Intrinsic factor is a protein produced in the stomach that is essential for the absorption of vitamin B12. Vitamin B12, also known as cobalamin, is an essential nutrient the body cannot produce and must be obtained through diet. It is needed for healthy nerve function, red blood cell formation, and DNA synthesis. Intrinsic factor acts as a carrier, ensuring this vitamin is properly absorbed.
The Roles of Intrinsic Factor and Vitamin B12
Intrinsic factor is a glycoprotein secreted by parietal cells in the stomach lining. Its primary function is to serve as a carrier protein for vitamin B12, enabling its absorption. Without sufficient intrinsic factor, the body struggles to absorb enough B12 from dietary sources.
Vitamin B12, or cobalamin, is a water-soluble vitamin involved in the formation of the myelin sheath that protects nerve cells, DNA synthesis, and the maturation of red blood cells. Since the human body cannot produce vitamin B12, it must be acquired from external sources. These include animal products like meat, fish, eggs, and dairy, as well as fortified foods for vegetarians and vegans.
How Intrinsic Factor Ensures B12 Absorption
The journey of vitamin B12 absorption begins in the stomach, where dietary B12, often bound to proteins, is released with the help of stomach acid and the enzyme pepsin. Once freed, vitamin B12 quickly binds to R-proteins, which are secreted by the salivary glands and gastric mucosal cells. This binding protects the vitamin B12 as it passes through the acidic environment of the stomach to the duodenum.
As the R-protein-B12 complex moves into the small intestine, pancreatic proteases degrade the R-proteins, liberating the vitamin B12. The free vitamin B12 then binds to intrinsic factor. This vitamin B12-intrinsic factor complex is resistant to degradation by digestive enzymes and proceeds through the small intestine.
The complex then travels to the terminal ileum, the final section of the small intestine. Here, specialized receptors recognize and bind to the vitamin B12-intrinsic factor complex. This facilitates absorption into the enterocytes, the cells lining the ileum. Once inside, vitamin B12 is released from intrinsic factor and binds to transcobalamin II. This transcobalamin II-B12 complex is then transported into the bloodstream, delivering the vitamin to the liver and other body tissues.
Health Consequences of Impaired B12 Absorption
When intrinsic factor-mediated absorption of vitamin B12 is compromised, health problems can arise. A primary consequence is megaloblastic anemia, characterized by the production of abnormally large, immature red blood cells that cannot function properly. This can lead to symptoms such as fatigue, weakness, pallor, and shortness of breath. Inadequate B12 levels impair red blood cell production, reducing oxygen delivery.
Beyond blood-related issues, impaired B12 absorption can lead to neurological symptoms because vitamin B12 is important for nerve health. Individuals may experience numbness or tingling sensations, known as paresthesia, particularly in the hands and feet. Other neurological manifestations can include balance problems, difficulty walking, and cognitive issues such as memory loss, confusion, and difficulty concentrating. Severe or prolonged deficiency can result in nerve damage, depression, irritability, psychosis, or dementia.
Additional symptoms associated with B12 deficiency can include glossitis, which presents as a sore, red, and swollen tongue. Digestive disturbances like nausea, vomiting, or diarrhea may also occur. Early recognition and intervention are important to prevent irreversible neurological damage, as these symptoms can sometimes appear even without anemia.
Common Causes and Management of Impaired B12 Absorption
Impaired vitamin B12 absorption can stem from several conditions. Pernicious anemia is a common cause, an autoimmune disorder where the immune system attacks the parietal cells in the stomach that produce intrinsic factor, or targets intrinsic factor itself. This autoimmune destruction leads to a reduction or absence of intrinsic factor, preventing B12 absorption. Individuals of Scandinavian or Northern European descent, or those with a family history, may have an increased risk.
Gastric surgeries, such as gastrectomy (the removal of part or all of the stomach), can significantly impact intrinsic factor production, as its primary synthesis site is removed or bypassed. Atrophic gastritis, a chronic inflammation of the stomach lining often seen in older adults, can lead to the gradual loss of parietal cells and, consequently, a decline in intrinsic factor secretion. Certain medications, including long-term use of proton pump inhibitors (PPIs) and H2 blockers, can reduce stomach acid, which is necessary to release B12 from food proteins, indirectly affecting B12 availability for binding with intrinsic factor. Metformin, a medication for diabetes, can also interfere with B12 absorption.
Diagnosing impaired B12 absorption involves blood tests to measure vitamin B12 levels. Further tests, such as methylmalonic acid (MMA) and homocysteine levels, can confirm a functional B12 deficiency, as these markers are elevated when B12 is insufficient. Specific tests like intrinsic factor blocking antibodies can help diagnose pernicious anemia. The Schilling test historically assessed B12 absorption by measuring radioactive B12 excretion after oral and injectable doses.
Management of impaired B12 absorption focuses on bypassing the compromised digestive pathway. Since the issue lies with absorption rather than dietary intake, increasing dietary B12 alone is often insufficient. The most common and effective treatment involves regular vitamin B12 injections to ensure the vitamin directly enters the bloodstream. High-dose oral B12 supplements can also be effective by allowing a small percentage of B12 to be absorbed through passive diffusion, a mechanism that does not rely on intrinsic factor. While treatment resolves B12 deficiency symptoms, it does not cure underlying conditions like atrophic gastritis.