What is cyanocobalamin (Vitamin B12)?

Cyanocobalamin (Vitamin B12): Definition and Clinical Significance

Cyanocobalamin is a synthetic form of vitamin B12, an essential water-soluble vitamin that plays crucial roles in various metabolic processes including DNA synthesis, red blood cell formation, and neurological function. Cyanocobalamin is an organometallic complex that participates in metabolic reactions involving DNA nucleotide synthesis, but it should be noted that methylcobalamin or hydroxycobalamin are preferred forms for clinical use due to better safety profiles, particularly in patients with renal dysfunction. 1

Biochemical Properties and Metabolism

• Cyanocobalamin is rapidly absorbed from intramuscular and subcutaneous injection sites, with plasma levels peaking within 1 hour after administration 2
• After absorption, vitamin B12 is transported via specific binding proteins (transcobalamin I and II) to various tissues, with the liver being the main storage organ 2
• Within 48 hours of injection, 50-98% of the administered dose may appear in urine, with the majority excreted within the first 8 hours 2
• Cyanocobalamin must be converted in the body to its active coenzyme forms: methylcobalamin and adenosylcobalamin, which have distinct metabolic functions 3

Physiological Functions

• Methylcobalamin is primarily involved in hematopoiesis and brain development during childhood 3
• Adenosylcobalamin is essential for carbohydrate, fat, and amino acid metabolism, and plays a key role in myelin formation 3
• Vitamin B12 is required for nucleoprotein and myelin synthesis, cell reproduction, and growth 2
• It plays a critical role in homocysteine metabolism, with deficiency leading to hyperhomocysteinemia, which is associated with increased stroke risk 1

Dietary Sources and Requirements

• Vitamin B12 is not present in foods of plant origin but is abundant in animal-derived foods including meat, fish, poultry, eggs, and dairy products 2
• The average diet provides approximately 5-15 mcg/day of vitamin B12 in a protein-bound form 2
• The recommended daily allowance (RNI) for vitamin B12 in the UK is 1.5 μg/day for adults, though this is among the lowest recommendations in Europe 1
• Other European guidelines recommend higher intakes: German Nutrition Society recommends 3 μg/day and EFSA recommends 4 μg/day 1
• Recent research suggests that intakes between 4.3-8.6 μg/day may be necessary to maintain normal ranges of functional markers 1

Clinical Applications

• Cyanocobalamin is primarily used to treat vitamin B12 deficiency, which can manifest as:

  • Megaloblastic anemia 1
  • Neurological symptoms including peripheral neuropathy, balance issues, impaired gait, and paresthesia 1
  • Cognitive difficulties such as concentration problems and short-term memory loss 1
  • Glossitis and other mucosal symptoms 1
  • Optic nerve dysfunction leading to visual disturbances 1

• For treatment of vitamin B12 deficiency:

  • Oral supplementation with 1000 μg/day of cyanocobalamin has been shown to effectively correct deficiency, even in pernicious anemia patients 4
  • Studies indicate that the lowest oral dose required to normalize mild vitamin B12 deficiency is approximately 647-1032 μg daily, which is over 200 times greater than the recommended dietary allowance 5

Important Considerations and Cautions

• In patients with renal dysfunction, methylcobalamin or hydroxycobalamin should be used instead of cyanocobalamin 1

• The DIVINe trial showed that high-dose B vitamin supplementation (including 1000 μg cyanocobalamin) in patients with diabetic nephropathy and reduced kidney function increased the risk of cardiovascular events 1

• Vitamin B12 deficiency is particularly common in:

  • Older adults 1
  • Individuals following vegan or vegetarian diets 1
  • Patients with malabsorption conditions or atrophic gastritis 1, 6
  • Those taking medications such as metformin, colchicine, H2 receptor antagonists, and certain anticonvulsants 1

• Testing for vitamin B12 deficiency:

  • Both total B12 (serum cobalamin) and active B12 (serum holotranscobalamin) can be used for initial assessment 1
  • Methylmalonic acid (MMA) and homocysteine levels provide more sensitive markers of functional B12 deficiency 1

Cyanocobalamin represents an important therapeutic option for vitamin B12 deficiency, but clinicians should be aware of its limitations in certain patient populations and consider alternative forms when appropriate.