The pathophysiology of elevated vitamin B12 in clinical practice

Abstract

Hypercobalaminemia (high serum vitamin B12 levels) is a frequent and underestimated anomaly. Clinically, it can be paradoxically accompanied by signs of deficiency, reflecting a functional deficiency linked to qualitative abnormalities, which are related to defects in tissue uptake and action of vitamin B12. The aetiological profile of high serum cobalamin predominantly encompasses severe disease entities for which early diagnosis is critical for prognosis. These entities are essentially comprised of solid neoplasms, haematological malignancies and liver and kidney diseases. This review reflects the potential importance of the vitamin B12 assay as an early diagnostic marker of these diseases. 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. 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. Functional cobalamin deficiency can thus occur at any serum level.

Vitamin B12 deficiency – A 21st century perspective

“…There is mounting evidence that raised serum vitamin B 12 levels are a common fi nding (values varied from 350 to 1,200 pmol/l), with a prevalence of up to 14% in hospitalised patients referred for vitamin B 12 measurement 28 and even up to 50% of older inpatients. 29 An elevation in serum vitamin B 12 levels may arise from increased oral or parenteral intake, decreased uptake by the liver or kidney, greater release from cells (especially hepatocytes), or a rise in the synthesis of the transcobalamins by hepatocytes or granulocytes.…”

“…29 An elevation in serum vitamin B 12 levels may arise from increased oral or parenteral intake, decreased uptake by the liver or kidney, greater release from cells (especially hepatocytes), or a rise in the synthesis of the transcobalamins by hepatocytes or granulocytes. 28 Table 3 28 lists the causes of raised vitamin B 12 levels. Although, elevated B 12 levels are associated with liver disorders and haematological disorders, other malignancies may cause an elevated B 12 as a reactive feature (like an acute phase protein).…”

“…Such functional cobalamin defi ciency may arise when there is increased binding of vitamin B 12 to haptocorrin as opposed to transcobalamin II, with subsequent reduction in delivery of the vitamin to peripheral cells. 28 Unless accompanied by the clinical manifestations of vitamin B 12 defi cit, functional cobalamin defi ciency is usually asymptomatic. In this situation, the BCSH recommend that homocysteine and MMA levels be assessed, with a trial of hydroxocobalamin therapy instituted.…”

Transcobalamin 776C→G polymorphism is associated with peripheral neuropathy in elderly individuals with high folate intake

“…From the total 1248 participants in the cohort, a planned subset of 366 participants who consented to additional tests and were able to visit the hospital by taxi or wheelchair van underwent an evaluation by physicians that included an assessment of peripheral neuropathy and gait and balance at Tufts Medical Center (20). Participants were excluded from the current study if data were missing for the TCN2 genotype (n = 53) or any of the covariates (n = 86), if they had a stroke (n = 43), or if they had a plasma vitamin B-12 concentration ,148 pmol/L (n = 2), which was indicative of deficiency, or .701 pmol/L (n = 11), which may have been indicative of malignancies or abnormalities (21)(22)(23). A total of 171 participants who underwent an evaluation by the physicians met the criteria for the current study (Supplemental Figure 1).…”

A pilot clinical trial assessing the efficacy and safety of supplementation with a B complex vitamin to reduce the incidence of chemotherapy induced peripheral neuropathy in patients diagnosed with a malignancy

“…therefore showing high vitamin B12 levels [378,379]. Hence, the increase 24 hours after chemotherapy administration may indicate liver damage than the decrease at 72 hours is the actual status of vitamin B12.…”