What are the clinical indications and benefits of vitamin B12 (cobalamin) supplementation?

What Vitamin B12 Is Good For

Vitamin B12 is essential for preventing irreversible neurological damage, treating megaloblastic anemia, supporting DNA synthesis and cell reproduction, maintaining myelin integrity in the nervous system, and preventing cardiovascular complications from elevated homocysteine. 1

Core Physiological Functions

Vitamin B12 serves critical roles in human metabolism:

• DNA synthesis and cell reproduction – B12 is required for nucleoprotein synthesis, making it essential for all rapidly dividing cells, particularly in the bone marrow where blood cells are produced 1
• Myelin synthesis – B12 maintains the protective myelin sheath around nerves; deficiency leads to demyelination and subacute combined degeneration of the spinal cord 1, 2
• Hematopoiesis – B12 is necessary for normal red blood cell maturation; deficiency causes megaloblastic anemia with macrocytic red cells and hypersegmented neutrophils 1, 3
• Homocysteine metabolism – B12 acts as a cofactor in converting homocysteine to methionine, preventing toxic homocysteine accumulation that damages blood vessels 4

Prevention of Irreversible Neurological Damage

The most critical indication for B12 is preventing permanent neurological injury:

• Subacute combined degeneration – B12 deficiency causes progressive spinal cord damage affecting the posterior and lateral columns, leading to gait ataxia, loss of proprioception, and motor dysfunction 4, 2
• Peripheral neuropathy – Deficiency impairs nerve conduction velocity and causes sensory loss (vibration, tactile, nociceptive sensation), paresthesias, numbness, and muscle weakness 4, 5
• Cognitive decline – B12 deficiency produces memory impairment, concentration difficulties, "brain fog," and depression; these neurocognitive symptoms often appear before hematologic changes 4, 5
• Irreversibility warning – Neurological symptoms can become permanent if treatment is delayed, even after B12 levels normalize 6, 3

Treatment of Megaloblastic Anemia

B12 corrects the characteristic blood abnormalities of deficiency:

• Macrocytic anemia – Elevated mean corpuscular volume (MCV >98 fL) is often the earliest laboratory sign, appearing before anemia develops 4, 3
• Hypersegmented neutrophils – This classic megaloblastic pattern indicates impaired DNA synthesis from B12 deficiency 7
• Pancytopenia – Severe deficiency can cause reduction in all three blood cell lines 3

Cardiovascular Protection Through Homocysteine Reduction

B12 supplementation reduces cardiovascular risk by lowering homocysteine:

• Stroke prevention – B vitamins including B12 reduced ischemic stroke by 43% in meta-analyses; targeting homocysteine <10 μmol/L provides optimal cardiovascular outcomes 7, 6
• Thrombotic risk – Moderate hyperhomocysteinemia (15–30 μmol/L) from B12 deficiency increases thrombosis and accelerates atherosclerosis 6
• Metabolic deficiency – Serum B12 <258 pmol/L with elevated homocysteine or methylmalonic acid defines metabolic B12 deficiency, which affects 10.6% of stroke patients overall and 18.1% of those >80 years 7

Improvement of Physical Function in Elderly

B12 status correlates with functional capacity in older adults:

• Frailty reduction – Elderly women with elevated methylmalonic acid (indicating functional B12 deficiency) had 1.66–2.33 times greater risk of frailty 4
• Walking speed – B12 supplementation improved walking speed (cumulative OR 1.3; 95% CI 1.1.5), suggesting enhanced neuromuscular interactions 4
• Disability prevention – B12 deficiency was associated with greater range of disabilities in social activity, leisure activity, and mobility when functional biomarkers were used 4
• Rehabilitation outcomes – B12 status significantly affected length of stay in rehabilitation following injury, which related to muscle mass decline and cachexia 4

Wound Healing Support

B12 plays multiple roles in tissue repair:

• Collagen formation – B12 deficiency disrupts collagen synthesis, impairing the proliferative phase of wound healing 6
• Immune function – Deficiency-related megaloblastic changes diminish immunoreactivity, increasing infection susceptibility and prolonging wound closure 6
• Pressure ulcer management – For malnourished individuals with pressure injuries, micronutrient supplementation including B12 supports all phases of wound repair 6
• Post-surgical healing – In surgical and trauma patients, B12-associated protein catabolism contributes to delayed wound healing, slower mobilization, longer hospital stays, and higher re-operation rates 6

High-Risk Populations Requiring B12

Specific groups have permanent malabsorption or increased needs:

• Pernicious anemia – Positive anti-intrinsic factor antibodies indicate lifelong need for B12 injections 7, 6
• Post-bariatric surgery – Roux-en-Y gastric bypass and biliopancreatic diversion cause permanent B12 malabsorption requiring 1000 μg IM monthly or 1000–2000 μg oral daily indefinitely 7, 6
• Ileal resection >20 cm – Removal of the terminal ileum eliminates the intrinsic factor-dependent absorption site, necessitating lifelong 1000 μg IM monthly 7, 6
• Crohn's disease – Ileal involvement >30–60 cm impairs B12 absorption even without resection; annual screening and prophylactic supplementation are required 7, 6
• Atrophic gastritis – Affects up to 20% of older adults, causing food-bound B12 malabsorption 7, 6
• Metformin use >4 months – Produces dose-dependent reduction in serum B12 (mean decrease ≈54 pmol/L) and approximately three-fold increased deficiency risk 7, 6
• PPI or H2 blocker use >12 months – Reduces gastric acid secretion, impairing B12 release from dietary proteins 7, 6
• Strict vegetarians/vegans – B12 is absent from plant foods; deficiency develops without animal products or fortified foods 4, 1
• Age >75 years – 18.1% of those >80 years have metabolic B12 deficiency despite "normal" serum levels 7, 6

Critical Pitfalls to Avoid

Never administer folic acid before correcting B12 deficiency – Folate can mask megaloblastic anemia while allowing irreversible subacute combined degeneration of the spinal cord to progress 7, 6, 1

Do not rely solely on serum B12 to rule out deficiency – Standard serum B12 testing misses functional deficiency in up to 50% of cases; the Framingham Study found 12% had low serum B12 but an additional 50% had elevated methylmalonic acid indicating metabolic deficiency despite "normal" serum levels 7

Neurological symptoms often precede hematologic changes – One-third of patients with B12 deficiency have neurological manifestations without anemia; cognitive difficulties, memory problems, and peripheral neuropathy can occur before macrocytosis develops 7, 5

Treatment must be lifelong for malabsorption – Patients with pernicious anemia, post-bariatric surgery, ileal resection >20 cm, or atrophic gastritis require indefinite supplementation regardless of normalized serum levels 7, 6