Causes of elevated B12 must be determined before intervention. Excess intake, especially of cyanocobalamin, must be ruled out. Elevated B12 without supplementation may indicate a functional deficiency or may be associated with underlying pathology.
Serum B12 may be elevated due to excess supplementation or reduced clearance by the liver or excretion via the kidney. Decreased cellular uptake or utilization can also occur, causing a functional deficiency despite an abundance of B12 in circulation. Other causes or associations of elevated serum B12 include (Andres 2013, Ermens 2003, Vollbracht 2020):
- Hematological or autoimmune process including lupus
- Chronic disorders such as hematological disorders, renal failure, cystic fibrosis, cancer
- Hepatic disease including cirrhosis, hepatitis, hepatocellular carcinoma, or hepatic metastases
- Inflammatory disorders including rheumatoid arthritis
- Oxidative stress
- Critical illness and, when combined with an elevated CRP, may be associated with poorer outcomes and mortality.
- Disease state including leukemia, polycythemia vera, and hypereosinophilic syndrome
- Chronic Myelogenous Leukemia (CML) may be associated with serum B12 levels ten times higher than the upper normal.
- Autoantibodies to transcobalamin proteins
Researchers recommend additional blood chemistry workup including complete blood count, creatinine, alkaline phosphatase, AST, ALT, CRP, and prothrombin to help identify underlying dysfunction that may contribute to hypercobalaminemia (Andres 2013).
If underlying pathology is ruled out, assess for a functional deficiency in which cellular uptake or processing is impaired:
- Symptomatology including neurological dysfunction
- Increased MCV, homocysteine, or methylmalonic acid
- Decreased holotranscobalamin
- Assess folate status as well, as B12 and folate are interdependent.
It would be prudent to withhold any vitamin B12 supplementation until causes of elevated levels are determined. Also, review all possible sources of B12 or compounds that may increase B12. In the case of a post-gastrectomy patient, consumption of a daily energy drink increased serum B12 to an exceedingly high level of 33,000 pg/mL (Takahashi 2013).
Future supplementation with active forms of vitamin B12 may be considered if appropriate, including methylcobalamin, hydroxocobalamin, and adenosylcobalamin. Adequate methylfolate is also important for vitamin B12 metabolism.
The naturally occurring forms of B12 include methylcobalamin (MeCbl), adenosylcobalamin (AdCbl), and hydroxocobalamin (OHCbl). Cyanocobalamin is a synthetic, less desirable form. It contains a cyanide moiety that must be removed before being utilized in the body. Cyanocobalamin is especially contraindicated in smokers who already have overexposure to cyanide (Thakkar 2015).
Also, pay close attention to folate status as the 5-methyltetrahydrofolate form is required to methylate cobalamin inside the cell (Harrington 2017).
For more information about vitamin B12 biochemistry, visit the ODX blog:
https://www.optimaldx.com/research-blog/b12-deficiency-part-1
https://www.optimaldx.com/blog/b12-active-holotranscobalamin
References
Andrès, E et al. “The pathophysiology of elevated vitamin B12 in clinical practice.” QJM : monthly journal of the Association of Physicians vol. 106,6 (2013): 505-15. doi:10.1093/qjmed/hct051
Ermens, A A M et al. “Significance of elevated cobalamin (vitamin B12) levels in blood.” Clinical biochemistry vol. 36,8 (2003): 585-90. doi:10.1016/j.clinbiochem.2003.08.004
Harrington, Dominic J. “Laboratory assessment of vitamin B12 status.” Journal of clinical pathology vol. 70,2 (2017): 168-173. doi:10.1136/jclinpath-2015-203502
Podzolkov, V I et al. Terapevticheskii arkhiv vol. 91,8 160-167. 15 Aug. 2019, doi:10.26442/00403660.2019.08.000378
Takahashi, Kazuhiro et al. “Hypercobalaminemia induced by an energy drink after total gastrectomy: a case report.” Journal of rural medicine : JRM vol. 8,1 (2013): 181-5. doi:10.2185/jrm.8.181
Thakkar, K, and G Billa. “Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine? Hydroxcobalamin?-clearing the confusion.” European journal of clinical nutrition vol. 69,1 (2015): 1-2. doi:10.1038/ejcn.2014.165
Vollbracht, C et al. “Supraphysiological vitamin B12 serum concentrations without supplementation: the pitfalls of interpretation.” QJM : monthly journal of the Association of Physicians vol. 113,9 (2020): 619-620. doi:10.1093/qjmed/hcz164