Does vitamin B12 deficiency delay wound healing, and who (e.g., adults >65, strict vegans/vegetarians, patients with pernicious anemia, Crohn disease, celiac disease, post‑gastric bypass, chronic alcohol users, or those on long‑term proton‑pump inhibitors, H2‑blockers, or metformin) is at greatest risk?

Vitamin B12 Deficiency and Wound Healing

Vitamin B12 deficiency can delay wound healing by impairing DNA synthesis in rapidly dividing cells, disrupting collagen formation, and compromising immune function, although the evidence linking B12 specifically to wound healing is less robust than for other micronutrients. 1

Mechanisms by Which B12 Deficiency May Impair Wound Healing

• Impaired DNA synthesis in rapidly dividing cells (fibroblasts, keratinocytes, endothelial cells) occurs because B12 is required for the methionine synthase reaction, which is essential for thymidine production and therefore DNA replication. 2

• Disrupted cellular proliferation and migration can result from B12 deficiency, as demonstrated in laboratory studies where B12 combinations improved keratinocyte and fibroblast migration rates by 25–30% and upregulated the migration marker CXCR4. 3

• Compromised immune function develops because B12 deficiency causes megaloblastic changes in bone marrow that affect all rapidly dividing hematopoietic cells, leading to diminished immunoreactivity and increased susceptibility to infection—both of which delay wound healing. 1, 2

• Protein catabolism and malnutrition are associated with B12 deficiency in surgical and trauma patients, contributing to delayed wound healing, delayed mobilization, prolonged hospital stays, and higher rates of reoperation. 1

High-Risk Populations for B12 Deficiency

Age-Related Risk

• Adults over 75 years have the highest risk, with 18.1% of those over 80 years having metabolic B12 deficiency despite "normal" serum levels. 4, 5

• Adults over 60 years show 25% prevalence of metabolic deficiency in those 85 years and older, driven by atrophic gastritis affecting up to 20% of older adults and causing food-bound B12 malabsorption. 4

Gastrointestinal Causes

• Pernicious anemia patients with positive intrinsic factor antibodies require lifelong B12 supplementation because they cannot absorb dietary B12. 4, 6

• Post-bariatric surgery patients (especially Roux-en-Y gastric bypass, sleeve gastrectomy, biliopancreatic diversion) have permanent malabsorption requiring indefinite supplementation at 1000 mcg IM monthly or 1000–2000 mcg oral daily. 1, 4, 6

• Ileal resection >20 cm or Crohn's disease involving >30–60 cm of terminal ileum causes B12 malabsorption because the intrinsic factor–B12 complex is absorbed exclusively in the distal ileum; these patients require prophylactic 1000 mcg IM monthly for life. 4, 6

• Celiac disease patients may have impaired B12 absorption due to small intestinal inflammation and villous atrophy. 7, 5

• Atrophic gastritis affecting the gastric body impairs B12 absorption by reducing intrinsic factor production and gastric acid secretion. 4

Medication-Induced Deficiency

• Metformin use >4 months causes dose-dependent reduction in serum B12 (mean decrease ≈54 pmol/L) with approximately three-fold increased risk of deficiency (adjusted OR 2.92; 95% CI 1.26–6.78). 4, 7, 5

• Proton pump inhibitors or H2-blockers used >12 months impair B12 absorption by reducing gastric acid needed to cleave B12 from food proteins. 1, 4, 7, 5

• Other medications including colchicine, anticonvulsants (phenobarbital, pregabalin), sulfasalazine, and methotrexate can contribute to B12 deficiency. 4

Dietary Risk

• Strict vegans and vegetarians have limited dietary B12 intake because B12 is found exclusively in animal products (meat, fish, dairy, eggs); they require oral supplementation of 500–1000 mcg daily. 4, 7, 5

Chronic Conditions

• Chronic alcohol users are at increased risk due to malnutrition, gastritis, and impaired absorption. 7, 5

• Post-stroke patients show 17.3% prevalence of biochemical or metabolic B12 deficiency, with 18.1% of those >80 years affected. 4

Clinical Implications for Wound Healing

• Pressure ulcers are associated with protein loss, hypermetabolism, and nutrient deficiencies critical to wound healing phases, including B12; micronutrient supplementation (B6, B12, folate, zinc, arginine) is recommended for patients with pressure injuries who are malnourished or at risk. 1

• Trauma and critical care patients experience 20–50% greater energy expenditure than elective surgery patients, and malnutrition (including B12 deficiency) is associated with delayed wound healing, higher morbidity and mortality, and prolonged ICU stays. 1

• Bariatric surgery patients frequently develop B12 deficiency affecting wound healing; surgical techniques causing restriction (sleeve gastrectomy, gastric banding) affect B12 absorption, while anatomy-altering surgeries (Roux-en-Y) cause more pronounced deficiencies. 1

Diagnostic Approach in At-Risk Patients

• Screen patients with ≥1 risk factor (age >75 years, gastric/intestinal resection, inflammatory bowel disease, metformin >4 months, PPI/H2-blocker >12 months, vegan/vegetarian diet) who present with anemia, macrocytosis, cognitive difficulties, neurological problems, or unexplained fatigue. 4, 7, 5

• Initial test: serum total B12 (<180 pg/mL confirms deficiency; 180–350 pg/mL is indeterminate and requires methylmalonic acid [MMA] testing; >350 pg/mL makes deficiency unlikely). 4, 5

• MMA >271 nmol/L confirms functional B12 deficiency with 98.4% sensitivity, detecting an additional 5–10% of patients with deficiency who have low-normal B12 levels. 4, 5

Treatment to Optimize Wound Healing

• For malabsorption with neurological involvement: hydroxocobalamin 1 mg IM on alternate days until no further improvement, then 1 mg IM every 2 months for life. 4, 6

• For malabsorption without neurological involvement: hydroxocobalamin 1 mg IM three times weekly for 2 weeks, then 1 mg IM every 2–3 months for life. 4, 6

• For dietary insufficiency: oral B12 1000–2000 mcg daily is as effective as IM administration. 4, 7, 5

• Critical pitfall: Never administer folic acid before treating B12 deficiency, as folic acid can mask anemia while allowing irreversible neurological damage (subacute combined degeneration) to progress. 4, 6

Monitoring During Wound Healing

• Recheck B12 levels at 3,6, and 12 months in the first year, then annually thereafter to detect treatment failures or recurrence. 4

• Target homocysteine <10 μmol/L for optimal cardiovascular and wound healing outcomes. 4, 6

• Check concurrent deficiencies (iron, folate, vitamin D, thiamin, zinc, copper) at the same intervals, as these often coexist and independently impair wound healing. 1, 4