Vitamin B depletion?

Vitamin B12

TABLE 5
Vitamin B12 and Folic Acid Preparations
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Preparation
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Dosage
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Cost*
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Cyanocobalamin tablets 1,000 µg daily $ 2.87
Cyanocobalamin injection 1,000 µg weekly† 2.88 to 5.60
Cyanocobalamin nasal gel (Nascobol) 500 µg weekly 67.19‡
Folic acid (Folvite) 1 mg daily 4.17

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*--Estimated cost to the pharmacist for a 30-day supply based on average wholesale prices in Red book, Montvale, N.J.: Medical Economics Data, 1999. Cost to the patient will be greater, depending on prescription filing fees.

†--The maintenance dosage is 1,000 µg once per month.

‡--Price for a 5-mL container holding 500 µg per mL.

Since body stores of vitamin B12 are adequate for up to five years, deficiency is generally the result of the body's prolonged failure to absorb it. Pernicious anemia, Crohn's disease and other intestinal disorders are the most frequent causes of vitamin B12 deficiency. Intramuscular, oral or intranasal preparations are available for B12 replacement (Table 5). The traditional approach to treatment consists of intramuscular injections of cyanocobalamin. In patients with severe vitamin B12 deficiency, daily injections of 1,000 µg of cyanocobalamin are recommended for five days, followed by weekly injections for four weeks.23 Cyanocobalamin injections are well tolerated and rarely produce side effects. Hematologic improvement should begin within five to seven days, and the deficiency should resolve after three to four weeks of treatment. However, six months of therapy or longer will be required for signs of improvement in the neurologic manifestations of vitamin B12 deficiency. Complete or partial resolution of neurologic symptoms occurs in as many as 80 percent of patients.24 Neurologic improvement is less likely to occur in patients with severe or longstanding deficiency, and in patients whose accompanying anemia is less severe.

Most causes of vitamin B12 deficiency, such as pernicious anemia and postsurgical malabsorption states, are chronic. As a result, patients usually require lifetime maintenance therapy consisting of 1,000 µg injections of cyanocobalamin every one to three months25 (Table 6). To determine whether maintenance therapy is adequate, serum cobalamin levels should be measured. The physician may want to consider serial measurement of cobalamin levels, since the neurologic symptoms of vitamin B12 deficiency do not consistently correlate with the severity of the anemia.24,26 However, elevated serum homocysteine or urinary methylmalonic acid levels may be more sensitive indicators of vitamin B12 deficiency.27

Oral and intranasal preparations of vitamin B12 are also available. These routes of administration were not previously considered practical.28 However, patients with pernicious anemia will absorb 1 to 2 percent of orally ingested cobalamin without the need for intrinsic factor.23 Treating these patients with high oral dosages of vitamin B12, such as 1,000 to 2,000 µg daily, may be an alternative to parenteral therapy. Combination products containing vitamin B12 and intrinsic factor are available but are not readily absorbed. These preparations frequently induce allergic sensitization, and their use is not recommended.14

An intranasal gel containing cyanocobalamin (Nascobol) has recently been labeled for maintenance therapy of patients in hematologic remission after intramuscular vitamin B12 therapy for a variety of deficiency states. Administration of this product once weekly provides a 500-µg dose of cyanocobalamin. The patient's hematologic parameters must be within normal limits at initiation of therapy and should be monitored very closely throughout treatment. Preliminary reports suggest that intranasal cyanocobalamin may also be effective as replacement therapy in patients with vitamin B12 deficiency, although further study is needed to confirm its long-term effectiveness.29

TABLE 6
Schedules for the Administration of Vitamin B12
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Route of administration
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Replacement therapy
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Maintenance therapy
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Intramuscular 1,000 µg daily for five days, then 1,000 mg weekly for four weeks 1,000 µg every one to three months
Oral 1,000 to 2,000 µg daily 25 to 100 µg daily25
Intranasal 1,500 µg weekly for three to four weeks* 500 µg weekly

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*--Experimental protocol; not yet labeled for this use by the U.S. Food and Drug Administration.

Folate

Folate deficiency is characterized by megaloblastic anemia and low serum folate levels. Effective management of folate deficiency requires understanding its cause. Most patients with folate deficiency have inadequate intake, increased folate requirements, or both. Drug therapy with folate antagonists such as methotrexate (Rheumatrex), pyrimethamine (Daraprim), trimethoprim (Proloprim) or triamterene (Dyrenium) may also lead to folate deficiency. Treatment of folate deficiency is straightforward. In the absence of a folate malabsorption state, a once-daily dosage of 1 mg of folic acid given orally will replenish body stores in about three weeks30 (Table 5).

After initial intramuscular replacement, intranasal cyanocobalamin can be used for maintenance therapy of patients with vitamin B12 deficiency.

Folate supplementation is also recommended for women of child-bearing age to reduce the incidence of fetal neural tube defects. Current recommendations include initiating folic acid supplementation at a dosage of 0.4 mg daily before conception. Most prenatal vitamins contain this amount of folic acid. Women who have previously given birth to a child with a neural tube defect should take 4 to 5 mg of folic acid daily.31 It is believed that higher dosages do not provide any additional protection against neural tube defects.32

Research is currently underway to determine whether folic acid supplementation may reduce the risk of premature atherosclerotic cardiovascular disease.33 Elevated serum homocysteine levels are associated with an increased risk for myocardial infarction,34 stroke35 and, possibly, deep venous thrombosis.36 It remains unclear whether an elevated serum homocysteine level is directly involved in the pathogenesis of these events or merely a marker for potential cardiovascular disease. If an elevated homocysteine level is found to be associated with the atherosclerotic process, folic acid supplementation could reduce these levels, thereby reducing the risk of adverse cardiovascular events.37

The opportunity to decrease the incidence of neural tube defects and the theoretic possibility of reducing the risk of cardiovascular disease has led some nutrition authorities to recommend routine folic acid fortification of bread and other food products.31 However, because the use of folic acid supplementation partially corrects the hematologic abnormalities of vitamin B12 deficiency but not the associated neurologic deterioration,10 other experts have recommended that all foods fortified with folic acid also include vitamin B12 supplementation.38