3.7 Vitamin B12 and Folate Deficiency Anemia
Vitamin B12 and folate are water-soluble vitamins required for the production of red blood cells, white blood cells, and platelets. A deficiency of either of these vitamins causes megaloblastic anemia (also called macrocytic anemia) because the red blood cells in these disorders are abnormally large when compared to a healthy red blood cell.
As water-soluble vitamins, vitamin B12 and folate are not stored in the body and adequate amounts must be consumed in a person’s daily diet. Vitamin B12 (also called cobalamin) is present in many animal products, such as meats, dairy products, and eggs. Most balanced diets contain sufficient amounts of B12 except for vegan diets. Folate (also called vitamin B9) is present in many animal products and plants, especially liver and dark leafy vegetables. Most diets contain sufficient folate because many countries have supplemented cereals, flours, and grains with folic acid since the late 1990s to reduce the risk of neural tube defects during fetal development that can occur due to folate deficiency.[1],[2],[3],[4]
There are three basic causes of vitamin B12 anemia, including dietary deficiency, decreased absorption of vitamin B12, and an autoimmune disorder called pernicious anemia. Populations at risk for these causes include the following[5],[6],[7]:
- Dietary Deficiency: Individuals who follow a strict vegetarian (vegan) diet and do not eat animal products are at risk for not consuming enough vitamin B12 in their daily diet and often require vitamin supplements. Additionally, people of low socioeconomic status may not be able to afford animal proteins that contain Vitamin B12.
- Decreased Absorption of Vitamin B12: Some people may consume adequate amounts of vitamin B12 but have issues with absorbing this vitamin. Risk factors for decreased absorption of vitamin B12 are a gastric bypass, Crohn’s disease or other inflammatory bowel disorder, chronic use of antacids or proton pump inhibitors (PPIs), chronic H. Pylori infection, gastric cancer, chronic use of metformin, and chronic excess alcohol intake.
- Autoimmune Disorder: Pernicious anemia is a specific type of vitamin B12 anemia. Pernicious anemia is an autoimmune disorder in which antibodies are formed that attack the stomach cells that produce intrinsic factor. Intrinsic factor is a protein produced by the parietal cells of the stomach that carry vitamin B12 into the small intestine. Without intrinsic factor, vitamin B12 cannot be absorbed by the gastrointestinal tract.
Folate deficiency has become less common because food has been routinely supplemented with folic acid, but risk factors are similar to vitamin B12 deficiency. People who do not consume a varied, nutrient-rich diet are at risk for folate deficiency. For example, people with restrictive diets, anorexia nervosa, or those with excessive chronic alcohol use and a limited diet are at risk. Gastric bypass and inflammatory bowel disorders, as well as chronic medications such as methotrexate, antiseizure medications, and certain antibiotics, can also impact the absorption of folate. Furthermore, there is an increased need for folate for DNA synthesis in people who are pregnant or lactating, have chronic hemolytic anemia or severe eczema, or are undergoing dialysis.[8]
Pathophysiology
In healthy clients, when food sources containing vitamin B12 are ingested, vitamin B12 binds to an intrinsic factor, which is released from the parietal cells in the stomach. The vitamin B12-intrinsic factor complex is then able to bind to receptors on the ileum of the small intestine, and vitamin B12 can be absorbed. If vitamin B12 is not absorbed, neurological and hematological impairments will be seen as this vitamin plays a role in many chemical reactions throughout the body.[9]
Vitamin B12 and folate play critical roles in DNA and RNA synthesis. Therefore, when these vitamins are not available, not only are typical signs of anemia seen due to impaired red blood cell formation, but also other rapidly dividing cells are also affected. This also leads to elevated homocysteine (an amino acid that is broken down in the process of DNA synthesis), which can be useful for diagnostic purposes.[10],[11]
Vitamin B12 is also needed as a cofactor for enzymes in the Kreb’s cycle (a complex cycle that regulates cellular energy production). When B12 is not present for this cycle, methylmalonic acid (MMA) accumulates, which can damage the myelin sheath that surrounds and insulates nerves. This can lead to the neurological symptoms that are seen with vitamin B12 deficiency. MMA levels are also useful as a diagnostic tool.[12]
Assessment
Physical Examination
Clinical manifestations of anemia caused by vitamin B12 and folate deficiencies are related to the body’s inability to form red blood cells and other rapidly dividing cells. Vitamin B12 deficiency is also more likely to affect the nervous system, although folate deficiency may also cause neurocognitive symptoms. See Table 3.7a for a summary of the clinical manifestations of vitamin B12 and folic acid anemia across body systems.
Table 3.7a. Clinical Manifestations of Vitamin B12 and Folate Anemia[13],[14],[15],[16]
| Body System | Clinical Manifestation |
|---|---|
| General | Fatigue, progressive weakness |
| Nervous | Vitamin B12 deficiency: Symmetrical paresthesia/peripheral neuropathy, especially in the legs causing gait problems; dizziness; headaches; and vision changes |
| Gastrointestinal | Loss of appetite, weight loss, diarrhea
Vitamin B12 deficiency: Glossitis (pain, swelling, and tenderness of the tongue) Folate deficiency: Oral ulcers and beefy, red tongue |
| Integumentary | Pallor |
| Cardiovascular | Tachycardia and lightheadedness |
| Respiratory | Shortness of breath and tachypnea |
| Behavioral/Psychological | Subtle cognitive or psychiatric changes, especially in older adults |
Diagnostic Testing
A variety of lab tests may be ordered by a provider to diagnose vitamin B12 or folate deficiency. See Table 3.7b for a summary of common diagnostic tests. Review normal reference ranges for common diagnostic tests in “Appendix A – Normal Reference Ranges.”
Table 3.7b. Common Diagnostic Tests for Vitamin B12 and Folate Deficiency Anemia[17],[18]
| Lab Test | Expected Findings |
|---|---|
| Complete Blood Count | Decreased RBCs, decreased hemoglobin and hematocrit, and increased MCV (measures size of red blood cells). |
| Serum B12 Level | Above 300 pg/mL is normal.
Between 200-300 pg/mL is borderline deficient.* Below 200 pg/mL is considered deficient.* *Additional testing is performed to determine the cause, which impacts the route of supplementation. |
| Folate Level | Above 4 ng/mL is normal.
Between 2- 4 ng/mL is borderline deficient. Below 2 ng/mL is considered deficient. |
| Homocysteine Level | Elevated in vitamin B12 and folate deficiencies. |
| MMA Levels | Elevated in vitamin B12 deficiency. A normal MMA with elevated homocysteine levels indicates folate deficiency. |
| Anti-intrinsic Factor Antibodies | Positive in pernicious anemia. |
| Various Tests to Ascertain Etiology | If surgical or dietary history is not a causative factor, other tests may be ordered to determine the etiology of the vitamin B12 deficiency. For example, GI tests may be ordered to detect malabsorption issues. |
Nursing Diagnoses
Nursing priorities for clients with vitamin B12 anemia include promoting adequate tissue perfusion and oxygenation, providing adequate pain relief, preventing long-term neurological damage, preventing injury, enhancing nutrition (if applicable), improving fatigue and activity tolerance, and providing health teaching to help the client self-manage their disease.
Nursing diagnoses for clients with vitamin B12 anemia are created based on the specific needs of the client, their signs and symptoms, and their etiology of the disorder. These nursing diagnoses guide the creation of client specific care plans that encompass client outcomes and nursing interventions, as well the evaluation of those outcomes. These individualized care plans then serve as a guide for client treatment.
Common nursing diagnoses for clients with vitamin B12 anemia include the following[19],[20],[21]:
- Inadequate Tissue Perfusion
- Acute Pain
- Chronic Pain
- Risk for Falls
- Disturbed Sensory Perception
- Imbalanced Nutrition: Less Than Body Requirements
- Fatigue
- Decreased Activity Intolerance
- Readiness for Enhanced Knowledge
Outcome Identification
Outcome identification encompasses the creation of short- and long-term goals for the client. These goals are used to create expected outcome statements that are based on the specific needs of the client. Expected outcomes should be specific, measurable, and realistic. These outcomes should be achievable within a set time frame based on the application of appropriate nursing interventions.
Sample expected outcomes related to the previous nursing diagnoses are as follows[22]:
- The client will demonstrate adequate perfusion as demonstrated by appropriate urine output, skin color appropriate for race, palpable peripheral pulses, and vital signs within normal limits for age.
- The client will engage in fall prevention activities as specified by the care plan.
- The client will accurately verbalize the presence of sharp and dull sensations on hands and feet.
- The client will include food sources high in vitamin B12 with every meal.
- The client will describe two methods of energy conservation to manage fatigue.
Interventions
Medical Interventions
Medical Interventions for vitamin B12 deficiency depend on the cause, as well as the severity of the disorder. Common medical treatments include the following[23],[24],[25],[26]:
- Vitamin B12 Supplements (Cyanocobalamin): Supplements are administered orally or parenterally, with the prescribed route determined by the severity and the cause of the deficiency. For example, individuals with pernicious anemia must receive lifelong vitamin B12 parenteral (IM) supplements because they cannot absorb oral vitamin B12 due to the lack of intrinsic factor. Clients with severe vitamin B12 deficiency may also be initially treated with parenteral B12. Vitamin B12 is also available in oral, sublingual, subcutaneous, and intranasal forms. Clients should also be urged to increase their dietary intake of vitamin B12 with food sources such as meat and dairy. For those who follow a vegan diet, fortified cereals and fortified vegan milk substitutes are good sources of vitamin B12.
- Routine Monitoring of Vitamin B12 Levels: Monitoring is especially important in those who are at risk due to malabsorption such as those with Crohn’s disease.
- Blood Transfusions: Blood transfusions may be necessary in severe cases of vitamin B12 anemia. When clients have extreme symptoms or their hemoglobin levels fall below 7 g/dL, a transfusion may be prescribed.
Folate deficiency is treated with oral or parenteral administration of folic acid. Parental administration may be prescribed for severe, symptomatic anemia and then switched to oral therapy after symptoms resolve.[27]
Nursing Interventions
Common nursing interventions for clients with vitamin B12 deficiency anemia include the following[28],[29],[30],[31]:
- Monitor vitals because anemia can cause tachycardia and tachypnea.
- Perform comprehensive neurological assessments due to the neurological effects of vitamin B12 deficiency. If the client has been deficient in vitamin B12 for a prolonged amount of time, neurological symptoms may not be completely reversed even with adequate treatment.
- Administer vitamin B12 via enteral or parenteral routes per provider order and provide related health teaching. The RN should also monitor for potential side effects and allergic reactions. Hypokalemia is a common side effect of cyanocobalamin and would manifest as muscle cramping/weakness and/or irregular heartbeat. Cyanocobalamin contains cobalt and may need to be avoided in those with a cobalt sensitivity/allergy.
- Encourage a diet rich in vitamin B12. The recommended daily intake for vitamin B12 for adults is 2.4 mcg and more for those who are pregnant or breastfeeding.
- Initiate fall precautions such as a bed/chair alarm and a low height bed. Those with vitamin B12 anemia frequently exhibit dizziness, lightheadedness, paresthesia, vision changes, or confusion. Any of these symptoms put the client at increased risk for falls.
- Monitor input and output. Due to the potential for glossitis and impaired taste, the client may have a decreased appetite. Decreased appetite could also worsen the dietary intake of vitamin B12. Diarrhea can also put the client at risk for dehydration. Decreased urine output can also indicate ineffective peripheral tissue perfusion due to decreased red blood cell production.
- Assess pain because paresthesia and peripheral neuropathy may be painful.
- Teach energy management techniques such as setting priorities, assigning tasks to others, and balancing rest with activity.
Nurses provide preventative interventions by providing health teaching about the importance of folic acid supplements to prevent neural tube defects to female clients who are pregnant or trying to get pregnant. The recommended daily allowance of folic acid for adults is 400 mcg per day. For pregnant and lactating women, the dietary guideline is 600 mcg per day. Treatment of folate deficiency is typically 1-5 mg daily.[32]
Evaluation
During the evaluation stage, nurses determine the effectiveness of nursing interventions for a specific client. Lab results showing improvement of anemia resulting from vitamin B12 or folate deficiency should improve within one to two weeks and normalize within one to two months.[33] The previously identified expected outcomes are reviewed to determine if they were met, partially met, or not met by the time frames indicated. If outcomes are not met or only partially met by the time frame indicated, the nursing care plan is revised. Evaluation should occur every time the nurse implements interventions with a client, reviews updated laboratory or diagnostic test results, or discusses the care plan with other members of the interprofessional team.
RN Recap: Vitamin B12 Deficiency Anemia
View a brief YouTube video overview of vitamin B deficiency anemia[34]:
- Means, R. T., & Fairifeld, K. M. (2023). Causes and physiology of vitamin B12 and folate deficiencies. UpToDate. https://www.uptodate.com/contents/causes-and-pathophysiology-of-vitamin-b12-and-folate-deficiencies. ↵
- National Heart, Lung, and Blood Institute. (2022). Anemia - vitamin B12 deficiency. National Institutes of Health. https://www.nhlbi.nih.gov/health/anemia/vitamin-b12-deficiency-anemia ↵
- Ankar, A., & Kumar, A. (2022). Vitamin B12 Deficiency. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK441923 ↵
- Khan, K. M. & Jialal, I. (2023). Folic Acid Deficiency. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK535377/ ↵
- National Heart, Lung, and Blood Institute. (2022). Anemia - vitamin B12 deficiency. National Institutes of Health. https://www.nhlbi.nih.gov/health/anemia/vitamin-b12-deficiency-anemia ↵
- Ankar, A., & Kumar, A. (2022). Vitamin B12 Deficiency. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK441923 ↵
- Means, R. T., & Fairifeld, K. M. (2023). Causes and physiology of vitamin B12 and folate deficiencies. UpToDate. https://www.uptodate.com/contents/causes-and-pathophysiology-of-vitamin-b12-and-folate-deficiencies. ↵
- Means, R. T., & Fairifeld, K. M. (2023). Causes and physiology of vitamin B12 and folate deficiencies. UpToDate. https://www.uptodate.com/contents/causes-and-pathophysiology-of-vitamin-b12-and-folate-deficiencies. ↵
- Ankar, A., & Kumar, A. (2022). Vitamin B12 Deficiency. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK441923 ↵
- Ankar, A., & Kumar, A. (2022). Vitamin B12 Deficiency. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK441923 ↵
- Means, R. T., & Fairifeld, K. M. (2023). Causes and physiology of vitamin B12 and folate deficiencies. UpToDate. https://www.uptodate.com/contents/causes-and-pathophysiology-of-vitamin-b12-and-folate-deficiencies. ↵
- Ankar, A., & Kumar, A. (2022). Vitamin B12 Deficiency. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK441923 ↵
- National Heart, Lung, and Blood Institute. (2022). Anemia - vitamin B12 deficiency. National Institutes of Health. https://www.nhlbi.nih.gov/health/anemia/vitamin-b12-deficiency-anemia ↵
- Ankar, A., & Kumar, A. (2022). Vitamin B12 Deficiency. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK441923 ↵
- Vaqar, S., Shackelford, K., & Rudolph, S. (2023). Pernicious Anemia (Nursing). StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK568700 ↵
- Means, R. T., & Fairifeld, K. M. (2023). Causes and physiology of vitamin B12 and folate deficiencies. UpToDate. https://www.uptodate.com/contents/causes-and-pathophysiology-of-vitamin-b12-and-folate-deficiencies. ↵
- Ankar, A., & Kumar, A. (2022). Vitamin B12 Deficiency. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK441923 ↵
- Means, R. T., & Fairifeld, K. M. (2023). Causes and physiology of vitamin B12 and folate deficiencies. UpToDate. https://www.uptodate.com/contents/causes-and-pathophysiology-of-vitamin-b12-and-folate-deficiencies. ↵
- Ankar, A., & Kumar, A. (2022). Vitamin B12 Deficiency. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK441923 ↵
- Vaqar, S., Shackelford, K., & Rudolph, S. (2023). Pernicious Anemia (Nursing). StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK568700 ↵
- NursesLabs. (2023). 7 anemia nursing care plans. https://nurseslabs.com/anemia-nursing-care-plans/#h-nursing-diagnosis ↵
- NursesLabs. (2023). 7 anemia nursing care plans. https://nurseslabs.com/anemia-nursing-care-plans/#h-nursing-diagnosis ↵
- National Heart, Lung, and Blood Institute. (2022). Anemia - vitamin B12 deficiency. National Institutes of Health. https://www.nhlbi.nih.gov/health/anemia/vitamin-b12-deficiency-anemia ↵
- Ankar, A., & Kumar, A. (2022). Vitamin B12 Deficiency. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK441923 ↵
- Vaqar, S., Shackelford, K., & Rudolph, S. (2023). Pernicious Anemia (Nursing). StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK568700 ↵
- Vasavada, A. & Sanghavi, D. K. (2023). Cyanocobalamin. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK555964 ↵
- Means, R. T., & Fairifeld, K. M. (2024). Treatment of vitamin B12 and folate deficiencies. UpToDate. Treatment of vitamin B12 and folate deficiencies ↵
- National Heart, Lung, and Blood Institute. (2022). Anemia - vitamin B12 deficiency. National Institutes of Health. https://www.nhlbi.nih.gov/health/anemia/vitamin-b12-deficiency-anemia ↵
- Ankar, A., & Kumar, A. (2022). Vitamin B12 Deficiency. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK441923 ↵
- Vaqar, S., Shackelford, K., & Rudolph, S. (2023). Pernicious Anemia (Nursing). StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK568700 ↵
- Vasavada, A. & Sanghavi, D. K. (2023). Cyanocobalamin. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK555964 ↵
- Means, R. T., & Fairifeld, K. M. (2024). Treatment of vitamin B12 and folate deficiencies. UpToDate. Treatment of vitamin B12 and folate deficiencies ↵
- Means, R. T., & Fairifeld, K. M. (2024). Treatment of vitamin B12 and folate deficiencies. UpToDate. Treatment of vitamin B12 and folate deficiencies ↵
- Open RN Project. (2024, June 23). Health Alterations - Chapter 3 Hematological - Vitamin B12 deficiency anemia [Video]. YouTube. CC BY-NC 4.0https://youtu.be/sf7LS9eULyE?feature=shared ↵
An autoimmune disorder in which antibodies are formed that attack the stomach cells that produce intrinsic factor.
A protein produced by the parietal cells of the stomach that allows vitamin B12 to be absorbed by the intestines.
Inflammation of the tongue.