Management of vitamin B12 deficiency

Overview ㅡ Vitamin B12 (cobalamin) is necessary for a variety of critical functions within the human body (e.g., blood cell production, DNA synthesis, and neurologic function). Dietary sources of cobalamin are mainly found in animal products and fortified foods (e.g., Cereal). Vitamin B12 deficiency is a common problem, especially in the elderly. It is one of the most frequent causes of megaloblastic, macrocytic anemia.

Studies have linked commonly used medications (e.g., metformin, proton pump inhibitors) with the potential for vitamin B12 deficiency. see figure 1 on Clinical and laboratory findings in vitamin B12 deficiency.

Figure (1)

Clinical and laboratory findings in vitamin B12 deficiency.

Management

Discover the essentials of Vitamin B12 with our interactive accordion. Dive into its crucial role in red blood cell production, DNA synthesis, and neurological health. Explore common causes of deficiency, symptoms, diagnosis, and supplementation strategies.

How is vitamin B12 used in the body?

Vitamin B12 plays a critical role in red blood cell production, DNA synthesis, and neurologic function. Vitamin B12 is required for the synthesis of methionine (required for DNA synthesis and neurologic function) and succinyl-Co-A (required for red blood cell production).

What are common causes of vitamin B12 deficiency?

Insufficient dietary intake. The adult vitamin B12 recommended daily allowance is 2.4 mcg/day. Vitamin B12 is commonly found in animal products (e.g., organ meat, shellfish). Deficiency is more common in vegetarians. Foods are fortified with vitamin B12 (e.g., cereals, processed meats, meal replacement drinks).

• Reduced absorption can occur due to lack of intrinsic factor, often called pernicious anemia. Intrinsic factor is a glycoprotein secreted by parietal cells within the stomach. Vitamin B12 combines with intrinsic factor, this complex is absorbed in the distal ileum.
• Approximately 1% of oral vitamin B12 is absorbed passively, even without intrinsic factor. Reduced absorption can occur due to drug interactions or structural abnormalities.

Common medications associated with reduced B12 absorption include metformin, proton pump inhibitors, and H2-blockers. Other meds also associated with reduced B12 absorption include isoniazid, colchicine, and neomycin.

GI surgeries (e.g., gastric bypass, ileal resection) or conditions (e.g., achlorhydria, atrophic gastritis) can reduce B12 absorption. Patients unable to absorb naturally occurring vitamin B12 due to atrophic gastritis can absorb synthetic vitamin B12 found in fortified foods and supplements.

How frequent are B12 deficiencies due to medications?

Not all patients receiving metformin, PPIs, or H2-blockers will develop vitamin B12 deficiency. Risk of vitamin B12 deficiency appears to increase with the duration of metformin use.

1. Consider checking vitamin B12 levels every two to three years or every one to two years in patients receiving chronic metformin therapy, especially those at high risk or with symptoms of deficiency. 
2. Treating with an H2-blocker or PPI for ≥ 1 year could lead to one additional patient developing vitamin B12 deficiency.
3. Recommend evaluating the risk versus benefit with chronic use of metformin, PPIs, or H2-blockers. With appropriate indications, benefit normally outweighs risk, since vitamin B12 deficiency is an inexpensive condition to treat.
4. Discourage use of preventative vitamin B12; not all patients will develop a deficiency and studies haven’t been done to show benefit.

What are signs and symptoms associated with B12 deficiency?

Generic symptoms of anemia include weakness, fatigue, loss of appetite, and weight loss. Additionally, neurologic symptoms associated with B12 deficiency may include difficulty with balance, confusion, numbness or tingling of hands and feet, or memory problems.

How is vitamin B12 deficiency diagnosed?

Serum B12 levels < 200 pg/mL (150 pmol/L) are considered deficient.

• Recommend levels on two separate occasions or one level combined with symptoms and/or hematologic abnormalities to confirm a diagnosis.
• Hematologic abnormalities include a low hemoglobin (males < 13 g/dL, females < 12 g/dL) and an elevated mean corpuscular volume (MCV) > 100 fL.

How should vitamin B12 be supplemented to address deficiencies?

Vitamin B12 is available as cyanocobalamin, hydroxocobalamin, or methylcobalamin in multiple formulations (e.g., oral tablets, sublingual tablets, injection). For most patients, recommend 1000 to 2000 mcg/day of oral or sublingual cyanocobalamin for treatment and maintenance of B12 deficiency. These doses will overcome any absorption issues, including intrinsic factor deficiency. Most patients prefer oral or sublingual supplementation over intramuscular injections. Consider IM vitamin B12 for patients with severe deficiencies or neurologic symptoms. If IM vitamin B12 is used, consider the following dosing options:

• Cyanocobalamin: 1000 mcg IM daily for one week, followed by 1000 mcg weekly for one month, and then 1000 mcg monthly.
• Cyanocobalamin: 100 to 1000 mcg monthly.
• Hydroxocobalamin: 100 to 1000 mcg every two to three months.

References

• P. Stabler S, 'Vitamin B12 Deficiency | NEJM' (New England Journal of Medicine, 2013); https://www.nejm.org/doi/full/10.1056/nejmcp1113996