Vitamin B12 Deficiency

What vitamin B12 does

Vitamin B12 is essential for:

• making DNA, so cells that divide quickly, such as red blood cells in the bone marrow and the cells lining the mouth and gut, depend on it
• maintaining myelin, the fatty sheath that insulates nerves in the brain, spinal cord and limbs
• processing homocysteine and methylmalonic acid, which build up in the blood when B12 is low

Adults need about 2.4 micrograms a day, a little more in pregnancy and breastfeeding. B12 comes almost only from animal foods: meat, fish, eggs and dairy, plus fortified cereals, plant milks and nutritional yeast. The liver stores several years' worth, so deficiency often takes years to appear after intake or absorption drops.

How B12 is absorbed

1. Stomach acid releases B12 from food proteins.
2. Cells in the stomach lining (parietal cells) make intrinsic factor, a protein that binds B12.
3. The B12 and intrinsic factor complex is absorbed at the end of the small intestine (the terminal ileum).

A problem at any step causes deficiency. About 1% of a large dose is also absorbed passively, without intrinsic factor, which is why high-dose tablets can work even in pernicious anemia.

Causes of vitamin B12 deficiency

Absorption problems (most common)

• Pernicious anemia: an autoimmune condition in which the immune system attacks the parietal cells or intrinsic factor. It is the most common cause in many countries and more frequent in older adults and people with other autoimmune diseases such as thyroid disease or type 1 diabetes.
• Atrophic gastritis and long-term H. pylori infection
• Stomach surgery, including gastrectomy and bariatric operations such as gastric bypass
• Ileal disease or surgery: Crohn's disease, removal of the terminal ileum, radiation
• Celiac disease and other malabsorption conditions
• Small intestinal bacterial overgrowth, and rarely fish tapeworm infection
• Older age: reduced stomach acid makes it harder to release B12 from food

Medicines and substances

• Metformin for diabetes, especially after several years
• Proton pump inhibitors (omeprazole and similar) and H2 blockers taken long term
• Nitrous oxide (laughing gas) misuse, which inactivates B12 and can cause severe spinal cord damage even when blood levels look normal
• Colchicine and some anti-seizure drugs, less commonly

Low intake

• Vegan diets without fortified foods or supplements, and some vegetarian diets
• Babies breastfed by mothers who are vegan or B12 deficient, who can develop deficiency within months
• Very poor diets and alcohol use disorder

Symptoms of B12 deficiency

Symptoms usually come on gradually. Some people have nerve symptoms with a normal blood count.

Blood-related (anemia)

• fatigue and weakness
• pale skin, sometimes with a lemon-yellow tinge
• shortness of breath and palpitations on exertion
• headaches

Mouth and gut

• a sore, red, smooth tongue (glossitis)
• mouth ulcers
• loss of appetite, weight loss, diarrhea

Neurological symptoms

• pins and needles, numbness or burning in the feet and hands
• loss of position sense and balance, especially in the dark
• clumsiness and difficulty walking
• muscle weakness
• vision changes from optic nerve damage
• in severe cases, spinal cord damage called subacute combined degeneration

Mental symptoms

• memory loss, poor concentration and brain fog
• depression, irritability or mood changes
• confusion and, rarely, psychosis or dementia-like decline

In babies and children

Poor feeding, failure to thrive, floppiness, developmental delay or regression, and irritability.

B12 deficiency vs folate and iron deficiency

Important: taking folic acid alone when B12 is low can correct the anemia while nerve damage continues to worsen. B12 levels should be checked before starting folic acid for large red cell anemia.

Who should be tested

• people with symptoms above, especially unexplained nerve or memory problems
• adults over 65 with symptoms
• long-term metformin or acid-reducer users
• after stomach, bariatric or ileal surgery
• people with Crohn's disease, celiac disease or autoimmune thyroid disease
• vegans, and pregnant or breastfeeding people on plant-based diets
• people who use nitrous oxide recreationally

Diagnosis

• Complete blood count: may show anemia with large red cells (macrocytosis), though both can be normal.
• Serum B12 or active B12 (holotranscobalamin): levels below about 200 pg/mL (148 pmol/L) usually indicate deficiency; results in a gray zone need further testing.
• Methylmalonic acid (MMA) and homocysteine: raised levels confirm a functional deficiency when B12 is borderline.
• Intrinsic factor antibodies: a positive result confirms pernicious anemia. Parietal cell antibodies are less specific.
• Other tests as needed: folate and iron levels, celiac antibodies, gastroscopy.

Treatment

B12 replacement

• Injections: hydroxocobalamin or cyanocobalamin given into a muscle. Treatment usually starts with a series of injections over a few weeks to rebuild stores, then maintenance injections every 1 to 3 months. People with neurological symptoms are treated more intensively at first.
• High-dose oral tablets: for many people, including some with pernicious anemia, high-dose daily tablets work as well as injections, because a small fraction is absorbed passively. Your doctor will advise whether tablets suit you.
• Diet-related deficiency: oral supplements and fortified foods are usually enough.

Treatment is lifelong when the cause is permanent, such as pernicious anemia or gastric surgery. Stopping injections leads to deficiency returning.

Treat the cause

Adjust or monitor medicines such as metformin and acid reducers, treat celiac disease or bacterial overgrowth, and stop nitrous oxide use.

Monitoring

Blood counts are checked after treatment starts. In severe anemia, potassium may be monitored, because rapid production of new red cells can lower it.

How long recovery takes

The sooner treatment starts, the better nerve symptoms recover.

Complications

• permanent nerve damage, balance problems and falls
• cognitive decline
• heart strain from severe anemia
• raised homocysteine, linked to blood vessel disease (hyperhomocysteinemia)
• in pregnancy, a higher risk of neural tube defects in the baby
• in pernicious anemia, a higher risk of stomach cancer and stomach neuroendocrine tumors, so new indigestion or weight loss should be reported

Prevention

• Vegans and many vegetarians should take a B12 supplement or eat fortified foods every day.
• Adults over 50 are advised to get much of their B12 from fortified foods or supplements, which are absorbed more easily than food-bound B12.
• People on metformin, long-term acid reducers or after gastric surgery should have regular B12 checks.
• Avoid recreational nitrous oxide.

Frequently asked questions

What are the first signs of B12 deficiency?

Early signs are often tiredness, lack of energy, pale skin, breathlessness on exertion, a sore or red tongue, and pins and needles in the hands or feet. Memory problems, low mood and unsteadiness can also be early clues, sometimes before anemia shows up on a blood test.

What causes vitamin B12 deficiency?

The commonest causes are poor absorption from pernicious anemia, atrophic gastritis, stomach or bowel surgery, Crohn's disease or celiac disease; long-term metformin or acid-reducing medicines; and diets without animal products or fortified foods. Recreational nitrous oxide can also cause sudden, severe deficiency effects.

How long does it take to recover from B12 deficiency?

Energy often improves within days to 2 weeks of starting treatment, and the blood count normalizes in about 6 to 8 weeks. Nerve symptoms such as numbness and balance problems recover more slowly, over 3 to 12 months, and may not fully resolve if deficiency lasted a long time.

Are B12 tablets as good as injections?

For many people, high-dose B12 tablets are as effective as injections, even when absorption is impaired, because a small amount is absorbed without intrinsic factor. Injections are usually preferred at first for severe deficiency or neurological symptoms, and when adherence or absorption is a concern.

Can B12 deficiency cause neurological problems?

Yes. Low B12 damages the protective coating of nerves, causing numbness, tingling, balance problems, weakness, vision changes, memory loss and mood changes. Severe cases affect the spinal cord. These problems can occur even without anemia and need prompt treatment to prevent permanent damage.

What level of B12 is considered deficient?

A serum B12 below about 200 pg/mL (148 pmol/L) is generally considered deficient. Levels between about 200 and 300 pg/mL are borderline, and doctors then measure methylmalonic acid or homocysteine. Reference ranges vary between laboratories, and symptoms matter as much as the number.