Vitamin B12 Deficiency

Causes and Risk Factors

• Pernicious anemia: An autoimmune condition that destroys the stomach cells making intrinsic factor, preventing B12 absorption.
• Atrophic gastritis: Chronic thinning of the stomach lining, often age-related or following long-standing gastritis, reduces the acid needed to free B12 from food.
• Medications: Long-term metformin use and long-term acid-suppressing medicines (proton pump inhibitors and H2 blockers) lower B12 levels.
• Digestive disease or surgery: Celiac disease, Crohn's disease involving the small intestine, and gastric or ileal surgery impair absorption.
• Vegan or vegetarian diets: B12 occurs naturally only in animal foods, so strict plant-based diets require supplementation.

Symptoms

• Fatigue, weakness, and pallor: Signs of the large-cell (megaloblastic) anemia that B12 deficiency causes.
• A sore, smooth tongue and mouth ulcers: Classic but often overlooked.
• Numbness and tingling: Typically starting in the feet and hands as nerves lose their insulation.
• Balance problems and unsteady walking: From involvement of the spinal cord's position-sense pathways.
• Memory difficulty, irritability, and depressed mood: B12 deficiency is a reversible contributor to cognitive symptoms, particularly in older adults.
• Shortness of breath with exertion: A less common sign reflecting more significant anemia.

Diagnosis

Treatment

• B12 injections: The standard approach when absorption is the problem, given frequently at first and then monthly for maintenance.
• High-dose oral B12: Effective for many people, including some with absorption problems, because a small fraction is absorbed without intrinsic factor.
• Treating the cause: Adjusting contributing medications when appropriate, treating digestive disease, and supplementing during strict plant-based diets.
• Follow-up: Blood counts recover within weeks; nerve symptoms improve more slowly, which is why early treatment matters most.

Complications

• Lasting nerve and spinal cord injury: Long-standing deficiency damages the insulating sheath around nerve fibers, a pattern called subacute combined degeneration that can leave permanent numbness, weakness, or unsteady walking.
• Falls and injury: Loss of position sense in the feet makes older adults more likely to fall, especially in the dark or on uneven ground.
• Strain from severe anemia: Deep anemia forces the heart to work harder and can worsen chest pain or breathlessness in someone with coronary artery disease.
• Stomach changes with pernicious anemia: The autoimmune stomach inflammation behind pernicious anemia carries a modestly increased long-term risk of stomach cancer, so persistent new digestive symptoms should be evaluated rather than assumed benign.

Getting B12 Replacement Right

Replacing B12 is simple; the mistakes are in the details: choosing tablets when the gut cannot absorb them, stopping once the blood count recovers, or treating a level that was never the problem.

Tablets or injections: how the choice is made

Pernicious anemia, previous stomach or ileal surgery, and any deficiency with nerve symptoms are usually started with injections, given several times in the first weeks and then monthly for life. Daily high-dose oral B12, typically a thousand micrograms or more, is absorbed by passive diffusion without intrinsic factor and works for most people with dietary deficiency, medication-related deficiency, or mild absorption problems, provided it is taken every day. Some people on injections can be switched to high-dose tablets once replete, with levels rechecked. Sublingual and nasal forms are not absorbed any better than swallowed tablets.

What recovery looks like, and how long it takes

Energy often improves within days, and the blood count normalizes over about two months; a rise in young red cells within a week is the first sign the diagnosis was right. Nerve symptoms improve over three to twelve months, and whatever remains after a year is usually permanent. Potassium can fall as new red cells are made after severe anemia, so it is checked early in people with a very low count. Feeling no better after two months of correct treatment means the fatigue had another cause, and hypothyroidism, anemia from iron deficiency, and depression are the usual candidates.

Metformin, acid suppressants, and nitrous oxide

People taking metformin long term have B12 checked periodically, and a low level is treated without stopping the metformin. The same applies to long-term omeprazole or pantoprazole; our long-term PPI risks article covers when a lower dose is possible. Nitrous oxide, whether from dental sedation or recreational use, inactivates the body's B12 within hours and can precipitate severe nerve damage in someone whose stores were already low.

Conditions it is mistaken for, and conditions that hide it

Numb feet in a person with diabetes are often blamed entirely on diabetic neuropathy when B12 deficiency from metformin is contributing; any new peripheral neuropathy gets a B12 level. Memory change in an older adult is checked for it before mild cognitive impairment or dementia is diagnosed. Untreated celiac disease and Crohn's disease of the small intestine keep levels low despite treatment until the gut disease is controlled.

Vegans, older adults, and prevention

Anyone on a fully plant-based diet needs a supplement or reliably fortified foods from the start, because stores run down over years and symptoms arrive late; our B12 in older adults and vegans article covers the practical choices. After 50, reduced stomach acid makes food-bound B12 harder to absorb, and fortified foods or a tablet are the reliable source. Our hematology team manages pernicious anemia. The NIH Office of Dietary Supplements and NHLBI publish patient guidance on deficiency and treatment.

If you take metformin or an acid reducer and have never had a B12 level checked, or have numb feet nobody has explained, schedule a visit.