Persistent fatigue is a tough mystery to solve. Causes include anemia, anxiety, depression, infection, cancer, chronic fatigue syndrome (CFS), poor diet, too little or too much exercise, poor sleep, liver or kidney disease, and the list goes on. One of the most overlooked conditions that can cause fatigue is autoimmune gastritis— a chronic inflammatory disease in which the immune system mistakenly destroys parietal cells— cells that produce the stomach acid and intrinsic factor (IF), which the body needs to be able to absorb vitamin B12.

As a result, people with autoimmune gastritis often suffer from pernicious anemia — a condition in which the body is unable to absorb the vitamin B12 needed to manufacture healthy red blood cells. Without sufficient numbers of healthy red blood cells to carry oxygen throughout the body, it is no surprise that people with pernicious anemia suffer persistent fatigue.

When we think about autoimmunity, a few specific conditions come to mind including rheumatoid arthritis (RA), multiple sclerosis (MS), juvenile diabetes, hyperthyroid, and Lupus. Of course, there are others.

What we don’t often consider are the less discussed or less aggressive autoimmune conditions that can have a large impact of how we feel day to day, lead to more progressive illness, and are often associated with the development of additional autoimmune conditions.

Unfortunately, conventional medical doctors often overlook autoimmune gastritis in patients who report chronic fatigue. They may test for anemia and treat it with iron supplements or test for B12 deficiency, see that your B12 level is fine, and never consider whether your body is actually able to absorb and use that B12. Even worse, some people who report fatigue are simply diagnosed as having anxiety or depression and prescribed sedatives or antidepressants. They may experience temporary relief, but the underlying condition remains undiagnosed and untreated.

Recognizing the Importance of Parietal Cells

The parietal cells secrete two important substances:

  • Hydrochloric (stomach) acid
  • Intrinsic factor

Although stomach acid is often blamed for indigestion and acid reflux, it is essential for proper digestion. It helps break down protein, and it stimulates the gallbladder to produce bile, allowing for adequate fat digestion. Stomach acid also helps to kill any infectious agents that enter the stomach through food or water; many pathogens cannot survive in a highly acidic environment.

When the parietal cells are under siege by the immune system, your ability to produce stomach acid is diminished and inadequate. Protein is not properly digested, adding stress to the gallbladder and lower parts of the digestive tract. In addition, lack of sufficient stomach acid makes the body more susceptible to infection from tainted food or beverages.

If stomach acid is essential for good digestion and for warding off infection, why do so many people take antacids, H2 blockers, and proton pump inhibitors (PPIs), such as Nexium (esomeprazole) and Prilosec (omeprazole), which are designed to shut down the production of stomach acid? Great question!

Antacids, H2 blockers, and PPIs generally do more harm than good. By reducing the concentration of stomach acid, they actually impair digestion and make the body more susceptible to infection. Many people who take PPIs long-term (even though pharmaceutical companies warn against doing so) suffer from nutritional deficiencies, particularly calcium and, to no surprise, vitamin B12.

I will write about the dangers of H2 blockers and PPIs in a future post, along with healthier, more effective ways to manage acid reflux.

The other substance lost as a result of autoimmune gastritis is intrinsic factor— a glycoprotein that binds B12, allowing it to be absorbed in the intestines and into the blood stream. Without sufficient intrinsic factor, B12 is lost through the intestines and must be replaced intramuscularly or through a liposomal preparation. The inability to absorb and use B12 leads to many symptoms described in this post.

More About Pernicious Anemia

“Pernicious” means having a harmful effect in a gradual or subtle way. The most common type of anemia is not pernicious; it is due to iron deficiency and is easy to spot on routine blood tests — the iron level and red blood cell counts are low. With pernicious anemia, the red blood cell count is lower, but the cells are larger (megaloblastic). In the early stages, circulating levels of B12 may appear normal, and the B12 deficiency and resulting anemia are easily overlooked using routine lab tests.

Without proper treatment, the gastric tissue continues to weaken and atrophy, resulting in a weakened stomach mucosa (stomach lining). Over time, people with untreated pernicious anemia often begin exhibiting signs of gastritis (inflammation of the stomach lining, which results in acid reflux) or cholestasis (gallbladder problems).

Autoimmune gastritis is not the only cause of pernicious anemia. Other causes include the following:

  • Vitamin B12 storage generally declines with age, so the prevalence of B12 deficiency increases as subjects get older. Studies show that the rate of B12 deficiency among people 65 and older can range from five to 40 percent.
  • Decreased absorption due to gastrectomy, bariatric surgery, Crohn’s disease, celiac disease, pancreatic insufficiency, bacterial overgrowth, fish tapeworm infection, and other conditions that negatively impact digestion.
  • Autoimmune conditions, such as thyroid disease.
  • Taking one or more medications known to interfere with vitamin absorption, metabolism, or stability, such as nitrous oxide, metformin, and proton pump inhibitors (PPIs).
  • H-pylori infection.

Vitamin B12 deficiency is silent and under-diagnosed, often because its onset and progression are slow and people get used to their symptoms. Nevertheless, the clinical consequences of undiagnosed vitamin B12 deficiency may be serious, including a wide range of neurological and mood disorders.

Suffering Downstream Consequences

Health issues caused by an inability to absorb vitamin B12 reach far beyond the stomach and gallbladder and can be much more serious than gastritis and cholestasis. These conditions are what I refer to as “downstream consequences.” Here are a few examples:

  • Severe neurological consequences can take place including demyelination of the spinal cord, as is seen in multiple sclerosis (MS). If treatment is initiated early, this is reversible, but for those whose treatment is postponed, the damage to the nerves can be irreversible.
  • Vitamin B12 is vital for DNA synthesis and repair. When DNA synthesis or repair is altered, cellular damage and programmed cell death (apoptosis) results. Merely taking B12 orally does not help, because the body’s ability to absorb it through the stomach is impaired.
  • When parietal cells produce insufficient amounts of stomach acid, calcium absorption is impaired, which can result in loss of bone density and increased susceptibility to bone fractures.

Recognizing the Symptoms of Autoimmune Gastritis and Pernicious Anemia

Symptoms of autoimmune gastritis and the resulting pernicious anemia are wide ranging and often subtle:

  • Fatigue
  • Depression or mood impairment
  • Irritability
  • Insomnia
  • Cognitive decline
  • Forgetfulness
  • Dementia
  • Psychosis
  • Visual disturbances, with atrophy of the optic nerve
  • Loss of sensation in limbs
  • Weakness
  • A shock-like sensation that radiates to the feet during neck flexion
  • Altered gait
  • Abnormal deep tendon reflexes
  • Muscle rigidity
  • Restless legs syndrome
  • Inability to lose weight

Testing for Autoimmune Gastritis and Pernicious Anemia

When treatment providers suspect a vitamin B12 deficiency, they take the logical step of testing for levels of B12 in the bloodstream. However, research indicates this approach does not provide an adequate assessment of B12 status. Just because there appears to be sufficient B12 in the bloodstream does not mean that the body is absorbing it and using it properly. Therefore, you may have normal B12 levels and still have problems associated with B12 deficiency. More thorough testing is necessary, such as the following:

  • Methylmalonic acid (MMA) testing: This test reveals whether the body is using B12 effectively. B12 is needed in order to convert MMA into Succinyl CoA — an intermediate that ultimately enters cells to provide energy. If B12 is not doing its job or is low, MMA may be elevated.
  • Parietal cell antibody (AB) test checks whether the body’s immune system has produced antibodies to attack parietal cells.
  • Intrinsic factor antibody (AB) test checks whether the body’s immune system has produced antibodies to attack intrinsic factor.
  • Testing genetic predispositions that relate to B12 and folate, another B vitamin that is essential for cell growth and reproduction. For example, the methylenetetrahydrofolate reductase (MTHFR) test examines whether a patient has one or more variants (mutations) of the MTHFR gene. With certain MTHFR mutations, the body lacks the enzymes necessary for converting folate into the active form, 5-Methyltetrahydrofolate, which the body needs to use B12 properly. This leads to a homocysteine imbalance, which is a serious health problem.

If all of this sounds technical, it is. Simply taking a quality B12 supplement or a B complex supplement that includes folate does not necessarily fix the problem. Testing and treatment should be entrusted to a doctor who regularly looks for these problems and knows how to correct them. Care should be individualized, and people who remain tired should be further evaluated even if the traditional health care system has chalked it up to, “there’s nothing wrong with you, your labs look normal.”

Testing may need to include endoscopy (a non-surgical procedure used to examine your digestive tract through the use of a camera), further blood evaluations, and genetic testing to name a few possibilities. When looking for B12 problems, other vitamin deficiencies must be considered, as well. That’s because B12 does not activate in isolation — it takes other coenzymes and minerals to make sure absorption and assimilation take place. A thorough provider like myself looks at a variety of factors influencing B12 and does not stop unraveling the mystery until your energy is restored!

If you are feeling burned out or experiencing any of the symptoms described in this post, I strongly encourage you to see a doctor who has the knowledge, training, and experience diagnosing and treating illness down to the cellular level, such as a doctor with functional medicine training. Your fatigue and other symptoms may or may not be related to autoimmune gastritis, so you want a doctor who is aware of all the possible conditions that may be causing your symptoms. Don’t accept anybody telling you that “there’s nothing wrong with you” or that you are simply stressed out or depressed. Any doctor you consult should dig deep to uncover and address the underlying causes of what is ailing you, and this doctor should not stop until your health and fitness are fully restored.


Disclaimer: The information in this blog post is provided for general informational purposes only and may not reflect current medical thinking or practices. No information contained in this post should be construed as medical advice from Dr. Matt Lewis, D.C., DACBN, CFMP®, nor is this post intended to be a substitute for medical counsel on any subject matter. No reader of this post should act or refrain from acting on the basis of any information included in, or accessible through, this post without seeking the appropriate medical advice on the particular facts and circumstances at issue from a licensed medical professional in the recipient’s state, country or other appropriate licensing jurisdiction.


About the Author: Dr. Matt Lewis, D.C., DACBN, CFMP®, specializes in diagnosing and treating the underlying causes of the symptoms related to chronic and unexplained illness through nutrition, lifestyle, chiropractic, and other natural approaches to whole-health healing in Tampa, Florida. He earned his B.S. in Biology from Shenandoah University, his Doctorate in Chiropractic from Life University, his Diplomate status in Clinical Nutrition from the American Clinical Board of Nutrition, his CFMP® from Functional Medicine University, and his certification as a Digestive Health Specialist (DHS) through the Food Enzyme Institute. Dr. Lewis’ passion for health and wellness stems from his own personal experience. With a family history of autoimmune conditions and diabetes, and his own lab tests showing his genetic susceptibility to Hashimoto’s thyroiditis (autoimmune thyroid), he has learned how to restore his own health and vigor to prevent the onset of these and other illnesses and live an incredibly active life. Through this process, he acquired a deeper understanding of health and wellness, which he now offers his patients in Tampa.

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