Pernicious Anemia and Intrinsic Factor: Why B12 Is Not Absorbed

See a clinician promptly

If you have numbness or tingling in the hands or feet, balance problems, confusion or memory changes, or unexplained tiredness with a pale look, see a clinician. The NHS stresses that vitamin B12 deficiency anaemia should be diagnosed and treated as soon as possible, because some problems can be irreversible. [1] MedlinePlus says nerve damage can be permanent if treatment does not start within 6 months of symptoms. [2] Pernicious anemia needs medical diagnosis and ongoing care. It is not something to manage with over-the-counter vitamins on your own.

What it is, in plain words

Vitamin B12 from food needs help to be absorbed. A protein called intrinsic factor (IF), released by cells in the stomach, binds B12 so the intestine can absorb it. When the stomach does not make enough intrinsic factor, the intestine cannot properly absorb vitamin B12. [2] The NHS adds that the B12 and intrinsic factor mix is absorbed in the distal ileum, a part of the gut. [3]

Pernicious anemia is the resulting drop in red blood cells. MedlinePlus calls it a type of vitamin B12 anemia, and lists common causes: a weakened, inflamed stomach lining (atrophic gastritis) and an autoimmune condition in which the immune system attacks the intrinsic factor protein or the stomach cells that make it. [2] A review of autoimmune gastritis explains that destruction of stomach parietal cells leads to loss of intrinsic factor and reduced acid output, and so to malabsorption of iron and of vitamin B12. [4] It notes that pernicious anemia and autoimmune gastritis have often been confused. [4]

Who is more likely to develop it

• The NHS says pernicious anaemia is the most common cause of vitamin B12 deficiency in the UK, and is more common in women around 60, people with a family history, and people with another autoimmune condition such as Addison's disease or vitiligo. [3]
• MedlinePlus says symptoms usually appear after age 30, the average age at diagnosis is 60, and risk is higher in people of Scandinavian or Northern European background and those with certain conditions, including type 1 diabetes, thyroid disease and celiac disease. [2]
• It can also occur after gastric bypass surgery, and rarely a congenital form is inherited. [2]

Other causes of low B12 are different from pernicious anemia: a strict vegan diet without supplements or fortified foods, stomach or bowel surgery, Crohn's disease, long-term acid-reducing medicines and metformin. [3] [5] See Vitamin B12 deficiency, Vitamin B12 and medicines and Vitamin B12 for vegetarians and vegans.

Signs and symptoms

Some people have no symptoms, or mild ones. MedlinePlus lists fatigue, lightheadedness, shortness of breath, pale skin, a swollen red tongue, diarrhea or constipation, and, after a long period of low B12, confusion, memory loss, depression, loss of balance, and numbness and tingling in the hands and feet. [2] Many of these also occur in other conditions. See Vitamin deficiency symptoms: what they can and cannot tell you.

How it is investigated

MedlinePlus lists a complete blood count, serum vitamin B12, methylmalonic acid (MMA), homocysteine, and antibodies against intrinsic factor or the stomach cells that make it. [2] The NHS says tests for pernicious anaemia are not always conclusive but can often give a good idea, and that some people have symptoms with seemingly normal B12 levels while others have low levels without symptoms. [6] Explanations of the B12 tests are on Vitamin B12 tests.

Treatment overview (clinician-led)

Treatment depends on the cause. MedlinePlus says it often involves a vitamin B12 shot about once a month, with more frequent shots at first if levels are very low; some people may be adequately treated with large doses of B12 by mouth, and a nasal spray form exists. [2] In the UK the NHS describes hydroxocobalamin injections, starting every other day, then every 2 to 3 months for life when the cause is not diet-related. [7] These describe how clinicians treat it, not a schedule for anyone to follow. For how injections are used see Vitamin B12 injections.

Possible complications and monitoring

MedlinePlus says people with pernicious anemia may have gastric polyps, are more likely to develop gastric cancer and gastric carcinoid tumors, and have more fractures of the back, upper leg and forearm. [2] Reviews of autoimmune gastritis recommend ongoing clinical management and vigilance for these downstream effects. [8] Discuss follow-up with your doctor.