What is the function of vitamin B12 in the human body?

What Do You Need B12 For?

Vitamin B12 is essential for DNA synthesis, red blood cell formation, neurological function through myelin maintenance, and cellular energy metabolism—deficiency causes irreversible neurological damage even before anemia develops. 1

Core Metabolic Functions

Vitamin B12 serves as a cofactor for only two critical enzymatic reactions in humans 2, 3:

• Methionine synthase (cytosolic): Converts homocysteine to methionine, enabling DNA methylation and synthesis of purines and pyrimidines—the building blocks of DNA 2, 1
• Methylmalonyl-CoA mutase (mitochondrial): Converts methylmalonyl-CoA to succinyl-CoA, a crucial intermediate in the citric acid cycle for cellular energy production 1

Hematological Role

Vitamin B12 is essential for normal red blood cell production through its role in DNA synthesis 4, 3:

• B12 deficiency impairs DNA synthesis while RNA and protein synthesis continue normally, creating nuclear-cytoplasmic asynchrony 5
• This leads to maturation arrest in rapidly dividing erythroblasts, causing them to undergo apoptosis during early erythropoiesis 5
• The result is ineffective erythropoiesis producing fewer but larger red blood cells (macrocytosis), though microcytosis can occur when combined with iron deficiency 5, 6
• Macrocytosis typically precedes anemia and represents the earliest laboratory sign of deficiency 5

Neurological Functions

B12 is critical for maintaining the nervous system, with deficiency causing irreversible damage if untreated 2, 1:

• Myelin preservation: B12 maintains the myelin sheath around neurons, essential for proper nerve conduction velocity 2, 1
• Neurotransmitter synthesis: Required for producing neurotransmitters necessary for normal neurological function 1
• Prevents demyelination: Deficiency causes extensive demyelination in the spinal cord (subacute combined degeneration) and focal demyelination in brain white matter 2, 4
• Peripheral nerve function: Deficiency damages peripheral nerve fibers, particularly axonal degeneration in distal afferent fibers of dorsal root ganglion neurons 2

Clinical Neurological Manifestations

Neurological symptoms often appear before hematological changes and include 2, 1:

• Paraesthesia and numbness in trunk and extremities
• Muscle weakness and abnormal reflexes
• Gait ataxia (loss of coordination)
• Impaired proprioception, vibratory sensation, and tactile sensation
• Cognitive difficulties, concentration problems, and short-term memory loss
• Depression and mood disturbances
• Visual problems including blurred vision and optic atrophy

Critical warning: Neurological damage from B12 deficiency becomes irreversible at advanced stages, making early detection crucial 2, 4

DNA Stability and Cell Division

Beyond basic DNA synthesis, B12 protects genetic integrity 7, 8:

• Acts as cofactor for enzymes involved in DNA replication and transcription 7
• Has antioxidant properties that protect DNA from reactive oxygen species damage 7
• Deficiency leads to uracil misincorporation into DNA, causing chromosomal instability and DNA deletions 2
• Essential for cell reproduction and growth across all rapidly dividing tissues 4

Metabolic Interdependence with Folate

B12 and folate metabolism are functionally interdependent—deficiency of one creates functional deficiency of the other 2:

• B12 deficiency causes a "methyl trap" where 5-methyltetrahydrofolate accumulates and cannot participate in one-carbon metabolism 5
• This creates functional folate deficiency even when folate levels appear normal 2, 5
• Critical pitfall: Giving folic acid before treating B12 deficiency may mask anemia while allowing irreversible neurological damage to progress 5
• Assessment of folate status should always include B12 evaluation 2

Cardiovascular and Homocysteine Regulation

B12 deficiency leads to elevated homocysteine (hyperhomocysteinemia) with significant consequences 2:

• Elevated homocysteine (≥15 µmol/L) is an independent risk factor for neurodegenerative disease and cardiovascular events 2
• Associated with reduced grip strength in men and increased functional limitations in both sexes 2
• Linked to brain atrophy and neuromuscular decline 2
• B12 treatment reduces stroke risk by 43% in patients with cardiovascular disease 1

Absorption and Storage

Understanding B12 absorption explains why deficiency occurs 1, 4:

• Dietary sources: Only found in animal products (meat, fish, dairy, eggs) and fortified foods—not present in plant foods 2, 1
• Complex absorption: Requires gastric acid, pepsin, intrinsic factor from stomach, and intact terminal ileum for absorption 1
• Liver storage: Unlike other B vitamins, B12 is stored in large quantities in the liver, with stores lasting 2-3 years 2, 1
• Daily requirement: Only 2.4 µg/day for healthy adults, the lowest requirement of all water-soluble vitamins 1, 3

Clinical Implications for Frailty and Aging

B12 status significantly impacts physical function in elderly populations 2, 9:

• Deficiency increases frailty risk 1.66-2.33 times in elderly women 2
• Associated with sarcopenia (muscle loss), reduced muscle strength, and impaired mobility 2, 9
• Supplementation improves walking speed and general physical function measures 2
• Deficiency prolongs rehabilitation time following injury, contributing to muscle cachexia 2