemia - Causes - NHS 89, 812819 (2008). Cite this article. Control patients were randomly selected among those with B12<1000ng/L at T1 and T2, with a ratio 1:1, matching for sex, age and the number of B12 measurements (2, 3,4) during the study period. IUBMB Life 68, 303310 (2016). Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Persistent elevation of plasma vitamin B12 is strongly - Nature & Nexo, E. Cobalamin related parameters and disease patterns in patients with increased serum cobalamin levels. The word "pernicious" means gradually harmful and damaging. Consequences include atrophic gastritis, B12 malabsorption, and, frequently, pernicious anemia. Both the cell membrane and transcobalamin proteins can be a part of the issue and solution. These are typical labs that are done in a general screening called CBC and Chem panel. 2012 Oct 31;8(360):2072-4, 2076-7. However, ICs were detected in 10 frozen samples and in seven cases (25%) of the prospective study, respectively. Cancer 116, 14991504 (2017). Disclaimer. Some causes can be explored with simple investigations (blood count, renal function evaluation, liver cytolysis and cholestasis parameters, and liver echography) but solid cancer exploration often requires imaging or endoscopic examinations. Most of these more serious causes are altering the transportation of B-12 via the transcobalamin transport proteins (more on this below). https://www.westonaprice.org/soy-alert . Compared with the NN group as a reference, only the EE group was significantly associated with incident cancer with HR 5.90 [95% CI 2.7912.45] (p<0.001), contrary to the EN group (HR 1.52 [95% CI 0.703.30], p=0.29) (Table 2). J. Clin. High serum vitamin B12 concentrations have been observed in patients with ALPS studied at NIH Clinical Center. BMC Med. Gimsing, P. Cobalamin metabolism in chronic myelogenous leukemia. Thanks for the replies guys I believe the High IgA is most definately polyclonal, paraprotein was checked on a previous test and was negative and the blood cancers have been checked out by the blood specialist are are also negative. I also high MCH. Functional cobalamin deficiency can thus occur at any serum level. Sign up for the Nature Briefing: Cancer newsletter what matters in cancer research, free to your inbox weekly. 24. Vitamin B12 - Critically Important but Often Not Diagnosed or Treated V.L. Rev. PubMedGoogle Scholar. However, a falsely normal or high value of vitamin B12 in the blood may occur if antibodies interfere with the test. The proportion of men was higher in the EE group, but with no significant difference (p=0.06). However, it can have more to do with the transportation of B-12 rather than the cell membrane. Whiteman, D. C. & Wilson, L. F. The fractions of cancer attributable to modifiable factors: A global review. It is the TCN 2 transporter that is the main transporter for B-12. . All Rights Reserved. The study population included patients with at least two plasma B12 measurements without already known elevated-B12-related causes. A codified approach is needed to determine the potential indications of a search for high serum cobalamin and the practical clinical strategy to adopt upon discovery of elevated cobalamin levels. Hampered vitamin B12 metabolism in gaucher disease?. J Clin Med. 49, 11 (2011). BMC Health Serv. Disclosures: No relevant conflicts of interest to declare. Provided by the Springer Nature SharedIt content-sharing initiative. When platelet levels are low, the blood does not clot well, and bleeding cannot be controlled following minor injuries. Essentially these transcobalamin molecules are carried through the cell membrane after binding to the B-12 receptor on the cell. What vitamin Am I lacking if my joints hurt? 2020 Oct 9;18(1):307. doi: 10.1186/s12916-020-01771-y. Thank you for visiting nature.com. The .gov means its official. What level of B12 is dangerously high? This part of the small intestine is where vitamin B 12 is absorbed. Thus, doctors should monitor patients with ALPS for symptoms of lymphoma, such as night sweats, fever, fatigue, weight loss, loss of appetite, and sudden lymph node enlargement. Joint pain. In the meantime, to ensure continued support, we are displaying the site without styles 76, 521525 (2006). J. Haematol. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. PLoS ONE 7, e45979 (2012). GP60 Clinical utility of elevated vitamin B12 levels with a Patients with pernicious anemia or those supplemented with vitamin B12 were also excluded. The influence of covariate (including age, sex, and all the elevated-B12-related causes) on the occurrence of solid cancer was evaluated with a survival competing risk model (package cmprsk from R) with the death as the competing risk. Search for other works by this author on: Thank you for submitting a comment on this article. Before 2022 Sep 28;11(10):1919. doi: 10.3390/antiox11101919. Raffick AR Bowen, Janet K Dale, Margaret Brown, Steven K Drake, Tarsilla Moura, Kennichi Dowdell, Alan T Remaley, Thomas A Fleisher, Glen L Hortin, Ebba Nexo, Stephen E Straus, V. Koneti Rao; Significantly Elevated Vitamin B12 Levels in Autoimmune Lymphoproliferative Syndrome (ALPS), a Rare Lymphoproliferative Disorder with Apoptosis Defect. That sounds like an oxymoron, "you're saying you're high in B-12 but you're actually deficient? A. Metab Target Organ Damage. Epub 2014 Oct 16. High or supraphysiological serum B12 levels without supplementation have been associated with many pathological conditions including renal failure, haematological disorders, cancer, and hepatic or autoimmune diseases. It also is normal for lymph nodes to change somewhat in size, shape, or feel over time. Significantly Elevated Vitamin B12 Levels in Autoimmune Lymphoproliferative Syndrome (ALPS), a Rare Lymphoproliferative DisorderLymphoproliferative DisorderLymphoproliferative disorders are a set of disorders characterized by the abnormal proliferation of lymphocytes into a monoclonal lymphocytosis. Article An official website of the United States government. Cancer-free survival in the 3 groups. 22. doi: 10.1002/pul2.12173. Federal government websites often end in .gov or .mil. Level was 33 (27-32). You are using a browser version with limited support for CSS. Nat. The quantitative data were presented in medians and quartiles and compared using a Student t test or an ANOVA. Persistent elevation of plasma vitamin B12 is strongly associated with solid cancer, https://doi.org/10.1038/s41598-021-92945-y. An association with autoimmune or hematological disorders was observed. J. Jo. Ermens AA, Vlasveld LT, van Marion-Kievit JA, Lensen CJ, Lindemans J. Ned Tijdschr Geneeskd. Measuring holotranscobalamin II, an early indicator of negative vitamin B12 balance, by radioimmunoassay in patients with ischemic cerebrovascular disease. Vitamin B 12 is an essential micronutrient that plays a fundamental role in cell division and one-carbon metabolism. Gimsing, P. Cobalamin forms and analogues in plasma and myeloid cells during chronic myelogenous leukaemia related to clinical condition. Precipitation with PEG is an easy method to confirm the presence of ICs and to evaluate serum vitamin B12 levels in these patients. Time-to-event curves for incident solid cancer were presented as KaplanMeier curves and were compared with a log-rank test. The results of this study show for the first time that elevated concentrations of vitamin B12 found in ALPS patients were due to increased leukocyte (including lymphocytes) expression of HC. All patient records have been fully reviewed. The most common rise in immunoglobulin levels is polyclonal, and due to immune system activity caused by infection or autoimmune diseases. The second hypothesis is that of the release of haptocorrins by the granulocytic cells involved in the anti-tumor response. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Results: Therefore, malabsorption of vitamin B-12 is quite likely to occur in patients with CD. An official website of the United States government. Vitamin B12 in serum is bound to two proteins, haptocorrin (HC) and transcobalamin (TC). Zibold J, von Livonius B, Kolarova H, Rudolph G, Priglinger CS, Klopstock T, Catarino CB. Careers. Pernicious Anemia: Definition, Symptoms, Causes & Treatment So how does B-12 get into the cell? Clin. Autoimmune Metaplastic Atrophic Gastritis - Merck Manuals Professional Please check for further notifications by email. Immune complexes and persistent high levels of serum vitamin B12 Autoimmune Lymphoproliferative Syndrome (ALPS) Symptoms & Diagnosis Serum B12 level in patients with rheumatoid arthritis was significantly higher than that in patients with osteoarthritis and normal subjects. Actually I now am like most people with autoimmune diseases because the test showed me deficient. Most commonly it would be liver tumors, hepatocellular carcinoma in particular. J. The analyses were carried out using GRAPHPAD Prism v6.01 (GRAPHPAD SOFTWARE, La Jolla, CA, USA) and R software (version 3.5.1, R-project.org, Vienna, Austria). Accessibility showed that the SIR of cancers was higher within the year following B12 measurement than in subsequent years16. Med. Kingma TJ, Bascoy S, Altaf MD, Surampudy A, Chaudhry B. Cureus. Patients with elevated plasma B12 (1000ng/L) at first measurement (n=344) were matched for age and sex with patients having 2 normal B12 measurements (<1000ng/L) (NN group, n=344). Berg, R. L. & Shaw, G. R. Laboratory evaluation for vitamin B12 deficiency: The case for cascade testing. Vitamin B12 is an essential micronutrient that plays a fundamental role in cell division and one-carbon metabolism. 44, 203221 (2016). Sci Rep 11, 13361 (2021). While low serum cobalamin levels do not necessarily imply deficiency, an abnormally high serum cobalamin level forms a warning sign requiring exclusion of a number of serious underlying pathologies. The proportional hazard assumption was checked with 2 different methods: graphically by plotting the log(minuslog) curves and by studying the interaction with time. Chocolate doesn't cause acne - but carrots do help you see in the dark Risk of gastric adenocarcinoma increases 3-fold. Clin. A low level of vitamin B12 in the blood indicates pernicious anemia. 2014 Southwest Integrative Medicine. Lambert, D. et al. These include inflammatory bowel disease (Crohn's disease), various types of . Nat. (Video) Dangers of vitamin B12 deficiency. government site. The authors declare no competing interests. Clinical findings that suggest ALPS include: Prominent findings suggesting an ALPS diagnosis include elevated levels of CD4- and CD8-negative T lymphocytes, called double-negative T cells. All Rights Reserved. Introduction: Med. contributed to analysis and interpretation of data and critically revised the manuscript for important intellectual content. and G.U. If your doctor diagnoses you with vitamin B12-deficiency anemia, your treatment will depend on the cause and seriousness of your condition. Anemia occurs when the body destroys its own red blood cells,causingweakness and fatigue. To get a true assessment of B12 . 19, 13571360 (1973). Greibe, E. et al. Nutr. F.C. Prev. Vitamin B12 or folate deficiency anaemia occurs when a lack of either of these vitamins affects the body's ability to produce fully functioning red blood cells. Total and holo-HC levels were 36- and 32-fold higher than the upper limit of the reference interval (Total HC: 250840 pmol/L; Holo-HC: 240680 pmol/L), respectively, in ALPS patients. 1989 Nov;44(11):70-3, 76, 79. Indeed, the frequency of incident diagnoses of chronic liver diseases (32/144, 22.2%) and myeloid blood malignancies (25/144, 17.4%) in the EE group also confirmed the interest in screening these pathologies in case of persistent elevated B125,18,19. Epub 2021 Jul 2. Keywords: Prevalence of high B12 was 1.3%. Presse Med. 2023 Cryptoguiding. In our own daily practice, we observed spontaneous normalizations of elevated B12 level after the resolution of acute disorders (severe infections, acute inflammatory state due to immune or inflammatory diseases). 45, 459479 (1998). Br. Andres, E., Serraj, K., Zhu, J. Jaundice , which is the yellowing of the skin and eyes. The persistence of elevated B12 was associated with a high incidence of solid cancer at 60months, in contrast to a transient B12 elevation.