Only rarely.
This is being brought up now by the recent shortage of injectable B12 (cyanocobalamin) in the U.S.
Many patients have trouble absorbing B12 from food due to reduced gastric acidity or lack of intrinsic factor.
We used to think that these patients needed B12 by injection...but in many cases supplements can be given orally instead.
About 1% of the B12 in oral supplements is absorbed passively...even in patients without gastric acid or intrinsic factor.
Feel comfortable recommending ORAL B12 for treating mild to moderate deficiencies...or for maintenance therapy.
The key is to give enough. Recommend 1000 to 2000 mcg/day of oral or sublingual B12 for mild to moderate deficiencies.
Steer patients away from sustained-release B12 supplements...because their absorption might not be adequate.
Recommend injectable B12 for initial treatment of more severe deficiencies...especially if there are neurologic symptoms.
Also recommend the injectable for patients who can't take or adhere to oral meds...or those who may not absorb it due to diarrhea, vomiting, inflammatory bowel disease, or bowel resection.
Treatment of Vitamin B12 Deficiency | ||
|
Introduction Cobalamin (vitamin B12) deficiency is a common problem, especially in the elderly population. While it is usually thought that this deficiency occurs due to a lack of intrinsic factor, there are a number of other mechanisms including food-cobalamin malabsorption and inadequate intake. In a survey of internists, 94% believed that the only effective method of treatment for cobalamin deficiency was intramuscular (IM) cyanocobalamin injections. However, with the recent unavailability of injectable cyanocobalamin, alternatives are needed. A number of studies show that replacement with oral cyanocobalamin is effective and safe. This document discusses the various options available for the treatment of vitamin B12 deficiency. Causes of Vitamin B12 Deficiency Vitamin B12 is a water-soluble B vitamin usually acquired from the diet. It belongs to the class of cobalt-containing compounds known as cobalamins. Cobalt serves as an enzyme cofactor for a number of vitamin B12-dependent, enzyme-catalyzed reactions in mammals. These reactions most commonly affect the production of red blood cells and neurological function. Methylcobalamin and deoxyadenosylcobalamin are two biologically functional cobalamin forms that are involved in human metabolism. Cyanocobalamin is a stable, synthetic form of vitamin B12 and it’s the most common form found in dietary supplements and fortified food. It is converted to biologically active forms once it is imported into cells. Methylcobalamin is less commonly found in some vitamin supplements. The daily requirement for vitamin B12 is 1 to 2 mcg/day. Vitamin B12 absorption is a complex process. In healthy adults, about one-half of the ingested vitamin B12 is absorbed. However, this is affected by many factors. Secreted gastric acid and pepsin in the stomach allow vitamin B12 to dissociate from proteins in food. Once in the stomach, B12 is bound to R-proteins or haptocorrins, which carry vitamin B12 into the intestines. R-proteins are then degraded in the small intestine, thereby releasing vitamin B12, where it then binds to intrinsic factor, a factor secreted by parietal cells in the stomach. Intrinsic factor requires an alkaline pH (as found in the intestines) to bind vitamin B12. The intrinsic factor-vitamin B12 complex is then transported into enterocytes where it then enters the circulation where it is bound by a protein known as transcobalamin II. An interruption of any of these steps can lead to impaired vitamin B12 absorption. In otherwise healthy adults, mild B12 deficiency can occur due to insufficient dietary intake of animal food sources, most commonly in patients who are strict vegetarians or vegans. Alternatively, vitamin B12 deficiency can occur as a result of changes in acid secretion due to aging or gastric dysfunction leading to hypochlorhydria or achlorhydria. Long-term use of acid suppressive agents (H2 antagonists or proton pump inhibitors) may also predispose patients to cobalamin deficiency. Physiologic changes in gastric pH or changes induced by the use of acid suppressive medications lead to food-cobalamin malabsorption due to impaired release of cobalamin from its binding proteins due the lack of an acidic environment. Food-cobalamin malabsorption is also found in people with certain gastric dysfunctions such as atrophic gastritis with or without Helicobacter pylori infection, post-gastric surgery, or postvagotomy with pyloroplasty. Other gastrointestinal alterations such as loss of parietal cells, small intestine disorders, and genetic mutations can also impair vitamin B12 absorption. The classic treatment of vitamin B12 deficiency is parenteral (intramuscular) cyanocobalamin. For example, some protocols recommend 1000 mcg intramuscularly daily for one week, followed by 1000 mcg weekly for one month, and then 1000 mcg monthly, for life. Oral Therapy Recent evidence suggests that vitamin B12 can be effectively given by the nonparenteral route, even when there is a lack of intrinsic factor or pernicious anemia. While it is generally thought that intrinsic factor is imperative for cyanocobalamin absorption, there is an absorption pathway that does not require intrinsic factor or the presence of an intact ileum. If very large doses of oral cyanocobalamin (1000 to 10,000 mcg/day) are administered to patients with pernicious anemia, approximately 1% of the dose is absorbed due to passive diffusion, which meets the daily requirements. This can be achieved using a variety of oral dosage forms including fast-dissolving tablets or strips, lozenges, sublingual tablets, or oral tablets. (Note: vitamin B12 is also available as a transdermal patch, but there is no published information to support its use.) In determining the lowest dose of cyanocobalamin that was associated with the greatest reduction in MMA (methylmalonic acid :a biochemical marker associated with vitamin B12 deficiency) levels and increase in holotranscobalamin levels, the closed test procedure (the optimum dose defined as that dose whose effect differed significantly from the lower doses but not from the higher doses) was used. It was found that a daily dose of 500 mcg was the lowest dose that was associated with a maximum reduction in MMA concentration and a maximum increase in holotranscobalamin concentration. The authors concluded that the lowest dose of oral cyanocobalamin that was associated with an 80% to 90% of the estimated maximum reduction in MMA concentrations in an elderly population with mild to moderate vitamin B12 deficiency was 647 mcg to 1032 mcg daily. The authors (of another study) concluded that a dose of cyanocobalamin 500 mcg daily given orally or sublingually is effective in correcting cobalamin deficiency. Oral cyanocobalamin should only be considered in mild vitamin B12 deficiency and in patients who have an intact gastrointestinal system. In patients with more severe cases; in those who cannot absorb oral vitamin B12 due to diarrhea, vomiting, or bowel resection; or in cases where there is neurologic involvement therapy should be initiated with intramuscular therapy. If oral therapy is deemed appropriate (mild cases of deficiency, maintenance of vitamin B12 stores, etc), a product with adequate bioavailability should be used. There are a variety of vitamin B12 preparations available (lozenges, liquid, tablets, strips), but because these are considered dietary supplements, the absorption characteristics vary significantly. A recent letter to the editor highlighted the possible inadequacies of “timed”- or “sustained-release” vitamin B12 preparations. Many studies use regular-release products, yet some pharmacies only carry “timed”- or “sustained-release” preparations. Since the impact of preparation upon effect is unknown, in order to assure adequate response, cobalamin levels, alone or with metabolite levels (methylmalonic acid or homocysteine), should be monitored periodically. Documentation of efficacy is essential because inadequate response (prolonged deficiency of cobalamin) can lead to irreversible neurological damage. Conclusions Oral therapy with cyanocobalamin is effective and safe for treatment and maintenance of B12 deficiency. It has a number of advantages over parenteral therapy. Although parenteral cyanocobalamin is inexpensive, the cost and inconvenience of an office visit must be considered. Oral therapy is inexpensive and does not require medical personnel for administration. Additionally, intramuscular injections can be painful, especially for an elderly person with little muscle mass. A recent study found that of patients who required vitamin B12 therapy, 76% of patients who had previously been treated with parenteral therapy were satisfied with oral therapy, and 71% chose to stay on oral therapy. There are a number of clinical situations in which parenteral cyanocobalamin therapy is warranted. Parenteral therapy should be considered in patients who are noncompliant with oral medications, who are hospitalized, have diarrhea or vomiting, or who are unable to take medications orally. Additionally, patients who have more severe vitamin B12 deficiency or those with severe neurological involvement should receive parenteral treatment. Finally, a number of medications may reduce the oral absorption of vitamin B12. These include proton pump inhibitors, H2-antagonists, and metformin. Consequently, oral therapy may be less effective in patients taking these agents. In conclusion, oral cyanocobalamin (B12) represents an attractive alternative to parenteral therapy for the treatment and maintenance of outpatients with mild to moderate cobalamin deficiency. Use doses of 1000 to 2000 mcg/day of oral or sublingual B12 for mild to moderate deficiencies. Remind patients to select a B12 supplement with the NPN on the label. These products have been tested for good quality. |
