Vitamin B12 deficiency: 9 symptoms doctors miss too often

B12 deficiency develops slowly — over two to five years. Symptoms are vague and are commonly blamed on stress, age or depression. Here are nine signs that should trigger a B12 check.

9 classic B12 deficiency symptoms

• Chronic fatigue that doesn't lift with rest
• Tingling or numbness in fingers and toes
• Memory and concentration problems ("brain fog")
• Pale, slightly yellowish skin
• Red, sore "glossitis" tongue
• Nausea, appetite loss, weight loss
• Depression, irritability
• Reduced tendon reflexes
• Balance problems, unsteady gait — late-stage sign

High-risk groups

• Vegans and strict vegetarians without supplementation
• Over 60 (declining stomach acid, reduced absorption)
• Long-term PPI users (omeprazole, esomeprazole)
• Metformin users (10–30% reduction in absorption)
• Gastritis, coeliac, Crohn's, partial gastric resection
• Autoimmune atrophic gastritis (pernicious anaemia)

Which tests

Serum B12 alone is insufficient — it mostly shows the biologically inactive fraction. Clinically: serum B12, holotranscobalamin (active B12), homocysteine, methylmalonic acid (MMA). A serum B12 of 200–300 pg/mL with elevated MMA means real deficiency despite "normal" B12.

How to restore

Mild: methylcobalamin 1000 μg oral daily for 8–12 weeks, then 500 μg long-term. Severe or neurological: hydroxycobalamin 1 mg IM every 2 days for 2 weeks, then 1 mg every 2–3 months maintenance. Methylcobalamin absorbs better in people carrying MTHFR variants.