Vitamin B12 Deficiency: Symptoms, Causes, Testing and Treatment

What vitamin B12 does

Vitamin B12 (cobalamin) is required for three things: making DNA, which is why deficiency shows first in rapidly dividing cells such as red blood cells; maintaining myelin, the fatty insulation around nerve fibres; and processing homocysteine and methylmalonic acid, two metabolites that accumulate when B12 is short and can be measured to confirm deficiency.

The body stores several years' worth of B12 in the liver, so deficiency develops slowly — often over two to five years — and symptoms creep in gradually enough to be attributed to age or stress.

Symptoms

Nervous system

• tingling, pins and needles or numbness in the feet and hands — see tingling in the hands and feet
• unsteadiness, especially in the dark, from loss of position sense
• weakness and stiffness in the legs
• memory difficulty, confusion, difficulty concentrating
• low mood, irritability, occasionally psychosis
• vision changes from optic nerve involvement (rare)

The neurological picture is a combination of peripheral neuropathy and damage to the spinal cord's posterior columns, a pattern called subacute combined degeneration. These symptoms can appear before any change in the blood, and they are the ones that can become permanent.

Blood

• fatigue, breathlessness on exertion, palpitations, pallor — from anemia
• the red cells are abnormally large (macrocytic), which is often the first laboratory clue

Other

• a sore, smooth, red tongue
• mouth ulcers
• loss of appetite, weight loss
• yellowish tinge to the skin

Causes

Absorption problems — the majority of cases in developed countries:

• Pernicious anemia — an autoimmune condition destroying the stomach cells that make intrinsic factor, the protein B12 needs to be absorbed. Common in older adults and in people with other autoimmune conditions (thyroid disease, type 1 diabetes, vitiligo).
• Atrophic gastritis and low stomach acid with age — B12 in food is bound to protein and needs acid to be released.
• Medications: metformin (reduces absorption in up to a third of long-term users), proton pump inhibitors and H2 blockers (reduce stomach acid), nitrous oxide (inactivates B12, relevant in recreational use and repeated anaesthesia).
• Bowel conditions and surgery: coeliac disease, Crohn's disease, gastric bypass or gastrectomy, removal of the terminal ileum where B12 is absorbed, bacterial overgrowth, fish tapeworm.

Dietary insufficiency:

• B12 occurs naturally only in animal foods. Vegans and long-term vegetarians without fortified foods or supplements become deficient over years; breastfed infants of deficient mothers can become deficient within months.

Who should be tested

Anyone with unexplained tingling or numbness, unsteadiness, cognitive change, anemia or large red cells; people on long-term metformin or acid-suppressing drugs; vegans and vegetarians; older adults with fatigue or memory change; people with autoimmune thyroid disease, type 1 diabetes, coeliac or Crohn's disease; anyone who has had stomach or bowel surgery; and recreational nitrous oxide users.

Test before starting supplements: B12 tablets normalize the blood level within days and make the diagnosis, and the search for its cause, impossible.

How it is tested

• Serum B12 — the standard first test. Below about 150–200 pg/mL (110–150 pmol/L) is deficient; 200–300 pg/mL is borderline; above that is usually adequate, though the test has limitations.
• Methylmalonic acid (MMA) — rises when B12 is functionally short at the cellular level. It clarifies borderline serum results and is the more reliable marker. Homocysteine also rises but is less specific.
• Full blood count — for anemia and large red cells.
• Intrinsic factor antibodies — positive in about half of pernicious anemia; a positive result confirms the diagnosis.
• Folate — often tested alongside, because folate deficiency causes similar anemia and the two must be distinguished: giving folate alone to someone deficient in B12 can worsen nerve damage.

Treatment

Injections of hydroxocobalamin (UK, Europe) or cyanocobalamin (US) — typically a loading course over one to two weeks, then every one to three months. Preferred when there are neurological symptoms, in pernicious anemia, and after bowel surgery.

High-dose oral B12 — 1,000–2,000 mcg daily is absorbed by passive diffusion even without intrinsic factor, and trials show it corrects deficiency as effectively as injections for most causes. Suitable for dietary deficiency, drug-related deficiency and maintenance.

Sublingual, nasal and dietary forms are alternatives; sublingual is not better absorbed than swallowed tablets.

Treatment is lifelong when the cause is permanent (pernicious anemia, bowel surgery); temporary when the cause is removed. Blood counts respond within weeks; nerve symptoms over months, and recovery is fullest when treatment is early.

Food sources and prevention

Meat, fish, shellfish, eggs and dairy provide B12; clams and liver are the richest sources. Plant foods contain none unless fortified — fortified breakfast cereals, plant milks and nutritional yeast are the usual vegan sources, and a daily supplement of 25–100 mcg (or a weekly 2,000 mcg dose) is recommended for anyone avoiding animal foods. The recommended intake for adults is 2.4 mcg a day; there is no upper limit, since excess is excreted.

When to see a doctor

Ask for testing if you have persistent tingling or numbness, unsteadiness, unexplained fatigue, memory change, or belong to any of the risk groups above. See a doctor promptly if tingling is spreading, walking is becoming unsteady, or there is confusion — the neurological effects are the ones that matter most, and they respond best to early treatment.

Frequently asked questions

References