Pernicious anemia is found in about 0.1% of the overall population, but it is much more common in older adults. In people over 60, the prevalence is around 2%.[ref] The lack of vitamin B12, though, can cause symptoms long before developing pernicious anemia. Knowing the risk factors and symptoms can give you a ‘heads up’ to test your vitamin B12 levels and stay ahead of the problem.
This article explains why pernicious anemia occurs, genetic variants that increase susceptibility to it, and possible next steps to take.
What is Pernicious Anemia?
Anemia is a general term that means you don’t have enough properly formed red blood cells to provide enough oxygen through the body.
Pernicious anemia is a type of B12 deficiency that causes fewer red blood cells to form. It is a type of megaloblastic anemia caused by defective DNA synthesis.
Red blood cells are constantly being formed in the bone marrow, and if the body doesn’t have enough of the micronutrients needed, the formation of new blood cells can be limited. For DNA to be replicated for new cells, both folate and vitamin B12 can be limiting factors. Vitamin B12 is a cofactor in synthesizing methionine, which is essential for protein formation.[ref]
If you are deficient in B12 or folate for a long time, you can develop megaloblastic anemia. Specifically, pernicious anemia is anemia caused by a deficiency of vitamin B12 due to a lack of absorption. The lack of B12 is the limiting factor for creating new blood cells.
Pernicious anemia symptoms:
Symptoms of B12 deficiency can include:[ref]
- fatigue, paleness, shortness of breath (anemia symptoms)
- headaches, dizziness
- tingling in the extremities
- trouble walking or uncontrollable muscle movements
- cognitive issues, brain fog
- depression or irritability
- intestinal issues
Vitamin B12 (cobalamin) is found in animal proteins such as meat and eggs – and in supplement forms. Note that you can have B12 deficiency symptoms long before it progresses to anemia.
Pernicious anemia tongue changes:
I mentioned above in the symptoms that there could be changes to the tongue, called glossitis. It is actually one of the symptoms of pernicious anemia that people may notice first — and is a symptom that may respond quickly to B12 supplementation.
Glossitis is the term for a tongue that is swollen and inflamed. You may notice that your tongue feels smooth and sore. It is like the feeling after you’ve burned your tongue eating something hot. Glossitis can be caused by a B12 deficiency or a deficiency in iron, thiamine, riboflavin, B3, B6, or B9.
What causes pernicious anemia?
Vitamin B12 is sensitive to acid, which is a problem in the stomach. A protein called haptocorrin is secreted in the salivary glands, which binds to B12 when you chew your food. Haptocorrin bound to B12 keeps it from being damaged in stomach acid.
In the stomach, the cells lining the stomach produce a protein called intrinsic factor. The intrinsic factor then binds with B12, facilitating the uptake of B12 in the small intestines.[ref]
Without intrinsic factor, you can’t absorb B12 from animal proteins. Pernicious anemia is a B12 deficiency anemia caused by the lack of intrinsic factor.[ref]
What causes the lack of intrinsic factor in pernicious anemia?
Damage to the epithelial cells lining the stomach stops the production of intrinsic factor. This type of damage is usually due to autoimmune gastritis.
It takes years to develop the full-blown symptoms of pernicious anemia. However, someone with decreased intrinsic factor may have symptoms of milder B12 deficiency long before pernicious anemia.[ref] The time to act is long before your body develops full-blown anemia.
Autoantibodies and Pernicious Anemia
Digging a little deeper into what is happening in the stomach…
The stomach lining contains a type of epithelial cell called parietal cells. These cells are found in the gastric glands, and parietal cells secrete intrinsic factor and hydrochloric acid (stomach acid).
How is stomach acid released?
- Histamine stimulates H2 (histamine 2) receptors on parietal cells to stimulate the release of stomach acid.
- Acetylcholine via the vagus nerve can also stimulate some stomach acid release by stimulating M3 (muscarinic acetylcholine) receptors.
Autoimmune gastritis is caused by the CD4+ T cells in the immune system attacking parietal cells. It can destroy the parietal cells, leading to dysregulation of stomach acid release as well as decreased intrinsic factor. If the damage goes on long enough, parietal cells can be lost entirely.[ref]
Antibodies to parietal cells are found in 90% of patients with autoimmune gastritis. Additionally, 50-70% of autoimmune gastritis patients have antibodies specific to intrinsic factor. These antibodies to intrinsic factor can be detected several years before the onset of symptoms of pernicious anemia.[ref]
What triggers autoimmune gastritis?
This question isn’t completely settled yet. The presence of H. pylori infection is one possibility. Helicobacter pylori is a bacteria that commonly infects the stomach and can cause gastritis or ulcers in some people. H. pylori infection is more common in people with certain autoimmune diseases, and some research points to H. pylori as a trigger for autoimmune gastritis.[ref] H. pylori infection or antibodies to H. pylori has been found in 83% of patients with autoimmune gastritis. However, H. pylori infections are fairly common, and most don’t result in autoimmune gastritis.[ref][ref]
Autoimmune gastritis and pernicious anemia often coincide with other autoimmune diseases, including vitiligo, oral lichen planus, Addison’s disease, and type 1 diabetes.[ref]
How is pernicious anemia diagnosed?
Your doctor usually diagnoses B12-deficiency anemia in conjunction with abnormal blood testing results. Hemoglobin tests can show if you have anemia or not, and low B12 points to B12 deficiency anemia.
For men, a normal hemoglobin level is 13.2 to 16.6 g/dL, and for women, 11.6 to 15 g/dL.[ref]
A normal vitamin B12 level is usually defined as 400 pg/mL or higher. It can change a bit, though, based on the lab used.
Pernicious Anemia Genotype Report:
Lifehacks for Pernicious Anemia:
Talk with your doctor, of course, about what to do about pernicious anemia. Often, vitamin B12 shots or supplements will be prescribed, and in rare cases, blood transfusions may be needed. Iron or folate may also be needed. Your doctor can run blood tests to know which vitamins and minerals are required, and you can also order blood tests on your own (sometimes cheaper that way).
Tamping down autoimmune disease with diet:
Autoimmune gastritis can occur along with other autoimmune diseases, and autoimmune diets may help to decrease symptoms and flares.
Treating pernicious anemia by diet alone, though, is likely not going to work due to the damage to the cells that make intrinsic factor. Instead, you may want to investigate an autoimmune diet, such as AutoImmune Paleo (AIP) or an autoimmune protocol diet to boost overall health with an autoimmune disease.[ref][ref] Essentially, the AIP diet removes many foods that are thought to either increase inflammation or cause some kind of immune system response. After a period, people can add foods back in one at a time to determine if the foods are causing any change to their autoimmune disease.
RDA for B12:
Keep in mind that vitamin B12 is a water-soluble vitamin with no known toxicity. The RDA for vitamin B12 is 2.4 mcg per day.
Intrinsic factor production often decreases with aging. For older adults, especially if their diet is limited, supplemental B12 is usually recommended.[ref]
Choosing the right type of vitamin B12 for your genes:
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