Vitamin B12 is a nutrient that supports the body’s nerve and blood cell health and helps make DNA. A deficiency in this vitamin is a health concern with various origins. While diet and lifestyle are common causes, specific genetic blueprints can be a factor in how the body processes B12.
The Genetic Pathways to B12 Deficiency
Hereditary factors directly influence the body’s ability to use vitamin B12, with certain gene mutations disrupting absorption, transport, or cellular metabolism. These rare genetic conditions demonstrate a clear link between DNA and B12 levels. A genetic issue at any point in this process leads to a deficiency, regardless of B12 consumption.
One area for B12 processing is the gut. The rare condition Imerslund-Gräsbeck syndrome, for example, is caused by mutations in the CUBN or AMN genes. These genes provide instructions for a protein receptor in the small intestine that takes up the B12-intrinsic factor complex. When this receptor is faulty, B12 cannot be effectively absorbed.
Once absorbed, vitamin B12 requires a transport system. This is the job of transcobalamin II, a protein produced from instructions in the TCN2 gene. Mutations in this gene result in a defective or insufficient supply of the transport protein. Even if B12 is absorbed, it cannot be delivered to the body’s tissues.
Inside the cells, vitamin B12 must be converted into its active forms. This metabolic conversion involves several enzymes coded by specific genes. For instance, the MUT gene is for an enzyme that uses B12 to process fats and proteins. A mutation in any of these metabolic genes blocks the vitamin’s final conversion, rendering it unusable.
Pernicious Anemia and Its Genetic Link
Pernicious anemia is a common cause of B12 deficiency that operates differently from direct genetic mutations. It is an autoimmune condition where the immune system attacks parietal cells in the stomach lining. These cells produce intrinsic factor, a substance necessary for vitamin B12 absorption.
The destruction of parietal cells or the neutralization of intrinsic factor leads to an inability to absorb B12 from food. This deficiency results in anemia, a condition characterized by a lack of healthy red blood cells.
While pernicious anemia is an autoimmune response, there is a genetic predisposition to it. Individuals with a family history of the condition are at a higher risk. The genetic link is indirect, involving a complex interplay of genes that regulate immune function and increase the likelihood of autoimmunity.
Common Non-Genetic Factors
External and physiological factors also cause B12 deficiency. Dietary choices are a significant factor, particularly for individuals on vegan or vegetarian diets. Because vitamin B12 is found almost exclusively in animal products, those who avoid these foods must rely on fortified foods or supplements.
The aging process contributes to lower B12 levels, as the stomach lining produces less hydrochloric acid over time. Stomach acid separates vitamin B12 from food proteins, which is the first step for absorption. Reduced acid production impairs the body’s ability to utilize B12 from dietary sources.
Certain medical conditions and procedures also interfere with B12 absorption. Gastrointestinal diseases like Crohn’s disease and celiac disease damage the parts of the intestine where B12 is absorbed. Surgical procedures that remove parts of the stomach or small intestine, like gastric bypass surgery, permanently reduce the body’s capacity to absorb the vitamin. Some medications for diabetes and acid reflux also disrupt B12 absorption.
Identifying and Addressing the Deficiency
Diagnosing a vitamin B12 deficiency begins with reviewing symptoms, which include:
- Fatigue
- Tingling in the hands and feet
- Memory difficulties
- Vision problems
Healthcare providers use blood tests to confirm a diagnosis. The most common test measures serum B12, but it does not always provide a complete picture.
More accurate tests measure substances like methylmalonic acid (MMA) and homocysteine, which accumulate in the blood when active B12 is low. Elevated levels of MMA and homocysteine are sensitive indicators of a deficiency. Genetic testing is considered for infants showing symptoms or when other causes have been ruled out.
Treatment for B12 deficiency is tailored to the cause. If the deficiency is from dietary choices, oral supplements or fortified foods are sufficient. When the cause is an absorption problem, like pernicious anemia or a genetic disorder, bypassing the digestive system is necessary. Treatment involves high-dose B12 injections or high-dose oral supplements that can be absorbed without intrinsic factor.