Increased level of b12
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Elevated Vitamin B12 Levels: Causes, Implications, and Health Risks
Introduction to Elevated Vitamin B12 Levels
Vitamin B12, also known as cobalamin, is a crucial micronutrient involved in DNA synthesis, methylation, and mitochondrial metabolism. While deficiency is a common concern, elevated levels of vitamin B12 can also indicate underlying health issues. This article explores the causes, implications, and health risks associated with increased vitamin B12 levels.
Causes of Elevated Vitamin B12 Levels
Cobalamin Macrocomplexes and Analytical Interference
Persistently high vitamin B12 levels can sometimes be attributed to cobalamin macrocomplexes, which are complexes of vitamin B12 with its binding proteins, transcobalamin (TC) and haptocorrin (HC). These complexes can lead to falsely elevated B12 readings in blood tests due to analytical interference1.
Increased Synthesis or Decreased Clearance of Carrier Proteins
Another cause of elevated B12 levels is the increased synthesis or decreased clearance of its carrier proteins, TC and HC. This can result from various metabolic alterations, including liver disease, kidney disease, and the presence of anti-TC antibodies1.
Disease Associations
High levels of vitamin B12 have been linked to several diseases, including myeloproliferative disorders (e.g., chronic myeloid leukemia, polycythemia vera), autoimmune lymphoproliferative syndrome, and fibrolaminar hepatocellular carcinoma. Additionally, elevated B12 levels can be associated with cancer, liver disease, and kidney disease1 3.
Health Implications of Elevated Vitamin B12 Levels
Cancer Risk
Elevated vitamin B12 levels have been associated with an increased short-term risk of cancer. A study using data from The Health Improvement Network primary care database in the UK found that individuals with B12 levels above 1,000 pmol/L had a significantly higher 1-year cancer risk, particularly for liver cancer, pancreatic cancer, and myeloid malignancies3. This suggests that elevated B12 levels may be a marker for occult cancer.
Non-Alcoholic Fatty Liver Disease (NAFLD)
Research indicates a bidirectional causal relationship between elevated vitamin B12 levels and non-alcoholic fatty liver disease (NAFLD). Higher B12 concentrations are associated with an increased risk of NAFLD, and NAFLD itself can lead to elevated B12 levels due to dysregulation of vitamin B12 metabolism4.
Mortality Risks in Hypertensive Populations
In hypertensive individuals, elevated B12 levels have been linked to increased all-cause and cardiovascular mortality. A study involving Chinese adults with hypertension found that those with higher B12 levels had a significantly higher risk of mortality, independent of other factors such as folate and homocysteine levels9.
Conclusion
Elevated vitamin B12 levels can be indicative of various underlying health conditions, including cancer, liver disease, and metabolic disorders. It is essential for healthcare providers to consider these potential causes and implications when encountering high B12 levels in patients. Further research is needed to fully understand the mechanisms and clinical significance of elevated vitamin B12 levels.
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Most relevant research papers on this topic
Persistently increased vitamin B12 concentration due to cobalamin macrocomplexes: a case report and review of the literature
High vitamin B12 levels in a 73-year-old woman were due to cobalamin macrocomplexes, not a deficiency or supplementation.
Case ReportVitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial
Oral methylcobalamin for 12 months improved B12 levels, neurophysiological parameters, and quality of life in patients with diabetic neuropathy, but did not significantly improve cardiovascular autonomic reflex tests.
RCT
Very Rigorous Journal
Highly CitedElevated Vitamin B12 Levels and Cancer Risk in UK Primary Care: A THIN Database Cohort Study
Elevated vitamin B12 levels are associated with a higher 1-year cancer risk in UK primary care, suggesting some cancers may affect B12 metabolism.
Observational StudyBi-directional causal effect between vitamin B12 and non-alcoholic fatty liver disease: Inferring from large population data
Increased serum vitamin B12 concentrations may increase the risk of non-alcoholic fatty liver disease, and NAFLD also has a causal impact on elevated vitamin B12 concentrations in the circulation in European individuals.
Meta-AnalysisVitamin B12 deficiency induces glucose intolerance, delays peak insulin levels and promotes ketogenesis in female rats.
B12 deficiency in female rats leads to glucose intolerance, delayed peak insulin levels, and increased ketogenesis, potentially promoting the development of metabolic disorders like diabetes mellitus.
RCT
Animal Study
Rigorous JournalEffect of two different sublingual dosages of vitamin B12 on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency: A randomized controlled trial.
Sublingual dosages of 350 g/week (350 g/day) of vitamin B12 are more effective than 2000 g/week (one large oral dose) in improving vitamin B12 nutritional status in vegans and vegetarians with a marginal deficiency.
RCTVery Rigorous JournalEffects of dietary supplementation of different levels of vitamin B12 on the liver metabolism of laying hens.
Vitamin B12 supplementation at 25 g/kg in laying hens' diets increases egg yolk vitamin B12 concentration and impacts vitamin B6 metabolism, while 100 g/kg increases egg yolk and liver vitamin B12 concentrations and impacts lipid, nucleic acid, and amino acid metabolic pathways.
RCTAnimal StudyRigorous JournalVitamin B12 deficiency
Vitamin B12 deficiency affects individuals of all ages, particularly the elderly, and is caused by inadequate intake, bioavailability, or malabsorption, with management relying on B12 supplementation.
Highly CitedAbstract 12719: The Association of High Vitamin B12 With Mortality Risks and Related Metabolisms Among Hypertensive Population
Elevated B12 levels are associated with increased risk of all-cause mortality in Chinese adults with hypertension, independent of baseline folate, tHcy, and other traditional risk factors.
In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations
Higher serum folate levels can worsen vitamin B12's enzymatic functions in people with vitamin B12 deficiency, potentially increasing the risk of cognitive impairment and anemia.
Observational StudyHighly Cited