There are a variety of causes of B12 and/or folate deficiencies. They include:
Insufficient dietary intake
B12 is found in animal products such as red meat, fish, poultry, milk, and eggs. Folate, also called folic acid or vitamin B9, is found in leafy green vegetables, citrus fruits, dry beans, yeast, and fortified cereals.
The human body stores several years' worth of B12 in the liver. Since a variety of foods consumed by Americans contain B12, a dietary deficiency of this vitamin is extremely rare in the U.S. It may be seen, for example, in people with generally poor nutrition or malnutrition, in vegans who do not consume any animal products, including milk and eggs, and in breastfed infants of vegans. In adults, dietary deficiencies do not usually cause symptoms until stores of the vitamins within the body have been depleted. Deficiencies in children and infants, however, show up fairly quickly since they have not had time to store as much of the vitamins as adults.
Folate deficiency used to be a common, but in 1997 the U.S. government mandated supplementation of cereals, breads, and other grain products with folic acid. Because folate is stored in tissue in smaller quantities than B12, folate must be consumed more regularly than B12.
Both B12 and folate deficiencies may be seen in people who have conditions that interfere with absorption of the vitamins in the small intestine. Vitamin B12 absorption occurs in a series of steps. B12 is normally released from food by stomach acid and then, in the small intestine, is bound to intrinsic factor (IF), a protein made by parietal cells in the stomach. This B12-IF complex is then absorbed by the small intestine, bound by carrier proteins (transcobalamins), and enters the circulation. If a disease or condition interferes with any of these steps, then B12 absorption is impaired.
Some examples of these conditions include:
- Pernicious anemia is the most common cause of B12 deficiency. A protein called intrinsic factor, made by parietal cells that line the stomach, is needed for B12 absorption. In pernicious anemia, inflammation damages the parietal cells, leading to little or no intrinsic factor, thus preventing the intestines from absorbing B12. With insufficient B12, the body produces enlarged but fewer RBCs. Because of the larger than normal RBCs, this is often referred to as megaloblastic or macrocytic anemia.
- Celiac disease
- Inflammatory bowel disease, including Crohns disease and ulcerative colitis
- Bacterial overgrowth or the presence of parasites in the intestines
- Reduced stomach acid production; stomach acid is necessary to separate B12 from the protein in food. This is the most common cause of B12 deficiency in the elderly and in individuals on drugs that suppress gastric acid production.
- Surgery that removes part of the stomach (and the parietal cells) or the intestines may greatly reduce absorption of nutrients. This is a concern that is considered when gastric by-pass procedures are performed.
- Chronic pancreatitis
All pregnant women need increased amounts of folate for proper fetal development. If a woman has a folate deficiency prior to pregnancy, it will be intensified during the pregnancy and may lead to premature birth and neural tube defects in the child. It is recommended that women with any chance of becoming pregnant take folic acid supplements because neural tube defects can develop in the first few weeks of pregnancy, before many women realize they are pregnant. (For more details, read the article on Neural Tube Defects.)
- Heavy alcohol drinking and chronic alcoholism can cause B12 and/or folate deficiency through a combination of poor nutrition and a decrease in the amount of B12 released from dietary proteins.
- Some drugs can cause B12 deficiency. For example, the diabetes drug metformin prevents B12 from being absorbed, while omeprazole (an acid reflux drug also known as Prilosec) reduces gastric acids and prevents B12 release from food.
- Anti-seizure medications such as phenytoin can decrease folate by blocking folate absorption.
- Methotrexate, an anti-cancer drug, affects body metabolism and use of folate.