Vitamin B12 Deficiency

What is Vitamin B12?

Vitamin B12 is an essential nutrient that plays an important role in DNA synthesis and nerve function.  It is contained in high amounts in animal derived foods such as milk, eggs, and meat.  The vitamin is stored in the liver long-term.  Individuals with vegetarian, vegan, or other forms of restricted diet may develop the condition after approximately 6 months as liver stores of vitamin B12 become depleted.  Some individuals develop the condition due to autoimmune destruction of cells in the stomach that produce intrinsic factor.  Intrinsic factor is necessary for proper absorption of vitamin B12 in the small intestine.

Individuals with vitamin B12 deficiency often develop hematologic abnormalities such as megaloblastic anemia.  Patients may also develop peripheral neuropathy, subacute-combined degeneration of the spinal cord, and dementia.  These neurologic deficits may be irreversible if not corrected soon enough.  Due to the importance of this condition, it is critical that patients understand its causes, symptoms, and treatment.

What Causes B12 Deficiency?

Vitamin B12 deficiency is usually caused by decreased intake or poor absorption of vitamin B12.  As mentioned, one way to develop the disease is by restricting the diet from animal products such as dairy and meat.  Vegetarians are at high risk of developing the disorder unless they supplement the diet with vitamin B12.  Elderly patients are at high risk of the disorder as well due to dietary habits such as the “tea and toast” diet.

Some cases of vitamin B12 deficiency are related to a condition called pernicious anemia.  This disease is characterized by autoantibodies against intrinsic factor producing cells in the stomach (atrophic gastritis).  Intrinsic factor is an important molecule that binds to vitamin B12 in the stomach, allowing the vitamin B12/intrinsic factor complex to become absorbed in the small intestine.  Other disorders associated with B12 deficiency include celiac disease and inflammatory bowel disease – this occurs as a result of malabsorption.  Individuals that have undergone bowel resection of the stomach or small intestine (e.g., ileum) are also at increased risk.

How Common is Vitamin B12 Deficiency?

Vitamin B12 deficiency is common in the United States and often responsible for anemia and neurologic symptoms, particularly in the elderly.

A study in the United Kingdom showed that the age-specific prevalence of vitamin B12 deficiency is about 5% in adults age 65-74 and 10% in adults age ≥75.  Another research group reported a 24% prevalence in adults age 75-80.  Studies in France show that 60%-70% of cases of vitamin B12 deficiency were related to gastric atrophy, while pernicious anemia was responsible for 15%-20% of cases.

Signs and Symptoms

The clinical features of vitamin B12 deficiency often include:

• Subacute combined degeneration of the spinal cord
• Dementia
• Peripheral neuropathy
• Anemia - fatigue

Patients with subacute combined degeneration frequently develop problems with sensation in the lower extremities as well as difficulty with balance.  They characteristically lose proprioception, meaning they cannot tell where their joint or limb is in space.  Patients normally have a positive Romberg sign as well.  This is tested by having the patient maintain their balance while closing the eyes and standing with the arms to the sides and feet together.  Dementia is characterized by loss of memory and problems making executive decisions such as planning and organizing.  Individuals with anemia may experience fatigue or difficulty breathing with exertion.

Diagnosis

The diagnosis of vitamin B12 deficiency is suggested based on symptoms and physical examination, but typically confirmed with laboratory studies.  Your doctor will normally check a vitamin B12 level in the serum.  If this level is low, the diagnosis is established.  A borderline vitamin B12 level is usually followed up with a methylmalonic acid level as this is a highly sensitive test.  If the methymalonic acid level is elevated, the diagnosis of B12 deficiency is highly likely.  When the diagnosis is confirmed, your doctor may also obtain a serum intrinsic factor antibody to evaluate for pernicious anemia.  A CBC (complete blood cell count) is often obtained to evaluate for anemia, neutropenia (low neutrophil count), or thrombocytopenia (low platelet count).  A folate level is also normally ordered to evaluate for coexisting folate deficiency.

If you have symptoms of dementia or peripheral neuropathy, your doctor will request additional blood tests including a CMP (comprehensive metabolic panel) and thyroid function studies (TSH, free T4).  They may also check your cholesterol levels and screen for diabetes.  Some individuals with atypical neurologic symptoms will require MRI of the brain or spinal cord.  Occasionally nerve conduction studies or a spinal tap (lumbar puncture) are performed to rule out other diseases.

How is Vitamin B12 Deficiency Treated?

Vitamin B12 deficiency is treated with oral or parenteral vitamin B12 supplementation.  Individuals with an inability to absorb oral vitamin B12 usually require life-long parenteral (intramuscular) therapy.  This may be the case in those with gastrectomy, surgical removal of the small intestine, or advanced pernicious anemia.

Individuals are often initially treated with parenteral B12, particularly in those with neurologic symptoms.  Studies show that oral B12 is likely just as effective as intramuscular therapy; however, parenteral treatment ensures patient compliance.  This is critical because B12 deficiency can lead to permanent neurologic deficits if left undertreated or untreated.  Your doctor will typically monitor your serum B12 levels while on therapy and asses for normalization of laboratory values.  Patients with normal values are usually continued on maintenance therapy.