What is vitamin B12 (cobalamin) responsible for?

Vitamin B12 Functions and Responsibilities

Vitamin B12 (cobalamin) is essential for mitochondrial metabolism, immune response, DNA integrity, myelin sheath preservation around neurons, and synthesis of neurotransmitters—all critical for normal blood cell formation and neurological functions. 1

Main Functions of Vitamin B12

Vitamin B12 serves as a cofactor for two crucial enzymes in humans:

• Acts as a cofactor for methionine synthase, which transfers methyl groups from methyl tetrahydrofolate to form methionine from homocysteine 1
• Functions as a cofactor for methyl malonyl-CoA mutase in the synthesis of succinyl CoA, an important intermediate in the citric acid cycle 1
• Essential for cellular metabolism, especially in DNA synthesis, methylation, and mitochondrial functionality 2
• Critical for growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis 3

Neurological Functions

Vitamin B12 plays a vital role in maintaining neurological health:

• Preserves the myelin sheath around neurons, which is essential for proper nerve conduction 1
• Supports synthesis of neurotransmitters necessary for normal neurological function 1
• Deficiency can lead to extensive demyelination in the central nervous system, particularly in the spinal cord, and focal demyelination in the brain's white matter 1
• Prevents progression of neurologic damage when administered promptly in cases of deficiency 3
• Maintains nerve conduction velocity, which is crucial for peripheral motor function 1

Hematological Functions

Vitamin B12 is critical for normal blood cell formation:

• Essential for proper red blood cell development and maturation 3
• Deficiency can lead to megaloblastic anemia, though atypical presentations with microcytosis can occur 4
• Works synergistically with folate in hematopoiesis 5

Clinical Manifestations of Deficiency

Deficiency of vitamin B12 can lead to various clinical manifestations:

• Neurological symptoms: paraesthesia, numbness, muscle weakness, abnormal reflexes, tendon jerks, spasticity, gait ataxia, myelopathies, and myelo-neuropathies 1
• Cognitive difficulties: concentration problems, short-term memory loss (sometimes described as "brain fog") 1
• Vision problems: blurred vision, optic atrophy, visual field loss 1
• Hematological manifestations: anemia, macrocytosis 1, 4
• Increased risk of frailty in older adults 6
• Glossitis and unexplained fatigue 1

Metabolism and Absorption

Understanding vitamin B12 metabolism is essential:

• Synthesized by fungi and microorganisms, including bacteria in the gastrointestinal tracts of animals 1
• Humans are dependent on animal sources or fortification as plants and mushrooms rarely contain significant amounts 1
• Absorption involves multiple steps: release from proteins by gastric acid and pepsin, binding to R-protein from salivary glands, then to gastric intrinsic factor, followed by absorption in the terminal ileum 1
• After absorption, vitamin B12 is transported via specific binding proteins (transcobalamin I and II) to various tissues 3
• The liver is the main storage organ, containing approximately 2500 μg in adults, which can last 12-36 months without sufficient intake 1, 3

Dietary Sources and Requirements

• Primary sources include ruminant meat, organs, milk, fish, shellfish, fortified cereals, and nutritional yeast 1
• Not present in foods of plant origin, making strict vegetarians at risk of deficiency 3
• Daily requirement for healthy adults is 2.4 μg/day according to DRI, while EFSA recommends 4 μg/day for healthy adults 1
• Requirements increase during pregnancy (5 μg/day) and lactation (4.5 μg/day) 1
• Physiological needs may increase with age, oxidative stress from prolonged illness, or use of certain medications 1

Clinical Considerations

• Vitamin B12 exists in multiple forms, with methylcobalamin and adenosylcobalamin being the active co-enzyme forms 5
• Deficiency can affect individuals of all ages but is particularly common in elderly populations 7, 6
• Early diagnosis is challenging as clinical manifestations often appear late in the deficiency process 2
• Assessment of vitamin B12 status is best performed using both direct markers (serum cobalamin or holotranscobalamin) and functional markers (methylmalonic acid and homocysteine) 1
• Prompt treatment of deficiency is essential to prevent irreversible neurological damage 3