Patients with persistent high levels of serum vitamin B12 were often referred to Hematology departments. This review reflects the potential importance of the vitamin B12 assay as an early diagnostic marker of these diseases. 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. As explained above, patients in the EE or EN groups could have had previous normal B12 measurements before the first elevated one (T1). J. Thorac. Is high vitamin B12 status a cause of lung cancer? 21. High B-12 levels may indicate liver disease, diabetes, or another condition. National Library of Medicine PubMedGoogle Scholar. A study suggests that vitamin B12 can provide relief from back pain due to the role it plays in the nervous system. 49, 11 (2011). Vlasveld, L. T., Bos, G. M. J., Ermens, A. A. These include inflammatory bowel disease (Crohn's disease), various types of . Rev. Clipboard, Search History, and several other advanced features are temporarily unavailable. We compared the cancer-free survival during 60months between the groups after adjustment for the other elevated-B12-related causes in a survival competing risk model. Subacute Combined Degeneration of the Spinal Cord: A Consequence of Recreational Nitrous Oxide Use. The alpha risk was 5%. In the case of solid cancer diagnosed between T1 and T2, patients were excluded if the T2 assay was performed at more than 1month after cancer treatment initiation. 2012 Oct 31;8(360):2072-4, 2076-7. Ermens AA, Vlasveld LT, van Marion-Kievit JA, Lensen CJ, Lindemans J. Ned Tijdschr Geneeskd. Arendt, J. F. H., Srensen, H. T., Horsfall, L. J. 2013 Apr;92(4):527-31. doi: 10.1007/s00277-012-1634-8. High Plasma Vitamin B12 and Cancer in Human Studies: A Scoping Review to Judge Causality and Alternative Explanations. Please enable it to take advantage of the complete set of features! Therefore the B-12 just, Role of Inflammation in High B12 Without Supplementation, What To Do With High B12 Without Supplementation. Drink more water to help flush your body of water-soluble elements in the blood, which includes vitamin B12. Without advertising income, we can't keep making this site awesome for you. 105, 17991805 (2013). Vollbracht C, Gndling PW, Kraft K, Friesecke I. J Int Med Res. Rev Med Suisse. TC is a 43 kDa non-glycosylated serum protein that is synthesized primarily in the enterocytes and carries vitamin B12 to the tissues via a specific receptor with a high affinity for holo-TC. The diagnosis of ALPS is based on clinical findings, laboratory findings, and identification of mutations in genes, such as FAS, that affect the programmed destruction of cells (apoptosis). As a result, there is more binding of the B-12 but less of it is getting taken up into the cells because it's all bound by non-functional transport proteins. Abstract. Autoimmune metaplastic atrophic gastritis is an inherited autoimmune disease that attacks parietal cells, resulting in hypochlorhydria and decreased production of intrinsic factor. Vitamin D supplements may treat joint pain in some people who have a vitamin D deficiency. Int. Indeed, few studies analyzed the incidence of solid cancers following the incidental finding of elevated B12 and no studies linked elevated B12 to solid cancer after adjusting for other causes of elevated B12. Clipboard, Search History, and several other advanced features are temporarily unavailable. So keep reading we are going to get into the details. The 344 patients in the NN group were randomly selected from the 7,889 patients with plasma B12<1000ng/L at T1 and T2. At least one cause of elevated B12 was diagnosed in the follow-up of 75/144 (52.1%) patients in the EE group, 34/200 (17.0%) in the EN group, and 38/448 (11.0%) in the NN group (p<0.001, Table 1). Let's look at that next. Doctors may perform additional blood tests to help diagnose ALPS. Symptoms may develop over time and include: 5. Bookshelf and C.L. This site needs JavaScript to work properly. On the contrary, elevated B12 levels encountered in some cancers could be correlated with the tumor mass or the granulocytic immune response5,6,20. All conditions may show elevated concentrations of B12 transport proteins. In patients with three or more B12 measurements and at least one B121000ng/L, T1 was selected as the first test with B121000ng/L. B12 at T1 was higher in the EE group than in the EN group (p<0.001). Actually I now am like most people with autoimmune diseases because the test showed me deficient. Elevated B12 has been associated with various diseases1,5,6: liver diseases7,8,9,10, myeloid blood malignancies10,11,12,13, chronic renal failure3,14, autoimmune or inflammatory diseases3, Gaucher disease15. CAS 2020 Jul 22;9(8):2326. doi: 10.3390/jcm9082326. These are disease of the bone marrow where the white blood cells come from. In other words, about 1 in 5 patients will develop ALPS lymphoma by the time they are 40. Research on the use of vitamin B-12 for specific activities and conditions shows: Heart and blood vessel disease. Careers. Internet Explorer). Previous studies have chosen a variety of levels to represent high or very high B12 (pmol/l) levels. Size exclusion chromatography was employed to demonstrate the presence of immune complexes (ICs) with plasma vitamin B12-binding proteins in some serum samples with high B12. Dis. Sci. In this article we will explore this topic in a little bit more detail. J Clin Med. Loss of follow-up was censored. 17, 235238 (1998). What causes falsely elevated B12 levels? Nutr. Functional cobalamin deficiency can thus occur at any serum level. Tingling sensation or Numbness In some patients, tingling sensation is experienced mostly in the right side of the body. 89, 812819 (2008). Radio- and enzyme immunoassays, size-exclusion chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), western blot, and flow cytometry techniques were used to identify and quantitate the source of the elevated vitamin B12 concentrations in peripheral blood specimens from ALPS patients and controls. Does anyone have extremely high B12 levels? All Rights Reserved. Department of Internal Medicine and Clinical Immunology, Angers University Hospital, Angers, France, Valentin Lacombe,Carole Lacout,Alaa Ghali,Christian Lavigne&Geoffrey Urbanski, Department of Biochemistry and Genetics, Angers University Hospital, Angers, France, Ouest Institute of Cancerology, Angers, France, Department of Internal Medicine and Clinical Immunology, Angers University Hospital, 4 rue Larrey, 49000, Angers, France, You can also search for this author in 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. The persistence of elevated B12 was associated with a high incidence of solid cancer at 60months, in contrast to a transient B12 elevation. Eur. 2015 Feb;101(4):302-10. doi: 10.1136/heartjnl-2014-306022. The aetiological profile of high serum cobalamin predominantly encompasses severe disease entities for which early diagnosis is critical for prognosis. What vitamin Am I lacking if my joints hurt? However only one of these transporters is actually functionally useful in delivering B-12 into its target cells. Separate from kidney disease, inflammation can be another cause for elevated B-12 levels. So double-check you are not getting B-12 from various sources that you are not aware. All Rights Reserved. Search for other works by this author on: Thank you for submitting a comment on this article. Only vitamin B12 bound to TC is available for cellular uptake and use as coenzymes for L-methylmalonyl-CoA mutase and methionine synthase that synthesize succinyl-CoA and methionine, respectively. Orphanet J Rare Dis. Slider with three articles shown per slide. Br. 10. Glomerulonephritis (inflammation of the kidneys). Solid cancers represent one of the main diagnoses found in patients with unexplained and persistent elevated B12. Therefore, anything that raises TCN 1 and TCN 3 will lower the functional activity of B-12 by limiting the binding of B-12 to the TCN 2. Baker, H., Leevy, C. B., DeAngelis, B., Frank, O. Elevated B12 has been associated with various diseases 1,5,6: liver diseases 7,8,9,10, myeloid blood malignancies 10,11,12,13, chronic renal failure 3,14, autoimmune or inflammatory diseases 3 . In this study, characteristic of patients with serum vitamin B12 levels higher than 2500 pmol/L (high B12) were studied. 2. Arendt, J. F. B., Pedersen, L., Nexo, E. & Srensen, H. T. Elevated plasma vitamin B12 levels as a marker for cancer: A population-based cohort study. I do have Hashimotos and have been on medication for years but had a relapse recently when all these symptoms appeared (TSH was 10). However, there is not enough evidence to recommend B12 supplementation to prevent heart . Complications. Neutropenia occurs when the body destroys infection-fighting cells called neutrophils. Of these patients, 10/26 (38%) had elevated ferritin levels secondary to liver disease, 7/26 (27%) malignancy/infection, 6/26 (23%) malignancy alone, 1/26 (4%) autoimmune disease, and 1/26 (4% . What should I study to work in blockchain? In this article we will discuss the causes of high B-12without supplementation. Therefore the B-12 justcirculates and never gets into the cells. Condoms are the most effective way to prevent HIV and STDs. In our study, an increased risk of cancer was associated with patients having a persistent elevated B12 (group EE) but not with those showing transient elevated B12 (group EN). eCollection 2022 Oct. Yang M, Zhou X, Tan X, Huang X, Yuan L, Zhang Z, Yang Y, Xu M, Wan Y, Li Z. Antioxidants (Basel). Prevalence of high B12 was evaluated during a 10-month period. Br. MeSH The quantitative data were presented in medians and quartiles and compared using a Student t test or an ANOVA. Berg, R. L. & Shaw, G. R. Laboratory evaluation for vitamin B12 deficiency: The case for cascade testing. I'm assuming these 2 abnormal tests will be linked, as in both being caused for potentially the same reason? Even though the title is "cause of high B-12 without supplementation," my experience helping people figure this out, they are taking B-12. Causes of High B12 Without Supplementation in Clinical Practice ). 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. Unauthorized use of these marks is strictly prohibited. With inflammation, there is damage to the cell membranes. If someone has been on any form of a supplement containing B12, it can leave the serum levels of B12 elevated for a long time afterwards. Large, visible lymph nodes are normal for many people with ALPS. The hazard ratios (HR) were presented with a confidence interval of 95%. Zibold J, von Livonius B, Kolarova H, Rudolph G, Priglinger CS, Klopstock T, Catarino CB. High serum concentration of cobalamin is a common but underestimated finding. . Vitamin B 12 in serum is bound to two proteins, haptocorrin (HC) and transcobalamin (TC). PMC The .gov means its official. Serum vitamin B12 decreased to normal values after precipitation with PEG, and size exclusion chromatography confirmed ICs. Hepatitis and Hepatocellular Carcinoma can also lead to increase release of B-12 from the cells being damaged. Cancer 49, 21872198 (2013). 26. 28, 814821 (2019). 36, 585590 (2003). Cancer 116, 14991504 (2017). 2022 Oct 1;12(4):e12173. Thrombocytopenia occurs when the body attacks and destroys blood components called platelets. J. Inborn Errors Metab. A. M., Bakker, J. The two major types of lymphocytes are B cells and T cells, which are derived from pluripotent hematopoietic stem cells in the bone marrow.https://en.wikipedia.org wiki Lymphoproliferative_disordersLymphoproliferative disorders - Wikipedia with Apoptosis Defect. Epub 2011 Oct 22. As the cell membranes are damaged there are a cascade of inflammatory molecules produced. Pernicious anemia is an autoimmune condition that happens when your immune system produces antibodies that attack cells in the mucosal lining of your stomach and nerve cells. Background and objectives: In Crohn's disease (CD), belonging to inflammatory bowel disease, the small intestine is involved in most cases. Your immune system's response affects your body's ability to absorb vitamin B12. Unauthorized use of these marks is strictly prohibited. Precipitation with PEG is an easy method to confirm the presence of ICs and to evaluate serum vitamin B12 levels in these patients. High serum vitamin B12 concentrations have been observed in patients with ALPS studied at NIH Clinical Center. Symptoms. Among these patients, plasma B121000ng/L at T1 were found in 344 patients without any known elevated-B12-related causes. Samples with high B12 were incubated with polyethylene glycol (PEG) and a new measurement of vitamin B12 was carried out using the supernatant. HHS Vulnerability Disclosure, Help The remainder of vitamin B12 is bound to TC (holo-TC). Biochem. Please enable it to take advantage of the complete set of features! [Therapeutic and clinical implications of elevated levels of vitamin B12]. Sviri, S. et al. Am. High B12 levels are found in many myloproliferative disease. Cappello, S. et al. J. Haematol. Moreover, thyroid disease is often caused by autoimmune disease (Hashimoto's thyroiditis). By submitting a comment you agree to abide by our Terms and Community Guidelines. Before Your comment will be reviewed and published at the journal's discretion. And if you have high blood pressure or poor cardiovascular health, having too much B12 may further complicate these issues. In patients with repeatedly high B12 levels, ICs were detected in approximately 25% of samples. Article However, total and holo-TC levels (1210 pmol/L; reference interval: 5001500 pmol/L and 143 pmol/L; reference interval: >40 pmol/L, respectively) were not elevated in ALPS patients. ALPS is a rare autoimmune disease in children resulting from defective lymphocyte apoptosis and is characterized by lymphoproliferation, peripheral accumulation of DNT cells (double-negative T cells; TCR alpha/beta +, CD3+ CD4 CD8), often leading to autoimmune multilineage cytopenias. Essentially if you remain having persistently elevated B-12 levels in the absence of supplementation you should explore this further with more testing. Hannibal, L. et al. 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). Abnormally elevated B12 has been attributed many causes [5,6], e.g., myeloid blood malignancies [7,8,9], acute or chronic liver diseases [10,11,12], chronic kidney failure, autoimmune or inflammatory diseases [3], and Gaucher disease [13]. Then, the patients with B121000ng/L at T1 were split into 2 groups, those having B121000ng/L at T2 (EE group) and those having B12<1000ng/L at T2 (EN group). These were younger, male, with kidney disease, lower serum calcium and higher 30-day mortality (all p<0.01). 19, 13571360 (1973). Paradoxically, hypercobalaminaemia can be associated with a functional B12 deficiency. 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. Federal government websites often end in .gov or .mil. Patients gave informed consent. Conditions that can increase B12 level include: Liver disease (such as cirrhosis or hepatitis) Myeloproliferative disorders (for example, polycythemia vera and chronic myelogenous leukemia). Arthritis, one of the leading causes of joint pain can also be worsened due to deficiency of Vitamin B12. & Li, Y. Keywords: Now this doesn't necessarily explain the elevated B-12 levels but it does explain how one can be deficient in B-12 in the presence of higher serum B-12 levels. Google Scholar. J. Gastroenterol. Marsey October 5, 2018, 9:31pm 1. Most of these more serious causes are altering the transportation of B-12 via the transcobalamin transport proteins (more on this below). This raises the question of the potential interest in repeating investigations 1year later. 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). 76, 521525 (2006). What autoimmune diseases cause high B12 levels? 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. People with severely low levels of B12 may need more shots in the beginning. Both of which would be elevated in the presence of B-12 deficiency. Relationship between serum B12 concentrations and mortality: experience in NHANES. For the first time, we demonstrate that the risk of incident solid cancer in the case of transiently elevated B12 is similar to that of patients without elevated B12, whereas this risk is strongly increased in the case of persistent elevated B12. CAS However, a falsely normal or high value of vitamin B12 in the blood may occur if antibodies interfere with the test. Assessment of the serum levels of hemoglobin, ferritin, and vitamin B12 in a sample of Iranian population with morbid obesity. Risk of gastric adenocarcinoma increases 3-fold. Such changes are usually not indicative oflymphoma. [Hypervitaminosis B12 - a new marker and predictor of prognostically unfavorable diseases]. We disclaim all responsibility for the professional qualifications and licensing of, and services provided by, any physician or other health providers posting on or otherwise referred to on this Site and/or any Third Party Site. Among the causes of elevated B12, incident myeloid blood malignancies and chronic liver diseases were more frequent in the EE group (p<0.001 and p<0.001, respectively). Hampered vitamin B12 metabolism in gaucher disease?. Jaundice , which is the yellowing of the skin and eyes. , All content found on the AutoimmuneSisters.com Website, including: text, images, audio, or other formats were created for informational purposes only. These particular transport proteins are made more commonly in certain cell lines like the granulocytes, a type of white blood cell. 1. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. We collected the incident elevated-B12-related causes, including solid cancers, which appeared within 60months following T1, and their date of occurrence. This symptom is one of the early warning indicators of Vitamin B12 overdose. Moreover, Arendt et al. Screen. It could be in a multivitamin, a workout drink, a protein powder, or something like this. IUBMB Life 68, 303310 (2016). The following vitamin B12 supplements all feature highly-absorbable forms of the vital vitamin. Dan. In the case of incidental finding of elevated B12, the relevance of an active search for solid cancer necessitating invasive and expensive examinations remains debated5,18,19. High levels of these substances in your body are a sign of pernicious anemia. (Video) Dangers of vitamin B12 deficiency. Use of vitamin B12 in patients with elevated serum homocysteine levels and cardiovascular disease does not reduce the risk of myocardial infarction or stroke, or alter cognitive decline. This type of B 12 deficiency anemia is called pernicious anemia. Introduction: What can I invest 20 dollars in to make money? The B12 normal range for healthy adults is between 160 to 950 picograms per milliliter (pg/mL). However, it can have more to do with the transportation of B-12 rather than the cell membrane. BMC Health Serv. Patients in whom active screening should be discussed need to be better targeted to allow early diagnosis and limit unnecessary investigations. (Video) What Does It Really Mean If You Have High B12 Levels? Would you like email updates of new search results? If you are having persistently elevated B-12 levels, this information will be helpful. 14, 343357 (2019). Vitamin B12 deficiency. The risk of solid cancer seems insufficient to systematically perform these invasive and expansive investigations in case of incidental discovery of elevated B12. They sometimes just are not aware of it. Geriatrics. doi: 10.1136/bcr-2021-247660. 2022 Sep 28;11(10):1919. doi: 10.3390/antiox11101919. One of them is called methylmalonic acid and the other one is called homocysteine.